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Recovery Audit Program Activity Trends
Much has been published in the academic literature and lay press regarding rising healthcare costs.[1] As the nations' largest payer, the Centers for Medicaid and Medicare Services (CMS) have been aggressive in trying to decrease Medicare expenditures. Each year Medicare processes over 1 billion claims, submitted by over 1 million healthcare providers. Starting in 2005, demonstration projects supported by the CMS identified more than $1.03 billion in improper Medicare payments.[2] Subsequently, section 1893(h) of the Affordable Care Act authorized expansion of the Recovery Audit Program nationwide by January 2010. Facilitated by third‐party vendors paid on a contingency fee basis, known as the Recovery Audit Contractors (RACs), the stated objective of the program is to identify and correct improper payments, not only identify overpayments to healthcare providers and organization, but also underpayments, in addition to reporting common billing errors, trends, and other Medicare payment issues to CMS. [2] Although CMS does have a prepayment review program,[3] much of the reported RAC activities to date have been focused on postbill overpayment activities. In 2013 (the most recent reported annual activity period), CMS reported that collectively the RACs identified and corrected 1,532,249 claims for improper payments, collected $3.65 billion in overpayments, and identified $102.4 million in underpayments that were repaid to providers and suppliers.
Sheehy et al., present the collective experience of 3 large academic medical centers with RAC audit activity.[4] They found that from 2010 to 2013, there has been a 3‐fold increase in RAC‐related activities. The RACs are selected by CMS via a competitive bidding process and are contractually incentivize via a contingency fee. This means that they receive a portion of the funds that they recover (anywhere from 9%12% depending on the contract). If the RAC's claim is overturned on appeal, the RAC must repay the contingency fee, but does not face an economic penalty. This creates a potential incentive for RACs to be overly aggressive in pursuing potential overpayments from hospitals and providers.
The institutions in this study disputed 91% of allegations of overpayment. This dispute rate is notably higher than the 50% that was reported by a survey conducted by the American Hospital Association.[5] What is unknown is what the actual rate of overturned decisions based on appeal would be, as 49% of all contested claims from the study institutions were withdrawn and rebilled, and did not go through the complete appeals process. The authors cite the lengthy and presumably expensive process of adjudication as the reason for the decision to rebill the claims at the typically lower payment levels available under Medicare Part B. A 2012 report by the Office of the Inspector General (OIG) found that most (72%) of RAC‐denied hospital inpatient claims were overturned on appeal, in favor of the hospital by an administrative law judge (ALJ). This high rate of turnover has initiated a national discussion about the unbalanced financial incentives of the process per current design.
Since 2009, there has been a 10‐fold increase in the number of appeals waiting for a decision, with hearing delays reported to be as long as 32 months.[5, 6] The ALJ is required to issue a decision within 90 days of an appeal request. However, despite the huge volume of audits and secondary appeals generated by the RAC process, CMS has done little to expand the appeal infrastructure and the ALJ resources to keep pace with the incentivized RAC contractors.
The ALJ appeal backlog became so substantial that the Office of Medicare Hearings and Appeals published the following statement: As noted in a Federal Register Notice released by the Office of Medicare Hearings and Appeals (OMHA) in January 2014, the unprecedented growth in claim appeals continues to exceed the available adjudication resources to address [such] appeals.The CMS supports OMHA's efforts to bring efficiencies to the OMHA appeals process. Ultimately CMS offered hospitals a blanket 68% settlement for outstanding appeals to simply settle the backlogged cases.[7]
Finally, the authors note that an average of 5 full‐time equivalents (FTEs) was required by each institution to support the compliance‐related activities, which the authors claim is onerous and expensive. Their experience is consistent with other national reports that have found that 69% of surveyed hospitals report spending more than $40,000 per year, whereas 11% spend more than $100,000 annually.[5]
Ultimately, the authors conclude that reform is needed. Nationally many have agreed. As such, based on feedback, the CMS announced changes to the RAC program in December 2014[8] including: (1) reduction of the RAC look back period to 6 months (vs 3 years) from the date of service for payment adjustments, (2) RAC review period decreases to 30 days (vs 60 days), (3) addition of a 30‐day discussion period for claims, (4) the RAC will not receive a contingency fee until the second level review is completed, (5) broadened scope beyond inpatient claims (eg, review of outpatient claims), (6) more transparency regarding the appeals process, (7) new requirements for RACs to maintain a <10% overturn rate at the first‐level review (if not met, the RAC will be placed on a corrective action plan), and (8) RACs are now required to maintain an overall accuracy rate of 95%. In addition, CMS must publically report through an annual Report to Congress a Recovery Auditor accuracy rate for each Recovery Auditor.[9] There is no doubt that the current RAC program has generated significant savings for CMS. However, it has resulted in a notable cost and administrative burden to others including hospitals and provider groups. With the implementation of measures that hold RACs more accountable for the quality of their reviews, it is unclear if these new reform measures proposed by CMS will substantially improve the postpayment refinement process. Only with continued, but expensive, vigilance by providers and hospitals to ensure that claims are accurately processed as was described by the study institutions by Sheehy et al.,[4] will we know the potential value of the postpayment system.
Disclosure
Nothing to report.
- , , The triple aim: care, health, and cost. Health Aff (Millwood). 2008;27(3):759–769.
- United States Department of Health and Human Services, Office of Inspector General Recovery Audit Contractors' Fraud Referrals. Available at: http://oig.hhs.gov/oei/reports/oei‐03‐09‐00130.pdf. Accessed January 30, 2015.
- Centers of Medicare
Much has been published in the academic literature and lay press regarding rising healthcare costs.[1] As the nations' largest payer, the Centers for Medicaid and Medicare Services (CMS) have been aggressive in trying to decrease Medicare expenditures. Each year Medicare processes over 1 billion claims, submitted by over 1 million healthcare providers. Starting in 2005, demonstration projects supported by the CMS identified more than $1.03 billion in improper Medicare payments.[2] Subsequently, section 1893(h) of the Affordable Care Act authorized expansion of the Recovery Audit Program nationwide by January 2010. Facilitated by third‐party vendors paid on a contingency fee basis, known as the Recovery Audit Contractors (RACs), the stated objective of the program is to identify and correct improper payments, not only identify overpayments to healthcare providers and organization, but also underpayments, in addition to reporting common billing errors, trends, and other Medicare payment issues to CMS. [2] Although CMS does have a prepayment review program,[3] much of the reported RAC activities to date have been focused on postbill overpayment activities. In 2013 (the most recent reported annual activity period), CMS reported that collectively the RACs identified and corrected 1,532,249 claims for improper payments, collected $3.65 billion in overpayments, and identified $102.4 million in underpayments that were repaid to providers and suppliers.
Sheehy et al., present the collective experience of 3 large academic medical centers with RAC audit activity.[4] They found that from 2010 to 2013, there has been a 3‐fold increase in RAC‐related activities. The RACs are selected by CMS via a competitive bidding process and are contractually incentivize via a contingency fee. This means that they receive a portion of the funds that they recover (anywhere from 9%12% depending on the contract). If the RAC's claim is overturned on appeal, the RAC must repay the contingency fee, but does not face an economic penalty. This creates a potential incentive for RACs to be overly aggressive in pursuing potential overpayments from hospitals and providers.
The institutions in this study disputed 91% of allegations of overpayment. This dispute rate is notably higher than the 50% that was reported by a survey conducted by the American Hospital Association.[5] What is unknown is what the actual rate of overturned decisions based on appeal would be, as 49% of all contested claims from the study institutions were withdrawn and rebilled, and did not go through the complete appeals process. The authors cite the lengthy and presumably expensive process of adjudication as the reason for the decision to rebill the claims at the typically lower payment levels available under Medicare Part B. A 2012 report by the Office of the Inspector General (OIG) found that most (72%) of RAC‐denied hospital inpatient claims were overturned on appeal, in favor of the hospital by an administrative law judge (ALJ). This high rate of turnover has initiated a national discussion about the unbalanced financial incentives of the process per current design.
Since 2009, there has been a 10‐fold increase in the number of appeals waiting for a decision, with hearing delays reported to be as long as 32 months.[5, 6] The ALJ is required to issue a decision within 90 days of an appeal request. However, despite the huge volume of audits and secondary appeals generated by the RAC process, CMS has done little to expand the appeal infrastructure and the ALJ resources to keep pace with the incentivized RAC contractors.
The ALJ appeal backlog became so substantial that the Office of Medicare Hearings and Appeals published the following statement: As noted in a Federal Register Notice released by the Office of Medicare Hearings and Appeals (OMHA) in January 2014, the unprecedented growth in claim appeals continues to exceed the available adjudication resources to address [such] appeals.The CMS supports OMHA's efforts to bring efficiencies to the OMHA appeals process. Ultimately CMS offered hospitals a blanket 68% settlement for outstanding appeals to simply settle the backlogged cases.[7]
Finally, the authors note that an average of 5 full‐time equivalents (FTEs) was required by each institution to support the compliance‐related activities, which the authors claim is onerous and expensive. Their experience is consistent with other national reports that have found that 69% of surveyed hospitals report spending more than $40,000 per year, whereas 11% spend more than $100,000 annually.[5]
Ultimately, the authors conclude that reform is needed. Nationally many have agreed. As such, based on feedback, the CMS announced changes to the RAC program in December 2014[8] including: (1) reduction of the RAC look back period to 6 months (vs 3 years) from the date of service for payment adjustments, (2) RAC review period decreases to 30 days (vs 60 days), (3) addition of a 30‐day discussion period for claims, (4) the RAC will not receive a contingency fee until the second level review is completed, (5) broadened scope beyond inpatient claims (eg, review of outpatient claims), (6) more transparency regarding the appeals process, (7) new requirements for RACs to maintain a <10% overturn rate at the first‐level review (if not met, the RAC will be placed on a corrective action plan), and (8) RACs are now required to maintain an overall accuracy rate of 95%. In addition, CMS must publically report through an annual Report to Congress a Recovery Auditor accuracy rate for each Recovery Auditor.[9] There is no doubt that the current RAC program has generated significant savings for CMS. However, it has resulted in a notable cost and administrative burden to others including hospitals and provider groups. With the implementation of measures that hold RACs more accountable for the quality of their reviews, it is unclear if these new reform measures proposed by CMS will substantially improve the postpayment refinement process. Only with continued, but expensive, vigilance by providers and hospitals to ensure that claims are accurately processed as was described by the study institutions by Sheehy et al.,[4] will we know the potential value of the postpayment system.
Disclosure
Nothing to report.
Much has been published in the academic literature and lay press regarding rising healthcare costs.[1] As the nations' largest payer, the Centers for Medicaid and Medicare Services (CMS) have been aggressive in trying to decrease Medicare expenditures. Each year Medicare processes over 1 billion claims, submitted by over 1 million healthcare providers. Starting in 2005, demonstration projects supported by the CMS identified more than $1.03 billion in improper Medicare payments.[2] Subsequently, section 1893(h) of the Affordable Care Act authorized expansion of the Recovery Audit Program nationwide by January 2010. Facilitated by third‐party vendors paid on a contingency fee basis, known as the Recovery Audit Contractors (RACs), the stated objective of the program is to identify and correct improper payments, not only identify overpayments to healthcare providers and organization, but also underpayments, in addition to reporting common billing errors, trends, and other Medicare payment issues to CMS. [2] Although CMS does have a prepayment review program,[3] much of the reported RAC activities to date have been focused on postbill overpayment activities. In 2013 (the most recent reported annual activity period), CMS reported that collectively the RACs identified and corrected 1,532,249 claims for improper payments, collected $3.65 billion in overpayments, and identified $102.4 million in underpayments that were repaid to providers and suppliers.
Sheehy et al., present the collective experience of 3 large academic medical centers with RAC audit activity.[4] They found that from 2010 to 2013, there has been a 3‐fold increase in RAC‐related activities. The RACs are selected by CMS via a competitive bidding process and are contractually incentivize via a contingency fee. This means that they receive a portion of the funds that they recover (anywhere from 9%12% depending on the contract). If the RAC's claim is overturned on appeal, the RAC must repay the contingency fee, but does not face an economic penalty. This creates a potential incentive for RACs to be overly aggressive in pursuing potential overpayments from hospitals and providers.
The institutions in this study disputed 91% of allegations of overpayment. This dispute rate is notably higher than the 50% that was reported by a survey conducted by the American Hospital Association.[5] What is unknown is what the actual rate of overturned decisions based on appeal would be, as 49% of all contested claims from the study institutions were withdrawn and rebilled, and did not go through the complete appeals process. The authors cite the lengthy and presumably expensive process of adjudication as the reason for the decision to rebill the claims at the typically lower payment levels available under Medicare Part B. A 2012 report by the Office of the Inspector General (OIG) found that most (72%) of RAC‐denied hospital inpatient claims were overturned on appeal, in favor of the hospital by an administrative law judge (ALJ). This high rate of turnover has initiated a national discussion about the unbalanced financial incentives of the process per current design.
Since 2009, there has been a 10‐fold increase in the number of appeals waiting for a decision, with hearing delays reported to be as long as 32 months.[5, 6] The ALJ is required to issue a decision within 90 days of an appeal request. However, despite the huge volume of audits and secondary appeals generated by the RAC process, CMS has done little to expand the appeal infrastructure and the ALJ resources to keep pace with the incentivized RAC contractors.
The ALJ appeal backlog became so substantial that the Office of Medicare Hearings and Appeals published the following statement: As noted in a Federal Register Notice released by the Office of Medicare Hearings and Appeals (OMHA) in January 2014, the unprecedented growth in claim appeals continues to exceed the available adjudication resources to address [such] appeals.The CMS supports OMHA's efforts to bring efficiencies to the OMHA appeals process. Ultimately CMS offered hospitals a blanket 68% settlement for outstanding appeals to simply settle the backlogged cases.[7]
Finally, the authors note that an average of 5 full‐time equivalents (FTEs) was required by each institution to support the compliance‐related activities, which the authors claim is onerous and expensive. Their experience is consistent with other national reports that have found that 69% of surveyed hospitals report spending more than $40,000 per year, whereas 11% spend more than $100,000 annually.[5]
Ultimately, the authors conclude that reform is needed. Nationally many have agreed. As such, based on feedback, the CMS announced changes to the RAC program in December 2014[8] including: (1) reduction of the RAC look back period to 6 months (vs 3 years) from the date of service for payment adjustments, (2) RAC review period decreases to 30 days (vs 60 days), (3) addition of a 30‐day discussion period for claims, (4) the RAC will not receive a contingency fee until the second level review is completed, (5) broadened scope beyond inpatient claims (eg, review of outpatient claims), (6) more transparency regarding the appeals process, (7) new requirements for RACs to maintain a <10% overturn rate at the first‐level review (if not met, the RAC will be placed on a corrective action plan), and (8) RACs are now required to maintain an overall accuracy rate of 95%. In addition, CMS must publically report through an annual Report to Congress a Recovery Auditor accuracy rate for each Recovery Auditor.[9] There is no doubt that the current RAC program has generated significant savings for CMS. However, it has resulted in a notable cost and administrative burden to others including hospitals and provider groups. With the implementation of measures that hold RACs more accountable for the quality of their reviews, it is unclear if these new reform measures proposed by CMS will substantially improve the postpayment refinement process. Only with continued, but expensive, vigilance by providers and hospitals to ensure that claims are accurately processed as was described by the study institutions by Sheehy et al.,[4] will we know the potential value of the postpayment system.
Disclosure
Nothing to report.
- , , The triple aim: care, health, and cost. Health Aff (Millwood). 2008;27(3):759–769.
- United States Department of Health and Human Services, Office of Inspector General Recovery Audit Contractors' Fraud Referrals. Available at: http://oig.hhs.gov/oei/reports/oei‐03‐09‐00130.pdf. Accessed January 30, 2015.
- Centers of Medicare
- , , The triple aim: care, health, and cost. Health Aff (Millwood). 2008;27(3):759–769.
- United States Department of Health and Human Services, Office of Inspector General Recovery Audit Contractors' Fraud Referrals. Available at: http://oig.hhs.gov/oei/reports/oei‐03‐09‐00130.pdf. Accessed January 30, 2015.
- Centers of Medicare
Reducing Inappropriate PPIs at Discharge
In 2013, there were more than 15 million Americans receiving proton pump inhibitors (PPIs),[1] with an associated drug cost of nearly $79 billion between 2007 and 2011.2 PPI use is reaching epidemic proportions, likely due to the medicalization of gastrointestinal symptoms coupled with pervasive marketing and academic detailing being performed by the pharmaceutical industry.
Although PPIs are generally considered safe, they are not as innocuous as many physicians believe. In 2011 and 2012, the US Food and Drug Administration and Health Canada, respectively, issued safety advisories regarding the use of these medications related to Clostridium difficile, fracture risk, and electrolyte derangement.[3, 4, 5, 6] There have also been numerous other harmful associations reported,[7, 8, 9, 10] suggesting it would be prudent to follow Health Canada's advice that: PPIs should be prescribed at the lowest dose and shortest duration of therapy appropriate to the condition being treated.[4] In many cases this implies stopping the PPI after an appropriate duration of therapy or attempting nonpharmacological or H2‐blocker therapy instead.
Nevertheless, despite numerous cautionary publications, PPI use for nonevidence‐based indications remains common. Because they are generally thought of as outpatient medications, PPIs are frequently continued in hospitalized patients, and inappropriate outpatient therapy is rarely addressed.[11, 12, 13] Likewise, inappropriate de novo use can also be observed during hospitalization and may continue on discharge.[13, 14, 15] Hospitalization may consequently present an opportunity to employ meaningful interventions targeting outpatient medication use.[16] We developed an opportune inpatient intervention targeting inappropriate PPI therapy.
Our study had 2 aims: first, to determine the magnitude of the problem in a contemporary Canadian medical inpatient population, and second, we sought to leverage the inpatient admission as an opportunity to promote change when the patient returned to the community through the application of an educational and web‐based quality‐improvement (QI) intervention.
METHODS
Patient Inclusion
Between January 2012 and December 2012, we included all consecutively admitted patients on our 46‐bed general medical clinical teaching unit belonging to a 417‐bed tertiary care teaching hospital in Montreal, Canada. There were no exclusion criteria. This time period was divided into 2 blocks: the preintervention control period from January 1 to June 3 and the intervention period from June 4 to December 16.
Intervention and Implementation Strategy
At the start of each academic period, we presented a 20‐minute information session on the benefits and harms of PPI use (see Supporting Information, Appendix, in the online version of this article). The unit's medical residents and faculty attended these rounds. The presentation described the project, consensus‐derived indications for PPI use, and potential adverse events attributable to PPIs (see Table 1 for indications based on internal consensus and similar studies[17, 18, 19, 20, 21, 22, 23]). All other indications were considered nonevidence based. At the end of the month, teams were given feedback on indications they provided using the Web tool and the proportion of patients they discharged on a PPI with and without indication.
|
| 1. Gastric or duodenal ulcer within the past 3 months |
| 2. Pathological hypersecretory conditions |
| 3. Gastroesophageal reflux disease with exacerbations within the last 3 months not responsive to H2 blockers and nonpharmacologic techniques |
| 4. Erosive esophagitis |
| 5. Recurring symptoms recently associated with severe indigestion within the last 3 months not responsive to H2 blocker or nonpharmacologic techniques |
| 6. Helicobacter pylori eradication |
| 7. Dual antiplatelet therapy |
| 8. Antiplatelet therapy with anticoagulants |
| 9. Antiplatelet or anticoagulant therapy with history of previous complicated ulcer |
| 10. Antiplatelet or NSAID with 2 of the following: concomitant systemic corticosteroids, age over 60 years, previous uncomplicated ulcer, concomitant NSAID, or antiplatelet/anticoagulant |
The process of evaluating and stopping PPIs was voluntary. Housestaff were encouraged to evaluate PPIs when ordering admission medications and upon preparing exit prescriptions. This was an opt‐in intervention. Once a patient on a PPI was identified, typically on admission to the unit, the indication for use could then be evaluated using the online tool, which was accessible on the internet via a link on all unit computers (see Supporting Information, Appendix, in the online version of this article).
The Web‐based tool was designed to be simple and informative. Users of the tool input anonymous data including comorbidities (check boxes provided). The tool collected the indication for PPI use, with available options including: the consensus‐derived evidence‐based indications, no identified indication, or free text. This was done purposefully to remind the teams of the consensus indications, with the goal that in choosing no identified indication the resident would consider cessation of unnecessary PPIs. The final step in the tool, discharge plan, presented the option of stopping the PPI in the absence of a satisfactory indication. We hypothesized that selecting this option would serve as an informal commitment to discontinuing the PPI during the creation of the discharge prescription; however, the tool was not automatically linked to these prescriptions.
If a home prescription was discontinued, the patient was counselled by the treating team and provided with an educational letter (see Supporting Information, Appendix, in the online version of this article), which was fastened to their discharge summary and given to the patient for delivery to all of their usual outpatient physician(s).
The design of the online tool was such that residents were to evaluate PPI use that would continue postdischarge from the hospital, rather than PPI use limited to the period of hospitalization.
Data Collection and Statistical Analysis
Data on baseline demographics and the specific indications for PPI use were collected through clinician interaction with the online tool. The proportion of patients on a PPI was ascertained through a separate data extraction of electronic discharge prescriptions. These involved medication reconciliation for all outpatient medications including whether or not they were continued, modified, or stopped. Thus, we could determine at discharge whether outpatient PPIs were continued or stopped or if a new PPI was initiated.
The proportion of patients admitted from home already receiving a PPI, those who received a new prescription for a PPI at discharge, and those whose PPI was stopped during admission were compared before and after the intervention using segmented regression analysis of an interrupted time series (see Supporting Information, Appendix, in the online version of this article).[24]
Post Hoc Power Calculations
For the pre‐post comparisons, given the preintervention number of admissions, proportions of PPI use in the community, new PPI use, and PPI discontinuation rates we would have had an 80% power to detect changes of 8.5%, 5%, and 5.5%, respectively.
Ethics
The McGill University Health Centre research ethics board approved this study. Informed consent was waived as the intervention was deemed to be best practice, and data collected were anonymous. Clinical consent was obtained by the treating team for all care decisions.
Funding
This initiative was conducted without any funding.
RESULTS
During the preintervention period, 464 patients were admitted, of whom 209 (45%) were taking a PPI prior to admission. During their hospitalization, an additional 53 patients (21% of nonusers) were newly prescribed a PPI that was continued at discharge. During the intervention period, a total of 640 patients were admitted, of whom 281 (44%) were taking a PPI prior to admission. During their hospitalization, 60 patients (17% of nonusers) were newly prescribed a PPI that was continued at discharge. Neither the monthly proportions admitted on PPIs from prior to admission (level P=0.59, slope P=0.46) or those newly initiated on a PPI (level P=0.36, slope P=0.18) were significantly different before compared to after the intervention. However, there was both a clinically and statistically significant difference in the proportion of preadmission PPIs that were discontinued at hospital discharge from a monthly mean of 7.7% (or 16/209) before intervention to 18.5% (or 52/281) afterward (Figure 1; level P=0.03, slope P=0.48).
During the intervention period, our teams prospectively captured PPI indications and patient comorbidities for 54% (152/281) of the patients admitted on a PPI using the online assessment tool. The baseline characteristics of the population in whom the online tool was applied are shown in Table 2. These patients had a mean age of 69.6 years, and 49% were male. Thirty‐two percent had diabetes, 20% had chronic renal insufficiency, and 13% had experienced a gastrointestinal hemorrhage within the 3 months prior to admission. It was frequent for PPI users to receive systemic antibiotics (44%) or to have diagnoses potentially associated with PPI use such as community‐acquired pneumonia (25%) or C difficile (11%).
| Characteristic | Value |
|---|---|
| |
| Age, y, mean (SD) | 69.615.1 |
| Male gender, N (%) | 75 (49) |
| Initiation of PPI, N (%) | |
| Prior to hospitalization | 127 (84) |
| During hospitalization | 10 (6) |
| In ICU | 7 (4) |
| In ER | 8 (5) |
| Comorbidities, N (%) | |
| Diabetes mellitus | 48 (32) |
| Chronic renal failure, GFR <45 | 29 (20) |
| GI bleed in the last 3 months | 20 (13) |
| No comorbidities | 11 (7) |
| Medications, N (%) | |
| Current antiplatelet agent | 67 (44) |
| Current corticosteroid use | 40 (26) |
| Current therapeutic anticoagulation | 35 (23) |
| Current NSAID use | 13 (8.5) |
| Current bisphosphonate | 13 (8.5) |
| Potential contraindications to PPI, N (%) | |
| Current antibiotic therapy | 67 (44) |
| Pneumonia | 38 (25) |
| Clostridium difficile infection ever | 16 (11) |
| Clostridium difficile infection on present admission | 9 (6) |
Fifty‐four percent (82/152) of patients in whom the online tool was applied had an evidence‐based indication (Table 3). The most common indication for PPI prescription was the receipt of antiplatelet/anticoagulant or nonsteroidal anti‐inflammatory drug with 2 other known risk factors for upper gastrointestinal bleeding (20%). In the remaining 46% (70/152) of patients, the prescription of a PPI was deemed nonevidence based. Of these, 34 (49%) had their PPI discontinued. When patients were approached to discontinue therapy, the rate of success was high, with only 2 refusals.
| Indications | N (%) |
|---|---|
| |
| Approved indications for therapy | |
| Antiplatelet or NSAID with 2 of the following: age >60 years, systemic corticosteroids, previous uncomplicated ulcer, NSAID, or antiplatelet/anticoagulant | 28 (20) |
| Gastric or duodenal ulcer within the past 3 months | 23 (15) |
| Antiplatelet therapy with anticoagulants | 17 (11) |
| GERD with exacerbations within the last 3 months | 17 (11) |
| Dual antiplatelet therapy | 7 (5) |
| Pathological hypersecretory conditions | 0 |
| Helicobactor pylori eradication | 0 |
| Total with consensus indications | 79 (54) |
| Other described indications for therapy | |
| No indication identified | 46 (30) |
| Othera | 22 (14) |
| Palliative patients GERD prophylaxis | 5 (3) |
| Total without consensus indications | 70 (46) |
DISCUSSION
In this prospective intervention, 44% of patients admitted to an acute‐care medical ward were prescribed a PPI prior to their admission. In the subgroup of patients for whom the indication for PPI use was recorded through our online tool, less than half had an evidence‐based indication for ongoing therapy. Our intervention was successful in increasing the proportion of patients in whom preadmission PPI prescriptions were stopped at discharge from an average of 7.7% in the preintervention phase to 18.5% during the intervention. This intervention is novel in that we were able to reduce active community prescriptions for PPIs in patients without obvious indication by nearly 50%.
Our population's rates of PPI prescription were consistent with previous reports,[11, 12, 13, 15, 25, 26, 27, 28] and it is clear that many hospitalized patients continue their PPIs at discharge without clear indications. We propose that hospitalization can serve as an opportunity to reassess the necessity of continuous PPI use. Previous systematic attempts to reduce inappropriate PPI prescriptions in hospital have met with varied success. Several of these studies were unable to achieve a demonstrable effect.[23, 29, 30, 31] In contrast, Hamzat et al.[30] described a successful educational intervention targeting inpatients on a geriatric ward. A 4‐week educational strategy was employed, and they were able to discontinue PPIs in 10 of 60 (17%) patients without indication during a limited period of study. Another successful intervention by Gupta et al.[32] involved a before‐and‐after study combining a half‐hour physician education session with the introduction of a medication reconciliation tool. They showed a decrease in inappropriate discharge prescriptions of 50%. Not only did our study demonstrate an equally sizable reduction in inappropriate discharge prescriptions, but we also employed a more methodologically sound time‐series analysis to control for unmeasured contemporaneous factors such as rotating staff practices or monthly differences in patient composition. We demonstrated an immediate and sustained improvement in performance that lasted over 6 months. Furthermore, in contrast to other interventions, which addressed inappropriate inpatient use persisting on discharge, our intervention also addressed the appropriateness of PPI use that antedated hospitalization.
There are common themes to the successful programs. The more time spent educating and reminding the prescribing physicians, the more successful the intervention. Nonetheless, we believe our intervention is not onerous or overly time consuming. We performed a short presentation each month to educate rotating physicians, and the tool took less than 1 minute to complete once the information on PPI indication was available. Frequent education sessions may be initially necessary given the comfort that many physicians have developed in prescribing PPIs. A further prerequisite for success may be a familiarity with PPI indications and potential adverse effects. Without this, the intervention may not show a demonstrable effect, as was seen in a study of pulmonologists.[23] We hypothesize that some subspecialist physicians may not have the same appreciation of the adverse effects of PPIs nor the confidence to stop them when not indicated, as compared to general internists or hospitalists.
The proportion of patients with newly initiated PPIs at discharge decreased after the intervention, but this did not reach statistical significance. Our study's power may have precluded this. However, we had also previously put in place unpublished interventions to diminish inappropriate gastric prophylaxis in the hospital, which may have diminished the effect of this intervention.
Unfortunately, although we demonstrated a clinically significant effect on PPI exit prescription rates, we still found that nearly half of the patients who were evaluated using the online tool were discharged on PPIs despite our physicians' acknowledgment that they had no identifiable indication. It is possible that clinicians do not feel comfortable stopping these medications, owing to a fear that there is an indication that they are not aware of. In certain cases, it is possible that a reappraisal of the benefits, risks, and costs might reassure the clinician that they could safely stop the drug; however, therapeutic inertia is often hard to overcome.
Limitations
Our single‐center study occurred over a limited time period and examined a sample of patients that were assessed based on convenience. Other limitations included the uptake of the online tool, which was only 54% of patients on a PPI. In particular, few patients who were newly started on a PPI had the online tool applied. This is likely because the tool was filled out on a volunteer basis and was applied most routinely during the admission medication reconciliation process. There were a number of other reasons why the tool was underused, including having the inpatient teams responsible for the data collection despite preexisting demands on their time and the lack of data from patients who were admitted and discharged before a thorough review of the indication for PPI use could take place. However, despite the incomplete use of the online tool, the demographics of patients who were assessed are similar to our usual patient population. As such, we believe the data captured are representative. Furthermore, despite the tool being underused, there remained a clearly objectified reduction in PPI exit prescriptions that occurred immediately postintervention and persisted throughout the entire period of study. Although our teams were not universally using the Web‐tool, it was clear that they were influenced by the project and were stopping unnecessary therapy.
Additionally, the absence of postdischarge follow‐up is also an important limitation. We had originally planned to audit all patients whose PPIs were stopped at 3 months postdischarge but were not systematically able to do so. We did, however, obtain a 1‐time convenience sample interview midway through the intervention. At that time, of 18 patients interviewed, all but 1 remained off of their PPI at 3 months postdischarge. The 1 restart was for reflux symptoms without a preceding trial of lifestyle therapy or H2 blocker.
One final limitation of this study design is that the implementation portion of the intervention took place at the beginning of the academic year. Trainees at the beginning of the year might differ from trainees at the end of the year in that they are more receptive to an educational intervention and less firmly fixed in their practice patterns. If one is considering implementing a similar strategy in their academic institution, we recommend doing so at the start of the academic year to capture the interest of new trainees, maximize the intervention's effectiveness, and establish good habits early in training.
CONCLUSION
We have demonstrated that in medical inpatients, both PPI use and misuse remain common; however, with a combined educational and Web‐based QI intervention, we could successfully decrease inappropriate exit prescriptions. Hospitalization, particularly at academic centers, should serve as an important point of contact for residents in training and expert faculty physicians to reconsider and rationalize patient medications. We should take the opportunity to engender a culture of responsibility for all of the medications that we represcribe at discharge, including an appraisal of the relevant harms and benefits, particularly when a medication is potentially unnecessary. We ought to then communicate the rationale for any changes to our community partners to maintain continuity of care. In this way, hospitalists can help treat the prescription indigestion that has become a common affliction in modern medicine.
Disclosure
Nothing to report.
- IMS Institute for Healthcare Informatics. Medicine Use and Shifting Costs of Healthcare. 2014. Available at: http://www.imshealth.com/deployedfiles/imshealth/Global/Content/Corporate/IMS%20Health%20Institute/Reports/Secure/IIHI_US_Use_of_Meds_for_2013.pdf. Accessed September 26, 2014.
- , , . National use of proton pump inhibitors from 2007 to 2011. JAMA Intern Med. 2014;174(11):1856–1858.
- Health Canada. Proton Pump Inhibitors (antacids): Possible Risk of Clostridium difficile‐Associated Diarrhea. 2012. Available at: http://www.healthycanadians.gc.ca/recall‐alert‐rappel‐avis/hc‐sc/2012/13651a‐eng.php. Accessed February 16, 2015.
- Health Canada. Proton Pump Inhibitors: Hypomagnesemia Accompanied by Hypocalcemia and Hypokalemia. 2011. Available at: http://www.hc‐sc.gc.ca/dhp‐mps/medeff/bulletin/carn‐bcei_v21n3‐eng.php#_Proton_pump_inhibitors. Accessed February 16, 2015.
- US Food and Drug Administration. FDA Drug Safety Communication: Possible Increased Risk of Fractures of the Hip, Wrist, and Spine With the Use of Proton Pump Inhibitors. 2012. Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213206.htm. Accessed February 15, 2015.
- US Food and Drug Administration. FDA Drug Safety Communication: Clostridium difficile‐Associated Diarrhea Can Be Associated With Stomach Acid Drugs Known as Proton Pump Inhibitors (PPIs). 2012. Available at: http://www.fda.gov/drugs/drugsafety/ucm290510.htm. Accessed February 15, 2015.
- , , . Meta‐analysis: proton pump inhibitor use and the risk of community‐acquired pneumonia. Aliment Pharmacol Ther. 2010;31(11):1165–1177.
- , , , et al. Proton pump inhibitors and risk of 1‐year mortality and rehospitalization in older patients discharged from acute care hospitals. JAMA Intern Med. 2013;173(7):518–523.
- , , , . Acid‐suppressive medication use and the risk for hospital‐acquired pneumonia. JAMA. 2009;301(20):2120–2128.
- , , , et al. Proton pump inhibitors and functional decline in older adults discharged from acute care hospitals. J Am Geriatr Soc. 2014;62(6):1110–1115.
- , , , , . Do hospitalists overuse proton pump inhibitors? Data from a contemporary cohort. J Hosp Med. 2014;9(11):731–733.
- , , , , , . Inappropriate prescribing of proton pump inhibitors in hospitalized patients. J Hosp Med. 2012;7(5):421–425.
- , , , , . Potential costs of inappropriate use of proton pump inhibitors. Am J Med Sci. 2014;347(6):446–451.
- , , , . Long‐term use of acid suppression started inappropriately during hospitalization. Aliment Pharmacol Ther. 2005;21(10):1203–1209.
- , , , , , . Continuation of proton pump inhibitors from hospital to community. Pharm World Sci. 2006;28(4):189–193.
- , , , , , . Hospitalist and primary care physician perspectives on medication management of chronic conditions for hospitalized patients. J Hosp Med. 2014;9(5):303–309.
- , , , et al. Antibacterial treatment of gastric ulcers associated with Helicobacter pylori. N Engl J Med. 1995;332(3):139–142.
- , , , et al. Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers. N Engl J Med. 2000;343(5):310–316.
- , , , et al. Lansoprazole for the prevention of recurrences of ulcer complications from long‐term low‐dose aspirin use. N Engl J Med. 2002;346(26):2033–2038.
- , . American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007;102(8):1808–1825.
- , , . Guidelines for prevention of NSAID‐related ulcer complications. Am J Gastroenterol. 2009;104(3):728–738.
- , , , Canadian consensus guidelines on long‐term nonsteroidal anti‐inflammatory drug therapy and the need for gastroprotection: benefits versus risks. Aliment Pharmacol Ther. 2009;29(5):481–496.
- , , , et al., The effects of guideline implementation for proton pump inhibitor prescription on two pulmonary medicine wards. Aliment Pharmacol Ther. 2009;29(2):213–221.
- , , , . Segmented regression analysis of interrupted time series studies in medication use research. J Clin Pharm Ther. 2002;27(4):299–309.
- , , . Overuse of acid‐suppressive therapy in hospitalized patients. Am J Gastroenterol. 2000;95(11):3118–3122.
- , , , . Proton pump inhibitors: a survey of prescribing in an Irish general hospital. Int J Clin Pract. 2005;59(1):31–34.
- , , . Overuse of proton pump inhibitors. J Clin Pharm Ther. 2000;25(5):333–340.
- , , , et al. Prevalence and appropriateness of drug prescriptions for peptic ulcer and gastro‐esophageal reflux disease in a cohort of hospitalized elderly. Eur J Intern Med. 2011;22(2):205–210.
- , , , . Inappropriate prescribing of proton pump inhibitors in primary care. Postgrad Med J. 2007;83(975):66–68.
- , , , , , . Inappropriate prescribing of proton pump inhibitors in older patients: effects of an educational strategy. Drugs Aging. 2012;29(8):681–690.
- , , , . Impact of academic detailing on proton pump inhibitor prescribing behaviour in a community hospital. Can Pharm J (Ott). 2011;144(2):66–71.
- , , , , , . Decreased acid suppression therapy overuse after education and medication reconciliation. Int J Clin Pract. 2013;67(1):60–65.
In 2013, there were more than 15 million Americans receiving proton pump inhibitors (PPIs),[1] with an associated drug cost of nearly $79 billion between 2007 and 2011.2 PPI use is reaching epidemic proportions, likely due to the medicalization of gastrointestinal symptoms coupled with pervasive marketing and academic detailing being performed by the pharmaceutical industry.
Although PPIs are generally considered safe, they are not as innocuous as many physicians believe. In 2011 and 2012, the US Food and Drug Administration and Health Canada, respectively, issued safety advisories regarding the use of these medications related to Clostridium difficile, fracture risk, and electrolyte derangement.[3, 4, 5, 6] There have also been numerous other harmful associations reported,[7, 8, 9, 10] suggesting it would be prudent to follow Health Canada's advice that: PPIs should be prescribed at the lowest dose and shortest duration of therapy appropriate to the condition being treated.[4] In many cases this implies stopping the PPI after an appropriate duration of therapy or attempting nonpharmacological or H2‐blocker therapy instead.
Nevertheless, despite numerous cautionary publications, PPI use for nonevidence‐based indications remains common. Because they are generally thought of as outpatient medications, PPIs are frequently continued in hospitalized patients, and inappropriate outpatient therapy is rarely addressed.[11, 12, 13] Likewise, inappropriate de novo use can also be observed during hospitalization and may continue on discharge.[13, 14, 15] Hospitalization may consequently present an opportunity to employ meaningful interventions targeting outpatient medication use.[16] We developed an opportune inpatient intervention targeting inappropriate PPI therapy.
Our study had 2 aims: first, to determine the magnitude of the problem in a contemporary Canadian medical inpatient population, and second, we sought to leverage the inpatient admission as an opportunity to promote change when the patient returned to the community through the application of an educational and web‐based quality‐improvement (QI) intervention.
METHODS
Patient Inclusion
Between January 2012 and December 2012, we included all consecutively admitted patients on our 46‐bed general medical clinical teaching unit belonging to a 417‐bed tertiary care teaching hospital in Montreal, Canada. There were no exclusion criteria. This time period was divided into 2 blocks: the preintervention control period from January 1 to June 3 and the intervention period from June 4 to December 16.
Intervention and Implementation Strategy
At the start of each academic period, we presented a 20‐minute information session on the benefits and harms of PPI use (see Supporting Information, Appendix, in the online version of this article). The unit's medical residents and faculty attended these rounds. The presentation described the project, consensus‐derived indications for PPI use, and potential adverse events attributable to PPIs (see Table 1 for indications based on internal consensus and similar studies[17, 18, 19, 20, 21, 22, 23]). All other indications were considered nonevidence based. At the end of the month, teams were given feedback on indications they provided using the Web tool and the proportion of patients they discharged on a PPI with and without indication.
|
| 1. Gastric or duodenal ulcer within the past 3 months |
| 2. Pathological hypersecretory conditions |
| 3. Gastroesophageal reflux disease with exacerbations within the last 3 months not responsive to H2 blockers and nonpharmacologic techniques |
| 4. Erosive esophagitis |
| 5. Recurring symptoms recently associated with severe indigestion within the last 3 months not responsive to H2 blocker or nonpharmacologic techniques |
| 6. Helicobacter pylori eradication |
| 7. Dual antiplatelet therapy |
| 8. Antiplatelet therapy with anticoagulants |
| 9. Antiplatelet or anticoagulant therapy with history of previous complicated ulcer |
| 10. Antiplatelet or NSAID with 2 of the following: concomitant systemic corticosteroids, age over 60 years, previous uncomplicated ulcer, concomitant NSAID, or antiplatelet/anticoagulant |
The process of evaluating and stopping PPIs was voluntary. Housestaff were encouraged to evaluate PPIs when ordering admission medications and upon preparing exit prescriptions. This was an opt‐in intervention. Once a patient on a PPI was identified, typically on admission to the unit, the indication for use could then be evaluated using the online tool, which was accessible on the internet via a link on all unit computers (see Supporting Information, Appendix, in the online version of this article).
The Web‐based tool was designed to be simple and informative. Users of the tool input anonymous data including comorbidities (check boxes provided). The tool collected the indication for PPI use, with available options including: the consensus‐derived evidence‐based indications, no identified indication, or free text. This was done purposefully to remind the teams of the consensus indications, with the goal that in choosing no identified indication the resident would consider cessation of unnecessary PPIs. The final step in the tool, discharge plan, presented the option of stopping the PPI in the absence of a satisfactory indication. We hypothesized that selecting this option would serve as an informal commitment to discontinuing the PPI during the creation of the discharge prescription; however, the tool was not automatically linked to these prescriptions.
If a home prescription was discontinued, the patient was counselled by the treating team and provided with an educational letter (see Supporting Information, Appendix, in the online version of this article), which was fastened to their discharge summary and given to the patient for delivery to all of their usual outpatient physician(s).
The design of the online tool was such that residents were to evaluate PPI use that would continue postdischarge from the hospital, rather than PPI use limited to the period of hospitalization.
Data Collection and Statistical Analysis
Data on baseline demographics and the specific indications for PPI use were collected through clinician interaction with the online tool. The proportion of patients on a PPI was ascertained through a separate data extraction of electronic discharge prescriptions. These involved medication reconciliation for all outpatient medications including whether or not they were continued, modified, or stopped. Thus, we could determine at discharge whether outpatient PPIs were continued or stopped or if a new PPI was initiated.
The proportion of patients admitted from home already receiving a PPI, those who received a new prescription for a PPI at discharge, and those whose PPI was stopped during admission were compared before and after the intervention using segmented regression analysis of an interrupted time series (see Supporting Information, Appendix, in the online version of this article).[24]
Post Hoc Power Calculations
For the pre‐post comparisons, given the preintervention number of admissions, proportions of PPI use in the community, new PPI use, and PPI discontinuation rates we would have had an 80% power to detect changes of 8.5%, 5%, and 5.5%, respectively.
Ethics
The McGill University Health Centre research ethics board approved this study. Informed consent was waived as the intervention was deemed to be best practice, and data collected were anonymous. Clinical consent was obtained by the treating team for all care decisions.
Funding
This initiative was conducted without any funding.
RESULTS
During the preintervention period, 464 patients were admitted, of whom 209 (45%) were taking a PPI prior to admission. During their hospitalization, an additional 53 patients (21% of nonusers) were newly prescribed a PPI that was continued at discharge. During the intervention period, a total of 640 patients were admitted, of whom 281 (44%) were taking a PPI prior to admission. During their hospitalization, 60 patients (17% of nonusers) were newly prescribed a PPI that was continued at discharge. Neither the monthly proportions admitted on PPIs from prior to admission (level P=0.59, slope P=0.46) or those newly initiated on a PPI (level P=0.36, slope P=0.18) were significantly different before compared to after the intervention. However, there was both a clinically and statistically significant difference in the proportion of preadmission PPIs that were discontinued at hospital discharge from a monthly mean of 7.7% (or 16/209) before intervention to 18.5% (or 52/281) afterward (Figure 1; level P=0.03, slope P=0.48).
During the intervention period, our teams prospectively captured PPI indications and patient comorbidities for 54% (152/281) of the patients admitted on a PPI using the online assessment tool. The baseline characteristics of the population in whom the online tool was applied are shown in Table 2. These patients had a mean age of 69.6 years, and 49% were male. Thirty‐two percent had diabetes, 20% had chronic renal insufficiency, and 13% had experienced a gastrointestinal hemorrhage within the 3 months prior to admission. It was frequent for PPI users to receive systemic antibiotics (44%) or to have diagnoses potentially associated with PPI use such as community‐acquired pneumonia (25%) or C difficile (11%).
| Characteristic | Value |
|---|---|
| |
| Age, y, mean (SD) | 69.615.1 |
| Male gender, N (%) | 75 (49) |
| Initiation of PPI, N (%) | |
| Prior to hospitalization | 127 (84) |
| During hospitalization | 10 (6) |
| In ICU | 7 (4) |
| In ER | 8 (5) |
| Comorbidities, N (%) | |
| Diabetes mellitus | 48 (32) |
| Chronic renal failure, GFR <45 | 29 (20) |
| GI bleed in the last 3 months | 20 (13) |
| No comorbidities | 11 (7) |
| Medications, N (%) | |
| Current antiplatelet agent | 67 (44) |
| Current corticosteroid use | 40 (26) |
| Current therapeutic anticoagulation | 35 (23) |
| Current NSAID use | 13 (8.5) |
| Current bisphosphonate | 13 (8.5) |
| Potential contraindications to PPI, N (%) | |
| Current antibiotic therapy | 67 (44) |
| Pneumonia | 38 (25) |
| Clostridium difficile infection ever | 16 (11) |
| Clostridium difficile infection on present admission | 9 (6) |
Fifty‐four percent (82/152) of patients in whom the online tool was applied had an evidence‐based indication (Table 3). The most common indication for PPI prescription was the receipt of antiplatelet/anticoagulant or nonsteroidal anti‐inflammatory drug with 2 other known risk factors for upper gastrointestinal bleeding (20%). In the remaining 46% (70/152) of patients, the prescription of a PPI was deemed nonevidence based. Of these, 34 (49%) had their PPI discontinued. When patients were approached to discontinue therapy, the rate of success was high, with only 2 refusals.
| Indications | N (%) |
|---|---|
| |
| Approved indications for therapy | |
| Antiplatelet or NSAID with 2 of the following: age >60 years, systemic corticosteroids, previous uncomplicated ulcer, NSAID, or antiplatelet/anticoagulant | 28 (20) |
| Gastric or duodenal ulcer within the past 3 months | 23 (15) |
| Antiplatelet therapy with anticoagulants | 17 (11) |
| GERD with exacerbations within the last 3 months | 17 (11) |
| Dual antiplatelet therapy | 7 (5) |
| Pathological hypersecretory conditions | 0 |
| Helicobactor pylori eradication | 0 |
| Total with consensus indications | 79 (54) |
| Other described indications for therapy | |
| No indication identified | 46 (30) |
| Othera | 22 (14) |
| Palliative patients GERD prophylaxis | 5 (3) |
| Total without consensus indications | 70 (46) |
DISCUSSION
In this prospective intervention, 44% of patients admitted to an acute‐care medical ward were prescribed a PPI prior to their admission. In the subgroup of patients for whom the indication for PPI use was recorded through our online tool, less than half had an evidence‐based indication for ongoing therapy. Our intervention was successful in increasing the proportion of patients in whom preadmission PPI prescriptions were stopped at discharge from an average of 7.7% in the preintervention phase to 18.5% during the intervention. This intervention is novel in that we were able to reduce active community prescriptions for PPIs in patients without obvious indication by nearly 50%.
Our population's rates of PPI prescription were consistent with previous reports,[11, 12, 13, 15, 25, 26, 27, 28] and it is clear that many hospitalized patients continue their PPIs at discharge without clear indications. We propose that hospitalization can serve as an opportunity to reassess the necessity of continuous PPI use. Previous systematic attempts to reduce inappropriate PPI prescriptions in hospital have met with varied success. Several of these studies were unable to achieve a demonstrable effect.[23, 29, 30, 31] In contrast, Hamzat et al.[30] described a successful educational intervention targeting inpatients on a geriatric ward. A 4‐week educational strategy was employed, and they were able to discontinue PPIs in 10 of 60 (17%) patients without indication during a limited period of study. Another successful intervention by Gupta et al.[32] involved a before‐and‐after study combining a half‐hour physician education session with the introduction of a medication reconciliation tool. They showed a decrease in inappropriate discharge prescriptions of 50%. Not only did our study demonstrate an equally sizable reduction in inappropriate discharge prescriptions, but we also employed a more methodologically sound time‐series analysis to control for unmeasured contemporaneous factors such as rotating staff practices or monthly differences in patient composition. We demonstrated an immediate and sustained improvement in performance that lasted over 6 months. Furthermore, in contrast to other interventions, which addressed inappropriate inpatient use persisting on discharge, our intervention also addressed the appropriateness of PPI use that antedated hospitalization.
There are common themes to the successful programs. The more time spent educating and reminding the prescribing physicians, the more successful the intervention. Nonetheless, we believe our intervention is not onerous or overly time consuming. We performed a short presentation each month to educate rotating physicians, and the tool took less than 1 minute to complete once the information on PPI indication was available. Frequent education sessions may be initially necessary given the comfort that many physicians have developed in prescribing PPIs. A further prerequisite for success may be a familiarity with PPI indications and potential adverse effects. Without this, the intervention may not show a demonstrable effect, as was seen in a study of pulmonologists.[23] We hypothesize that some subspecialist physicians may not have the same appreciation of the adverse effects of PPIs nor the confidence to stop them when not indicated, as compared to general internists or hospitalists.
The proportion of patients with newly initiated PPIs at discharge decreased after the intervention, but this did not reach statistical significance. Our study's power may have precluded this. However, we had also previously put in place unpublished interventions to diminish inappropriate gastric prophylaxis in the hospital, which may have diminished the effect of this intervention.
Unfortunately, although we demonstrated a clinically significant effect on PPI exit prescription rates, we still found that nearly half of the patients who were evaluated using the online tool were discharged on PPIs despite our physicians' acknowledgment that they had no identifiable indication. It is possible that clinicians do not feel comfortable stopping these medications, owing to a fear that there is an indication that they are not aware of. In certain cases, it is possible that a reappraisal of the benefits, risks, and costs might reassure the clinician that they could safely stop the drug; however, therapeutic inertia is often hard to overcome.
Limitations
Our single‐center study occurred over a limited time period and examined a sample of patients that were assessed based on convenience. Other limitations included the uptake of the online tool, which was only 54% of patients on a PPI. In particular, few patients who were newly started on a PPI had the online tool applied. This is likely because the tool was filled out on a volunteer basis and was applied most routinely during the admission medication reconciliation process. There were a number of other reasons why the tool was underused, including having the inpatient teams responsible for the data collection despite preexisting demands on their time and the lack of data from patients who were admitted and discharged before a thorough review of the indication for PPI use could take place. However, despite the incomplete use of the online tool, the demographics of patients who were assessed are similar to our usual patient population. As such, we believe the data captured are representative. Furthermore, despite the tool being underused, there remained a clearly objectified reduction in PPI exit prescriptions that occurred immediately postintervention and persisted throughout the entire period of study. Although our teams were not universally using the Web‐tool, it was clear that they were influenced by the project and were stopping unnecessary therapy.
Additionally, the absence of postdischarge follow‐up is also an important limitation. We had originally planned to audit all patients whose PPIs were stopped at 3 months postdischarge but were not systematically able to do so. We did, however, obtain a 1‐time convenience sample interview midway through the intervention. At that time, of 18 patients interviewed, all but 1 remained off of their PPI at 3 months postdischarge. The 1 restart was for reflux symptoms without a preceding trial of lifestyle therapy or H2 blocker.
One final limitation of this study design is that the implementation portion of the intervention took place at the beginning of the academic year. Trainees at the beginning of the year might differ from trainees at the end of the year in that they are more receptive to an educational intervention and less firmly fixed in their practice patterns. If one is considering implementing a similar strategy in their academic institution, we recommend doing so at the start of the academic year to capture the interest of new trainees, maximize the intervention's effectiveness, and establish good habits early in training.
CONCLUSION
We have demonstrated that in medical inpatients, both PPI use and misuse remain common; however, with a combined educational and Web‐based QI intervention, we could successfully decrease inappropriate exit prescriptions. Hospitalization, particularly at academic centers, should serve as an important point of contact for residents in training and expert faculty physicians to reconsider and rationalize patient medications. We should take the opportunity to engender a culture of responsibility for all of the medications that we represcribe at discharge, including an appraisal of the relevant harms and benefits, particularly when a medication is potentially unnecessary. We ought to then communicate the rationale for any changes to our community partners to maintain continuity of care. In this way, hospitalists can help treat the prescription indigestion that has become a common affliction in modern medicine.
Disclosure
Nothing to report.
In 2013, there were more than 15 million Americans receiving proton pump inhibitors (PPIs),[1] with an associated drug cost of nearly $79 billion between 2007 and 2011.2 PPI use is reaching epidemic proportions, likely due to the medicalization of gastrointestinal symptoms coupled with pervasive marketing and academic detailing being performed by the pharmaceutical industry.
Although PPIs are generally considered safe, they are not as innocuous as many physicians believe. In 2011 and 2012, the US Food and Drug Administration and Health Canada, respectively, issued safety advisories regarding the use of these medications related to Clostridium difficile, fracture risk, and electrolyte derangement.[3, 4, 5, 6] There have also been numerous other harmful associations reported,[7, 8, 9, 10] suggesting it would be prudent to follow Health Canada's advice that: PPIs should be prescribed at the lowest dose and shortest duration of therapy appropriate to the condition being treated.[4] In many cases this implies stopping the PPI after an appropriate duration of therapy or attempting nonpharmacological or H2‐blocker therapy instead.
Nevertheless, despite numerous cautionary publications, PPI use for nonevidence‐based indications remains common. Because they are generally thought of as outpatient medications, PPIs are frequently continued in hospitalized patients, and inappropriate outpatient therapy is rarely addressed.[11, 12, 13] Likewise, inappropriate de novo use can also be observed during hospitalization and may continue on discharge.[13, 14, 15] Hospitalization may consequently present an opportunity to employ meaningful interventions targeting outpatient medication use.[16] We developed an opportune inpatient intervention targeting inappropriate PPI therapy.
Our study had 2 aims: first, to determine the magnitude of the problem in a contemporary Canadian medical inpatient population, and second, we sought to leverage the inpatient admission as an opportunity to promote change when the patient returned to the community through the application of an educational and web‐based quality‐improvement (QI) intervention.
METHODS
Patient Inclusion
Between January 2012 and December 2012, we included all consecutively admitted patients on our 46‐bed general medical clinical teaching unit belonging to a 417‐bed tertiary care teaching hospital in Montreal, Canada. There were no exclusion criteria. This time period was divided into 2 blocks: the preintervention control period from January 1 to June 3 and the intervention period from June 4 to December 16.
Intervention and Implementation Strategy
At the start of each academic period, we presented a 20‐minute information session on the benefits and harms of PPI use (see Supporting Information, Appendix, in the online version of this article). The unit's medical residents and faculty attended these rounds. The presentation described the project, consensus‐derived indications for PPI use, and potential adverse events attributable to PPIs (see Table 1 for indications based on internal consensus and similar studies[17, 18, 19, 20, 21, 22, 23]). All other indications were considered nonevidence based. At the end of the month, teams were given feedback on indications they provided using the Web tool and the proportion of patients they discharged on a PPI with and without indication.
|
| 1. Gastric or duodenal ulcer within the past 3 months |
| 2. Pathological hypersecretory conditions |
| 3. Gastroesophageal reflux disease with exacerbations within the last 3 months not responsive to H2 blockers and nonpharmacologic techniques |
| 4. Erosive esophagitis |
| 5. Recurring symptoms recently associated with severe indigestion within the last 3 months not responsive to H2 blocker or nonpharmacologic techniques |
| 6. Helicobacter pylori eradication |
| 7. Dual antiplatelet therapy |
| 8. Antiplatelet therapy with anticoagulants |
| 9. Antiplatelet or anticoagulant therapy with history of previous complicated ulcer |
| 10. Antiplatelet or NSAID with 2 of the following: concomitant systemic corticosteroids, age over 60 years, previous uncomplicated ulcer, concomitant NSAID, or antiplatelet/anticoagulant |
The process of evaluating and stopping PPIs was voluntary. Housestaff were encouraged to evaluate PPIs when ordering admission medications and upon preparing exit prescriptions. This was an opt‐in intervention. Once a patient on a PPI was identified, typically on admission to the unit, the indication for use could then be evaluated using the online tool, which was accessible on the internet via a link on all unit computers (see Supporting Information, Appendix, in the online version of this article).
The Web‐based tool was designed to be simple and informative. Users of the tool input anonymous data including comorbidities (check boxes provided). The tool collected the indication for PPI use, with available options including: the consensus‐derived evidence‐based indications, no identified indication, or free text. This was done purposefully to remind the teams of the consensus indications, with the goal that in choosing no identified indication the resident would consider cessation of unnecessary PPIs. The final step in the tool, discharge plan, presented the option of stopping the PPI in the absence of a satisfactory indication. We hypothesized that selecting this option would serve as an informal commitment to discontinuing the PPI during the creation of the discharge prescription; however, the tool was not automatically linked to these prescriptions.
If a home prescription was discontinued, the patient was counselled by the treating team and provided with an educational letter (see Supporting Information, Appendix, in the online version of this article), which was fastened to their discharge summary and given to the patient for delivery to all of their usual outpatient physician(s).
The design of the online tool was such that residents were to evaluate PPI use that would continue postdischarge from the hospital, rather than PPI use limited to the period of hospitalization.
Data Collection and Statistical Analysis
Data on baseline demographics and the specific indications for PPI use were collected through clinician interaction with the online tool. The proportion of patients on a PPI was ascertained through a separate data extraction of electronic discharge prescriptions. These involved medication reconciliation for all outpatient medications including whether or not they were continued, modified, or stopped. Thus, we could determine at discharge whether outpatient PPIs were continued or stopped or if a new PPI was initiated.
The proportion of patients admitted from home already receiving a PPI, those who received a new prescription for a PPI at discharge, and those whose PPI was stopped during admission were compared before and after the intervention using segmented regression analysis of an interrupted time series (see Supporting Information, Appendix, in the online version of this article).[24]
Post Hoc Power Calculations
For the pre‐post comparisons, given the preintervention number of admissions, proportions of PPI use in the community, new PPI use, and PPI discontinuation rates we would have had an 80% power to detect changes of 8.5%, 5%, and 5.5%, respectively.
Ethics
The McGill University Health Centre research ethics board approved this study. Informed consent was waived as the intervention was deemed to be best practice, and data collected were anonymous. Clinical consent was obtained by the treating team for all care decisions.
Funding
This initiative was conducted without any funding.
RESULTS
During the preintervention period, 464 patients were admitted, of whom 209 (45%) were taking a PPI prior to admission. During their hospitalization, an additional 53 patients (21% of nonusers) were newly prescribed a PPI that was continued at discharge. During the intervention period, a total of 640 patients were admitted, of whom 281 (44%) were taking a PPI prior to admission. During their hospitalization, 60 patients (17% of nonusers) were newly prescribed a PPI that was continued at discharge. Neither the monthly proportions admitted on PPIs from prior to admission (level P=0.59, slope P=0.46) or those newly initiated on a PPI (level P=0.36, slope P=0.18) were significantly different before compared to after the intervention. However, there was both a clinically and statistically significant difference in the proportion of preadmission PPIs that were discontinued at hospital discharge from a monthly mean of 7.7% (or 16/209) before intervention to 18.5% (or 52/281) afterward (Figure 1; level P=0.03, slope P=0.48).
During the intervention period, our teams prospectively captured PPI indications and patient comorbidities for 54% (152/281) of the patients admitted on a PPI using the online assessment tool. The baseline characteristics of the population in whom the online tool was applied are shown in Table 2. These patients had a mean age of 69.6 years, and 49% were male. Thirty‐two percent had diabetes, 20% had chronic renal insufficiency, and 13% had experienced a gastrointestinal hemorrhage within the 3 months prior to admission. It was frequent for PPI users to receive systemic antibiotics (44%) or to have diagnoses potentially associated with PPI use such as community‐acquired pneumonia (25%) or C difficile (11%).
| Characteristic | Value |
|---|---|
| |
| Age, y, mean (SD) | 69.615.1 |
| Male gender, N (%) | 75 (49) |
| Initiation of PPI, N (%) | |
| Prior to hospitalization | 127 (84) |
| During hospitalization | 10 (6) |
| In ICU | 7 (4) |
| In ER | 8 (5) |
| Comorbidities, N (%) | |
| Diabetes mellitus | 48 (32) |
| Chronic renal failure, GFR <45 | 29 (20) |
| GI bleed in the last 3 months | 20 (13) |
| No comorbidities | 11 (7) |
| Medications, N (%) | |
| Current antiplatelet agent | 67 (44) |
| Current corticosteroid use | 40 (26) |
| Current therapeutic anticoagulation | 35 (23) |
| Current NSAID use | 13 (8.5) |
| Current bisphosphonate | 13 (8.5) |
| Potential contraindications to PPI, N (%) | |
| Current antibiotic therapy | 67 (44) |
| Pneumonia | 38 (25) |
| Clostridium difficile infection ever | 16 (11) |
| Clostridium difficile infection on present admission | 9 (6) |
Fifty‐four percent (82/152) of patients in whom the online tool was applied had an evidence‐based indication (Table 3). The most common indication for PPI prescription was the receipt of antiplatelet/anticoagulant or nonsteroidal anti‐inflammatory drug with 2 other known risk factors for upper gastrointestinal bleeding (20%). In the remaining 46% (70/152) of patients, the prescription of a PPI was deemed nonevidence based. Of these, 34 (49%) had their PPI discontinued. When patients were approached to discontinue therapy, the rate of success was high, with only 2 refusals.
| Indications | N (%) |
|---|---|
| |
| Approved indications for therapy | |
| Antiplatelet or NSAID with 2 of the following: age >60 years, systemic corticosteroids, previous uncomplicated ulcer, NSAID, or antiplatelet/anticoagulant | 28 (20) |
| Gastric or duodenal ulcer within the past 3 months | 23 (15) |
| Antiplatelet therapy with anticoagulants | 17 (11) |
| GERD with exacerbations within the last 3 months | 17 (11) |
| Dual antiplatelet therapy | 7 (5) |
| Pathological hypersecretory conditions | 0 |
| Helicobactor pylori eradication | 0 |
| Total with consensus indications | 79 (54) |
| Other described indications for therapy | |
| No indication identified | 46 (30) |
| Othera | 22 (14) |
| Palliative patients GERD prophylaxis | 5 (3) |
| Total without consensus indications | 70 (46) |
DISCUSSION
In this prospective intervention, 44% of patients admitted to an acute‐care medical ward were prescribed a PPI prior to their admission. In the subgroup of patients for whom the indication for PPI use was recorded through our online tool, less than half had an evidence‐based indication for ongoing therapy. Our intervention was successful in increasing the proportion of patients in whom preadmission PPI prescriptions were stopped at discharge from an average of 7.7% in the preintervention phase to 18.5% during the intervention. This intervention is novel in that we were able to reduce active community prescriptions for PPIs in patients without obvious indication by nearly 50%.
Our population's rates of PPI prescription were consistent with previous reports,[11, 12, 13, 15, 25, 26, 27, 28] and it is clear that many hospitalized patients continue their PPIs at discharge without clear indications. We propose that hospitalization can serve as an opportunity to reassess the necessity of continuous PPI use. Previous systematic attempts to reduce inappropriate PPI prescriptions in hospital have met with varied success. Several of these studies were unable to achieve a demonstrable effect.[23, 29, 30, 31] In contrast, Hamzat et al.[30] described a successful educational intervention targeting inpatients on a geriatric ward. A 4‐week educational strategy was employed, and they were able to discontinue PPIs in 10 of 60 (17%) patients without indication during a limited period of study. Another successful intervention by Gupta et al.[32] involved a before‐and‐after study combining a half‐hour physician education session with the introduction of a medication reconciliation tool. They showed a decrease in inappropriate discharge prescriptions of 50%. Not only did our study demonstrate an equally sizable reduction in inappropriate discharge prescriptions, but we also employed a more methodologically sound time‐series analysis to control for unmeasured contemporaneous factors such as rotating staff practices or monthly differences in patient composition. We demonstrated an immediate and sustained improvement in performance that lasted over 6 months. Furthermore, in contrast to other interventions, which addressed inappropriate inpatient use persisting on discharge, our intervention also addressed the appropriateness of PPI use that antedated hospitalization.
There are common themes to the successful programs. The more time spent educating and reminding the prescribing physicians, the more successful the intervention. Nonetheless, we believe our intervention is not onerous or overly time consuming. We performed a short presentation each month to educate rotating physicians, and the tool took less than 1 minute to complete once the information on PPI indication was available. Frequent education sessions may be initially necessary given the comfort that many physicians have developed in prescribing PPIs. A further prerequisite for success may be a familiarity with PPI indications and potential adverse effects. Without this, the intervention may not show a demonstrable effect, as was seen in a study of pulmonologists.[23] We hypothesize that some subspecialist physicians may not have the same appreciation of the adverse effects of PPIs nor the confidence to stop them when not indicated, as compared to general internists or hospitalists.
The proportion of patients with newly initiated PPIs at discharge decreased after the intervention, but this did not reach statistical significance. Our study's power may have precluded this. However, we had also previously put in place unpublished interventions to diminish inappropriate gastric prophylaxis in the hospital, which may have diminished the effect of this intervention.
Unfortunately, although we demonstrated a clinically significant effect on PPI exit prescription rates, we still found that nearly half of the patients who were evaluated using the online tool were discharged on PPIs despite our physicians' acknowledgment that they had no identifiable indication. It is possible that clinicians do not feel comfortable stopping these medications, owing to a fear that there is an indication that they are not aware of. In certain cases, it is possible that a reappraisal of the benefits, risks, and costs might reassure the clinician that they could safely stop the drug; however, therapeutic inertia is often hard to overcome.
Limitations
Our single‐center study occurred over a limited time period and examined a sample of patients that were assessed based on convenience. Other limitations included the uptake of the online tool, which was only 54% of patients on a PPI. In particular, few patients who were newly started on a PPI had the online tool applied. This is likely because the tool was filled out on a volunteer basis and was applied most routinely during the admission medication reconciliation process. There were a number of other reasons why the tool was underused, including having the inpatient teams responsible for the data collection despite preexisting demands on their time and the lack of data from patients who were admitted and discharged before a thorough review of the indication for PPI use could take place. However, despite the incomplete use of the online tool, the demographics of patients who were assessed are similar to our usual patient population. As such, we believe the data captured are representative. Furthermore, despite the tool being underused, there remained a clearly objectified reduction in PPI exit prescriptions that occurred immediately postintervention and persisted throughout the entire period of study. Although our teams were not universally using the Web‐tool, it was clear that they were influenced by the project and were stopping unnecessary therapy.
Additionally, the absence of postdischarge follow‐up is also an important limitation. We had originally planned to audit all patients whose PPIs were stopped at 3 months postdischarge but were not systematically able to do so. We did, however, obtain a 1‐time convenience sample interview midway through the intervention. At that time, of 18 patients interviewed, all but 1 remained off of their PPI at 3 months postdischarge. The 1 restart was for reflux symptoms without a preceding trial of lifestyle therapy or H2 blocker.
One final limitation of this study design is that the implementation portion of the intervention took place at the beginning of the academic year. Trainees at the beginning of the year might differ from trainees at the end of the year in that they are more receptive to an educational intervention and less firmly fixed in their practice patterns. If one is considering implementing a similar strategy in their academic institution, we recommend doing so at the start of the academic year to capture the interest of new trainees, maximize the intervention's effectiveness, and establish good habits early in training.
CONCLUSION
We have demonstrated that in medical inpatients, both PPI use and misuse remain common; however, with a combined educational and Web‐based QI intervention, we could successfully decrease inappropriate exit prescriptions. Hospitalization, particularly at academic centers, should serve as an important point of contact for residents in training and expert faculty physicians to reconsider and rationalize patient medications. We should take the opportunity to engender a culture of responsibility for all of the medications that we represcribe at discharge, including an appraisal of the relevant harms and benefits, particularly when a medication is potentially unnecessary. We ought to then communicate the rationale for any changes to our community partners to maintain continuity of care. In this way, hospitalists can help treat the prescription indigestion that has become a common affliction in modern medicine.
Disclosure
Nothing to report.
- IMS Institute for Healthcare Informatics. Medicine Use and Shifting Costs of Healthcare. 2014. Available at: http://www.imshealth.com/deployedfiles/imshealth/Global/Content/Corporate/IMS%20Health%20Institute/Reports/Secure/IIHI_US_Use_of_Meds_for_2013.pdf. Accessed September 26, 2014.
- , , . National use of proton pump inhibitors from 2007 to 2011. JAMA Intern Med. 2014;174(11):1856–1858.
- Health Canada. Proton Pump Inhibitors (antacids): Possible Risk of Clostridium difficile‐Associated Diarrhea. 2012. Available at: http://www.healthycanadians.gc.ca/recall‐alert‐rappel‐avis/hc‐sc/2012/13651a‐eng.php. Accessed February 16, 2015.
- Health Canada. Proton Pump Inhibitors: Hypomagnesemia Accompanied by Hypocalcemia and Hypokalemia. 2011. Available at: http://www.hc‐sc.gc.ca/dhp‐mps/medeff/bulletin/carn‐bcei_v21n3‐eng.php#_Proton_pump_inhibitors. Accessed February 16, 2015.
- US Food and Drug Administration. FDA Drug Safety Communication: Possible Increased Risk of Fractures of the Hip, Wrist, and Spine With the Use of Proton Pump Inhibitors. 2012. Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213206.htm. Accessed February 15, 2015.
- US Food and Drug Administration. FDA Drug Safety Communication: Clostridium difficile‐Associated Diarrhea Can Be Associated With Stomach Acid Drugs Known as Proton Pump Inhibitors (PPIs). 2012. Available at: http://www.fda.gov/drugs/drugsafety/ucm290510.htm. Accessed February 15, 2015.
- , , . Meta‐analysis: proton pump inhibitor use and the risk of community‐acquired pneumonia. Aliment Pharmacol Ther. 2010;31(11):1165–1177.
- , , , et al. Proton pump inhibitors and risk of 1‐year mortality and rehospitalization in older patients discharged from acute care hospitals. JAMA Intern Med. 2013;173(7):518–523.
- , , , . Acid‐suppressive medication use and the risk for hospital‐acquired pneumonia. JAMA. 2009;301(20):2120–2128.
- , , , et al. Proton pump inhibitors and functional decline in older adults discharged from acute care hospitals. J Am Geriatr Soc. 2014;62(6):1110–1115.
- , , , , . Do hospitalists overuse proton pump inhibitors? Data from a contemporary cohort. J Hosp Med. 2014;9(11):731–733.
- , , , , , . Inappropriate prescribing of proton pump inhibitors in hospitalized patients. J Hosp Med. 2012;7(5):421–425.
- , , , , . Potential costs of inappropriate use of proton pump inhibitors. Am J Med Sci. 2014;347(6):446–451.
- , , , . Long‐term use of acid suppression started inappropriately during hospitalization. Aliment Pharmacol Ther. 2005;21(10):1203–1209.
- , , , , , . Continuation of proton pump inhibitors from hospital to community. Pharm World Sci. 2006;28(4):189–193.
- , , , , , . Hospitalist and primary care physician perspectives on medication management of chronic conditions for hospitalized patients. J Hosp Med. 2014;9(5):303–309.
- , , , et al. Antibacterial treatment of gastric ulcers associated with Helicobacter pylori. N Engl J Med. 1995;332(3):139–142.
- , , , et al. Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers. N Engl J Med. 2000;343(5):310–316.
- , , , et al. Lansoprazole for the prevention of recurrences of ulcer complications from long‐term low‐dose aspirin use. N Engl J Med. 2002;346(26):2033–2038.
- , . American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007;102(8):1808–1825.
- , , . Guidelines for prevention of NSAID‐related ulcer complications. Am J Gastroenterol. 2009;104(3):728–738.
- , , , Canadian consensus guidelines on long‐term nonsteroidal anti‐inflammatory drug therapy and the need for gastroprotection: benefits versus risks. Aliment Pharmacol Ther. 2009;29(5):481–496.
- , , , et al., The effects of guideline implementation for proton pump inhibitor prescription on two pulmonary medicine wards. Aliment Pharmacol Ther. 2009;29(2):213–221.
- , , , . Segmented regression analysis of interrupted time series studies in medication use research. J Clin Pharm Ther. 2002;27(4):299–309.
- , , . Overuse of acid‐suppressive therapy in hospitalized patients. Am J Gastroenterol. 2000;95(11):3118–3122.
- , , , . Proton pump inhibitors: a survey of prescribing in an Irish general hospital. Int J Clin Pract. 2005;59(1):31–34.
- , , . Overuse of proton pump inhibitors. J Clin Pharm Ther. 2000;25(5):333–340.
- , , , et al. Prevalence and appropriateness of drug prescriptions for peptic ulcer and gastro‐esophageal reflux disease in a cohort of hospitalized elderly. Eur J Intern Med. 2011;22(2):205–210.
- , , , . Inappropriate prescribing of proton pump inhibitors in primary care. Postgrad Med J. 2007;83(975):66–68.
- , , , , , . Inappropriate prescribing of proton pump inhibitors in older patients: effects of an educational strategy. Drugs Aging. 2012;29(8):681–690.
- , , , . Impact of academic detailing on proton pump inhibitor prescribing behaviour in a community hospital. Can Pharm J (Ott). 2011;144(2):66–71.
- , , , , , . Decreased acid suppression therapy overuse after education and medication reconciliation. Int J Clin Pract. 2013;67(1):60–65.
- IMS Institute for Healthcare Informatics. Medicine Use and Shifting Costs of Healthcare. 2014. Available at: http://www.imshealth.com/deployedfiles/imshealth/Global/Content/Corporate/IMS%20Health%20Institute/Reports/Secure/IIHI_US_Use_of_Meds_for_2013.pdf. Accessed September 26, 2014.
- , , . National use of proton pump inhibitors from 2007 to 2011. JAMA Intern Med. 2014;174(11):1856–1858.
- Health Canada. Proton Pump Inhibitors (antacids): Possible Risk of Clostridium difficile‐Associated Diarrhea. 2012. Available at: http://www.healthycanadians.gc.ca/recall‐alert‐rappel‐avis/hc‐sc/2012/13651a‐eng.php. Accessed February 16, 2015.
- Health Canada. Proton Pump Inhibitors: Hypomagnesemia Accompanied by Hypocalcemia and Hypokalemia. 2011. Available at: http://www.hc‐sc.gc.ca/dhp‐mps/medeff/bulletin/carn‐bcei_v21n3‐eng.php#_Proton_pump_inhibitors. Accessed February 16, 2015.
- US Food and Drug Administration. FDA Drug Safety Communication: Possible Increased Risk of Fractures of the Hip, Wrist, and Spine With the Use of Proton Pump Inhibitors. 2012. Available at: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm213206.htm. Accessed February 15, 2015.
- US Food and Drug Administration. FDA Drug Safety Communication: Clostridium difficile‐Associated Diarrhea Can Be Associated With Stomach Acid Drugs Known as Proton Pump Inhibitors (PPIs). 2012. Available at: http://www.fda.gov/drugs/drugsafety/ucm290510.htm. Accessed February 15, 2015.
- , , . Meta‐analysis: proton pump inhibitor use and the risk of community‐acquired pneumonia. Aliment Pharmacol Ther. 2010;31(11):1165–1177.
- , , , et al. Proton pump inhibitors and risk of 1‐year mortality and rehospitalization in older patients discharged from acute care hospitals. JAMA Intern Med. 2013;173(7):518–523.
- , , , . Acid‐suppressive medication use and the risk for hospital‐acquired pneumonia. JAMA. 2009;301(20):2120–2128.
- , , , et al. Proton pump inhibitors and functional decline in older adults discharged from acute care hospitals. J Am Geriatr Soc. 2014;62(6):1110–1115.
- , , , , . Do hospitalists overuse proton pump inhibitors? Data from a contemporary cohort. J Hosp Med. 2014;9(11):731–733.
- , , , , , . Inappropriate prescribing of proton pump inhibitors in hospitalized patients. J Hosp Med. 2012;7(5):421–425.
- , , , , . Potential costs of inappropriate use of proton pump inhibitors. Am J Med Sci. 2014;347(6):446–451.
- , , , . Long‐term use of acid suppression started inappropriately during hospitalization. Aliment Pharmacol Ther. 2005;21(10):1203–1209.
- , , , , , . Continuation of proton pump inhibitors from hospital to community. Pharm World Sci. 2006;28(4):189–193.
- , , , , , . Hospitalist and primary care physician perspectives on medication management of chronic conditions for hospitalized patients. J Hosp Med. 2014;9(5):303–309.
- , , , et al. Antibacterial treatment of gastric ulcers associated with Helicobacter pylori. N Engl J Med. 1995;332(3):139–142.
- , , , et al. Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers. N Engl J Med. 2000;343(5):310–316.
- , , , et al. Lansoprazole for the prevention of recurrences of ulcer complications from long‐term low‐dose aspirin use. N Engl J Med. 2002;346(26):2033–2038.
- , . American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007;102(8):1808–1825.
- , , . Guidelines for prevention of NSAID‐related ulcer complications. Am J Gastroenterol. 2009;104(3):728–738.
- , , , Canadian consensus guidelines on long‐term nonsteroidal anti‐inflammatory drug therapy and the need for gastroprotection: benefits versus risks. Aliment Pharmacol Ther. 2009;29(5):481–496.
- , , , et al., The effects of guideline implementation for proton pump inhibitor prescription on two pulmonary medicine wards. Aliment Pharmacol Ther. 2009;29(2):213–221.
- , , , . Segmented regression analysis of interrupted time series studies in medication use research. J Clin Pharm Ther. 2002;27(4):299–309.
- , , . Overuse of acid‐suppressive therapy in hospitalized patients. Am J Gastroenterol. 2000;95(11):3118–3122.
- , , , . Proton pump inhibitors: a survey of prescribing in an Irish general hospital. Int J Clin Pract. 2005;59(1):31–34.
- , , . Overuse of proton pump inhibitors. J Clin Pharm Ther. 2000;25(5):333–340.
- , , , et al. Prevalence and appropriateness of drug prescriptions for peptic ulcer and gastro‐esophageal reflux disease in a cohort of hospitalized elderly. Eur J Intern Med. 2011;22(2):205–210.
- , , , . Inappropriate prescribing of proton pump inhibitors in primary care. Postgrad Med J. 2007;83(975):66–68.
- , , , , , . Inappropriate prescribing of proton pump inhibitors in older patients: effects of an educational strategy. Drugs Aging. 2012;29(8):681–690.
- , , , . Impact of academic detailing on proton pump inhibitor prescribing behaviour in a community hospital. Can Pharm J (Ott). 2011;144(2):66–71.
- , , , , , . Decreased acid suppression therapy overuse after education and medication reconciliation. Int J Clin Pract. 2013;67(1):60–65.
© 2015 Society of Hospital Medicine
5 reasons why EHRs can’t be called failures
Much has been said about the failures of electronic health records. The shortcomings discussed have ranged from lack of cost benefits to interoperability with medical devices and security of interoperability with medical devices. We use IT via computers or smartphones daily for social, financial, or consumer aspects of lives. Health care has lagged behind other sectors of society in the adoption of digital technology because of regulatory issues, cost, and resistance to change. There are many positive aspects of EHRs, some more obvious than others.
They are what patients expect.
Patients live in the digital world. Seventy-eight percent of office-based physicians use an EHR, according to a study in the journal Health Affairs. Patients expect that their test results and records are easily accessible by all their providers. The promise of interoperability – the easy digital transfer of data from one data source or EHR system to another – has yet to be realized. This is one of the fundamental potential benefits of digital health technology. HIMSS, an advocacy organization focused on better health with information technology, has sent to Congress its recommendations on achieving interoperability within the next 3 years. This is a pivotal issue in creating the EHR envisioned by both patients and physicians.
They can be used to mitigate risk management.
Adoption of any significant change in health care practice presents challenges specifically with regards to risk management. HIPAA privacy regulations and security are of paramount importance. Most risk managers deal with legal issues after an incident has occurred. Digital health technologies can also potentially mitigate risk.
They can (Yes!) enhance the patient encounter.
While many physicians believe that EHRs destroy the patient encounter, there is another way of viewing the interaction. It all depends upon how it is presented in the office. The computer screen may impede the all-important eye contact between the physician and patient (either because of the physical presence of the screen or the physician’s persistent gaze at it). This is a surefire recipe for disengagement and subsequent destruction of the patient-physician relationship. However, the introduction of the computer (asking permission to use it) with physician and patient triangulated with the screen produces a care team atmosphere. Demonstrating the EHR’s functionality while highlighting pertinent clinical information provides a positive experience for both participants.
They brought health care into the digital age.
EHRs are not the face of all of digital health technologies. They do represent the hub around which other technologies need to flow, because this is where the patient interfaces (pun intended) with the physician. Digital technologies will enhance patient engagement. EHRs are the first experience many physicians have with digital health technologies, and they have yet to fulfill their intended goals. They are in their first iteration. Physician groups and health care enterprises have made themselves heard to the EHR vendors and change is coming. Other digital health technologies are here and will improve health care on many fronts. They themselves will transform the EHR into a more useful clinical tool, which will increase patient education, engagement, and connectivity.
They will be much different and better in the near future.
The American Medical Association got it right, in my opinion, with respect to its recommendations for design overhaul of EHRs. The organization outlined an extension of its study with the Rand Corp. and listed priorities of what should constitute design overhaul of the EHR. These include the incorporation of tools that support team-based care, promotion of care coordination among providers, product modularity and ability for configuration, the reduction of cognitive workload, the promotion of data liquidity, the facilitation of digital and mobile patient engagement, and the ability to expedite user input into design and postimplementation feedback.
As digital technology becomes a more substantive part of health care, there will be a need for physician IT champions who can make this process easier and more fulfilling for others. I look forward to seeing this happen.
Dr. Scher is an electrophysiologist with the Heart Group of Lancaster (Pa.) General Health. He is also director of DLS Healthcare Consulting, Harrisburg, Pa., and clinical associate professor of medicine at the Pennsylvania State University, Hershey.
Much has been said about the failures of electronic health records. The shortcomings discussed have ranged from lack of cost benefits to interoperability with medical devices and security of interoperability with medical devices. We use IT via computers or smartphones daily for social, financial, or consumer aspects of lives. Health care has lagged behind other sectors of society in the adoption of digital technology because of regulatory issues, cost, and resistance to change. There are many positive aspects of EHRs, some more obvious than others.
They are what patients expect.
Patients live in the digital world. Seventy-eight percent of office-based physicians use an EHR, according to a study in the journal Health Affairs. Patients expect that their test results and records are easily accessible by all their providers. The promise of interoperability – the easy digital transfer of data from one data source or EHR system to another – has yet to be realized. This is one of the fundamental potential benefits of digital health technology. HIMSS, an advocacy organization focused on better health with information technology, has sent to Congress its recommendations on achieving interoperability within the next 3 years. This is a pivotal issue in creating the EHR envisioned by both patients and physicians.
They can be used to mitigate risk management.
Adoption of any significant change in health care practice presents challenges specifically with regards to risk management. HIPAA privacy regulations and security are of paramount importance. Most risk managers deal with legal issues after an incident has occurred. Digital health technologies can also potentially mitigate risk.
They can (Yes!) enhance the patient encounter.
While many physicians believe that EHRs destroy the patient encounter, there is another way of viewing the interaction. It all depends upon how it is presented in the office. The computer screen may impede the all-important eye contact between the physician and patient (either because of the physical presence of the screen or the physician’s persistent gaze at it). This is a surefire recipe for disengagement and subsequent destruction of the patient-physician relationship. However, the introduction of the computer (asking permission to use it) with physician and patient triangulated with the screen produces a care team atmosphere. Demonstrating the EHR’s functionality while highlighting pertinent clinical information provides a positive experience for both participants.
They brought health care into the digital age.
EHRs are not the face of all of digital health technologies. They do represent the hub around which other technologies need to flow, because this is where the patient interfaces (pun intended) with the physician. Digital technologies will enhance patient engagement. EHRs are the first experience many physicians have with digital health technologies, and they have yet to fulfill their intended goals. They are in their first iteration. Physician groups and health care enterprises have made themselves heard to the EHR vendors and change is coming. Other digital health technologies are here and will improve health care on many fronts. They themselves will transform the EHR into a more useful clinical tool, which will increase patient education, engagement, and connectivity.
They will be much different and better in the near future.
The American Medical Association got it right, in my opinion, with respect to its recommendations for design overhaul of EHRs. The organization outlined an extension of its study with the Rand Corp. and listed priorities of what should constitute design overhaul of the EHR. These include the incorporation of tools that support team-based care, promotion of care coordination among providers, product modularity and ability for configuration, the reduction of cognitive workload, the promotion of data liquidity, the facilitation of digital and mobile patient engagement, and the ability to expedite user input into design and postimplementation feedback.
As digital technology becomes a more substantive part of health care, there will be a need for physician IT champions who can make this process easier and more fulfilling for others. I look forward to seeing this happen.
Dr. Scher is an electrophysiologist with the Heart Group of Lancaster (Pa.) General Health. He is also director of DLS Healthcare Consulting, Harrisburg, Pa., and clinical associate professor of medicine at the Pennsylvania State University, Hershey.
Much has been said about the failures of electronic health records. The shortcomings discussed have ranged from lack of cost benefits to interoperability with medical devices and security of interoperability with medical devices. We use IT via computers or smartphones daily for social, financial, or consumer aspects of lives. Health care has lagged behind other sectors of society in the adoption of digital technology because of regulatory issues, cost, and resistance to change. There are many positive aspects of EHRs, some more obvious than others.
They are what patients expect.
Patients live in the digital world. Seventy-eight percent of office-based physicians use an EHR, according to a study in the journal Health Affairs. Patients expect that their test results and records are easily accessible by all their providers. The promise of interoperability – the easy digital transfer of data from one data source or EHR system to another – has yet to be realized. This is one of the fundamental potential benefits of digital health technology. HIMSS, an advocacy organization focused on better health with information technology, has sent to Congress its recommendations on achieving interoperability within the next 3 years. This is a pivotal issue in creating the EHR envisioned by both patients and physicians.
They can be used to mitigate risk management.
Adoption of any significant change in health care practice presents challenges specifically with regards to risk management. HIPAA privacy regulations and security are of paramount importance. Most risk managers deal with legal issues after an incident has occurred. Digital health technologies can also potentially mitigate risk.
They can (Yes!) enhance the patient encounter.
While many physicians believe that EHRs destroy the patient encounter, there is another way of viewing the interaction. It all depends upon how it is presented in the office. The computer screen may impede the all-important eye contact between the physician and patient (either because of the physical presence of the screen or the physician’s persistent gaze at it). This is a surefire recipe for disengagement and subsequent destruction of the patient-physician relationship. However, the introduction of the computer (asking permission to use it) with physician and patient triangulated with the screen produces a care team atmosphere. Demonstrating the EHR’s functionality while highlighting pertinent clinical information provides a positive experience for both participants.
They brought health care into the digital age.
EHRs are not the face of all of digital health technologies. They do represent the hub around which other technologies need to flow, because this is where the patient interfaces (pun intended) with the physician. Digital technologies will enhance patient engagement. EHRs are the first experience many physicians have with digital health technologies, and they have yet to fulfill their intended goals. They are in their first iteration. Physician groups and health care enterprises have made themselves heard to the EHR vendors and change is coming. Other digital health technologies are here and will improve health care on many fronts. They themselves will transform the EHR into a more useful clinical tool, which will increase patient education, engagement, and connectivity.
They will be much different and better in the near future.
The American Medical Association got it right, in my opinion, with respect to its recommendations for design overhaul of EHRs. The organization outlined an extension of its study with the Rand Corp. and listed priorities of what should constitute design overhaul of the EHR. These include the incorporation of tools that support team-based care, promotion of care coordination among providers, product modularity and ability for configuration, the reduction of cognitive workload, the promotion of data liquidity, the facilitation of digital and mobile patient engagement, and the ability to expedite user input into design and postimplementation feedback.
As digital technology becomes a more substantive part of health care, there will be a need for physician IT champions who can make this process easier and more fulfilling for others. I look forward to seeing this happen.
Dr. Scher is an electrophysiologist with the Heart Group of Lancaster (Pa.) General Health. He is also director of DLS Healthcare Consulting, Harrisburg, Pa., and clinical associate professor of medicine at the Pennsylvania State University, Hershey.
Larger and more severe strokes seen with aspirin resistance
Patients with acute ischemic stroke who test positive for aspirin resistance had both larger stroke volume and increased severity, compared with patients without resistance, in an observational study of 311 patients at Korean centers.
Given that previous studies have shown that the use of aspirin is associated with lower stroke severity and decreased infarction growth, the current study’s findings may help to define the effect of aspirin resistance (AR) on stroke severity, since previous studies had provided inconclusive results, Dr. Mi Sun Oh and colleagues at Hallym University Sacred Heart Hospital, Anyang, South Korea, wrote in their abstract. The findings were released Feb. 23 in advance of the annual meeting in April of the American Academy of Neurology.
The investigators enrolled patients with acute ischemic stroke confirmed by diffusion-weighted imaging (DWI) who had received at least 7 days of aspirin therapy before initial stroke symptoms and had been checked for AR within 24 hours of hospital admission. Patients with high prestroke disability scores (modified Rankin Scale score > 2) were excluded, as were those who were taking another antiplatelet or anticoagulant medication concurrently with aspirin on hospital admission.
The abstract did not report detailed patient characteristics or information about type or dose of aspirin; the full results of the study will be presented at the meeting in Washington.
Enrollees were deemed aspirin resistant if a rapid assay detected greater than 550 Aspirin Reaction Units. DWI-observed stroke volume was assessed via a semiautomated threshold technique, and investigators employed the National Institutes of Health Stroke Scale (NIHSS) score to measure initial stroke severity.
Seventy-eight of the 311 patients (25.1%) had AR. Dr. Oh and colleagues reported that median stroke volume was higher for these patients, compared with the aspirin-sensitive group (2.8 cc vs. 1.6 cc), as was least-square mean on multivariate analysis (1.6 cc [95% CI, 1.1-2.1] vs. 1.1 cc [95% CI, 0.7-1.4], P = .036). Median NIHSS scores were also higher for the AR group (4 vs. 3), indicating greater stroke severity, a result that was confirmed by multivariate analysis.
Aspirin resistance is a complicated and heterogeneous concept, and not a well defined entity, according to vascular neurologist Dr. Philip Gorelick, head of the Hauenstein Neuroscience Center at St. Mary’s Health Care in Grand Rapids, Mich. Dr. Gorelick is an honorary member of the Korean Stroke Society but was not involved in the present study. In an interview, he expanded on the diverse mechanisms that can impede the stroke prevention effect of antiplatelet agents such as aspirin (Stroke Res. Treat. 2013;Article ID 727842 [doi:10.1155/2013/727842]).
In contrast to the traditional notion of “resistance” as an inherent or acquired defense or chemical blockage of a drug, whether by a microbe or the host, aspirin resistance may be either a laboratory-defined lack of inhibition of thromboxane A2, or a clinically-defined entity. In either case, a host of factors may contribute, Dr. Gorelick said. Poor adherence to an aspirin therapy regimen may be a primary contributor to AR. Further, enterically coated aspirin may not be as well absorbed in the gut, leading to lower effective aspirin dosing. A host of other factors, including concurrent medication administration, comorbidities impacting platelet turnover, and genetic polymorphisms may also contribute to aspirin failure.
Although patient characteristics were not reported in this study, Dr. Gorelick did issue a general note of caution: “Another major issue in these types of studies,” he noted, is to determine if “patients are similar in terms of background factors. Patients on aspirin therapy may be more likely to have more severe preexisting vascular disease,” predisposing them to more severe stroke.
The Korea Healthcare Technology R&D Project, Ministry of Health and Family Welfare, and the Republic of Korea supported the study. The authors had no disclosures.
Patients with acute ischemic stroke who test positive for aspirin resistance had both larger stroke volume and increased severity, compared with patients without resistance, in an observational study of 311 patients at Korean centers.
Given that previous studies have shown that the use of aspirin is associated with lower stroke severity and decreased infarction growth, the current study’s findings may help to define the effect of aspirin resistance (AR) on stroke severity, since previous studies had provided inconclusive results, Dr. Mi Sun Oh and colleagues at Hallym University Sacred Heart Hospital, Anyang, South Korea, wrote in their abstract. The findings were released Feb. 23 in advance of the annual meeting in April of the American Academy of Neurology.
The investigators enrolled patients with acute ischemic stroke confirmed by diffusion-weighted imaging (DWI) who had received at least 7 days of aspirin therapy before initial stroke symptoms and had been checked for AR within 24 hours of hospital admission. Patients with high prestroke disability scores (modified Rankin Scale score > 2) were excluded, as were those who were taking another antiplatelet or anticoagulant medication concurrently with aspirin on hospital admission.
The abstract did not report detailed patient characteristics or information about type or dose of aspirin; the full results of the study will be presented at the meeting in Washington.
Enrollees were deemed aspirin resistant if a rapid assay detected greater than 550 Aspirin Reaction Units. DWI-observed stroke volume was assessed via a semiautomated threshold technique, and investigators employed the National Institutes of Health Stroke Scale (NIHSS) score to measure initial stroke severity.
Seventy-eight of the 311 patients (25.1%) had AR. Dr. Oh and colleagues reported that median stroke volume was higher for these patients, compared with the aspirin-sensitive group (2.8 cc vs. 1.6 cc), as was least-square mean on multivariate analysis (1.6 cc [95% CI, 1.1-2.1] vs. 1.1 cc [95% CI, 0.7-1.4], P = .036). Median NIHSS scores were also higher for the AR group (4 vs. 3), indicating greater stroke severity, a result that was confirmed by multivariate analysis.
Aspirin resistance is a complicated and heterogeneous concept, and not a well defined entity, according to vascular neurologist Dr. Philip Gorelick, head of the Hauenstein Neuroscience Center at St. Mary’s Health Care in Grand Rapids, Mich. Dr. Gorelick is an honorary member of the Korean Stroke Society but was not involved in the present study. In an interview, he expanded on the diverse mechanisms that can impede the stroke prevention effect of antiplatelet agents such as aspirin (Stroke Res. Treat. 2013;Article ID 727842 [doi:10.1155/2013/727842]).
In contrast to the traditional notion of “resistance” as an inherent or acquired defense or chemical blockage of a drug, whether by a microbe or the host, aspirin resistance may be either a laboratory-defined lack of inhibition of thromboxane A2, or a clinically-defined entity. In either case, a host of factors may contribute, Dr. Gorelick said. Poor adherence to an aspirin therapy regimen may be a primary contributor to AR. Further, enterically coated aspirin may not be as well absorbed in the gut, leading to lower effective aspirin dosing. A host of other factors, including concurrent medication administration, comorbidities impacting platelet turnover, and genetic polymorphisms may also contribute to aspirin failure.
Although patient characteristics were not reported in this study, Dr. Gorelick did issue a general note of caution: “Another major issue in these types of studies,” he noted, is to determine if “patients are similar in terms of background factors. Patients on aspirin therapy may be more likely to have more severe preexisting vascular disease,” predisposing them to more severe stroke.
The Korea Healthcare Technology R&D Project, Ministry of Health and Family Welfare, and the Republic of Korea supported the study. The authors had no disclosures.
Patients with acute ischemic stroke who test positive for aspirin resistance had both larger stroke volume and increased severity, compared with patients without resistance, in an observational study of 311 patients at Korean centers.
Given that previous studies have shown that the use of aspirin is associated with lower stroke severity and decreased infarction growth, the current study’s findings may help to define the effect of aspirin resistance (AR) on stroke severity, since previous studies had provided inconclusive results, Dr. Mi Sun Oh and colleagues at Hallym University Sacred Heart Hospital, Anyang, South Korea, wrote in their abstract. The findings were released Feb. 23 in advance of the annual meeting in April of the American Academy of Neurology.
The investigators enrolled patients with acute ischemic stroke confirmed by diffusion-weighted imaging (DWI) who had received at least 7 days of aspirin therapy before initial stroke symptoms and had been checked for AR within 24 hours of hospital admission. Patients with high prestroke disability scores (modified Rankin Scale score > 2) were excluded, as were those who were taking another antiplatelet or anticoagulant medication concurrently with aspirin on hospital admission.
The abstract did not report detailed patient characteristics or information about type or dose of aspirin; the full results of the study will be presented at the meeting in Washington.
Enrollees were deemed aspirin resistant if a rapid assay detected greater than 550 Aspirin Reaction Units. DWI-observed stroke volume was assessed via a semiautomated threshold technique, and investigators employed the National Institutes of Health Stroke Scale (NIHSS) score to measure initial stroke severity.
Seventy-eight of the 311 patients (25.1%) had AR. Dr. Oh and colleagues reported that median stroke volume was higher for these patients, compared with the aspirin-sensitive group (2.8 cc vs. 1.6 cc), as was least-square mean on multivariate analysis (1.6 cc [95% CI, 1.1-2.1] vs. 1.1 cc [95% CI, 0.7-1.4], P = .036). Median NIHSS scores were also higher for the AR group (4 vs. 3), indicating greater stroke severity, a result that was confirmed by multivariate analysis.
Aspirin resistance is a complicated and heterogeneous concept, and not a well defined entity, according to vascular neurologist Dr. Philip Gorelick, head of the Hauenstein Neuroscience Center at St. Mary’s Health Care in Grand Rapids, Mich. Dr. Gorelick is an honorary member of the Korean Stroke Society but was not involved in the present study. In an interview, he expanded on the diverse mechanisms that can impede the stroke prevention effect of antiplatelet agents such as aspirin (Stroke Res. Treat. 2013;Article ID 727842 [doi:10.1155/2013/727842]).
In contrast to the traditional notion of “resistance” as an inherent or acquired defense or chemical blockage of a drug, whether by a microbe or the host, aspirin resistance may be either a laboratory-defined lack of inhibition of thromboxane A2, or a clinically-defined entity. In either case, a host of factors may contribute, Dr. Gorelick said. Poor adherence to an aspirin therapy regimen may be a primary contributor to AR. Further, enterically coated aspirin may not be as well absorbed in the gut, leading to lower effective aspirin dosing. A host of other factors, including concurrent medication administration, comorbidities impacting platelet turnover, and genetic polymorphisms may also contribute to aspirin failure.
Although patient characteristics were not reported in this study, Dr. Gorelick did issue a general note of caution: “Another major issue in these types of studies,” he noted, is to determine if “patients are similar in terms of background factors. Patients on aspirin therapy may be more likely to have more severe preexisting vascular disease,” predisposing them to more severe stroke.
The Korea Healthcare Technology R&D Project, Ministry of Health and Family Welfare, and the Republic of Korea supported the study. The authors had no disclosures.
FROM THE AAN 2015 ANNUAL MEETING
Key clinical point: Volume and severity of ischemic stroke were larger in patients with aspirin resistance.
Major finding: Patients with acute ischemic stroke and aspirin resistance had greater median stroke volume than did aspirin-sensitive patients (2.8 cc vs. 1.6 cc) and had more severe strokes according to median NIHSS score (4 vs. 3).
Data source: Study of 311 patients with MRI-confirmed acute ischemic stroke and at least 7 days of aspirin therapy preceding stroke.
Disclosures: The Korea Healthcare Technology R&D Project, Ministry of Health and Family Welfare, and the Republic of Korea supported the study. The authors had no disclosures.
Oral bisphosphonates linked with lower risk of endometrial cancer
A large prospective study found that among 89,918 women aged 50-79 years, bisphosphonate use was inversely associated with age-adjusted endometrial cancer risk, investigators reported. The study was published online Feb. 23 in the Journal of Clinical Oncology.
Crude incidence of endometrial cancer was 12 per 10,000 person-years for nonusers and 8 per 10,000 years for bisphosphonate users (bisphosphonate users: HR 0.76, 95% CI 0.61 to 0.94; P = .01). During the median 12.5-year follow up, 1,123 women (1,070 nonusers and 53 users) were diagnosed with endometrial cancer, reported Dr. Polly A. Newcomb and associates (J. Clin. Oncol. 2015 Feb. 23 [doi:10.1200/JCO.2014.58.6842]).
Bisphosphonate use was 2% at baseline and increased to 10% by year 6. It was treated as a time-varying never/ever variable that was updated at 1, 3, and 6 years. Compared with nonusers, bisphosphonate users were slightly older, leaner, more educated, and less likely to smoke.
This observational study is limited by the possibility of confounding factors. Women may have taken oral bisphosphonates because they had high fracture risk due to low endogenous estrogen from low weight, which is associated with low endometrial cancer risk. After the researchers controlled for weight and other confounding factors, such as fracture risk, the statistical analysis yielded similar measures of association (HR 0.80, 0.64 to 1.00; P = .05).
“In summary, our findings suggest that use of bisphosphonates is modestly associated with reduced endometrial cancer risk, a finding consistent with the inverse association between use of this medication and breast cancer risk,” wrote Dr. Newcomb of Fred Hutchinson Cancer and University of Washington Research Center, Seattle, and associates.
Dr. Newcomb and most coauthors had no disclosures. One coauthor reported consulting or advisory roles with Novartis, Pfizer, Genentech, Novo Nordisk, Genomic Health.
A large prospective study found that among 89,918 women aged 50-79 years, bisphosphonate use was inversely associated with age-adjusted endometrial cancer risk, investigators reported. The study was published online Feb. 23 in the Journal of Clinical Oncology.
Crude incidence of endometrial cancer was 12 per 10,000 person-years for nonusers and 8 per 10,000 years for bisphosphonate users (bisphosphonate users: HR 0.76, 95% CI 0.61 to 0.94; P = .01). During the median 12.5-year follow up, 1,123 women (1,070 nonusers and 53 users) were diagnosed with endometrial cancer, reported Dr. Polly A. Newcomb and associates (J. Clin. Oncol. 2015 Feb. 23 [doi:10.1200/JCO.2014.58.6842]).
Bisphosphonate use was 2% at baseline and increased to 10% by year 6. It was treated as a time-varying never/ever variable that was updated at 1, 3, and 6 years. Compared with nonusers, bisphosphonate users were slightly older, leaner, more educated, and less likely to smoke.
This observational study is limited by the possibility of confounding factors. Women may have taken oral bisphosphonates because they had high fracture risk due to low endogenous estrogen from low weight, which is associated with low endometrial cancer risk. After the researchers controlled for weight and other confounding factors, such as fracture risk, the statistical analysis yielded similar measures of association (HR 0.80, 0.64 to 1.00; P = .05).
“In summary, our findings suggest that use of bisphosphonates is modestly associated with reduced endometrial cancer risk, a finding consistent with the inverse association between use of this medication and breast cancer risk,” wrote Dr. Newcomb of Fred Hutchinson Cancer and University of Washington Research Center, Seattle, and associates.
Dr. Newcomb and most coauthors had no disclosures. One coauthor reported consulting or advisory roles with Novartis, Pfizer, Genentech, Novo Nordisk, Genomic Health.
A large prospective study found that among 89,918 women aged 50-79 years, bisphosphonate use was inversely associated with age-adjusted endometrial cancer risk, investigators reported. The study was published online Feb. 23 in the Journal of Clinical Oncology.
Crude incidence of endometrial cancer was 12 per 10,000 person-years for nonusers and 8 per 10,000 years for bisphosphonate users (bisphosphonate users: HR 0.76, 95% CI 0.61 to 0.94; P = .01). During the median 12.5-year follow up, 1,123 women (1,070 nonusers and 53 users) were diagnosed with endometrial cancer, reported Dr. Polly A. Newcomb and associates (J. Clin. Oncol. 2015 Feb. 23 [doi:10.1200/JCO.2014.58.6842]).
Bisphosphonate use was 2% at baseline and increased to 10% by year 6. It was treated as a time-varying never/ever variable that was updated at 1, 3, and 6 years. Compared with nonusers, bisphosphonate users were slightly older, leaner, more educated, and less likely to smoke.
This observational study is limited by the possibility of confounding factors. Women may have taken oral bisphosphonates because they had high fracture risk due to low endogenous estrogen from low weight, which is associated with low endometrial cancer risk. After the researchers controlled for weight and other confounding factors, such as fracture risk, the statistical analysis yielded similar measures of association (HR 0.80, 0.64 to 1.00; P = .05).
“In summary, our findings suggest that use of bisphosphonates is modestly associated with reduced endometrial cancer risk, a finding consistent with the inverse association between use of this medication and breast cancer risk,” wrote Dr. Newcomb of Fred Hutchinson Cancer and University of Washington Research Center, Seattle, and associates.
Dr. Newcomb and most coauthors had no disclosures. One coauthor reported consulting or advisory roles with Novartis, Pfizer, Genentech, Novo Nordisk, Genomic Health.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: Oral bisphosphonate use was modestly associated with reduced risk of endometrial cancer.
Major finding: Risk of endometrial cancer was lower among bisphosphonate users: hazard ratio 0.76, 95% CI 0.61 to 0.94, P = .01.
Data source: The Women’s Health Initiative prospective cohort of 89,918 women with 1,123 cases of incident endometrial cancer.
Disclosures: Dr. Newcomb and most coauthors had no disclosures. One coauthor reported consulting or advisory roles with Novartis, Pfizer, Genentech, Novo Nordisk, Genomic Health.
Outcomes: Getting to the patient’s bottom line
It’s easy to get so caught up in our day-to-day routines. At the hospital, we’re meeting core measures, documenting correctly, following clinical guidelines, and simply striving to stay up to date with the literature. At home, there are soccer games, recitals, and homework – and some rare personal time. We often shift to automatic pilot in a desperate attempt to balance the seemingly never-ending demands.
But does the very nature of our hectic lives sometimes prevent us from seeing the bigger picture, especially when it comes to the things that are really important to our patients? Yes, we know what lab values automatically trigger an order for a statin, and what ejection fraction on the echocardiogram warrants an ACE inhibitor, but how often do we really take the time to find out about the outcomes that are important to our patients? Sometimes they aren’t the evidence-based clinical outcomes we are trying to reproduce with our treatments.
For many patients, the desired outcome is to feel better, plain and simple. All the fancy lingo and drugs with unpronounceable names and unintelligible indications can be overwhelming. They make some patients shut down, and ultimately shut us out. We may not even realize it until our patients are readmitted as a result of noncompliance with our well-thought-out treatment plans.
There are our male patients who rarely take their blood pressure medicine because of the side effect of sexual dysfunction. And then there are those patients who don’t take their medications or see their doctors regularly because they just cannot afford it. While they seem to be in agreement with the follow-up plan for medical visits and testing, patients may be ashamed to admit they are uninsured or underinsured. They know they will never be adherent because they just cannot afford the costs of our treatment plan.
Instead of getting frustrated with our noncompliant patients, we could better serve them by getting more personal – gaining their trust as we carefully and respectfully uncover the layers of the limitations they face and the outcomes that matter to them. We need to aim to be viewed as our patients’ caring advocates and not just aloof professionals with no clue about their daily struggles.
Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at [email protected].
It’s easy to get so caught up in our day-to-day routines. At the hospital, we’re meeting core measures, documenting correctly, following clinical guidelines, and simply striving to stay up to date with the literature. At home, there are soccer games, recitals, and homework – and some rare personal time. We often shift to automatic pilot in a desperate attempt to balance the seemingly never-ending demands.
But does the very nature of our hectic lives sometimes prevent us from seeing the bigger picture, especially when it comes to the things that are really important to our patients? Yes, we know what lab values automatically trigger an order for a statin, and what ejection fraction on the echocardiogram warrants an ACE inhibitor, but how often do we really take the time to find out about the outcomes that are important to our patients? Sometimes they aren’t the evidence-based clinical outcomes we are trying to reproduce with our treatments.
For many patients, the desired outcome is to feel better, plain and simple. All the fancy lingo and drugs with unpronounceable names and unintelligible indications can be overwhelming. They make some patients shut down, and ultimately shut us out. We may not even realize it until our patients are readmitted as a result of noncompliance with our well-thought-out treatment plans.
There are our male patients who rarely take their blood pressure medicine because of the side effect of sexual dysfunction. And then there are those patients who don’t take their medications or see their doctors regularly because they just cannot afford it. While they seem to be in agreement with the follow-up plan for medical visits and testing, patients may be ashamed to admit they are uninsured or underinsured. They know they will never be adherent because they just cannot afford the costs of our treatment plan.
Instead of getting frustrated with our noncompliant patients, we could better serve them by getting more personal – gaining their trust as we carefully and respectfully uncover the layers of the limitations they face and the outcomes that matter to them. We need to aim to be viewed as our patients’ caring advocates and not just aloof professionals with no clue about their daily struggles.
Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at [email protected].
It’s easy to get so caught up in our day-to-day routines. At the hospital, we’re meeting core measures, documenting correctly, following clinical guidelines, and simply striving to stay up to date with the literature. At home, there are soccer games, recitals, and homework – and some rare personal time. We often shift to automatic pilot in a desperate attempt to balance the seemingly never-ending demands.
But does the very nature of our hectic lives sometimes prevent us from seeing the bigger picture, especially when it comes to the things that are really important to our patients? Yes, we know what lab values automatically trigger an order for a statin, and what ejection fraction on the echocardiogram warrants an ACE inhibitor, but how often do we really take the time to find out about the outcomes that are important to our patients? Sometimes they aren’t the evidence-based clinical outcomes we are trying to reproduce with our treatments.
For many patients, the desired outcome is to feel better, plain and simple. All the fancy lingo and drugs with unpronounceable names and unintelligible indications can be overwhelming. They make some patients shut down, and ultimately shut us out. We may not even realize it until our patients are readmitted as a result of noncompliance with our well-thought-out treatment plans.
There are our male patients who rarely take their blood pressure medicine because of the side effect of sexual dysfunction. And then there are those patients who don’t take their medications or see their doctors regularly because they just cannot afford it. While they seem to be in agreement with the follow-up plan for medical visits and testing, patients may be ashamed to admit they are uninsured or underinsured. They know they will never be adherent because they just cannot afford the costs of our treatment plan.
Instead of getting frustrated with our noncompliant patients, we could better serve them by getting more personal – gaining their trust as we carefully and respectfully uncover the layers of the limitations they face and the outcomes that matter to them. We need to aim to be viewed as our patients’ caring advocates and not just aloof professionals with no clue about their daily struggles.
Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at [email protected].
Woman, 64, With Eye Pain, Swelling, and Tearing
A 64-year-old woman presented to the clinic with a two-to-three-week history of significant pain, swelling, and excessive tearing of the left eye. The patient had a persistent cough but denied wheezing or shortness of breath.
Medical history was remarkable for uveitis, severe recurrent sinusitis, and allergic rhinitis. The patient reported that she had been exposed to benzene and burning paint fumes about 10 years ago but had no known symptoms or problems at the time.
Vital signs included a temperature of 97.0°F; respiratory rate, 18 breaths/min; pulse, 100 beats/min; and blood pressure, 144/80 mm Hg. Her height was 65 in; weight, 122 lb; and O2 saturation, 100% on room air.
Physical examination revealed a left palpebral lacrimal mass with an enlarged lacrimal gland. The left lacrimal gland and conjunctiva were mildly erythematous, with a cobblestone appearance. The right eye was stable, with no significant inflammation. Pupils were equal, round, and reactive to light and accommodation. Extraocular movements were intact. Nasal turbinates were swollen and mildly erythematous. Oropharynx was stable and tonsils absent. Left parotid gland was slightly swollen and tender.
The neck was supple with no jugular venous distension. Palpable cervical and supraclavicular lymphadenopathy, measuring approximately 1.5 x 1.5 cm bilaterally, was present. The lungs were clear to auscultation and percussion. The heart rate and rhythm were regular, with normal S1 and S2 sounds. The abdomen was soft, nontender, and without hepatosplenomegaly. Extremities were stable, with no rashes, lesions, or cutaneous skin nodules.
The patient was referred to a specialist for a complete ophthalmologic examination and further work-up. This included a complete blood count, comprehensive metabolic panel, tissue biopsies of the affected lacrimal gland and parotid gland, CT, and x-rays; results are shown in Table 1. In addition, the patient’s persistent nasosinus congestion was determined, by otolaryngologic consultation, to be the result of a deviated septum, for which she underwent endoscopic nasal septal repair with tissue biopsy.
The lacrimal gland biopsy led to a diagnosis of chronic noncaseating granulomatous dacryoadenitis, with an extensive area of necrosis. Significant findings included histiocytes and discrete nodules in the gland. Biopsies of the parotid gland and nasal tissue also identified noncaseating granulomas.
The patient’s test results suggested several possible diagnoses, including
• Granulomatosis with polyangiitis
• Tuberculosis (TB) or similar pulmonary infectious disease
• Sarcoidosis (ocular and/or pulmonary)
Continue for differential diagnosis >>
DISCUSSION
Differential diagnosis
Granulomatosis with polyangiitis. GPA, also known as Wegener granulomatosis, is characterized by necrotizing granulomatous inflammation with necrotizing vasculitis, usually of small and medium vessels; ocular involvement is frequent.1 Ocular granulomas of GPA can be mistaken for those caused by other diseases, such as mycobacterial or syphilitic infection or idiopathic uveitis.2
Tuberculosis. Common symptoms of TB include fever, cough, dyspnea, weight loss, malaise, and fatigue. Granulomas are typically necrotizing but are occasionally nonnecrotizing.3 TB can manifest with hilar and diffuse lymphadenopathy,4 which the patient’s chest imaging revealed (see Figure 1). Granulomas produced by Mycobacterium tuberculosis and atypical mycobacteria are similar histopathologically to sarcoidosis granulomas, complicating the diagnostic process.5
Next page: Sarcoidosis >>
Sarcoidosis. Sarcoidosis is a multisystem inflammatory disease characterized by noncaseating epithelioid granulomas in affected organs.6 More than 90% of patients with sarcoidosis present with pulmonary symptoms, including shortness of breath, cough, and pleuritic chest pain.6-8 Ocular manifestations, such as uveitis, iritis, or conjunctivitis, are less common, developing in 30% to 60% of patients.2,9,10 In addition, rashes, lesions, or cutaneous skin nodules, including erythema nodosum and lupus pernio, are seen in 25% to 35% of patients.2,6
In up to two-thirds of patients, sarcoidosis resolves spontaneously2; in others, it may become chronic and progressive.4 Patients may have few or no symptoms; some require no treatment, while others may be severely affected by the disease.
Ocular involvement in sarcoidosis generally manifests as uveitis, most commonly in the anterior chamber. Uveitis is a potentially vision-threatening inflammatory disease involving both the uveal tract and adjacent structures.11 In a review of records for 2,619 patients with uveitis, 59.9% had anterior disease, of whom 2.1% were diagnosed with sarcoidosis.11
While the etiology of sarcoidosis continues to be studied,7 the prevailing theory is that, in genetically predisposed individuals, sarcoidosis is a cell-mediated immune response to as-yet unknown antigen triggers that leads to granuloma formation.3,6,7
CD4+ activated T-cells stimulate the immune reaction against an antigen, producing cytokines that activate immune cells (eg, B cells, macrophages, monocytes, and neutrophils).2 Immune cells accumulate and aggregate at antigen sites in an exaggerated response, resulting in the formation of granulomas (see Figure 2).7,12,13
Infectious agents have long been investigated as possible causative agents in sarcoidosis, with Mycobacterium species most frequently identified.5 Additional possibilities include Propionibacterium acnes (found predominantly in skin lesions) and herpesviruses, although viruses are not known to cause epitheliod granulomas.14
Environmental triggers have also been explored. One large study found a possible association between exposure to insecticides, agricultural environments, and microbial bioaerosols and sarcoidosis.15
The difficulty of pinpointing a single etiology for sarcoidosis—with its varying clinical manifestations, severity, and disease course—suggests that sarcoidosis may be a spectrum of disorders caused by the interaction of genetic, immunologic, infectious, and environmental factors.14
Next page: Diagnosis of sarcoidosis >>
Diagnosis
The diagnosis of sarcoidosis is based on clinical and radiologic features, histologic evidence of noncaseating granulomas, and exclusion of other possible causes of granulomas.2,12 In addition, when ocular sarcoidosis is suspected, other possible causes of uveitis must be excluded.
In an effort to address these challenges, the International Workshop on Ocular Sarcoidosis (IWOS) developed a standardized approach to diagnosis.9 The group first identified seven intraocular signs of ocular sarcoidosis and then five laboratory or imaging tests that are of value in making the diagnosis in patients with these signs. Last, they established four levels of certainty for the diagnosis of ocular sarcoidosis, based on these signs, tests, and biopsy results, if available (see Table 2).
Treatment
Anterior uveitis in sarcoidosis is usually treated initially with a topical corticosteroid (eg, prednisolone or difluprednate drops), particularly if the patient’s symptoms are mild. In more severe cases (eg, posterior or bilateral uveitis) or when topical corticosteroids are ineffective, systemic (oral) corticosteroids (eg, prednisone) may be initiated. Topical therapy can also be added to an oral regimen as a means of decreasing the oral dosage and thereby reducing the adverse effects of systemic corticosteroids. When the patient’s disease is refractory to corticosteroids or there are concerns about long-term adverse effects, chronic cases may be treated with immunosuppressive agents (eg, methotrexate, azathioprine, mycophenolate mofetil). Finally, refractory cases of ocular sarcoidosis may be treated with anti–tumor necrosis factor α (TNF-α) biologic agents such as infliximab and adalimumab.10,17
Continue for case patient outcome >>
OUTCOME FOR THE CASE PATIENT
Histologic evaluation of tissue from the lacrimal gland, parotid gland, and sinus cavity revealed inflammatory noncaseating granulomas, strongly suggestive of sarcoidosis. Diagnosis of ocular sarcoidosis was based on the noncaseating granulomas in the lacrimal gland.9,16 Pulmonary sarcoidosis was also diagnosed, based on the presence of hilar and mediastinal lymphadenopathy.7
The mass in the patient’s lacrimal gland was surgically removed. She was treated with a combination of topical and oral corticosteroids tapered over two weeks, which induced remission of her ocular disease. The patient will be seen annually by an ophthalmologic specialist and was advised to contact her clinician immediately if acute ocular symptoms recurred.10,17
The patient’s persistent cough was determined to be secondary to acute bronchitis, rather than to her pulmonary sarcoidosis, which required no treatment. She received a short course of antibiotics and antitussives for her bronchitis. Systemic corticosteroid treatment of her ocular sarcoidosis also had the benefit of decreasing the size of her pulmonary nodules. She will be followed with annual CT and chest x-rays to monitor the status of her hilar and mediastinal lymphadenopathy and the nodules.3 Periodic pulmonary function testing will also be performed.7
Continue for conclusion >>
CONCLUSION
The elusive nature of the diagnosis of sarcoidosis is well documented in the medical literature. In this case, histologic evaluation of biopsied tissue, correlated with clinical symptoms and radiographic findings, were essential in making the diagnosis.
Primary care providers may be the first to evaluate patients with ocular sarcoidosis and will oversee long-term management. Patients who present with symptoms of eye pain, visual disturbances, abnormal inflammatory ocular features, or swollen lacrimal glands should be referred to an ophthalmologic specialist for further evaluation.
REFERENCES
1. Jennette JC, Falk RJ, Bacon PA, et al. 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65(1):1-11.
2. Culver DA. Sarcoidosis. Immunol Allergy Clin North Am. 2012;32(4):487-511.
3. Spagnolo P, Luppi F, Roversi P, et al. Sarcoidosis: challenging diagnostic aspects of an old disease. Am J Med. 2012;125(2):118-125.
4. Dempsey OJ, Peterson EW, Kerr KM, Denison AR. Sarcoidosis. BMJ. 2009;339:620-625.
5. Brownell I, Ramirez-Valle F, Sanchez M, Prystowsky S. Evidence for mycobacteria in sarcoidosis. Am J Respir Cell Mol Biol. 2011;45(5):899-905.
6. Iannuzzi MC, Fontana JR. Sarcoidosis: clinical presentation, immunopathogenesis, and therapeutics. JAMA. 2011;305(4):391-399.
7. Baughman MD, Culver DA, Judson MA. A concise review of pulmonary sarcoidosis. Am J Respir Crit Care Med. 2011;183(5):573-581.
8. Koyama T, Ueda H, Togashi K, et al. Radiologic manifestations of sarcoidosis in various organs. Radiographics. 2004;24(1):87-104.
9. Herbort CP, Rao NA, Mochizuki M; for the Scientific Committee of First International Workshop on Ocular Sarcoidosis. International criteria for the diagnosis of ocular sarcoidosis: results of the first International Workshop on Ocular Sarcoidosis (IWOS). Ocul Immunol Inflamm. 2009; 17(3):160-169.
10. Jamilloux Y, Kodjikian L, Broussolle C, Seve P. Sarcoidosis and uveitis. Autoimmun Rev. 2014;13(8):840-849.
11. Barisani-Asenbauer T, Maca SM, Mejdoubi L, et al. Uveitis—a rare disease often associated with systemic diseases and infections—a systematic review of 2619 patients. Orphanet J Rare Dis. 2012;7:57.
12. Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. New Engl J Med. 2007;357(21):2153-2165.
13. Fontenot A, King T. Pathogenesis of sarcoidosis. www.uptodate.com/contents/pathogenesis-of-sarcoidosis?source=search_result&search=Pathogenesis+of+sarcoidosis&selectedTitle=1%7E150. Accessed February 17, 2015.
14. Saidha S, Sotirchos ES, Eckstein C. Etiology of sarcoidosis: does infection play a role? Yale J Biol Med. 2012;85(1):133-141.
15. Newman LS, Rose CS, Bresnitz EA, et al; for the ACCESS Research Group. A case control etiologic study of sarcoidosis. Environmental and occupational risk factors. Am J Respir Crit Care Med. 2004;170:1324-1330.
16. Kawaguchi T, Hanada A, Horie S, et al. Evaluation of characteristic ocular signs and systemic investigations in ocular sarcoidosis patients. Jpn J Opthalmol. 2007;51(2):121-126.
17. Bodaghi B, Touitou V, Fardeau C, et al. Ocular sarcoidosis. Presse Med. 2012;41(6 Pt 2):e349-e354.
A 64-year-old woman presented to the clinic with a two-to-three-week history of significant pain, swelling, and excessive tearing of the left eye. The patient had a persistent cough but denied wheezing or shortness of breath.
Medical history was remarkable for uveitis, severe recurrent sinusitis, and allergic rhinitis. The patient reported that she had been exposed to benzene and burning paint fumes about 10 years ago but had no known symptoms or problems at the time.
Vital signs included a temperature of 97.0°F; respiratory rate, 18 breaths/min; pulse, 100 beats/min; and blood pressure, 144/80 mm Hg. Her height was 65 in; weight, 122 lb; and O2 saturation, 100% on room air.
Physical examination revealed a left palpebral lacrimal mass with an enlarged lacrimal gland. The left lacrimal gland and conjunctiva were mildly erythematous, with a cobblestone appearance. The right eye was stable, with no significant inflammation. Pupils were equal, round, and reactive to light and accommodation. Extraocular movements were intact. Nasal turbinates were swollen and mildly erythematous. Oropharynx was stable and tonsils absent. Left parotid gland was slightly swollen and tender.
The neck was supple with no jugular venous distension. Palpable cervical and supraclavicular lymphadenopathy, measuring approximately 1.5 x 1.5 cm bilaterally, was present. The lungs were clear to auscultation and percussion. The heart rate and rhythm were regular, with normal S1 and S2 sounds. The abdomen was soft, nontender, and without hepatosplenomegaly. Extremities were stable, with no rashes, lesions, or cutaneous skin nodules.
The patient was referred to a specialist for a complete ophthalmologic examination and further work-up. This included a complete blood count, comprehensive metabolic panel, tissue biopsies of the affected lacrimal gland and parotid gland, CT, and x-rays; results are shown in Table 1. In addition, the patient’s persistent nasosinus congestion was determined, by otolaryngologic consultation, to be the result of a deviated septum, for which she underwent endoscopic nasal septal repair with tissue biopsy.
The lacrimal gland biopsy led to a diagnosis of chronic noncaseating granulomatous dacryoadenitis, with an extensive area of necrosis. Significant findings included histiocytes and discrete nodules in the gland. Biopsies of the parotid gland and nasal tissue also identified noncaseating granulomas.
The patient’s test results suggested several possible diagnoses, including
• Granulomatosis with polyangiitis
• Tuberculosis (TB) or similar pulmonary infectious disease
• Sarcoidosis (ocular and/or pulmonary)
Continue for differential diagnosis >>
DISCUSSION
Differential diagnosis
Granulomatosis with polyangiitis. GPA, also known as Wegener granulomatosis, is characterized by necrotizing granulomatous inflammation with necrotizing vasculitis, usually of small and medium vessels; ocular involvement is frequent.1 Ocular granulomas of GPA can be mistaken for those caused by other diseases, such as mycobacterial or syphilitic infection or idiopathic uveitis.2
Tuberculosis. Common symptoms of TB include fever, cough, dyspnea, weight loss, malaise, and fatigue. Granulomas are typically necrotizing but are occasionally nonnecrotizing.3 TB can manifest with hilar and diffuse lymphadenopathy,4 which the patient’s chest imaging revealed (see Figure 1). Granulomas produced by Mycobacterium tuberculosis and atypical mycobacteria are similar histopathologically to sarcoidosis granulomas, complicating the diagnostic process.5
Next page: Sarcoidosis >>
Sarcoidosis. Sarcoidosis is a multisystem inflammatory disease characterized by noncaseating epithelioid granulomas in affected organs.6 More than 90% of patients with sarcoidosis present with pulmonary symptoms, including shortness of breath, cough, and pleuritic chest pain.6-8 Ocular manifestations, such as uveitis, iritis, or conjunctivitis, are less common, developing in 30% to 60% of patients.2,9,10 In addition, rashes, lesions, or cutaneous skin nodules, including erythema nodosum and lupus pernio, are seen in 25% to 35% of patients.2,6
In up to two-thirds of patients, sarcoidosis resolves spontaneously2; in others, it may become chronic and progressive.4 Patients may have few or no symptoms; some require no treatment, while others may be severely affected by the disease.
Ocular involvement in sarcoidosis generally manifests as uveitis, most commonly in the anterior chamber. Uveitis is a potentially vision-threatening inflammatory disease involving both the uveal tract and adjacent structures.11 In a review of records for 2,619 patients with uveitis, 59.9% had anterior disease, of whom 2.1% were diagnosed with sarcoidosis.11
While the etiology of sarcoidosis continues to be studied,7 the prevailing theory is that, in genetically predisposed individuals, sarcoidosis is a cell-mediated immune response to as-yet unknown antigen triggers that leads to granuloma formation.3,6,7
CD4+ activated T-cells stimulate the immune reaction against an antigen, producing cytokines that activate immune cells (eg, B cells, macrophages, monocytes, and neutrophils).2 Immune cells accumulate and aggregate at antigen sites in an exaggerated response, resulting in the formation of granulomas (see Figure 2).7,12,13
Infectious agents have long been investigated as possible causative agents in sarcoidosis, with Mycobacterium species most frequently identified.5 Additional possibilities include Propionibacterium acnes (found predominantly in skin lesions) and herpesviruses, although viruses are not known to cause epitheliod granulomas.14
Environmental triggers have also been explored. One large study found a possible association between exposure to insecticides, agricultural environments, and microbial bioaerosols and sarcoidosis.15
The difficulty of pinpointing a single etiology for sarcoidosis—with its varying clinical manifestations, severity, and disease course—suggests that sarcoidosis may be a spectrum of disorders caused by the interaction of genetic, immunologic, infectious, and environmental factors.14
Next page: Diagnosis of sarcoidosis >>
Diagnosis
The diagnosis of sarcoidosis is based on clinical and radiologic features, histologic evidence of noncaseating granulomas, and exclusion of other possible causes of granulomas.2,12 In addition, when ocular sarcoidosis is suspected, other possible causes of uveitis must be excluded.
In an effort to address these challenges, the International Workshop on Ocular Sarcoidosis (IWOS) developed a standardized approach to diagnosis.9 The group first identified seven intraocular signs of ocular sarcoidosis and then five laboratory or imaging tests that are of value in making the diagnosis in patients with these signs. Last, they established four levels of certainty for the diagnosis of ocular sarcoidosis, based on these signs, tests, and biopsy results, if available (see Table 2).
Treatment
Anterior uveitis in sarcoidosis is usually treated initially with a topical corticosteroid (eg, prednisolone or difluprednate drops), particularly if the patient’s symptoms are mild. In more severe cases (eg, posterior or bilateral uveitis) or when topical corticosteroids are ineffective, systemic (oral) corticosteroids (eg, prednisone) may be initiated. Topical therapy can also be added to an oral regimen as a means of decreasing the oral dosage and thereby reducing the adverse effects of systemic corticosteroids. When the patient’s disease is refractory to corticosteroids or there are concerns about long-term adverse effects, chronic cases may be treated with immunosuppressive agents (eg, methotrexate, azathioprine, mycophenolate mofetil). Finally, refractory cases of ocular sarcoidosis may be treated with anti–tumor necrosis factor α (TNF-α) biologic agents such as infliximab and adalimumab.10,17
Continue for case patient outcome >>
OUTCOME FOR THE CASE PATIENT
Histologic evaluation of tissue from the lacrimal gland, parotid gland, and sinus cavity revealed inflammatory noncaseating granulomas, strongly suggestive of sarcoidosis. Diagnosis of ocular sarcoidosis was based on the noncaseating granulomas in the lacrimal gland.9,16 Pulmonary sarcoidosis was also diagnosed, based on the presence of hilar and mediastinal lymphadenopathy.7
The mass in the patient’s lacrimal gland was surgically removed. She was treated with a combination of topical and oral corticosteroids tapered over two weeks, which induced remission of her ocular disease. The patient will be seen annually by an ophthalmologic specialist and was advised to contact her clinician immediately if acute ocular symptoms recurred.10,17
The patient’s persistent cough was determined to be secondary to acute bronchitis, rather than to her pulmonary sarcoidosis, which required no treatment. She received a short course of antibiotics and antitussives for her bronchitis. Systemic corticosteroid treatment of her ocular sarcoidosis also had the benefit of decreasing the size of her pulmonary nodules. She will be followed with annual CT and chest x-rays to monitor the status of her hilar and mediastinal lymphadenopathy and the nodules.3 Periodic pulmonary function testing will also be performed.7
Continue for conclusion >>
CONCLUSION
The elusive nature of the diagnosis of sarcoidosis is well documented in the medical literature. In this case, histologic evaluation of biopsied tissue, correlated with clinical symptoms and radiographic findings, were essential in making the diagnosis.
Primary care providers may be the first to evaluate patients with ocular sarcoidosis and will oversee long-term management. Patients who present with symptoms of eye pain, visual disturbances, abnormal inflammatory ocular features, or swollen lacrimal glands should be referred to an ophthalmologic specialist for further evaluation.
REFERENCES
1. Jennette JC, Falk RJ, Bacon PA, et al. 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65(1):1-11.
2. Culver DA. Sarcoidosis. Immunol Allergy Clin North Am. 2012;32(4):487-511.
3. Spagnolo P, Luppi F, Roversi P, et al. Sarcoidosis: challenging diagnostic aspects of an old disease. Am J Med. 2012;125(2):118-125.
4. Dempsey OJ, Peterson EW, Kerr KM, Denison AR. Sarcoidosis. BMJ. 2009;339:620-625.
5. Brownell I, Ramirez-Valle F, Sanchez M, Prystowsky S. Evidence for mycobacteria in sarcoidosis. Am J Respir Cell Mol Biol. 2011;45(5):899-905.
6. Iannuzzi MC, Fontana JR. Sarcoidosis: clinical presentation, immunopathogenesis, and therapeutics. JAMA. 2011;305(4):391-399.
7. Baughman MD, Culver DA, Judson MA. A concise review of pulmonary sarcoidosis. Am J Respir Crit Care Med. 2011;183(5):573-581.
8. Koyama T, Ueda H, Togashi K, et al. Radiologic manifestations of sarcoidosis in various organs. Radiographics. 2004;24(1):87-104.
9. Herbort CP, Rao NA, Mochizuki M; for the Scientific Committee of First International Workshop on Ocular Sarcoidosis. International criteria for the diagnosis of ocular sarcoidosis: results of the first International Workshop on Ocular Sarcoidosis (IWOS). Ocul Immunol Inflamm. 2009; 17(3):160-169.
10. Jamilloux Y, Kodjikian L, Broussolle C, Seve P. Sarcoidosis and uveitis. Autoimmun Rev. 2014;13(8):840-849.
11. Barisani-Asenbauer T, Maca SM, Mejdoubi L, et al. Uveitis—a rare disease often associated with systemic diseases and infections—a systematic review of 2619 patients. Orphanet J Rare Dis. 2012;7:57.
12. Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. New Engl J Med. 2007;357(21):2153-2165.
13. Fontenot A, King T. Pathogenesis of sarcoidosis. www.uptodate.com/contents/pathogenesis-of-sarcoidosis?source=search_result&search=Pathogenesis+of+sarcoidosis&selectedTitle=1%7E150. Accessed February 17, 2015.
14. Saidha S, Sotirchos ES, Eckstein C. Etiology of sarcoidosis: does infection play a role? Yale J Biol Med. 2012;85(1):133-141.
15. Newman LS, Rose CS, Bresnitz EA, et al; for the ACCESS Research Group. A case control etiologic study of sarcoidosis. Environmental and occupational risk factors. Am J Respir Crit Care Med. 2004;170:1324-1330.
16. Kawaguchi T, Hanada A, Horie S, et al. Evaluation of characteristic ocular signs and systemic investigations in ocular sarcoidosis patients. Jpn J Opthalmol. 2007;51(2):121-126.
17. Bodaghi B, Touitou V, Fardeau C, et al. Ocular sarcoidosis. Presse Med. 2012;41(6 Pt 2):e349-e354.
A 64-year-old woman presented to the clinic with a two-to-three-week history of significant pain, swelling, and excessive tearing of the left eye. The patient had a persistent cough but denied wheezing or shortness of breath.
Medical history was remarkable for uveitis, severe recurrent sinusitis, and allergic rhinitis. The patient reported that she had been exposed to benzene and burning paint fumes about 10 years ago but had no known symptoms or problems at the time.
Vital signs included a temperature of 97.0°F; respiratory rate, 18 breaths/min; pulse, 100 beats/min; and blood pressure, 144/80 mm Hg. Her height was 65 in; weight, 122 lb; and O2 saturation, 100% on room air.
Physical examination revealed a left palpebral lacrimal mass with an enlarged lacrimal gland. The left lacrimal gland and conjunctiva were mildly erythematous, with a cobblestone appearance. The right eye was stable, with no significant inflammation. Pupils were equal, round, and reactive to light and accommodation. Extraocular movements were intact. Nasal turbinates were swollen and mildly erythematous. Oropharynx was stable and tonsils absent. Left parotid gland was slightly swollen and tender.
The neck was supple with no jugular venous distension. Palpable cervical and supraclavicular lymphadenopathy, measuring approximately 1.5 x 1.5 cm bilaterally, was present. The lungs were clear to auscultation and percussion. The heart rate and rhythm were regular, with normal S1 and S2 sounds. The abdomen was soft, nontender, and without hepatosplenomegaly. Extremities were stable, with no rashes, lesions, or cutaneous skin nodules.
The patient was referred to a specialist for a complete ophthalmologic examination and further work-up. This included a complete blood count, comprehensive metabolic panel, tissue biopsies of the affected lacrimal gland and parotid gland, CT, and x-rays; results are shown in Table 1. In addition, the patient’s persistent nasosinus congestion was determined, by otolaryngologic consultation, to be the result of a deviated septum, for which she underwent endoscopic nasal septal repair with tissue biopsy.
The lacrimal gland biopsy led to a diagnosis of chronic noncaseating granulomatous dacryoadenitis, with an extensive area of necrosis. Significant findings included histiocytes and discrete nodules in the gland. Biopsies of the parotid gland and nasal tissue also identified noncaseating granulomas.
The patient’s test results suggested several possible diagnoses, including
• Granulomatosis with polyangiitis
• Tuberculosis (TB) or similar pulmonary infectious disease
• Sarcoidosis (ocular and/or pulmonary)
Continue for differential diagnosis >>
DISCUSSION
Differential diagnosis
Granulomatosis with polyangiitis. GPA, also known as Wegener granulomatosis, is characterized by necrotizing granulomatous inflammation with necrotizing vasculitis, usually of small and medium vessels; ocular involvement is frequent.1 Ocular granulomas of GPA can be mistaken for those caused by other diseases, such as mycobacterial or syphilitic infection or idiopathic uveitis.2
Tuberculosis. Common symptoms of TB include fever, cough, dyspnea, weight loss, malaise, and fatigue. Granulomas are typically necrotizing but are occasionally nonnecrotizing.3 TB can manifest with hilar and diffuse lymphadenopathy,4 which the patient’s chest imaging revealed (see Figure 1). Granulomas produced by Mycobacterium tuberculosis and atypical mycobacteria are similar histopathologically to sarcoidosis granulomas, complicating the diagnostic process.5
Next page: Sarcoidosis >>
Sarcoidosis. Sarcoidosis is a multisystem inflammatory disease characterized by noncaseating epithelioid granulomas in affected organs.6 More than 90% of patients with sarcoidosis present with pulmonary symptoms, including shortness of breath, cough, and pleuritic chest pain.6-8 Ocular manifestations, such as uveitis, iritis, or conjunctivitis, are less common, developing in 30% to 60% of patients.2,9,10 In addition, rashes, lesions, or cutaneous skin nodules, including erythema nodosum and lupus pernio, are seen in 25% to 35% of patients.2,6
In up to two-thirds of patients, sarcoidosis resolves spontaneously2; in others, it may become chronic and progressive.4 Patients may have few or no symptoms; some require no treatment, while others may be severely affected by the disease.
Ocular involvement in sarcoidosis generally manifests as uveitis, most commonly in the anterior chamber. Uveitis is a potentially vision-threatening inflammatory disease involving both the uveal tract and adjacent structures.11 In a review of records for 2,619 patients with uveitis, 59.9% had anterior disease, of whom 2.1% were diagnosed with sarcoidosis.11
While the etiology of sarcoidosis continues to be studied,7 the prevailing theory is that, in genetically predisposed individuals, sarcoidosis is a cell-mediated immune response to as-yet unknown antigen triggers that leads to granuloma formation.3,6,7
CD4+ activated T-cells stimulate the immune reaction against an antigen, producing cytokines that activate immune cells (eg, B cells, macrophages, monocytes, and neutrophils).2 Immune cells accumulate and aggregate at antigen sites in an exaggerated response, resulting in the formation of granulomas (see Figure 2).7,12,13
Infectious agents have long been investigated as possible causative agents in sarcoidosis, with Mycobacterium species most frequently identified.5 Additional possibilities include Propionibacterium acnes (found predominantly in skin lesions) and herpesviruses, although viruses are not known to cause epitheliod granulomas.14
Environmental triggers have also been explored. One large study found a possible association between exposure to insecticides, agricultural environments, and microbial bioaerosols and sarcoidosis.15
The difficulty of pinpointing a single etiology for sarcoidosis—with its varying clinical manifestations, severity, and disease course—suggests that sarcoidosis may be a spectrum of disorders caused by the interaction of genetic, immunologic, infectious, and environmental factors.14
Next page: Diagnosis of sarcoidosis >>
Diagnosis
The diagnosis of sarcoidosis is based on clinical and radiologic features, histologic evidence of noncaseating granulomas, and exclusion of other possible causes of granulomas.2,12 In addition, when ocular sarcoidosis is suspected, other possible causes of uveitis must be excluded.
In an effort to address these challenges, the International Workshop on Ocular Sarcoidosis (IWOS) developed a standardized approach to diagnosis.9 The group first identified seven intraocular signs of ocular sarcoidosis and then five laboratory or imaging tests that are of value in making the diagnosis in patients with these signs. Last, they established four levels of certainty for the diagnosis of ocular sarcoidosis, based on these signs, tests, and biopsy results, if available (see Table 2).
Treatment
Anterior uveitis in sarcoidosis is usually treated initially with a topical corticosteroid (eg, prednisolone or difluprednate drops), particularly if the patient’s symptoms are mild. In more severe cases (eg, posterior or bilateral uveitis) or when topical corticosteroids are ineffective, systemic (oral) corticosteroids (eg, prednisone) may be initiated. Topical therapy can also be added to an oral regimen as a means of decreasing the oral dosage and thereby reducing the adverse effects of systemic corticosteroids. When the patient’s disease is refractory to corticosteroids or there are concerns about long-term adverse effects, chronic cases may be treated with immunosuppressive agents (eg, methotrexate, azathioprine, mycophenolate mofetil). Finally, refractory cases of ocular sarcoidosis may be treated with anti–tumor necrosis factor α (TNF-α) biologic agents such as infliximab and adalimumab.10,17
Continue for case patient outcome >>
OUTCOME FOR THE CASE PATIENT
Histologic evaluation of tissue from the lacrimal gland, parotid gland, and sinus cavity revealed inflammatory noncaseating granulomas, strongly suggestive of sarcoidosis. Diagnosis of ocular sarcoidosis was based on the noncaseating granulomas in the lacrimal gland.9,16 Pulmonary sarcoidosis was also diagnosed, based on the presence of hilar and mediastinal lymphadenopathy.7
The mass in the patient’s lacrimal gland was surgically removed. She was treated with a combination of topical and oral corticosteroids tapered over two weeks, which induced remission of her ocular disease. The patient will be seen annually by an ophthalmologic specialist and was advised to contact her clinician immediately if acute ocular symptoms recurred.10,17
The patient’s persistent cough was determined to be secondary to acute bronchitis, rather than to her pulmonary sarcoidosis, which required no treatment. She received a short course of antibiotics and antitussives for her bronchitis. Systemic corticosteroid treatment of her ocular sarcoidosis also had the benefit of decreasing the size of her pulmonary nodules. She will be followed with annual CT and chest x-rays to monitor the status of her hilar and mediastinal lymphadenopathy and the nodules.3 Periodic pulmonary function testing will also be performed.7
Continue for conclusion >>
CONCLUSION
The elusive nature of the diagnosis of sarcoidosis is well documented in the medical literature. In this case, histologic evaluation of biopsied tissue, correlated with clinical symptoms and radiographic findings, were essential in making the diagnosis.
Primary care providers may be the first to evaluate patients with ocular sarcoidosis and will oversee long-term management. Patients who present with symptoms of eye pain, visual disturbances, abnormal inflammatory ocular features, or swollen lacrimal glands should be referred to an ophthalmologic specialist for further evaluation.
REFERENCES
1. Jennette JC, Falk RJ, Bacon PA, et al. 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Arthritis Rheum. 2013;65(1):1-11.
2. Culver DA. Sarcoidosis. Immunol Allergy Clin North Am. 2012;32(4):487-511.
3. Spagnolo P, Luppi F, Roversi P, et al. Sarcoidosis: challenging diagnostic aspects of an old disease. Am J Med. 2012;125(2):118-125.
4. Dempsey OJ, Peterson EW, Kerr KM, Denison AR. Sarcoidosis. BMJ. 2009;339:620-625.
5. Brownell I, Ramirez-Valle F, Sanchez M, Prystowsky S. Evidence for mycobacteria in sarcoidosis. Am J Respir Cell Mol Biol. 2011;45(5):899-905.
6. Iannuzzi MC, Fontana JR. Sarcoidosis: clinical presentation, immunopathogenesis, and therapeutics. JAMA. 2011;305(4):391-399.
7. Baughman MD, Culver DA, Judson MA. A concise review of pulmonary sarcoidosis. Am J Respir Crit Care Med. 2011;183(5):573-581.
8. Koyama T, Ueda H, Togashi K, et al. Radiologic manifestations of sarcoidosis in various organs. Radiographics. 2004;24(1):87-104.
9. Herbort CP, Rao NA, Mochizuki M; for the Scientific Committee of First International Workshop on Ocular Sarcoidosis. International criteria for the diagnosis of ocular sarcoidosis: results of the first International Workshop on Ocular Sarcoidosis (IWOS). Ocul Immunol Inflamm. 2009; 17(3):160-169.
10. Jamilloux Y, Kodjikian L, Broussolle C, Seve P. Sarcoidosis and uveitis. Autoimmun Rev. 2014;13(8):840-849.
11. Barisani-Asenbauer T, Maca SM, Mejdoubi L, et al. Uveitis—a rare disease often associated with systemic diseases and infections—a systematic review of 2619 patients. Orphanet J Rare Dis. 2012;7:57.
12. Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. New Engl J Med. 2007;357(21):2153-2165.
13. Fontenot A, King T. Pathogenesis of sarcoidosis. www.uptodate.com/contents/pathogenesis-of-sarcoidosis?source=search_result&search=Pathogenesis+of+sarcoidosis&selectedTitle=1%7E150. Accessed February 17, 2015.
14. Saidha S, Sotirchos ES, Eckstein C. Etiology of sarcoidosis: does infection play a role? Yale J Biol Med. 2012;85(1):133-141.
15. Newman LS, Rose CS, Bresnitz EA, et al; for the ACCESS Research Group. A case control etiologic study of sarcoidosis. Environmental and occupational risk factors. Am J Respir Crit Care Med. 2004;170:1324-1330.
16. Kawaguchi T, Hanada A, Horie S, et al. Evaluation of characteristic ocular signs and systemic investigations in ocular sarcoidosis patients. Jpn J Opthalmol. 2007;51(2):121-126.
17. Bodaghi B, Touitou V, Fardeau C, et al. Ocular sarcoidosis. Presse Med. 2012;41(6 Pt 2):e349-e354.
FDA approves adhesive treatment for superficial varicose veins
The VenaSeal closure system, which uses an adhesive directly injected into the vein, has been approved as a permanent treatment for symptomatic, superficial varicose veins, the Food and Drug Administration announced on Feb. 20.
“This new system is the first to permanently treat varicose veins by sealing them with an adhesive,” Dr. William Maisel, acting director of the Office of Device Evaluation in the FDA’s Center for Devices and Radiological Health, said in the FDA’s statement. Because the system “does not incorporate heat application or cutting, the in-office procedure can allow patients to quickly return to their normal activities, with less bruising,” he added.
The VenaSeal system differs from other procedures used to treat varicose veins, which use drugs, lasers, radiofrequency, or incisions, the FDA statement points out. The complete sterile kit includes the adhesive (n-butyl-2-cyanoacrylate), which solidifies when injected directly into the target vein via a catheter, under ultrasound guidance. The additional system components include the catheter, the adhesive, a guidewire, dispenser gun, dispenser tips, and syringes.
Approval was based on data from three clinical trials sponsored by the manufacturer. In the U.S. study that compared results in 108 patients treated with the VenaSeal system and 114 patients treated with radiofrequency ablation therapy, the device was shown “to be safe and effective for vein closure for the treatment of symptomatic superficial varicose veins of the legs,” according to the FDA. In the study, adverse events associated with the VenaSeal treatment included phlebitis and paresthesias in the treated areas, which are “generally associated with treatments of this condition,” the FDA statement noted.
The agency reviewed the VenaSeal System as a class III medical device, considered the highest risk type of medical devices that are subjected to the highest level of regulatory control, and which must be approved before marketing.
VenaSeal is manufactured by Covidien, which acquired Sapheon, the company that developed VenaSeal, in 2014. The system has also been approved in Canada, Europe, and Hong Kong, according to a Covidien statement issued last year.
The VenaSeal closure system, which uses an adhesive directly injected into the vein, has been approved as a permanent treatment for symptomatic, superficial varicose veins, the Food and Drug Administration announced on Feb. 20.
“This new system is the first to permanently treat varicose veins by sealing them with an adhesive,” Dr. William Maisel, acting director of the Office of Device Evaluation in the FDA’s Center for Devices and Radiological Health, said in the FDA’s statement. Because the system “does not incorporate heat application or cutting, the in-office procedure can allow patients to quickly return to their normal activities, with less bruising,” he added.
The VenaSeal system differs from other procedures used to treat varicose veins, which use drugs, lasers, radiofrequency, or incisions, the FDA statement points out. The complete sterile kit includes the adhesive (n-butyl-2-cyanoacrylate), which solidifies when injected directly into the target vein via a catheter, under ultrasound guidance. The additional system components include the catheter, the adhesive, a guidewire, dispenser gun, dispenser tips, and syringes.
Approval was based on data from three clinical trials sponsored by the manufacturer. In the U.S. study that compared results in 108 patients treated with the VenaSeal system and 114 patients treated with radiofrequency ablation therapy, the device was shown “to be safe and effective for vein closure for the treatment of symptomatic superficial varicose veins of the legs,” according to the FDA. In the study, adverse events associated with the VenaSeal treatment included phlebitis and paresthesias in the treated areas, which are “generally associated with treatments of this condition,” the FDA statement noted.
The agency reviewed the VenaSeal System as a class III medical device, considered the highest risk type of medical devices that are subjected to the highest level of regulatory control, and which must be approved before marketing.
VenaSeal is manufactured by Covidien, which acquired Sapheon, the company that developed VenaSeal, in 2014. The system has also been approved in Canada, Europe, and Hong Kong, according to a Covidien statement issued last year.
The VenaSeal closure system, which uses an adhesive directly injected into the vein, has been approved as a permanent treatment for symptomatic, superficial varicose veins, the Food and Drug Administration announced on Feb. 20.
“This new system is the first to permanently treat varicose veins by sealing them with an adhesive,” Dr. William Maisel, acting director of the Office of Device Evaluation in the FDA’s Center for Devices and Radiological Health, said in the FDA’s statement. Because the system “does not incorporate heat application or cutting, the in-office procedure can allow patients to quickly return to their normal activities, with less bruising,” he added.
The VenaSeal system differs from other procedures used to treat varicose veins, which use drugs, lasers, radiofrequency, or incisions, the FDA statement points out. The complete sterile kit includes the adhesive (n-butyl-2-cyanoacrylate), which solidifies when injected directly into the target vein via a catheter, under ultrasound guidance. The additional system components include the catheter, the adhesive, a guidewire, dispenser gun, dispenser tips, and syringes.
Approval was based on data from three clinical trials sponsored by the manufacturer. In the U.S. study that compared results in 108 patients treated with the VenaSeal system and 114 patients treated with radiofrequency ablation therapy, the device was shown “to be safe and effective for vein closure for the treatment of symptomatic superficial varicose veins of the legs,” according to the FDA. In the study, adverse events associated with the VenaSeal treatment included phlebitis and paresthesias in the treated areas, which are “generally associated with treatments of this condition,” the FDA statement noted.
The agency reviewed the VenaSeal System as a class III medical device, considered the highest risk type of medical devices that are subjected to the highest level of regulatory control, and which must be approved before marketing.
VenaSeal is manufactured by Covidien, which acquired Sapheon, the company that developed VenaSeal, in 2014. The system has also been approved in Canada, Europe, and Hong Kong, according to a Covidien statement issued last year.
Abnormal calcium level in a psychiatric presentation? Rule out parathyroid disease
In some patients, symptoms of depression, psychosis, delirium, or dementia exist concomitantly with, or as a result of, an abnormal (elevated or low) serum calcium concentration that has been precipitated by an unrecognized endocrinopathy. The apparent psychiatric presentations of such patients might reflect parathyroid pathology—not psychopathology.
Hypercalcemia and hypocalcemia often are related to a distinct spectrum of conditions, such as diseases of the parathyroid glands, kidneys, and various neoplasms including malignancies. Be alert to the possibility of parathyroid disease in patients whose presentation suggests mental illness concurrent with, or as a direct consequence of, an abnormal calcium level, and investigate appropriately.
The Table1-9 illustrates how 3 clinical laboratory tests—serum calcium, serum parathyroid hormone (PTH), and phosphate—can narrow the differential diagnosis when the clinical impression is parathyroid-related illness. Seek endocrinology consultation whenever a parathyroid-associated ailment is discovered or suspected. Serum calcium is routinely assayed in hospitalized patients; when managing a patient with treatment-refractory psychiatric illness, (1) always check the reported result of that test and (2) consider measuring PTH.
Case reports1
Case 1: Woman with chronic depression. The patient was hospitalized while suicidal. Serial serum calcium levels were 12.5 mg/dL and 15.8 mg/dL (reference range, 8.2–10.2 mg/dL). The PTH level was elevated at 287 pg/mL (reference range, 10–65 pg/mL).
After thyroid imaging, surgery revealed a parathyroid mass, which was resected. Histologic examination confirmed an adenoma.
The calcium concentration declined to 8.6 mg/dL postoperatively and stabilized at 9.2 mg/dL. Psychiatric symptoms resolved fully; she experienced a complete recovery.
Case 2: Man on long-term lithium maintenance. The patient was admitted in a delusional psychotic state. The serum calcium level was 14.3 mg/dL initially, decreasing to 11.5 mg/dL after lithium was discontinued. The PTH level was elevated at 97 pg/mL at admission, consistent with hyperparathyroidism.
A parathyroid adenoma was resected. Serum calcium level normalized at 10.7 mg/dL; psychosis resolved with striking, sustained improvement in mental status.
Full return to mental, physical health
The diagnosis of parathyroid adenoma in these 2 patients, which began with a psychiatric presentation, was properly made after an abnormal serum calcium level was documented. Surgical treatment of the endocrinopathy produced full remission and a return to normal mental and physical health.
Although psychiatric manifestations are associated with an abnormal serum calcium concentration, the severity of those presentations does not correlate with the degree of abnormality of the calcium level.10
Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.
1. Velasco PJ, Manshadi M, Breen K, et al. Psychiatric aspects of parathyroid disease. Psychosomatics. 1999;40(6):486-490.
2. Harrop JS, Bailey JE, Woodhead JS. Incidence of hypercalcaemia and primary hyperparathyroidism in relation to the biochemical profile. J Clin Pathol. 1982; 35(4):395-400.
3. Assadi F. Hypophosphatemia: an evidence-based problem-solving approach to clinical cases. Iran J Kidney Dis. 2010;4(3):195-201.
4. Ozkhan B, Hatun S, Bereket A. Vitamin D intoxication. Turk J Pediatr. 2012;54(2):93-98.
5. Studdy PR, Bird R, Neville E, et al. Biochemical findings in sarcoidosis. J Clin Pathol. 1980;33(6):528-533.
6. Geller JL, Adam JS. Vitamin D therapy. Curr Osteoporos Rep. 2008;6(1):5-11.
7. Albaaj F, Hutchison A. Hyperphosphatemia in renal failure: causes, consequences and current management. Drugs. 2003;63(6):577-596.
8. Al-Azem H, Khan AA. Hypoparathyroidism. Best Pract Res Clin Endocrinol Metab. 2012;26(4):517-522.
9. Brown H, Englert E, Wallach S. The syndrome of pseudo-pseudohypoparathyroidism. AMA Arch Intern Med. 1956;98(4):517-524.
10. Pfitzenmeyer P, Besancenot JF, Verges B, et al. Primary hyperparathyroidism in very old patients. Eur J Med. 1993;2(8):453-456.
In some patients, symptoms of depression, psychosis, delirium, or dementia exist concomitantly with, or as a result of, an abnormal (elevated or low) serum calcium concentration that has been precipitated by an unrecognized endocrinopathy. The apparent psychiatric presentations of such patients might reflect parathyroid pathology—not psychopathology.
Hypercalcemia and hypocalcemia often are related to a distinct spectrum of conditions, such as diseases of the parathyroid glands, kidneys, and various neoplasms including malignancies. Be alert to the possibility of parathyroid disease in patients whose presentation suggests mental illness concurrent with, or as a direct consequence of, an abnormal calcium level, and investigate appropriately.
The Table1-9 illustrates how 3 clinical laboratory tests—serum calcium, serum parathyroid hormone (PTH), and phosphate—can narrow the differential diagnosis when the clinical impression is parathyroid-related illness. Seek endocrinology consultation whenever a parathyroid-associated ailment is discovered or suspected. Serum calcium is routinely assayed in hospitalized patients; when managing a patient with treatment-refractory psychiatric illness, (1) always check the reported result of that test and (2) consider measuring PTH.
Case reports1
Case 1: Woman with chronic depression. The patient was hospitalized while suicidal. Serial serum calcium levels were 12.5 mg/dL and 15.8 mg/dL (reference range, 8.2–10.2 mg/dL). The PTH level was elevated at 287 pg/mL (reference range, 10–65 pg/mL).
After thyroid imaging, surgery revealed a parathyroid mass, which was resected. Histologic examination confirmed an adenoma.
The calcium concentration declined to 8.6 mg/dL postoperatively and stabilized at 9.2 mg/dL. Psychiatric symptoms resolved fully; she experienced a complete recovery.
Case 2: Man on long-term lithium maintenance. The patient was admitted in a delusional psychotic state. The serum calcium level was 14.3 mg/dL initially, decreasing to 11.5 mg/dL after lithium was discontinued. The PTH level was elevated at 97 pg/mL at admission, consistent with hyperparathyroidism.
A parathyroid adenoma was resected. Serum calcium level normalized at 10.7 mg/dL; psychosis resolved with striking, sustained improvement in mental status.
Full return to mental, physical health
The diagnosis of parathyroid adenoma in these 2 patients, which began with a psychiatric presentation, was properly made after an abnormal serum calcium level was documented. Surgical treatment of the endocrinopathy produced full remission and a return to normal mental and physical health.
Although psychiatric manifestations are associated with an abnormal serum calcium concentration, the severity of those presentations does not correlate with the degree of abnormality of the calcium level.10
Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.
In some patients, symptoms of depression, psychosis, delirium, or dementia exist concomitantly with, or as a result of, an abnormal (elevated or low) serum calcium concentration that has been precipitated by an unrecognized endocrinopathy. The apparent psychiatric presentations of such patients might reflect parathyroid pathology—not psychopathology.
Hypercalcemia and hypocalcemia often are related to a distinct spectrum of conditions, such as diseases of the parathyroid glands, kidneys, and various neoplasms including malignancies. Be alert to the possibility of parathyroid disease in patients whose presentation suggests mental illness concurrent with, or as a direct consequence of, an abnormal calcium level, and investigate appropriately.
The Table1-9 illustrates how 3 clinical laboratory tests—serum calcium, serum parathyroid hormone (PTH), and phosphate—can narrow the differential diagnosis when the clinical impression is parathyroid-related illness. Seek endocrinology consultation whenever a parathyroid-associated ailment is discovered or suspected. Serum calcium is routinely assayed in hospitalized patients; when managing a patient with treatment-refractory psychiatric illness, (1) always check the reported result of that test and (2) consider measuring PTH.
Case reports1
Case 1: Woman with chronic depression. The patient was hospitalized while suicidal. Serial serum calcium levels were 12.5 mg/dL and 15.8 mg/dL (reference range, 8.2–10.2 mg/dL). The PTH level was elevated at 287 pg/mL (reference range, 10–65 pg/mL).
After thyroid imaging, surgery revealed a parathyroid mass, which was resected. Histologic examination confirmed an adenoma.
The calcium concentration declined to 8.6 mg/dL postoperatively and stabilized at 9.2 mg/dL. Psychiatric symptoms resolved fully; she experienced a complete recovery.
Case 2: Man on long-term lithium maintenance. The patient was admitted in a delusional psychotic state. The serum calcium level was 14.3 mg/dL initially, decreasing to 11.5 mg/dL after lithium was discontinued. The PTH level was elevated at 97 pg/mL at admission, consistent with hyperparathyroidism.
A parathyroid adenoma was resected. Serum calcium level normalized at 10.7 mg/dL; psychosis resolved with striking, sustained improvement in mental status.
Full return to mental, physical health
The diagnosis of parathyroid adenoma in these 2 patients, which began with a psychiatric presentation, was properly made after an abnormal serum calcium level was documented. Surgical treatment of the endocrinopathy produced full remission and a return to normal mental and physical health.
Although psychiatric manifestations are associated with an abnormal serum calcium concentration, the severity of those presentations does not correlate with the degree of abnormality of the calcium level.10
Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.
1. Velasco PJ, Manshadi M, Breen K, et al. Psychiatric aspects of parathyroid disease. Psychosomatics. 1999;40(6):486-490.
2. Harrop JS, Bailey JE, Woodhead JS. Incidence of hypercalcaemia and primary hyperparathyroidism in relation to the biochemical profile. J Clin Pathol. 1982; 35(4):395-400.
3. Assadi F. Hypophosphatemia: an evidence-based problem-solving approach to clinical cases. Iran J Kidney Dis. 2010;4(3):195-201.
4. Ozkhan B, Hatun S, Bereket A. Vitamin D intoxication. Turk J Pediatr. 2012;54(2):93-98.
5. Studdy PR, Bird R, Neville E, et al. Biochemical findings in sarcoidosis. J Clin Pathol. 1980;33(6):528-533.
6. Geller JL, Adam JS. Vitamin D therapy. Curr Osteoporos Rep. 2008;6(1):5-11.
7. Albaaj F, Hutchison A. Hyperphosphatemia in renal failure: causes, consequences and current management. Drugs. 2003;63(6):577-596.
8. Al-Azem H, Khan AA. Hypoparathyroidism. Best Pract Res Clin Endocrinol Metab. 2012;26(4):517-522.
9. Brown H, Englert E, Wallach S. The syndrome of pseudo-pseudohypoparathyroidism. AMA Arch Intern Med. 1956;98(4):517-524.
10. Pfitzenmeyer P, Besancenot JF, Verges B, et al. Primary hyperparathyroidism in very old patients. Eur J Med. 1993;2(8):453-456.
1. Velasco PJ, Manshadi M, Breen K, et al. Psychiatric aspects of parathyroid disease. Psychosomatics. 1999;40(6):486-490.
2. Harrop JS, Bailey JE, Woodhead JS. Incidence of hypercalcaemia and primary hyperparathyroidism in relation to the biochemical profile. J Clin Pathol. 1982; 35(4):395-400.
3. Assadi F. Hypophosphatemia: an evidence-based problem-solving approach to clinical cases. Iran J Kidney Dis. 2010;4(3):195-201.
4. Ozkhan B, Hatun S, Bereket A. Vitamin D intoxication. Turk J Pediatr. 2012;54(2):93-98.
5. Studdy PR, Bird R, Neville E, et al. Biochemical findings in sarcoidosis. J Clin Pathol. 1980;33(6):528-533.
6. Geller JL, Adam JS. Vitamin D therapy. Curr Osteoporos Rep. 2008;6(1):5-11.
7. Albaaj F, Hutchison A. Hyperphosphatemia in renal failure: causes, consequences and current management. Drugs. 2003;63(6):577-596.
8. Al-Azem H, Khan AA. Hypoparathyroidism. Best Pract Res Clin Endocrinol Metab. 2012;26(4):517-522.
9. Brown H, Englert E, Wallach S. The syndrome of pseudo-pseudohypoparathyroidism. AMA Arch Intern Med. 1956;98(4):517-524.
10. Pfitzenmeyer P, Besancenot JF, Verges B, et al. Primary hyperparathyroidism in very old patients. Eur J Med. 1993;2(8):453-456.
Can Vitamin D Supplements Help With Hypertension?
Q) One of my patients came in and said he had read that vitamin D supplementation will help with hypertension. Now he wants to quit his blood pressure meds and use vitamin D instead. Do you have any background on this?
Vitamin D is critical for utilization of calcium, a vital nutrient for multiple metabolic and cellular processes; deficiency is associated with worsening of autoimmune disorders, osteoporosis, and certain cardiovascular conditions, among others.7 An association between vitamin D level and blood pressure has been recognized for some time, but the pathophysiology is not well understood.
A literature review of studies from 1988 to 2013 found contradictory results regarding vitamin D deficiency and concurrent elevated blood pressure (systolic and/or diastolic), as well as the impact on blood pressure with restoration of vitamin D levels. The findings were limited by several factors, including differences in study design, variables evaluated, and type of vitamin D compound used. The results suggested a link between the renin-angiotensin-aldosterone system, fibroblast growth factor 23/klotho axis, and vitamin D level.8
A study of 158 subjects (98 with newly diagnosed essential hypertension, 60 with normal blood pressure) found significantly lower 25(OH)D3 serum levels in hypertensive patients. Furthermore, the 25(OH)D3 level was significantly correlated with both systolic (r = –0.33) and diastolic blood pressure (r = –0.26). Using multiple regression analysis, after adjustment for age, smoking status, and BMI, the impact of 25(OH)D3 level accounted for 10% of the variation in systolic blood pressure.9
In a mendelian randomization study of 108,173 subjects from 35 studies, an inverse association between vitamin D level and systolic blood pressure (P = .0003) was found. A reduced risk for essential hypertension with increased vitamin D level (P = .0003) was also noted. However, no association was found between increasing vitamin D level and a reduction in diastolic blood pressure
(P = .37).10
With the ever-increasing access to health information from sources such as “Doctor Google,” it can be difficult for a non–health care professional to separate hype from evidence-based recommendations. While current evidence suggests optimal vitamin D levels may be beneficial for improving blood pressure control and may be a useful adjunctive therapy, there is no evidence to support discontinuing antihypertensive therapy and replacing it with vitamin D therapy.
Cynthia A. Smith, DNP, APRN, FNP-BC
Renal Consultants, South Charleston, West Virginia
REFERENCES
1. Monfared A, Heidarzadeh A, Ghaffari M, Akbarpour M. Effect of megestrol acetate on serum albumin level in malnourished dialysis patients. J Renal Nutr. 2009;19(2):167-171.
2. Byham-Gray L, Stover J, Wiesen K. A clinical guide to nutrition care in kidney disease. Acad Nutr Diet. 2013.
3. White JV, Guenter P, Jensen G, Malone A, Schofield M; Academy of Nutrition and Dietetics Malnutrition Work Group; ASPEN Malnutrition Task Force; ASPEN Board of Directors. Consensus statement of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition: characteristics recommended for the identification and documentation of adult malnutrition (undernutrition) [erratum appears in J Acad Nutr Diet. 2012 Nov;112(11):1899].
J Acad Nutr Diet. 2012;112(5):730-738.
4. Rammohan M, Kalantar-Zedeh K, Liang A, Ghossein C. Megestrol acetate in a moderate dose for the treatment of malnutrition-inflammation complex in maintenance dialysis patients. J Ren Nutr. 2005;15(3):345-355.
5. Yeh S, Marandi M, Thode H Jr, et al. Report of a pilot, double blind, placebo-controlled study of megestrol acetate in elderly dialysis patients with cachexia. J Ren Nutr. 2010; 20(1):52-62.
6. Golebiewska JE, Lichodziejewska-Niemierko M, Aleksandrowicz-Wrona E, et al. Megestrol acetate use in hypoalbuminemic dialysis patients [comment]. J Ren Nutr. 2011;21(2): 200-202.
7. Bendik I, Friedel A, Roos FF, et al. Vitamin D: a critical and necessary micronutrient for human health. Front Physiol. 2014;5:248.
8. Cabone F, Mach F, Vuilleumier N, Montecucco F. Potential pathophysiological role for the vitamin D deficiency in essential hypertension. World J Cardiol. 2014;6(5):260-276.
9. Sypniewska G, Pollak J, Strozecki P, et al. 25-hydroxyvitamin D, biomarkers of endothelial dysfunction and subclinical organ damage in adults with hypertension. Am J Hypertens. 2014;27(1):114-121.
10. Vimaleswaran KS, Cavadino A, Berry DJ, et al. Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study. Lancet Diabetes Endocrinol. 2014;2(9):719-729.
| Clinician Reviews in partnership with |
 |
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National Kidney Foundation’s Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, who is a physician assistant with Metropolitan Nephrology in Alexandria, Virginia, and Clinton, Maryland; she is also past chair of the NKF-CAP. This month’s responses were authored by Luanne DiGuglielmo, MS, RD, CSR, who practices at DaVita Summit Renal Center in Mountainside, New Jersey, and is the Clinical Coordinator for the Dietetic Internship at the College of Saint Elizabeth in Morristown, New Jersey, and Cynthia A. Smith, DNP, APRN, FNP-BC, who practices at Renal Consultants, South Charleston, West Virginia.
| Clinician Reviews in partnership with |
|
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National Kidney Foundation’s Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, who is a physician assistant with Metropolitan Nephrology in Alexandria, Virginia, and Clinton, Maryland; she is also past chair of the NKF-CAP. This month’s responses were authored by Luanne DiGuglielmo, MS, RD, CSR, who practices at DaVita Summit Renal Center in Mountainside, New Jersey, and is the Clinical Coordinator for the Dietetic Internship at the College of Saint Elizabeth in Morristown, New Jersey, and Cynthia A. Smith, DNP, APRN, FNP-BC, who practices at Renal Consultants, South Charleston, West Virginia.
| Clinician Reviews in partnership with |
|
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National Kidney Foundation’s Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, who is a physician assistant with Metropolitan Nephrology in Alexandria, Virginia, and Clinton, Maryland; she is also past chair of the NKF-CAP. This month’s responses were authored by Luanne DiGuglielmo, MS, RD, CSR, who practices at DaVita Summit Renal Center in Mountainside, New Jersey, and is the Clinical Coordinator for the Dietetic Internship at the College of Saint Elizabeth in Morristown, New Jersey, and Cynthia A. Smith, DNP, APRN, FNP-BC, who practices at Renal Consultants, South Charleston, West Virginia.
Q) One of my patients came in and said he had read that vitamin D supplementation will help with hypertension. Now he wants to quit his blood pressure meds and use vitamin D instead. Do you have any background on this?
Vitamin D is critical for utilization of calcium, a vital nutrient for multiple metabolic and cellular processes; deficiency is associated with worsening of autoimmune disorders, osteoporosis, and certain cardiovascular conditions, among others.7 An association between vitamin D level and blood pressure has been recognized for some time, but the pathophysiology is not well understood.
A literature review of studies from 1988 to 2013 found contradictory results regarding vitamin D deficiency and concurrent elevated blood pressure (systolic and/or diastolic), as well as the impact on blood pressure with restoration of vitamin D levels. The findings were limited by several factors, including differences in study design, variables evaluated, and type of vitamin D compound used. The results suggested a link between the renin-angiotensin-aldosterone system, fibroblast growth factor 23/klotho axis, and vitamin D level.8
A study of 158 subjects (98 with newly diagnosed essential hypertension, 60 with normal blood pressure) found significantly lower 25(OH)D3 serum levels in hypertensive patients. Furthermore, the 25(OH)D3 level was significantly correlated with both systolic (r = –0.33) and diastolic blood pressure (r = –0.26). Using multiple regression analysis, after adjustment for age, smoking status, and BMI, the impact of 25(OH)D3 level accounted for 10% of the variation in systolic blood pressure.9
In a mendelian randomization study of 108,173 subjects from 35 studies, an inverse association between vitamin D level and systolic blood pressure (P = .0003) was found. A reduced risk for essential hypertension with increased vitamin D level (P = .0003) was also noted. However, no association was found between increasing vitamin D level and a reduction in diastolic blood pressure
(P = .37).10
With the ever-increasing access to health information from sources such as “Doctor Google,” it can be difficult for a non–health care professional to separate hype from evidence-based recommendations. While current evidence suggests optimal vitamin D levels may be beneficial for improving blood pressure control and may be a useful adjunctive therapy, there is no evidence to support discontinuing antihypertensive therapy and replacing it with vitamin D therapy.
Cynthia A. Smith, DNP, APRN, FNP-BC
Renal Consultants, South Charleston, West Virginia
REFERENCES
1. Monfared A, Heidarzadeh A, Ghaffari M, Akbarpour M. Effect of megestrol acetate on serum albumin level in malnourished dialysis patients. J Renal Nutr. 2009;19(2):167-171.
2. Byham-Gray L, Stover J, Wiesen K. A clinical guide to nutrition care in kidney disease. Acad Nutr Diet. 2013.
3. White JV, Guenter P, Jensen G, Malone A, Schofield M; Academy of Nutrition and Dietetics Malnutrition Work Group; ASPEN Malnutrition Task Force; ASPEN Board of Directors. Consensus statement of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition: characteristics recommended for the identification and documentation of adult malnutrition (undernutrition) [erratum appears in J Acad Nutr Diet. 2012 Nov;112(11):1899].
J Acad Nutr Diet. 2012;112(5):730-738.
4. Rammohan M, Kalantar-Zedeh K, Liang A, Ghossein C. Megestrol acetate in a moderate dose for the treatment of malnutrition-inflammation complex in maintenance dialysis patients. J Ren Nutr. 2005;15(3):345-355.
5. Yeh S, Marandi M, Thode H Jr, et al. Report of a pilot, double blind, placebo-controlled study of megestrol acetate in elderly dialysis patients with cachexia. J Ren Nutr. 2010; 20(1):52-62.
6. Golebiewska JE, Lichodziejewska-Niemierko M, Aleksandrowicz-Wrona E, et al. Megestrol acetate use in hypoalbuminemic dialysis patients [comment]. J Ren Nutr. 2011;21(2): 200-202.
7. Bendik I, Friedel A, Roos FF, et al. Vitamin D: a critical and necessary micronutrient for human health. Front Physiol. 2014;5:248.
8. Cabone F, Mach F, Vuilleumier N, Montecucco F. Potential pathophysiological role for the vitamin D deficiency in essential hypertension. World J Cardiol. 2014;6(5):260-276.
9. Sypniewska G, Pollak J, Strozecki P, et al. 25-hydroxyvitamin D, biomarkers of endothelial dysfunction and subclinical organ damage in adults with hypertension. Am J Hypertens. 2014;27(1):114-121.
10. Vimaleswaran KS, Cavadino A, Berry DJ, et al. Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study. Lancet Diabetes Endocrinol. 2014;2(9):719-729.
Q) One of my patients came in and said he had read that vitamin D supplementation will help with hypertension. Now he wants to quit his blood pressure meds and use vitamin D instead. Do you have any background on this?
Vitamin D is critical for utilization of calcium, a vital nutrient for multiple metabolic and cellular processes; deficiency is associated with worsening of autoimmune disorders, osteoporosis, and certain cardiovascular conditions, among others.7 An association between vitamin D level and blood pressure has been recognized for some time, but the pathophysiology is not well understood.
A literature review of studies from 1988 to 2013 found contradictory results regarding vitamin D deficiency and concurrent elevated blood pressure (systolic and/or diastolic), as well as the impact on blood pressure with restoration of vitamin D levels. The findings were limited by several factors, including differences in study design, variables evaluated, and type of vitamin D compound used. The results suggested a link between the renin-angiotensin-aldosterone system, fibroblast growth factor 23/klotho axis, and vitamin D level.8
A study of 158 subjects (98 with newly diagnosed essential hypertension, 60 with normal blood pressure) found significantly lower 25(OH)D3 serum levels in hypertensive patients. Furthermore, the 25(OH)D3 level was significantly correlated with both systolic (r = –0.33) and diastolic blood pressure (r = –0.26). Using multiple regression analysis, after adjustment for age, smoking status, and BMI, the impact of 25(OH)D3 level accounted for 10% of the variation in systolic blood pressure.9
In a mendelian randomization study of 108,173 subjects from 35 studies, an inverse association between vitamin D level and systolic blood pressure (P = .0003) was found. A reduced risk for essential hypertension with increased vitamin D level (P = .0003) was also noted. However, no association was found between increasing vitamin D level and a reduction in diastolic blood pressure
(P = .37).10
With the ever-increasing access to health information from sources such as “Doctor Google,” it can be difficult for a non–health care professional to separate hype from evidence-based recommendations. While current evidence suggests optimal vitamin D levels may be beneficial for improving blood pressure control and may be a useful adjunctive therapy, there is no evidence to support discontinuing antihypertensive therapy and replacing it with vitamin D therapy.
Cynthia A. Smith, DNP, APRN, FNP-BC
Renal Consultants, South Charleston, West Virginia
REFERENCES
1. Monfared A, Heidarzadeh A, Ghaffari M, Akbarpour M. Effect of megestrol acetate on serum albumin level in malnourished dialysis patients. J Renal Nutr. 2009;19(2):167-171.
2. Byham-Gray L, Stover J, Wiesen K. A clinical guide to nutrition care in kidney disease. Acad Nutr Diet. 2013.
3. White JV, Guenter P, Jensen G, Malone A, Schofield M; Academy of Nutrition and Dietetics Malnutrition Work Group; ASPEN Malnutrition Task Force; ASPEN Board of Directors. Consensus statement of the Academy of Nutrition and Dietetics/American Society for Parenteral and Enteral Nutrition: characteristics recommended for the identification and documentation of adult malnutrition (undernutrition) [erratum appears in J Acad Nutr Diet. 2012 Nov;112(11):1899].
J Acad Nutr Diet. 2012;112(5):730-738.
4. Rammohan M, Kalantar-Zedeh K, Liang A, Ghossein C. Megestrol acetate in a moderate dose for the treatment of malnutrition-inflammation complex in maintenance dialysis patients. J Ren Nutr. 2005;15(3):345-355.
5. Yeh S, Marandi M, Thode H Jr, et al. Report of a pilot, double blind, placebo-controlled study of megestrol acetate in elderly dialysis patients with cachexia. J Ren Nutr. 2010; 20(1):52-62.
6. Golebiewska JE, Lichodziejewska-Niemierko M, Aleksandrowicz-Wrona E, et al. Megestrol acetate use in hypoalbuminemic dialysis patients [comment]. J Ren Nutr. 2011;21(2): 200-202.
7. Bendik I, Friedel A, Roos FF, et al. Vitamin D: a critical and necessary micronutrient for human health. Front Physiol. 2014;5:248.
8. Cabone F, Mach F, Vuilleumier N, Montecucco F. Potential pathophysiological role for the vitamin D deficiency in essential hypertension. World J Cardiol. 2014;6(5):260-276.
9. Sypniewska G, Pollak J, Strozecki P, et al. 25-hydroxyvitamin D, biomarkers of endothelial dysfunction and subclinical organ damage in adults with hypertension. Am J Hypertens. 2014;27(1):114-121.
10. Vimaleswaran KS, Cavadino A, Berry DJ, et al. Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study. Lancet Diabetes Endocrinol. 2014;2(9):719-729.