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Pregnancy registries add to the clinical picture
Pregnancy registries are valuable sources of information. For many drugs, they are the primary source of human pregnancy experience. The new Food and Drug Administration prescription drug information format may increase the amount of information available, at least from registries conducted by drug manufacturers, because they will be required to list all substantive changes made within the year. Although most of the registries use the word “pregnancy,” it is important to note that many also enroll women who took the target drug shortly before conception.
The strengths of pregnancy registries are their prospective nature and enrollment across a wide geographical area. Typically, two types of pregnancy outcomes are obtained: those with birth defects and those without known birth defects (classified as live births, fetal deaths, and spontaneous abortions).
Registries can identify early signals of teratogenicity, but they have several limitations, including voluntary reporting that results in selection bias, pregnancies lost to follow-up that may have had different outcomes than those with documented outcomes, and a lack of control groups (with some exceptions).
Other limitations are that registry cases are not representative of target populations, and pregnancies lost to follow-up lack details on elective terminations and fetal deaths without birth defects, as well as all spontaneous abortions. Additionally, publication of results may be delayed and does not appear in a peer-reviewed journal.
Since the total number of exposed pregnancies is unknown, registry data cannot be used to calculate prevalence, but can be used to estimate the proportion of birth defects. Some registries also collect data on retrospective reports, which are less representative of the target population because they can be biased toward the reporting of more unusual and severe outcomes. However, they may be helpful in detecting unusual patterns of birth defects.
MothertoBaby Registry
The large Organization of Teratology Information Specialists (OTIS) MothertoBaby registry (877-311-8972) involves four different categories: autoimmune diseases(rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, psoriasis, Crohn’s disease, and multiple sclerosis); asthma; antiviral agents; and vaccines.
The drugs for autoimmune diseases are tocilizumab (Actemra), leflunomide (Arava), teriflunomide (Aubagio), certolizumab pegol (Cimzia), etanercept (Enbrel), adalimumab (Humira), abatacept (Orencia), apremilast (Otezla), ustekinumab (Stelara), tofacitinib (Xeljanz), infliximab (Remicade), and methotrexate.
The asthma drugs are formoterol (Foradil, Perforomist, Symbicort, Dulera), albuterol, levalbuterol, metaproterenol, pirbuterol (Maxair), and terbutaline.
The antiviral agents are oseltamivir (Tamiflu) and zanamivir (Relenza).
The vaccines include pertussis (Tdap), seasonal influenza, and meningococcal disease (Menveo). In addition to a control group in each category, a unique aspect of this registry is that many exposed infants will undergo dysmorphology examinations.
Vaccine registries
A second vaccine for meningococcal disease (Menactra) is being studied in the Menactra vaccine Pregnancy Registry (800-822-2463 / www.sanofipasteurpregnancy.com).
Two other registries also include influenza vaccines: Flu vaccine Pregnancy Registry, PPD (Flucelvax) (877-413-4759 / email: [email protected]) and the GSK Seasonal Influenza Vaccine Pregnancy Registry, GlaxoSmithKline (888-825-5249 / pregnancyregistry.gsk.com/seasonalinfluenzavaccines.html), which includes the Fluarix and FluLaval vaccines.
Asthma
Women with asthma who are being treated with omalizumab (Xolair) are the target population for the EXPECT Pregnancy Registry (866-496-5247 Option 3 / www.xolairpregnancyregistry.com).
GSK registries
GlaxoSmithKline is also conducting three other registries: the Belimumab (Benlysta) Pregnancy Registry for patients with systemic lupus erythematosus treated with belimumab (877-681-6296 / [email protected]); and the Twinrix Pregnancy Registry for women who have received the Twinrix hepatitis A and B vaccine (888-825-5249).
Atypical antipsychotics
TheNational Pregnancy Registry for Atypical Antipsychotics (866-961-2388 / registry@womens mentalhealth.org) is studying 10 drugs: aripiprazole (Abilify), clozapine (Clozaril), iloperidone (Fanapt), paliperidone (Invega), lurasidone (Latuda), risperidone (Risperdal), asenapine (Saphris), quetiapine (Seroquel), ziprasidone (Geodon), and olanzapine (Zyprexa).
TAPP registry
Acitretin is under study by the Take Action to Prevent Pregnancy (T.A.P.P.) registry (855-850-2138 / www.tevagenerics.com/acitretin).
MPS I registry
The MPS I (Mucopolysaccharidosis I) Registry, Genzyme Corp (617-591-5500 / [email protected]), is studying the use of laronidase (Aldurazyme) for Hurler syndrome, Scheie syndrome, and Hurler-Scheie syndrome.
MPS VI registry
The use of galsulfase (Naglazyme) for Maroteaux-Lamy syndrome during pregnancy is under study by the Mucopolysaccharidosis VI (MPS VI) Clinical Surveillance Program(415-506-6849 or 415-506-6703)
Epilepsy drugs
The Antiepileptic Drug Pregnancy Registry (888-233-2334 / www.aedpregnancyregistry.org) is studying antiepileptic drugs.
Type 2 diabetes
The Exenatide Pregnancy Registry, conducted by INC Research for AstraZeneca (800-633-9081 / www.exenatidepregnancyregistry.com), examines the use of exenatide (Byetta, Bydureon) for the treatment of type 2 diabetes.
Renal transplant
Renal transplant patients exposed to mycophenolate (Cellcept) can be enrolled in the Mycophenolate Pregnancy Registry (800-617-8191) or the National Transplantation Pregnancy Registry (877-955-6877). The NTPR is enrolling renal transplant patients exposed to belatacept (Nulojix).
Cymbalta
The antidepressant duloxetine (Cymbalta), when used for major depressive or generalized anxiety disorders, diabetic peripheral neuropathic pain, or fibromyalgia is being studied by the Cymbalta Pregnancy Registry, INC Research ([email protected] / www.cymbaltapregancyregistry.com).
Fabry disease
The Fabry Registry, Genzyme Corp (617-581-5500 / [email protected]) is studying the use in pregnancy of agalsidase beta (Fabrazyme) for Fabry disease.
MS registry
Novartis Pharmaceuticals is conducting the Gilenya (fingolimod) Pregnancy Registry (877-598-7237 / [email protected]) for patients with multiple sclerosis who are taking fingolimod (Gilenya).
Cancer
The MotHER Pregnancy Registry, INC Research (800-690-6720 / [email protected] / themotherpregnancyregistry.com) is enrolling breast cancer patients who have been treated during pregnancy with ado-trastuzumab (Kadcyla), trastuzumab (Herceptin), or pertuzumab (Perjeta).
Merck registries
Merck Pregnancy Registries (800-986-8999) include a registry for type 2 diabetes – sitagliptin/metformin (Janumet) or sitagliptin (Januvia) (www.merckpregancyregistries.com/januvia.html); a registry for rizatriptan (Maxalt) (www.merckpregancyregistries.com/maxalt.html), for migraine headaches; and a registry for the 9-valent human papillomavirus (HPV) (Gardasil 9) vaccine (www.merckpregnancyregistries.com/gardasil9.html).
The registry for the asthma drug montelukast (Singulair) and the registry for Gardasil, the quadrivalent HPV vaccine, are now closed to new enrollment, but new cases of pregnancy exposures can be reported to the company at: 877-888-4231.
Osteoporosis
Amgen’s Pregnancy Surveillance Program (800-772-6436) is enrolling pregnant subjects with osteoporosis who are being treated with denosumab (Prolia).
Hepatitis C
The Ribavirin Pregnancy Registry, INC Research (800-593-2214/ [email protected] / ribavirinpregnancyregistry.com) is looking for subjects with hepatitis C who have been treated with ribavirin (Copegus).
Fibromyalgia
The Savella Pregnancy Registry (877-643-3010/ [email protected] / savellapregnancyregistry.com) is looking for patients with fibromyalgia who are being treated with milnacipran (Savella).
Skin infections
An antibacterial, telavancin (Vibativ), indicated for skin infections is being studied by the Vibativ Pregnancy Registry (888-658-4228 / www.clinicaltrial.gov).
Pompe disease
Pregnant women treated with alglucosidase alfa (Myozyme) for Pompe disease can enroll in the Pompe Registry (800-745-4447 x 15500 / www.pompe.com/en/healthcare-professionals/pompe-registry.aspx).
Sleep disorders
Armodafinil (Nuvigil) used to treat excessive sleepiness associated with narcolepsy and other sleep disorders is being studied in the Nuvigil Pregnancy Registry (866-404-4106 / www.nuvigilpregnancyregistry.com). A second drug with the same indication and telephone number, modafinil (Provigil), is in the Provigil Pregnancy Registry (provigilpregnancyregistry.com).
Additional details, including fax numbers and addresses of the registries reviewed above, can be obtained from the FDA website, List of Pregnancy Exposure Registries. Since the strength of a registry is based on numbers, health care professionals are encouraged to enroll potential subjects or have their patients call to enroll themselves.
Before retirement, Mr. Briggs was a pharmacist clinical specialist at the outpatient clinics of Memorial Care Center for Women at Miller Children’s Hospital in Long Beach, Calif.; he remains a clinical professor of pharmacy at the University of California, San Francisco; and adjunct professor of pharmacy at the University of Southern California, Los Angeles, and Washington State University, Spokane. He also is coauthor of “Drugs in Pregnancy and Lactation,” and coeditor of “Diseases, Complications, and Drug Therapy in Obstetrics.” He had no relevant financial disclosures. Contact him at [email protected].
Pregnancy registries are valuable sources of information. For many drugs, they are the primary source of human pregnancy experience. The new Food and Drug Administration prescription drug information format may increase the amount of information available, at least from registries conducted by drug manufacturers, because they will be required to list all substantive changes made within the year. Although most of the registries use the word “pregnancy,” it is important to note that many also enroll women who took the target drug shortly before conception.
The strengths of pregnancy registries are their prospective nature and enrollment across a wide geographical area. Typically, two types of pregnancy outcomes are obtained: those with birth defects and those without known birth defects (classified as live births, fetal deaths, and spontaneous abortions).
Registries can identify early signals of teratogenicity, but they have several limitations, including voluntary reporting that results in selection bias, pregnancies lost to follow-up that may have had different outcomes than those with documented outcomes, and a lack of control groups (with some exceptions).
Other limitations are that registry cases are not representative of target populations, and pregnancies lost to follow-up lack details on elective terminations and fetal deaths without birth defects, as well as all spontaneous abortions. Additionally, publication of results may be delayed and does not appear in a peer-reviewed journal.
Since the total number of exposed pregnancies is unknown, registry data cannot be used to calculate prevalence, but can be used to estimate the proportion of birth defects. Some registries also collect data on retrospective reports, which are less representative of the target population because they can be biased toward the reporting of more unusual and severe outcomes. However, they may be helpful in detecting unusual patterns of birth defects.
MothertoBaby Registry
The large Organization of Teratology Information Specialists (OTIS) MothertoBaby registry (877-311-8972) involves four different categories: autoimmune diseases(rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, psoriasis, Crohn’s disease, and multiple sclerosis); asthma; antiviral agents; and vaccines.
The drugs for autoimmune diseases are tocilizumab (Actemra), leflunomide (Arava), teriflunomide (Aubagio), certolizumab pegol (Cimzia), etanercept (Enbrel), adalimumab (Humira), abatacept (Orencia), apremilast (Otezla), ustekinumab (Stelara), tofacitinib (Xeljanz), infliximab (Remicade), and methotrexate.
The asthma drugs are formoterol (Foradil, Perforomist, Symbicort, Dulera), albuterol, levalbuterol, metaproterenol, pirbuterol (Maxair), and terbutaline.
The antiviral agents are oseltamivir (Tamiflu) and zanamivir (Relenza).
The vaccines include pertussis (Tdap), seasonal influenza, and meningococcal disease (Menveo). In addition to a control group in each category, a unique aspect of this registry is that many exposed infants will undergo dysmorphology examinations.
Vaccine registries
A second vaccine for meningococcal disease (Menactra) is being studied in the Menactra vaccine Pregnancy Registry (800-822-2463 / www.sanofipasteurpregnancy.com).
Two other registries also include influenza vaccines: Flu vaccine Pregnancy Registry, PPD (Flucelvax) (877-413-4759 / email: [email protected]) and the GSK Seasonal Influenza Vaccine Pregnancy Registry, GlaxoSmithKline (888-825-5249 / pregnancyregistry.gsk.com/seasonalinfluenzavaccines.html), which includes the Fluarix and FluLaval vaccines.
Asthma
Women with asthma who are being treated with omalizumab (Xolair) are the target population for the EXPECT Pregnancy Registry (866-496-5247 Option 3 / www.xolairpregnancyregistry.com).
GSK registries
GlaxoSmithKline is also conducting three other registries: the Belimumab (Benlysta) Pregnancy Registry for patients with systemic lupus erythematosus treated with belimumab (877-681-6296 / [email protected]); and the Twinrix Pregnancy Registry for women who have received the Twinrix hepatitis A and B vaccine (888-825-5249).
Atypical antipsychotics
TheNational Pregnancy Registry for Atypical Antipsychotics (866-961-2388 / registry@womens mentalhealth.org) is studying 10 drugs: aripiprazole (Abilify), clozapine (Clozaril), iloperidone (Fanapt), paliperidone (Invega), lurasidone (Latuda), risperidone (Risperdal), asenapine (Saphris), quetiapine (Seroquel), ziprasidone (Geodon), and olanzapine (Zyprexa).
TAPP registry
Acitretin is under study by the Take Action to Prevent Pregnancy (T.A.P.P.) registry (855-850-2138 / www.tevagenerics.com/acitretin).
MPS I registry
The MPS I (Mucopolysaccharidosis I) Registry, Genzyme Corp (617-591-5500 / [email protected]), is studying the use of laronidase (Aldurazyme) for Hurler syndrome, Scheie syndrome, and Hurler-Scheie syndrome.
MPS VI registry
The use of galsulfase (Naglazyme) for Maroteaux-Lamy syndrome during pregnancy is under study by the Mucopolysaccharidosis VI (MPS VI) Clinical Surveillance Program(415-506-6849 or 415-506-6703)
Epilepsy drugs
The Antiepileptic Drug Pregnancy Registry (888-233-2334 / www.aedpregnancyregistry.org) is studying antiepileptic drugs.
Type 2 diabetes
The Exenatide Pregnancy Registry, conducted by INC Research for AstraZeneca (800-633-9081 / www.exenatidepregnancyregistry.com), examines the use of exenatide (Byetta, Bydureon) for the treatment of type 2 diabetes.
Renal transplant
Renal transplant patients exposed to mycophenolate (Cellcept) can be enrolled in the Mycophenolate Pregnancy Registry (800-617-8191) or the National Transplantation Pregnancy Registry (877-955-6877). The NTPR is enrolling renal transplant patients exposed to belatacept (Nulojix).
Cymbalta
The antidepressant duloxetine (Cymbalta), when used for major depressive or generalized anxiety disorders, diabetic peripheral neuropathic pain, or fibromyalgia is being studied by the Cymbalta Pregnancy Registry, INC Research ([email protected] / www.cymbaltapregancyregistry.com).
Fabry disease
The Fabry Registry, Genzyme Corp (617-581-5500 / [email protected]) is studying the use in pregnancy of agalsidase beta (Fabrazyme) for Fabry disease.
MS registry
Novartis Pharmaceuticals is conducting the Gilenya (fingolimod) Pregnancy Registry (877-598-7237 / [email protected]) for patients with multiple sclerosis who are taking fingolimod (Gilenya).
Cancer
The MotHER Pregnancy Registry, INC Research (800-690-6720 / [email protected] / themotherpregnancyregistry.com) is enrolling breast cancer patients who have been treated during pregnancy with ado-trastuzumab (Kadcyla), trastuzumab (Herceptin), or pertuzumab (Perjeta).
Merck registries
Merck Pregnancy Registries (800-986-8999) include a registry for type 2 diabetes – sitagliptin/metformin (Janumet) or sitagliptin (Januvia) (www.merckpregancyregistries.com/januvia.html); a registry for rizatriptan (Maxalt) (www.merckpregancyregistries.com/maxalt.html), for migraine headaches; and a registry for the 9-valent human papillomavirus (HPV) (Gardasil 9) vaccine (www.merckpregnancyregistries.com/gardasil9.html).
The registry for the asthma drug montelukast (Singulair) and the registry for Gardasil, the quadrivalent HPV vaccine, are now closed to new enrollment, but new cases of pregnancy exposures can be reported to the company at: 877-888-4231.
Osteoporosis
Amgen’s Pregnancy Surveillance Program (800-772-6436) is enrolling pregnant subjects with osteoporosis who are being treated with denosumab (Prolia).
Hepatitis C
The Ribavirin Pregnancy Registry, INC Research (800-593-2214/ [email protected] / ribavirinpregnancyregistry.com) is looking for subjects with hepatitis C who have been treated with ribavirin (Copegus).
Fibromyalgia
The Savella Pregnancy Registry (877-643-3010/ [email protected] / savellapregnancyregistry.com) is looking for patients with fibromyalgia who are being treated with milnacipran (Savella).
Skin infections
An antibacterial, telavancin (Vibativ), indicated for skin infections is being studied by the Vibativ Pregnancy Registry (888-658-4228 / www.clinicaltrial.gov).
Pompe disease
Pregnant women treated with alglucosidase alfa (Myozyme) for Pompe disease can enroll in the Pompe Registry (800-745-4447 x 15500 / www.pompe.com/en/healthcare-professionals/pompe-registry.aspx).
Sleep disorders
Armodafinil (Nuvigil) used to treat excessive sleepiness associated with narcolepsy and other sleep disorders is being studied in the Nuvigil Pregnancy Registry (866-404-4106 / www.nuvigilpregnancyregistry.com). A second drug with the same indication and telephone number, modafinil (Provigil), is in the Provigil Pregnancy Registry (provigilpregnancyregistry.com).
Additional details, including fax numbers and addresses of the registries reviewed above, can be obtained from the FDA website, List of Pregnancy Exposure Registries. Since the strength of a registry is based on numbers, health care professionals are encouraged to enroll potential subjects or have their patients call to enroll themselves.
Before retirement, Mr. Briggs was a pharmacist clinical specialist at the outpatient clinics of Memorial Care Center for Women at Miller Children’s Hospital in Long Beach, Calif.; he remains a clinical professor of pharmacy at the University of California, San Francisco; and adjunct professor of pharmacy at the University of Southern California, Los Angeles, and Washington State University, Spokane. He also is coauthor of “Drugs in Pregnancy and Lactation,” and coeditor of “Diseases, Complications, and Drug Therapy in Obstetrics.” He had no relevant financial disclosures. Contact him at [email protected].
Pregnancy registries are valuable sources of information. For many drugs, they are the primary source of human pregnancy experience. The new Food and Drug Administration prescription drug information format may increase the amount of information available, at least from registries conducted by drug manufacturers, because they will be required to list all substantive changes made within the year. Although most of the registries use the word “pregnancy,” it is important to note that many also enroll women who took the target drug shortly before conception.
The strengths of pregnancy registries are their prospective nature and enrollment across a wide geographical area. Typically, two types of pregnancy outcomes are obtained: those with birth defects and those without known birth defects (classified as live births, fetal deaths, and spontaneous abortions).
Registries can identify early signals of teratogenicity, but they have several limitations, including voluntary reporting that results in selection bias, pregnancies lost to follow-up that may have had different outcomes than those with documented outcomes, and a lack of control groups (with some exceptions).
Other limitations are that registry cases are not representative of target populations, and pregnancies lost to follow-up lack details on elective terminations and fetal deaths without birth defects, as well as all spontaneous abortions. Additionally, publication of results may be delayed and does not appear in a peer-reviewed journal.
Since the total number of exposed pregnancies is unknown, registry data cannot be used to calculate prevalence, but can be used to estimate the proportion of birth defects. Some registries also collect data on retrospective reports, which are less representative of the target population because they can be biased toward the reporting of more unusual and severe outcomes. However, they may be helpful in detecting unusual patterns of birth defects.
MothertoBaby Registry
The large Organization of Teratology Information Specialists (OTIS) MothertoBaby registry (877-311-8972) involves four different categories: autoimmune diseases(rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, psoriasis, Crohn’s disease, and multiple sclerosis); asthma; antiviral agents; and vaccines.
The drugs for autoimmune diseases are tocilizumab (Actemra), leflunomide (Arava), teriflunomide (Aubagio), certolizumab pegol (Cimzia), etanercept (Enbrel), adalimumab (Humira), abatacept (Orencia), apremilast (Otezla), ustekinumab (Stelara), tofacitinib (Xeljanz), infliximab (Remicade), and methotrexate.
The asthma drugs are formoterol (Foradil, Perforomist, Symbicort, Dulera), albuterol, levalbuterol, metaproterenol, pirbuterol (Maxair), and terbutaline.
The antiviral agents are oseltamivir (Tamiflu) and zanamivir (Relenza).
The vaccines include pertussis (Tdap), seasonal influenza, and meningococcal disease (Menveo). In addition to a control group in each category, a unique aspect of this registry is that many exposed infants will undergo dysmorphology examinations.
Vaccine registries
A second vaccine for meningococcal disease (Menactra) is being studied in the Menactra vaccine Pregnancy Registry (800-822-2463 / www.sanofipasteurpregnancy.com).
Two other registries also include influenza vaccines: Flu vaccine Pregnancy Registry, PPD (Flucelvax) (877-413-4759 / email: [email protected]) and the GSK Seasonal Influenza Vaccine Pregnancy Registry, GlaxoSmithKline (888-825-5249 / pregnancyregistry.gsk.com/seasonalinfluenzavaccines.html), which includes the Fluarix and FluLaval vaccines.
Asthma
Women with asthma who are being treated with omalizumab (Xolair) are the target population for the EXPECT Pregnancy Registry (866-496-5247 Option 3 / www.xolairpregnancyregistry.com).
GSK registries
GlaxoSmithKline is also conducting three other registries: the Belimumab (Benlysta) Pregnancy Registry for patients with systemic lupus erythematosus treated with belimumab (877-681-6296 / [email protected]); and the Twinrix Pregnancy Registry for women who have received the Twinrix hepatitis A and B vaccine (888-825-5249).
Atypical antipsychotics
TheNational Pregnancy Registry for Atypical Antipsychotics (866-961-2388 / registry@womens mentalhealth.org) is studying 10 drugs: aripiprazole (Abilify), clozapine (Clozaril), iloperidone (Fanapt), paliperidone (Invega), lurasidone (Latuda), risperidone (Risperdal), asenapine (Saphris), quetiapine (Seroquel), ziprasidone (Geodon), and olanzapine (Zyprexa).
TAPP registry
Acitretin is under study by the Take Action to Prevent Pregnancy (T.A.P.P.) registry (855-850-2138 / www.tevagenerics.com/acitretin).
MPS I registry
The MPS I (Mucopolysaccharidosis I) Registry, Genzyme Corp (617-591-5500 / [email protected]), is studying the use of laronidase (Aldurazyme) for Hurler syndrome, Scheie syndrome, and Hurler-Scheie syndrome.
MPS VI registry
The use of galsulfase (Naglazyme) for Maroteaux-Lamy syndrome during pregnancy is under study by the Mucopolysaccharidosis VI (MPS VI) Clinical Surveillance Program(415-506-6849 or 415-506-6703)
Epilepsy drugs
The Antiepileptic Drug Pregnancy Registry (888-233-2334 / www.aedpregnancyregistry.org) is studying antiepileptic drugs.
Type 2 diabetes
The Exenatide Pregnancy Registry, conducted by INC Research for AstraZeneca (800-633-9081 / www.exenatidepregnancyregistry.com), examines the use of exenatide (Byetta, Bydureon) for the treatment of type 2 diabetes.
Renal transplant
Renal transplant patients exposed to mycophenolate (Cellcept) can be enrolled in the Mycophenolate Pregnancy Registry (800-617-8191) or the National Transplantation Pregnancy Registry (877-955-6877). The NTPR is enrolling renal transplant patients exposed to belatacept (Nulojix).
Cymbalta
The antidepressant duloxetine (Cymbalta), when used for major depressive or generalized anxiety disorders, diabetic peripheral neuropathic pain, or fibromyalgia is being studied by the Cymbalta Pregnancy Registry, INC Research ([email protected] / www.cymbaltapregancyregistry.com).
Fabry disease
The Fabry Registry, Genzyme Corp (617-581-5500 / [email protected]) is studying the use in pregnancy of agalsidase beta (Fabrazyme) for Fabry disease.
MS registry
Novartis Pharmaceuticals is conducting the Gilenya (fingolimod) Pregnancy Registry (877-598-7237 / [email protected]) for patients with multiple sclerosis who are taking fingolimod (Gilenya).
Cancer
The MotHER Pregnancy Registry, INC Research (800-690-6720 / [email protected] / themotherpregnancyregistry.com) is enrolling breast cancer patients who have been treated during pregnancy with ado-trastuzumab (Kadcyla), trastuzumab (Herceptin), or pertuzumab (Perjeta).
Merck registries
Merck Pregnancy Registries (800-986-8999) include a registry for type 2 diabetes – sitagliptin/metformin (Janumet) or sitagliptin (Januvia) (www.merckpregancyregistries.com/januvia.html); a registry for rizatriptan (Maxalt) (www.merckpregancyregistries.com/maxalt.html), for migraine headaches; and a registry for the 9-valent human papillomavirus (HPV) (Gardasil 9) vaccine (www.merckpregnancyregistries.com/gardasil9.html).
The registry for the asthma drug montelukast (Singulair) and the registry for Gardasil, the quadrivalent HPV vaccine, are now closed to new enrollment, but new cases of pregnancy exposures can be reported to the company at: 877-888-4231.
Osteoporosis
Amgen’s Pregnancy Surveillance Program (800-772-6436) is enrolling pregnant subjects with osteoporosis who are being treated with denosumab (Prolia).
Hepatitis C
The Ribavirin Pregnancy Registry, INC Research (800-593-2214/ [email protected] / ribavirinpregnancyregistry.com) is looking for subjects with hepatitis C who have been treated with ribavirin (Copegus).
Fibromyalgia
The Savella Pregnancy Registry (877-643-3010/ [email protected] / savellapregnancyregistry.com) is looking for patients with fibromyalgia who are being treated with milnacipran (Savella).
Skin infections
An antibacterial, telavancin (Vibativ), indicated for skin infections is being studied by the Vibativ Pregnancy Registry (888-658-4228 / www.clinicaltrial.gov).
Pompe disease
Pregnant women treated with alglucosidase alfa (Myozyme) for Pompe disease can enroll in the Pompe Registry (800-745-4447 x 15500 / www.pompe.com/en/healthcare-professionals/pompe-registry.aspx).
Sleep disorders
Armodafinil (Nuvigil) used to treat excessive sleepiness associated with narcolepsy and other sleep disorders is being studied in the Nuvigil Pregnancy Registry (866-404-4106 / www.nuvigilpregnancyregistry.com). A second drug with the same indication and telephone number, modafinil (Provigil), is in the Provigil Pregnancy Registry (provigilpregnancyregistry.com).
Additional details, including fax numbers and addresses of the registries reviewed above, can be obtained from the FDA website, List of Pregnancy Exposure Registries. Since the strength of a registry is based on numbers, health care professionals are encouraged to enroll potential subjects or have their patients call to enroll themselves.
Before retirement, Mr. Briggs was a pharmacist clinical specialist at the outpatient clinics of Memorial Care Center for Women at Miller Children’s Hospital in Long Beach, Calif.; he remains a clinical professor of pharmacy at the University of California, San Francisco; and adjunct professor of pharmacy at the University of Southern California, Los Angeles, and Washington State University, Spokane. He also is coauthor of “Drugs in Pregnancy and Lactation,” and coeditor of “Diseases, Complications, and Drug Therapy in Obstetrics.” He had no relevant financial disclosures. Contact him at [email protected].
Most hospitals overestimate their door-to-needle performance
Personnel at most hospitals that treat acute stroke, particularly the lowest-performing hospitals, greatly overestimate their ability to deliver TPA to eligible patients within 1 hour, according to a report published online July 22 in Journal of the American Heart Association.
Overestimating the quality of care they actually provide may perpetuate this suboptimal performance, “whereas accurate measurements of current performance and realistic comparison to other, more successful, sites might provide the needed motivation to fuel quality improvement,” said Dr. Cheryl B. Lin of Tufts Medical Center Floating Hospital for Children, Boston, and her associates.
They compared stroke teams’ perceptions of their door-to-needle performance, as measured on survey questionnaires answered by nurses, neurologists, and other staff members, against the hospitals’ actual performance, which was recorded in a large stroke registry. The investigators focused on 141 hospitals that treated 48,201 stroke patients during a 1-year period. This included 49 top-performing, 52 average-performing, and 40 low-performing hospitals. The top category had door-to-needle rates of 45%-93%, while the bottom category had consistent door-to-needle rates of 0%. The middle category had door-to-needle rates of 16%-25%.
Regardless of their hospital’s performance category, 61% of the respondents overestimated how many eligible patients there actually received TPA within 1 hour. The lowest-performing hospitals had the most unrealistic estimates, with 68% of them guessing that 20% of their patients received timely TPA when in fact 0% of patients did so. Low-performing hospitals also overestimated their performance in comparison with other hospitals, with 85% of them characterizing their performance as average, above average, or even superior relative to other hospitals, when in fact it was very poor, Dr. Lin and her associates wrote (J. Am. Heart Assoc. 2015 July 22 [doi:10.1161/JAHA.114.001298]).
“Addressing misperceptions that one’s performance is average or above average when it actually is not is an important step in addressing motivation for change,” they added.
The study was supported by the U.S. Agency for Healthcare Research and Quality. Dr. Lin reported having no relevant financial disclosures; her associates reported ties to Genentech, Lilly, Johnson & Johnson, Bristol-Myers Squibb, Sanofi-Aventis, and Merck Schering-Plough.
Personnel at most hospitals that treat acute stroke, particularly the lowest-performing hospitals, greatly overestimate their ability to deliver TPA to eligible patients within 1 hour, according to a report published online July 22 in Journal of the American Heart Association.
Overestimating the quality of care they actually provide may perpetuate this suboptimal performance, “whereas accurate measurements of current performance and realistic comparison to other, more successful, sites might provide the needed motivation to fuel quality improvement,” said Dr. Cheryl B. Lin of Tufts Medical Center Floating Hospital for Children, Boston, and her associates.
They compared stroke teams’ perceptions of their door-to-needle performance, as measured on survey questionnaires answered by nurses, neurologists, and other staff members, against the hospitals’ actual performance, which was recorded in a large stroke registry. The investigators focused on 141 hospitals that treated 48,201 stroke patients during a 1-year period. This included 49 top-performing, 52 average-performing, and 40 low-performing hospitals. The top category had door-to-needle rates of 45%-93%, while the bottom category had consistent door-to-needle rates of 0%. The middle category had door-to-needle rates of 16%-25%.
Regardless of their hospital’s performance category, 61% of the respondents overestimated how many eligible patients there actually received TPA within 1 hour. The lowest-performing hospitals had the most unrealistic estimates, with 68% of them guessing that 20% of their patients received timely TPA when in fact 0% of patients did so. Low-performing hospitals also overestimated their performance in comparison with other hospitals, with 85% of them characterizing their performance as average, above average, or even superior relative to other hospitals, when in fact it was very poor, Dr. Lin and her associates wrote (J. Am. Heart Assoc. 2015 July 22 [doi:10.1161/JAHA.114.001298]).
“Addressing misperceptions that one’s performance is average or above average when it actually is not is an important step in addressing motivation for change,” they added.
The study was supported by the U.S. Agency for Healthcare Research and Quality. Dr. Lin reported having no relevant financial disclosures; her associates reported ties to Genentech, Lilly, Johnson & Johnson, Bristol-Myers Squibb, Sanofi-Aventis, and Merck Schering-Plough.
Personnel at most hospitals that treat acute stroke, particularly the lowest-performing hospitals, greatly overestimate their ability to deliver TPA to eligible patients within 1 hour, according to a report published online July 22 in Journal of the American Heart Association.
Overestimating the quality of care they actually provide may perpetuate this suboptimal performance, “whereas accurate measurements of current performance and realistic comparison to other, more successful, sites might provide the needed motivation to fuel quality improvement,” said Dr. Cheryl B. Lin of Tufts Medical Center Floating Hospital for Children, Boston, and her associates.
They compared stroke teams’ perceptions of their door-to-needle performance, as measured on survey questionnaires answered by nurses, neurologists, and other staff members, against the hospitals’ actual performance, which was recorded in a large stroke registry. The investigators focused on 141 hospitals that treated 48,201 stroke patients during a 1-year period. This included 49 top-performing, 52 average-performing, and 40 low-performing hospitals. The top category had door-to-needle rates of 45%-93%, while the bottom category had consistent door-to-needle rates of 0%. The middle category had door-to-needle rates of 16%-25%.
Regardless of their hospital’s performance category, 61% of the respondents overestimated how many eligible patients there actually received TPA within 1 hour. The lowest-performing hospitals had the most unrealistic estimates, with 68% of them guessing that 20% of their patients received timely TPA when in fact 0% of patients did so. Low-performing hospitals also overestimated their performance in comparison with other hospitals, with 85% of them characterizing their performance as average, above average, or even superior relative to other hospitals, when in fact it was very poor, Dr. Lin and her associates wrote (J. Am. Heart Assoc. 2015 July 22 [doi:10.1161/JAHA.114.001298]).
“Addressing misperceptions that one’s performance is average or above average when it actually is not is an important step in addressing motivation for change,” they added.
The study was supported by the U.S. Agency for Healthcare Research and Quality. Dr. Lin reported having no relevant financial disclosures; her associates reported ties to Genentech, Lilly, Johnson & Johnson, Bristol-Myers Squibb, Sanofi-Aventis, and Merck Schering-Plough.
FROM THE JOURNAL OF THE AMERICAN HEART ASSOCIATION
Key clinical point: Personnel at most hospitals, particularly the lowest-performing hospitals, greatly overestimate their performance at giving stroke patients TPA within 1 hour of arrival.
Major finding: The lowest-performing hospitals had the most unrealistic estimates of their door-to-needle times, with 68% of them guessing that 20% of their patients received timely TPA when in fact 0% of their patients did so.
Data source: An analysis of data in a stroke registry regarding 141 hospitals that treated 48,201 patients during a 1-year period, plus a survey of stroke personnel at those hospitals.
Disclosures: This study was supported by the U.S. Agency for Healthcare Research and Quality. Dr. Lin reported having no relevant financial disclosures; her associates reported ties to Genentech, Lilly, Johnson & Johnson, Bristol-Myers Squibb, Sanofi-Aventis and Merck Schering-Plough.
Harnessing new data on immunotherapies
Immunotherapies once again took center stage at the 2015 annual meeting of the American Society for Clinical Oncology in Chicago, though many other groundbreaking clinical advances were also presented. The meeting’s theme, “Illumination and innovation: transforming data into learning,” captured the current focus, by both researchers and practicing oncologists, on the importance of being able to draw on new and enticing data and use it as the basis for improving the care of and outcomes for cancer patients.
CheckMate 067: Two immunotherapies better than one for advanced melanoma
Key clinical point Nivolumab alone or combined with ipilimumab significantly improves progression-free survival (PFS) and objective response rates (ORRs), compared with ipilimumab alone in previously untreated metastatic melanoma. Major finding Median PFS was 11.5 months with nivolumab plus ipilimumab, 6.9 months with nivolumab, and 2.9 months with ipilimumab. Data source Phase 3, double-blind randomized trial in 945 patients with previously untreated metastatic melanoma. Disclosures Bristol-Myers Squibb funded the trial. Dr Wolchok reported financial relationships with several firms including research funding from and consulting or advising for Bristol-Myers Squibb…
Click on the PDF icon at the top of this introduction to read the full article.
Immunotherapies once again took center stage at the 2015 annual meeting of the American Society for Clinical Oncology in Chicago, though many other groundbreaking clinical advances were also presented. The meeting’s theme, “Illumination and innovation: transforming data into learning,” captured the current focus, by both researchers and practicing oncologists, on the importance of being able to draw on new and enticing data and use it as the basis for improving the care of and outcomes for cancer patients.
CheckMate 067: Two immunotherapies better than one for advanced melanoma
Key clinical point Nivolumab alone or combined with ipilimumab significantly improves progression-free survival (PFS) and objective response rates (ORRs), compared with ipilimumab alone in previously untreated metastatic melanoma. Major finding Median PFS was 11.5 months with nivolumab plus ipilimumab, 6.9 months with nivolumab, and 2.9 months with ipilimumab. Data source Phase 3, double-blind randomized trial in 945 patients with previously untreated metastatic melanoma. Disclosures Bristol-Myers Squibb funded the trial. Dr Wolchok reported financial relationships with several firms including research funding from and consulting or advising for Bristol-Myers Squibb…
Click on the PDF icon at the top of this introduction to read the full article.
Immunotherapies once again took center stage at the 2015 annual meeting of the American Society for Clinical Oncology in Chicago, though many other groundbreaking clinical advances were also presented. The meeting’s theme, “Illumination and innovation: transforming data into learning,” captured the current focus, by both researchers and practicing oncologists, on the importance of being able to draw on new and enticing data and use it as the basis for improving the care of and outcomes for cancer patients.
CheckMate 067: Two immunotherapies better than one for advanced melanoma
Key clinical point Nivolumab alone or combined with ipilimumab significantly improves progression-free survival (PFS) and objective response rates (ORRs), compared with ipilimumab alone in previously untreated metastatic melanoma. Major finding Median PFS was 11.5 months with nivolumab plus ipilimumab, 6.9 months with nivolumab, and 2.9 months with ipilimumab. Data source Phase 3, double-blind randomized trial in 945 patients with previously untreated metastatic melanoma. Disclosures Bristol-Myers Squibb funded the trial. Dr Wolchok reported financial relationships with several firms including research funding from and consulting or advising for Bristol-Myers Squibb…
Click on the PDF icon at the top of this introduction to read the full article.
Oncogenic drivers and immunotherapy: staying one step ahead of lung cancer
The majority of newly diagnosed lung cancers are NSCLC, and about half of those are adenocarcinomas (Figure 1).2 Over the past decade there has been a significant evolution in the understanding and treatment of lung adenocarcinoma, mostly stemming from a greater appreciation of the distinct pathologies and unique molecular signatures of these tumors. Genomic characterization of the molecular signatures has led to the identification of numerous key genetic alterations that drive lung cancer. The dependency of lung tumors on these genetic drivers has enabled the pharmacological development of targeted therapies that exploit this vulnerability...
Click on the PDF icon at the top of this introduction to read the full article.
The majority of newly diagnosed lung cancers are NSCLC, and about half of those are adenocarcinomas (Figure 1).2 Over the past decade there has been a significant evolution in the understanding and treatment of lung adenocarcinoma, mostly stemming from a greater appreciation of the distinct pathologies and unique molecular signatures of these tumors. Genomic characterization of the molecular signatures has led to the identification of numerous key genetic alterations that drive lung cancer. The dependency of lung tumors on these genetic drivers has enabled the pharmacological development of targeted therapies that exploit this vulnerability...
Click on the PDF icon at the top of this introduction to read the full article.
The majority of newly diagnosed lung cancers are NSCLC, and about half of those are adenocarcinomas (Figure 1).2 Over the past decade there has been a significant evolution in the understanding and treatment of lung adenocarcinoma, mostly stemming from a greater appreciation of the distinct pathologies and unique molecular signatures of these tumors. Genomic characterization of the molecular signatures has led to the identification of numerous key genetic alterations that drive lung cancer. The dependency of lung tumors on these genetic drivers has enabled the pharmacological development of targeted therapies that exploit this vulnerability...
Click on the PDF icon at the top of this introduction to read the full article.
Estrogen therapy linked to brain atrophy in women with diabetes
WASHINGTON – Women with type 2 diabetes who take estrogen therapy showed lower total gray matter volume, with atrophy particularly evident in the hippocampus.
A new analysis of the Women’s Health Initiative Memory study suggested that these hormone therapy–related decrements in brain volume seem to stabilize in the years after treatment ends. However, said Christina E. Hugenschmidt, Ph.D., the findings also suggested caution when considering a prescription for estrogen therapy for a woman with emerging or frank diabetes.
“The concern is that prescribing estrogen to a woman with diabetes could increase her risk of brain atrophy,” she said at the Alzheimer’s Association International Conference 2015.
Dr. Hugenschmidt of Wake Forest University, Winston-Salem, N.C., reviewed data from the Women’s Health Initiate Memory Study–MRI (WHIMS-MRI).
The parallel placebo-controlled trial randomized women aged 65 years and older to placebo, or 0.625 mg conjugated equine estrogen with or without 2.5 mg progesterone. They were all free of cognitive decline at baseline.
Dr. Hugenschmidt focused on 1,400 women who underwent two magnetic resonance imaging brain scans: one 2.5 years after beginning the study and another about 5 years after that. The primary outcomes were total brain volume, including any ischemic lesions, total gray matter, total white matter, frontal lobe and hippocampal volume, and ischemic white matter lesion load.
At enrollment, the women were a mean age of 70 years old; 124 had type 2 diabetes. About 42% had long-standing disease of 10 years or longer. Not surprisingly, there were some significant differences between the diabetic and nondiabetic groups: Body mass index, waist girth, and waist/hip ratio were all significantly larger in the women with diabetes.
At the first scan, women with diabetes who had been randomized to estrogen therapy had about 18 cc less total brain volume than those without diabetes. The brain volumes of women with diabetes who were taking placebo were nearly identical to those of the nondiabetic women, regardless of what treatment they were taking.
The difference seemed to be driven by a loss of gray matter, Dr. Hugenschmidt said. There was no significant effect on white matter. The hippocampus appeared to have a similar amount of shrinkage. However, she added, there were no differences in cognitive scores on the Mini Mental State Exam.
Insulin use didn’t appear to ameliorate the findings of smaller brain volume among those with diabetes. Atrophy didn’t progress, however; findings at the same scan were similar.
The findings may be linked to the suppression of a natural process that occurs during the perimenopausal transition, Dr. Hugenschmidt said. Estrogen is crucial in maintaining the brain’s energy metabolism. It works by increasing glucose transport and aerobic glycolysis. But during this time of life, as estrogen wanes, it becomes uncoupled from the glucose metabolism pathway. The female brain then begins to use ketone bodies as its primary source of energy. Intact estrogen levels normally downregulate the use of alternative energy sources before menopause; supplementing them seems to prevent this transition from occurring.
“Among older women with diabetes for whom the glucose-based energy metabolism promoted by estrogen is already compromised, this downregulation of alternative energy sources may lead to increased atrophy of gray matter, which has a greater metabolic demand relative to white matter,” Dr. Hugenschmidt and her colleagues wrote in a paper published in Neurology (2015 July 10 [doi:10.1212/WNL.0000000000001816]).
Dr. Hugenschmidt reported having no relevant financial disclosures.
On Twitter @Alz_Gal
WASHINGTON – Women with type 2 diabetes who take estrogen therapy showed lower total gray matter volume, with atrophy particularly evident in the hippocampus.
A new analysis of the Women’s Health Initiative Memory study suggested that these hormone therapy–related decrements in brain volume seem to stabilize in the years after treatment ends. However, said Christina E. Hugenschmidt, Ph.D., the findings also suggested caution when considering a prescription for estrogen therapy for a woman with emerging or frank diabetes.
“The concern is that prescribing estrogen to a woman with diabetes could increase her risk of brain atrophy,” she said at the Alzheimer’s Association International Conference 2015.
Dr. Hugenschmidt of Wake Forest University, Winston-Salem, N.C., reviewed data from the Women’s Health Initiate Memory Study–MRI (WHIMS-MRI).
The parallel placebo-controlled trial randomized women aged 65 years and older to placebo, or 0.625 mg conjugated equine estrogen with or without 2.5 mg progesterone. They were all free of cognitive decline at baseline.
Dr. Hugenschmidt focused on 1,400 women who underwent two magnetic resonance imaging brain scans: one 2.5 years after beginning the study and another about 5 years after that. The primary outcomes were total brain volume, including any ischemic lesions, total gray matter, total white matter, frontal lobe and hippocampal volume, and ischemic white matter lesion load.
At enrollment, the women were a mean age of 70 years old; 124 had type 2 diabetes. About 42% had long-standing disease of 10 years or longer. Not surprisingly, there were some significant differences between the diabetic and nondiabetic groups: Body mass index, waist girth, and waist/hip ratio were all significantly larger in the women with diabetes.
At the first scan, women with diabetes who had been randomized to estrogen therapy had about 18 cc less total brain volume than those without diabetes. The brain volumes of women with diabetes who were taking placebo were nearly identical to those of the nondiabetic women, regardless of what treatment they were taking.
The difference seemed to be driven by a loss of gray matter, Dr. Hugenschmidt said. There was no significant effect on white matter. The hippocampus appeared to have a similar amount of shrinkage. However, she added, there were no differences in cognitive scores on the Mini Mental State Exam.
Insulin use didn’t appear to ameliorate the findings of smaller brain volume among those with diabetes. Atrophy didn’t progress, however; findings at the same scan were similar.
The findings may be linked to the suppression of a natural process that occurs during the perimenopausal transition, Dr. Hugenschmidt said. Estrogen is crucial in maintaining the brain’s energy metabolism. It works by increasing glucose transport and aerobic glycolysis. But during this time of life, as estrogen wanes, it becomes uncoupled from the glucose metabolism pathway. The female brain then begins to use ketone bodies as its primary source of energy. Intact estrogen levels normally downregulate the use of alternative energy sources before menopause; supplementing them seems to prevent this transition from occurring.
“Among older women with diabetes for whom the glucose-based energy metabolism promoted by estrogen is already compromised, this downregulation of alternative energy sources may lead to increased atrophy of gray matter, which has a greater metabolic demand relative to white matter,” Dr. Hugenschmidt and her colleagues wrote in a paper published in Neurology (2015 July 10 [doi:10.1212/WNL.0000000000001816]).
Dr. Hugenschmidt reported having no relevant financial disclosures.
On Twitter @Alz_Gal
WASHINGTON – Women with type 2 diabetes who take estrogen therapy showed lower total gray matter volume, with atrophy particularly evident in the hippocampus.
A new analysis of the Women’s Health Initiative Memory study suggested that these hormone therapy–related decrements in brain volume seem to stabilize in the years after treatment ends. However, said Christina E. Hugenschmidt, Ph.D., the findings also suggested caution when considering a prescription for estrogen therapy for a woman with emerging or frank diabetes.
“The concern is that prescribing estrogen to a woman with diabetes could increase her risk of brain atrophy,” she said at the Alzheimer’s Association International Conference 2015.
Dr. Hugenschmidt of Wake Forest University, Winston-Salem, N.C., reviewed data from the Women’s Health Initiate Memory Study–MRI (WHIMS-MRI).
The parallel placebo-controlled trial randomized women aged 65 years and older to placebo, or 0.625 mg conjugated equine estrogen with or without 2.5 mg progesterone. They were all free of cognitive decline at baseline.
Dr. Hugenschmidt focused on 1,400 women who underwent two magnetic resonance imaging brain scans: one 2.5 years after beginning the study and another about 5 years after that. The primary outcomes were total brain volume, including any ischemic lesions, total gray matter, total white matter, frontal lobe and hippocampal volume, and ischemic white matter lesion load.
At enrollment, the women were a mean age of 70 years old; 124 had type 2 diabetes. About 42% had long-standing disease of 10 years or longer. Not surprisingly, there were some significant differences between the diabetic and nondiabetic groups: Body mass index, waist girth, and waist/hip ratio were all significantly larger in the women with diabetes.
At the first scan, women with diabetes who had been randomized to estrogen therapy had about 18 cc less total brain volume than those without diabetes. The brain volumes of women with diabetes who were taking placebo were nearly identical to those of the nondiabetic women, regardless of what treatment they were taking.
The difference seemed to be driven by a loss of gray matter, Dr. Hugenschmidt said. There was no significant effect on white matter. The hippocampus appeared to have a similar amount of shrinkage. However, she added, there were no differences in cognitive scores on the Mini Mental State Exam.
Insulin use didn’t appear to ameliorate the findings of smaller brain volume among those with diabetes. Atrophy didn’t progress, however; findings at the same scan were similar.
The findings may be linked to the suppression of a natural process that occurs during the perimenopausal transition, Dr. Hugenschmidt said. Estrogen is crucial in maintaining the brain’s energy metabolism. It works by increasing glucose transport and aerobic glycolysis. But during this time of life, as estrogen wanes, it becomes uncoupled from the glucose metabolism pathway. The female brain then begins to use ketone bodies as its primary source of energy. Intact estrogen levels normally downregulate the use of alternative energy sources before menopause; supplementing them seems to prevent this transition from occurring.
“Among older women with diabetes for whom the glucose-based energy metabolism promoted by estrogen is already compromised, this downregulation of alternative energy sources may lead to increased atrophy of gray matter, which has a greater metabolic demand relative to white matter,” Dr. Hugenschmidt and her colleagues wrote in a paper published in Neurology (2015 July 10 [doi:10.1212/WNL.0000000000001816]).
Dr. Hugenschmidt reported having no relevant financial disclosures.
On Twitter @Alz_Gal
AT AAIC 2015
Key clinical point: Prescribing estrogen therapy for older women with type 2 diabetes could increase the risk of brain atrophy.
Major finding: Older women with type 2 diabetes who took estrogen therapy had about an 18-cc lower total brain volume than women with diabetes who took placebo and than women without the disease.
Data source: WHIMS-MRI was a large parallel-group study that examined the effect of hormone therapy on the brain and cognition in postmenopausal women.
Disclosures: Dr. Hugenschmidt reported having no relevant financial disclosures.
A weekly speech and language therapy service for head and neck radiotherapy patients during treatment: maximizing accessibility and efficiency
Background Our hospital did not provide a weekly speech and language therapy (SLT) service for head and neck cancer patients during radiotherapy treatment. SLT is recommended in the international guidelines, but many centers do not offer this service. In the case of our hospital, SLT was not provided because there were no funds to cover the costs of additional staff.
Objectives To create a new service model within a multidisciplinary setting to comply with the international SLT guidelines and without increasing staff. We aimed to measure the accessibility and efficiency of a new model of service delivery at our center both for patients and for the service.
Methods 79 patients were recruited for the study. We followed 1 group of patients (n = 29; observation group) throughout their treatment for 6 weeks to establish if there was a clinical need to offer SLT at the treatment center. A second group of patients (n = 50; intervention group) received a weekly SLT review at the treatment center throughout their radiotherapy. Data collected at the tertiary cancer center for 6 months included: age, gender, tumor site and size, treatment modality, swallowing outcomes, communication outcomes, patient satisfaction, multidisciplinary team feedback, and time efficiency. The observation group did not participate in the intervention group because the data was collected between 2 different groups of participants. However, all participants were referred to their local SLT service at the end of their treatment if that was clinically indicated, regardless of the group they had been in.
Results The proportion of patients accessing SLT services during treatment and the time efficiency of the service were both improved with this model of delivery. The service’s compliance with international guidelines was met. More patients continued with oral intake during their treatment at our center with the new service. Improvements were also reported in communication clarity and communication confidence in the same group.
Conclusion Offering head and neck cancer patients SLT at the same time and place as their radiotherapy treatment improves patient outcomes and increases SLT efficiencies. As this was not a treatment study, further clinical trials are required with regards to functional outcomes.
Click on the PDF icon at the top of this introduction to read the full article.
Background Our hospital did not provide a weekly speech and language therapy (SLT) service for head and neck cancer patients during radiotherapy treatment. SLT is recommended in the international guidelines, but many centers do not offer this service. In the case of our hospital, SLT was not provided because there were no funds to cover the costs of additional staff.
Objectives To create a new service model within a multidisciplinary setting to comply with the international SLT guidelines and without increasing staff. We aimed to measure the accessibility and efficiency of a new model of service delivery at our center both for patients and for the service.
Methods 79 patients were recruited for the study. We followed 1 group of patients (n = 29; observation group) throughout their treatment for 6 weeks to establish if there was a clinical need to offer SLT at the treatment center. A second group of patients (n = 50; intervention group) received a weekly SLT review at the treatment center throughout their radiotherapy. Data collected at the tertiary cancer center for 6 months included: age, gender, tumor site and size, treatment modality, swallowing outcomes, communication outcomes, patient satisfaction, multidisciplinary team feedback, and time efficiency. The observation group did not participate in the intervention group because the data was collected between 2 different groups of participants. However, all participants were referred to their local SLT service at the end of their treatment if that was clinically indicated, regardless of the group they had been in.
Results The proportion of patients accessing SLT services during treatment and the time efficiency of the service were both improved with this model of delivery. The service’s compliance with international guidelines was met. More patients continued with oral intake during their treatment at our center with the new service. Improvements were also reported in communication clarity and communication confidence in the same group.
Conclusion Offering head and neck cancer patients SLT at the same time and place as their radiotherapy treatment improves patient outcomes and increases SLT efficiencies. As this was not a treatment study, further clinical trials are required with regards to functional outcomes.
Click on the PDF icon at the top of this introduction to read the full article.
Background Our hospital did not provide a weekly speech and language therapy (SLT) service for head and neck cancer patients during radiotherapy treatment. SLT is recommended in the international guidelines, but many centers do not offer this service. In the case of our hospital, SLT was not provided because there were no funds to cover the costs of additional staff.
Objectives To create a new service model within a multidisciplinary setting to comply with the international SLT guidelines and without increasing staff. We aimed to measure the accessibility and efficiency of a new model of service delivery at our center both for patients and for the service.
Methods 79 patients were recruited for the study. We followed 1 group of patients (n = 29; observation group) throughout their treatment for 6 weeks to establish if there was a clinical need to offer SLT at the treatment center. A second group of patients (n = 50; intervention group) received a weekly SLT review at the treatment center throughout their radiotherapy. Data collected at the tertiary cancer center for 6 months included: age, gender, tumor site and size, treatment modality, swallowing outcomes, communication outcomes, patient satisfaction, multidisciplinary team feedback, and time efficiency. The observation group did not participate in the intervention group because the data was collected between 2 different groups of participants. However, all participants were referred to their local SLT service at the end of their treatment if that was clinically indicated, regardless of the group they had been in.
Results The proportion of patients accessing SLT services during treatment and the time efficiency of the service were both improved with this model of delivery. The service’s compliance with international guidelines was met. More patients continued with oral intake during their treatment at our center with the new service. Improvements were also reported in communication clarity and communication confidence in the same group.
Conclusion Offering head and neck cancer patients SLT at the same time and place as their radiotherapy treatment improves patient outcomes and increases SLT efficiencies. As this was not a treatment study, further clinical trials are required with regards to functional outcomes.
Click on the PDF icon at the top of this introduction to read the full article.
Health care expenditures associated with depression in adults with cancer
Background The rates of depression in adults with cancer have been reported as high as 38%-58%. How depression affects overall health care expenditures in individuals with cancer is an under-researched area.
Objective To estimate excess average total health care expenditures associated with depression in adults with cancer by comparing those with and without depression after controlling for demographic, socioeconomic, access to care, and other health status variables.
Methods Cross-sectional data on 4,766 adult survivors of cancer from 2006-2009 of the nationally representative household survey, Medical Expenditure Panel Survey (MEPS), were used. The patients were older than 21 years. Cancer and depression were identified from the patients’ medical conditions files. Dependent variables consisted of total, inpatient, outpatient, emergency department, prescription drugs, and other expenditures. Ordinary least square (OLS) on logged dollars and generalized linear models with log-link function were performed. All analyses (SAS 9.3 and STATA12) accounted for the complex survey design of the MEPS.
Results Overall, 14% of individuals with cancer reported having depression. In those with cancer and depression, the average annual health care expenditures were $18,401 compared with $12,091 in those without depression. After adjusting for demographic, socioeconomic, access to care, and other health status variables, those with depression had about 31.7% greater total expenditures compared with those without depression. Total, outpatient, and prescription expenditures were higher in individuals with depression than in those without depression. Individuals with cancer and depression were significantly more likely to use emergency departments (adjusted odds ratio, 1.46) compared with their counterparts without depression.
Limitations Cancer patients who died during the reporting year were excluded. The financial burden of depression may have been underestimated because the costs of end-of-life care are high. The burden for each cancer type was not analyzed because of the small sample size.
Conclusion In adults with cancer, those with depression had higher health care utilization and expenditures compared with those without depression.
Funding/sponsorship One author partially supported by the National Institute of General Medical Sciences, U54GM104942.
Click on the PDF icon at the top of this introduction to read the full article.
Background The rates of depression in adults with cancer have been reported as high as 38%-58%. How depression affects overall health care expenditures in individuals with cancer is an under-researched area.
Objective To estimate excess average total health care expenditures associated with depression in adults with cancer by comparing those with and without depression after controlling for demographic, socioeconomic, access to care, and other health status variables.
Methods Cross-sectional data on 4,766 adult survivors of cancer from 2006-2009 of the nationally representative household survey, Medical Expenditure Panel Survey (MEPS), were used. The patients were older than 21 years. Cancer and depression were identified from the patients’ medical conditions files. Dependent variables consisted of total, inpatient, outpatient, emergency department, prescription drugs, and other expenditures. Ordinary least square (OLS) on logged dollars and generalized linear models with log-link function were performed. All analyses (SAS 9.3 and STATA12) accounted for the complex survey design of the MEPS.
Results Overall, 14% of individuals with cancer reported having depression. In those with cancer and depression, the average annual health care expenditures were $18,401 compared with $12,091 in those without depression. After adjusting for demographic, socioeconomic, access to care, and other health status variables, those with depression had about 31.7% greater total expenditures compared with those without depression. Total, outpatient, and prescription expenditures were higher in individuals with depression than in those without depression. Individuals with cancer and depression were significantly more likely to use emergency departments (adjusted odds ratio, 1.46) compared with their counterparts without depression.
Limitations Cancer patients who died during the reporting year were excluded. The financial burden of depression may have been underestimated because the costs of end-of-life care are high. The burden for each cancer type was not analyzed because of the small sample size.
Conclusion In adults with cancer, those with depression had higher health care utilization and expenditures compared with those without depression.
Funding/sponsorship One author partially supported by the National Institute of General Medical Sciences, U54GM104942.
Click on the PDF icon at the top of this introduction to read the full article.
Background The rates of depression in adults with cancer have been reported as high as 38%-58%. How depression affects overall health care expenditures in individuals with cancer is an under-researched area.
Objective To estimate excess average total health care expenditures associated with depression in adults with cancer by comparing those with and without depression after controlling for demographic, socioeconomic, access to care, and other health status variables.
Methods Cross-sectional data on 4,766 adult survivors of cancer from 2006-2009 of the nationally representative household survey, Medical Expenditure Panel Survey (MEPS), were used. The patients were older than 21 years. Cancer and depression were identified from the patients’ medical conditions files. Dependent variables consisted of total, inpatient, outpatient, emergency department, prescription drugs, and other expenditures. Ordinary least square (OLS) on logged dollars and generalized linear models with log-link function were performed. All analyses (SAS 9.3 and STATA12) accounted for the complex survey design of the MEPS.
Results Overall, 14% of individuals with cancer reported having depression. In those with cancer and depression, the average annual health care expenditures were $18,401 compared with $12,091 in those without depression. After adjusting for demographic, socioeconomic, access to care, and other health status variables, those with depression had about 31.7% greater total expenditures compared with those without depression. Total, outpatient, and prescription expenditures were higher in individuals with depression than in those without depression. Individuals with cancer and depression were significantly more likely to use emergency departments (adjusted odds ratio, 1.46) compared with their counterparts without depression.
Limitations Cancer patients who died during the reporting year were excluded. The financial burden of depression may have been underestimated because the costs of end-of-life care are high. The burden for each cancer type was not analyzed because of the small sample size.
Conclusion In adults with cancer, those with depression had higher health care utilization and expenditures compared with those without depression.
Funding/sponsorship One author partially supported by the National Institute of General Medical Sciences, U54GM104942.
Click on the PDF icon at the top of this introduction to read the full article.
Pain, quality of life measures improve more in OA than RA after knee arthroplasty
Total knee arthroplasty provides osteoarthritis patients with greater improvement in pain and health-related quality of life than it does for rheumatoid arthritis patients, possibly relating to the lower pain and younger age of RA patients at the time of surgery, according to a study based on patients’ responses to semiannual questionnaires.
The study included 834 patients diagnosed with RA and 315 patients diagnosed with osteoarthritis (OA), who had a primary total knee arthroplasty (TKA) between Jan. 1, 1999, and June 30, 2012. The patients were probed on their demographic characteristics, disease duration, mental health, functional status, health-related quality of life (HRQoL), pain, and usage of pain medication. All study participants participated in at least three consecutive sampling intervals: a 6-month preoperative period, a 6-month immediate postoperative period, and a subsequent 6-month “recovery” period. Of the patients who underwent a TKA, 144 (11%) did not complete all three sampling intervals.
At baseline, compared with OA patients, RA patients had significantly less severe scores for measures of pain, lesser usage of pain medications, and significantly more severe scores for measures of disease activity.
After recovering from a TKA, the RA and OA patients improved in almost all outcome measures of pain, function, and HRQoL. The surgery had a larger beneficial effect in OA patients than in RA patients for all measures of pain and HRQoL indices, except for the RA disease activity index (RADAI)/total joint count. In contrast to the OA patients, RA patients showed greater improvements in joint involvement.
For both groups, all outcome measures of pain and function worsened a year before TKA and improved immediately after the surgery; however, the improvement leveled off in the 6-12 months after the procedure.
“After adjusting for preoperative variables, post TKA, a diagnosis of RA (vs. OA) (P = .03), income (P < .01), and anxiety (P = .03) were most useful in predicting the reduction in [visual analog scale] pain scores,” noted Dr. Anand Dusad of the Veterans Affairs Nebraska–Western Iowa Health Care System, Omaha, and his colleagues.
“In summary, using a large cohort of arthritis patients, we have shown that TKA is performed in patients with severe disease and leads to marked improvements in pain function and HRQoL,” according to the researchers.
Read the full study published online July 20 in Arthritis & Rheumatology (doi:10.1002/art.39221).
Total knee arthroplasty provides osteoarthritis patients with greater improvement in pain and health-related quality of life than it does for rheumatoid arthritis patients, possibly relating to the lower pain and younger age of RA patients at the time of surgery, according to a study based on patients’ responses to semiannual questionnaires.
The study included 834 patients diagnosed with RA and 315 patients diagnosed with osteoarthritis (OA), who had a primary total knee arthroplasty (TKA) between Jan. 1, 1999, and June 30, 2012. The patients were probed on their demographic characteristics, disease duration, mental health, functional status, health-related quality of life (HRQoL), pain, and usage of pain medication. All study participants participated in at least three consecutive sampling intervals: a 6-month preoperative period, a 6-month immediate postoperative period, and a subsequent 6-month “recovery” period. Of the patients who underwent a TKA, 144 (11%) did not complete all three sampling intervals.
At baseline, compared with OA patients, RA patients had significantly less severe scores for measures of pain, lesser usage of pain medications, and significantly more severe scores for measures of disease activity.
After recovering from a TKA, the RA and OA patients improved in almost all outcome measures of pain, function, and HRQoL. The surgery had a larger beneficial effect in OA patients than in RA patients for all measures of pain and HRQoL indices, except for the RA disease activity index (RADAI)/total joint count. In contrast to the OA patients, RA patients showed greater improvements in joint involvement.
For both groups, all outcome measures of pain and function worsened a year before TKA and improved immediately after the surgery; however, the improvement leveled off in the 6-12 months after the procedure.
“After adjusting for preoperative variables, post TKA, a diagnosis of RA (vs. OA) (P = .03), income (P < .01), and anxiety (P = .03) were most useful in predicting the reduction in [visual analog scale] pain scores,” noted Dr. Anand Dusad of the Veterans Affairs Nebraska–Western Iowa Health Care System, Omaha, and his colleagues.
“In summary, using a large cohort of arthritis patients, we have shown that TKA is performed in patients with severe disease and leads to marked improvements in pain function and HRQoL,” according to the researchers.
Read the full study published online July 20 in Arthritis & Rheumatology (doi:10.1002/art.39221).
Total knee arthroplasty provides osteoarthritis patients with greater improvement in pain and health-related quality of life than it does for rheumatoid arthritis patients, possibly relating to the lower pain and younger age of RA patients at the time of surgery, according to a study based on patients’ responses to semiannual questionnaires.
The study included 834 patients diagnosed with RA and 315 patients diagnosed with osteoarthritis (OA), who had a primary total knee arthroplasty (TKA) between Jan. 1, 1999, and June 30, 2012. The patients were probed on their demographic characteristics, disease duration, mental health, functional status, health-related quality of life (HRQoL), pain, and usage of pain medication. All study participants participated in at least three consecutive sampling intervals: a 6-month preoperative period, a 6-month immediate postoperative period, and a subsequent 6-month “recovery” period. Of the patients who underwent a TKA, 144 (11%) did not complete all three sampling intervals.
At baseline, compared with OA patients, RA patients had significantly less severe scores for measures of pain, lesser usage of pain medications, and significantly more severe scores for measures of disease activity.
After recovering from a TKA, the RA and OA patients improved in almost all outcome measures of pain, function, and HRQoL. The surgery had a larger beneficial effect in OA patients than in RA patients for all measures of pain and HRQoL indices, except for the RA disease activity index (RADAI)/total joint count. In contrast to the OA patients, RA patients showed greater improvements in joint involvement.
For both groups, all outcome measures of pain and function worsened a year before TKA and improved immediately after the surgery; however, the improvement leveled off in the 6-12 months after the procedure.
“After adjusting for preoperative variables, post TKA, a diagnosis of RA (vs. OA) (P = .03), income (P < .01), and anxiety (P = .03) were most useful in predicting the reduction in [visual analog scale] pain scores,” noted Dr. Anand Dusad of the Veterans Affairs Nebraska–Western Iowa Health Care System, Omaha, and his colleagues.
“In summary, using a large cohort of arthritis patients, we have shown that TKA is performed in patients with severe disease and leads to marked improvements in pain function and HRQoL,” according to the researchers.
Read the full study published online July 20 in Arthritis & Rheumatology (doi:10.1002/art.39221).
FROM ARTHRITIS & RHEUMATOLOGY
Database may help predict cancer patients’ survival
Photo by Darren Baker
A newly developed database may help physicians predict survival outcomes in patients with hematologic and solid tumor malignancies, according to a paper published in Nature Medicine.
The database, known as PRECOG, integrates gene expression patterns of 39 types of cancer from nearly 18,000 patients with data about how long those patients lived.
By combining these data, researchers were able to see broad patterns that correlate with survival. They also believe this information could help them pinpoint potential therapeutic targets for a range of cancers.
“We were able to identify key pathways that can dramatically stratify survival across diverse cancer types,” said Ash Alizadeh, MD, PhD, of Stanford University in California.
“The patterns were very striking, especially because few such examples are currently available for the use of genes or immune cells for cancer prognosis.”
In addition to identifying potentially useful gene expression patterns, the researchers used an analytical tool called CIBERSORT to determine the composition of leukocytes that flock to a tumor.
“We were able to infer which immune cells are present or absent in individual solid tumors, to estimate their prevalence, and to correlate that information with patient survival,” said Aaron Newman, PhD, of Stanford University.
“We found you can even broadly distinguish cancer types just based on what kind of immune cells have infiltrated the tumor.”
Compiling the data
Researchers have tried for years to identify specific patterns of gene expression in cancerous tumors that differ from those in normal tissue. But the extreme variability among individual patients and tumors has made the process difficult, even when focused on particular cancer types.
“There are many more genes in a cell than there are patients with any one type of cancer, and this makes discovering the important genes for cancer outcomes a tough problem,” said Andrew Gentles, PhD, of Stanford University.
“Because it’s easy to find spurious associations that don’t hold up in follow-up studies, we combined information from a vast array of cancer types to better see meaningful correlations.”
The researchers first collected publicly available data on gene expression patterns of many types of cancers.
They then matched the gene expression profiles with clinical information about the patients, including their age, disease status, and how long they survived after diagnosis. Finally, the team combined the studies in a database.
“We wanted to be able to connect gene expression data with patient outcome for thousands of people at once,” Dr Alizadeh said. “Then, we could ask what we could learn more broadly.”
Surprising findings
The researchers were surprised to find that prognostic genes were often shared among distinct cancer types, suggesting that similar biological programs impact survival across cancers.
They were able to identify the top 10 genes that seemed to confer adverse outcomes—FOXM1, BIRC5, TOP2A, TPX2, NME1, CCNB1, CEP55, TYMS, CENPF, and CDKN3—and the top 10 genes associated with more positive outcomes—KLRB1, ITM2B, CBX7, CD2, CREBL2, SATB1, NR3C1, TMEM66, KLRK1, and FUCA1.
Many of these genes are involved in aspects of cell division or are associated with distinct leukocytes that flood a tumor.
The researchers were also able to identify combinations of leukocytes that appear to be correlated with outcomes.
In particular, elevated numbers of plasma cells and certain types of T cells correlated with better patient survival rates across many different solid tumors. But a high proportion of granulocytes was associated with adverse outcomes.
The researchers hope that PRECOG and CIBERSORT will increase our understanding of cancer biology and aid the development of new therapies for cancer patients. The team is applying these tools to better predict which patients will respond to new and emerging anticancer therapies.
Dr Alizadeh said this is especially important given recent advances in the development of drugs that engage immune responses but work well only for a subset of cancer patients. 
Photo by Darren Baker
A newly developed database may help physicians predict survival outcomes in patients with hematologic and solid tumor malignancies, according to a paper published in Nature Medicine.
The database, known as PRECOG, integrates gene expression patterns of 39 types of cancer from nearly 18,000 patients with data about how long those patients lived.
By combining these data, researchers were able to see broad patterns that correlate with survival. They also believe this information could help them pinpoint potential therapeutic targets for a range of cancers.
“We were able to identify key pathways that can dramatically stratify survival across diverse cancer types,” said Ash Alizadeh, MD, PhD, of Stanford University in California.
“The patterns were very striking, especially because few such examples are currently available for the use of genes or immune cells for cancer prognosis.”
In addition to identifying potentially useful gene expression patterns, the researchers used an analytical tool called CIBERSORT to determine the composition of leukocytes that flock to a tumor.
“We were able to infer which immune cells are present or absent in individual solid tumors, to estimate their prevalence, and to correlate that information with patient survival,” said Aaron Newman, PhD, of Stanford University.
“We found you can even broadly distinguish cancer types just based on what kind of immune cells have infiltrated the tumor.”
Compiling the data
Researchers have tried for years to identify specific patterns of gene expression in cancerous tumors that differ from those in normal tissue. But the extreme variability among individual patients and tumors has made the process difficult, even when focused on particular cancer types.
“There are many more genes in a cell than there are patients with any one type of cancer, and this makes discovering the important genes for cancer outcomes a tough problem,” said Andrew Gentles, PhD, of Stanford University.
“Because it’s easy to find spurious associations that don’t hold up in follow-up studies, we combined information from a vast array of cancer types to better see meaningful correlations.”
The researchers first collected publicly available data on gene expression patterns of many types of cancers.
They then matched the gene expression profiles with clinical information about the patients, including their age, disease status, and how long they survived after diagnosis. Finally, the team combined the studies in a database.
“We wanted to be able to connect gene expression data with patient outcome for thousands of people at once,” Dr Alizadeh said. “Then, we could ask what we could learn more broadly.”
Surprising findings
The researchers were surprised to find that prognostic genes were often shared among distinct cancer types, suggesting that similar biological programs impact survival across cancers.
They were able to identify the top 10 genes that seemed to confer adverse outcomes—FOXM1, BIRC5, TOP2A, TPX2, NME1, CCNB1, CEP55, TYMS, CENPF, and CDKN3—and the top 10 genes associated with more positive outcomes—KLRB1, ITM2B, CBX7, CD2, CREBL2, SATB1, NR3C1, TMEM66, KLRK1, and FUCA1.
Many of these genes are involved in aspects of cell division or are associated with distinct leukocytes that flood a tumor.
The researchers were also able to identify combinations of leukocytes that appear to be correlated with outcomes.
In particular, elevated numbers of plasma cells and certain types of T cells correlated with better patient survival rates across many different solid tumors. But a high proportion of granulocytes was associated with adverse outcomes.
The researchers hope that PRECOG and CIBERSORT will increase our understanding of cancer biology and aid the development of new therapies for cancer patients. The team is applying these tools to better predict which patients will respond to new and emerging anticancer therapies.
Dr Alizadeh said this is especially important given recent advances in the development of drugs that engage immune responses but work well only for a subset of cancer patients.
Photo by Darren Baker
A newly developed database may help physicians predict survival outcomes in patients with hematologic and solid tumor malignancies, according to a paper published in Nature Medicine.
The database, known as PRECOG, integrates gene expression patterns of 39 types of cancer from nearly 18,000 patients with data about how long those patients lived.
By combining these data, researchers were able to see broad patterns that correlate with survival. They also believe this information could help them pinpoint potential therapeutic targets for a range of cancers.
“We were able to identify key pathways that can dramatically stratify survival across diverse cancer types,” said Ash Alizadeh, MD, PhD, of Stanford University in California.
“The patterns were very striking, especially because few such examples are currently available for the use of genes or immune cells for cancer prognosis.”
In addition to identifying potentially useful gene expression patterns, the researchers used an analytical tool called CIBERSORT to determine the composition of leukocytes that flock to a tumor.
“We were able to infer which immune cells are present or absent in individual solid tumors, to estimate their prevalence, and to correlate that information with patient survival,” said Aaron Newman, PhD, of Stanford University.
“We found you can even broadly distinguish cancer types just based on what kind of immune cells have infiltrated the tumor.”
Compiling the data
Researchers have tried for years to identify specific patterns of gene expression in cancerous tumors that differ from those in normal tissue. But the extreme variability among individual patients and tumors has made the process difficult, even when focused on particular cancer types.
“There are many more genes in a cell than there are patients with any one type of cancer, and this makes discovering the important genes for cancer outcomes a tough problem,” said Andrew Gentles, PhD, of Stanford University.
“Because it’s easy to find spurious associations that don’t hold up in follow-up studies, we combined information from a vast array of cancer types to better see meaningful correlations.”
The researchers first collected publicly available data on gene expression patterns of many types of cancers.
They then matched the gene expression profiles with clinical information about the patients, including their age, disease status, and how long they survived after diagnosis. Finally, the team combined the studies in a database.
“We wanted to be able to connect gene expression data with patient outcome for thousands of people at once,” Dr Alizadeh said. “Then, we could ask what we could learn more broadly.”
Surprising findings
The researchers were surprised to find that prognostic genes were often shared among distinct cancer types, suggesting that similar biological programs impact survival across cancers.
They were able to identify the top 10 genes that seemed to confer adverse outcomes—FOXM1, BIRC5, TOP2A, TPX2, NME1, CCNB1, CEP55, TYMS, CENPF, and CDKN3—and the top 10 genes associated with more positive outcomes—KLRB1, ITM2B, CBX7, CD2, CREBL2, SATB1, NR3C1, TMEM66, KLRK1, and FUCA1.
Many of these genes are involved in aspects of cell division or are associated with distinct leukocytes that flood a tumor.
The researchers were also able to identify combinations of leukocytes that appear to be correlated with outcomes.
In particular, elevated numbers of plasma cells and certain types of T cells correlated with better patient survival rates across many different solid tumors. But a high proportion of granulocytes was associated with adverse outcomes.
The researchers hope that PRECOG and CIBERSORT will increase our understanding of cancer biology and aid the development of new therapies for cancer patients. The team is applying these tools to better predict which patients will respond to new and emerging anticancer therapies.
Dr Alizadeh said this is especially important given recent advances in the development of drugs that engage immune responses but work well only for a subset of cancer patients.
Antibiotic can affect INR levels
Treatment with the antibiotic dicloxacillin may cause a significant decrease in international normalized ratio (INR) levels among patients taking vitamin K antagonists (VKAs), according to research published in JAMA.
Researchers studied 7400 patients on VKA therapy and found that 61% of patients taking warfarin and dicloxacillin experienced a decrease in INR after dicloxacillin exposure.
Forty-one percent of patients taking phenprocoumon had a decrease in INR after exposure to the antibiotic.
Anton Pottegard, PhD, of the University of Southern Denmark, Odense, and his colleagues conducted this research using Thrombobase, a clinical database of all VKA-treated patients followed up by 3 outpatient clinics and 50 general practitioners in Funen, Denmark.
The researchers included all patients who filled a prescription for dicloxacillin while receiving warfarin or phenprocoumon between March 1998 and November 2012.
INR results were grouped by the week relative to dicloxacillin exposure. The last INR measurement before dicloxacillin exposure was compared with the first measurement within weeks 2 to 4 after dicloxacillin exposure.
Of the 519 patients taking warfarin and initiating treatment with dicloxacillin, 236 met inclusion criteria. The average INR level was 2.6 prior to dicloxacillin exposure and 2 at two to four weeks after dicloxacillin exposure.
In total, 61% of patients (n=144) experienced sub-therapeutic INR levels (<2.0) within 2 to 4 weeks of dicloxacillin exposure.
Among patients taking phenprocoumon (n=64), average INR levels were 2.6 before exposure to dicloxacillin and 2.3 at two to four weeks after exposure. The proportion of patients with sub-therapeutic INR levels after dicloxacillin exposure was 41% (n=26).
The researchers said these results suggest treatment with dicloxacillin can cause a significant decrease in INR levels among patients taking VKAs.
Treatment with the antibiotic dicloxacillin may cause a significant decrease in international normalized ratio (INR) levels among patients taking vitamin K antagonists (VKAs), according to research published in JAMA.
Researchers studied 7400 patients on VKA therapy and found that 61% of patients taking warfarin and dicloxacillin experienced a decrease in INR after dicloxacillin exposure.
Forty-one percent of patients taking phenprocoumon had a decrease in INR after exposure to the antibiotic.
Anton Pottegard, PhD, of the University of Southern Denmark, Odense, and his colleagues conducted this research using Thrombobase, a clinical database of all VKA-treated patients followed up by 3 outpatient clinics and 50 general practitioners in Funen, Denmark.
The researchers included all patients who filled a prescription for dicloxacillin while receiving warfarin or phenprocoumon between March 1998 and November 2012.
INR results were grouped by the week relative to dicloxacillin exposure. The last INR measurement before dicloxacillin exposure was compared with the first measurement within weeks 2 to 4 after dicloxacillin exposure.
Of the 519 patients taking warfarin and initiating treatment with dicloxacillin, 236 met inclusion criteria. The average INR level was 2.6 prior to dicloxacillin exposure and 2 at two to four weeks after dicloxacillin exposure.
In total, 61% of patients (n=144) experienced sub-therapeutic INR levels (<2.0) within 2 to 4 weeks of dicloxacillin exposure.
Among patients taking phenprocoumon (n=64), average INR levels were 2.6 before exposure to dicloxacillin and 2.3 at two to four weeks after exposure. The proportion of patients with sub-therapeutic INR levels after dicloxacillin exposure was 41% (n=26).
The researchers said these results suggest treatment with dicloxacillin can cause a significant decrease in INR levels among patients taking VKAs.
Treatment with the antibiotic dicloxacillin may cause a significant decrease in international normalized ratio (INR) levels among patients taking vitamin K antagonists (VKAs), according to research published in JAMA.
Researchers studied 7400 patients on VKA therapy and found that 61% of patients taking warfarin and dicloxacillin experienced a decrease in INR after dicloxacillin exposure.
Forty-one percent of patients taking phenprocoumon had a decrease in INR after exposure to the antibiotic.
Anton Pottegard, PhD, of the University of Southern Denmark, Odense, and his colleagues conducted this research using Thrombobase, a clinical database of all VKA-treated patients followed up by 3 outpatient clinics and 50 general practitioners in Funen, Denmark.
The researchers included all patients who filled a prescription for dicloxacillin while receiving warfarin or phenprocoumon between March 1998 and November 2012.
INR results were grouped by the week relative to dicloxacillin exposure. The last INR measurement before dicloxacillin exposure was compared with the first measurement within weeks 2 to 4 after dicloxacillin exposure.
Of the 519 patients taking warfarin and initiating treatment with dicloxacillin, 236 met inclusion criteria. The average INR level was 2.6 prior to dicloxacillin exposure and 2 at two to four weeks after dicloxacillin exposure.
In total, 61% of patients (n=144) experienced sub-therapeutic INR levels (<2.0) within 2 to 4 weeks of dicloxacillin exposure.
Among patients taking phenprocoumon (n=64), average INR levels were 2.6 before exposure to dicloxacillin and 2.3 at two to four weeks after exposure. The proportion of patients with sub-therapeutic INR levels after dicloxacillin exposure was 41% (n=26).
The researchers said these results suggest treatment with dicloxacillin can cause a significant decrease in INR levels among patients taking VKAs.