Key clinical point: Secukinumab improved disease burden in patients with psoriatic arthritis (PsA), regardless of previous tumor necrosis factor inhibitor (TNFi) exposure.

Major finding: Higher proportion of TNFi-naive patients receiving secukinumab 300 and 150 mg vs placebo showed resolution in 66 swollen joint count (SJC66; 41.5% and 27.7% vs 16.8%, respectively) and 68 tender joint counts (24.4% and 13.4% vs 5.7%, respectively; all P less than .05). Among patients with inadequate response to TNFi (TNFi-IR), those who received secukinumab 150 mg vs placebo experienced significant SJC66 resolution (20.8% vs 12.3%; P less than .05).

Study details: Findings are from a pooled analysis of 4 phase 3 randomized controlled trials (FUTURE 2, FUTURE 3, FUTURE 4, and FUTURE 5) involving 2049 patients with PsA who were either TNFi naive (n=1436) or TNFi-IR (n=613). Patients received either secukinumab 300 mg (n=461), secukinumab 150 mg (n=907), or placebo (n=681).

Disclosures: This study was sponsored by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. The authors including the lead author reported receiving grant support, speaker fees, and/or consulting fees from various sources. O Chambenoit and X Meng reported being employees and stockholders of Novartis.

Source: Orbai AM et al. Rheumatol Ther. 2021 Jul 3. doi: 10.1007/s40744-021-00337-5.

Key clinical point: Secukinumab improved disease burden in patients with psoriatic arthritis (PsA), regardless of previous tumor necrosis factor inhibitor (TNFi) exposure.

Major finding: Higher proportion of TNFi-naive patients receiving secukinumab 300 and 150 mg vs placebo showed resolution in 66 swollen joint count (SJC66; 41.5% and 27.7% vs 16.8%, respectively) and 68 tender joint counts (24.4% and 13.4% vs 5.7%, respectively; all P less than .05). Among patients with inadequate response to TNFi (TNFi-IR), those who received secukinumab 150 mg vs placebo experienced significant SJC66 resolution (20.8% vs 12.3%; P less than .05).

Study details: Findings are from a pooled analysis of 4 phase 3 randomized controlled trials (FUTURE 2, FUTURE 3, FUTURE 4, and FUTURE 5) involving 2049 patients with PsA who were either TNFi naive (n=1436) or TNFi-IR (n=613). Patients received either secukinumab 300 mg (n=461), secukinumab 150 mg (n=907), or placebo (n=681).

Disclosures: This study was sponsored by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. The authors including the lead author reported receiving grant support, speaker fees, and/or consulting fees from various sources. O Chambenoit and X Meng reported being employees and stockholders of Novartis.

Source: Orbai AM et al. Rheumatol Ther. 2021 Jul 3. doi: 10.1007/s40744-021-00337-5.

Key clinical point: Secukinumab improved disease burden in patients with psoriatic arthritis (PsA), regardless of previous tumor necrosis factor inhibitor (TNFi) exposure.

Major finding: Higher proportion of TNFi-naive patients receiving secukinumab 300 and 150 mg vs placebo showed resolution in 66 swollen joint count (SJC66; 41.5% and 27.7% vs 16.8%, respectively) and 68 tender joint counts (24.4% and 13.4% vs 5.7%, respectively; all P less than .05). Among patients with inadequate response to TNFi (TNFi-IR), those who received secukinumab 150 mg vs placebo experienced significant SJC66 resolution (20.8% vs 12.3%; P less than .05).

Study details: Findings are from a pooled analysis of 4 phase 3 randomized controlled trials (FUTURE 2, FUTURE 3, FUTURE 4, and FUTURE 5) involving 2049 patients with PsA who were either TNFi naive (n=1436) or TNFi-IR (n=613). Patients received either secukinumab 300 mg (n=461), secukinumab 150 mg (n=907), or placebo (n=681).

Disclosures: This study was sponsored by Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA. The authors including the lead author reported receiving grant support, speaker fees, and/or consulting fees from various sources. O Chambenoit and X Meng reported being employees and stockholders of Novartis.

Source: Orbai AM et al. Rheumatol Ther. 2021 Jul 3. doi: 10.1007/s40744-021-00337-5.

Key clinical point: In a real-world cohort of patients with psoriatic arthritis (PsA), achievement of treatment targets was similar after 6 months of treatment with ustekinumab or tumor necrosis factor (TNF) inhibitors.

Major finding: After 6 months of treatment, the proportion of patients achieving clinical Disease Activity Index for PsA (odds ratio [OR], 0.73; 95% confidence interval [CI], 0.46-1.15), low disease activity (LDA; OR, 0.74; 95% CI, 0.53-1.04), minimal disease activity (OR, 0.87; 95% CI, 0.61-1.25), and very LDA (OR, 0.74; 95% CI, 0.42-1.30) was not significantly different in ustekinumab vs TNF inhibitor groups. Both the groups reported similar adverse and serious adverse events.

Study details: Findings are from an analysis of 868 patients with PsA from the observational PsABio study, who were treated with first-line to third-line ustekinumab or TNF inhibitors.

Disclosures: PsABio study was sponsored by Janssen. The authors including the lead author reported receiving grants/research support and/or personal fees from various sources including Janssen. W Noël, P Bergmans, and E Theander reported being full-time employees of Janssen.

Source: Smolen JS et al. Ann Rheum Dis. 2021 Jun 23. doi: 10.1136/annrheumdis-2021-220263.

Key clinical point: In a real-world cohort of patients with psoriatic arthritis (PsA), achievement of treatment targets was similar after 6 months of treatment with ustekinumab or tumor necrosis factor (TNF) inhibitors.

Major finding: After 6 months of treatment, the proportion of patients achieving clinical Disease Activity Index for PsA (odds ratio [OR], 0.73; 95% confidence interval [CI], 0.46-1.15), low disease activity (LDA; OR, 0.74; 95% CI, 0.53-1.04), minimal disease activity (OR, 0.87; 95% CI, 0.61-1.25), and very LDA (OR, 0.74; 95% CI, 0.42-1.30) was not significantly different in ustekinumab vs TNF inhibitor groups. Both the groups reported similar adverse and serious adverse events.

Study details: Findings are from an analysis of 868 patients with PsA from the observational PsABio study, who were treated with first-line to third-line ustekinumab or TNF inhibitors.

Disclosures: PsABio study was sponsored by Janssen. The authors including the lead author reported receiving grants/research support and/or personal fees from various sources including Janssen. W Noël, P Bergmans, and E Theander reported being full-time employees of Janssen.

Source: Smolen JS et al. Ann Rheum Dis. 2021 Jun 23. doi: 10.1136/annrheumdis-2021-220263.

Key clinical point: In a real-world cohort of patients with psoriatic arthritis (PsA), achievement of treatment targets was similar after 6 months of treatment with ustekinumab or tumor necrosis factor (TNF) inhibitors.

Major finding: After 6 months of treatment, the proportion of patients achieving clinical Disease Activity Index for PsA (odds ratio [OR], 0.73; 95% confidence interval [CI], 0.46-1.15), low disease activity (LDA; OR, 0.74; 95% CI, 0.53-1.04), minimal disease activity (OR, 0.87; 95% CI, 0.61-1.25), and very LDA (OR, 0.74; 95% CI, 0.42-1.30) was not significantly different in ustekinumab vs TNF inhibitor groups. Both the groups reported similar adverse and serious adverse events.

Study details: Findings are from an analysis of 868 patients with PsA from the observational PsABio study, who were treated with first-line to third-line ustekinumab or TNF inhibitors.

Disclosures: PsABio study was sponsored by Janssen. The authors including the lead author reported receiving grants/research support and/or personal fees from various sources including Janssen. W Noël, P Bergmans, and E Theander reported being full-time employees of Janssen.

Source: Smolen JS et al. Ann Rheum Dis. 2021 Jun 23. doi: 10.1136/annrheumdis-2021-220263.

Key clinical point: The composite ultrasonography scores showed a significantly greater value for assessment of disease activity than clinical scores in patients with psoriatic arthritis (PsA) with coexisting fibromyalgia syndrome (FMS).

Major finding: Patients with coexisting PsA and FMS vs those without FMS had higher scores for several disease activity indices, including Composite Psoriatic Disease Activity Index, Disease Activity for PsA, and PsA Disease Activity Score (P less than .001). However, both groups had similar total ultrasonographic scores regardless of FMS (P = .68). A significant association was observed between FMS and higher scores on clinical activity indices (P less than .001) but not with the ultrasonography score.

Study details: The data come from a prospective study of 156 patients with PsA who were categorized into those with (n=42) and without (n=114) FMS.

Disclosures: No specific funding or conflicts of interest were reported.

Source: Polachek A et al. Ann Rheum Dis. 2021 Jul 2. doi: 10.1136/annrheumdis-2021-220562.

Key clinical point: The composite ultrasonography scores showed a significantly greater value for assessment of disease activity than clinical scores in patients with psoriatic arthritis (PsA) with coexisting fibromyalgia syndrome (FMS).

Major finding: Patients with coexisting PsA and FMS vs those without FMS had higher scores for several disease activity indices, including Composite Psoriatic Disease Activity Index, Disease Activity for PsA, and PsA Disease Activity Score (P less than .001). However, both groups had similar total ultrasonographic scores regardless of FMS (P = .68). A significant association was observed between FMS and higher scores on clinical activity indices (P less than .001) but not with the ultrasonography score.

Study details: The data come from a prospective study of 156 patients with PsA who were categorized into those with (n=42) and without (n=114) FMS.

Disclosures: No specific funding or conflicts of interest were reported.

Source: Polachek A et al. Ann Rheum Dis. 2021 Jul 2. doi: 10.1136/annrheumdis-2021-220562.

Key clinical point: The composite ultrasonography scores showed a significantly greater value for assessment of disease activity than clinical scores in patients with psoriatic arthritis (PsA) with coexisting fibromyalgia syndrome (FMS).

Major finding: Patients with coexisting PsA and FMS vs those without FMS had higher scores for several disease activity indices, including Composite Psoriatic Disease Activity Index, Disease Activity for PsA, and PsA Disease Activity Score (P less than .001). However, both groups had similar total ultrasonographic scores regardless of FMS (P = .68). A significant association was observed between FMS and higher scores on clinical activity indices (P less than .001) but not with the ultrasonography score.

Study details: The data come from a prospective study of 156 patients with PsA who were categorized into those with (n=42) and without (n=114) FMS.

Disclosures: No specific funding or conflicts of interest were reported.

Source: Polachek A et al. Ann Rheum Dis. 2021 Jul 2. doi: 10.1136/annrheumdis-2021-220562.

Key clinical point: Findings from this real-life cohort of patients with early psoriatic arthritis (PsA) confirm the safety and efficacy of guselkumab on peripheral and axial manifestations.

Major finding: After 12 months of guselkumab treatment, the mean Patient Global Assessment (P less than .0001), Visual Analogue Scale of Pain (P less than .001), and Disease Activity Score of PsA (P less than .0001) decreased significantly. Inflammatory low back pain disappeared as early as 24 weeks in all patients with concomitant axial disease. Low disease activity and remission were achieved by 65% and 35% of patients, respectively. No adverse events were reported.

Study details: The data come from an observational study involving 24 patients with early PsA who initiated therapy with guselkumab for severe skin involvement.

Disclosures: No specific funding was received for this study. The authors declared no conflicts of interest.

 Source: Pantano I et al. Rheumatology (Oxford). 2021 Jun 21. doi: 10.1093/rheumatology/keab509.

Key clinical point: Findings from this real-life cohort of patients with early psoriatic arthritis (PsA) confirm the safety and efficacy of guselkumab on peripheral and axial manifestations.

Major finding: After 12 months of guselkumab treatment, the mean Patient Global Assessment (P less than .0001), Visual Analogue Scale of Pain (P less than .001), and Disease Activity Score of PsA (P less than .0001) decreased significantly. Inflammatory low back pain disappeared as early as 24 weeks in all patients with concomitant axial disease. Low disease activity and remission were achieved by 65% and 35% of patients, respectively. No adverse events were reported.

Study details: The data come from an observational study involving 24 patients with early PsA who initiated therapy with guselkumab for severe skin involvement.

Disclosures: No specific funding was received for this study. The authors declared no conflicts of interest.

 Source: Pantano I et al. Rheumatology (Oxford). 2021 Jun 21. doi: 10.1093/rheumatology/keab509.

Key clinical point: Findings from this real-life cohort of patients with early psoriatic arthritis (PsA) confirm the safety and efficacy of guselkumab on peripheral and axial manifestations.

Major finding: After 12 months of guselkumab treatment, the mean Patient Global Assessment (P less than .0001), Visual Analogue Scale of Pain (P less than .001), and Disease Activity Score of PsA (P less than .0001) decreased significantly. Inflammatory low back pain disappeared as early as 24 weeks in all patients with concomitant axial disease. Low disease activity and remission were achieved by 65% and 35% of patients, respectively. No adverse events were reported.

Study details: The data come from an observational study involving 24 patients with early PsA who initiated therapy with guselkumab for severe skin involvement.

Disclosures: No specific funding was received for this study. The authors declared no conflicts of interest.

 Source: Pantano I et al. Rheumatology (Oxford). 2021 Jun 21. doi: 10.1093/rheumatology/keab509.

Key clinical point: Patients with psoriatic arthritis (PsA) with vs without nail involvement had higher rates of carotid plaque (CP) and carotid intima-media thickness (cIMT). Additionally, nail involvement in PsA was independently associated with CP risk.

Major finding: Patients with vs without nail involvement showed a higher prevalence of CP (53.1% vs 25.0%; P = .021) and cIMT (0.85 vs 0.59 mm; P = .026). The nail involvement was an independent risk factor for the presence of CP (odds ratio, 6.64; P = .006).

Study details: Findings are from a cross-sectional, observational study involving 64 patients with PsA. Patients with nail involvement were matched by age, gender, and type 2 diabetes mellitus diagnosis to those without nail involvement.

Disclosures: No specific funding or conflicts of interest were declared.

Source: Colunga-Pedraza IJ et al. Ann Rheum Dis. 2021 Jun 24. doi: 10.1136/annrheumdis-2021-220782.

Key clinical point: Patients with psoriatic arthritis (PsA) with vs without nail involvement had higher rates of carotid plaque (CP) and carotid intima-media thickness (cIMT). Additionally, nail involvement in PsA was independently associated with CP risk.

Major finding: Patients with vs without nail involvement showed a higher prevalence of CP (53.1% vs 25.0%; P = .021) and cIMT (0.85 vs 0.59 mm; P = .026). The nail involvement was an independent risk factor for the presence of CP (odds ratio, 6.64; P = .006).

Study details: Findings are from a cross-sectional, observational study involving 64 patients with PsA. Patients with nail involvement were matched by age, gender, and type 2 diabetes mellitus diagnosis to those without nail involvement.

Disclosures: No specific funding or conflicts of interest were declared.

Source: Colunga-Pedraza IJ et al. Ann Rheum Dis. 2021 Jun 24. doi: 10.1136/annrheumdis-2021-220782.

Key clinical point: Patients with psoriatic arthritis (PsA) with vs without nail involvement had higher rates of carotid plaque (CP) and carotid intima-media thickness (cIMT). Additionally, nail involvement in PsA was independently associated with CP risk.

Major finding: Patients with vs without nail involvement showed a higher prevalence of CP (53.1% vs 25.0%; P = .021) and cIMT (0.85 vs 0.59 mm; P = .026). The nail involvement was an independent risk factor for the presence of CP (odds ratio, 6.64; P = .006).

Study details: Findings are from a cross-sectional, observational study involving 64 patients with PsA. Patients with nail involvement were matched by age, gender, and type 2 diabetes mellitus diagnosis to those without nail involvement.

Disclosures: No specific funding or conflicts of interest were declared.

Source: Colunga-Pedraza IJ et al. Ann Rheum Dis. 2021 Jun 24. doi: 10.1136/annrheumdis-2021-220782.

Key clinical point: Patients with active psoriatic arthritis (PsA) and imaging-confirmed sacroiliitis treated with guselkumab every 4 weeks (Q4) or every 8 weeks (Q8) had greater mean improvements in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) score than placebo.

Major finding: At week 24, guselkumab Q4 and Q8 groups vs placebo showed higher least-squares mean changes in BASDAI (−2.7 and −2.7 vs −1.3; P less than .0001) and ASDAS (−1.4 and −1.4 vs −0.7; P less than .0001) scores, which were maintained until week 52.

Study details: This was a post hoc analysis of 2 DISCOVER studies including 312 patients with PsA with imaging-confirmed sacroiliitis who were randomly assigned to either placebo (n=118), guselkumab Q4 (n=103), or Q8 (n=91).

Disclosures: This study was funded by Janssen Research & Development LLC. The authors including the lead author reported grants and/or personal fees from various sources. Some of the authors declared being employees of Janssen Scientific Affairs LLC and Janssen Global Services LLC. Ten authors owned shares/stock options in Johnson & Johnson.

Source: Mease PJ et al. Lancet Rheumatol. 2021 Jun 29. doi: 10.1016/S2665-9913(21)00105-3.

Key clinical point: Patients with active psoriatic arthritis (PsA) and imaging-confirmed sacroiliitis treated with guselkumab every 4 weeks (Q4) or every 8 weeks (Q8) had greater mean improvements in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) score than placebo.

Major finding: At week 24, guselkumab Q4 and Q8 groups vs placebo showed higher least-squares mean changes in BASDAI (−2.7 and −2.7 vs −1.3; P less than .0001) and ASDAS (−1.4 and −1.4 vs −0.7; P less than .0001) scores, which were maintained until week 52.

Study details: This was a post hoc analysis of 2 DISCOVER studies including 312 patients with PsA with imaging-confirmed sacroiliitis who were randomly assigned to either placebo (n=118), guselkumab Q4 (n=103), or Q8 (n=91).

Disclosures: This study was funded by Janssen Research & Development LLC. The authors including the lead author reported grants and/or personal fees from various sources. Some of the authors declared being employees of Janssen Scientific Affairs LLC and Janssen Global Services LLC. Ten authors owned shares/stock options in Johnson & Johnson.

Source: Mease PJ et al. Lancet Rheumatol. 2021 Jun 29. doi: 10.1016/S2665-9913(21)00105-3.

Key clinical point: Patients with active psoriatic arthritis (PsA) and imaging-confirmed sacroiliitis treated with guselkumab every 4 weeks (Q4) or every 8 weeks (Q8) had greater mean improvements in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS) score than placebo.

Major finding: At week 24, guselkumab Q4 and Q8 groups vs placebo showed higher least-squares mean changes in BASDAI (−2.7 and −2.7 vs −1.3; P less than .0001) and ASDAS (−1.4 and −1.4 vs −0.7; P less than .0001) scores, which were maintained until week 52.

Study details: This was a post hoc analysis of 2 DISCOVER studies including 312 patients with PsA with imaging-confirmed sacroiliitis who were randomly assigned to either placebo (n=118), guselkumab Q4 (n=103), or Q8 (n=91).

Disclosures: This study was funded by Janssen Research & Development LLC. The authors including the lead author reported grants and/or personal fees from various sources. Some of the authors declared being employees of Janssen Scientific Affairs LLC and Janssen Global Services LLC. Ten authors owned shares/stock options in Johnson & Johnson.

Source: Mease PJ et al. Lancet Rheumatol. 2021 Jun 29. doi: 10.1016/S2665-9913(21)00105-3.

For patients with hepatocellular carcinoma (HCC) and liver-dominant disease, liver-directed therapy is frequently used as the initial attempt to control this malignancy. This month we will review several journal articles that address different forms of localized HCC management.

Ding W et al. analyzed 401 patients with early HCC who were treated in one center, either with microwave ablation (MWA, n=240) or robotic-assisted hepatectomy (RH, n=161). Following propensity-score matching (PSM) and inverse probability of treatment weight analysis, the authors found that both treatments can achieve safe, comparable therapeutic effects. The 3-year recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS) of MWA group and RH group were 52.2% vs 65.8%, 91.5% vs 91.3% and 91.5% vs 91.3%, respectively. OS and CSS were comparable (P = 0.44 and 0.96), while RFS of patients treated with MWA was slightly lower but not significantly so (P = 0.097). The authors concluded that both minimally-invasive approaches are effective in the treatment of early HCC. MWA was less invasive, while RH had better accuracy and caused less damage to the liver parenchyma.

Transarterial therapies are frequently withheld in patients who have major vascular invasion (HCC-MVI), and patients usually receive palliative systemic therapy instead. Kwee et al. examined the National Cancer Database (NCDB) data to comparatively evaluate overall survival (OS) between transarterial radioembolization (TARE) and systemic therapy in hepatocellular carcinoma (HCC) with major vascular invasion (HCC-MVI). OS was compared by propensity-score matched Cox regression and landmark analysis in 1514 patients with HCC-MVI who were treated between 2010 and 2015. Propensity-score matched and landmark-time adjusted analysis associated TARE with a median OS 7.1 months (95% CI 5.0 to 10.5) vs 4.9 months (95% CI 3.9 to 6.5) for patients treated with systemic therapy only, HR 0.74 (95% CI 0.60 to 0.91, P = 0.005). The authors were encouraged by these results, and suggested that additional prospective studies using TARE as treatment of HCC-MVI should be undertaken.

The SARAH trial (Vilgrain et al., Lancet Oncology 2017) compared the efficacy and safety of sorafenib to that of selective internal radiotherapy (SIRT) with yttrium-90 (90Y) resin microspheres (also termed TARE, transarterial radioembolization) in patients with hepatocellular carcinoma. The final conclusion was that overall survival did not significantly differ between the two groups. Pereira et al. published this ancillary study of the SARAH trial that compares health-related quality of life (HRQoL) between the two groups. HRQoL was preserved longer with TARE than with sorafenib in locally advanced HCC. The median time to deterioration for the global health status was 3.9 months (95% confidence interval [CI] 3.7–4.3) in the TARE group, vs 2.6 months (95% CI 2.0–3.0) in the sorafenib group. The authors concluded that the differences in HRQoL should inform decisions when recommending initial treatment of patients with HCC, though it does not take into account recently developed advancements in systemic therapy including immunotherapy.

For patients with hepatocellular carcinoma (HCC) and liver-dominant disease, liver-directed therapy is frequently used as the initial attempt to control this malignancy. This month we will review several journal articles that address different forms of localized HCC management.

Ding W et al. analyzed 401 patients with early HCC who were treated in one center, either with microwave ablation (MWA, n=240) or robotic-assisted hepatectomy (RH, n=161). Following propensity-score matching (PSM) and inverse probability of treatment weight analysis, the authors found that both treatments can achieve safe, comparable therapeutic effects. The 3-year recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS) of MWA group and RH group were 52.2% vs 65.8%, 91.5% vs 91.3% and 91.5% vs 91.3%, respectively. OS and CSS were comparable (P = 0.44 and 0.96), while RFS of patients treated with MWA was slightly lower but not significantly so (P = 0.097). The authors concluded that both minimally-invasive approaches are effective in the treatment of early HCC. MWA was less invasive, while RH had better accuracy and caused less damage to the liver parenchyma.

Transarterial therapies are frequently withheld in patients who have major vascular invasion (HCC-MVI), and patients usually receive palliative systemic therapy instead. Kwee et al. examined the National Cancer Database (NCDB) data to comparatively evaluate overall survival (OS) between transarterial radioembolization (TARE) and systemic therapy in hepatocellular carcinoma (HCC) with major vascular invasion (HCC-MVI). OS was compared by propensity-score matched Cox regression and landmark analysis in 1514 patients with HCC-MVI who were treated between 2010 and 2015. Propensity-score matched and landmark-time adjusted analysis associated TARE with a median OS 7.1 months (95% CI 5.0 to 10.5) vs 4.9 months (95% CI 3.9 to 6.5) for patients treated with systemic therapy only, HR 0.74 (95% CI 0.60 to 0.91, P = 0.005). The authors were encouraged by these results, and suggested that additional prospective studies using TARE as treatment of HCC-MVI should be undertaken.

The SARAH trial (Vilgrain et al., Lancet Oncology 2017) compared the efficacy and safety of sorafenib to that of selective internal radiotherapy (SIRT) with yttrium-90 (90Y) resin microspheres (also termed TARE, transarterial radioembolization) in patients with hepatocellular carcinoma. The final conclusion was that overall survival did not significantly differ between the two groups. Pereira et al. published this ancillary study of the SARAH trial that compares health-related quality of life (HRQoL) between the two groups. HRQoL was preserved longer with TARE than with sorafenib in locally advanced HCC. The median time to deterioration for the global health status was 3.9 months (95% confidence interval [CI] 3.7–4.3) in the TARE group, vs 2.6 months (95% CI 2.0–3.0) in the sorafenib group. The authors concluded that the differences in HRQoL should inform decisions when recommending initial treatment of patients with HCC, though it does not take into account recently developed advancements in systemic therapy including immunotherapy.

For patients with hepatocellular carcinoma (HCC) and liver-dominant disease, liver-directed therapy is frequently used as the initial attempt to control this malignancy. This month we will review several journal articles that address different forms of localized HCC management.

Ding W et al. analyzed 401 patients with early HCC who were treated in one center, either with microwave ablation (MWA, n=240) or robotic-assisted hepatectomy (RH, n=161). Following propensity-score matching (PSM) and inverse probability of treatment weight analysis, the authors found that both treatments can achieve safe, comparable therapeutic effects. The 3-year recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS) of MWA group and RH group were 52.2% vs 65.8%, 91.5% vs 91.3% and 91.5% vs 91.3%, respectively. OS and CSS were comparable (P = 0.44 and 0.96), while RFS of patients treated with MWA was slightly lower but not significantly so (P = 0.097). The authors concluded that both minimally-invasive approaches are effective in the treatment of early HCC. MWA was less invasive, while RH had better accuracy and caused less damage to the liver parenchyma.

Transarterial therapies are frequently withheld in patients who have major vascular invasion (HCC-MVI), and patients usually receive palliative systemic therapy instead. Kwee et al. examined the National Cancer Database (NCDB) data to comparatively evaluate overall survival (OS) between transarterial radioembolization (TARE) and systemic therapy in hepatocellular carcinoma (HCC) with major vascular invasion (HCC-MVI). OS was compared by propensity-score matched Cox regression and landmark analysis in 1514 patients with HCC-MVI who were treated between 2010 and 2015. Propensity-score matched and landmark-time adjusted analysis associated TARE with a median OS 7.1 months (95% CI 5.0 to 10.5) vs 4.9 months (95% CI 3.9 to 6.5) for patients treated with systemic therapy only, HR 0.74 (95% CI 0.60 to 0.91, P = 0.005). The authors were encouraged by these results, and suggested that additional prospective studies using TARE as treatment of HCC-MVI should be undertaken.

The SARAH trial (Vilgrain et al., Lancet Oncology 2017) compared the efficacy and safety of sorafenib to that of selective internal radiotherapy (SIRT) with yttrium-90 (90Y) resin microspheres (also termed TARE, transarterial radioembolization) in patients with hepatocellular carcinoma. The final conclusion was that overall survival did not significantly differ between the two groups. Pereira et al. published this ancillary study of the SARAH trial that compares health-related quality of life (HRQoL) between the two groups. HRQoL was preserved longer with TARE than with sorafenib in locally advanced HCC. The median time to deterioration for the global health status was 3.9 months (95% confidence interval [CI] 3.7–4.3) in the TARE group, vs 2.6 months (95% CI 2.0–3.0) in the sorafenib group. The authors concluded that the differences in HRQoL should inform decisions when recommending initial treatment of patients with HCC, though it does not take into account recently developed advancements in systemic therapy including immunotherapy.

For the first time, an HIV prevention trial that was limited to adolescent girls and young women found that, given sufficient support, girls will use either daily oral pre-exposure prophylaxis (PrEP) or the vaginal dapivirine ring to protect themselves from HIV.

The secret, said Gonasagrie Nair, MBChB, faculty of medicine and health sciences at Stellenbosch University, Zimbabwe, is offering intensive wraparound services to support teenagers – a lesson that may be useful as adolescent and family medicine professionals in the United States begin to roll out HIV prevention in their clinics.

This is important in the United States because cisgender Black women make up 60% of all new HIV cases in the United States while accounting for just 14% of the overall U.S. population. The Centers for Disease Control and Prevention has found that only about 1% of Black Americans who could benefit from PrEP have access to it.

“Younger women and adolescent girls in particular face a number of cultural and social challenges that impact their ability to make decisions related to their own health,” said Dr. Nair, who presented the data at the International AIDS Society (IAS) Conference 2021. “The adherence support provided by this study empowered them to make choices and stick to these choices,” she said.

In total, 247 women and girls aged 16 to 21 who were without HIV were enrolled in the Reversing the Epidemic in Africa with Choices in HIV Prevention (REACH) trial in two sites in South Africa and one each in Uganda and Zimbabwe beginning in February 2019. One-third of the participants were minors; the average age was 18.2 years.

The women were good candidates for PrEP. More than 1 in 3 of the women started the study with a sexually transmitted infection (STI), the most prevalent of which was chlamydia. This is often a good marker for condomless sex. Of the participants, 89% had a primary sex partner; a quarter of those thought their partner was having sex with other people. Only 7% of participants reported being very worried about acquiring HIV. More than 1 in 3 (39%) weren’t worried about HIV at all. This conforms to previous data suggesting that those who could most benefit from PrEP often don’t perceive their own vulnerability.

In the study, the women were randomly assigned two groups. In one group, the participants used the dapivirine ring for 6 months; in the other, participants used oral PrEP for 6 months. The participants then swapped prevention methods and used the alternative method for 6 more months. After a year of trying both methods, the women will be asked to choose one of the two prevention method or to stop PrEP altogether. At the IAS conference, the researchers reported interim data from the first year of the study, before the girls had the opportunity to choose for themselves.

During that first year, girls received intensive adherence support, including daily or weekly text check-ins, phone check-ins, peer buddy support, additional onsite counseling visits, access to adherence support groups, participation in online support groups via apps such as WhatsApp, and in-person social events designed to empower young women and to teach them skills. Support included discussion of adherence, contraceptives, and STIs. In addition, when girls came in for study visits, staff provided feedback on how adherent the girls had been, as determined on the basis of residual levels of dapivirine in the rings or, with regard to oral pills, drug levels as determined with blood spots.

Girls were considered to have had high adherence if they were found to have oral PrEP concentrations equivalent to four or more doses per week or if residual levels of dapivirine in their rings were 0.1071 mg/d. Moderate adherence was the equivalent of one to three doses of oral PrEP a week or dapivirine levels between 0.0321 mg/d and 0.1071 mg/d.

In total, 95.6% of ring users showed some adherence to the ring. Of those, adherence was high for 50.2%; 49.8% used the ring perfectly. For oral PrEP, 98.5% showed some level of PrEP use; for 58.6%, lab results suggested adherence high enough to provide protection from HIV, and 22% took their pills at least six times a week. Between the two arms, 54.3% of all participants used the medication sufficiently to be protected from HIV.

One person acquired HIV during the study. Dr. Nair did not say which study arm that participant was in or how adherent that person has been to their prevention method.

That level of adherence is on par with studies in the United States, which have found 56% adherence to PrEP among adolescent and young men who have sex with men. But the level of adherence is far higher than has been found in other studies that tested oral PrEP among women who did not have a partner with HIV. In particular, the VOICE and FEM-PrEP trials were both stopped early for lack of adherence. In those placebo-controlled oral-PrEP trials, fewer than 25% of participants used the oral prevention pills. Although adherence to the vaginal ring was estimated to be 61% for women older than 25 in the ASPIRE trial, it was effectively zero among women aged 18 to 21 years. Adherence has been the “bugaboo of efficacy for PrEP in young women,” said Judith Auerbach, PhD, independent science and policy consultant and professor of medicine at the University of California, San Francisco. But health care professionals have a long way to go to support young people in general in using PrEP.

“Yes, this shows improvement compared to previous studies,” Dr. Auerbach told this news organization. “But is it sufficient to have an epidemiological impact at the population level?”

Medical Advocacy and Outreach (MAO) is an HIV clinic and services program in Montgomery, Alabama, that offers a clinic specifically for some of their 144 clients to receive oral PrEP. In addition to in-person testing, MAO offers home HIV testing and lab work and televisits to support the college students they serve in taking PrEP whether they’re at school or at home on break. Currently, MAO provides a series of support groups and other social support programs for their clients living with HIV, but there are none for those receiving PrEP. The organization is in the process of hiring a social worker for the PrEP side of the clinic.

Until that person is on board, “I’m their support system in an unofficial capacity,” Shericka Williams, MPH, told this news organization. She runs education programs at MAO and handles all the phone calls from PrEP clients. “My title changes a lot, but the one I like to go with most often is the PrEP navigator,” she said.

She said she was intrigued by the dapivirine ring and oral PrEP data but said that currently, the women they serve are still learning that PrEP is for them, too. The women report that all the ads and all the information they receive is aimed at gay or bisexual men or transgender women. It takes a while for them to recognize that they could benefit, so a lot of the work that Ms. Williams does is focused on explaining the benefit of PrEP.

In MAO, the number of women receiving PrEP fluctuates more than for men. Mostly, women start PrEP because of they are in a relationship with someone who receives HIV care from MAO’s other wing – women who potentially would experience less vulnerability to HIV if their partners had undetectable viral loads. The other reason women take it is because they suspect that their partner is cheating or because they are in abusive relationships in which they want their partner to use a condom but the partner won’t. As in the PrEP trials, they often see women discontinue PrEP when they leave those relationships. In part, her job is to educate women regarding all the ways PrEP could serve them.

“Most of the time, they’re just no longer in that relationship, and they’re just taking some time for themselves,” she said in an interview. “We definitely try to bring up other reasons to stay on PrEP, but we don’t want to seem like we’re bullying someone to stay on it.”

Dr. Nair, Dr. Auerbach, and Ms. Williams report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

For the first time, an HIV prevention trial that was limited to adolescent girls and young women found that, given sufficient support, girls will use either daily oral pre-exposure prophylaxis (PrEP) or the vaginal dapivirine ring to protect themselves from HIV.

The secret, said Gonasagrie Nair, MBChB, faculty of medicine and health sciences at Stellenbosch University, Zimbabwe, is offering intensive wraparound services to support teenagers – a lesson that may be useful as adolescent and family medicine professionals in the United States begin to roll out HIV prevention in their clinics.

This is important in the United States because cisgender Black women make up 60% of all new HIV cases in the United States while accounting for just 14% of the overall U.S. population. The Centers for Disease Control and Prevention has found that only about 1% of Black Americans who could benefit from PrEP have access to it.

“Younger women and adolescent girls in particular face a number of cultural and social challenges that impact their ability to make decisions related to their own health,” said Dr. Nair, who presented the data at the International AIDS Society (IAS) Conference 2021. “The adherence support provided by this study empowered them to make choices and stick to these choices,” she said.

In total, 247 women and girls aged 16 to 21 who were without HIV were enrolled in the Reversing the Epidemic in Africa with Choices in HIV Prevention (REACH) trial in two sites in South Africa and one each in Uganda and Zimbabwe beginning in February 2019. One-third of the participants were minors; the average age was 18.2 years.

The women were good candidates for PrEP. More than 1 in 3 of the women started the study with a sexually transmitted infection (STI), the most prevalent of which was chlamydia. This is often a good marker for condomless sex. Of the participants, 89% had a primary sex partner; a quarter of those thought their partner was having sex with other people. Only 7% of participants reported being very worried about acquiring HIV. More than 1 in 3 (39%) weren’t worried about HIV at all. This conforms to previous data suggesting that those who could most benefit from PrEP often don’t perceive their own vulnerability.

In the study, the women were randomly assigned two groups. In one group, the participants used the dapivirine ring for 6 months; in the other, participants used oral PrEP for 6 months. The participants then swapped prevention methods and used the alternative method for 6 more months. After a year of trying both methods, the women will be asked to choose one of the two prevention method or to stop PrEP altogether. At the IAS conference, the researchers reported interim data from the first year of the study, before the girls had the opportunity to choose for themselves.

During that first year, girls received intensive adherence support, including daily or weekly text check-ins, phone check-ins, peer buddy support, additional onsite counseling visits, access to adherence support groups, participation in online support groups via apps such as WhatsApp, and in-person social events designed to empower young women and to teach them skills. Support included discussion of adherence, contraceptives, and STIs. In addition, when girls came in for study visits, staff provided feedback on how adherent the girls had been, as determined on the basis of residual levels of dapivirine in the rings or, with regard to oral pills, drug levels as determined with blood spots.

Girls were considered to have had high adherence if they were found to have oral PrEP concentrations equivalent to four or more doses per week or if residual levels of dapivirine in their rings were 0.1071 mg/d. Moderate adherence was the equivalent of one to three doses of oral PrEP a week or dapivirine levels between 0.0321 mg/d and 0.1071 mg/d.

In total, 95.6% of ring users showed some adherence to the ring. Of those, adherence was high for 50.2%; 49.8% used the ring perfectly. For oral PrEP, 98.5% showed some level of PrEP use; for 58.6%, lab results suggested adherence high enough to provide protection from HIV, and 22% took their pills at least six times a week. Between the two arms, 54.3% of all participants used the medication sufficiently to be protected from HIV.

One person acquired HIV during the study. Dr. Nair did not say which study arm that participant was in or how adherent that person has been to their prevention method.

That level of adherence is on par with studies in the United States, which have found 56% adherence to PrEP among adolescent and young men who have sex with men. But the level of adherence is far higher than has been found in other studies that tested oral PrEP among women who did not have a partner with HIV. In particular, the VOICE and FEM-PrEP trials were both stopped early for lack of adherence. In those placebo-controlled oral-PrEP trials, fewer than 25% of participants used the oral prevention pills. Although adherence to the vaginal ring was estimated to be 61% for women older than 25 in the ASPIRE trial, it was effectively zero among women aged 18 to 21 years. Adherence has been the “bugaboo of efficacy for PrEP in young women,” said Judith Auerbach, PhD, independent science and policy consultant and professor of medicine at the University of California, San Francisco. But health care professionals have a long way to go to support young people in general in using PrEP.

“Yes, this shows improvement compared to previous studies,” Dr. Auerbach told this news organization. “But is it sufficient to have an epidemiological impact at the population level?”

Medical Advocacy and Outreach (MAO) is an HIV clinic and services program in Montgomery, Alabama, that offers a clinic specifically for some of their 144 clients to receive oral PrEP. In addition to in-person testing, MAO offers home HIV testing and lab work and televisits to support the college students they serve in taking PrEP whether they’re at school or at home on break. Currently, MAO provides a series of support groups and other social support programs for their clients living with HIV, but there are none for those receiving PrEP. The organization is in the process of hiring a social worker for the PrEP side of the clinic.

Until that person is on board, “I’m their support system in an unofficial capacity,” Shericka Williams, MPH, told this news organization. She runs education programs at MAO and handles all the phone calls from PrEP clients. “My title changes a lot, but the one I like to go with most often is the PrEP navigator,” she said.

She said she was intrigued by the dapivirine ring and oral PrEP data but said that currently, the women they serve are still learning that PrEP is for them, too. The women report that all the ads and all the information they receive is aimed at gay or bisexual men or transgender women. It takes a while for them to recognize that they could benefit, so a lot of the work that Ms. Williams does is focused on explaining the benefit of PrEP.

In MAO, the number of women receiving PrEP fluctuates more than for men. Mostly, women start PrEP because of they are in a relationship with someone who receives HIV care from MAO’s other wing – women who potentially would experience less vulnerability to HIV if their partners had undetectable viral loads. The other reason women take it is because they suspect that their partner is cheating or because they are in abusive relationships in which they want their partner to use a condom but the partner won’t. As in the PrEP trials, they often see women discontinue PrEP when they leave those relationships. In part, her job is to educate women regarding all the ways PrEP could serve them.

“Most of the time, they’re just no longer in that relationship, and they’re just taking some time for themselves,” she said in an interview. “We definitely try to bring up other reasons to stay on PrEP, but we don’t want to seem like we’re bullying someone to stay on it.”

Dr. Nair, Dr. Auerbach, and Ms. Williams report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

For the first time, an HIV prevention trial that was limited to adolescent girls and young women found that, given sufficient support, girls will use either daily oral pre-exposure prophylaxis (PrEP) or the vaginal dapivirine ring to protect themselves from HIV.

The secret, said Gonasagrie Nair, MBChB, faculty of medicine and health sciences at Stellenbosch University, Zimbabwe, is offering intensive wraparound services to support teenagers – a lesson that may be useful as adolescent and family medicine professionals in the United States begin to roll out HIV prevention in their clinics.

This is important in the United States because cisgender Black women make up 60% of all new HIV cases in the United States while accounting for just 14% of the overall U.S. population. The Centers for Disease Control and Prevention has found that only about 1% of Black Americans who could benefit from PrEP have access to it.

“Younger women and adolescent girls in particular face a number of cultural and social challenges that impact their ability to make decisions related to their own health,” said Dr. Nair, who presented the data at the International AIDS Society (IAS) Conference 2021. “The adherence support provided by this study empowered them to make choices and stick to these choices,” she said.

In total, 247 women and girls aged 16 to 21 who were without HIV were enrolled in the Reversing the Epidemic in Africa with Choices in HIV Prevention (REACH) trial in two sites in South Africa and one each in Uganda and Zimbabwe beginning in February 2019. One-third of the participants were minors; the average age was 18.2 years.

The women were good candidates for PrEP. More than 1 in 3 of the women started the study with a sexually transmitted infection (STI), the most prevalent of which was chlamydia. This is often a good marker for condomless sex. Of the participants, 89% had a primary sex partner; a quarter of those thought their partner was having sex with other people. Only 7% of participants reported being very worried about acquiring HIV. More than 1 in 3 (39%) weren’t worried about HIV at all. This conforms to previous data suggesting that those who could most benefit from PrEP often don’t perceive their own vulnerability.

In the study, the women were randomly assigned two groups. In one group, the participants used the dapivirine ring for 6 months; in the other, participants used oral PrEP for 6 months. The participants then swapped prevention methods and used the alternative method for 6 more months. After a year of trying both methods, the women will be asked to choose one of the two prevention method or to stop PrEP altogether. At the IAS conference, the researchers reported interim data from the first year of the study, before the girls had the opportunity to choose for themselves.

During that first year, girls received intensive adherence support, including daily or weekly text check-ins, phone check-ins, peer buddy support, additional onsite counseling visits, access to adherence support groups, participation in online support groups via apps such as WhatsApp, and in-person social events designed to empower young women and to teach them skills. Support included discussion of adherence, contraceptives, and STIs. In addition, when girls came in for study visits, staff provided feedback on how adherent the girls had been, as determined on the basis of residual levels of dapivirine in the rings or, with regard to oral pills, drug levels as determined with blood spots.

Girls were considered to have had high adherence if they were found to have oral PrEP concentrations equivalent to four or more doses per week or if residual levels of dapivirine in their rings were 0.1071 mg/d. Moderate adherence was the equivalent of one to three doses of oral PrEP a week or dapivirine levels between 0.0321 mg/d and 0.1071 mg/d.

In total, 95.6% of ring users showed some adherence to the ring. Of those, adherence was high for 50.2%; 49.8% used the ring perfectly. For oral PrEP, 98.5% showed some level of PrEP use; for 58.6%, lab results suggested adherence high enough to provide protection from HIV, and 22% took their pills at least six times a week. Between the two arms, 54.3% of all participants used the medication sufficiently to be protected from HIV.

One person acquired HIV during the study. Dr. Nair did not say which study arm that participant was in or how adherent that person has been to their prevention method.

That level of adherence is on par with studies in the United States, which have found 56% adherence to PrEP among adolescent and young men who have sex with men. But the level of adherence is far higher than has been found in other studies that tested oral PrEP among women who did not have a partner with HIV. In particular, the VOICE and FEM-PrEP trials were both stopped early for lack of adherence. In those placebo-controlled oral-PrEP trials, fewer than 25% of participants used the oral prevention pills. Although adherence to the vaginal ring was estimated to be 61% for women older than 25 in the ASPIRE trial, it was effectively zero among women aged 18 to 21 years. Adherence has been the “bugaboo of efficacy for PrEP in young women,” said Judith Auerbach, PhD, independent science and policy consultant and professor of medicine at the University of California, San Francisco. But health care professionals have a long way to go to support young people in general in using PrEP.

“Yes, this shows improvement compared to previous studies,” Dr. Auerbach told this news organization. “But is it sufficient to have an epidemiological impact at the population level?”

Medical Advocacy and Outreach (MAO) is an HIV clinic and services program in Montgomery, Alabama, that offers a clinic specifically for some of their 144 clients to receive oral PrEP. In addition to in-person testing, MAO offers home HIV testing and lab work and televisits to support the college students they serve in taking PrEP whether they’re at school or at home on break. Currently, MAO provides a series of support groups and other social support programs for their clients living with HIV, but there are none for those receiving PrEP. The organization is in the process of hiring a social worker for the PrEP side of the clinic.

Until that person is on board, “I’m their support system in an unofficial capacity,” Shericka Williams, MPH, told this news organization. She runs education programs at MAO and handles all the phone calls from PrEP clients. “My title changes a lot, but the one I like to go with most often is the PrEP navigator,” she said.

She said she was intrigued by the dapivirine ring and oral PrEP data but said that currently, the women they serve are still learning that PrEP is for them, too. The women report that all the ads and all the information they receive is aimed at gay or bisexual men or transgender women. It takes a while for them to recognize that they could benefit, so a lot of the work that Ms. Williams does is focused on explaining the benefit of PrEP.

In MAO, the number of women receiving PrEP fluctuates more than for men. Mostly, women start PrEP because of they are in a relationship with someone who receives HIV care from MAO’s other wing – women who potentially would experience less vulnerability to HIV if their partners had undetectable viral loads. The other reason women take it is because they suspect that their partner is cheating or because they are in abusive relationships in which they want their partner to use a condom but the partner won’t. As in the PrEP trials, they often see women discontinue PrEP when they leave those relationships. In part, her job is to educate women regarding all the ways PrEP could serve them.

“Most of the time, they’re just no longer in that relationship, and they’re just taking some time for themselves,” she said in an interview. “We definitely try to bring up other reasons to stay on PrEP, but we don’t want to seem like we’re bullying someone to stay on it.”

Dr. Nair, Dr. Auerbach, and Ms. Williams report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Ketamine used to treat severe depression in patients with a history of psychosis does not exacerbate psychosis risk, new research suggests.

A meta-analysis of nine studies, encompassing 41 patients with TRD and a history of psychosis, suggests ketamine is safe and effective and did not exacerbate psychotic symptoms in this patient population.

“We believe our findings could encourage clinicians and researchers to examine a broadened indication for ketamine treatment in individual patients with high levels of treatment resistance, carefully monitoring both clinical response and side effects, specifically looking at possible increases in psychotic symptoms,” study investigator Jolien K. E. Veraart, MD, University of Groningen, University Medical Center Groningen, the Netherlands, told this news organization.

The study was published online July 13 in the Journal of Clinical Psychiatry.
 

Rapid, robust effects

Ketamine has shown “rapid and robust antidepressant effects” in clinical studies. However, this research has not included patients with past or current psychosis, based on the assumption that psychosis will increase with ketamine administration, since side effects of ketamine can include transient “schizophrenia-like” psychotomimetic phenomena, including perceptual disorders and hallucinations in healthy individuals, the investigators note.

Dr. Veraart said psychotic symptoms are “common in people with severe depression,” and these patients have poorer outcomes with pharmacotherapy, psychotherapy, and electroconvulsive therapy.

Additionally, up to 60% of patients with schizophrenia experience negative symptomatology, including loss of motivation, affective blunting, and anhedonia, which “has a clear phenomenological overlap with depression,” the authors write. They also note anti-anhedonic effects of subanesthetic ketamine doses have been reported, without adversely impacting long-term psychotic symptoms in patients with schizophrenia.

“Positive results from carefully monitored trials with ketamine treatment in these patients have motivated us to summarize the currently available knowledge to inform our colleagues,” she said.

To investigate, the researchers conducted a literature search and selected 9 articles (N = 41 patients) that reported on ketamine treatment in patients with a history of psychosis or current psychotic symptoms.

All studies were either case reports or pilot studies, the authors report. Types of patients included those with bipolar or unipolar depression, or depression in schizoaffective disorder , or patients with schizophrenia and concurrent depression. Depressive symptomatology was the treatment target in eight studies, and one study targeted negative symptoms in patients with schizophrenia.

Dosing, frequency, and types of administration (ketamine IV, esketamine IV, or esketamine subcutaneous) varied from study to study.

In seven studies, ketamine was found to improve depressive symptoms, and in two studies, improvement in psychotic symptoms was also shown. Two studies revealed improvement in symptoms of suicidality. Results of the study that measured negative symptoms showed “significant improvement” in five of six patients, with a -37.3% decrease in mean Brief Negative Symptoms Scale (BNSS) from the baseline to the end of four infusions.

“Ketamine showed good antidepressant effects, and, in some cases, the comorbid symptoms even improved or disappeared after ketamine treatment,” Dr. Veraart summarized. However, the effect size of ketamine might be lower in those with a history of psychosis, she added.

She also noted that ketamine administration did not negatively influence the course of psychotic illness or induce psychotic exacerbations in patients.

She pointed to one study limitation, which is that only small, uncontrolled trials were included and that there is a risk for publication bias.
 

Larger trials needed

Commenting on the study, Dan Iosifescu, MD, MSc, associate professor of psychiatry, New York University School of Medicine, said that if the finding “were based on a larger study it would be very important, as a theoretical risk of psychosis is preventing such patients from access to an otherwise beneficial treatment.”

However, “since the review is based on a small sample, a low risk of psychosis exacerbation after IV ketamine is still possible,” said Dr. Iosifescu, who is also the director of clinical research at the Kline Institute for Psychiatric Research in Orangeburg, New York, and was not involved with the study.

Dr. Veraart agreed, adding that the “efficacy, safety, and tolerability of ketamine in depressed patients with a vulnerability to psychosis should be investigated in well-designed randomized controlled trials before application on a large scale is promoted.”

The study had no specific funding. Dr. Veraart has received speaker honoraria from Janssen outside of the submitted work. The other authors’ disclosures are listed in the original article. Dr. Iosifescu has been a consultant to the Centers of Psychiatric Excellence, advising clinics on the best methods of providing treatment with IV ketamine.

A version of this article first appeared on Medscape.com.

Ketamine used to treat severe depression in patients with a history of psychosis does not exacerbate psychosis risk, new research suggests.

A meta-analysis of nine studies, encompassing 41 patients with TRD and a history of psychosis, suggests ketamine is safe and effective and did not exacerbate psychotic symptoms in this patient population.

“We believe our findings could encourage clinicians and researchers to examine a broadened indication for ketamine treatment in individual patients with high levels of treatment resistance, carefully monitoring both clinical response and side effects, specifically looking at possible increases in psychotic symptoms,” study investigator Jolien K. E. Veraart, MD, University of Groningen, University Medical Center Groningen, the Netherlands, told this news organization.

The study was published online July 13 in the Journal of Clinical Psychiatry.
 

Rapid, robust effects

Ketamine has shown “rapid and robust antidepressant effects” in clinical studies. However, this research has not included patients with past or current psychosis, based on the assumption that psychosis will increase with ketamine administration, since side effects of ketamine can include transient “schizophrenia-like” psychotomimetic phenomena, including perceptual disorders and hallucinations in healthy individuals, the investigators note.

Dr. Veraart said psychotic symptoms are “common in people with severe depression,” and these patients have poorer outcomes with pharmacotherapy, psychotherapy, and electroconvulsive therapy.

Additionally, up to 60% of patients with schizophrenia experience negative symptomatology, including loss of motivation, affective blunting, and anhedonia, which “has a clear phenomenological overlap with depression,” the authors write. They also note anti-anhedonic effects of subanesthetic ketamine doses have been reported, without adversely impacting long-term psychotic symptoms in patients with schizophrenia.

“Positive results from carefully monitored trials with ketamine treatment in these patients have motivated us to summarize the currently available knowledge to inform our colleagues,” she said.

To investigate, the researchers conducted a literature search and selected 9 articles (N = 41 patients) that reported on ketamine treatment in patients with a history of psychosis or current psychotic symptoms.

All studies were either case reports or pilot studies, the authors report. Types of patients included those with bipolar or unipolar depression, or depression in schizoaffective disorder , or patients with schizophrenia and concurrent depression. Depressive symptomatology was the treatment target in eight studies, and one study targeted negative symptoms in patients with schizophrenia.

Dosing, frequency, and types of administration (ketamine IV, esketamine IV, or esketamine subcutaneous) varied from study to study.

In seven studies, ketamine was found to improve depressive symptoms, and in two studies, improvement in psychotic symptoms was also shown. Two studies revealed improvement in symptoms of suicidality. Results of the study that measured negative symptoms showed “significant improvement” in five of six patients, with a -37.3% decrease in mean Brief Negative Symptoms Scale (BNSS) from the baseline to the end of four infusions.

“Ketamine showed good antidepressant effects, and, in some cases, the comorbid symptoms even improved or disappeared after ketamine treatment,” Dr. Veraart summarized. However, the effect size of ketamine might be lower in those with a history of psychosis, she added.

She also noted that ketamine administration did not negatively influence the course of psychotic illness or induce psychotic exacerbations in patients.

She pointed to one study limitation, which is that only small, uncontrolled trials were included and that there is a risk for publication bias.
 

Larger trials needed

Commenting on the study, Dan Iosifescu, MD, MSc, associate professor of psychiatry, New York University School of Medicine, said that if the finding “were based on a larger study it would be very important, as a theoretical risk of psychosis is preventing such patients from access to an otherwise beneficial treatment.”

However, “since the review is based on a small sample, a low risk of psychosis exacerbation after IV ketamine is still possible,” said Dr. Iosifescu, who is also the director of clinical research at the Kline Institute for Psychiatric Research in Orangeburg, New York, and was not involved with the study.

Dr. Veraart agreed, adding that the “efficacy, safety, and tolerability of ketamine in depressed patients with a vulnerability to psychosis should be investigated in well-designed randomized controlled trials before application on a large scale is promoted.”

The study had no specific funding. Dr. Veraart has received speaker honoraria from Janssen outside of the submitted work. The other authors’ disclosures are listed in the original article. Dr. Iosifescu has been a consultant to the Centers of Psychiatric Excellence, advising clinics on the best methods of providing treatment with IV ketamine.

A version of this article first appeared on Medscape.com.

Ketamine used to treat severe depression in patients with a history of psychosis does not exacerbate psychosis risk, new research suggests.

A meta-analysis of nine studies, encompassing 41 patients with TRD and a history of psychosis, suggests ketamine is safe and effective and did not exacerbate psychotic symptoms in this patient population.

“We believe our findings could encourage clinicians and researchers to examine a broadened indication for ketamine treatment in individual patients with high levels of treatment resistance, carefully monitoring both clinical response and side effects, specifically looking at possible increases in psychotic symptoms,” study investigator Jolien K. E. Veraart, MD, University of Groningen, University Medical Center Groningen, the Netherlands, told this news organization.

The study was published online July 13 in the Journal of Clinical Psychiatry.
 

Rapid, robust effects

Ketamine has shown “rapid and robust antidepressant effects” in clinical studies. However, this research has not included patients with past or current psychosis, based on the assumption that psychosis will increase with ketamine administration, since side effects of ketamine can include transient “schizophrenia-like” psychotomimetic phenomena, including perceptual disorders and hallucinations in healthy individuals, the investigators note.

Dr. Veraart said psychotic symptoms are “common in people with severe depression,” and these patients have poorer outcomes with pharmacotherapy, psychotherapy, and electroconvulsive therapy.

Additionally, up to 60% of patients with schizophrenia experience negative symptomatology, including loss of motivation, affective blunting, and anhedonia, which “has a clear phenomenological overlap with depression,” the authors write. They also note anti-anhedonic effects of subanesthetic ketamine doses have been reported, without adversely impacting long-term psychotic symptoms in patients with schizophrenia.

“Positive results from carefully monitored trials with ketamine treatment in these patients have motivated us to summarize the currently available knowledge to inform our colleagues,” she said.

To investigate, the researchers conducted a literature search and selected 9 articles (N = 41 patients) that reported on ketamine treatment in patients with a history of psychosis or current psychotic symptoms.

All studies were either case reports or pilot studies, the authors report. Types of patients included those with bipolar or unipolar depression, or depression in schizoaffective disorder , or patients with schizophrenia and concurrent depression. Depressive symptomatology was the treatment target in eight studies, and one study targeted negative symptoms in patients with schizophrenia.

Dosing, frequency, and types of administration (ketamine IV, esketamine IV, or esketamine subcutaneous) varied from study to study.

In seven studies, ketamine was found to improve depressive symptoms, and in two studies, improvement in psychotic symptoms was also shown. Two studies revealed improvement in symptoms of suicidality. Results of the study that measured negative symptoms showed “significant improvement” in five of six patients, with a -37.3% decrease in mean Brief Negative Symptoms Scale (BNSS) from the baseline to the end of four infusions.

“Ketamine showed good antidepressant effects, and, in some cases, the comorbid symptoms even improved or disappeared after ketamine treatment,” Dr. Veraart summarized. However, the effect size of ketamine might be lower in those with a history of psychosis, she added.

She also noted that ketamine administration did not negatively influence the course of psychotic illness or induce psychotic exacerbations in patients.

She pointed to one study limitation, which is that only small, uncontrolled trials were included and that there is a risk for publication bias.
 

Larger trials needed

Commenting on the study, Dan Iosifescu, MD, MSc, associate professor of psychiatry, New York University School of Medicine, said that if the finding “were based on a larger study it would be very important, as a theoretical risk of psychosis is preventing such patients from access to an otherwise beneficial treatment.”

However, “since the review is based on a small sample, a low risk of psychosis exacerbation after IV ketamine is still possible,” said Dr. Iosifescu, who is also the director of clinical research at the Kline Institute for Psychiatric Research in Orangeburg, New York, and was not involved with the study.

Dr. Veraart agreed, adding that the “efficacy, safety, and tolerability of ketamine in depressed patients with a vulnerability to psychosis should be investigated in well-designed randomized controlled trials before application on a large scale is promoted.”

The study had no specific funding. Dr. Veraart has received speaker honoraria from Janssen outside of the submitted work. The other authors’ disclosures are listed in the original article. Dr. Iosifescu has been a consultant to the Centers of Psychiatric Excellence, advising clinics on the best methods of providing treatment with IV ketamine.

A version of this article first appeared on Medscape.com.

At a recent town hall meeting in Cincinnati, President Joe Biden was asked about COVID-19 cases, hospitalizations, and deaths rising in response to the Delta variant.

Touting the importance of vaccination, “We have a pandemic for those who haven’t gotten a vaccination. It’s that basic, that simple,” President Biden said at the event, which was broadcast live on CNN.

Andriy Onufriyenko

“If you’re vaccinated, you’re not going to be hospitalized, not going to the ICU unit, and not going to die,” he said, adding “you’re not going to get COVID if you have these vaccinations.”

Unfortunately, it’s not so simple. Fully vaccinated people continue to be well protected against severe disease and death, even with Delta, but so-called breakthrough cases, where a person gets infected despite being fully vaccinated, are on the rise. Because of that, many experts continue to advise caution, even if fully vaccinated.

“I was disappointed,” Leana Wen, MD, MSc, an emergency physician and visiting professor of health policy and management at George Washington University’s Milken School of Public Health in Washington, told CNN in response to the president’s statement.

“I actually thought he was answering questions as if it were a month ago. He’s not really meeting the realities of what’s happening on the ground,” she said. “I think he may have led people astray.”
 

Vaccines still work

Recent cases support Dr. Wen’s claim. Fully vaccinated Olympic athletes, wedding guests, healthcare workers, and even White House staff have recently tested positive. So what gives?

The vast majority of these illnesses are mild, and public health officials say they are to be expected. 

“The vaccines were designed to keep us out of the hospital and to keep us from dying. That was the whole purpose of the vaccine and they’re even more successful than we anticipated,” says William Schaffner, MD, an infectious disease expert at Vanderbilt University in Nashville.

As good as they are, these shots aren’t perfect. Their protection differs from person to person depending on age and underlying health. People with immune function that’s weakened because of age or a health condition can still become seriously ill, and, in very rare cases, die after vaccination.

When people are infected with Delta, they carry approximately 1,000 times more virus compared with previous versions of the virus, according to a recent study. All that virus can overwhelm even the strong protection from the vaccines.

“Three months ago, breakthroughs didn’t occur nearly at this rate because there was just so much less virus exposure in the community,” said Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota in Minneapolis.
 

Breakthroughs by the numbers

In Los Angeles County, where 69% of residents over age 12 have been fully vaccinated, COVID-19 cases are rising, and so, too, are cases that break through the protection of the vaccine.

In June, fully vaccinated people accounted for 20%, or 1 in 5, COVID cases in the county, which is the most populous in the United States. The increase mirrors Delta’s rise. The proportion of breakthrough cases is up from 11% in May, 5% in April, and 2% in March, according to the Los Angeles County Department of Public Health. 

In the United Kingdom, which is collecting the best information on infections caused by variants, the estimated effectiveness of the vaccines to prevent an illness that causes symptoms dropped by about 10 points against Delta compared with Alpha (or B.1.1.7). 

After two doses, vaccines prevent symptomatic infection about 79% of the time against Delta, according to data compiled by Public Health England. They are still highly effective at preventing hospitalization, 96% after two doses.

Out of 229,218 COVID infections in the United Kingdom between February and July 19, 28,773 — or 12.5% — were in fully vaccinated people. Of those breakthrough infections, 1,101, or 3.8%, required a visit to an emergency room, according to Public Health England. Just 474, or 2.9%, of fully vaccinated people required hospital admission, and 229, or less than 1%, died.
 

Unanswered questions

One of the biggest questions about breakthrough cases is how often people who have it may pass the virus to others.

“We know the vaccine reduces the likelihood of carrying the virus and the amount of virus you would carry,” Dr. Wen told CNN. But we don’t yet know whether a vaccinated person with a breakthrough infection may still be contagious to others.

For that reason, the Centers for Disease Control and Prevention says that fully vaccinated people still need to be tested if they have symptoms and shouldn’t be out in public for at least 10 days after a positive test. 

How should fully vaccinated people behave? That depends a lot on their underlying health and whether or not they have vulnerable people around them. 

If you’re older or immunocompromised, Dr. Schaffner recommends what he calls the “belt-and-suspenders approach,” in other words, do everything you can to stay safe.

“Get vaccinated for sure, but since we can’t be absolutely certain that the vaccines are going to be optimally protective and you are particularly susceptible to serious disease, you would be well advised to adopt at least one and perhaps more of the other mitigation measures,” he said.

These include wearing a mask, social distancing, making sure your spaces are well ventilated, and not spending prolonged periods of time indoors in crowded places.

Taking young children to visit vaccinated, elderly grandparents demands extra caution, again, with Delta circulating, particularly as they go back to school and start mixing with other kids.

Dr. Schaffner recommends explaining the ground rules before the visit: Hugs around the waist. No kissing. Wearing a mask while indoors with them.

Other important unanswered questions are whether breakthrough infections can lead to prolonged symptoms, or “long covid.” Most experts think that’s less likely in vaccinated people.

And Dr. Osterholm said it will be important to see whether there’s anything unusual about the breakthrough cases happening in the community.

“I think some of us have been challenged by the number of clusters that we’ve seen,” he said. “I think that really needs to be examined more.”

A version of this article first appeared on Medscape.com.

At a recent town hall meeting in Cincinnati, President Joe Biden was asked about COVID-19 cases, hospitalizations, and deaths rising in response to the Delta variant.

Touting the importance of vaccination, “We have a pandemic for those who haven’t gotten a vaccination. It’s that basic, that simple,” President Biden said at the event, which was broadcast live on CNN.

Andriy Onufriyenko

“If you’re vaccinated, you’re not going to be hospitalized, not going to the ICU unit, and not going to die,” he said, adding “you’re not going to get COVID if you have these vaccinations.”

Unfortunately, it’s not so simple. Fully vaccinated people continue to be well protected against severe disease and death, even with Delta, but so-called breakthrough cases, where a person gets infected despite being fully vaccinated, are on the rise. Because of that, many experts continue to advise caution, even if fully vaccinated.

“I was disappointed,” Leana Wen, MD, MSc, an emergency physician and visiting professor of health policy and management at George Washington University’s Milken School of Public Health in Washington, told CNN in response to the president’s statement.

“I actually thought he was answering questions as if it were a month ago. He’s not really meeting the realities of what’s happening on the ground,” she said. “I think he may have led people astray.”
 

Vaccines still work

Recent cases support Dr. Wen’s claim. Fully vaccinated Olympic athletes, wedding guests, healthcare workers, and even White House staff have recently tested positive. So what gives?

The vast majority of these illnesses are mild, and public health officials say they are to be expected. 

“The vaccines were designed to keep us out of the hospital and to keep us from dying. That was the whole purpose of the vaccine and they’re even more successful than we anticipated,” says William Schaffner, MD, an infectious disease expert at Vanderbilt University in Nashville.

As good as they are, these shots aren’t perfect. Their protection differs from person to person depending on age and underlying health. People with immune function that’s weakened because of age or a health condition can still become seriously ill, and, in very rare cases, die after vaccination.

When people are infected with Delta, they carry approximately 1,000 times more virus compared with previous versions of the virus, according to a recent study. All that virus can overwhelm even the strong protection from the vaccines.

“Three months ago, breakthroughs didn’t occur nearly at this rate because there was just so much less virus exposure in the community,” said Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota in Minneapolis.
 

Breakthroughs by the numbers

In Los Angeles County, where 69% of residents over age 12 have been fully vaccinated, COVID-19 cases are rising, and so, too, are cases that break through the protection of the vaccine.

In June, fully vaccinated people accounted for 20%, or 1 in 5, COVID cases in the county, which is the most populous in the United States. The increase mirrors Delta’s rise. The proportion of breakthrough cases is up from 11% in May, 5% in April, and 2% in March, according to the Los Angeles County Department of Public Health. 

In the United Kingdom, which is collecting the best information on infections caused by variants, the estimated effectiveness of the vaccines to prevent an illness that causes symptoms dropped by about 10 points against Delta compared with Alpha (or B.1.1.7). 

After two doses, vaccines prevent symptomatic infection about 79% of the time against Delta, according to data compiled by Public Health England. They are still highly effective at preventing hospitalization, 96% after two doses.

Out of 229,218 COVID infections in the United Kingdom between February and July 19, 28,773 — or 12.5% — were in fully vaccinated people. Of those breakthrough infections, 1,101, or 3.8%, required a visit to an emergency room, according to Public Health England. Just 474, or 2.9%, of fully vaccinated people required hospital admission, and 229, or less than 1%, died.
 

Unanswered questions

One of the biggest questions about breakthrough cases is how often people who have it may pass the virus to others.

“We know the vaccine reduces the likelihood of carrying the virus and the amount of virus you would carry,” Dr. Wen told CNN. But we don’t yet know whether a vaccinated person with a breakthrough infection may still be contagious to others.

For that reason, the Centers for Disease Control and Prevention says that fully vaccinated people still need to be tested if they have symptoms and shouldn’t be out in public for at least 10 days after a positive test. 

How should fully vaccinated people behave? That depends a lot on their underlying health and whether or not they have vulnerable people around them. 

If you’re older or immunocompromised, Dr. Schaffner recommends what he calls the “belt-and-suspenders approach,” in other words, do everything you can to stay safe.

“Get vaccinated for sure, but since we can’t be absolutely certain that the vaccines are going to be optimally protective and you are particularly susceptible to serious disease, you would be well advised to adopt at least one and perhaps more of the other mitigation measures,” he said.

These include wearing a mask, social distancing, making sure your spaces are well ventilated, and not spending prolonged periods of time indoors in crowded places.

Taking young children to visit vaccinated, elderly grandparents demands extra caution, again, with Delta circulating, particularly as they go back to school and start mixing with other kids.

Dr. Schaffner recommends explaining the ground rules before the visit: Hugs around the waist. No kissing. Wearing a mask while indoors with them.

Other important unanswered questions are whether breakthrough infections can lead to prolonged symptoms, or “long covid.” Most experts think that’s less likely in vaccinated people.

And Dr. Osterholm said it will be important to see whether there’s anything unusual about the breakthrough cases happening in the community.

“I think some of us have been challenged by the number of clusters that we’ve seen,” he said. “I think that really needs to be examined more.”

A version of this article first appeared on Medscape.com.

At a recent town hall meeting in Cincinnati, President Joe Biden was asked about COVID-19 cases, hospitalizations, and deaths rising in response to the Delta variant.

Touting the importance of vaccination, “We have a pandemic for those who haven’t gotten a vaccination. It’s that basic, that simple,” President Biden said at the event, which was broadcast live on CNN.

Andriy Onufriyenko

“If you’re vaccinated, you’re not going to be hospitalized, not going to the ICU unit, and not going to die,” he said, adding “you’re not going to get COVID if you have these vaccinations.”

Unfortunately, it’s not so simple. Fully vaccinated people continue to be well protected against severe disease and death, even with Delta, but so-called breakthrough cases, where a person gets infected despite being fully vaccinated, are on the rise. Because of that, many experts continue to advise caution, even if fully vaccinated.

“I was disappointed,” Leana Wen, MD, MSc, an emergency physician and visiting professor of health policy and management at George Washington University’s Milken School of Public Health in Washington, told CNN in response to the president’s statement.

“I actually thought he was answering questions as if it were a month ago. He’s not really meeting the realities of what’s happening on the ground,” she said. “I think he may have led people astray.”
 

Vaccines still work

Recent cases support Dr. Wen’s claim. Fully vaccinated Olympic athletes, wedding guests, healthcare workers, and even White House staff have recently tested positive. So what gives?

The vast majority of these illnesses are mild, and public health officials say they are to be expected. 

“The vaccines were designed to keep us out of the hospital and to keep us from dying. That was the whole purpose of the vaccine and they’re even more successful than we anticipated,” says William Schaffner, MD, an infectious disease expert at Vanderbilt University in Nashville.

As good as they are, these shots aren’t perfect. Their protection differs from person to person depending on age and underlying health. People with immune function that’s weakened because of age or a health condition can still become seriously ill, and, in very rare cases, die after vaccination.

When people are infected with Delta, they carry approximately 1,000 times more virus compared with previous versions of the virus, according to a recent study. All that virus can overwhelm even the strong protection from the vaccines.

“Three months ago, breakthroughs didn’t occur nearly at this rate because there was just so much less virus exposure in the community,” said Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota in Minneapolis.
 

Breakthroughs by the numbers

In Los Angeles County, where 69% of residents over age 12 have been fully vaccinated, COVID-19 cases are rising, and so, too, are cases that break through the protection of the vaccine.

In June, fully vaccinated people accounted for 20%, or 1 in 5, COVID cases in the county, which is the most populous in the United States. The increase mirrors Delta’s rise. The proportion of breakthrough cases is up from 11% in May, 5% in April, and 2% in March, according to the Los Angeles County Department of Public Health. 

In the United Kingdom, which is collecting the best information on infections caused by variants, the estimated effectiveness of the vaccines to prevent an illness that causes symptoms dropped by about 10 points against Delta compared with Alpha (or B.1.1.7). 

After two doses, vaccines prevent symptomatic infection about 79% of the time against Delta, according to data compiled by Public Health England. They are still highly effective at preventing hospitalization, 96% after two doses.

Out of 229,218 COVID infections in the United Kingdom between February and July 19, 28,773 — or 12.5% — were in fully vaccinated people. Of those breakthrough infections, 1,101, or 3.8%, required a visit to an emergency room, according to Public Health England. Just 474, or 2.9%, of fully vaccinated people required hospital admission, and 229, or less than 1%, died.
 

Unanswered questions

One of the biggest questions about breakthrough cases is how often people who have it may pass the virus to others.

“We know the vaccine reduces the likelihood of carrying the virus and the amount of virus you would carry,” Dr. Wen told CNN. But we don’t yet know whether a vaccinated person with a breakthrough infection may still be contagious to others.

For that reason, the Centers for Disease Control and Prevention says that fully vaccinated people still need to be tested if they have symptoms and shouldn’t be out in public for at least 10 days after a positive test. 

How should fully vaccinated people behave? That depends a lot on their underlying health and whether or not they have vulnerable people around them. 

If you’re older or immunocompromised, Dr. Schaffner recommends what he calls the “belt-and-suspenders approach,” in other words, do everything you can to stay safe.

“Get vaccinated for sure, but since we can’t be absolutely certain that the vaccines are going to be optimally protective and you are particularly susceptible to serious disease, you would be well advised to adopt at least one and perhaps more of the other mitigation measures,” he said.

These include wearing a mask, social distancing, making sure your spaces are well ventilated, and not spending prolonged periods of time indoors in crowded places.

Taking young children to visit vaccinated, elderly grandparents demands extra caution, again, with Delta circulating, particularly as they go back to school and start mixing with other kids.

Dr. Schaffner recommends explaining the ground rules before the visit: Hugs around the waist. No kissing. Wearing a mask while indoors with them.

Other important unanswered questions are whether breakthrough infections can lead to prolonged symptoms, or “long covid.” Most experts think that’s less likely in vaccinated people.

And Dr. Osterholm said it will be important to see whether there’s anything unusual about the breakthrough cases happening in the community.

“I think some of us have been challenged by the number of clusters that we’ve seen,” he said. “I think that really needs to be examined more.”

A version of this article first appeared on Medscape.com.