Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.

BACKGROUND: Psoriasis is an immune-mediated disease with either skin or joints manifestations, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. The relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head-to-head, which is why we chose to conduct a network meta-analysis. OBJECTIVES: To compare the benefits and harms of non-biological systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis using a network meta-analysis, and to provide a ranking of these treatments according to their benefits and harms. SEARCH METHODS: For this update of the living systematic review, we updated our searches of the following databases monthly to October 2022: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase. SELECTION CRITERIA: Randomised controlled trials (RCTs) of systemic treatments in adults over 18 years with moderate-to-severe plaque psoriasis, at any stage of treatment, compared to placebo or another active agent. The primary outcomes were: proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90; proportion of participants with serious adverse events (SAEs) at induction phase (8 to 24 weeks after randomisation). DATA COLLECTION AND ANALYSIS: We conducted duplicate study selection, data extraction, risk of bias assessment, and analyses. We synthesised data using pairwise and network meta-analysis (NMA) to compare treatments and rank them according to effectiveness (PASI 90 score) and acceptability (inverse of SAEs). We assessed the certainty of NMA evidence for the two primary outcomes and all comparisons using CINeMA, as very low, low, moderate, or high. We contacted study authors when data were unclear or missing. We used the surface under the cumulative ranking curve (SUCRA) to infer treatment hierarchy, from 0% (worst for effectiveness or safety) to 100% (best for effectiveness or safety). MAIN RESULTS: This update includes an additional 12 studies, taking the total number of included studies to 179, and randomised participants to 62,339, 67.1% men, mainly recruited from hospitals. Average age was 44.6 years, mean PASI score at baseline was 20.4 (range: 9.5 to 39). Most studies were placebo-controlled (56%). We assessed a total of 20 treatments. Most (152) trials were multicentric (two to 231 centres). One-third of the studies (65/179) had high risk of bias, 24 unclear risk, and most (90) low risk. Most studies (138/179) declared funding by a pharmaceutical company, and 24 studies did not report a funding source. Network meta-analysis at class level showed that all interventions (non-biological systemic agents, small molecules, and biological treatments) showed a higher proportion of patients reaching PASI 90 than placebo. Anti-IL17 treatment showed a higher proportion of patients reaching PASI 90 compared to all the interventions. Biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha showed a higher proportion of patients reaching PASI 90 than the non-biological systemic agents. For reaching PASI 90, the most effective drugs when compared to placebo were (SUCRA rank order, all high-certainty evidence): infliximab (risk ratio (RR) 49.16, 95% CI 20.49 to 117.95), bimekizumab (RR 27.86, 95% CI 23.56 to 32.94), ixekizumab (RR 27.35, 95% CI 23.15 to 32.29), risankizumab (RR 26.16, 95% CI 22.03 to 31.07). Clinical effectiveness of these drugs was similar when compared against each other. Bimekizumab and ixekizumab were significantly more likely to reach PASI 90 than secukinumab. Bimekizumab, ixekizumab, and risankizumab were significantly more likely to reach PASI 90 than brodalumab and guselkumab. Infliximab, anti-IL17 drugs (bimekizumab, ixekizumab, secukinumab, and brodalumab), and anti-IL23 drugs except tildrakizumab were significantly more likely to reach PASI 90 than ustekinumab, three anti-TNF alpha agents, and deucravacitinib. Ustekinumab was superior to certolizumab. Adalimumab, tildrakizumab, and ustekinumab were superior to etanercept. No significant difference was shown between apremilast and two non-biological drugs: ciclosporin and methotrexate. We found no significant difference between any of the interventions and the placebo for the risk of SAEs. The risk of SAEs was significantly lower for participants on methotrexate compared with most of the interventions. Nevertheless, the SAE analyses were based on a very low number of events with very low- to moderate-certainty evidence for all the comparisons. The findings therefore have to be viewed with caution. For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1), the results were similar to the results for PASI 90. Information on quality of life was often poorly reported and was absent for several of the interventions. AUTHORS' CONCLUSIONS: Our review shows that, compared to placebo, the biologics infliximab, bimekizumab, ixekizumab, and risankizumab were the most effective treatments for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of high-certainty evidence. This NMA evidence is limited to induction therapy (outcomes measured from 8 to 24 weeks after randomisation), and is not sufficient for evaluating longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean 44.6 years) and high level of disease severity (PASI 20.4 at baseline) may not be typical of patients seen in daily clinical practice. We found no significant difference in the assessed interventions and placebo in terms of SAEs, and the safety evidence for most interventions was very low to moderate quality. More randomised trials directly comparing active agents are needed, and these should include systematic subgroup analyses (sex, age, ethnicity, comorbidities, psoriatic arthritis). To provide long-term information on the safety of treatments included in this review, an evaluation of non-randomised studies is needed. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

Cost analysis of an intrapartum quality improvement package for improving preterm survival and reinforcing best practices in Kenya and Uganda.

INTRODUCTION: Preterm birth is a leading cause of under-5 mortality, with the greatest burden in lower-resource settings. Strategies to improve preterm survival have been tested, but strategy costs are less understood. We estimate costs of a highly effective Preterm Birth Initiative (PTBi) intrapartum intervention package (data strengthening, WHO Safe Childbirth Checklist, simulation and team training, quality improvement collaboratives) and active control (data strengthening, Safe Childbirth Checklist). METHODS: In our analysis, we estimated costs incremental to current cost of intrapartum care (in 2020 $US) for the PTBi intervention package and active control in Kenya and Uganda. We costed the intervention package and control in two scenarios: 1) non-research implementation costs as observed in the PTBi study (Scenario 1, mix of public and private inputs), and 2) hypothetical costs for a model of implementation into Ministry of Health programming (Scenario 2, mostly public inputs). Using a healthcare system perspective, we employed micro-costing of personnel, supplies, physical space, and travel, including 3 sequential phases: program planning/adaptation (9 months); high-intensity implementation (15 months); lower-intensity maintenance (annual). One-way sensitivity analyses explored the effects of uncertainty in Scenario 2. RESULTS: Scenario 1 PTBi package total costs were $1.11M in Kenya ($48.13/birth) and $0.74M in Uganda ($17.19/birtth). Scenario 2 total costs were $0.86M in Kenya ($23.91/birth) and $0.28M in Uganda ($5.47/birth); annual maintenance phase costs per birth were $16.36 in Kenya and $3.47 in Uganda. In each scenario and country, personnel made up at least 72% of total PTBi package costs. Total Scenario 2 costs in Uganda were consistently one-third those of Kenya, largely driven by differences in facility delivery volume and personnel salaries. CONCLUSIONS: If taken up and implemented, the PTBi package has the potential to save preterm lives, with potential steady-state (maintenance) costs that would be roughly 5-15% of total per-birth healthcare costs in Uganda and Kenya.

Preventing HIV and achieving pregnancy among HIV sero-different couples: Pilot study of a safer conception intervention in Zimbabwe.

Safer conception services are needed to minimize HIV transmission among HIV sero-different couples desiring pregnancy. Few studies have evaluated the choices couples make when offered multiple safer conception methods or real-world method acceptability and effectiveness. We piloted a comprehensive safer conception program (Clintrials.gov identifier: NCT03049176) for HIV sero-different couples planning pregnancy in Zimbabwe to measure feasibility, method uptake, acceptability, pregnancy outcome, and HIV transmission. This study was not designed to compare rates of HIV transmission by safer conception method choice but rather to understand choices couples make when seeking to minimize risk of HIV transmission and maximize likelihood of pregnancy. Couples in this prospective, non-randomized study were given a choice of one or more currently available safer conception methods: antiretroviral therapy (ART) with monthly viral load (VL) monitoring for the HIV-positive partner (ART/VL), pre-exposure prophylaxis (PrEP) for the HIV-negative partner, vaginal insemination (VI) for couples with an HIV-positive woman, and semen washing (SW) for couples with an HIV-positive man. Couples were followed monthly for up to 12 months of pregnancy attempts, quarterly during pregnancy, and 12 weeks post-partum. At each visit, data on method use, urine for pregnancy testing, and blood for HIV antibody testing, or viral load if HIV-positive, were obtained. Infants born to HIV-positive women were tested for HIV at 6 and 12 weeks. Between March 2017 and June 2019, 46 individuals from 23 HIV sero-different partnerships were enrolled and followed. At enrollment, all couples chose ART/VL, and all couples chose at least one additional method; 74% chose PrEP, 36% chose SW, and 25% chose VI. During pre-pregnancy follow-up visits, three couples discontinued SW, and one couple discontinued VI; all four of these couples opted for ART/VL plus PrEP. Satisfaction with safer conception methods was high among those who chose ART/VL and PrEP. Twelve couples achieved pregnancy. There were no cases of HIV transmission to partners, and no infants tested positive for HIV. This safer conception program is feasible and acceptable, allowing sero-different couples to safely achieve pregnancy. Sero-different couples in Zimbabwe seek a combination of HIV prevention methods, particularly ART/VL plus PrEP. Trial Registration: Clintrials.gov, NCT03049176.

Unequal impacts of the COVID-19 pandemic on women's fertility preferences: Evidence from a longitudinal cohort in the United States.

•The COVID-19 pandemic suppressed fertility desires among US women.•Impacts on fertility preferences persisted from summer 2020 to early 2021.•The fertility preferences of younger women, women of color and those facing financial stress were most impacted.

Perceptions and predictors of respectful maternity care in Malawi: A quantitative cross-sectional analysis.

OBJECTIVE: Access to high-quality, respectful care is a basic human right. A lack of respectful care during childbirth is associated with poor outcomes and can negatively influence care-seeking and maternal mental health. We aimed to describe how women perceive their experience of maternity care in Malawi. METHODS: We implemented a cross-sectional survey of women (n = 660) who delivered in 25 birth facilities in four districts in Malawi in March 2020 using a validated 30-item, 90-point person-centered maternity care (PCMC) scale. We used descriptive statistics to examine women's experience of care and analyzed bivariable and multivariable mixed-effects models to evaluate predictors of PCMC. Statistical models accounted for clustering of women at the facility level and included maternal age, marital status, education, parity, mother or infant complications, timing of antenatal care (ANC), provider cadre and gender, facility type and sector, and district. RESULTS: Mean PCMC score was 57.5 (range 21-84), with the lowest score (12.4 of 27 points) in communication and autonomy. Women reported: being prohibited from having a birth companion during labor (49.4%) or delivery (60.3%); providers did not introduce themselves (81.1%); providers did not ask consent before procedures/examinations (42.4%); women felt they could not ask questions (40.9%); and were not involved in care decisions (61.5%). Few women reported being frequently abused physically (2%) or verbally (3.5%); almost all had water/electricity available (>95%). In bivariate analyses, statistically significant positive associations were found between PCMC score and early ANC, male accompaniment to the facility, male provider, and a lack of complications; all associations remained at least potentially statistically significant in multivariable modeling. CONCLUSIONS: Physical and verbal abuse and a lack of basic amenities were rare, while a lack of communication with patients and social support were common. Maternal characteristics (like timing of ANC and maternal or newborn complications) were predictors of RMC, while facility/system factors, like facility type and sector, were not. Continued efforts to improve respectful care will require strengthening provider communication skills and encouraging patient and companion involvement in care.

Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.

BACKGROUND: Psoriasis is an immune-mediated disease with either skin or joints manifestations, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. The relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head-to-head, which is why we chose to conduct a network meta-analysis. OBJECTIVES: To compare the efficacy and safety of non-biological systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis using a network meta-analysis, and to provide a ranking of these treatments according to their efficacy and safety. SEARCH METHODS: For this update of the living systematic review, we updated our searches of the following databases monthly to October 2021: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase. SELECTION CRITERIA: Randomised controlled trials (RCTs) of systemic treatments in adults over 18 years with moderate-to-severe plaque psoriasis, at any stage of treatment, compared to placebo or another active agent. The primary outcomes were: proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90; proportion of participants with serious adverse events (SAEs) at induction phase (8 to 24 weeks after randomisation). DATA COLLECTION AND ANALYSIS: We conducted duplicate study selection, data extraction, risk of bias assessment and analyses. We synthesised data using pairwise and network meta-analysis (NMA) to compare treatments and rank them according to effectiveness (PASI 90 score) and acceptability (inverse of SAEs). We assessed the certainty of NMA evidence for the two primary outcomes and all comparisons using CINeMA, as very low, low, moderate, or high. We contacted study authors when data were unclear or missing. We used the surface under the cumulative ranking curve (SUCRA) to infer treatment hierarchy, from 0% (worst for effectiveness or safety) to 100% (best for effectiveness or safety). MAIN RESULTS: This update includes an additional 19 studies, taking the total number of included studies to 167, and randomised participants to 58,912, 67.2% men, mainly recruited from hospitals. Average age was 44.5 years, mean PASI score at baseline was 20.4 (range: 9.5 to 39). Most studies were placebo-controlled (57%). We assessed a total of 20 treatments. Most (140) trials were multicentric (two to 231 centres). One-third of the studies (57/167) had high risk of bias; 23 unclear risk, and most (87) low risk. Most studies (127/167) declared funding by a pharmaceutical company, and 24 studies did not report a funding source. Network meta-analysis at class level showed that all interventions (non-biological systemic agents, small molecules, and biological treatments) showed a higher proportion of patients reaching PASI 90 than placebo. Anti-IL17 treatment showed a higher proportion of patients reaching PASI 90 compared to all the interventions, except anti-IL23. Biologic treatments anti-IL17, anti-IL12/23, anti-IL23 and anti-TNF alpha showed a higher proportion of patients reaching PASI 90 than the non-biological systemic agents. For reaching PASI 90, the most effective drugs when compared to placebo were (SUCRA rank order, all high-certainty evidence): infliximab (risk ratio (RR) 50.19, 95% CI 20.92 to 120.45), bimekizumab (RR 30.27, 95% CI 25.45 to 36.01), ixekizumab (RR 30.19, 95% CI 25.38 to 35.93), risankizumab (RR 28.75, 95% CI 24.03 to 34.39). Clinical effectiveness of these drugs was similar when compared against each other. Bimekizumab, ixekizumab and risankizumab showed a higher proportion of patients reaching PASI 90 than other anti-IL17 drugs (secukinumab and brodalumab) and guselkumab. Infliximab, anti-IL17 drugs (bimekizumab, ixekizumab, secukinumab and brodalumab) and anti-IL23 drugs (risankizumab and guselkumab) except tildrakizumab showed a higher proportion of patients reaching PASI 90 than ustekinumab and three anti-TNF alpha agents (adalimumab, certolizumab and etanercept). Ustekinumab was superior to certolizumab; adalimumab and ustekinumab were superior to etanercept. No significant difference was shown between apremilast and two non-biological drugs: ciclosporin and methotrexate. We found no significant difference between any of the interventions and the placebo for the risk of SAEs. The risk of SAEs was significantly lower for participants on methotrexate compared with most of the interventions. Nevertheless, the SAE analyses were based on a very low number of events with low- to moderate-certainty for all the comparisons (except methotrexate versus placebo, which was high-certainty). The findings therefore have to be viewed with caution. For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1), the results were similar to the results for PASI 90. Information on quality of life was often poorly reported and was absent for several of the interventions. AUTHORS' CONCLUSIONS: Our review shows that, compared to placebo, the biologics infliximab, bimekizumab, ixekizumab, and risankizumab were the most effective treatments for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of high-certainty evidence. This NMA evidence is limited to induction therapy (outcomes measured from 8 to 24 weeks after randomisation), and is not sufficient for evaluating longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean 44.5 years) and high level of disease severity (PASI 20.4 at baseline) may not be typical of patients seen in daily clinical practice. We found no significant difference in the assessed interventions and placebo in terms of SAEs, and the safety evidence for most interventions was low to moderate quality. More randomised trials directly comparing active agents are needed, and these should include systematic subgroup analyses (sex, age, ethnicity, comorbidities, psoriatic arthritis). To provide long-term information on the safety of treatments included in this review, an evaluation of non-randomised studies and postmarketing reports from regulatory agencies is needed. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

Family satisfaction in a neuro trauma ICU.

OBJECTIVE: The purpose of this quality improvement initiative was to evaluate satisfaction of family members of patients in a neuro trauma ICU (NTICU). METHODS: Adult patients (age 18+) admitted to the NTICU for at least 24 hours between June 2017 and November 2018 were identified. Near or at the time of discharge from the NTICU, the health unit coordinator or registered nurse identified the family member who was either the next-of-kin, surrogate decision-maker, or person who had been most frequently present at the patient's bedside. This person was provided a packet containing a letter of consent and the Critical Care Family Satisfaction Survey (CCFSS). RESULTS: Surveys were completed by 78 family members, the majority of whom were the wife of the patient (n = 35, 44%), 60 years and older (n = 48, 60.8%). Fifty-seven percent of patients (n = 45) were in the ICU less than 3 days and 59% (n = 47) of medical events were injury-related. Total CCFSS scores ranged from 69 to 100 (median 95). The item with the largest number of dissatisfied responses was "Noise level in the critical care unit" (n = 4, 5.3% not satisfied). Open-ended question comments were primarily positive (n = 60, 66%), with 32% (n = 29) representing areas for improvement. CONCLUSIONS: Results of this satisfaction survey have been disseminated to leadership and have been taken into consideration in the planning of a new hospital building currently being built, including ICU patient rooms that allow for more privacy and reduced noise, and more comfortable family rooms. RELEVANCE TO CLINICAL PRACTICE: Family members are a very useful source of feedback for ICU care. Several concerns identified by family members in this study are likely to be relevant to other sites. These included: communication between health care providers and family about patient status, noise in the ICU, peaceful waiting areas for family, and slow transfers.

Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.

BACKGROUND: Psoriasis is an immune-mediated disease for which some people have a genetic predisposition. The condition manifests in inflammatory effects on either the skin or joints, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. Several randomised controlled trials (RCTs) have compared the efficacy of the different systemic treatments in psoriasis against placebo. However, the relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head-to-head, which is why we chose to conduct a network meta-analysis. OBJECTIVES: To compare the efficacy and safety of non-biological systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis using a network meta-analysis, and to provide a ranking of these treatments according to their efficacy and safety. SEARCH METHODS: For this living systematic review we updated our searches of the following databases monthly to September 2020: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase. We searched two trials registers to the same date. We checked the reference lists of included studies and relevant systematic reviews for further references to eligible RCTs. SELECTION CRITERIA: Randomised controlled trials (RCTs) of systemic treatments in adults (over 18 years of age) with moderate-to-severe plaque psoriasis or psoriatic arthritis whose skin had been clinically diagnosed with moderate-to-severe psoriasis, at any stage of treatment, in comparison to placebo or another active agent. The primary outcomes of this review were: the proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90 at induction phase (from 8 to 24 weeks after the randomisation), and the proportion of participants with serious adverse events (SAEs) at induction phase. We did not evaluate differences in specific adverse events. DATA COLLECTION AND ANALYSIS: Several groups of two review authors independently undertook study selection, data extraction, 'Risk of bias' assessment, and analyses. We synthesised the data using pair-wise and network meta-analysis (NMA) to compare the treatments of interest and rank them according to their effectiveness (as measured by the PASI 90 score) and acceptability (the inverse of serious adverse events). We assessed the certainty of the body of evidence from the NMA for the two primary outcomes and all comparisons, according to CINeMA, as either very low, low, moderate, or high. We contacted study authors when data were unclear or missing. We used the surface under the cumulative ranking curve (SUCRA) to infer on treatment hierarchy: 0% (treatment is the worst for effectiveness or safety) to 100% (treatment is the best for effectiveness or safety). MAIN RESULTS: We included 158 studies (18 new studies for the update) in our review (57,831 randomised participants, 67.2% men, mainly recruited from hospitals). The overall average age was 45 years; the overall mean PASI score at baseline was 20 (range: 9.5 to 39). Most of these studies were placebo-controlled (58%), 30% were head-to-head studies, and 11% were multi-armed studies with both an active comparator and a placebo. We have assessed a total of 20 treatments. In all, 133 trials were multicentric (two to 231 centres). All but two of the outcomes included in this review were limited to the induction phase (assessment from 8 to 24 weeks after randomisation). We assessed many studies (53/158) as being at high risk of bias; 25 were at an unclear risk, and 80 at low risk. Most studies (123/158) declared funding by a pharmaceutical company, and 22 studies did not report their source of funding. Network meta-analysis at class level showed that all of the interventions (non-biological systemic agents, small molecules, and biological treatments) were significantly more effective than placebo in reaching PASI 90. At class level, in reaching PASI 90, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the non-biological systemic agents. At drug level, infliximab, ixekizumab, secukinumab, brodalumab, risankizumab and guselkumab were significantly more effective in reaching PASI 90 than ustekinumab and three anti-TNF alpha agents: adalimumab, certolizumab, and etanercept. Ustekinumab and adalimumab were significantly more effective in reaching PASI 90 than etanercept; ustekinumab was more effective than certolizumab, and the clinical effectiveness of ustekinumab and adalimumab was similar. There was no significant difference between tofacitinib or apremilast and three non-biological drugs: fumaric acid esters (FAEs), ciclosporin and methotrexate. Network meta-analysis also showed that infliximab, ixekizumab, risankizumab, bimekizumab, secukinumab, guselkumab, and brodalumab outperformed other drugs when compared to placebo in reaching PASI 90. The clinical effectiveness of these drugs was similar, except for ixekizumab which had a better chance of reaching PASI 90 compared with secukinumab, guselkumab and brodalumab. The clinical effectiveness of these seven drugs was: infliximab (versus placebo): risk ratio (RR) 50.29, 95% confidence interval (CI) 20.96 to 120.67, SUCRA = 93.6; high-certainty evidence; ixekizumab (versus placebo): RR 32.48, 95% CI 27.13 to 38.87; SUCRA = 90.5; high-certainty evidence; risankizumab (versus placebo): RR 28.76, 95% CI 23.96 to 34.54; SUCRA = 84.6; high-certainty evidence; bimekizumab (versus placebo): RR 58.64, 95% CI 3.72 to 923.86; SUCRA = 81.4; high-certainty evidence; secukinumab (versus placebo): RR 25.79, 95% CI 21.61 to 30.78; SUCRA = 76.2; high-certainty evidence; guselkumab (versus placebo): RR 25.52, 95% CI 21.25 to 30.64; SUCRA = 75; high-certainty evidence; and brodalumab (versus placebo): RR 23.55, 95% CI 19.48 to 28.48; SUCRA = 68.4; moderate-certainty evidence. Conservative interpretation is warranted for the results for bimekizumab (as well as mirikizumab, tyrosine kinase 2 inhibitor, acitretin, ciclosporin, fumaric acid esters, and methotrexate), as these drugs, in the NMA, have been evaluated in few trials. We found no significant difference between any of the interventions and the placebo for the risk of SAEs. Nevertheless, the SAE analyses were based on a very low number of events with low to moderate certainty for all the comparisons. Thus, the results have to be viewed with caution and we cannot be sure of the ranking. For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1) the results were similar to the results for PASI 90. Information on quality of life was often poorly reported and was absent for several of the interventions. AUTHORS' CONCLUSIONS: Our review shows that compared to placebo, the biologics infliximab, ixekizumab, risankizumab, bimekizumab, secukinumab, guselkumab and brodalumab were the most effective treatments for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of moderate- to high-certainty evidence. This NMA evidence is limited to induction therapy (outcomes were measured from 8 to 24 weeks after randomisation) and is not sufficient for evaluation of longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean age of 45 years) and high level of disease severity (PASI 20 at baseline) may not be typical of patients seen in daily clinical practice. Another major concern is that short-term trials provide scanty and sometimes poorly-reported safety data and thus do not provide useful evidence to create a reliable risk profile of treatments. We found no significant difference in the assessed interventions and placebo in terms of SAEs, and the evidence for all the interventions was of low to moderate quality. In order to provide long-term information on the safety of the treatments included in this review, it will also be necessary to evaluate non-randomised studies and postmarketing reports released from regulatory agencies. In terms of future research, randomised trials directly comparing active agents are necessary once high-quality evidence of benefit against placebo is established, including head-to-head trials amongst and between non-biological systemic agents and small molecules, and between biological agents (anti-IL17 versus anti-IL23, anti-IL23 versus anti-IL12/23, anti-TNF alpha versus anti-IL12/23). Future trials should also undertake systematic subgroup analyses (e.g. assessing biological-naïve participants, baseline psoriasis severity, presence of psoriatic arthritis, etc.). Finally, outcome measure harmonisation is needed in psoriasis trials, and researchers should look at the medium- and long-term benefit and safety of the interventions and the comparative safety of different agents. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

Estimated costs for the delivery of safer conception strategies for HIV-discordant couples in Zimbabwe: a cost analysis.

BACKGROUND: In recent years, safer conception strategies have been developed to help HIV-serodiscordant couples conceive a child without transmitting HIV to the seronegative partner. The SAFER clinical trial assessed implementation of these strategies in Zimbabwe. METHODS: As a part of the SAFER study, we estimated the costs (in 2017 $US) associated with individual and combination strategies, in the trial setting and real-world practice, from a healthcare system perspective. Safer conception strategies included: 1) ART with frequent viral load testing until achieving undetectable viral load (ART-VL); 2) daily oral pre-exposure prophylaxis (PrEP); 3) semen-washing with intrauterine insemination; and 4) manual self-insemination at home. For costs in the trial, we used a micro-costing approach, including a time and motion study to quantify personnel effort, and estimated the cost per couple for individual and combination strategies for a mean of 6 months of safer services. For real-world practice, we modeled costs for three implementation scenarios, representing differences from the trial in input prices (paid by the Ministry of Health and Child Care [MOHCC]), intervention intensity, and increments to current HIV prevention and treatment practices and guidelines. We used one-way sensitivity analyses to assess the impact of uncertainty in input variables. RESULTS: Individual strategy costs were $769-$1615 per couple in the trial; $185-$563 if using MOHCC prices. Under the target intervention intensity and using MOHCC prices, individual strategy costs were $73-$360 per couple over and above the cost of current HIV clinical practices. The cost of delivering the most commonly selected combination, ART-VL plus PrEP, ranged from $166-$517 per couple under the three real-world scenarios. Highest costs were for personnel, lab tests, and strategy-specific consumables, in variable proportions by clinical strategy and analysis scenario. Total costs were most affected by uncertainty in the price of PrEP, number of semen-washing attempts, and scale-up of semen-washing capacity. CONCLUSIONS: Safer conception methods have costs that may be affordable in many low-resource settings. These cost data will help implementers and policymakers add safer conception services. Cost-effectiveness analysis is needed to assess value for money for safer conception services overall and for safer strategy combinations. TRIAL REGISTRATION: Registry Name: Clinicaltrials.gov. TRIAL REGISTRATION NUMBER: NCT03049176 . Registration date: February 9, 2017.

Interventions for chronic palmoplantar pustulosis.

BACKGROUND: Palmoplantar pustulosis is a chronic inflammatory disease in which sterile, relapsing pustules appear on the palms and soles, possibly in conjunction with other symptoms. The previous Cochrane Review on this topic was published in 2006, before biological treatments were extensively used. OBJECTIVES: To assess the effects of interventions for chronic palmoplantar pustulosis to induce and maintain complete remission. SEARCH METHODS: We searched the following databases up to March 2019: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers and checked the reference lists of the included studies for further references to relevant randomised controlled trials (RCTs). SELECTION CRITERIA: We considered RCTs including people with palmoplantar pustulosis or chronic palmoplantar pustular psoriasis assessing topical therapy, systemic therapy, combinations of topical or systemic therapies, or non-pharmacological therapies compared with placebo, no intervention, or each other. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Our outcomes included 'Proportion of participants cleared or almost cleared', 'Proportion of participants with adverse effects serious or severe enough to cause withdrawal', 'Proportion of participants with at least 50% improvement in disease severity', and 'Proportion of participants with adverse effects'. MAIN RESULTS: We included 37 studies (1663 participants; mean age 50 years (range 34 to 63); 24% males). These studies reported condition severity differently. Around half of the included trials stated the setting (hospitals, community clinics, or both). More than half of the studies were at high risk of bias in at least one domain. Our included studies assessed mainly systemic treatments (retinoids, ciclosporin, biologics, etretinate + PUVA (combination of psoralens and long-wave ultraviolet radiation) therapy combined, and antibiotics), but also topical treatments (dermocorticoids, vitamin D) and phototherapy (PUVA, ultraviolet A1 (UVA1)). Other interventions were assessed by single studies. The most common comparator was placebo. All results presented in this abstract were assessed in the short term (mean treatment duration was 11 weeks (range 8 to 24 weeks)) and are based on participants with chronic palmoplantar pustulosis. All outcome time point measurements were taken from baseline and assessed at the end of treatment. Short-term and long-term outcomes were defined as measurement up to 24 weeks after randomisation and between 24 and 104 weeks after randomisation, respectively. One trial (188 participants) assessed the topical vitamin D derivative maxacalcitol versus placebo and found that maxacalcitol may be more effective than placebo in achieving clearance (risk ratio (RR) 7.83, 95% confidence interval (CI) 1.85 to 33.12; low-quality evidence), and the risk of adverse effects (such as mild local irritation, pruritus, and haematological or urinary test abnormalities) is probably similar in both groups (RR 0.87, 95% CI 0.64 to 1.19; moderate-quality evidence). Severity was not reported. Two trials (49 participants) assessed PUVA therapy versus placebo or no treatment, providing very low-quality evidence. Adverse effects were reported with oral PUVA (including nausea, ankle swelling, and non-purulent conjunctivitis) and with local PUVA (including blistering, erythema, and pruritus). With regard to the systemic retinoid alitretinoin, one trial (33 participants; moderate-quality evidence) showed that alitretinoin probably makes little or no difference in reducing severity when compared to placebo (RR 0.69, 95% CI 0.36 to 1.30). A similar number of adverse events were reported in both treatment groups, including headache, cheilitis, nausea, arthralgia, and nasopharyngitis (RR 0.84, 95% CI 0.61 to 1.17). Clearance was not reported. There may be little or no difference between etanercept and placebo in achieving clearance (RR 1.64, 95% CI 0.08 to 34.28; 1 study; 15 participants; low-quality evidence); however, the 95% CI was very wide, showing there may be a difference between groups. Severity was not measured. More patients treated with placebo may achieve reduced severity than those treated with ustekinumab, but the wide 95% CI indicates there might be little or no difference between groups and there might be greater effect with ustekinumab (RR 0.48, 95% CI 0.11 to 2.13; 1 study; 33 participants; low-quality evidence). Clearance was not reported. It is uncertain whether guselkumab increases clearance when compared to placebo (2 studies; 154 participants) because the quality of evidence is very low, but guselkumab probably better reduces disease severity (RR 2.88, 95% CI 1.24 to 6.69; 1 study; 49 participants; moderate-quality evidence). Secukinumab is probably superior to placebo in reducing severity (RR 1.55, 95% CI 1.02 to 2.35; 1 study; 157 participants; moderate-quality evidence), but our clearance outcome was not reported. None of these trials reported on occurrence of adverse effects. Only two of the studies discussed above reported adverse effects serious or severe enough to cause withdrawal. Guselkumab may cause more serious adverse events when compared to placebo, but there is uncertainty due to the very wide 95% CI showing there may be little or no difference and showing more events with placebo (RR 2.88, 95% CI 0.32 to 25.80; 1 study; 49 participants; low-quality evidence). Secukinumab probably causes more serious adverse events than placebo (RR 3.29, 95% CI 1.40 to 7.75; 1 study; 157 participants; moderate-quality evidence). AUTHORS' CONCLUSIONS: Evidence is lacking for major chronic palmoplantar pustulosis treatments such as superpotent corticosteroids, phototherapy, acitretin, methotrexate, and ciclosporin. Risk of bias and imprecision limit our confidence. Maxacalcitol may be more effective than placebo in achieving clearance in the short term (low-quality evidence), and the risk of adverse effects is probably similar (moderate-quality evidence). Oral alitretinoin is probably no more effective than placebo in reducing severity, with a similar risk of adverse effects (moderate-quality evidence). Regarding biological treatments, we are uncertain of the effect of etanercept on clearance and the effect of ustekinumab on severity (low-quality evidence). Secukinumab and guselkumab are probably superior to placebo in reducing severity (moderate-quality evidence). Adverse events not requiring withdrawal were not reported for these treatments. Reporting of serious adverse effects was incomplete: compared to placebo, secukinumab probably caused more participant withdrawals (moderate-quality evidence), but we are uncertain of the effect of guselkumab (low-quality evidence). Future trials should assess commonly used treatments using validated severity and quality of life scales.

Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.

BACKGROUND: Psoriasis is an immune-mediated disease for which some people have a genetic predisposition. The condition manifests in inflammatory effects on either the skin or joints, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. Several randomised controlled trials (RCTs) have compared the efficacy of the different systemic treatments in psoriasis against placebo. However, the relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head-to-head, which is why we chose to conduct a network meta-analysis. This is the baseline update of a Cochrane Review first published in 2017, in preparation for this Cochrane Review becoming a living systematic review. OBJECTIVES: To compare the efficacy and safety of conventional systemic agents, small molecules, and biologics for people with moderate-to-severe psoriasis, and to provide a ranking of these treatments according to their efficacy and safety. SEARCH METHODS: We updated our research using the following databases to January 2019: the Cochrane Skin Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS and the conference proceedings of a number of dermatology meetings. We also searched five trials registers and the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) reports (until June 2019). We checked the reference lists of included and excluded studies for further references to relevant RCTs. SELECTION CRITERIA: Randomised controlled trials (RCTs) of systemic treatments in adults (over 18 years of age) with moderate-to-severe plaque psoriasis or psoriatic arthritis whose skin had been clinically diagnosed with moderate-to-severe psoriasis, at any stage of treatment, in comparison to placebo or another active agent. The primary outcomes of this review were: the proportion of participants who achieved clear or almost clear skin, that is, at least Psoriasis Area and Severity Index (PASI) 90 at induction phase (from 8 to 24 weeks after the randomisation), and the proportion of participants with serious adverse effects (SAEs) at induction phase. We did not evaluate differences in specific adverse effects. DATA COLLECTION AND ANALYSIS: Several groups of two review authors independently undertook study selection, data extraction, 'Risk of bias' assessment, and analyses. We synthesised the data using pair-wise and network meta-analysis (NMA) to compare the treatments of interest and rank them according to their effectiveness (as measured by the PASI 90 score) and acceptability (the inverse of serious adverse effects). We assessed the certainty of the body of evidence from the NMA for the two primary outcomes, according to GRADE, as either very low, low, moderate, or high. We contacted study authors when data were unclear or missing. MAIN RESULTS: We included 140 studies (31 new studies for the update) in our review (51,749 randomised participants, 68% men, mainly recruited from hospitals). The overall average age was 45 years; the overall mean PASI score at baseline was 20 (range: 9.5 to 39). Most of these studies were placebo-controlled (59%), 30% were head-to-head studies, and 11% were multi-armed studies with both an active comparator and a placebo. We have assessed a total of 19 treatments. In all, 117 trials were multicentric (two to 231 centres). All but two of the outcomes included in this review were limited to the induction phase (assessment from 8 to 24 weeks after randomisation). We assessed many studies (57/140) as being at high risk of bias; 42 were at an unclear risk, and 41 at low risk. Most studies (107/140) declared funding by a pharmaceutical company, and 22 studies did not report the source of funding. Network meta-analysis at class level showed that all of the interventions (conventional systemic agents, small molecules, and biological treatments) were significantly more effective than placebo in terms of reaching PASI 90. At class level, in terms of reaching PASI 90, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the conventional systemic agents. At drug level, in terms of reaching PASI 90, infliximab, all of the anti-IL17 drugs (ixekizumab, secukinumab, bimekizumab and brodalumab) and the anti-IL23 drugs (risankizumab and guselkumab, but not tildrakizumab) were significantly more effective in reaching PASI 90 than ustekinumab and 3 anti-TNF alpha agents: adalimumab, certolizumab and etanercept. Adalimumab and ustekinumab were significantly more effective in reaching PASI 90 than certolizumab and etanercept. There was no significant difference between tofacitinib or apremilast and between two conventional drugs: ciclosporin and methotrexate. Network meta-analysis also showed that infliximab, ixekizumab, risankizumab, bimekizumab, guselkumab, secukinumab and brodalumab outperformed other drugs when compared to placebo in reaching PASI 90. The clinical effectiveness for these seven drugs was similar: infliximab (versus placebo): risk ratio (RR) 29.52, 95% confidence interval (CI) 19.94 to 43.70, Surface Under the Cumulative Ranking (SUCRA) = 88.5; moderate-certainty evidence; ixekizumab (versus placebo): RR 28.12, 95% CI 23.17 to 34.12, SUCRA = 88.3, moderate-certainty evidence; risankizumab (versus placebo): RR 27.67, 95% CI 22.86 to 33.49, SUCRA = 87.5, high-certainty evidence; bimekizumab (versus placebo): RR 58.64, 95% CI 3.72 to 923.86, SUCRA = 83.5, low-certainty evidence; guselkumab (versus placebo): RR 25.84, 95% CI 20.90 to 31.95; SUCRA = 81; moderate-certainty evidence; secukinumab (versus placebo): RR 23.97, 95% CI 20.03 to 28.70, SUCRA = 75.4; high-certainty evidence; and brodalumab (versus placebo): RR 21.96, 95% CI 18.17 to 26.53, SUCRA = 68.7; moderate-certainty evidence. Conservative interpretation is warranted for the results for bimekizumab (as well as tyrosine kinase 2 inhibitor, acitretin, ciclosporin, fumaric acid esters, and methotrexate), as these drugs, in the NMA, have been evaluated in few trials. We found no significant difference between any of the interventions and the placebo for the risk of SAEs. Nevertheless, the SAE analyses were based on a very low number of events with low to very low certainty for just under half of the treatment estimates in total, and moderate for the others. Thus, the results have to be viewed with caution and we cannot be sure of the ranking. For other efficacy outcomes (PASI 75 and Physician Global Assessment (PGA) 0/1) the results were very similar to the results for PASI 90. Information on quality of life was often poorly reported and was absent for several of the interventions. AUTHORS' CONCLUSIONS: Our review shows that compared to placebo, the biologics infliximab, ixekizumab, risankizumab, bimekizumab, guselkumab, secukinumab and brodalumab were the best choices for achieving PASI 90 in people with moderate-to-severe psoriasis on the basis of moderate- to high-certainty evidence (low-certainty evidence for bimekizumab). This NMA evidence is limited to induction therapy (outcomes were measured from 8 to 24 weeks after randomisation) and is not sufficient for evaluation of longer-term outcomes in this chronic disease. Moreover, we found low numbers of studies for some of the interventions, and the young age (mean age of 45 years) and high level of disease severity (PASI 20 at baseline) may not be typical of patients seen in daily clinical practice. Another major concern is that short-term trials provide scanty and sometimes poorly-reported safety data and thus do not provide useful evidence to create a reliable risk profile of treatments. Indeed, we found no significant difference in the assessed interventions and placebo in terms of SAEs, but the evidence for all the interventions was of very low to moderate quality. In order to provide long-term information on the safety of the treatments included in this review, it will also be necessary to evaluate non-randomised studies and postmarketing reports released from regulatory agencies. In terms of future research, randomised trials comparing directly active agents are necessary once high-quality evidence of benefit against placebo is established, including head-to-head trials amongst and between conventional systemic and small molecules, and between biological agents (anti-IL17 versus anti-IL23, anti-IL23 versus anti-IL12/23, anti-TNF alpha versus anti-IL12/23). Future trials should also undertake systematic subgroup analyses (e.g. assessing biological-naïve participants, baseline psoriasis severity, presence of psoriatic arthritis, etc.). Finally, outcome measure harmonisation is needed in psoriasis trials, and researchers should look at the medium- and long-term benefit and safety of the interventions and the comparative safety of different agents. Editorial note: This is a living systematic review. Living systematic reviews offer a new approach to review updating, in which the review is continually updated, incorporating relevant new evidence as it becomes available. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review.

Protocol for a case-control diagnostic accuracy study to develop diagnostic criteria for psoriasis in children (DIPSOC study): a multicentre study recruiting in UK paediatric dermatology clinics.

INTRODUCTION: Diagnosing psoriasis in children can be challenging. Early and accurate diagnosis is important to ensure patients receive psoriasis specific treatment and monitoring. It is recognised that the physical, psychological, quality of life, financial and comorbid burden of psoriasis are significant. The aim of this study is to develop clinical examination and history-based diagnostic criteria for psoriasis in children to help differentiate psoriasis from other scaly inflammatory rashes. The criteria tested in this study were developed through a consensus study with a group of international psoriasis experts (International Psoriasis Council). METHODS AND ANALYSIS: Children and young people (<18 years) with psoriasis (cases) and other scaly inflammatory skin diseases (controls) diagnosed by a dermatologist are eligible for recruitment. All participants complete a single research visit including a diagnostic criteria assessment by a trained investigator blinded to the participant's diagnosis. The reference standard of a dermatologist's diagnosis is extracted from the medical record. Sensitivity and specificity of the consensus derived diagnostic criteria will be calculated and the best predictive criteria developed using multivariate logistic regression. ETHICS AND DISSEMINATION: Health Regulatory Authority and National Health Service Research Ethics Committee approvals were granted in February 2017 (REC Ref: 17/EM/0035). Dissemination will be guided by stakeholders; patients, children and young people, dermatologists, primary care and paediatric rheumatologists. The aim is to publish the study results in a high-quality peer-reviewed journal, present the findings at international academic meetings and disseminate more widely through social media and working with patient associations. TRIAL REGISTRATION NUMBER: ISRCTN98851260.

Non-antistreptococcal interventions for acute guttate psoriasis or an acute guttate flare of chronic psoriasis.

BACKGROUND: Guttate psoriasis displays distinctive epidemiological and clinical features, making it a separate entity within the heterogeneous group of cutaneous psoriasis types. It is associated with genetic, immune, and environmental factors (such as stress and infections) and usually arises in younger age groups (including children, teenagers, and young adults). There is currently no cure for psoriasis, but various treatments can help to relieve the symptoms and signs. The objectives of treatment when managing an acute flare of guttate psoriasis are to reduce time to clearance and induction of long-term remission after resolution. This is an update of a Cochrane Review first published in 2000; since then, new treatments have expanded the therapeutic spectrum of systemic treatments used for psoriasis. OBJECTIVES: To assess the effects of non-antistreptococcal interventions for acute guttate psoriasis or an acute guttate flare of chronic psoriasis. SEARCH METHODS: We searched the following databases up to June 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We searched five trials registers and checked the reference lists of included studies for further references to relevant randomised controlled trials. We checked the proceedings of key dermatology conferences from 2004 to 2018, and also searched for trials in the US Food and Drug Administration (FDA) database for drug registration. SELECTION CRITERIA: All randomised controlled trials assessing the effects of treatments for acute guttate psoriasis or an acute guttate flare of chronic psoriasis clinically diagnosed in children and adults. This included all topical and systemic drugs, biological therapy, phototherapy (all forms: topical and systemic), and complementary and alternative therapies. We compared these treatments against placebo or against another treatment. We did not include studies on drugs that aim to eradicate streptococcal infection. We did not include studies when separate results for guttate psoriasis participants were not available. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility and methodological quality and extracted data. We used standard methodological procedures expected by Cochrane. Our primary outcomes were 'percentage of participants clear or almost clear (i.e. obtaining Psoriasis Area Severity Index (PASI) 100/90 and/or Physician's Global Assessment (PGA) of 0 or 1)' and 'percentage of participants with adverse effects and severe adverse effects'. Our secondary outcomes were 'number of relapses of guttate psoriasis or flares within a period of six months after the treatment has finished', 'percentage of participants achieving a PASI 75 or PGA of 1 or 2', and 'improvement in participant satisfaction measures and quality of life assessment measures'. We used GRADE to assess the quality of the evidence for each outcome. MAIN RESULTS: This review included only one trial (21 participants), which compared fish oil-derived (n-3) fatty acid-based lipid emulsion (50 mL per infusion (1.05 g eicosapentaenoic and 10.5 g docosahexaenoic acid)) (10 participants) to soya oil-derived (n-6) fatty acid-based lipid emulsion (50 mL per infusion (1.05 g eicosapentaenoic and 10.5 g docosahexaenoic acid)) (11 participants) administered intravenously twice daily for 10 days, with a total follow-up of 40 days. The study was conducted in a single centre in Germany in 18 men and three women, aged between 21 and 65 years, who were in hospital with acute guttate psoriasis and had mean total body surface involvement of 25.7% ± 20.4% (range 10 to 90). The study was funded by a company that produces the oil emulsions. We found no other evidence regarding non-antistreptococcal interventions used in clinical practice for guttate psoriasis, such as topical treatments (corticosteroids, vitamin D3 analogues), systemic drugs, biological therapy, and phototherapy.The primary outcomes of the review were not measured, and only one of our secondary outcomes was measured: improvement in participant satisfaction measures and quality of life assessment measures. However, the study authors did report that there was rare skin irritation at the site of peripheral intravenous route, but the number of affected participants was not provided.Improvement between baseline and day 10, using a non-validated score assessed by participants themselves daily based on five items (appearance of lesions, impairment of daily life, pruritus, burning, and pain), was greater in the group that received the fish oil-derived (n-3) fatty acid-based lipid emulsion (75%) than in the group receiving the soya oil-derived (n-6) fatty acid-based lipid emulsion (18%) (one trial, 21 participants). However, these results are uncertain as they are based on very low-quality evidence. AUTHORS' CONCLUSIONS: There is no evidence regarding topical and systemic drugs, biotherapy, or phototherapy in guttate psoriasis (we did not consider drugs that aimed to eradicate streptococcal infection because these are assessed in another Cochrane Review). We are uncertain of the effect of intravenously administered lipid emulsion on guttate psoriasis because the quality of the evidence is very low, due to risk of bias (unclear risk of bias for all domains), indirectness (the trial only included adults, and the follow-up from baseline was only 10 days), and imprecision (small number of participants).This review highlights the need for trials assessing the efficacy and safety of phototherapy and topical and systemic drugs for guttate psoriasis. There is also a need for studies that clearly distinguish the specific population with guttate psoriasis from the larger group of people with chronic plaque psoriasis, and children and young adults should be assessed as a distinct group.

Antistreptococcal interventions for guttate and chronic plaque psoriasis.

BACKGROUND: Psoriasis is a chronic skin disease that affects approximately two per cent of the general population. Plaque psoriasis is the most common form: it usually appears as raised, red patches of inflamed skin, covered with silvery white scales. The patches often occur in a symmetrical pattern. Guttate psoriasis is a particular form of psoriasis with widespread, small erythematosquamous lesions. Streptococcal infection is suspected to be a triggering factor for the onset of guttate psoriasis, and flare-up of chronic plaque psoriasis. The previous Cochrane Review on this topic was published in 2000; it required an update because antistreptococcal treatment continues to be used to treat psoriasis, especially for the acute form of guttate psoriasis. OBJECTIVES: To assess the effects of antistreptococcal interventions for guttate and chronic plaque psoriasis. SEARCH METHODS: We searched Cochrane Skin Specialised Register, Cochrane Register of Studies Online, CENTRAL, MEDLINE, Embase, LILACS, and five trials registers (January 2019). We checked the reference lists of included and excluded studies and searched conference proceedings from the American Academy of Dermatology, Society for Investigative Dermatology, and European Academy of Dermatology and Venereology. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) assessing antistreptococcal interventions (tonsillectomy or systemic antibiotic treatment) in people with clinically diagnosed acute guttate and chronic plaque psoriasis compared with placebo, no intervention, or each other. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Primary outcome measures were: 1) time-to-resolution; achieving clear or almost clear skin (Physician Global Assessment (PGA) 0 or 1 or Psoriasis Area and Severity Index (PASI) 90 or 100); 2) proportion of participants with adverse effects and severe adverse effects. Secondary outcomes were: 1) proportion of participants achieving clear or almost clear skin; 2) proportion of participants achieving PASI 75 or PGA 1 to 2; 3) risk of having at least one relapse at long-term follow-up. Short-term assessment was defined as within eight weeks of the start of treatment; long-term was at least one year after the start of treatment. MAIN RESULTS: We included five trials (162 randomised participants); three were conducted in a hospital dermatology department. One study declared funding by a pharmaceutical company. Participants' ages ranged from 12 to 77 years; only two participants were younger than 15 years. Mean PASI score at baseline varied from 5.7 (i.e. mild) to 23 (i.e. severe) in four studies. Twenty-three of 162 participants had streptococcus-positive throat swab culture. We did not perform a meta-analysis due to heterogeneity of participants' characteristics and interventions.None of the trials measured our efficacy primary outcome, time-to-resolution, or the secondary outcome, risk of having at least one relapse at long-term follow-up.We rated the quality of the results as very low-quality evidence, due to high risk of bias (absence of blinding of participants and caregivers, and high risk of outcome reporting bias) and imprecision (single study data with a low number of events). Hence, we are very uncertain about the results presented.Guttate psoriasisOne three-armed trial (N = 43) assessed penicillin (50,000 international units (IU)/kg/day in three doses) versus erythromycin (250 mg four times per day) versus no treatment (treatment for 14 days, with six-week follow-up from start of treatment). Adverse events and the proportion of participants achieving clear or almost clear skin were not measured.One trial (N = 20) assessed penicillin (1.6 MU (million units) intramuscularly once a day) versus no treatment (six weeks of treatment, with eight-week follow-up from start of treatment). At six-week (short-term) follow-up, no adverse events were observed in either group, and there was no statistically significant difference between the two groups in the proportion of participants with clear or almost clear skin (risk ratio (RR) 2.00, 95% confidence interval (CI) 0.68 to 5.85).One trial (N = 20) assessed rifampicin (300 mg twice daily) versus placebo (14-day treatment duration; six-week follow-up from start of treatment); none of the review outcomes were measured.These trials did not measure the proportion of participants achieving PASI 75 or PGA 1 to 2.Chronic plaque psoriasisOne trial (N = 50) assessed long-term azithromycin treatment (500 mg daily dose) versus vitamin C. Adverse events were reported in the azithromycin group (10 out of 30 had nausea and mild abdominal upset), but not in the vitamin C group. The proportion of participants who achieved clear or almost clear skin was not measured. In the azithromycin group, 18/30 versus 0/20 participants in the vitamin C group reached PASI 75 at the end of 48 weeks of treatment (RR 25.06, 95% CI 1.60 to 393.59).One trial (N = 29) assessed tonsillectomy versus no treatment, with 24-month follow-up after surgery. One participant in the tonsillectomy group had minor bleeding. At eight-week follow-up, 1/15 in the tonsillectomy group, and 0/14 in the no treatment group achieved PASI 90; and 3/15 participants in the tonsillectomy group, and 0/14 in the no treatment group achieved PASI 75 (RR 6.56, 95% CI 0.37 to 116.7). AUTHORS' CONCLUSIONS: We found only five trials (N = 162), which assessed the effects of five comparisons (systemic antibiotic treatment (penicillin, azithromycin) or tonsillectomy). Two comparisons (erythromycin compared to no treatment, and rifampicin compared to placebo) did not measure any of the outcomes of interest. There was very low-quality evidence for the outcomes that were measured, Therefore, we are uncertain of both the efficacy and safety of antistreptococcal interventions for guttate and chronic plaque psoriasis.The included trials were at unclear or high risk of bias and involved only a small number of unrepresentative participants, with limited measurement of our outcomes of interest. The studies did not allow investigation into the influence of Streptococcal infection, and a key intervention (amoxicillin) was not assessed.Further trials assessing the efficacy and tolerance of penicillin V or amoxicillin are needed in children and young adults with guttate psoriasis.

Interventions for necrotizing soft tissue infections in adults.

BACKGROUND: Necrotizing soft tissue infections (NSTIs) are severe and rapidly spreading soft tissue infections of the subcutaneous tissue, fascia, or muscle, which are mostly caused by bacteria. Associated rates of mortality and morbidity are high, with the former estimated at around 23%, and disability, sequelae, and limb loss occurring in 15% of patients. Standard management includes intravenous empiric antimicrobial therapy, early surgical debridement of necrotic tissues, intensive care support, and adjuvant therapies such as intravenous immunoglobulin (IVIG). OBJECTIVES: To assess the effects of medical and surgical treatments for necrotizing soft tissue infections (NSTIs) in adults in hospital settings. SEARCH METHODS: We searched the following databases up to April 2018: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers, pharmaceutical company trial results databases, and the US Food and Drug Administration and the European Medicines Agency websites. We checked the reference lists of included studies and reviews for further references to relevant randomised controlled trials (RCTs). SELECTION CRITERIA: RCTs conducted in hospital settings, that evaluated any medical or surgical treatment for adults with NSTI were eligible for inclusion. Eligible medical treatments included 1) comparisons between different antimicrobials or with placebo; 2) adjuvant therapies such as intravenous immunoglobulin (IGIV) therapy compared with placebo; no treatment; or other adjuvant therapies. Eligible surgical treatments included surgical debridement compared with amputation, immediate versus delayed intervention, or comparisons of number of interventions.RCTs of hyperbaric oxygen (HBO) therapy for NSTI were ineligible because HBO is the focus of another Cochrane Review. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The primary outcome measures were 1) mortality within 30 days, and 2) proportion of participants who experience a serious adverse event. Secondary outcomes were 1) survival time, and 2) assessment of long-term morbidity. We used GRADE to assess the quality of the evidence for each outcome. MAIN RESULTS: We included three trials randomising 197 participants (62% men) who had a mean age of 55 years. One trial compared two antibiotic treatments, and two trials compared adjuvant therapies with placebo. In all trials, participants concomitantly received standard interventions, such as intravenous empiric antimicrobial therapy, surgical debridement of necrotic tissues, intensive care support, and adjuvant therapies. All trials were at risk of attrition bias and one trial was not blinded.Moxifloxacin versus amoxicillin-clavulanate One trial included 54 participants who had a NSTI; it compared a third-generation quinolone, moxifloxacin, at a dose of 400 mg given once daily, against a penicillin, amoxicillin-clavulanate, at a dose of 3 g given three times daily for at least three days, followed by 1.5 g three times daily. Duration of treatment varied from 7 to 21 days. We are uncertain of the effects of these treatments on mortality within 30 days (risk ratio (RR) 3.00, 95% confidence interval (CI) 0.39 to 23.07) and serious adverse events at 28 days (RR 0.63, 95% CI 0.30 to 1.31) because the quality of the evidence is very low.AB103 versus placebo One trial of 43 randomised participants compared two doses, 0.5 mg/kg and 0.25 mg/kg, of an adjuvant drug, a CD28 antagonist receptor (AB103), with placebo. Treatment was given via infusion pump for 10 minutes before, after, or during surgery within six hours after the diagnosis of NSTI. We are uncertain of the effects of AB103 on mortality rate within 30 days (RR of 0.34, 95% CI 0.05 to 2.16) and serious adverse events measured at 28 days (RR 1.49, 95% CI 0.52 to 4.27) because the quality of the evidence is very low.Intravenous immunoglobulin (IVIG) versus placebo One trial of 100 randomised participants assessed IVIG as an adjuvant drug, given at a dose of 25 g/day, compared with placebo, given for three consecutive days. There may be no clear difference between IVIG and placebo in terms of mortality within 30 days (RR 1.17, 95% CI 0.42 to 3.23) (low-certainty evidence), nor serious adverse events experienced in the intensive care unit (ICU) (RR 0.73 CI 95% 0.32 to 1.65) (low-certainty evidence).Serious adverse events were only described in one RCT (the IVIG versus placebo trial) and included acute kidney injury, allergic reactions, aseptic meningitis syndrome, haemolytic anaemia, thrombi, and transmissible agents.Only one trial reported assessment of long-term morbidity, but the outcome was not defined in the way we prespecified in our protocol. The trial used the Short Form Health Survey (SF36). Data on survival time were provided upon request for the trials comparing amoxicillin-clavulanate versus moxifloxacin and IVIG versus placebo. However, even with data provided, it was not possible to perform survival analysis. AUTHORS' CONCLUSIONS: We found very little evidence on the effects of medical and surgical treatments for NSTI. We cannot draw conclusions regarding the relative effects of any of the interventions on 30-day mortality or serious adverse events due to the very low quality of the evidence.The quality of the evidence is limited by the very small number of trials, the small sample sizes, and the risks of bias in the included trials. It is important for future trials to clearly define their inclusion criteria, which will help with the applicability of future trial results to a real-life population.Management of NSTI participants (critically-ill participants) is complex, involving multiple interventions; thus, observational studies and prospective registries might be a better foundation for future research, which should assess empiric antimicrobial therapy, as well as surgical debridement, along with the placebo-controlled comparison of adjuvant therapy. Key outcomes to assess include mortality (in the acute phase of the condition) and long-term functional outcomes, e.g. quality of life (in the chronic phase).

Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.

BACKGROUND: Psoriasis is an immune-mediated disease for which some people have a genetic predisposition. The condition manifests in inflammatory effects on either the skin or joints, or both, and it has a major impact on quality of life. Although there is currently no cure for psoriasis, various treatment strategies allow sustained control of disease signs and symptoms. Several randomised controlled trials (RCTs) have compared the efficacy of the different systemic treatments in psoriasis against placebo. However, the relative benefit of these treatments remains unclear due to the limited number of trials comparing them directly head to head, which is why we chose to conduct a network meta-analysis. OBJECTIVES: To compare the efficacy and safety of conventional systemic agents (acitretin, ciclosporin, fumaric acid esters, methotrexate), small molecules (apremilast, tofacitinib, ponesimod), anti-TNF alpha (etanercept, infliximab, adalimumab, certolizumab), anti-IL12/23 (ustekinumab), anti-IL17 (secukinumab, ixekizumab, brodalumab), anti-IL23 (guselkumab, tildrakizumab), and other biologics (alefacept, itolizumab) for patients with moderate to severe psoriasis and to provide a ranking of these treatments according to their efficacy and safety. SEARCH METHODS: We searched the following databases to December 2016: the Cochrane Skin Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and LILACS. We also searched five trials registers and the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) reports. We checked the reference lists of included and excluded studies for further references to relevant RCTs. We searched the trial results databases of a number of pharmaceutical companies and handsearched the conference proceedings of a number of dermatology meetings. SELECTION CRITERIA: Randomised controlled trials (RCTs) of systemic and biological treatments in adults (over 18 years of age) with moderate to severe plaque psoriasis or psoriatic arthritis whose skin had been clinically diagnosed with moderate to severe psoriasis, at any stage of treatment, in comparison to placebo or another active agent. DATA COLLECTION AND ANALYSIS: Three groups of two review authors independently undertook study selection, data extraction, 'Risk of bias' assessment, and analyses. We synthesised the data using pair-wise and network meta-analysis (NMA) to compare the treatments of interest and rank them according to their effectiveness (as measured by the Psoriasis Area and Severity Index score (PASI) 90) and acceptability (the inverse of serious adverse effects). We assessed the certainty of the body of evidence from the NMA for the two primary outcomes, according to GRADE; we evaluated evidence as either very low, low, moderate, or high. We contacted study authors when data were unclear or missing. MAIN RESULTS: We included 109 studies in our review (39,882 randomised participants, 68% men, all recruited from a hospital). The overall average age was 44 years; the overall mean PASI score at baseline was 20 (range: 9.5 to 39). Most of these studies were placebo controlled (67%), 23% were head-to-head studies, and 10% were multi-armed studies with both an active comparator and placebo. We have assessed all treatments listed in the objectives (19 in total). In all, 86 trials were multicentric trials (two to 231 centres). All of the trials included in this review were limited to the induction phase (assessment at less than 24 weeks after randomisation); in fact, all trials included in the network meta-analysis were measured between 12 and 16 weeks after randomisation. We assessed the majority of studies (48/109) as being at high risk of bias; 38 were assessed as at an unclear risk, and 23, low risk.Network meta-analysis at class level showed that all of the interventions (conventional systemic agents, small molecules, and biological treatments) were significantly more effective than placebo in terms of reaching PASI 90.In terms of reaching PASI 90, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the conventional systemic agents. Small molecules were associated with a higher chance of reaching PASI 90 compared to conventional systemic agents.At drug level, in terms of reaching PASI 90, all of the anti-IL17 agents and guselkumab (an anti-IL23 drug) were significantly more effective than the anti-TNF alpha agents infliximab, adalimumab, and etanercept, but not certolizumab. Ustekinumab was superior to etanercept. No clear difference was shown between infliximab, adalimumab, and etanercept. Only one trial assessed the efficacy of infliximab in this network; thus, these results have to be interpreted with caution. Tofacitinib was significantly superior to methotrexate, and no clear difference was shown between any of the other small molecules versus conventional treatments.Network meta-analysis also showed that ixekizumab, secukinumab, brodalumab, guselkumab, certolizumab, and ustekinumab outperformed other drugs when compared to placebo in terms of reaching PASI 90: the most effective drug was ixekizumab (risk ratio (RR) 32.45, 95% confidence interval (CI) 23.61 to 44.60; Surface Under the Cumulative Ranking (SUCRA) = 94.3; high-certainty evidence), followed by secukinumab (RR 26.55, 95% CI 20.32 to 34.69; SUCRA = 86.5; high-certainty evidence), brodalumab (RR 25.45, 95% CI 18.74 to 34.57; SUCRA = 84.3; moderate-certainty evidence), guselkumab (RR 21.03, 95% CI 14.56 to 30.38; SUCRA = 77; moderate-certainty evidence), certolizumab (RR 24.58, 95% CI 3.46 to 174.73; SUCRA = 75.7; moderate-certainty evidence), and ustekinumab (RR 19.91, 95% CI 15.11 to 26.23; SUCRA = 72.6; high-certainty evidence).We found no significant difference between all of the interventions and the placebo regarding the risk of serious adverse effects (SAEs): the relative ranking strongly suggested that methotrexate was associated with the best safety profile regarding all of the SAEs (RR 0.23, 95% CI 0.05 to 0.99; SUCRA = 90.7; moderate-certainty evidence), followed by ciclosporin (RR 0.23, 95% CI 0.01 to 5.10; SUCRA = 78.2; very low-certainty evidence), certolizumab (RR 0.49, 95% CI 0.10 to 2.36; SUCRA = 70.9; moderate-certainty evidence), infliximab (RR 0.56, 95% CI 0.10 to 3.00; SUCRA = 64.4; very low-certainty evidence), alefacept (RR 0.72, 95% CI 0.34 to 1.55; SUCRA = 62.6; low-certainty evidence), and fumaric acid esters (RR 0.77, 95% CI 0.30 to 1.99; SUCRA = 57.7; very low-certainty evidence). Major adverse cardiac events, serious infections, or malignancies were reported in both the placebo and intervention groups. Nevertheless, the SAEs analyses were based on a very low number of events with low to very low certainty for just over half of the treatment estimates in total, moderate for the others. Thus, the results have to be considered with caution.Considering both efficacy (PASI 90 outcome) and acceptability (SAEs outcome), highly effective treatments also had more SAEs compared to the other treatments, and ustekinumab, infliximab, and certolizumab appeared to have the better trade-off between efficacy and acceptability.Regarding the other efficacy outcomes, PASI 75 and Physician Global Assessment (PGA) 0/1, the results were very similar to the results for PASI 90.Information on quality of life was often poorly reported and was absent for a third of the interventions. AUTHORS' CONCLUSIONS: Our review shows that compared to placebo, the biologics ixekizumab, secukinumab, brodalumab, guselkumab, certolizumab, and ustekinumab are the best choices for achieving PASI 90 in people with moderate to severe psoriasis on the basis of moderate- to high-certainty evidence. At class level, the biologic treatments anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha were significantly more effective than the small molecules and the conventional systemic agents, too. This NMA evidence is limited to induction therapy (outcomes were measured between 12 to 16 weeks after randomisation) and is not sufficiently relevant for a chronic disease. Moreover, low numbers of studies were found for some of the interventions, and the young age (mean age of 44 years) and high level of disease severity (PASI 20 at baseline) may not be typical of patients seen in daily clinical practice.Another major concern is that short-term trials provide scanty and sometimes poorly reported safety data and thus do not provide useful evidence to create a reliable risk profile of treatments. Indeed, we found no significant difference in the assessed interventions and placebo in terms of SAEs. Methotrexate appeared to have the best safety profile, but as the evidence was of very low to moderate quality, we cannot be sure of the ranking. In order to provide long-term information on the safety of the treatments included in this review, it will be necessary to evaluate non-randomised studies and postmarketing reports released from regulatory agencies as well.In terms of future research, randomised trials comparing directly active agents are necessary once high-quality evidence of benefit against placebo is established, including head-to-head trials amongst and between conventional systemic and small molecules, and between biological agents (anti-IL17 versus anti-IL23, anti-IL23 versus anti-IL12/23, anti-TNF alpha versus anti-IL12/23). Future trials should also undertake systematic subgroup analyses (e.g. assessing biological-naïve patients, baseline psoriasis severity, presence of psoriatic arthritis, etc.). Finally, outcome measure harmonisation is needed in psoriasis trials, and researchers should look at the medium- and long-term benefit and safety of the interventions and the comparative safety of different agents.

Onset timing, thoughts of self-harm, and diagnoses in postpartum women with screen-positive depression findings.

IMPORTANCE: The period prevalence of depression among women is 21.9% during the first postpartum year; however, questions remain about the value of screening for depression. OBJECTIVES: To screen for depression in postpartum women and evaluate positive screen findings to determine the timing of episode onset, rate and intensity of self-harm ideation, and primary and secondary DSM-IV disorders to inform treatment and policy decisions. DESIGN: Sequential case series of women who recently gave birth. SETTING: Urban academic women's hospital. PARTICIPANTS: During the maternity hospitalization, women were offered screening at 4 to 6 weeks post partum by telephone. Screen-positive women were invited to undergo psychiatric evaluations in their homes. MAIN OUTCOMES AND MEASURES: A positive screen finding was an Edinburgh Postnatal Depression Scale (EPDS) score of 10 or higher. Self-harm ideation was assessed on EPDS item 10: "The thought of harming myself has occurred to me" (yes, quite often; sometimes; hardly ever; never). Screen-positive women underwent evaluation with the Structured Clinical Interview for DSM-IV for Axis I primary and secondary diagnoses. RESULTS: Ten thousand mothers underwent screening, with positive findings in 1396 (14.0%); of these, 826 (59.2%) completed the home visits and 147 (10.5%) completed a telephone diagnostic interview. Screen-positive women were more likely to be younger, African American, publicly insured, single, and less well educated. More episodes began post partum (40.1%), followed by during pregnancy (33.4%) and before pregnancy (26.5%). In this population, 19.3% had self-harm ideation. All mothers with the highest intensity of self-harm ideation were identified with the EPDS score of 10 or higher. The most common primary diagnoses were unipolar depressive disorders (68.5%), and almost two-thirds had comorbid anxiety disorders. A striking 22.6% had bipolar disorders. CONCLUSIONS AND RELEVANCE: The most common diagnosis in screen-positive women was major depressive disorder with comorbid generalized anxiety disorder. Strategies to differentiate women with bipolar from unipolar disorders are needed. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00282776.

Does fetal exposure to SSRIs or maternal depression impact infant growth?

OBJECTIVE: The aim of this study was to compare the growth of infants born to women with antenatal major depressive disorder, either untreated or treated with selective serotonin reuptake inhibitor (SSRI) antidepressants, and infants born to a nondepressed, nonmedicated comparison group across the first year of life. METHOD: In this prospective observational study, pregnant women were evaluated at weeks 20, 30, and 36 of gestation, and mother and infant pairs were assessed at 2, 12, 26, and 52 weeks postpartum. Three nonoverlapping groups of women were defined according to their pregnancy exposures: 1) no SSRI and no depression (N=97), 2) SSRI (N=46), and 3) major depression without SSRI (N=31). Maternal demographic and clinical characteristics and newborn outcomes were compared across exposure groups. Infant weight, length, and head circumference were measured by a physician or physician's assistant who was blind to depression and SSRI exposure status at each postpartum time point. RESULTS: Both adjusted and unadjusted analyses revealed neither antenatal major depression nor SSRI exposure was significantly associated with infant weight, length, or head circumference relative to nonexposure to either. In addition, the interaction of group and prepregnancy body mass index was also evaluated, and no significant synergistic effect was identified. Similarly, no differential effect of group over time was observed for weight, length, or head circumference. CONCLUSIONS: In utero exposure to major depression or SSRI antidepressants did not affect infant growth with respect to weight, length, or head circumference from birth through 12 months of age.

The effect of gastric bypass on the pharmacokinetics of serotonin reuptake inhibitors.

OBJECTIVE: Morbidly obese patients frequently present with mood and anxiety disorders, which are often treated with serotonin reuptake inhibitors (SRIs). Having observed that patients treated with SRIs frequently relapse after Roux-en-Y gastric bypass surgery, the authors sought to assess whether SRI bioavailability is reduced postoperatively. METHOD: Twelve gastric bypass candidates treated with an SRI for primary mood or anxiety disorders were studied prospectively. Timed blood samples for SRI plasma levels were drawn for pharmacokinetic studies before surgery and 1, 6, and 12 months afterward. Maximum concentration, time to maximum concentration, and area under the concentration/time curve (AUC) were determined. RESULTS: In eight of the 12 patients, AUC values 1 month after surgery dropped to an average of 54% (SD=18) of preoperative levels (range=36%-80%); in six of these patients, AUC values returned to baseline levels (or greater) by 6 months. Four patients had an exacerbation of depressive symptoms, which resolved by 12 months in three of them. Three of the four patients had a reduced AUC level at 1 month and either gained weight or failed to lose weight between 6 and 12 months. Normalization of the AUC was associated with improvement in symptom scores. CONCLUSIONS: Patients taking SRIs in this study were at risk for reduced drug bioavailability 1 month after Roux-en-Y gastric bypass. The authors recommend close psychiatric monitoring after surgery.

Factors influencing social interaction among high school students with intellectual disabilities and their general education peers.

Recent legislative, policy, and research initiatives affirm the importance of improving social outcomes for adolescents with moderate to severe intellectual disabilities. Using observational methodology, we examined the influence of level of integration and Peer Buddy proximity on social interaction between students with intellectual disabilities and their general education peers in high school settings. Similarities and differences were found between more and less integrated settings with respect to contextual variables and measures of social interaction. Across settings, the proximity of a Peer Buddy was associated with higher frequency interactions and more positive student affect. Implications regarding increasing social interaction among high school students are discussed.