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Background: Improving a patient's ability to self-monitor and manage changes in chronic obstructive pulmonary disease (COPD) symptoms may improve outcomes.Objective: To determine the efficacy of a comprehensive care management program (CCMP) in reducing the risk for COPD hospitalization.Design: A randomized, controlled trial comparing CCMP with guideline-based usual care. (ClinicalTrials.gov registration number: NCT00395083) SETTING: 20 Veterans Affairs hospital-based outpatient clinics.Participants: Patients hospitalized for COPD in the past year.Intervention: The CCMP included COPD education during 4 individual sessions and 1 group session, an action plan for identification and treatment of exacerbations, and scheduled proactive telephone calls for case management. Patients in both the intervention and usual care groups received a COPD informational booklet; their primary care providers received a copy of COPD guidelines and were advised to manage their patients according to these guidelines. Patients were randomly assigned, stratifying by site based on random, permuted blocks of variable size.Measurements: The primary outcome was time to first COPD hospitalization. Staff blinded to study group performed telephone-based assessment of COPD exacerbations and hospitalizations, and all hospitalizations were blindly adjudicated. Secondary outcomes included non-COPD health care use, all-cause mortality, health-related quality of life, patient satisfaction, disease knowledge, and self-efficacy.Results: Of the eligible patients, 209 were randomly assigned to the intervention group and 217 to the usual care group. Citing serious safety concerns, the data monitoring committee terminated the intervention before the trial's planned completion after 426 (44%) of the planned total of 960 patients were enrolled. Mean follow-up was 250 days. When the study was stopped, the 1-year cumulative incidence of COPD-related hospitalization was 27% in the intervention group and 24% in the usual care group (hazard ratio, 1.13 [95% CI, 0.70 to 1.80]; P= 0.62). There were 28 deaths from all causes in the intervention group versus 10 in the usual care group (hazard ratio, 3.00 [CI, 1.46 to 6.17]; P= 0.003). Cause could be assigned in 27 (71%) deaths. Deaths due to COPD accounted for the largest difference: 10 in the intervention group versus 3 in the usual care group (hazard ratio, 3.60 [CI, 0.99 to 13.08]; P= 0.053).Limitations: Available data could not fully explain the excess mortality in the intervention group. Ability to assess the quality of the educational sessions provided by the case managers was limited.Conclusion: A CCMP in patients with severe COPD had not decreased COPD-related hospitalizations when the trial was stopped prematurely. The CCMP was associated with unanticipated excess mortality, results that differ markedly from similar previous trials. A data monitoring committee should be considered in the design of clinical trials involving behavioral interventions. [ABSTRACT FROM AUTHOR]

Objectives: The objectives of this study were to determine whether tamoxifen recommendation differs by physician specialty, to determine whether perception affects tamoxifen recommendation, and to investigate the association between the physician's specialty and the perception of risks and benefits of tamoxifen.Methods: We enrolled a cohort of geographically diverse women aged 65 and older with stage I through IIIa breast cancer in a prospective cohort study. We recruited their surgeons and, when applicable, their medical oncologists to provide patient-specific information about their perceptions of the risks and benefits of tamoxifen and whether they recommended tamoxifen. Each physician also completed a questionnaire regarding his or her demographic and practice characteristics. Patient data were collected through medical record review and a patient interview 3 months after definitive breast cancer surgery.Results: We collected physician treatment recommendation forms for 585 women. Oncologists were 2.5 times more likely to recommend tamoxifen, compared with surgeons, after adjusting for patient and tumor characteristics (95% confidence interval, 1.5-4.2). For both specialties, their perceptions of the risks and benefits of tamoxifen were strong predictors of tamoxifen recommendation. However, there were differences in perception by physician specialty. Distant metastases and tolerance of tamoxifen side effects were more important to oncologists, whereas local recurrence and risk of cataracts were more important to surgeons.Conclusion: Physicians' perceptions of the risks and benefits of tamoxifen therapy for older women are important in their decision-making process. [ABSTRACT FROM AUTHOR]

Past assessments of comorbidity indices have sought to recommend a single index that performs better than others. The authors used a multiple informants approach as an alternative method to simultaneously assess five indices of comorbidity. This approach provides a single estimate of the overall effect of comorbidity and evaluates the relation any individual index has to the outcomes of interest. Association of comorbidity with definitive primary therapy, discussion of tamoxifen, and receipt of tamoxifen was evaluated in a cohort of 830 older breast cancer patients enrolled at four geographically distinct centers in the United States from 1996 to 1999. The estimated adjusted effect of a unit increase in comorbidity on the odds of discussing tamoxifen therapy was 0.70 (95% confidence interval: 0.56, 0.88). An increase in comorbidity was not associated with receipt of definitive primary therapy (odds ratio = 0.94, 95% confidence interval: 0.79, 1.13) or receipt of tamoxifen (odds ratio = 0.96, 95% confidence interval: 0.72, 1.27). The multiple informants regression proved superior to separate regression models that included only one index. In analyses that require comorbidity adjustment and for which no single index is expected to be ideal, the multiple informants approach is an attractive alternative to selecting a single index and to other methods of using multiple indices. [ABSTRACT FROM AUTHOR]

Background: TB is a leading infectious cause of death worldwide. The COVID-19 pandemic raised concerns that the burden of TB disease and death would increase due to the synergy between the two conditions., Methods: We used individual-level data submitted to the WHO Global Clinical Platform for COVID-19 on hospitalised patients to explore associations of TB with mortality using multivariable logistic regression., Results: Data were available from 453,233 persons with COVID-19 and known TB status and mortality outcomes from 62 countries (96% SARS-CoV-2 test-positive). Of these, 48% were male, and the median age was 53 years (IQR 38-67). There were 8,214 cases with current TB reported by 46 countries, mainly from Africa. Of people with current TB, 31.4% were admitted with severe illness, and 24.5% died. Current TB was independently associated with higher mortality when adjusted for age, sex, HIV status, illness severity at hospital admission, and underlying conditions (adjusted RR 1.47, 95% CI 1.35-1.61)., Conclusion: Current or past TB were independent risk factors for in-hospital mortality regardless of illness severity at admission. Caveats for interpretation include changes during the data collection period (viral variation, vaccination coverage) and opportunistic sampling. However, the platform exemplifies how timely, coordinated global reporting can inform our understanding of health emergencies and the vulnerable populations affected., (© 2024 The Authors.)

Introduction: There is limited evidence on effective health systems interventions for preventing female genital mutilation (FGM). This study tested a two-level intervention package at primary care applying person-centred communication (PCC) for FGM prevention., Methods: A cluster randomised trial was conducted in 2020-2021 in 180 antenatal care (ANC) clinics in Guinea, Kenya and Somalia. At baseline, all clinics received guidance and materials on FGM prevention and care; at month 3, ANC providers at intervention sites received PCC training. Data were collected from clinic managers, ANC providers and clients at baseline, month 3 and month 6 on primary outcomes, including delivery of PCC counselling, utilisation of level one materials, health facility preparedness for FGM prevention and care services and secondary outcomes related to clients' and providers' knowledge and attitudes. Data were analysed using multilevel and single-level logistic regression models., Results: Providers in the intervention arm were more likely to deliver PCC for FGM prevention compared with those in the control arm, including inquiring about clients' FGM status (adjusted OR (AOR): 8.9, 95% CI: 6.9 to 11.5; p<0.001) and FGM-related beliefs (AOR: 9.7, 95% CI: 7.5 to 12.5; p<0.001) and discussing why (AOR: 9.2, 95% CI: 7.1 to 11.9; p<0.001) or how (AOR: 7.7, 95% CI: 6.0 to 9.9; p<0.001) FGM should be prevented. They were more confident in their FGM-related knowledge (AOR: 7.0, 95% CI: 1.5 to 32.3; p=0.012) and communication skills (AOR: 1.8; 95% CI: 1.0 to 3.2; p=0.035). Intervention clients were less supportive of FGM (AOR: 5.4, 95% CI: 2.4 to 12.4; p<0.001) and had lower intentions of having their daughters undergo FGM (AOR: 0.3, 95% CI: 0.1 to 0.7; p=0.004) or seeking medicalised FGM (AOR: 0.2, 95% CI: 0.1 to 0.5; p<0.001) compared with those in the control arm., Conclusion: This is the first study to provide evidence of an effective FGM prevention intervention that can be delivered in primary care settings in high-prevalence countries., Trial Registration and Date: PACTR201906696419769 (3 June 2019)., Competing Interests: Competing interests: None declared., (© World Health Organization 2024. Licensee BMJ.)

Introduction: In 2016, WHO estimated there were roughly 374 million new infections among adults of the following four curable sexually transmitted infections (STIs): chlamydia (caused by Chlamydia trachomatis (CT)), gonorrhoea ( Neisseria gonorrhoeae (NG)), syphilis ( Treponema pallidum ) and trichomoniasis ( Trichomonas vaginalis (TV)). Accurate point-of-care tests (POCTs) for screening of genital and extragenital CT, NG and TV infections are of great value and have been developed during recent decade. Several tests are commercially available and have shown encouraging performance compared with 'gold-standard' reference tests in laboratory-based studies. However, there is limited data on their clinical performance, including at the POC. Key populations, such as men who have sex with men (MSM), are at higher risk of these STIs at genital and extragenital sites and these STIs are often asymptomatic, especially in extragenital sites and in women. We will conduct a clinical-based evaluation to assess the performance characteristics and acceptability to end-users of molecular-based diagnostic technology for POC/near patient use of the Xpert CT/NG (Cepheid, Sunnyvale, California, USA) test for screening of genital, anorectal and pharyngeal CT and NG infections in MSM and the Xpert CT/NG and Xpert TV (Cepheid, Sunnyvale, California, USA) for screening of genital CT, NG and TV among women at risk for these STIs compared with gold-standard reference nucleic acid amplification tests. This master protocol outlines the overall research approach that will be used in seven countries., Method and Analyses: Consecutive MSM and women at risk presenting at the clinical sites in high, and low- and middle-income countries will be enrolled. The POCTs to be evaluated are Xpert CT/NG and Xpert TV. All procedures will be carried out by trained healthcare staff and tests performed in strict accordance with the manufacturer's instructions. The sensitivity, specificity, positive and negative predictive values for each POCT will be calculated. The study is ongoing with recruitment expected to be completed in all countries by mid-2022 to late-2022., Ethics and Dissemination: Prior to enrolment, this core protocol was independently peer-reviewed and approved by the research project review panel (RP2) of the WHO Department of Sexual and Reproductive Health and Research and by the WHO Ethics Review Committee (ERC). The core protocol has been slightly adapted accordingly to individual countries and adaptations approved by both RP2 and ERC, as well as all relevant institutional review boards at each participating site. Results will be disseminated through peer-reviewed journals and presented at relevant national/international conferences., Competing Interests: Competing interests: The POCT manufacturer discloses and furnishes free of charge to WHO the information and sufficient quantities of the product(s) in order to enable this evaluation as part of the WHO/RHR STI POC initiative. WHO is entitled to evaluate and publish the trial results, and to exclusively control this evaluation and the content of the aforesaid publication. WHO shall submit any proposed publication to the POCT manufacturer for review, comments received will be considered in good faith, but the decision to publish rests with WHO., (© World Health Organization 2024. Licensee BMJ.)

Background: In 2018, the World Health Organization commenced a multi-country validation study of the Cepheid GeneXpert for a range of molecular-based point-of-care (POC) tests in primary care settings. One study arm focused on the evaluation of POC tests for screening 'women at risk' for chlamydia (CT), gonorrhoea (NG) and trichomonas (TV) in four countries - Australia, Guatemala, Morocco and South Africa., Methods: Study participants completed a pre-test questionnaire which included demographics, clinical information and general questions on POC testing (POCT). Two vaginal swab samples (either self-collected or clinician collected) from each patient were tested on the GeneXpert at the POC and at a reference laboratory using quality-assured nucleic acid amplification tests (NAATs)., Results: One thousand three hundred and eighty-three women were enrolled: 58.6% from South Africa, 29.2% from Morocco, 6.2% from Guatemala, and 6.0% from Australia. 1296 samples for CT/NG and 1380 samples for TV were tested by the GeneXpert and the reference NAAT. The rate of unsuccessful tests on the GeneXpert was 1.9% for CT, 1.5% for NG and 0.96% for TV. The prevalence of CT, NG and TV was 31%, 13% and 23%, respectively. 1.5% of samples were positive for all three infections; 7.8% were positive for CT and NG; 2.4% were positive for NG and TV; and 7.3% were positive for CT and TV. Compared to reference NAATs, pooled estimates of sensitivity for the GeneXpert tests were 83.7% (95% confidence intervals 69.2-92.1) for CT, 90.5% (85.1-94.1) for NG and 64.7% (58.1-70.7) for TV (although estimates varied considerably between countries). Estimates for specificity were ≥96% for all three tests both within- and between-countries. Pooled positive and negative likelihood ratios were: 32.7 ([CI] 21.2-50.5) and 0.17 (0.08-0.33) for CT; 95.3 (36.9-245.7) and 0.10 (0.06-0.15) for NG; and 56.5 (31.6-101.1) and 0.35 (0.27-0.47) for TV., Conclusion: This multi-country evaluation is the first of its kind world-wide. Positive likelihood ratios, as well as specificity estimates, indicate the GeneXpert POC test results for CT, NG and TV were clinically acceptable for ruling in the presence of disease. However, negative likelihood ratios and variable sensitivity estimates from this study were poorer than expected for ruling out these infections, particularly for TV., Trial Registration: Ethics approval to conduct the ProSPeRo study was granted by the WHO Ethics Review Committee, as well as local ethics committees from all participating countries., (© 2024. The Author(s).)

Background: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections have increased globally. Asymptomatic infections represent a significant risk of long-term complications. Men who have sex with men (MSM) are disproportionally affected, underscoring the need to offer screening programmes to this population. CT/NG Point of Care Testing (POCT) constitutes a strategic tool to improve the continuum of STI care, however extensive real-life evaluations amongst at risk populations are lacking. The aim of this study is to estimate the GeneXpert CT/NG assay performance and usability for CT and NG at genital and extragenital sites for screening amongst MSM., Methods: This study was a multi-site sexual health clinic-based evaluation (Italy, Malta and Peru) with consecutive enrolment. A first void urine sample (divided in two aliquots), two oropharyngeal and two anorectal swabs were collected for each study participant. One specimen set (one for each anatomical site) was tested with the dual index test (Cepheid) at the clinics by the healthcare staff, the other set with FDA/CE approved Nucleic Acid Amplification Tests (NAATs) at the laboratory. Clinical sites and reference laboratories participated in an internal and external quality control programme. Sensitivity, specificity, positive and negative likelihood ratios, positive and negative predictive values for each anatomical site were estimated using a meta-analytic approach., Results: One thousand seven hundred two MSM were recruited across all clinical sites for a total of 5049 biological specimens. NG and CT were respectively detected in 274 and 287 of samples. Overall, the NG POCT sensitivity and specificity was 91.43% and 99.75% in urine (LR + 372.80, LR- 0.09), 89.68% and 99.55% in rectal specimens (LR + 197.30, LR- 0.10) and 75.87% and 98.77% at the pharynx respectively (LR + 61.94, LR- 0.24). The CT component of the POCT sensitivity was 84.82% and specificity 99.63% in urine (LR + 228.68, LR- 0.15), 78.07% and 99.19% respectively on rectal site (LR + 96.23, LR-0.22), 67.79% and 99.88% respectively at pharyngeal site (LR + 554.89, LR- 0.32). 95.95% of MSM reported to be willing to wait for POCT results and no provider reported difficulties in terms of performance or interpretation of the results of the Xpert CT/NG., Conclusion: Rapid turnaround time, ease of use and high acceptability make the Xpert CT/NG testing system a strategic tool for increasing testing frequency, reaching those not yet tested and offering the possibility of immediate treatment if needed. The assay showed good negative likelihood ratios and confirms its use to rule out CT/NG infections. Sensitivity varied across sites and pathogens. Periodic staff training at the testing sites should be mandatory., (© 2024. The Author(s).)

Introduction: Globally, the incidence of HIV and syphilis can be reduced by the use of validated point of care tests (POCTs). As part of the WHO PRoSPeRo Network, we aimed to evaluate the performance, acceptability, and operational characteristics of two dual HIV/syphilis POCTs (Bioline HIV/Syphilis Duo (Abbott) and DPP® HIV-Syphilis assay (Chembio) for the screening of HIV and syphilis amongst men who have sex with men (MSM)., Method and Analyses: A cross sectional study of 2,577 MSM in Italy, Malta, Peru, and the United Kingdom (UK) presenting to seven clinic sites, were enrolled. Finger prick blood was collected to perform POCTs and results compared with standard laboratory investigations on venepuncture blood. Acceptability and operational characteristics were assessed using questionnaires. Diagnostic meta-analysis was used to combine data from the evaluation sites., Results: Based on laboratory tests, 23.46% (n = 598/2549) of participants were confirmed HIV positive, and 35.88% of participants (n = 901/2511) were positive on treponemal reference testing. Of all participants showing evidence of antibodies to Treponema pallidum, 50.56% (n = 455/900) were Rapid Plasma Reagin (RPR) test reactive. Of HIV positive individuals, 60.62% (n = 354/584) had evidence of antibodies to T. pallidum, and of these 60.45% (n = 214/354) exhibited reactive RPR tests indicating probable (co)infection. For Bioline POCT, pooled sensitivities and specificities for HIV were 98.95% and 99.89% respectively, and for syphilis were 73.79% and 99.57%. For Chembio pooled sensitivities and specificities for HIV were 98.66% and 99.55%, and for syphilis were 78.60% and 99.48%. Both tests can detect greater than 90% of probable active syphilis cases, as defined by reactive RPR and treponemal test results. These dual POCTs were preferred by 74.77% (n = 1,926) of participants, due to their convenience, and the operational characteristics made them acceptable to health care providers (HCPs)., Conclusions: Both the Bioline and the Chembio dual POCT for syphilis and HIV had acceptable performance, acceptability and operational characteristics amongst MSM in the PRoSPeRo network. These dual POCTs could serve as a strategic, more cost effective, patient and healthcare provider (HCP) friendly alternative to conventional testing; in clinical and other field settings, especially those in resource-limited settings., (© 2024. The Author(s).)

Background: Dual point-of-care tests (POCTs) for the simultaneous detection of antibodies to HIV and syphilis have been developed. Since community-based organisations (CBO) are effective providers of HIV and syphilis testing among men who have sex with men (MSM), evaluation of the utility of these dual tests at CBO testing services is a high priority. The aim of this study is to determine the feasibility of performing dual HIV-syphilis POCT testing among both users and providers at these non-clinical sites., Methods: This evaluation assessed the utility of two lateral flow immunochromatographic antibody technologies for dual screening for HIV/syphilis among MSM seeking testing in four CBO testing services in Spain, Slovenia, Latvia, and Ukraine. The study's conceptual framework divides the concept of feasibility into two inter-related domains, acceptability, and usability and further breaks it down into six subdomains: learnability, willingness, suitability, satisfaction, efficacy, and effectiveness. The feasibility analysis was performed by calculating the median score in 3 stages (for individual questions, subdomains, and domains), using a summated scores method., Results: The final sample included 844 participants, 60 of which were found to be HIV test positive (7.1%) and 61 (7.2%) positive on testing for syphilis. There was a small difference (1.1%) when comparing the results of the two dual POCTs under evaluation to the tests routinely used at each site. The inter-rater agreement showed a high concordance between two independent readings. The analysis of the feasibility for the users of the services indicated good satisfaction, suitability, and willingness. In addition, among 18 providers the total mean score showed good acceptability and usability, good willingness, easy learnability, high suitability, and good efficacy, but lower satisfaction and effectiveness. The operational characteristics of both dual study POCTs were well evaluated by providers., Conclusions: The introduction of dual HIV and syphilis  POCTs in CBO testing services for screening of MSM is feasible, with a high acceptability and usability both for users and providers. Implementation of dual POCTs for HIV and syphilis in CBO testing services is an opportunity for scaling up integrated HIV/syphilis testing for MSM., (© 2024. The Author(s).)

Objective: To identify and summarise the evidence on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA detection and persistence in body fluids associated with sexual activity (saliva, semen, vaginal secretion, urine and faeces/rectal secretion)., Eligibility: All studies that reported detection of SARS-CoV-2 in saliva, semen, vaginal secretion, urine and faeces/rectal swabs., Information Sources: The WHO COVID-19 database from inception to 20 April 2022., Risk of Bias Assessment: The National Institutes of Health tools., Synthesis of Results: The proportion of patients with positive results for SARS-CoV-2 and the proportion of patients with a viral duration/persistence of at least 14 days in each fluid was calculated using fixed or random effects models., Included Studies: A total of 182 studies with 10 023 participants., Results: The combined proportion of individuals with detection of SARS-CoV-2 was 82.6% (95% CI: 68.8% to 91.0%) in saliva, 1.6% (95% CI: 0.9% to 2.6%) in semen, 2.7% (95% CI: 1.8% to 4.0%) in vaginal secretion, 3.8% (95% CI: 1.9% to 7.6%) in urine and 31.8% (95% CI: 26.4% to 37.7%) in faeces/rectal swabs. The maximum viral persistence for faeces/rectal secretions was 210 days, followed by semen 121 days, saliva 112 days, urine 77 days and vaginal secretions 13 days. Culturable SARS-CoV-2 was positive for saliva and faeces., Limitations: Scarcity of longitudinal studies with follow-up until negative results., Interpretation: SARS-CoV-2 RNA was detected in all fluids associated with sexual activity but was rare in semen and vaginal secretions. Ongoing droplet precautions and awareness of the potential risk of contact with faecal matter/rectal mucosa are needed., Prospero Registration Number: CRD42020204741., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate the association between Colombia's third wave when the Mu variant was predominant epidemiologically (until 75%) in Colombia and COVID-19 all-cause in-hospital mortality., Methods: In this retrospective cohort, we included hospitalized patients ≥18 years with SARS-CoV-2 infection between March 2020 to September 2021 in ten hospitals from three cities in Colombia. Description analysis, survival, and multivariate Cox regression analyses were performed to evaluate the association between the third epidemic wave and in-hospital mortality., Results: A total of 25,371 patients were included. The age-stratified time-to-mortality curves showed differences according to epidemic waves in patients ≥75 years (log-rank test p = 0.012). In the multivariate Cox analysis, the third wave was not associated with increased mortality relative to the first wave (aHR 0.95; 95%CI 0.84-1.08), but there was an interaction between age ≥75 years and the third wave finding a lower HR for mortality (aHR 0.56, 95%CI 0.36-0.86)., Conclusions: We did not find an increase in in-hospital mortality during the third epidemic wave in which the Mu variant was predominant in Colombia. The reduced hazard in mortality in patients ≥75 years hospitalized in the third wave could be explained by the high coverage of SARS-CoV-2 vaccination in this population and patients with underlying conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Undetected and unmonitored hypertension carries substantial mortality and morbidity, especially during pregnancy. We assessed the accuracy of OptiBP TM , a smartphone application for estimating blood pressure (BP), across diverse settings. The study was conducted in community settings: Gaibandha, Bangladesh and Ifakara, Tanzania for general populations, and Kalafong Provincial Tertiary Hospital, South Africa for pregnant populations. Based on guidance from the International Organization for Standardization (ISO) 81,060-2:2018 for non-invasive BP devices and global consensus statement, we compared BP measurements taken by two independent trained nurses on a standard auscultatory cuff to the BP measurements taken by a research version of OptiBP TM called CamBP. For ISO criterion 1, the mean error was 0.5 ± 5.8 mm Hg for the systolic blood pressure (SBP) and 0.1 ± 3.9 mmHg for the diastolic blood pressure (DBP) in South Africa; 0.8 ± 7.0 mmHg for the SBP and -0.4 ± 4.0 mmHg for the DBP in Tanzania; 3.3 ± 7.4 mmHg for the SBP and -0.4 ± 4.3 mmHg for the DBP in Bangladesh. For ISO criterion 2, the average standard deviation of the mean error per subject was 4.9 mmHg for the SBP and 3.4 mmHg for the DBP in South Africa; 6.3 mmHg for the SBP and 3.6 mmHg for the DBP in Tanzania; 6.4 mmHg for the SBP and 3.8 mmHg for the DBP in Bangladesh. OptiBP TM demonstrated accuracy against ISO standards in study populations, including pregnant populations, except in Bangladesh for SBP (criterion 2). Further research is needed to improve performance across different populations and integration within health systems., (© 2023. The Author(s).)

Background: Multi-arm multi-stage trials are an efficient, adaptive approach for testing many treatments simultaneously within one protocol. In settings where numbers of patients available to be entered into trials and resources might be limited, such as primary postpartum haemorrhage, it may be necessary to select a pre-specified subset of arms at interim stages even if they are all showing some promise against the control arm. This will put a limit on the maximum number of patients required and reduce the associated costs. Motivated by the World Health Organization Refractory HaEmorrhage Devices trial in postpartum haemorrhage, we explored the properties of such a selection design in a randomised phase III setting and compared it with other alternatives. The objectives are: (1) to investigate how the timing of treatment selection affects the operating characteristics; (2) to explore the use of an information-rich (continuous) intermediate outcome to select the best-performing arm, out of four treatment arms, compared with using the primary (binary) outcome for selection at the interim stage; and (3) to identify factors that can affect the efficiency of the design., Methods: We conducted simulations based on the refractory haemorrhage devices multi-arm multi-stage selection trial to investigate the impact of the timing of treatment selection and applying an adaptive allocation ratio on the probability of correct selection, overall power and familywise type I error rate. Simulations were also conducted to explore how other design parameters will affect both the maximum sample size and trial timelines., Results: The results indicate that the overall power of the trial is bounded by the probability of 'correct' selection at the selection stage. The results showed that good operating characteristics are achieved if the treatment selection is conducted at around 17% of information time. Our results also showed that although randomising more patients to research arms before selection will increase the probability of selecting correctly, this will not increase the overall efficiency of the (selection) design compared with the fixed allocation ratio of 1:1 to all arms throughout., Conclusions: Multi-arm multi-stage selection designs are efficient and flexible with desirable operating characteristics. We give guidance on many aspects of these designs including selecting the intermediate outcome measure, the timing of treatment selection, and choosing the operating characteristics.

Objective: This sequential, prospective meta-analysis sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to disease severity, maternal morbidities, neonatal mortality and morbidity, and adverse birth outcomes., Data Sources: We prospectively invited study investigators to join the sequential, prospective meta-analysis via professional research networks beginning in March 2020., Study Eligibility Criteria: Eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area., Methods: We included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a 2-stage meta-analysis., Results: We collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (preexisting diabetes mellitus, hypertension, cardiovascular disease) vs those without were at higher risk for COVID-19 severity and adverse pregnancy outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% confidence interval, 1.12-2.71) more likely to be admitted to the intensive care unit. Pregnant women who were underweight before pregnancy were at higher risk of intensive care unit admission (relative risk, 5.53; 95% confidence interval, 2.27-13.44), ventilation (relative risk, 9.36; 95% confidence interval, 3.87-22.63), and pregnancy-related death (relative risk, 14.10; 95% confidence interval, 2.83-70.36). Prepregnancy obesity was also a risk factor for severe COVID-19 outcomes including intensive care unit admission (relative risk, 1.81; 95% confidence interval, 1.26-2.60), ventilation (relative risk, 2.05; 95% confidence interval, 1.20-3.51), any critical care (relative risk, 1.89; 95% confidence interval, 1.28-2.77), and pneumonia (relative risk, 1.66; 95% confidence interval, 1.18-2.33). Anemic pregnant women with COVID-19 also had increased risk of intensive care unit admission (relative risk, 1.63; 95% confidence interval, 1.25-2.11) and death (relative risk, 2.36; 95% confidence interval, 1.15-4.81)., Conclusion: We found that pregnant women with comorbidities including diabetes mellitus, hypertension, and cardiovascular disease were at increased risk for severe COVID-19-related outcomes, maternal morbidities, and adverse birth outcomes. We also identified several less commonly known risk factors, including HIV infection, prepregnancy underweight, and anemia. Although pregnant women are already considered a high-risk population, special priority for prevention and treatment should be given to pregnant women with these additional risk factors., (Copyright © 2022. Published by Elsevier Inc.)

Background: Whilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, individual-level data on infecting variants are typically only available for a minority of patients and settings., Methods: Here, we propose an innovative approach to study changes in COVID-19 hospital presentation and outcomes after the Omicron variant emergence using publicly available population-level data on variant relative frequency to infer SARS-CoV-2 variants likely responsible for clinical cases. We apply this method to data collected by a large international clinical consortium before and after the emergence of the Omicron variant in different countries., Results: Our analysis, that includes more than 100,000 patients from 28 countries, suggests that in many settings patients hospitalised with Omicron variant infection less often presented with commonly reported symptoms compared to patients infected with pre-Omicron variants. Patients with COVID-19 admitted to hospital after Omicron variant emergence had lower mortality compared to patients admitted during the period when Omicron variant was responsible for only a minority of infections (odds ratio in a mixed-effects logistic regression adjusted for likely confounders, 0.67 [95% confidence interval 0.61-0.75]). Qualitatively similar findings were observed in sensitivity analyses with different assumptions on population-level Omicron variant relative frequencies, and in analyses using available individual-level data on infecting variant for a subset of the study population., Conclusions: Although clinical studies with matching viral genomic information should remain a priority, our approach combining publicly available data on variant frequency and a multi-country clinical characterisation dataset with more than 100,000 records allowed analysis of data from a wide range of settings and novel insights on real-world heterogeneity of COVID-19 presentation and clinical outcome., Funding: Bronner P. Gonçalves, Peter Horby, Gail Carson, Piero L. Olliaro, Valeria Balan, Barbara Wanjiru Citarella, and research costs were supported by the UK Foreign, Commonwealth and Development Office (FCDO) and Wellcome [215091/Z/18/Z, 222410/Z/21/Z, 225288/Z/22/Z]; and Janice Caoili and Madiha Hashmi were supported by the UK FCDO and Wellcome [222048/Z/20/Z]. Peter Horby, Gail Carson, Piero L. Olliaro, Kalynn Kennon and Joaquin Baruch were supported by the Bill & Melinda Gates Foundation [OPP1209135]; Laura Merson was supported by University of Oxford's COVID-19 Research Response Fund - with thanks to its donors for their philanthropic support. Matthew Hall was supported by a Li Ka Shing Foundation award to Christophe Fraser. Moritz U.G. Kraemer was supported by the Branco Weiss Fellowship, Google.org, the Oxford Martin School, the Rockefeller Foundation, and the European Union Horizon 2020 project MOOD (#874850). The contents of this publication are the sole responsibility of the authors and do not necessarily reflect the views of the European Commission. Contributions from Srinivas Murthy, Asgar Rishu, Rob Fowler, James Joshua Douglas, François Martin Carrier were supported by CIHR Coronavirus Rapid Research Funding Opportunity OV2170359 and coordinated out of Sunnybrook Research Institute. Contributions from Evert-Jan Wils and David S.Y. Ong were supported by a grant from foundation Bevordering Onderzoek Franciscus; and Andrea Angheben by the Italian Ministry of Health "Fondi Ricerca corrente-L1P6" to IRCCS Ospedale Sacro Cuore-Don Calabria. The data contributions of J.Kenneth Baillie, Malcolm G. Semple, and Ewen M. Harrison were supported by grants from the National Institute for Health Research (NIHR; award CO-CIN-01), the Medical Research Council (MRC; grant MC&#95;PC&#95;19059), and by the NIHR Health Protection Research Unit (HPRU) in Emerging and Zoonotic Infections at University of Liverpool in partnership with Public Health England (PHE) (award 200907), NIHR HPRU in Respiratory Infections at Imperial College London with PHE (award 200927), Liverpool Experimental Cancer Medicine Centre (grant C18616/A25153), NIHR Biomedical Research Centre at Imperial College London (award IS-BRC-1215-20013), and NIHR Clinical Research Network providing infrastructure support. All funders of the ISARIC Clinical Characterisation Group are listed in the appendix., Competing Interests: BG, MH, WJ, VB, CK, AR, JB, LR, AD, JD, BC, MP, US, JB, DA, YA, AR, JC, EH, CF, MM, YC, XW, SB, ST, LS, AR, RR, DO, MH, GC, JD, MK, EW, PH, LM, PO No competing interests declared, SM declares receiving salary support from the Health Research Foundation and Innovative Medicines Canada Chair in Pandemic Preparedness Research, MS reports grants from DHSC National Institute of Health Research UK, from the Medical Research Council UK, and from the Health Protection Research Unit in Emerging & Zoonotic Infections, University of Liverpool, supporting the conduct of the study; other interest in Integrum Scientific LLC, Greensboro, NC, USA, outside the submitted work, AM declares consulting fees for Gilead and MSD, presentation fees for GILEAD, Pfizer and MSD, support for attending ECCMID from Gilead, and advisory board fees for MSD and Gilead, AA declares support from Italian Ministry of Health - "Fondi Ricerca Corrente" Line1 Project 5 to IRCCS Sacro Cuore - Don Calabria Hospital, FC declares a grant from the Canadian Institute of Health Research, JG declares support by Pfizer, Angelini and MSD to attend meetings (registration to meetings only), JD declares personal fees from lectures from Sunovion and Merck and consulting fees from Pfizer, AS has been an investigator in COVID-19 clinical trials by Algernon Pharmaceuticals, Atea Pharmaceuticals, Regeneron Pharmaceuticals, Diffusion Pharmaceuticals, Celltrion, Inc and Atriva Therapeutics, outside the scope of the submitted work, RF declares a peer reviewed research grant from the Canadian Institutes of Health Research, See Appendix 1 for competing interests for group author members, (© 2022, Gonçalves et al.)

Background: WHO has established a Global Clinical Platform for the clinical characterisation of COVID-19 among hospitalised individuals. We assessed whether people living with HIV hospitalised with COVID-19 had increased odds of severe presentation and of in-hospital mortality compared with individuals who were HIV-negative and associated risk factors., Methods: Between Jan 1, 2020, and July 1, 2021, anonymised individual-level data from 338 566 patients in 38 countries were reported to WHO. Using the Platform pooled dataset, we performed descriptive statistics and regression analyses to compare outcomes in the two populations and identify risk factors., Findings: Of 197 479 patients reporting HIV status, 16 955 (8·6%) were people living with HIV. 16 283 (96.0%) of the 16 955 people living with HIV were from Africa; 10 603 (62·9%) were female and 6271 (37·1%) were male; the mean age was 45·5 years (SD 13·7); 6339 (38·3%) were admitted to hospital with severe illness; and 3913 (24·3%) died in hospital. Of the 10 166 people living with HIV with known antiretroviral therapy (ART) status, 9302 (91·5%) were on ART. Compared with individuals without HIV, people living with HIV had 15% increased odds of severe presentation with COVID-19 (aOR 1·15, 95% CI 1·10-1·20) and were 38% more likely to die in hospital (aHR 1·38, 1·34-1·41). Among people living with HIV, male sex, age 45-75 years, and having chronic cardiac disease or hypertension increased the odds of severe COVID-19; male sex, age older than 18 years, having diabetes, hypertension, malignancy, tuberculosis, or chronic kidney disease increased the risk of in-hospital mortality. The use of ART or viral load suppression were associated with a reduced risk of poor outcomes; however, HIV infection remained a risk factor for severity and mortality regardless of ART and viral load suppression status., Interpretation: In this sample of hospitalised people contributing data to the WHO Global Clinical Platform for COVID-19, HIV was an independent risk factor for both severe COVID-19 at admission and in-hospital mortality. These findings have informed WHO immunisation policy that prioritises vaccination for people living with HIV. As the results mostly reflect the data contribution from Africa, this analysis will be updated as more data from other regions become available., Funding: None., Translation: For the French translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests RH received funding from the Wellcome Trust, Canadian Institute of Health Research, UK Research and Innovation/Medical Research Council, and International COVID-19 Data Alliance–Health Data Research UK. All other authors declare no competing interests., (© 2022 This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Background: In 2016, WHO launched the Global Health Sector Strategy on STIs, 2016-2021 (GHSS) to provide guidance and benchmarks for country achievement by 2020 and four global targets for achievement by 2030., Methods: A country survey jointly developed by experienced technical personnel at WHO Headquarters (HQ) and WHO regional offices was reviewed and distributed by WHO regional advisors to 194 WHO Member States in September-March 2020. The survey sought to assess implementation and prioritization of STI policy, surveillance, service delivery, commodity availability, and surveillance based on targets of the GHSS., Results: A majority (58%, 112/194) of countries returned a completed survey reflecting current (2019) STI activities. The regions with the highest survey completion rates were South-East Asia Region (91%, 10/11), Region of the Americas (71%, 25/35) and Western Pacific Region (67%, 18/27). Having a national STI strategy was reported by 64% (72/112) and performing STI surveillance activities by 88% (97/110) of reporting countries. Availability of STI services within primary health clinics was reported by 88% of countries (99/112); within HIV clinics by 92% (103/112), and within reproductive health services by 85% (95/112). Existence of a national strategy to eliminate mother-to-child transmission of HIV and syphilis (EMTCT) was reported by 70% of countries (78/112). Antimicrobial resistance (AMR) monitoring for gonococcal infection (gonorrhoea) was reported by 64% (57/89) of reporting countries with this laboratory capacity. Inclusion of HPV vaccine for young women in the national immunization schedule was reported by 59% (65/110) and availability of cervical cancer screening was reported by 91% (95/104). Stockouts of STI medicines, primarily benzathine penicillin, within the prior four years were reported by 34% (37/110) of countries., Conclusions: Mechanisms to support improvements to STI service delivery through national-level policy, commitment, programming and surveillance are needed to operationalize, accelerate and monitor progress towards achievement of the 2030 global STI strategy targets., Competing Interests: The authors have declared that no competing interests exist.

Importance: Suicide and suicide attempts are persistent and increasing public health problems. Observational studies and meta-analyses of randomized clinical trials have suggested that lithium may prevent suicide in patients with bipolar disorder or depression., Objective: To assess whether lithium augmentation of usual care reduces the rate of repeated episodes of suicide-related events (repeated suicide attempts, interrupted attempts, hospitalizations to prevent suicide, and deaths from suicide) in participants with bipolar disorder or depression who have survived a recent event., Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial assessed lithium vs placebo augmentation of usual care in veterans with bipolar disorder or depression who had survived a recent suicide-related event. Veterans at 29 VA medical centers who had an episode of suicidal behavior or an inpatient admission to prevent suicide within 6 months were screened between July 1, 2015, and March 31, 2019., Interventions: Participants were randomized to receive extended-release lithium carbonate beginning at 600 mg/d or placebo., Main Outcomes and Measures: Time to the first repeated suicide-related event, including suicide attempts, interrupted attempts, hospitalizations specifically to prevent suicide, and deaths from suicide., Results: The trial was stopped for futility after 519 veterans (mean [SD] age, 42.8 [12.4] years; 437 [84.2%] male) were randomized: 255 to lithium and 264 to placebo. Mean lithium concentrations at 3 months were 0.54 mEq/L for patients with bipolar disorder and 0.46 mEq/L for patients with major depressive disorder. No overall difference in repeated suicide-related events between treatments was found (hazard ratio, 1.10; 95% CI, 0.77-1.55). No unanticipated safety concerns were observed. A total of 127 participants (24.5%) had suicide-related outcomes: 65 in the lithium group and 62 in the placebo group. One death occurred in the lithium group and 3 in the placebo group., Conclusions and Relevance: In this randomized clinical trial, the addition of lithium to usual Veterans Affairs mental health care did not reduce the incidence of suicide-related events in veterans with major depression or bipolar disorders who experienced a recent suicide event. Therefore, simply adding lithium to existing medication regimens is unlikely to be effective for preventing a broad range of suicide-related events in patients who are actively being treated for mood disorders and substantial comorbidities., Trial Registration: ClinicalTrials.gov Identifier: NCT01928446.

Background: Violence against women is a serious public health concern, and is highly prevalent globally, including in India. Health-care providers [HCPs] can play an important role in addressing and reducing negative consequences of violence against women. We implemented a pre-post intervention study of HCP training in three tertiary care facilities in Maharashtra, India., Methods: The study used a pre-post intervention design with assessment of HCPs' (n = 201) knowledge, attitudes, perceived preparedness and practice at three time points: before training, after training and at 6 months follow- up., Results: Total median score of knowledge about common signs and symptoms of violence (8.89 vs, 10.00), attitudes towards acceptability of violence (9.05 vs. 10.00), individual (6.74 vs. 10.00) and system level preparedness (6.11 vs. 8.14) improved from pre to post- training. The generalized estimating equation [GEE] model, adjusted for age, sex, site and department, showed an improvement in knowledge, attitudes and preparedness post- training. The change from pre to 6 months follow- up was not significant for attitude., Conclusions: This package of interventions, including training of HCPs, improved HCPs' knowledge, attitudes and practices, yet changes in attitudes and preparedness did not sustain over time. This study indicates feasibility and positive influence of a multi-component intervention to improve HCP readiness to respond to violence against women in a low-resource setting. Future phases of intervention development include adapting this intervention package for primary and secondary health facilities in this context, and future research should assess these interventions using a rigorous experimental design. Finally, these results can be used to advocate for multi-layered, systems-based approaches to strengthening health response to violence against women., (© 2021. The Author(s).)

Introduction: Abortion-related complications are a significant cause of morbidity and mortality among women in many Latin American and Caribbean (LAC) countries. The objective of this study was to characterise abortion-related complication severity, describe the management of these complications and report women's experiences with abortion care in selected countries of the Americas region., Methods: This is a cross-sectional study of 70 health facilities across six countries in the region. We collected data on women's characteristics including socio-demographics, obstetric history, clinical information, management procedures and using Audio Computer-Assisted Self-Interviewing (ACASI) survey the experience of abortion care. Descriptive bivariate analysis was performed for women's characteristics, management of complications and reported experiences of abortion care by severity of complications, organised in five hierarchical mutually exclusive categories based on indicators present at assessment. Generalised linear estimation models were used to assess the association between women's characteristics and severity of complications., Results: We collected data on 7983 women with abortion-related complications. Complications were classified as mild (46.3%), moderate (49.5%), potentially life-threatening (3.1%), near-miss cases (1.1%) and deaths (0.2%). Being single, having a gestational age of ≥13 weeks and having expelled products of conception before arrival at the facility were significantly associated with experiencing severe maternal outcomes compared with mild complications.Management of abortion-related complications included both uterotonics and uterine evacuation for two-thirds of the women while one-third received uterine evacuation only. Surgical uterine evacuation was performed in 93.2% (7437/7983) of women, being vacuum aspiration the most common one (5007/7437, 67.4%).Of the 327 women who completed the ACASI survey, 16.5% reported having an induced abortion, 12.5% of the women stated that they were not given explanations regarding their care nor were able to ask questions during their examination and treatment with percentages increasing with the severity of morbidity., Conclusions: This is one of the first studies using a standardised methodology to measure severity of abortion-related complications and women's experiences with abortion care in LAC. Results aim to inform policies and programmes addressing sexual and reproductive rights and health in the region., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Inclusion of pregnant women in COVID-19 clinical trials would allow evaluation of effective therapies that might improve maternal health, pregnancy, and birth outcomes, and avoid the delay of developing treatment recommendations for pregnant women. We explored the inclusion of pregnant women in treatment trials of COVID-19 by reviewing ten international clinical trial registries at two timepoints in 2020. We identified 155 COVID-19 treatment studies of non-biological drugs for the April 7-10, 2020 timepoint, of which 124 (80%) specifically excluded pregnant women. The same registry search for the July 10-15, 2020 timepoint, yielded 722 treatment studies, of which 538 (75%) specifically excluded pregnant women. We then focused on studies that included at least one of six drugs (remdesivir, lopinavir-ritonavir, interferon beta, corticosteroids, chloroquine and hydroxychloroquine, and ivermectin) under evaluation for COVID-19. Of 176 such studies, 130 (74%) listed pregnancy as an exclusion criterion. Of 35 studies that evaluated high-dose vitamin treatment for COVID-19, 27 (77%) excluded pregnant women. Despite the surge in treatment studies for COVID-19, the proportion excluding pregnant women remains consistent. Exclusion was not well justified as many of the treatments being evaluated have no or low safety concerns during pregnancy. Inclusion of pregnant women in clinical treatment trials is urgently needed to identify effective COVID-19 treatment for this population., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

An interrupted time series with a parallel control group (ITS-CG) design is a powerful quasi-experimental design commonly used to evaluate the effectiveness of an intervention, on accelerating uptake of useful public health products, and can be used in the presence of regularly collected data. This paper illustrates how a segmented Poisson model that utilizes general estimating equations (GEE) can be used for the ITS-CG study design to evaluate the effectiveness of a complex social accountability intervention on the level and rate of uptake of modern contraception. The intervention was gradually rolled-out over time to targeted intervention communities in Ghana and Tanzania, with control communities receiving standard of care, as per national guidelines. Two ITS GEE segmented regression models are proposed for evaluating of the uptake. The first, a two-segmented model, fits the data collected during pre-intervention and post-intervention excluding that collected during intervention roll-out. The second, a three-segmented model, fits all data including that collected during the roll-out. A much simpler difference-in-difference (DID) GEE Poisson regression model is also illustrated. Mathematical formulation of both ITS-segmented Poisson models and that of the DID Poisson model, interpretation and significance of resulting regression parameters, and accounting for different sources of variation and lags in intervention effect are respectively discussed. Strengths and limitations of these models are highlighted. Segmented ITS modelling remains valuable for studying the effect of intervention interruptions whether gradual changes, over time, in the level or trend in uptake of public health practices are attributed by the introduced intervention. Trial Registration : The Australian New Zealand Clinical Trials registry. Trial registration number : ACTRN12619000378123. Trial Registration date : 11-March-2019., Competing Interests: Conflict of interestNo competing interests were declared., (© The Author(s) 2020.)

Introduction: Complications due to unsafe abortions are an important cause of morbidity and mortality in many sub-Saharan African countries. We aimed to characterise abortion-related complication severity, describe their management, and to report women's experience of abortion care in Africa., Methods: A cross-sectional study was implemented in 210 health facilities across 11 sub-Saharan African countries. Data were collected on women's characteristics, clinical information and women's experience of abortion care (using the audio computer-assisted self-interviewing (ACASI) system). Severity of abortion complications were organised in five hierarchical mutually exclusive categories based on indicators present at assessment. Descriptive bivariate analysis was performed for women's characteristics, management of complications and reported experiences of abortion care by severity. Generalised linear estimation models were used to assess the association between women's characteristics and severity of complications., Results: There were 13 657 women who had an abortion-related complication: 323 (2.4%) women were classified with severe maternal outcomes, 957 (7.0%) had potentially life-threatening complications, 7953 (58.2%) had moderate complications and 4424 (32.4%) women had mild complications. Women who were single, multiparous, presenting ≥13 weeks of gestational age and where expulsion of products of conception occurred prior to arrival to facility were more likely to experience severe complications. For management, the commonly used mechanical methods of uterine evacuation were manual vacuum aspiration (76.9%), followed by dilation and curettage (D&C) (20.1%). Most frequently used uterotonics were oxytocin (50∙9%) and misoprostol (22.7%). Via ACASI, 602 (19.5%) women reported having an induced abortion. Of those, misoprostol was the most commonly reported method (54.3%)., Conclusion: There is a critical need to increase access to and quality of evidence-based safe abortion, postabortion care and to improve understanding around women's experiences of abortion care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: Amid efforts to improve the quality of care for women and neonates during childbirth, there is growing interest in the experience of care, including respectful care practices. However, there is little research on the prevalence of practices that might constitute mistreatment of neonates. This study aims to describe the care received by neonates up to 2 h after birth in a sample of three countries in west Africa., Methods: Data from this multicountry, facility-based, observational study were collected on 15 neonatal care practices across nine facilities in Ghana, Guinea, and Nigeria, as part of WHO's wider multicountry study on how women are treated during childbirth. Women were eligible if they were admitted to the participating health facilities for childbirth, in early established labour or active labour, aged 15 years or older, and provided written informed consent on behalf of themselves and their neonate. All labour observations were continuous, one-to-one observations of women and neonates by independent data collectors. Descriptive statistics and multivariate logistic regressions were used to examine associations between these neonatal care practices, maternal and neonate characteristics, and maternal mistreatment. Early neonate deaths, stillbirths, and higher order multiple births were excluded from analysis., Findings: Data collection took place from Sept 19, 2016, to Feb 26, 2017, in Nigeria; from Aug 1, 2017, to Jan 18, 2018, in Ghana; and from July 1 to Oct 30, 2017, in Guinea. We included data for 362 women-neonate dyads (356 [98%] with available data for neonatal care practices) in Nigeria, 760 (749 [99%]) in Ghana, and 558 (522 [94%]) in Guinea. Delayed cord clamping was done for most neonates (1493 [91·8%] of 1627); other practices, such as skin-to-skin contact, were less commonly done (1048 [64·4%]). During the first 2 h after birth, separation of the mother and neonate occurred in 844 (51·9%) of 1627 cases; and was more common for mothers who were single (adjusted odds ratio [AOR; adjusting for country, maternal age, education, marital status, neonate weight at birth, and neonate sex] 1·8, 95% CI 1·3-2·6) than those who were married or cohabiting. Lack of maternal education was associated with increased likelihood of neonates not receiving recommended breastfeeding practices. Neonates with a low birthweight (<2·5 kg) were more likely (1·7, 1·1-2·8) to not begin breastfeeding on demand than full weight neonates. When women experienced physical abuse from providers within 1 h before childbirth, their neonates were more likely to be slapped (AOR 1·9, 1·1-3·9)., Interpretation: A high proportion of neonates did not receive recommended care practices, and some received practices that might constitute mistreatment. Further research is needed on understanding and measuring mistreatment to improve care, including respectful care, for mothers and neonates., Funding: US Agency for International Development, and the UNDP/UN Population Fund/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, WHO., (Copyright © 2021 This is an Open Access article published under the CC BY-NC-ND 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Background: Evidence has shown the benefits of labour companions during childbirth. Few studies have documented the relationship between the absence of labour companions and mistreatment of women during childbirth in low-income and middle-income countries using a standardised tool., Methods: We conducted a secondary analysis of the WHO multi-country study on how women are treated during childbirth, where a cross-sectional community survey was conducted with women up to 8 weeks after childbirth in Ghana, Guinea, Nigeria and Myanmar. Descriptive analysis and multivariable logistic regression were used to examine whether labour companionship was associated with various types of mistreatment., Results: Of 2672 women, about half (50.4%) reported the presence of a labour companion. Approximately half (49.6%) of these women reported that the timing of support was during labour and after childbirth and most of the labour companions (47.0%) were their family members. Across Ghana, Guinea and Nigeria, women without a labour companion were more likely to report physical abuse, non-consented medical procedures and poor communication compared with women with a labour companion. However, there were country-level variations. In Guinea, the absence of labour companionship was associated with any physical abuse, verbal abuse, or stigma or discrimination (adjusted OR (AOR) 3.6, 1.9-6.9) and non-consented vaginal examinations (AOR 3.2, 1.6-6.4). In Ghana, it was associated with non-consented vaginal examinations (AOR 2.3, 1.7-3.1) and poor communication (AOR 2.0, 1.3-3.2). In Nigeria, it was associated with longer wait times (AOR 0.6, 0.3-0.9)., Conclusion: Labour companionship is associated with lower levels of some forms of mistreatment that women experience during childbirth, depending on the setting. Further work is needed to ascertain how best to implement context-specific labour companionship to ensure benefits while maintaining women's choices and autonomy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Background: Syphilis is a sexually and vertically transmitted infection caused by the bacteria Treponema pallidum for which there are few proven alternatives to penicillin for treatment. For pregnant women infected with syphilis, penicillin is the only WHO-recommended treatment that will treat the mother and cross the placenta to treat the unborn infant and prevent congenital syphilis. Recent shortages, national level stockouts as well as other barriers to penicillin use call for the urgent identification of alternative therapies to treat pregnant women infected with syphilis., Methods: This prospective, randomized, non-comparative trial will enroll non-pregnant women aged 18 years and older with active syphilis, defined as a positive rapid treponemal and a positive non-treponemal RPR test with titer ≥1:16. Women will be a, domized in a 2:1 ratio to receive the oral third generation cephalosporin cefixime at a dose of 400 mg two times per day for 10 days (n = 140) or benzathine penicillin G 2.4 million units intramuscularly based on the stage of syphilis infection (n = 70). RPR titers will be collected at enrolment, and at three, six, and nine months following treatment. Participants experiencing a 4-fold (2 titer) decline by 6 months will be considered as having an adequate or curative treatment response., Discussion: Demonstration of efficacy of cefixime in the treatment of active syphilis in this Phase 2 trial among non-pregnant women will inform a proposed randomized controlled trial to evaluate cefixime as an alternative treatment for pregnant women with active syphilis to evaluate prevention of congenital syphilis., Trial Registration: Trial identifier: www.Clinicaltrials.gov, NCT03752112. Registration Date: November 22, 2018.

An amendment to this paper has been published and can be accessed via the original article.

Background: Women across the world are mistreated during childbirth. We aimed to develop and implement evidence-informed, validated tools to measure mistreatment during childbirth, and report results from a cross-sectional study in four low-income and middle-income countries., Methods: We prospectively recruited women aged at least 15 years in twelve health facilities (three per country) in Ghana, Guinea, Myanmar, and Nigeria between Sept 19, 2016, and Jan 18, 2018. Continuous observations of labour and childbirth were done from admission up to 2 h post partum. Surveys were administered by interviewers in the community to women up to 8 weeks post partum. Labour observations were not done in Myanmar. Data were collected on sociodemographics, obstetric history, and experiences of mistreatment., Findings: 2016 labour observations and 2672 surveys were done. 838 (41·6%) of 2016 observed women and 945 (35·4%) of 2672 surveyed women experienced physical or verbal abuse, or stigma or discrimination. Physical and verbal abuse peaked 30 min before birth until 15 min after birth (observation). Many women did not consent for episiotomy (observation: 190 [75·1%] of 253; survey: 295 [56·1%] of 526) or caesarean section (observation: 35 [13·4%] of 261; survey: 52 [10·8%] of 483), despite receiving these procedures. 133 (5·0%) of 2672 women or their babies were detained in the facility because they were unable to pay the bill (survey). Younger age (15-19 years) and lack of education were the primary determinants of mistreatment (survey). For example, younger women with no education (odds ratio [OR] 3·6, 95% CI 1·6-8·0) and younger women with some education (OR 1·6, 1·1-2·3) were more likely to experience verbal abuse, compared with older women (≥30 years), adjusting for marital status and parity., Interpretation: More than a third of women experienced mistreatment and were particularly vulnerable around the time of birth. Women who were younger and less educated were most at risk, suggesting inequalities in how women are treated during childbirth. Understanding drivers and structural dimensions of mistreatment, including gender and social inequalities, is essential to ensure that interventions adequately account for the broader context., Funding: United States Agency for International Development and the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, WHO., (This is an Open Access article published under the CC BY 3.0 IGO license which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. In any use of this article, there should be no suggestion that WHO endorses any specific organisation, products or services. The use of the WHO logo is not permitted. This notice should be preserved along with the article's original URL.)

Objective: To generate estimates of the global prevalence and incidence of urogenital infection with chlamydia, gonorrhoea, trichomoniasis and syphilis in women and men, aged 15-49 years, in 2016., Methods: For chlamydia, gonorrhoea and trichomoniasis, we systematically searched for studies conducted between 2009 and 2016 reporting prevalence. We also consulted regional experts. To generate estimates, we used Bayesian meta-analysis. For syphilis, we aggregated the national estimates generated by using Spectrum-STI., Findings: For chlamydia, gonorrhoea and/or trichomoniasis, 130 studies were eligible. For syphilis, the Spectrum-STI database contained 978 data points for the same period. The 2016 global prevalence estimates in women were: chlamydia 3.8% (95% uncertainty interval, UI: 3.3-4.5); gonorrhoea 0.9% (95% UI: 0.7-1.1); trichomoniasis 5.3% (95% UI:4.0-7.2); and syphilis 0.5% (95% UI: 0.4-0.6). In men prevalence estimates were: chlamydia 2.7% (95% UI: 1.9-3.7); gonorrhoea 0.7% (95% UI: 0.5-1.1); trichomoniasis 0.6% (95% UI: 0.4-0.9); and syphilis 0.5% (95% UI: 0.4-0.6). Total estimated incident cases were 376.4 million: 127.2 million (95% UI: 95.1-165.9 million) chlamydia cases; 86.9 million (95% UI: 58.6-123.4 million) gonorrhoea cases; 156.0 million (95% UI: 103.4-231.2 million) trichomoniasis cases; and 6.3 million (95% UI: 5.5-7.1 million) syphilis cases., Conclusion: Global estimates of prevalence and incidence of these four curable sexually transmitted infections remain high. The study highlights the need to expand data collection efforts at country level and provides an initial baseline for monitoring progress of the World Health Organization global health sector strategy on sexually transmitted infections 2016-202 1.

Background: The call for women-centred approaches to reduce labour interventions, particularly primary caesarean section, has renewed an interest in gaining a better understanding of natural labour progression., Objective: To synthesise available data on the cervical dilatation patterns during spontaneous labour of 'low-risk' women with normal perinatal outcomes., Search Strategy: PubMed, EMBASE, CINAHL, POPLINE, Global Health Library, and reference lists of eligible studies., Selection Criteria: Observational studies and other study designs., Data Collection and Analysis: Two authors extracted data on: maternal characteristics; labour interventions; the duration of labour centimetre by centimetre; and the duration of labour from dilatation at admission through to 10 cm. We pooled data across studies using weighted medians and employed the Bootstrap-t method to generate the corresponding confidence bounds., Main Results: Seven observational studies describing labour patterns for 99 971 women met our inclusion criteria. The median time to advance by 1 cm in nulliparous women was longer than 1 hour until a dilatation of 5 cm was reached, with markedly rapid progress after 6 cm. Similar labour progression patterns were observed in parous women. The 95th percentiles for both parity groups suggest that it was not uncommon for some women to reach 10 cm, despite dilatation rates that were much slower than the 1-cm/hour threshold for most part of their first stage of labours., Conclusion: An expectation of a minimum cervical dilatation threshold of 1 cm/hour throughout the first stage of labour is unrealistic for most healthy nulliparous and parous women. Our findings call into question the universal application of clinical standards that are conceptually based on an expectation of linear labour progress in all women., Funding: UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research, World Health Organization, and the United States Agency for International Development (USAID)., Tweetable Abstract: Cervical dilatation threshold of 1 cm/hour throughout labour is unrealistic for most women, regardless of parity., (© 2017 World Health Organization; licensed by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.)

Background: Intravenous sodium bicarbonate and oral acetylcysteine are widely used to prevent acute kidney injury and associated adverse outcomes after angiography without definitive evidence of their efficacy., Methods: Using a 2-by-2 factorial design, we randomly assigned 5177 patients at high risk for renal complications who were scheduled for angiography to receive intravenous 1.26% sodium bicarbonate or intravenous 0.9% sodium chloride and 5 days of oral acetylcysteine or oral placebo; of these patients, 4993 were included in the modified intention-to-treat analysis. The primary end point was a composite of death, the need for dialysis, or a persistent increase of at least 50% from baseline in the serum creatinine level at 90 days. Contrast-associated acute kidney injury was a secondary end point., Results: The sponsor stopped the trial after a prespecified interim analysis. There was no interaction between sodium bicarbonate and acetylcysteine with respect to the primary end point (P=0.33). The primary end point occurred in 110 of 2511 patients (4.4%) in the sodium bicarbonate group as compared with 116 of 2482 (4.7%) in the sodium chloride group (odds ratio, 0.93; 95% confidence interval [CI], 0.72 to 1.22; P=0.62) and in 114 of 2495 patients (4.6%) in the acetylcysteine group as compared with 112 of 2498 (4.5%) in the placebo group (odds ratio, 1.02; 95% CI, 0.78 to 1.33; P=0.88). There were no significant between-group differences in the rates of contrast-associated acute kidney injury., Conclusions: Among patients at high risk for renal complications who were undergoing angiography, there was no benefit of intravenous sodium bicarbonate over intravenous sodium chloride or of oral acetylcysteine over placebo for the prevention of death, need for dialysis, or persistent decline in kidney function at 90 days or for the prevention of contrast-associated acute kidney injury. (Funded by the U.S. Department of Veterans Affairs Office of Research and Development and the National Health and Medical Research Council of Australia; PRESERVE ClinicalTrials.gov number, NCT01467466 .).

Importance: Keratinocyte carcinoma (ie, cutaneous basal and squamous cell carcinoma) is the most common cancer in the United States., Objective: To determine whether topical fluorouracil could prevent surgically treated keratinocyte carcinoma., Design, Setting, and Participants: The Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial was a randomized, double-blind, placebo-controlled trial of topical fluorouracil for chemoprevention of keratinocyte carcinoma. Participants were recruited from May 2009 to September 2011 from 12 Veterans Affairs medical centers and followed until June 30, 2013. Participants were veterans (n = 932) with a history of at least 2 keratinocyte carcinomas in the past 5 years; almost all were white males and the median age was 70 years., Interventions: Application of fluorouracil, 5%, (n = 468) or vehicle control cream (n = 464) to the face and ears twice daily for 2 to 4 weeks upon randomization., Main Outcomes and Measures: Surgically treated keratinocyte, basal cell, and squamous cell carcinoma risk on the face and ears in the first year after enrollment; and time to first surgically treated keratinocyte, basal cell, and squamous cell carcinoma. The a priori hypothesis was that fluorouracil would be effective in preventing these cancers., Results: Of 932 participants (916 men [98%]; 926 white [99%]; median age, 70 years), 299 developed a basal cell carcinoma end point (95 in year 1) and 108 developed a squamous cell carcinoma end point (25 in year 1) over 4 years (median follow-up, 2.8 years). Over the entire study, there was no difference between treatment groups in time to first keratinocyte, basal cell, or squamous cell carcinoma. During the first year, however, 5 participants (1%) in the fluorouracil group developed a squamous cell carcinoma vs 20 (4%) in the control group, a 75% (95% CI, 35%-91%) risk reduction (P = .002). The 11% reduction in basal cell carcinoma risk during year 1 (45 [10%] in the fluorouracil group vs 50 [11%] in the control group) was not statistically significant (95% CI, 39% reduction to 31% increase), nor was there a significant effect on keratinocyte carcinoma risk. However, a reduction in keratinocyte carcinomas treated with Mohs surgery was observed., Conclusions and Relevance: A conventional course of fluorouracil to the face and ears substantially reduces surgery for squamous cell carcinoma for 1 year without significantly affecting the corresponding risk for basal cell carcinoma., Trial Registration: clinicaltrials.gov Identifier: NCT00847912.

Background: The estimation of an effect size is an important step in designing an adequately powered, feasible clinical trial intended to change clinical practice. During the planning phase of VA Cooperative Study #590, "Double-Blind Placebo-Controlled Study of Lithium for Preventing Repeated Suicidal Self-Directed Violence in Patients with Depression or Bipolar Disorder (Li+)," it was not clear what effect size would be considered large enough to influence prescribing behavior among practicing clinicians., Methods: We conducted an online survey of VA psychiatrists to assess their interest in the study question, their clinical experience with lithium, and their opinion about what suicide reduction rate would change their prescribing habits. The 9-item survey was hosted on SurveyMonkey © and VA psychiatrists were individually emailed an invitation to complete an anonymous online survey. Three email waves were sent over three weeks., Results: Overall, 862 of 2713 VA psychiatrists (response rate = 31.8%) responded to the anonymous survey. 74% of the respondents would refer a patient to the proposed trial, 9% would not, and 17% were unsure. Presented with suicide reduction rates in 10% increments ranging from 10 to 100%, 61% of respondents indicated that they would use lithium if suicide attempts were reduced by at least 40%; 83% would use lithium if it reduced attempts by at least 50%., Conclusions: Even with the limitations of response bias and the reliability of responses on future prescribing behavior, a survey of potential users of a clinical trial's results offers a convenient, empirical method for determining and justifying clinically relevant effect sizes.

Five-year breast cancer survivors, diagnosed after 65 years of age, may develop more incident comorbidities than similar populations free of cancer. We investigated whether older breast cancer survivors have a similar comorbidity burden 6-15 years after cancer diagnosis to matched women free of breast cancer at start of follow-up and whether incident comorbidities are associated with all-cause mortality. In this prospective cohort study, 1,361 older 5-year early-stage breast cancer survivors diagnosed between 1990 and 1994 and 1,361 age- and health system-matched women were followed for 10 years. Adjudicated medical record review captured prevalent and incident comorbidities during follow-up or until death as collected from the National Death Index. Older 5-year breast cancer survivors did not acquire incident comorbidities more often than matched women free of breast cancer in the subsequent 10 years [hazard ratio (HR) 1.0, 95 % confidence interval (95 % CI) 0.93, 1.1]. Adjusted for cohort membership, women with incident comorbidities had a higher mortality rate than those without incident comorbidities (HR 4.8, 95 % CI 4.1, 5.6). A breast cancer history continued to be a hazard for mortality 6-15 years after diagnosis (HR 1.3, 95 % CI 1.1, 1.4). We found that older breast cancer survivors who developed comorbidities had an increased all-cause mortality rate even after adjusting for age and prevalent comorbidity burden. Additionally, survivors acquire comorbidities at a rate similar to older women free of breast cancer. These results highlight the association between comorbidity burden and long-term mortality risk among older breast cancer survivors and their need for appropriate oncology and primary care follow-up.

Late effects of breast cancer affect the quality of survivorship. Using administrative data, we compared the occurrence of almost all ICD9 codes among older breast cancer survivors to that among a matched comparison cohort to generate new hypotheses. Breast cancer patients 65 years or older diagnosed 1990-1994 in 6 integrated care settings and who survived at least 5 years were matched with a cohort of women without a history of breast cancer on care setting, age, and calendar time. We collected data on the occurrence of incident ICD9 codes beginning 6 years after the breast cancer diagnosis date and continuing to year 15, and comparable data for the matched woman. We calculated hazard ratios (HRs) and 95 % confidence intervals associating breast cancer survivorship with incidence of each ICD9 code. We used semi-Bayes methods to address multiple comparisons. Older breast cancer survivors had about the same occurrence of diseases and conditions 6-15 years after breast cancer diagnosis as comparable women. The median of 564 adjusted HRs equaled 1.06, with interquartile range 0.92-1.3. The distribution of HRs pertaining to cancer-related ICD codes was shifted toward positive associations, and the distribution pertaining to cardiovascular-related ICD codes was shifted toward negative associations. In this hypothesis-scanning study, we observed little difference in the occurrence of non-breast cancer-related diseases and conditions among older, long-term breast cancer survivors, and comparable women without a history of breast cancer.

Following up on recommendations made at the time of a hospital discharge is important to patient safety. While data is lacking, specifically around the transition of patient to nursing home, it has been postulated that missed items such as laboratory tests may result in adverse patient outcomes. To determine the extent of this problem, a retrospective cohort study of subjects discharged from an academic medical center and admitted to nursing homes (NH) was followed to determine the type of discharge recommendations and the rate of completion. In addition, for the purpose of generalizability, the 30-day hospital readmission rate was calculated. 152 recommendations were made on 51 subjects. Almost a quarter of the recommendations made by the hospital discharging team were not acted upon. Furthermore, for the majority of those recommendations that were not acted upon, a reason could not be determined. In concert with national data, 20% of the subjects returned to the hospital within 30 days. Further investigation is warranted to determine if an association exists between missed recommendations and hospital readmission from the nursing home setting.

Objective: To evaluate cardiovascular disease (CVD) risk factors in older breast cancer survivors compared with a group of women without breast cancer., Study Design: The retrospective study included (1) women aged 65 or more years who were initially diagnosed with stage I or II breast cancer from 1990 to 1994 in 6 US health plans and who survived at least 5 years post-diagnosis (cases) and (2) a matched comparison group. They were followed for a maximum of 15 years., Methods: Data sources included medical charts and electronic health records. Cases (n = 1361) were matched on age, health plan site, and enrollment year to women in the comparison group (n = 1361). Subjects were followed to the first CVD outcome, health plan disenrollment, death, or study end. We compared rates of CVD in these 2 groups and used Cox proportional hazard models to estimate the hazard ratio (HR), considering body mass index, smoking history, diabetes, and hypertension., Results: The strongest predictors of CVD were smoking history (HR = 1.29; 95% confidence interval [CI], 1.15-1.46), diabetes (HR = 1.72; 95% CI, 1.48-1.99), and hypertension (HR = 1.48; 95% CI, 1.31-1.67) rather than breast cancer case-comparison status (HR = 0.97; 95% CI, 0.87-1.09)., Conclusion: Results suggest that long-term prognosis in breast cancer patients is affected by management of preexisting conditions. Assessment of comorbid conditions and effective management of diabetes and hypertension in older breast cancer survivors may lead to longer overall survival.

Introduction: Multiple tendons of the abductor pollicis longus (APL) in the anatomical snuffbox of the wrist can lead to the development of de Quervain's syndrome, which is caused by stenosing tenosynovitis. A cadaveric study was performed to establish the variations present in the tendons of the anatomical snuffbox in a Malaysian population, in the hope that this knowledge would aid clinical investigation and surgical treatment of de Quervain's tenosynovitis., Methods: Routine dissection of ten upper limbs was performed to determine the variations in the tendons of the anatomical snuffbox of the wrist., Results: In all the dissected upper limbs, the APL tendon of the first extensor compartment was found to have several (3-14) tendon slips. The insertion of the APL tendon slips in all upper limbs were at the base of the first metacarpal bone, trapezium and fascia of the opponens pollicis muscle; however, in seven specimens, they were also found to be attached to the fleshy belly of the abductor pollicis brevis muscle. In two specimens, double tendons of the extensor pollicis longus located in the third extensor compartment were inserted into the capsule of the proximal interphalangeal joints before being joined to the extensor expansion. In two other specimens, the first extensor compartment had two osseofibrous tunnels divided by a septum that separated the APL tendon from the extensor pollicis brevis tendon., Conclusion: Multiple variations were found in the anatomical snuffbox region of the dissected upper limbs. Knowledge of these variations would be useful in interventional radiology and orthopaedic surgery.

A long-term randomized trial of unstable patients with schizophrenia found no benefit of long-acting injectable (LAI) risperidone over oral treatment in preventing or delaying time to psychiatric hospitalizations or on clinical outcomes. The initial analyses did not examine whether benefits of LAI emerged in selected subgroups.Patients with schizophrenia or schizoaffective disorder who had been hospitalized within the past 2 years or judged to be at risk for hospitalization because of increasing psychiatric service use were randomly assigned to LAI risperidone 12.5 to 50 mg per injection biweekly or to the psychiatrist's choice of oral antipsychotics and followed for up to 2 years. The primary endpoint was psychiatric rehospitalization. Symptoms, quality of life, and global functioning were assessed through blinded videoconference interviews. Cox's regression and mixed effects models were used to assess difference in treatment effect within 12 subgroups defined by hospitalization at study entry, substance abuse, race, symptom severity, quality of life, body mass index, age, race or sex, or reported medication compliance.Mixed models and Cox's regression using up to 24 months of follow-up data showed no significant differences in treatment effect in 10 of 12 subgroups on psychiatric symptoms, quality of life, or time to hospitalization. With adjustment for multiple comparisons, treatment effect differed by race on substance use outcomes, with white participants showing more benefit from LAI than other groups.LAI risperidone showed no superiority to psychiatrist's choice of oral treatment in most clinically defined subgroups, although the white patients benefited more than the other groups on substance abuse outcomes.

This study examines the psychometric properties of the Quality of Well Being Scale (QWB), the Positive and Negative Syndrome Scale (PANSS), the Heinrich-Carpenter Quality of Life Scale (QOLS), and the Lenert PANSS-based utility measure in a cohort of patients with schizophrenia and identifies threshold values of clinically meaningful change using the Clinical Global Impressions scale (CGI), as the anchor. The correlation of these measures at baseline and change at 6 and 12 months post enrollment in a comparative effectiveness trial was evaluated in 350 veterans with schizophrenia or schizoaffective disorder. An equipercentile method was used to estimate the minimum clinically important difference (MCID) for each measure. Effect size of 0.30-0.50 for baseline quality of life associated with inpatient status supported concurrent validity. The QWB was moderately correlated with disease-specific measures. The MCID as detected by the CGI at 6 months was 0.17 for QWB, 0.15 for the Lenert utility score, 1.13 for the QOLS, and 20.2 for the PANSS. These differences were stable at 12 months. The QWB is significantly correlated with disease specific measures of health related quality of life in schizophrenia., (Published by Elsevier Ireland Ltd.)

Objectives: To examine the effect of breast cancer and its treatment on fracture risk in older breast cancer survivors., Design: A 10-year prospective cohort study beginning 5 years after a diagnosis of breast cancer for survivors and match date for comparison women., Setting: Six integrated healthcare systems., Participants: Women aged 65 and older (1,286 survivors, 1,286 comparison women, mean age 77.7 in both groups, white, non-Hispanic: survivors, 81.6%; comparison women, 85.2%) who were alive and recurrence free 5 years after a diagnosis of early-stage breast cancer and matched on age, study site, and enrollment year to a comparison cohort without breast cancer., Measurements: Cox proportional hazards models were used to estimate the association between fracture risk and survivor-comparison status, adjusting for drugs and risk factors associated with bone health. A subanalysis was used to evaluate the association between tamoxifen exposure and fracture risk., Results: No difference was observed in fracture rates between groups (hazard ratio (HR) = 1.1, 95% confidence interval (CI) = 0.9-1.3). The protective effect of tamoxifen was not statistically significant (HR = 0.9, 95% CI = 0.6-1.2)., Conclusion: Long-term survivors of early-stage breast cancer diagnosed at age 65 and older are not at greater risk of osteoporotic fractures than age-matched women without breast cancer. There appears to be no long-term protection from fractures with tamoxifen use., (© 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.)

Background: Of the approximately 2.4 million American women with a history of breast cancer, 43% are aged ≥ 65 years and are at risk for developing subsequent malignancies., Methods: Women from 6 geographically diverse sites included 5-year breast cancer survivors (N = 1361) who were diagnosed between 1990 and 1994 at age ≥ 65 years with stage I or II disease and a comparison group of women without breast cancer (N = 1361). Women in the comparison group were age-matched and site-matched to breast cancer survivors on the date of breast cancer diagnosis. Follow-up began 5 years after the index date (survivor diagnosis date or comparison enrollment date) until death, disenrollment, or through 15 years after the index date. Data were collected from medical records and electronic sources (cancer registry, administrative, clinical, National Death Index). Analyses included descriptive statistics, crude incidence rates, and Cox proportional hazards regression models for estimating the risk of incident malignancy and were adjusted for death as a competing risk., Results: Survivors and women in the comparison group were similar: >82% were white, 55% had a Charlson Comorbidity Index of 0, and ≥ 73% had a body mass index ≤ 30 kg/m(2) . Of all 306 women (N = 160 in the survivor group, N = 146 in the comparison group) who developed a first incident malignancy during follow-up, the mean time to malignancy was similar (4.37 ± 2.81 years vs 4.03 ± 2.76 years, respectively; P = .28), whereas unadjusted incidence rates were slightly higher in survivors (1882 vs 1620 per 100,000 person years). The adjusted hazard of developing a first incident malignancy was slightly elevated in survivors in relation to women in the comparison group, but it was not statistically significant (hazard ratio, 1.17; 95% confidence interval, 0.94-1.47)., Conclusions: Older women who survived 5 years after an early stage breast cancer diagnosis were not at an elevated risk for developing subsequent incident malignancies up to 15 years after their breast cancer diagnosis., (Copyright © 2012 American Cancer Society.)

Purpose: To examine five- and ten-year survival based on cancer-specific geriatric assessment (C-SGA) in older women with early stage breast cancer., Methods: We evaluated 660 women ≥65-years old diagnosed with stage I-IIIA primary breast cancer and attending physician permission to contact in four geographic regions in the United States of America (USA). Data were collected over ten-years of follow-up from consenting women's medical records, telephone interviews, National Death Index and Social Security Death Index. C-SGA was described by four domains using six measures: socio-demographic (financial resources); clinical (comorbidity, obesity); function (physical function limitations); and psychosocial (general mental health, social support). Survival from all-cause and breast-cancer-specific mortality and receipt of guideline-recommended therapy was assessed for different groups of subjects with C-SGA domain deficits (cut-off ≥3 deficits)., Results: The proportion of women with ≥3 C-SGA deficits surviving ten-years was consistently statistically significantly lower (all-cause 26% versus 46% and breast-cancer-specific 76% versus 89%, p≤0.04). The proportion significantly decreased as number of C-SGA deficits increased (linear trend p<0.0001). Receipt of guideline-recommended therapy decreased with age but not consistently by number of C-SGA deficits. The all-cause and breast-cancer-specific death rate at five- and ten-years was consistently approximately two times higher in women with ≥3 C-SGA deficits even when fully adjusted for confounding factors (HR(5-yrAllCauseFullyAdjusted)=1.87 [1.36-2.57], HR(10-yrAllCauseFullyAdjusted)=1.74 [1.35-2.15], HR(5-yrBreastCancerFullyAdjusted)=1.95 [1.18-3.20], HR(10-yrBreastCancerFullyAdjusted)=1.99 [1.21-3.28])., Conclusion: Regardless of age and stage of disease, C-SGA predicts five- and ten-year all-cause and breast-cancer-specific survival in older women. Hence, C-SGA may provide an effective strategy to guide treatment decision-making and to identify risk factors for intervention., (Copyright © 2011 Elsevier Ltd. All rights reserved.)