Methodological issues of retrospective surveys for measuring mortality of highly clustered diseases: case study of the 2014-16 Ebola outbreak in Bo District, Sierra Leone.

BACKGROUND: There is a lack of empirical data on design effects (DEFF) for mortality rate for highly clustered data such as with Ebola virus disease (EVD), along with a lack of documentation of methodological limitations and operational utility of mortality estimated from cluster-sampled studies when the DEFF is high. OBJECTIVES: The objectives of this paper are to report EVD mortality rate and DEFF estimates, and discuss the methodological limitations of cluster surveys when data are highly clustered such as during an EVD outbreak. METHODS: We analysed the outputs of two independent population-based surveys conducted at the end of the 2014-2016 EVD outbreak in Bo District, Sierra Leone, in urban and rural areas. In each area, 35 clusters of 14 households were selected with probability proportional to population size. We collected information on morbidity, mortality and changes in household composition during the recall period (May 2014 to April 2015). Rates were calculated for all-cause, all-age, under-5 and EVD-specific mortality, respectively, by areas and overall. Crude and adjusted mortality rates were estimated using Poisson regression, accounting for the surveys sample weights and the clustered design. RESULTS: Overall 980 households and 6,522 individuals participated in both surveys. A total of 64 deaths were reported, of which 20 were attributed to EVD. The crude and EVD-specific mortality rates were 0.35/10,000 person-days (95%CI: 0.23-0.52) and 0.12/10,000 person-days (95%CI: 0.05-0.32), respectively. The DEFF for EVD mortality was 5.53, and for non-EVD mortality, it was 1.53. DEFF for EVD-specific mortality was 6.18 in the rural area and 0.58 in the urban area. DEFF for non-EVD-specific mortality was 1.87 in the rural area and 0.44 in the urban area. CONCLUSION: Our findings demonstrate a high degree of clustering; this contributed to imprecise mortality estimates, which have limited utility when assessing the impact of disease. We provide DEFF estimates that can inform future cluster surveys and discuss design improvements to mitigate the limitations of surveys for highly clustered data.

Main findings: For humanitarian organizations it is imperative to document the methodological limitations of cluster surveys and discuss the utility.Added knowledge: This paper adds new knowledge on cluster surveys for highly clustered data such us in Ebola virus disease.Global health impact of policy and action: We provided empirical estimates and discuss design improvements to inform future study.

Social norms, diffusion, and women's risk of intimate partner violence in Nepal: Impact assessment of a social and behavior Change communication intervention (Change Starts at home).

Introduction: Intimate partner violence (IPV) is a significant public health, human rights, and development issue. While existing evidence posits that addressing social norms is key to IPV prevention, successful IPV interventions that include a norms approach are limited in number and methodological rigor and rarely include a formal investigation of the diffusion of intervention impact. We contribute novel findings to this intellectual and programmatic space with evidence on a social and behavior change communication (SBCC) intervention (Change Starts at Home) in Nepal designed to prevent IPV and shift social norms towards greater gender equity. Methods: Participants included 442 married women across 13 communities assessed at three timepoints: before intervention (baseline), at the completion of the core couple's curriculum and edutainment (midline), and at the conclusion of the diffusion curriculum (endline). Generalized estimating equations with propensity-score adjustments were used to determine change in outcomes at midline and endline for two intervention conditions (direct beneficiary, N = 173; and resident of the intervention community, (N = 178) relative to control (N = 91). Results: IPV victimization significantly decreased in both intervention conditions at midline, with larger reductions in direct beneficiaries. At endline, direct beneficiaries had sustained reduction in IPV relative to control participants. Positive injunctive norms also significantly improved by midline for both intervention groups, whereas improvements in descriptive norms for intervention groups were matched by improvements in the control group at both midline and endline. Several secondary outcomes showed significant improvements for both intervention groups at midline and/or endline, including in-law violence, financial decision-making, communication, and relationship quality, with additional improvements for the direct beneficiaries in attitudes, leadership, GBV advocacy, and diffusion. Conclusion: This study sheds light on the effectiveness of the Change intervention, the role of addressing social norms in IPV prevention efforts, and the benefits of organized diffusion.

The Role of Gender Norms on Intimate Partner Violence Among Newly Married Adolescent Girls and Young Women in India: A Longitudinal Multilevel Analysis.

Gender norms have been posited to impact intimate partner violence (IPV), but there is scant evidence of the longitudinal association between community-level gender norms and IPV. Using longitudinal data on 3,965 married girls surveyed in India, we fitted mixed-effects ordinal and binary logistic regression models for physical IPV intensity and occurrence of sexual IPV. We found a 26% increase in the odds that women experience frequent physical IPV per one unit increase in greater community-level equitable gender norms. We did not find an association between community-level equitable gender norms and sexual IPV. Findings suggest that the relationship between gender norms and physical and sexual IPV differs, indicating the need for tailored interventions for different types of IPV.

Effect of a gender-synchronized family planning intervention on inequitable gender norms in a cluster randomized control trial among husbands of married adolescent girls in Dosso, Niger.

Gender inequity is pervasive globally and has severe consequences for health and well-being, particularly for women and girls in Niger. The Reaching Married Adolescents in Niger (RMA) intervention aimed to promote equitable gender norms in order to increase modern contraceptive use and reduce intimate partner violence among married adolescent girls and their husbands in Niger. Using data from a 4-arm factorial cluster randomized control trial of the RMA intervention (2016-2019), the current study assesses effects of the RMA intervention on gender norms among husbands. We used an adjusted hierarchical difference-in-differences linear regression model to assess these effects. The mean score for perceived gender inequitable norms at baseline was 4.1 (n=1,055; range: 0-5). Assignment to the RMA small groups intervention was associated with a 0.62 lower score (95% CI: -1.05, -0.18) relative to controls at follow-up, after adjusting for baseline differences. No significant effects were detected for other intervention arms. As a low-cost, simple, scalable, and transferrable intervention with rigorous evidence of being able to change such gender norms, this community health worker-based small group intervention could be valuable to the field of public health for reducing the negative impact of inequitable gender norms on health and wellbeing in similar settings.

Effects of the reaching married adolescents program on modern contraceptive use and intimate partner violence: results of a cluster randomized controlled trial among married adolescent girls and their husbands in Dosso, Niger.

BACKGROUND: Niger has the highest rate of adolescent fertility in the world, with early marriage, early childbearing and high gender inequity. This study assesses the impact of Reaching Married Adolescents (RMA), a gender-synchronized social behavioral intervention designed to improve modern contraceptive use and reduce intimate partner violence (IPV) among married adolescent couples in rural Niger. METHODS: We conducted a four-armed cluster-randomized trial in 48 villages across three districts in Dosso region, Niger. Married adolescent girls (ages 13-19) and their husbands were recruited within selected villages. Intervention arms included home visits by gender-matched community health workers (CHWs) (Arm 1), gender-segregated, group discussion sessions (Arm 2), and both approaches (Arm 3). We used multilevel mixed-effects Poisson regression models to assess intervention effects for our primary outcome, current modern contraceptive use, and our secondary outcome, past year IPV. RESULTS: Baseline and 24-month follow-up data were collected April-June 2016 and April-June 2018. At baseline, 1072 adolescent wives were interviewed (88% participation), with 90% retention at follow-up; 1080 husbands were interviewed (88% participation), with 72% retention at follow-up. Adolescent wives had higher likelihood of modern contraceptive use at follow-up relative to controls in Arm 1 (aIRR 3.65, 95% CI 1.41-8.78) and Arm 3 (aIRR 2.99, 95% CI 1.68-5.32); no Arm 2 effects were observed. Relative to those in the control arm, Arm 2 and Arm 3 participants were significantly less likely to report past year IPV (aIRR 0.40, 95% CI 0.18-0.88 for Arm 2; aIRR 0.46, 95% CI 0.21-1.01 for Arm 3). No Arm 1 effects were observed. CONCLUSIONS: The RMA approach blending home visits by CHWs and gender-segregated group discussion sessions is the optimal format for increasing modern contraceptive use and decreasing IPV among married adolescents in Niger. Trial registration This trial is retrospectively registered with ClinicalTrials.gov, Identifier NCT03226730.

Although Niger has both the highest levels of fertility and of child marriage in the world, as well as substantial gender inequity, there have been no high-quality evaluations of public health programs aiming to increase contraceptive use or decrease intimate partner violence. In this study, we conducted a high quality, randomized controlled trial to evaluate whether the Reaching Married Adolescents public health program could increase modern contraceptive use and decrease intimate partner violence among married adolescent girls (13­19 years old) and their husbands in the Dosso region of Niger. The results of this evaluation provide evidence of the value of individual home visits for wives and their husbands in increasing modern contraceptive use, the value of small group discussions in reducing intimate partner violence, and the combined value of receiving both approaches at the same time for both increasing modern contraceptive use and decreasing intimate partner violence. The current study advances the state of evidence regarding contraceptive use and IPV among married adolescents and their husbands in Niger, highlighting the importance of engaging male partners in such public health programs, as well as of using multiple modes of delivery of programs. The success of this intervention in the high-risk context of Niger suggests that other countries in the region may benefit from testing this approach to improve the health and well-being of young wives.

Measuring social norms of intimate partner violence to exert control over wife agency, sexuality, and reproductive autonomy: an item response modelling of the IPV-ASRA scale.

BACKGROUND: The field of violence prevention research is unequivocal that interventions must target contextual factors, like social norms, to reduce gender-based violence. Limited research, however, on the social norms contributing to intimate partner violence or reproductive coercion exists. One of the driving factors is lack of measurement tools to accurately assess social norms. METHODS: Using an item response modelling approach, this study psychometrically assesses the reliability and validity of a social norms measure of the acceptability of intimate partner violence to exert control over wife agency, sexuality, and reproductive autonomy with data from a population-based sample of married adolescent girls (ages 13-18) and their husbands in rural Niger (n = 559 husband-wife dyads) collected in 2019. RESULTS: A two-dimensional Partial Credit Model for polytomous items was fit, showing evidence of reliability and validity. Higher scores on the "challenging husband authority" dimension were statistically associated with husband perpetration of intimate partner violence. CONCLUSIONS: This brief scale is a short (5 items), practical measure with strong reliability and validity evidence. This scale can help identify populations with high-need for social norms-focused IPV prevention and to help measure the impact of such efforts.

Long-term prevention of gender-based violence, like intimate partner violence and reproductive coercion, requires efforts to change the social environment that facilitates violence against women, yet limited research is available on how to change social environments. One reason is that there are few tools to accurately measure social environments, including social norms, which are the unspoken rules about what behavior is acceptable and what behavior is not. The present research assessed a new social norms measurement tool on the acceptability of intimate partner violence to exert control over wife agency, sexuality, and reproductive autonomy using data from a population-based sample of married adolescents and their husbands in rural Niger (n = 559 husband-wife dyads) collected in 2019. We found that this scale had strong reliability and validity, and that the group of questions about challenging husband authority were related to husband perpetration of intimate partner violence against his wife. This brief scale is a short (5 questions), practical measure with strong reliability and validity evidence that can help identify populations with high-need for social norms-focused prevention and to help measure the impact of such efforts. This evidence strengthens the current set of measurement tools on social norms available to researchers and practitioners.

Adolescents' lived experience of panic disorder: an interpretative phenomenological analysis.

BACKGROUND: Panic disorder is a debilitating anxiety disorder that has a serious impact on adolescents' social and academic functioning and general wellbeing. Panic disorder is experienced by around 1 to 3% of the adolescent population. The aim of this study was to examine adolescents' experiences of having panic disorder. METHODS: Semi-structured interviews were conducted with eight adolescents with a primary diagnosis of panic disorder. Interpretative Phenomenological Analysis was used to gain an understanding of adolescents' lived experience of panic disorder. RESULTS: Two superordinate themes were identified: (1) Drowning in sensations, and (2) An unacceptable self. The findings show that adolescents experience panic disorder as extremely overwhelming and unpleasant, with debilitating feelings of drowning in sensations. Adolescents' experiences largely fit with the cognitive model of panic, in which catastrophic misinterpretation of bodily sensations is associated with anxiety, avoidance, and safety behaviours, creating a vicious cycle. Attempts to avoid or prevent the attacks appear to inadvertently make them worse. Social worries, feeling broadly misunderstood, and unhelpful responses from others, contributed to feelings of being different or abnormal and were connected to a negative self-concept. Negative social interactions with teachers and peers in the school environment were particularly damaging. CONCLUSIONS: These findings offer new insight into these adolescents' lived experience of panic disorder and highlight the need for adolescents to access timely, evidence-based treatment, as well as the need for increased awareness and understanding of panic disorder in schools.

Bicarbonate-controlled reduction of oxygen by the QA semiquinone in Photosystem II in membranes.

Photosystem II (PSII), the water/plastoquinone photo-oxidoreductase, plays a key energy input role in the biosphere. [Formula: see text], the reduced semiquinone form of the nonexchangeable quinone, is often considered capable of a side reaction with O2, forming superoxide, but this reaction has not yet been demonstrated experimentally. Here, using chlorophyll fluorescence in plant PSII membranes, we show that O2 does oxidize [Formula: see text] at physiological O2 concentrations with a t1/2 of 10 s. Superoxide is formed stoichiometrically, and the reaction kinetics are controlled by the accessibility of O2 to a binding site near [Formula: see text], with an apparent dissociation constant of 70 ± 20 µM. Unexpectedly, [Formula: see text] could only reduce O2 when bicarbonate was absent from its binding site on the nonheme iron (Fe2+) and the addition of bicarbonate or formate blocked the O2-dependant decay of [Formula: see text] These results, together with molecular dynamics simulations and hybrid quantum mechanics/molecular mechanics calculations, indicate that electron transfer from [Formula: see text] to O2 occurs when the O2 is bound to the empty bicarbonate site on Fe2+ A protective role for bicarbonate in PSII was recently reported, involving long-lived [Formula: see text] triggering bicarbonate dissociation from Fe2+ [Brinkert et al, Proc. Natl. Acad. Sci. U.S.A. 113, 12144-12149 (2016)]. The present findings extend this mechanism by showing that bicarbonate release allows O2 to bind to Fe2+ and to oxidize [Formula: see text] This could be beneficial by oxidizing [Formula: see text] and by producing superoxide, a chemical signal for the overreduced state of the electron transfer chain.

The Effectiveness of Psychological Therapies for Anxiety Disorders in Adolescents: A Meta-Analysis.

Anxiety disorders are common in adolescence but outcomes for adolescents are unclear and we do not know what factors moderate treatment outcome for this age group. We conducted meta-analyses to establish the effectiveness of psychological therapies for adolescent anxiety disorders in (i) reducing anxiety disorder symptoms, and (ii) remission from the primary anxiety disorder, compared with controls, and examine potential moderators of treatment effects. The protocol was registered with PROSPERO (CRD42018091744). Electronic databases (Web of Science, MEDLINE, Psycinfo, EMBASE) were searched from January 1990 to December 2019. 2511 articles were reviewed, those meeting strict criteria were included. Random effects meta-analyses were conducted. Analyses of symptom severity outcomes comprised sixteen studies (CBT k = 15, non-CBT k = 1; n = 766 adolescents), and analyses of diagnostic remission outcomes comprised nine (CBT k = 9; n = 563 adolescents). Post-treatment, those receiving treatment were significantly more likely to experience reduced symptom severity (SMD = 0.454, 95% CI 0.22-0.69) and remission from the primary anxiety disorder than controls (RR = 7.94, 95% CI 3.19-12.7) (36% treatment vs. 9% controls in remission). None of the moderators analysed were statistically significant. Psychological therapies targeting anxiety disorders in adolescents are more effective than controls. However, with only just over a third in remission post-treatment, there is a clear need to develop more effective treatments for adolescents, evaluated through high-quality randomised controlled trials incorporating active controls and follow-up data.

Safety and Treatment Outcomes of Nivolumab for the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: Retrospective Multicenter Cohort Study.

Nivolumab is an anti-PD-1 monoclonal antibody currently used as immunotherapy for patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) with evidence of disease progression after platinum-based chemotherapy. This study evaluates real-world safety and treatment outcomes of non-trial nivolumab use. A retrospective multicenter cohort study of patients with recurrent/metastatic HNSCC treated with nivolumab between January 2017 and March 2020 was performed. Overall, 123 patients were included. The median age was 64 years, the majority of patients were male (80.5%) and had a smoking history (69.9%). Primary outcomes included overall response rate (ORR) of 19.3%, median progression-free survival (PFS) of 3.9 months, 1-year PFS rate of 16.8%, a median overall survival (OS) of 6.5 months and 1-year OS rate of 28.6%. These results are comparable to the CHECKMATE-141 study. Of 27 patients who had PD-L1 status tested, positive PD-L1 status did not significantly affect PFS (p = 0.86) or OS (p = 0.84). Nivolumab was well tolerated with only 15.1% experiencing immune-related toxicities (IRT) and only 6.7% of patients stopping due to toxicity. The occurrence of IRT appeared to significantly affect PFS (p = 0.01) but not OS (p = 0.07). Nivolumab in recurrent/metastatic HNSCC is well tolerated and may be more efficacious in patients who develop IRT.

Functional recovery in older women undergoing surgery for gynaecological malignancies: A systematic review and narrative synthesis.

OBJECTIVES: Older women are increasingly undergoing surgery for gynaecological malignancies. Although survival data is available other outcomes such as functional recovery are less well described. This systematic review and narrative synthesis describes functional recovery after gynaeoncology surgery with respect to baseline characteristics. MATERIALS AND METHODS: Systematic search of MEDLINE and EMBASE databases and Cochrane Library between 1974 to 2018. Two reviewers independently reviewed abstracts/papers for inclusion against the following criteria: Results analysed and presented using narrative synthesis. RESULTS: Fifteen studies identified (8 Endometrial, 2 Ovarian, 2 Vulval, 3 mixed cancer types). 1/15 used a standalone functional assessment tool, 14/15 used Health-Related Quality of Life tools (EORTC QLQ C30 (8), FACT-G (3), SF-36 (3)) comprising items describing function. More studies showed full recovery to baseline (n = 13) than incomplete recovery (n = 2). Four studies reported a negative association between older age and functional trajectory. Recovery was more likely and occurred faster in minimally-invasive surgery. Few studies reported baseline characteristics including cognition, frailty or comorbidities and none examined associations with functional recovery. CONCLUSION: There is inadequate data on functional recovery of older women following gynaeoncology surgery. Future studies are needed to identify factors associated with poorer/better outcomes. This may enable identification of opportunities for risk reduction, improve equity of access and better shared-decision making.

The identification and psychological treatment of panic disorder in adolescents: a survey of CAMHS clinicians.

BACKGROUND: Panic disorder is experienced by around 1% of adolescents and has a significant impact on social and academic functioning. Preliminary evidence supports the effectiveness of panic disorder-specific treatment in adolescents with panic disorder; however, panic disorder may be overlooked in adolescents due to overlapping symptoms with other anxiety disorders and other difficulties being more noticeable to others. The aim of this study was to establish what training National Health Service (NHS) Child and Adolescent Mental Health Services (CAMHS) clinicians have received in psychological therapies and panic disorder and how they identify and treat panic disorder in adolescents. METHOD: CAMHS clinicians from a range of professions (n = 427), who were delivering psychological treatments to children and adolescents with anxiety disorders, participated. They completed a cross-sectional, online survey, including a vignette describing an adolescent with panic disorder, and were asked to identify the main diagnosis or presenting problem. RESULTS: Less than half the clinicians (48.6%) identified panic disorder or panic symptoms as the main presenting problem from the vignette. The majority of clinicians suggested CBT would be their treatment approach. However, few identified an evidence-based treatment protocol for working with young people with panic disorder. Almost half the sample had received no training in cognitive behaviour therapy (CBT), and around a fifth had received no training in delivering psychological treatments. CONCLUSIONS: Only half of CAMHS clinicians identified panic disorder from a vignette and although CBT treatments are widely offered, only a minority of adolescents with panic disorder are receiving treatments developed for and evaluated with young people with panic disorder. There is a vital need for clinician training, the use of tools that aid identification and the implementation of evidence-based treatments within CAMHS. KEY PRACTITIONER MESSAGE: Panic disorder affects around 1% of adolescents, adversely impacting social, academic and long-term life functioning. There is preliminary evidence for the effectiveness of a panic disorder-specific treatment of panic disorder in adolescents. Clinicians struggle to identify panic disorder or suitable treatment protocols for treating adolescents, although most would use CBT as the treatment approach. There is a vital need for clinician training, tools that aid identification of young people with panic disorder and evidence-based treatments that can be delivered in routine clinical settings.