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BackgroundThe costs associated with healthcare are of critical importance to both decision-makers and users, given the limited resources allocated to the health sector. However, the available scientific evidence on healthcare costs in low- and middle-income countries, such as Peru, is scarce. In the Peruvian context, the health system is fragmented, and the private health insurance and its financing models have received less research attention. We aimed to analyse user cost-sharing and associated factors within the private healthcare system.MethodsOur study was cross-sectional, using open data from the Electronic Transaction Model of Standardized Billing Data-TEDEF-SUSALUD, between 2021-2022. Our unit of analysis is the user's medical bills. We considered the total amount of cost-sharing, proportion of total payments as cost-sharing, and cost-sharing as a proportion of minimum salaries. We use a multiple regression model to perform the analyses.ResultsOur study included 5,286,556 health services provided to users of the private health insurance in Peru. We found a significant difference was observed in the cost-sharing for hospitalization-related services, with an average of 419.64 soles per day (95% CI: 413.44 to 425.85). Also, we identified that for hospitalization-related services per day is, on average, 0.41 (95% CI: 0.41 to 0.41) minimum salaries more expensive than outpatient care, although cost-sharing per day of hospitalization represent on average only 14% of the total amount submitted.ConclusionsOur study provides a detailed overview of cost-sharing in the private healthcare system in Peru and the factors associated with them. Policymakers can use the study's finding that higher cost-sharing for inpatient hospitalization compared to outpatient care in private insurance can create inequities in access to healthcare to design policies aimed at reducing these costs and promoting a more equitable and accessible healthcare system in Peru.

Parental domestic violence and abuse (DVA), mental ill-health (MH), and substance misuse (SU) are three public health issues that tend to cluster within families, risking negative impacts for both parents and children. Despite this, service provision for these issues has been historically siloed, increasing the barriers families face to accessing support. Our review aimed to identify family focused interventions that have combined impacts on parental DVA, MH, and/or SU. We searched 10 databases (MEDLINE, PsycINFO, Embase, CINAHL, Education Research Information Centre, Sociological Abstracts, Applied Social Sciences Index & Abstracts, ProQuest Dissertations and Theses Global, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials) from inception to July 2021 for randomised controlled trials examining the effectiveness of family focused, psychosocial, preventive interventions targeting parents/carers at risk of, or experiencing, DVA, MH, and/or SU. Studies were included if they measured impacts on two or more of these issues. The Cochrane Risk of Bias Tool 2 was used to quality appraise studies, which were synthesised narratively, grouped in relation to the combination of DVA, MH, and/or SU outcomes measured. Harvest plots were used to illustrate the findings. Thirty-seven unique studies were identified for inclusion. Of these, none had a combined positive impact on all three outcomes and only one study demonstrated a combined positive impact on two outcomes. We also found studies that had combined adverse, mixed, or singular impacts. Most studies were based in the U.S., targeted mothers, and were rated as 'some concerns' or 'high risk' of bias. The results highlight the distinct lack of evidence for, and no 'best bet', family focused interventions targeting these often-clustered risks. This may, in part, be due to the ways interventions are currently conceptualised or designed to influence the relationships between DVA, MH, and/or SU. Trial registration: PROSPERO registration: CRD42020210350.

BackgroundUntil a vaccine is developed, a test, trace and isolate strategy is the most effective method of controlling the COVID-19 outbreak. Contact tracing and case isolation are common methods for controlling infectious disease outbreaks. However, the effectiveness of any contact tracing system rests on public engagement. Numerous factors may influence an individual's willingness to engage with a contact tracing system. Understanding these factors has become urgent during the COVID-19 pandemic.ObjectiveTo identify facilitators and barriers to uptake of, and engagement with, contact tracing during infectious disease outbreaks.MethodA rapid systematic review was conducted to identify papers based on primary research, written in English, and that assessed facilitators, barriers, and other factors associated with the uptake of, and engagement with, a contact tracing system.Principal findingsFour themes were identified as facilitators to the uptake of, and engagement with, contact tracing: collective responsibility; personal benefit; co-production of contact tracing systems; and the perception of the system as efficient, rigorous and reliable. Five themes were identified as barriers to the uptake of, and engagement with, contact tracing: privacy concerns; mistrust and/or apprehension; unmet need for more information and support; fear of stigmatization; and mode-specific challenges.ConclusionsBy focusing on the factors that have been identified, contact tracing services are more likely to get people to engage with them, identify more potentially ill contacts, and reduce transmission.

BACKGROUND:The lack of established measurement tools in the study of menstrual health and hygiene has been a significant limitation of quantitative studies to date. However, there has been limited exploration of existing measurement to identify avenues for improvement. METHODS:We undertook two linked systematic reviews of (1) trials of menstrual health interventions and their nested studies in low- and middle-income countries, (2) studies developing or validating measures of menstrual experiences from any location. Systematic searching was undertaken in 12 databases, together with handsearching. We iteratively grouped and audited concepts measured across included studies and extracted and compared measures of each concept. RESULTS:A total of 23 trials, 9 nested studies and 22 measure development studies were included. Trials measured a range of outcomes including menstrual knowledge, attitudes, and practices, school absenteeism, and health. Most measure validation studies focused on assessing attitudes towards menstruation, while a group of five studies assessed the accuracy of women's recall of their menstrual characteristics such as timing and cycle length. Measures of menstrual knowledge, attitudes, beliefs and restrictions were inconsistent and frequently overlapped. No two studies measured the same menstrual or hygiene practices, with 44 different practices assessed. This audit provides a summary of current measures and extant efforts to pilot or test their performance. CONCLUSIONS:Inconsistencies in both the definition and operationalisation of concepts measured in menstrual health and hygiene research should be addressed. To improve measurement, authors should clearly define the constructs they aim to measure and outline how these were operationalised for measurement. Results of this audit indicate the need for the development and validation of new measures, and the evaluation of the performance of existing measures across contexts. In particular, the definition and measurement of menstrual practices, knowledge, attitudes, norms and restrictions should be addressed. REVIEW PROTOCOL REGISTRATION:CRD42018089884.

OBJECTIVE:Analyze the measurement invariance and the factor structure of the Patient Health Questionnaire-9 (PHQ-9) in the Peruvian population. METHOD:Secondary data analysis performed using cross-sectional data from the Health Questionnaire of the Demographic and Health Survey in Peru. Variables of interest were the PHQ-9 and demographic characteristics (sex, age group, level of education, socioeconomic status, marital status, and area of residence). Factor structure was evaluated by standard confirmatory factor analysis (CFA), and measurement invariance by multi-group CFA, using standard goodness-of-fit indices criteria for interpreting results from both CFAs. Analysis of the internal consistency (α and ω) was also pursued. RESULTS:Data from 30,449 study participants were analyzed, 56.7% were women, average age was 40.5 years (standard deviation (SD) = 16.3), 65.9% lived in urban areas, 74.6% were married, and had 9 years of education on average (SD = 4.6). From standard CFA, a one-dimensional model presented the best fit (CFI = 0.936; RMSEA = 0.089; SRMR = 0.039). From multi-group CFA, all progressively restricted models had ΔCFI

BACKGROUND:What are the parenting behaviors that shape child compliance? Most research on parent-child interactions relies on correlational research or evaluations of "package deal" interventions that manipulate many aspects of parenting at the same time. Neither approach allows for identifying the specific parenting behaviors that shape child compliance. To overcome this, we systematically reviewed and meta-analyzed available evidence on the effects of experimentally manipulated, discrete parenting behaviors-a niche in parent-child interaction research that contributes unique information on the specific parenting behaviors that shape child behavior. METHODS:We identified studies by systematically searching databases and through contacting experts. Nineteen studies (75 effect sizes) on four discrete parenting behaviors were included: praise, verbal reprimands, time-out, and ignore. In multilevel models, we tested for each parenting behavior whether it increased child compliance, including both observed and parent-reported measures of child compliance. RESULTS:Providing "time-out" for noncompliance robustly increased both observed and parent-reported child compliance (ds = 0.84-1.72; 95% CI 0.30 to 2.54). The same holds for briefly ignoring the child after non-compliance (ds = 0.36-1.77; 95% CI 0.04 to 2.90). When observed and parent-reported outcomes were combined, but not when they were examined separately, verbal reprimands also increased child compliance (d = 0.72; 95% CI 0.26 to 1.19). Praise did not increase child compliance (ds = -0.27-1.19; 95% CI -2.04 to 1.59). CONCLUSION:Our findings suggest that of the discrete parenting behaviors that are experimentally studied in multiple trials, especially time-out and ignore, and to some extent verbal reprimands, shape child compliance.

PURPOSE:This systematic review with network meta-analysis compared the efficacy and safety of currently licensed second-line treatments in patients with late stage non-small cell lung cancer (NSCLC). METHODS:Randomised controlled trials (RCTs) of participants with advanced/metastatic NSCLC receiving second/third line treatments were screened. We searched electronic databases (MEDLINE; EMBASE; Web of Science) from January, 2000 to July, 2017. Two reviewers screened bibliographic records, extracted data, and assessed risk of bias of included studies. The outcomes were overall survival (OS), progression-free survival (PFS), and drug-related grade 3-5 adverse-events (AEs). We pooled study-specific hazard ratios (HR; for OS and PFS) and risk ratios (RR; for AEs) using conventional and network-meta-analyses, and ranked interventions by the surface under the cumulative ranking curve. FINDINGS:We included 11 RCTs (7,581 participants) comparing nine drugs. All drugs except for erlotinib significantly improved OS compared to docetaxel. Nivolumab was the highest ranking drug followed by atezolizumab and pembrolizumab. There was no significant difference in OS across these three drugs (HR = 0.98, 95% CI 0.79, 1.21 for nivolumab vs atezolizumab; HR = 0.98, 95% CI 0.77, 1.25 for nivolumab vs pembrolizumab). For PFS, ramucirumab + docetaxel and nivolumab were the drugs with the highest ranking. All interventions except ramucirumab + docetaxel had a reduced risk for severe drug-related AEs vs. docetaxel. Of the drugs with the highest ranking on AEs, nivolumab was significantly safer compared to atezolizumab (RR = 0.55, 95% CI 0.38, 0.79) or pembrolizumab (RR = 0.52, 95% CI 0.34, 0.81). IMPLICATIONS:Nivolumab, pembrolizumab and atezolizumab exhibited superior benefit/risk balance compared to other licensed drugs used late stage NSCLC. Our results indicate that the use of immunotherapies in people diagnosed with non-specific late stage NSCLC should be promoted. The use of docetaxel may now be judged irrelevant as a comparator intervention for approval of new drugs for second line treatment of NSCLC. STUDY REGISTRATION NUMBER:PROSPERO CRD42017065928.

BACKGROUND: Previous reviews show that reporting guidelines have improved the quality of trial reports in medicine, yet existing guidelines may not be fully suited for social and psychological intervention trials. OBJECTIVE/DESIGN: We conducted a two-part study that reviewed (1) reporting guidelines for and (2) the reporting quality of social and psychological intervention trials. DATA SOURCES: (1) To identify reporting guidelines, we systematically searched multiple electronic databases and reporting guideline registries. (2) To identify trials, we hand-searched 40 journals with the 10 highest impact factors in clinical psychology, criminology, education, and social work. ELIGIBILITY: (1) Reporting guidelines consisted of articles introducing a checklist of reporting standards relevant to social and psychological intervention trials. (2) Trials reported randomised experiments of complex interventions with psychological, social, or health outcomes. RESULTS: (1) We identified 19 reporting guidelines that yielded 147 reporting standards relevant to social and psychological interventions. Social and behavioural science guidelines included 89 standards not found in CONSORT guidelines. However, CONSORT guidelines used more recommended techniques for development and dissemination compared to other guidelines. (2) Our review of trials (n = 239) revealed that many standards were poorly reported, such as identification as a randomised trial in titles (20% reported the information) and abstracts (55%); information about blinding (15%), sequence generation (23%), and allocation concealment (17%); and details about actual delivery of experimental (43%) and control interventions (34%), participant uptake (25%), and service environment (28%). Only 11 of 40 journals referenced reporting guidelines in "Instructions to Authors." CONCLUSION: Existing reporting guidelines have important limitations in content, development, and/or dissemination. Important details are routinely missing from trial publications; most leading journals in social and behavioural sciences do not ask authors to follow reporting standards. Findings demonstrate a need to develop a CONSORT extension with updated standards for social and psychological intervention trials.

Tumor Necrosis Factor alpha (TNFalpha) is a pleiotropic cytokine extensively studied for its role in the pathogenesis of a variety of disease conditions, including in inflammatory diseases. We have recently shown that, in vitro, that TNFalpha utilizes PLD1 to mediate the activation of NFkappaB and ERK1/2 in human monocytes. The aim of this study was to investigate the role(s) played by phospholipase D1 (PLD1) in TNFalpha-mediated inflammatory responses in vivo.Studies were performed in vivo using a mouse model of TNFalpha-induced peritonitis. The role of PLD1 was investigated by functional genomics, utilizing a specific siRNA to silence the expression of PLD1. Administration of the siRNA against PLD1 significantly reduced PLD1 levels in vivo. TNFalpha triggers a rapid pyrogenic response, but the in vivo silencing of PLD1 protects mice from the TNFalpha-induced rise in temperature. Similarly TNFalpha caused an increase in the serum levels of IL-6, MIP-1alpha and MIP-1beta: this increase in cytokine/chemokine levels was inhibited in mice where PLD1 had been silenced. We then induced acute peritonitis with TNFalpha. Intraperitoneal injection of TNFalpha triggered a rapid increase in vascular permeability, and the influx of neutrophils and monocytes into the peritoneal cavity. By contrast, in mice where PLD1 had been silenced, the TNFalpha-triggered increase in vascular permeability and phagocyte influx was substantially reduced. Furthermore, we also show that the TNFalpha-mediated upregulation of the cell adhesion molecules VCAM and ICAM1, in the vascular endothelium, were dependent on PLD1.These novel data demonstrate a critical role for PLD1 in TNFalpha-induced inflammation in vivo and warrant further investigation. Indeed, our results suggest PLD1 as a novel target for treating inflammatory diseases, where TNFalpha play key roles: these include diseases ranging from sepsis to respiratory and autoimmune diseases; all diseases with considerable unmet medical need.

Introduction: HIV continues to be a major health concern with approximately 2.1 million new infections occurring worldwide in 2015. In Central America, Guatemala had the highest incident number of HIV infections (3,700) in 2015. Antiretroviral pre-exposure prophylaxis (PrEP) was recently recommended by the World Health Organization (WHO) as an efficacious intervention to prevent HIV transmission. PrEP implementation efforts are underway in Guatemala and success will require providers that are knowledgeable and willing to prescribe PrEP. We sought to explore current PrEP awareness and prescribing attitudes among Guatemalan physicians in order to inform future PrEP implementation efforts., Methods: We conducted a cross-sectional survey of adult internal medicine physicians at the main teaching hospital in Guatemala City in March 2015. The survey included demographics, medical specialty, years of HIV patient care, PrEP awareness, willingness to prescribe PrEP, previous experience with post-exposure prophylaxis, and concerns about PrEP. The primary outcome was willingness to prescribe PrEP, which was assessed using a 5-point Likert scale for different at-risk population scenarios. Univariate and multivariate logistic regression was performed to identify predictors for willingness to prescribe PrEP., Results: Eighty-seven physicians completed the survey; 66% were male, 64% were internal medicine residency trainees, and 10% were infectious disease (ID) specialists. Sixty-nine percent of physicians were PrEP aware, of which 9% had previously prescribed PrEP. Most (87%) of respondents were willing to prescribe PrEP to men who have sex with men (MSM), sex workers, injection drug users, or HIV-uninfected persons having known HIV-positive sexual partners. Concerns regarding PrEP included development of resistance (92%), risk compensation (90%), and cost (64%). Univariate logistic regression showed that younger age, being a resident trainee, and being a non-ID specialist were significant predictors for willingness to prescribe PrEP. In multivariate logistic regression, being a non-ID specialist was a significant predictor., Conclusions: Guatemalan physicians at an urban public hospital were PrEP aware and willing to prescribe, but few have actually done so yet. Future education programs should address the concerns identified, including the low potential for the development of antiretroviral resistance. These findings can aid PrEP implementation efforts in Guatemala.

Tissue inhibitor of metalloproteinase-4 (TIMP-4) is a member of extracellular matrix (ECM) metalloproteinases inhibitors that has pleiotropic functions. However, TIMP-4 roles in carcinogenesis are not well understood. Cell viability and flow cytometer assays were employed to evaluate cell death differences between H-Vector and H-TIMP-4 cell lines. Immunobloting and semi-quantitative RT-PCR were used to evaluate the expression of apoptosis regulators. We showed that TIMP-4 has apoptosis-sensitizing effects towards several death stimuli. Consistent with these findings, regulators of apoptosis from Inhibitors of Apoptosis Proteins (IAP), FLICE-like inhibitor proteins (FLIP) and Bcl-2 family members were modulated by TIMP-4. In addition, TIMP-4 knockdown resulted in cell survival increase after serum deprivation, as assessed by clonogenic cell analyses. This report shows that TIMP-4 regulates carcinogenesis through apoptosis activation in cervical cancer cells. Understanding TIMP-4 effects in tumorigenesis may provide clues for future therapies.