Interventions addressing family violence and mental illness or substance use in low- and middle-income countries: A systematic review.

Most family violence research has been conducted in high-income countries, although family violence rates are higher in low- and middle-income countries (LMICs), and outcomes more severe. Given the strong associations of family violence with substance use and mental illness, the aim of this systematic review was to examine interventions that targeted familial violence and at least one other condition of substance use or mental illness to determine effective treatments in LMICs. We conducted a systematic review of interventions that addressed family violence and mental illness or substance use. A committee of three researchers independently screened titles and abstracts and conducted full-text eligibility assessments. Two researchers conducted a risk of bias assessment. Data were extracted using a structured spreadsheet and narratively synthesized. Our search identified 29 articles produced from 19 studies conducted in 13 LMICs. Most (n = 15) studies randomized to study condition. Lack of blinding was the most common threat. The external validity of studies was generally poor. Fourteen studies had a primary intervention target of family violence, mental health, substance use, economic improvement, or HIV. None of the studies showed improvements in all intervention areas. Child maltreatment was less likely to be addressed than intimate partner violence (IPV). Targeted interventions for substance and mental health mostly improved primary outcomes, although they were less effective in reducing IPV. Evidence-based treatments must be rigorously evaluated before innovations in implementation can occur. Interventions overwhelmingly addressed IPV victimization and should consider how to work with couples and include men and children.

Evaluation of the Early Adolescent Skills for Emotions (EASE) intervention in Lebanon: A randomized controlled trial.

BACKGROUND: There is a need for scalable evidence-based psychological interventions for young adolescents experiencing high levels of psychological distress in humanitarian settings and low- and middle-income countries. Poor mental health during adolescence presents a serious public health concern as it is a known predictor of persistent mental disorders in adulthood. This study evaluates the effectiveness of a new group-based intervention developed by the World Health Organization (Early Adolescent Skills for Emotions; EASE), implemented by non-specialists, to reduce young adolescents' psychological distress among mostly Syrian refugees in Lebanon. METHODS: We conducted a two-arm, single-blind, individually randomized group treatment trial. Adolescents aged 10 to 14 years who screened positive for psychological distress using the Pediatric Symptom Checklist (PSC) were randomly allocated to EASE or enhanced treatment as usual (ETAU) (1:1.6). ETAU consisted of a single scripted psycho-education home-visit session with the adolescent and their caregivers. EASE consists of seven group sessions with adolescents and three sessions with caregivers. The primary outcome was adolescent-reported psychological distress as measured with the PSC (internalizing, externalizing, and attentional symptoms). Secondary outcomes included depression, posttraumatic stress, well-being, functioning, and caregivers' parenting and distress. All outcomes were assessed at baseline, endline, and 3 months (primary time point) and 12 months follow-up. RESULTS: Due to the COVID-19 pandemic and other adversities in Lebanon at the time of this research, the study was prematurely terminated, resulting in an under-powered trial sample (n = 198 enrolled compared to n = 445 targeted). We screened 604 children for eligibility. The 198 enrolled adolescents were assigned to EASE (n = 80) and ETAU (n = 118), with retention rates between 76.1 and 88.4% across all timepoints. Intent-to-treat analyses demonstrated no between-group differences on any of the outcome measures between the EASE and ETAU. We did observe a significant improvement on the primary outcome equally in the EASE and ETAU groups (-0.90, 95% CI: -3.6, 1.8; p = .52), - a trend that was sustained at three months follow-up. Sub-group analyses, for those with higher depression symptoms at baseline, showed ETAU outperformed EASE on reducing depression symptoms (difference in mean change = 2.7, 95% CI: 0.1, 5.3; p = .04; d = 0.59) and internalizing problems (difference in mean change 1.0, 95% CI: 0.08, 1.9; p = .03; d = 0.56) . CONCLUSION: No conclusions can be drawn about the comparative effectiveness of the intervention given that the sample was underpowered as a result of early termination. Both EASE and single session psycho-education home visits resulted in meaningful improvements in reducing psychological distress. We did not identify any indications in the data suggesting that EASE was more effective than a single session family intervention in the context of the COVID-19 pandemic and other crises in Lebanon. Fully powered research is needed to evaluate the effectiveness of EASE.

Examination of the Factor Structure of Psychopathology in a Mozambican Sample.

Factor-analytic studies are needed in global samples to advance understanding of psychopathology. We aimed to examine the structure of psychopathology and a general psychopathology ('p') factor using data from a cross-sectional study of 971 adults (63% women) from Maputo City, Mozambique. We used confirmatory factor analyses of symptoms from 15 psychiatric disorders to test common models of the structure of psychopathology. Models including internalizing, substance use, and thought disorder factors as well as a general p-factor fit the data well. Measurement invariance testing revealed that factor loadings on p differed by gender. Higher levels of p, internalizing, and thought disorder factors were associated with greater suicide risk, psychiatric comorbidity, chronic medical illnesses, and poorer functioning. A general psychopathology ('p') factor and internalizing, substance use, and thought disorder factors are identifiable in this Mozambican sample. Understanding psychopathology dimensions is a step toward building more scalable mental health service approaches globally.

Community Health Workers' Knowledge, Attitudes, and Practices towards Epilepsy in Sofala, Central Mozambique.

BACKGROUND: Epilepsy is the most common neurological disease in the world, affecting 50 million people, with the majority living in low- and middle-income countries (LMICs). A major focus of epilepsy treatment in LMICs has been task-sharing the identification and care for epilepsy by community health workers (CHWs). The present study aimed to assess the knowledge, attitudes, and practices (KAPs) of CHWs towards epilepsy in Mozambique. METHODS: One hundred and thirty-five CHWs completed a questionnaire that included socio-demographic characteristics and 44-items divided into six subscales pertaining to KAPs towards epilepsy (QKAP-EPI) across nine districts of Sofala, Mozambique. The internal consistency was examined to evaluate the reliability of the instrument (QKAP-EPI). The association between sociodemographic variables and QKAP-EPI subscales was examined using linear regression models. RESULTS: The internal consistency was moderate for two subscales (causes of epilepsy, α = 0.65; medical treatment, α = 0.694), acceptable for cultural treatment (α = 0.797) and excellent for 2 subscales (safety and risks, α = 0.926; negative attitudes, α = 0.904). Overall, CHWs demonstrated accurate epilepsy knowledge (medical treatment: mean = 1.63, SD = 0.28; safety/risks: mean = 1.62, SD = 0.59). However, CHWs reported inaccurate epilepsy knowledge of the causes, negative attitudes, as well as culturally specific treatments for epilepsy, such as: "if a person with epilepsy burns when set on fire they cannot be treated". Knowledge about how to manage epileptic seizures varied across the different emergency care practices, from the accurate belief that it is not advisable to place objects in the individual's mouth during an epileptic seizure, to the wrong perception of the need to hold the person in seizures to control seizures. Heterogeneity in the level of epilepsy knowledge was observed among CHWs, when considering epilepsy according to the local names as treatable ("Dzumba") and other forms as untreatable ("Nzwiti"). CONCLUSION: CHWs knowledge of medical treatment and epilepsy safety/risks were adequate. However, information on the causes of epilepsy, stigmatizing attitudes, cultural treatment, and some knowledge of epileptic seizure management were low. These areas of poor knowledge should be the focus of educating CHWs in increasing their ability to provide quality care for patients with epilepsy in Mozambique.

Child Labor and Psychosocial Wellbeing: Findings from Ethiopia.

For children who work, there has been little research into the intricate relationship between their home lives and their work lives and the implications that this relationship might hold for their psychosocial development and functioning. This cross-sectional study was conducted in the Amhara region, Ethiopia, between March and April 2020 on a sample of 1311 working children with the aim, in part, of exploring ways in which various dimensions of children's psychological wellbeing are influenced by their working conditions and their family contexts. In addition to collecting data on some personal traits, family relationships, home environments, and detailed occupational characteristics, we gathered information on psychosocial wellbeing using 22 items from the Instrument for the Psychosocial Assessment of Working Children (IPAC). Exploratory factor analysis enabled us to identify five factors characterizing the dimensions of psychosocial wellbeing: work-related self-esteem, work-related stress, workplace supervision, emotional and somatic wellbeing, and self-determination. Linear regressions of these factors were then conducted on social, occupational, and environmental variables. We found that all dimensions of psychosocial wellbeing were significantly associated with the children's working conditions. Of particular interest, work-related dimensions of wellbeing, such as stress, self-esteem, and supervision, were significantly associated with the characteristics of the home and family environment. These findings illustrate that work and working conditions must be considered jointly, along with family life and home environments, as factors in both environments affect working children's socioemotional development and wellbeing. They also strengthen the call for a systemic approach to protecting children involved in child labor, in which families are central to all discussions.

Lower Urinary Tract Diseases in Guinea Pigs: A 14-Year Retrospective Study (2004-2018).

The clinical records of all guinea pigs diagnosed with a lower urinary tract disease in a single veterinary hospital, over a period of 14 years (2004−2018), were retrospectively searched in order to characterize this population and investigate the potential association between the epidemiological and clinical variables. A total of 117 clinical cases were identified, corresponding to 57 animals. Urolithiasis was the most common diagnosis (n = 52; 44.4%), followed by cystitis and/or a urinary tract infection (UTI). Several statistically significant associations (p < 0.05) were found between different variables, showing that female guinea pigs were more likely than the male ones to have a previous family history of urinary disease, to present dysuria and stranguria at admission, and to suffer recurrence. Moreover, males were more prone to urolithiasis and females to cystitis/UTI, and animals diagnosed with cystitis/UTI frequently had more clinical urinary signs and abdominal pain on palpation compared to those diagnosed with urolithiasis. Finally, the use of potassium citrate and the urethrotomy approach were associated with a better therapeutic response. Further studies are needed in larger populations of guinea pigs to confirm the present findings, especially as some of them were described for the first time.

Improved Control of Tyrosine Kinase Inhibitor-Induced Diarrhea with a Novel Chloride Channel Modulator: A Case Report.

Despite the efficacy of tyrosine kinase inhibitors (TKIs) across multiple cancers, side effects including treatment-related diarrhea can impede a patient's ability to reach therapeutic doses or stay on therapy. Below, we present the case of a 72-year-old patient with metastatic papillary renal cell carcinoma recurrent despite nephrectomy. Over the course of treatment, the patient received multiple different tyrosine kinase inhibitors with varying efficacy. Treatment with the TKI cabozantinib after failure of two prior TKIs resulted in a clinical response with shrinkage of his nodal metastatic disease. However, the severe treatment-related diarrhea refractory to conventional management required both dose holds and dose reductions of cabozantinib. Off-label administration of crofelemer, a novel FDA-approved antidiarrheal agent, successfully controlled the treatment-related diarrhea and allowed resumption and partial dose increase of cabozantinib. This case suggests that crofelemer could be a viable therapeutic strategy to address TKI-induced diarrhea.

Gut microbiome composition and risk factors in a large cross-sectional IBS cohort.

Objective: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is difficult to diagnose and treat due to its inherent heterogeneity and unclear aetiology. Although there is evidence suggesting the importance of the microbiome in IBS, this association remains poorly defined. In the current study, we aimed to characterise a large cross-sectional cohort of patients with self-reported IBS in terms of microbiome composition, demographics, and risk factors. Design: Individuals who had previously submitted a stool sample for 16S microbiome sequencing were sent a comprehensive survey regarding IBS diagnosis, demographics, health history, comorbidities, family history, and symptoms. Log ratio-transformed abundances of microbial taxa were compared between individuals reporting a diagnosis of IBS without any comorbidities and individuals reporting no health conditions. Univariable testing was followed by a multivariable logistic regression model controlling for relevant confounders. Results: Out of 6386 respondents, 1692 reported a diagnosis of IBS without comorbidities and 1124 reported no health conditions. We identified 3 phyla, 15 genera, and 19 species as significantly associated with IBS after adjustment for confounding factors. Demographic risk factors include a family history of gut disorders and reported use of antibiotics in the last year. Conclusion: The results of this study confirm important IBS risk factors in a large cohort and support a connection for microbiome compositional changes in IBS pathogenesis. The results also suggest clinical relevance in monitoring and investigating the microbiome in patients with IBS. Further, the exploratory models described here provide a foundation for future studies.

Enforcement trends in the city of St. Louis from 2007 to 2017: Exploring variability in arrests and criminal summonses over time and across communities.

The goal of this study is twofold: (a) to describe trends in enforcement activity in the city of St. Louis from 2007 through 2017 and (b) to document community variation in these trends. Five types of enforcement actions are examined: felony, misdemeanor, municipal, and bench warrant arrests and criminal summonses-in-lieu of arrest. Results indicate that enforcement activity decreased over the study period, particularly for nonfelony arrests among Blacks. City-wide trends obscure some variability in neighborhood enforcement. Neighborhood trends in enforcement varied by type of action, but in all cases, trends were conditioned by racial composition. For example, misdemeanor and bench warrant arrests exhibited steeper declines in neighborhoods with a higher percentage of Black residents, resulting in a narrowing of the race gap. In contrast, differences in criminal summonses across neighborhoods of varying racial compositions increased. The effects persisted net of measures of economic disadvantage, community location, residential mobility, household composition, calls for service, and population size. The findings highlight the importance of disaggregating enforcement trends by race and place and documenting changes in less serious, but more prevalent, types of law enforcement activity.

A systematic review of comprehensive interventions for substance abuse: Focus on victimization.

Violence victimization is common among men and women who use substances and is associated with co-occurring health issues such as PTSD, depression and HIV. Substance use interventions, therefore, should include integrated components that are designed to address co-occurring health issues among victimized substance-using individuals. This systematic review synthesized the evidence on efficacy of comprehensive, integrated, multicomponent interventions for victimized substance-using individuals. The efficacy of integrated multicomponent intervention strategies was assessed for the following syndemic conditions: mental health, substance misuse, violence, and HIV risk. Seventeen studies were identified. Examples of effective components were empowerment strategies for violence, mindfulness-based stress reduction for mental health, social cognitive skill building for addressing HIV risk and psychoeducation for substance misuse. Although in this review, some components were found to be effective, we identified methodological limitations of included studies which calls for more rigorous research in this area. Further, there is lack of evidence base for multicomponent interventions for victimized substance-using individuals in developing countries. Additional studies are needed to establish rigorous evidence base for multicomponent interventions for victimized substance using individuals that help them cope effectively with their trauma of violence and address their needs.

Gastrocutaneous Fistula in a Patient with Locally Recurrent MSI-High Colorectal Cancer: Local Complications Arising from Therapeutic Response to Immune Checkpoint Blockade.

Colorectal cancers with high microsatellite instability (MSI-H) have distinct clinical features in terms of their prognosis, recurrence patterns, and sensitivity to immunotherapeutic agents. We present the case of a woman with a left-sided MSI-H colon cancer who had repeated recurrences concentrated exclusively in the left upper quadrant of the abdomen, including gastric involvement. Despite multiple surgical resections, radiation, and several lines of chemotherapy, her disease eventually eroded through the chest wall. Treatment with an immune checkpoint inhibitor produced a rapid clinical response with significant tumor necrosis; however, this necessitated surgical debridement that ultimately led to a large gastrocutaneous fistula. This case highlights the importance of recognizing locoregional tumor-associated complications that may result from robust therapeutic responses to immuno-oncology drugs, which are increasingly being used in clinical practice today.

Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer: A Randomized Clinical Trial.

Importance: Combining biologic monoclonal antibodies with chemotherapeutic cytotoxic drugs provides clinical benefit to patients with advanced or metastatic colorectal cancer, but the optimal choice of the initial biologic therapy in previously untreated patients is unknown. Objective: To determine if the addition of cetuximab vs bevacizumab to the combination of leucovorin, fluorouracil, and oxaliplatin (mFOLFOX6) regimen or the combination of leucovorin, fluorouracil, and irinotecan (FOLFIRI) regimen is superior as first-line therapy in advanced or metastatic KRAS wild-type (wt) colorectal cancer. Design, Setting, and Participants: Patients (≥18 years) enrolled at community and academic centers throughout the National Clinical Trials Network in the United States and Canada (November 2005-March 2012) with previously untreated advanced or metastatic colorectal cancer whose tumors were KRAS wt chose to take either the mFOLFOX6 regimen or the FOLFIRI regimen as chemotherapy and were randomized to receive either cetuximab (n = 578) or bevacizumab (n = 559). The last date of follow-up was December 15, 2015. Interventions: Cetuximab vs bevacizumab combined with either mFOLFOX6 or FOLFIRI chemotherapy regimen chosen by the treating physician and patient. Main Outcomes and Measures: The primary end point was overall survival. Secondary objectives included progression-free survival and overall response rate, site-reported confirmed or unconfirmed complete or partial response. Results: Among 1137 patients (median age, 59 years; 440 [39%] women), 1074 (94%) of patients met eligibility criteria. As of December 15, 2015, median follow-up for 263 surviving patients was 47.4 months (range, 0-110.7 months), and 82% of patients (938 of 1137) experienced disease progression. The median overall survival was 30.0 months in the cetuximab-chemotherapy group and 29.0 months in the bevacizumab-chemotherapy group with a stratified hazard ratio (HR) of 0.88 (95% CI, 0.77-1.01; P = .08). The median progression-free survival was 10.5 months in the cetuximab-chemotherapy group and 10.6 months in the bevacizumab-chemotherapy group with a stratified HR of 0.95 (95% CI, 0.84-1.08; P = .45). Response rates were not significantly different, 59.6% vs 55.2% for cetuximab and bevacizumab, respectively (difference, 4.4%, 95% CI, 1.0%-9.0%, P = .13). Conclusions and Relevance: Among patients with KRAS wt untreated advanced or metastatic colorectal cancer, there was no significant difference in overall survival between the addition of cetuximab vs bevacizumab to chemotherapy as initial biologic treatment. Trial Registration: clinicaltrials.gov identifier: NCT00265850.

Differential Radiographic Appearance of BRAF V600E-Mutant Metastatic Colorectal Cancer in Patients Matched by Primary Tumor Location.

BACKGROUND: BRAF-mutant metastatic colorectal cancers (mCRCs) share many clinicopathologic features with right-sided colon tumors, including frequent peritoneal involvement. Because of the poorer outcomes associated with BRAF mutations, early enrollment in clinical trials has been encouraged. However, the use of standard eligibility and assessment criteria, such as measurable disease, has anecdotally impeded patient accrual and restricted appraisal of treatment response. We investigated whether the presence of a BRAF V600E mutation is differentially associated with sites and appearance of metastatic disease in patients matched by primary tumor location. METHODS: A total of 40 patients with BRAF-mutant mCRC were matched to 80 patients with BRAF wild-type mCRC by location of primary tumor (right or left colon; rectum), sex, and age. Associations between BRAF mutation status and clinicopathologic characteristics and metastatic sites were analyzed using proportion tests. Survival was summarized with Kaplan-Meier and Cox regression methods. RESULTS: The distribution of primary tumor locations was: 60% right colon, 30% left colon, and 10% rectum. Compared with BRAF wild-type tumors, BRAF-mutant tumors more commonly associated with peritoneal metastases (50% vs 31%; P=.045) and ascites (50% vs 24%; P=.0038). In patients with left colon primaries, BRAF mutations were associated with more frequent ascites (58% vs 12%; P=.0038) and less frequent liver metastases (42% vs 79%; P=.024). Among patients with right colon primaries, no significant difference in sites of disease by BRAF mutation status was observed. Disease was not measurable by RECIST 1.1 in 24% of patients with right-sided primary tumors, irrespective of BRAF mutation status. In the BRAF-mutated cohort, ascites correlated unfavorably with survival (hazard ratio, 2.35; 95% CI, 1.14, 4.83; P=.02). CONCLUSIONS: Greater frequency of ascites and peritoneal metastases, which pose challenges for RECIST 1.1 interpretation of therapeutic outcomes, are seen with BRAF-mutant mCRC, even when patients are matched for primary tumor location.

Lithium or Valproate Adjunctive Therapy to Second-generation Antipsychotics and Metabolic Variables in Patients With Schizophrenia or Schizoaffective Disorder.

OBJECTIVE: People with schizophrenia are at greater risk for cardiovascular disease and their overall mortality rate is elevated compared to the general population. The metabolic side effects of antipsychotic medications have been widely studied; however, the effect of adding conventional mood stabilizers, such as lithium and valproate, to antipsychotic medication has not been assessed in terms of metabolic risk. The primary purpose of this secondary analysis was to examine whether treatment with lithium or valproate in addition to a second-generation antipsychotic is associated with poorer metabolic outcomes than treatment with a second-generation antipsychotic without lithium or depakote. METHODS: Baseline data from 3 studies, which included measurement of body mass index, waist circumference, fasting glucose, insulin, homeostatic model assessment of insulin resistance, insulin sensitivity index, glucose utilization, and acute insulin response to glucose, were included in the analysis. RESULTS: No differences were found between those taking lithium or valproate and those who were not in terms of fasting glucose, fasting insulin, and homeostatic model assessment of insulin resistance. Insulin sensitivity was lower among participants taking lithium or valproate. Participants taking lithium or valproate had a higher body mass index than those not taking conventional mood stabilizers, although the difference did not reach statistical significance. CONCLUSIONS: These cross-sectional findings suggest it may be beneficial to monitor insulin sensitivity and body mass index in patients taking lithium or valproate in combination with a second-generation antipsychotic.

Cell-Free DNA Next-Generation Sequencing in Pancreatobiliary Carcinomas.

UNLABELLED: Patients with pancreatic and biliary carcinomas lack personalized treatment options, in part because biopsies are often inadequate for molecular characterization. Cell-free DNA (cfDNA) sequencing may enable a precision oncology approach in this setting. We attempted to prospectively analyze 54 genes in tumor and cfDNA for 26 patients. Tumor sequencing failed in 9 patients (35%). In the remaining 17, 90.3% (95% confidence interval, 73.1%-97.5%) of mutations detected in tumor biopsies were also detected in cfDNA. The diagnostic accuracy of cfDNA sequencing was 97.7%, with 92.3% average sensitivity and 100% specificity across five informative genes. Changes in cfDNA correlated well with tumor marker dynamics in serial sampling (r = 0.93). We demonstrate that cfDNA sequencing is feasible, accurate, and sensitive in identifying tumor-derived mutations without prior knowledge of tumor genotype or the abundance of circulating tumor DNA. cfDNA sequencing should be considered in pancreatobiliary cancer trials where tissue sampling is unsafe, infeasible, or otherwise unsuccessful. SIGNIFICANCE: Precision medicine efforts in biliary and pancreatic cancers have been frustrated by difficulties in obtaining adequate tumor tissue for next-generation sequencing. cfDNA sequencing reliably and accurately detects tumor-derived mutations, paving the way for precision oncology approaches in these deadly diseases.

The importance of age composition of 12-step meetings as a moderating factor in the relation between young adults' 12-step participation and abstinence.

BACKGROUND: Participation in 12-step mutual help organizations (MHO) is a common continuing care recommendation for adults; however, little is known about the effects of MHO participation among young adults (i.e., ages 18-25 years) for whom the typically older age composition at meetings may serve as a barrier to engagement and benefits. This study examined whether the age composition of 12-step meetings moderated the recovery benefits derived from attending MHOs. METHOD: Young adults (n=302; 18-24 years; 26% female; 94% White) enrolled in a naturalistic study of residential treatment effectiveness were assessed at intake, and 3, 6, and 12 months later on 12-step attendance, age composition of attended 12-step groups, and treatment outcome (Percent Days Abstinent [PDA]). Hierarchical linear models (HLM) tested the moderating effect of age composition on PDA concurrently and in lagged models controlling for confounds. RESULTS: A significant three-way interaction between attendance, age composition, and time was detected in the concurrent (p=0.002), but not lagged, model (b=0.38, p=0.46). Specifically, a similar age composition was helpful early post-treatment among low 12-step attendees, but became detrimental over time. CONCLUSIONS: Treatment and other referral agencies might enhance the likelihood of successful remission and recovery among young adults by locating and initially linking such individuals to age appropriate groups. Once engaged, however, it may be prudent to encourage gradual integration into the broader mixed-age range of 12-step meetings, wherein it is possible that older members may provide the depth and length of sober experience needed to carry young adults forward into long-term recovery.