Lesotho is one of the 30 countries with the highest tuberculosis incidence rates in the world, estimated at 650 per 100,000 population. Tuberculosis case detection is extremely low, particularly with ...the rapid spread of COVID-19, dropping from an estimated 51% in 2020 to 33% in 2021. The aim of this study is to understand the barriers to tuberculosis diagnosis and treatment completion.
We used a convergent mixed methods study design. We collected data on the number of clients reporting symptoms upon tuberculosis screening, their sputum test results, the number of clients diagnosed, and the number of clients who started treatment from one district hospital and one health center in Berea district, Lesotho. We conducted in-depth interviews and focus group discussions with 53 health workers and patients. We used a content analysis approach to analyze qualitative data and integrated quantitative and qualitative findings in a joint display.
During March-August, 2019, 218 clients at the hospital and 292 clients at the health center reported tuberculosis symptoms. The full diagnostic testing process was completed for 66% of clients at the hospital and 68% at the health center. Among clients who initiated tuberculosis treatment, 68% (61/90) at the hospital and 74% (32/43) at the health center completed treatment. The main barriers to testing and treatment completion were challenges at sample collection, lack of decentralized diagnostic services, and socioeconomic factors such as food insecurity and high patient movement to search for jobs.
Tuberculosis diagnosis could be improved through the effective decentralization of laboratory services at the health facility level, and treatment completion could be improved by providing food and other forms of social support to patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The objective of the study was to assess the effectiveness of group counseling, using a problem-solving therapy approach, on reducing depressive symptoms and increasing prenatal disclosure rates of ...HIV status among HIV-positive pregnant women living in Dar es Salaam, Tanzania. A randomized controlled trial was performed comparing a six-week structured nurse-midwife facilitated psychosocial support group with the standard of care. Sixty percent of women in the intervention group were depressed post-intervention, versus 73% in the control group Relative Risk (RR) = 0.82, 95% confidence interval (CI): 0.67-1.01, p=0.066. HIV disclosure rates did not differ across the two study arms. However, among those women who disclosed, there was a significantly higher level of overall personal satisfaction with the response to disclosure from family and friends among women in the treatment (88%) compared to the control group (62%; p=0.004). The results indicate reductions in the level of depressive symptoms comparable with major depressive disorder (MDD) for HIV-positive pregnant women participating in a group counseling intervention. Although the psychosocial group counseling did not significantly increase disclosure rates, an improvement in the level of personal satisfaction resulting from disclosure was associated with the intervention. This suggests that the counseling sessions have likely reduced the burden of depression and helped clients better manage partner reactions to disclosure. Public agencies and non-governmental organizations working in Tanzania and similar settings should consider offering structured psychosocial support groups to HIV-positive pregnant women to prevent poor mental health outcomes, promote early childhood development, and potentially impact HIV-related disease outcomes in the long term.
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Perinatal women living with HIV (PWLH) have a greater risk of depression compared to other women; however, there are limited specialized mental health services available to them. We aimed to ...determine whether a stepped-care intervention facilitated by trained lay providers can improve mental health outcomes postpartum for PWLH.
Healthy Options is a cluster-randomized controlled study conducted in 16 government-managed antenatal care clinics that provided HIV care for pregnant women in urban Tanzania. Recruitment occurred from May 2015 through April 2016, with the final round of data collection completed in October 2017. Participants included a consecutive sample of pregnant women under 30 weeks of gestation, living with HIV and depression, and attending the study clinics. Control sites received enhanced usual care for depression (EUDC). Intervention sites received EUDC plus the Healthy Options intervention, which includes prenatal group sessions of problem-solving therapy (PST) plus cognitive behavioral therapy (CBT) sessions for individuals showing depressive symptoms at 6 weeks postdelivery. We assessed depressive symptoms comparable to major depressive disorder (MDD) using the Patient Health Questionnaire-9 (PHQ-9) with a locally validated cutoff at 9 months and 6 weeks postpartum. The primary time point is 9 months postpartum. We examined differences in outcomes using an intent-to-treat analysis with a complete case approach, meaning those with data at the relevant time point were included in the analysis. We used generalized estimating equations accounting for clustering. Of 818 women screened using the PHQ-9, 742 were determined eligible and enrolled (395 intervention; 347 control); 649 women (87.5%) participated in the first follow-up and 641 women (86.4%) in the second. A majority (270, 74.6%) of women in the intervention arm attended 5 or more PST sessions. Women enrolled in Healthy Options demonstrated a 67% (RR 0.33; 95% CI: 0.22, 0.51; p-value: <0.001; corresponding to a 25.7% difference in absolute risk) lower likelihood of depressive symptoms than women in control clusters at 6 weeks postpartum. At 9 months postpartum, women enrolled in Healthy Options demonstrated a nonsignificant 26% (RR 0.74; 95% CI: 0.42, 1.3; p-value: 0.281; corresponding to a 3.2% difference in absolute risk) lower likelihood of depressive symptoms than women in control clusters. Study limitations include not using diagnostic interviews to measure depression and not blinding data collectors to intervention status during follow-up.
The Healthy Options intervention did not demonstrate reduction in depressive symptoms at 9 months postpartum, the primary outcome. Significant reductions were seen in depression symptoms at 6 weeks postpartum, the secondary outcome. Stepped-care interventions may be relevant for improving outcomes in the critical early postpartum window.
Clinical Trial registration number (closed to new participants) NCT02039973.
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To maintain mechanical homeostasis, cells must recognize and respond to changes in cytoskeletal integrity. By imaging live cells expressing fluorescently tagged cytoskeletal proteins, we observed ...that actin stress fibers undergo local, acute, force-induced elongation and thinning events that compromise their stress transmission function, followed by stress fiber repair that restores this capability. The LIM protein zyxin rapidly accumulates at sites of strain-induced stress fiber damage and is essential for stress fiber repair and generation of traction force. Zyxin promotes recruitment of the actin regulatory proteins α-actinin and VASP to compromised stress fiber zones. α-Actinin plays a critical role in restoration of actin integrity at sites of local stress fiber damage, whereas both α-actinin and VASP independently contribute to limiting stress fiber elongation at strain sites, thus promoting stabilization of the stress fiber. Our findings demonstrate a mechanism for rapid repair and maintenance of the structural integrity of the actin cytoskeleton.
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► Actin stress fibers undergo cycles of localized, force-induced strain and repair ► Sites of stress fiber strain recruit a zyxin-dependent repair complex ► Defects in the repair machinery cause stress fiber breaks and reduced traction
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Understanding the pathogenic mechanisms of disease mutations is critical to advancing treatments. ALS-associated mutations in the gene encoding the microtubule motor KIF5A result in skipping of exon ...27 (KIF5AΔExon27) and the encoding of a protein with a novel 39 amino acid residue C-terminal sequence. Here, we report that expression of ALS-linked mutant KIF5A results in dysregulated motor activity, cellular mislocalization, altered axonal transport, and decreased neuronal survival. Single-molecule analysis revealed that the altered C terminus of mutant KIF5A results in a constitutively active state. Furthermore, mutant KIF5A possesses altered protein and RNA interactions and its expression results in altered gene expression/splicing. Taken together, our data support the hypothesis that causative ALS mutations result in a toxic gain of function in the intracellular motor KIF5A that disrupts intracellular trafficking and neuronal homeostasis.
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•ALS-associated KIF5A mutations result in a common novel toxic C-terminal sequence•ALS mutant KIF5A lacks autoinhibition resulting in a constitutively active kinesin•ALS mutant KIF5A displays a distal accumulation and altered axonal transport•ALS-associated KIF5A mutations result in novel protein and RNA interactions
ALS-associated KIF5A mutations alter the C terminus, the effect of which had yet to be elucidated. Here, Baron et al. discover that these mutations impair KIF5A autoinhibition resulting in a hyperactive kinesin that displays altered protein function and aberrant cellular interactions. These observations shed light on the mechanisms contributing to ALS.
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Intimate partner violence (IPV) exacts a heavy burden on women, resulting in poor health outcomes. This study had the following aims: (1) estimate the prevalence of IPV post-disclosure of HIV status ...among pregnant women living with HIV and depression; and (2) evaluate risk and protective factors for IPV post-disclosure. Participants were women accessing PMTCT services at 16 health facilities in Dar es Salaam and screened at the threshold of 9 on the PHQ-9. Generalized linear equations with a log link and standard errors clustered at the facility level were used to calculate associations between predictors and IPV post-disclosure. Among 659 women who were in an intimate relationship, 10.2% had experienced physical violence and 11.6% had reported sexual violence from their partner in the past six months; 327 had disclosed their HIV status to their partners. After disclosure to their partners 279 women (85.3%) experienced IPV. HIV-related stigma was associated with increased risk of IPV following disclosure and appreciative relationships with partners and higher hope were associated with reduced risk of IPV. There is a need to identify and advance approaches to HIV disclosure that prevent IPV. Interventions should be developed based on known risk and protective factors for IPV following HIV disclosure in Tanzania and similar settings.
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DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Food allergy (FA) is a prevalent condition in the United States, but little is known about its phenotypes in racial minority groups.
The objective of this study was to characterize disease phenotypes ...and disparities in health care utilization among African American (AA), Hispanic, and white children with FA.
We conducted a large, 2-center, retrospective cohort study of children aged 0-17 years with FA seen in allergy/immunology clinics at 2 urban tertiary care centers in the United States. We used multiple logistic regression analyses adjusted for age, gender, and insurance.
The cohort of 817 children was composed of 35% AA, 12% Hispanic, and 53% non-Hispanic white. Compared with non-Hispanic white children, AA children had significantly higher odds of having asthma and eczema (P < .01), and significantly higher odds of allergy to wheat, soy, corn, fish, and shellfish (P < .01). Compared with non-Hispanic white children, Hispanic children had significantly higher odds of allergy to corn, fish, and shellfish (P < .01), and higher odds of eczema (P < .01), but a similar rate of asthma (P = .44). In this cohort, 55%, 18%, and 11% of AA, Hispanic, and white children were covered by Medicaid, respectively (P < .00001). Compared with whites, AA and Hispanic children had a shorter duration of follow-up for FA with an allergy specialist and higher rates of FA-related anaphylaxis and emergency department visits (P < .01).
FA phenotypes and health care utilization differ among children of different racial and/or ethnic backgrounds in the United States that put AA and Hispanic children at higher risks of adverse outcome than white children. These differences include coexistent atopic conditions, less well recognized food allergens, and higher rates of anaphylaxis.
IMPORTANCE: Immunization with tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended in the United States during weeks 27 through 36 of pregnancy to prevent life-threatening ...infant pertussis. The optimal gestation for immunization to maximize concentrations of neonatal pertussis toxin antibodies is unknown. OBJECTIVE: To determine pertussis toxin antibody concentrations in cord blood from neonates born to women immunized and unimmunized with Tdap vaccine in pregnancy and optimal gestational age for immunization to maximize concentrations of neonatal antibodies. DESIGN, SETTING, AND PARTICIPANTS: Prospective, observational, cohort study of term neonates in Houston, Texas (December 2013-March 2014). EXPOSURES: Tdap immunization during weeks 27 through 36 of pregnancy or no Tdap immunization. MAIN OUTCOMES AND MEASURES: Primary outcome was geometric mean concentrations (GMCs) of pertussis toxin antibodies in cord blood of Tdap-exposed and Tdap-unexposed neonates and proportions of Tdap-exposed and Tdap-unexposed neonates with pertussis toxin antibody concentrations of 15 IU/mL or higher, 30 IU/mL or higher, and 40 IU/mL or higher, cutoffs representing quantifiable antibodies or levels that may be protective until the infant immunization series begins. Secondary outcome was the optimal gestation for immunization to achieve maximum pertussis toxin antibodies. RESULTS: Six hundred twenty-six pregnancies (mean maternal age, 29.7 years; 41% white, 27% Hispanic, 26% black, 5% Asian, 1% other; mean gestation, 39.4 weeks) were included. Three hundred twelve women received Tdap vaccine at a mean gestation of 31.2 weeks (range, 27.3-36.4); 314 were unimmunized. GMC of neonatal cord pertussis toxin antibodies from the Tdap-exposed group was 47.3 IU/mL (95% CI, 42.1-53.2) compared with 12.9 IU/mL (95% CI, 11.7-14.3) in the Tdap-unexposed group, for a GMC ratio of 3.6 (95% CI, 3.1-4.2; P < .001). More Tdap-exposed than Tdap-unexposed neonates had pertussis toxin antibody concentrations of 15 IU/mL or higher (86% vs 37%; difference, 49% 95% CI, 42%-55%), 30 IU/mL or higher (72% vs 17%; difference, 55% 95% CI, 49%-61%), and 40 IU/mL or higher (59% vs 12%; difference, 47% 95% CI, 41%-54%); P < .001 for each analysis. GMCs of pertussis toxin antibodies were highest when Tdap vaccine was administered during weeks 27 through 30 and declined thereafter, reaching a peak at week 30 (57.3 IU/mL 95% CI, 44.0-74.6). CONCLUSIONS AND RELEVANCE: Immunization with Tdap vaccine during the third trimester of pregnancy, compared with no immunization, was associated with higher neonatal concentrations of pertussis toxin antibodies. Immunization early in the third trimester was associated with the highest concentrations.
A "risk of harm" protocol to identify youth in need of immediate emergency assistance in a study on mental health and HIV in Rwanda among 680 youth ages 10-17 is described. Cases are presented that ...describe the experience in using this protocol to ensure safety of participants, with ethical and logistical challenges considered. Among the population of the study, 3.2% were deemed "risk of harm." The most prevalent presenting problem was non-fatal suicidal behavior (91% of risk of harm cases), with 36% having a history of a reported previous attempt. Challenges included: acute food insecurity/significant poverty; lack of support/adequate supervision from family members; family violence; alcohol abuse; and HIV-related stigma. Development of a "risk of harm" protocol and collaboration between study staff, community leadership, health authorities, and health workers are critical to ensuring participants' safety in research among vulnerable populations.
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Given the increased access of antiretroviral therapy (ART) throughout the developing world, what was once a terminal illness is now a chronic disease for those receiving treatment. This requires a ...paradigmatic shift in service provision for those affected by HIV/AIDS in low-resource settings. Although there is a need for psychosocial support interventions for HIV-affected youth and their caregivers, to date there has been limited empirical evidence on the effectiveness of curriculum-based psychosocial support groups in HIV-affected families in low-income countries. Therefore, the purpose of this study is to examine the feasibility and assess the preliminary effectiveness of a psychosocial support group intervention for HIV-affected youth and their caregivers in central Haiti. The study was conducted at six Partners In Health-affiliated sites between February 2006 and September 2008 and included quantitative as well as qualitative methods. HIV-affected youth (n = 168) and their caregivers (n = 130) completed a baseline structured questionnaire prior to participation in a psychosocial support group intervention. Ninety-five percent of families completed the intervention and a follow-up questionnaire. Psychological symptoms, psychosocial functioning, social support, and HIV-related stigma at baseline were compared with outcomes one year later. Qualitative methods were also used to assess the participants' perspectives of the intervention. Comparing pre- and post-intervention assessment, youth affected by HIV experienced decreased psychological symptoms as well as improved psychosocial functioning and social support. Caregivers (95% HIV-positive) demonstrated a significant reduction in depressive symptoms, improved social support, and decreased HIV-related stigma. Although further study is needed to assess effectiveness in a randomized controlled trial, corroborative findings from qualitative data reflected reduced psychological distress, less social isolation and greater hope for the future for families affected by HIV/AIDS following the intervention.
► A psychosocial support group for HIV-affected families demonstrated feasibility and a high retention rate in central Haiti. ► Findings reveal high rates of psychological symptoms at baseline in youth and their caregivers in this at-risk population. ► Post-intervention HIV-affected youth experienced decreased psychological symptoms and improved psychosocial functioning. ► Post-intervention HIV-affected caregivers demonstrated reduction in depressive symptoms and HIV-related stigma. ► Qualitative findings demonstrated an improvement in coping and hope for the future among the youth and their caregivers.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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