A social enterprise model for TB detection and treatment through the private sector in Pakistan.

BACKGROUND: Existing models to increase TB case notifications from the private sector in Pakistan are financially unsustainable and have achieved modest success due to limited coverage. OBJECTIVE: To evaluate the impact of a social enterprise model (SEM) intervention on TB case detection in Karachi, Pakistan, and to assess its financial sustainability. METHODS: Purpose-built centres were established within the private sector that integrated TB screening, diagnostics and treatment and operated 12 hours per day with convenient locations to improve access. TB services were offered free of cost, and revenue generation took place through user fees from other diagnostics. Private providers with a focus on the informal sector were engaged through community workers to generate screening referrals. RESULTS: Overall 171,488 people were screened and 18,683 cases were notified, including 197 individuals with drug-resistant TB. Annual TB notifications in Karachi increased from 18,105 in 2014 to a maximum of 25,840 (40% increase). The proportion of cases in Karachi notified by the centres grew to 27% in 2020. Commercial revenue reached USD288,065 and enabled operating cost recovery of 15%. Average cost per TB case notified was USD203. CONCLUSION: The SEM intervention contributed a large proportion of notifications in Karachi and achieved modest cost recovery.

CONTEXTE: Les modèles existants visant à augmenter les notifications de cas de TB par le secteur privé au Pakistan ne sont pas viables financièrement et n'ont obtenu qu'un succès modeste en raison d'une couverture limitée. OBJECTIF: Évaluer l'impact d'un modèle déntreprise sociale (SEM, pour l'anglais « social entreprise model ¼) sur la détection des cas de TB à Karachi, au Pakistan, et évaluer sa viabilité financière. MÉTHODES: Des centres spécialisés ont été créés dans le secteur privé. Ils intègrent le dépistage, le diagnostic et le traitement de la TB et fonctionnent 12 heures par jour dans des lieux adaptés afin dén faciliter l'accès. Les services de lutte contre la TB étaient gratuits et les recettes provenaient des frais d'utilisation des autres diagnostics. Des prestataires privés, axés sur le secteur informel, ont été engagés par l'intermédiaire d'agents communautaires pour orienter les patients vers les services de dépistage. RÉSULTATS: Au total, 171 488 personnes ont été dépistées et 18 683 cas ont été notifiés, dont 197 personnes atteintes de TB résistante aux médicaments. Les notifications annuelles de TB à Karachi sont passées de 18 105 en 2014 à un maximum de 25 840 (augmentation de 40%). La proportion de cas à Karachi notifiés par les centres est passée à 27% en 2020. Les recettes commerciales ont atteint 288 065 USD et ont permis un recouvrement des coûts déxploitation de 15%. Le coût moyen par cas de TB notifié était de 203 USD. CONCLUSION: L'intervention SEM a contribué à une grande proportion de notifications à Karachi et a permis un modeste recouvrement des coûts.

COVID-19 related moral injury: Associations with pandemic-related perceived threat and risky and protective behaviors.

BACKGROUND: The coronavirus-2019 (COVID-19) pandemic is associated with increased potential for morally injurious events, during which individuals may experience, witness, or learn about situations that violate deeply held moral beliefs. However, it is unknown how pandemic risk and resilience factors are associated with COVID-related moral injury. METHODS: Individuals residing in the U.S. (N = 839; Mage = 37.09, SD = 11.06; 78% women; 63% White; 33% PTSD) participating in an online survey reported on COVID-19 related moral injury (modified Moral Injury Events Scale), perceived current and future threat of pandemic on life domains (social, financial, health), and COVID-19 risky and protective behaviors. Multivariate linear regressions examined associations of perceived threat and risky and protective behaviors on type of COVID-19 related moral injury (betrayal, transgression by others, self). RESULTS: Participants endorsed MI betrayal (57%, N = 482), transgression by other (59%, N = 497), and by self 17% (N = 145). Adjusting for sociodemographics, only future threat of COVID-19 to health was significantly associated with betrayal (B = 0.21, p = .001) and transgression by other (B = 0.16, p = .01), but not by self. In contrast, high frequency of risky behaviors was associated with transgressions by self (B = 0.23, p < .001). Sensitivity analyses showed PTSD did not moderate the observed effects. CONCLUSIONS: Betrayal and transgression by others was associated with greater perceived future threat of COVID-19 to health, but not financial or social domains. Stronger endorsement of transgression by self was associated with more frequently engaging in risky behaviors for contracting COVID-19. These findings may suggest the need for individual, community, and system level interventions to address COVID-19 related moral injury.

Expressive suppression and cognitive reappraisal in veterans with PTSD: Results from the mind your heart study.

OBJECTIVE: This study examined whether expressive suppression (ES), a maladaptive regulation strategy, was more strongly associated with PTSD diagnosis and symptom clusters in veterans than cognitive reappraisal (CR), an adaptive regulation strategy. METHOD: In a cohort study, 746 participants recruited from VHA facilities completed Clinician Administered PTSD Scale-IV, Emotion Regulation Questionnaire, and Patient Health Questionnaire. Participants were categorized into groups: Current, Remitted/Lifetime, and Never PTSD. RESULTS: One-way ANOVA revealed significant differences between Current PTSD and both Remitted and Never PTSD for ES, but not CR. The Remitted and Never PTSD groups did not vary significantly from each other and were collapsed into one group for regressions. Adjusting for sex, race, employment, and comorbid depression, binary logistic regression showed ES, but not CR, was associated with increased likelihood of Current PTSD (p < .001, OR: 1.43). ES was also significantly associated with increased odds of meeting criteria for all symptom clusters (ps < 0.001). CR was not significantly associated with meeting criteria for Current PTSD or any symptom cluster. LIMITATIONS: Cross-sectional design and use of self-report limit causality inferences that can be drawn. CONCLUSIONS: ES is associated with increased odds of Current PTSD diagnosis and symptom clusters. Veterans in the Remitted and Never PTSD groups did not differ significantly. Greater suppression of emotional expression is more strongly linked with PTSD criteria in veterans than decreased cognitive reappraisal.

Suppression, but not reappraisal, is associated with inflammation in trauma-exposed veterans.

BACKGROUND: Emotion dysregulation can elicit inflammatory activity. The current study examined whether specific maladaptive and adaptive emotion regulation strategies were associated with inflammatory markers in trauma-exposed veterans, above and beyond PTSD. METHODS: In a cohort study, 606 participants exposed to a Criterion A trauma and recruited from Veteran Health Administration facilities completed fasting blood draws, the Emotion Regulation Questionnaire, and the Clinician Administered PTSD Scale-IV. Inflammation was assessed with high sensitivity C-reactive protein (hsCRP), white blood cell count (WBC), and fibrinogen levels. An inflammation index was created by summing standardized log-transformed levels of the three biomarkers. Our primary linear regression models were adjusted for sex, age, race, education, income, creatinine, and PTSD. RESULTS: Suppression, but not cognitive reappraisal, was significantly associated with higher levels of the inflammatory index (ß = 0.14, p = 0.001). Parallel analyses for the individual inflammatory markers also showed suppression, but not reappraisal, was significantly associated with higher hsCRP (ß = 0.11, p = 0.01), WBC (ß = 0.11, p = 0.01), and fibrinogen (ß = 0.10, p = 0.02). CONCLUSIONS: Emotional suppression is related to elevated systemic inflammation independent of PTSD. Cognitive reappraisal is unrelated to inflammation. Findings suggest over-utilization of maladaptive, rather than under-utilization of adaptive, emotion regulation strategies may be associated with systemic inflammation in trauma-exposed veterans.

Introducing new and repurposed TB drugs: the endTB experience.

In 2015, the initiative Expand New Drug Markets for TB (endTB) began, with the objective of reducing barriers to access to the new and repurposed TB drugs. Here we describe the major implementation challenges encountered in 17 endTB countries. We provide insights on how national TB programmes and other stakeholders can scale-up the programmatic use of new and repurposed TB drugs, while building scientific evidence about their safety and efficacy. For any new drug or diagnostic, multiple market barriers can slow the pace of scale-up. During 2015-2019, endTB was successful in increasing the number of patients receiving new and repurposed TB drugs in 17 countries. The endTB experience has many lessons, which are relevant to country level introduction of new TB drugs, as well as non-TB drugs and diagnostics. For example: the importation of TB drugs is possible even in the absence of registration; emphasis on good clinical monitoring is more important than pharmacovigilance reporting; national guidelines and expert committees can both facilitate and hinder innovative practice; clinicians use new and repurposed TB drugs when they are available; data collection to generate scientific evidence requires financial and human resources; pilot projects can drive national scale-up.

How do gender and military sexual trauma impact PTSD symptoms in cognitive processing therapy and prolonged exposure?

OBJECTIVE: Effectiveness of evidence-based psychotherapy (EBP) for PTSD can vary based on gender and trauma type, with poorer outcomes for men and sexual traumas. Among veterans receiving EBPs for PTSD, the effects of the interaction between gender and military sexual trauma (MST) on treatment outcome are unclear. This study examined how gender and MST impact PTSD symptoms following cognitive processing therapy (CPT) and prolonged exposure (PE). METHOD: We conducted a national, retrospective cohort study of all post 9/11 veterans who had a PTSD diagnosis from 10/2001-9/2017 at VHA facilities and >1 psychotherapy visit. Inclusion criteria included completion of ≥8 CPT/PE sessions and pre- and post-treatment PCL (N = 9711). Mixed-effects linear regression models were conducted, separately by treatment, to examine associations between changes in PTSD symptoms and gender, MST, and their interactions with time. RESULTS: For both treatments, there were no significant differences in pre-treatment PCL by gender or MST, and PCL decreased significantly over time. In adjusted models, only the gender by time interaction on pre-to-post-CPT change was significant (p < .001); the decrease in women's PCL was 2.67 points greater, compared to men. CONCLUSIONS: Women veterans demonstrated greater reductions in PTSD symptoms from CPT. There were no differences by gender for PE, suggesting men and women veterans benefit similarly. Results suggest outcomes may be impacted by gender socialization when utilizing certain cognitive behavioral techniques. MST, regardless of gender, did not impact PTSD outcomes for either treatment. Both CPT and PE may thus be effective for veterans irrespective of MST history.

Automated chest radiography and mass systematic screening for tuberculosis.

BACKGROUND: Systematic screening for TB using automated chest radiography (ACR) with computer-aided detection software (CAD4TB) has been implemented at scale in Karachi, Pakistan. Despite evidence supporting the use of ACR as a pre-screen prior to Xpert® MTB/RIF diagnostic testing in presumptive TB patients, there has been no data published on its use in mass screening in real-world settings.METHOD: Screening was undertaken using mobile digital X-ray vehicles at hospital facilities and community camps. Chest X-rays were offered to individuals aged ≥15 years, regardless of symptoms. Those with a CAD4TB score of ≥70 were offered Xpert testing. The association between Xpert positivity and CAD4TB scores was examined using data collected between 1 January and 30 June 2018 using a custom-built data collection tool.RESULTS: Of the 127 062 individuals screened, 97.2% had a valid CAD4TB score; 11 184 (9.1%) individuals had a CAD4TB score ≥70. Prevalence of Xpert positivity rose from 0.7% in the <50 category to 23.5% in the >90 category. The strong linear association between CAD4TB score and Xpert positivity was found in both community and hospital settings.CONCLUSION: The strong association between CAD4TB scores and Xpert positivity provide evidence that an ACR-based pre-screening performs well when implemented at scale in a high-burden setting.

Examining the impact of different types of military trauma on suicidality in women veterans.

Suicide rates amongst women veterans are significantly higher than rates for their civilian counterparts. However, risk factors for suicide among women veterans remain unclear. The current study examined the impact of exposure to a number of military stressors (e.g., perceived life threat, killing in combat, military sexual trauma) on suicidal ideation (SI) in women veterans. A total of 403 women veterans responded to mailed self-report surveys, 383 (ages 24-70 years) returned fully completed surveys and were included in analyses, and 16% of those included endorsed current SI. Rates of endorsement for military stressors were as follows: 43% being wounded, 34% loss of someone close, 36% perceived life threat, 30% witnessing a killing or injury, 4% seeing injured or dead bodies, 4% killing in combat, 65% military sexual harassment, and 33% military sexual assault. A logistic regression analysis was conducted with all of the military stressors entered simultaneously to determine the effect on SI. Life threat and sexual harassment had the strongest associations with SI compared to other military stressors. These findings suggest that particular military stressors may play an especially important role in SI in women veterans. Implications and future research considerations are discussed.

The Association between Distress Tolerance and Alcohol Related Problems: The Pathway of Drinking to Cope.

Binge drinking (BD) and alcohol related problems (ARP) are highly prevalent among college students. However, current models examining ARP suggest drinking quantity only accounts for a portion of the variance, suggesting other variables contribute to ARP. Distress tolerance (DT), or the ability to withstand negative affect, is associated with alcohol misuse and may be an important mechanism related to ARP. However, studies have reported inconsistent findings on this association, which may be due to the use of only global scores to measure DT rather than specific DT components. Furthermore, the mechanisms underlying this association remain unknown. Drinking to cope with negative affect has been associated with both DT and ARP, suggesting it may be a mechanism explaining the relationship between DT and ARP. The current study examined the association between specific proposed DT components (i.e., tolerance, absorption, appraisal, and regulation) and drinking to cope and ARP in 147 college students who BD. A hierarchical linear regression was performed in order to examine which DT component best predicted ARP. Four follow-up mediation models were then tested to examine whether drinking to cope mediated the relationship between each DT component and ARP. Appraisal of DT was the only DT component that significantly predicted ARP, in the model controlling for drinking quantity and sex differences. Drinking to cope mediated the relationship between ARP and tolerance, absorption, and regulation, but not appraisal of DT. Implications for furthering our understanding of DT and treatment of BD as it relates to DT are explored.

UK families with children with rare chromosome disorders: Changing experiences of diagnosis and counselling (2003-2013).

The latest United Kingdom (UK) strategy for rare diseases emphasises the need to empower affected populations to improve diagnosis, intervention, and coordination of care. Families who have a child with a rare chromosome disorder (RCD) are a challenging group to include. We report the findings of 2 large-scale surveys, undertaken by the UK RCD Support Group Unique, of these families' experiences over a 10-year period. Seven stages of the patient journey were examined. From pre-testing, through diagnosis, genetics consultation, clinical follow-up and peer support. Overall, 1158 families replied; 36.4% response rate (2003) and 53.6% (2013). Analysis of responses identifies significant differences (P < .001) over time with a decrease in results reported face to face (76%-62%), doubling by telephone (12%-22%), improved explanation of chromosome disorder (57%-75%), and increased signposting to peer support group (34%-62%). However, conduct of the consultation raises a number of important questions. Overall, 28 aspects of the patient journey are recognised as requiring improvement; only 12/28 are currently incorporated in UK service specifications. Involvement of RCD families has identified key service improvements. This approach can empower those affected by such extremely rare disorders, and also enable professionals to design improved services in partnership with "expert families." Further surveys are planned.

Sugar before bed: a simple dietary risk factor for caries experience.

Clinical care pathways have placed renewed emphasis on caries risk assessment and the ability to predict and prevent further disease. With diet considered a key factor in the development of caries, the level of caries risk posed by dietary habits, such as the frequency of intake and timing of free sugars is questioned. OBJECTIVE: To identify reliable and simple dietary risk factors for caries experience. RESEARCH DESIGN: A cross-sectional observational study of a convenience sample with data gained from clinical examinations, questionnaire and a 24 hour dietary-recall interview. PARTICIPANTS: 128 subjects aged 11-12 from comprehensive schools in Greater Manchester and Newcastle upon-Tyne, UK. OUTCOME MEASURES: free sugars consumed between meals, before bed and total % of total free sugars consumed were assessed from dietary assessments led by a dietitian. D4-6MFT was generated with a caries threshold of ICDAS stage 4 from clinical examinations. RESULTS: Analysis revealed no significant differences in caries experience when looking specifically at caries into dentine, referred to as the cavity group (split at D4-6MFT), between high and low deprivation, consumption of free sugars between meals and free sugars (%). The consumption of free sugars within the hour before bed revealed a statistically significant difference between the cavity/no cavity groups (p=0.002). Logistic regression analysis on the cavity/no cavity groups revealed an odds ratio of 2.4 (95%CI 1.3,4.4) for free sugars consumption before bedtime. CONCLUSIONS: The study suggests that the consumption of free sugars before bedtime may be an important risk factor for adolescent caries into dentine experience.

Association of interleukin-10 polymorphisms with chronic hepatitis C virus infection in a case-control study and its effect on the response to combined pegylated interferon/ribavirin therapy.

We conducted a case-control study involving 150 genotype 3 chronic hepatitis C virus (HCV) patients and 150 healthy controls to investigate the association of polymorphisms in the interleukin-10 (IL-10) gene with chronic HCV infection and the association of these polymorphic variants with the combination of pegylated interferon (Peg-IFN) and ribavirin therapy response. Our data revealed that the GG genotype of IL-10 -1082A/G exhibited significant association with genotype 3 chronic HCV infection compared to controls. Treatment response data also showed a significant increase in risk for the GG genotype of IL-10 -1082A/G in response-relapse patients or non-responder patients compared to sustained virological response patients. Further, a significant increase in risk was also revealed for the CC genotype of IL-10 -592A/C in response-relapse patients or non-responder patients compared to sustained virological response patients, suggesting a role of the GG genotype of IL-10 -1082A/G and CC genotype of IL-10 -592A/C in the treatment outcome of combined Peg-IFN/ribavirin therapy.

High tuberculosis prevalence in children exposed at home to drug-resistant tuberculosis.

SETTING: Urban Karachi, Pakistan. OBJECTIVE: To describe the yield of a contact investigation protocol implemented among children living with drug-resistant tuberculosis (DR-TB) patients. DESIGN: We implemented a contact investigation protocol in households of DR-TB patients treated at the Indus Hospital, Karachi, between January 2008 and April 2011. This included a detailed history and physical examination, tuberculin skin test, chest radiograph, smear microscopy and culture of sputum or gastric aspirate specimens, and drug susceptibility testing. Treatment supporters who visited DR-TB patients at home referred all child contacts for baseline evaluation and performed monthly assessments. We evaluated two age groups: 1) children aged <5 years, and 2) those aged 5-14 years. RESULTS: Among 133 children aged <15 years in 40 households, 40.4% (51/125) were moderately to severely underweight (weight-for-age Z-score <-2). Overall, 7.5% (10/133) had TB disease. This proportion was 6.5% (2/31) in those aged <5 years and 7.8% (8/102) in those aged 5-14 years. Seven (7/10) were smear-positive, and 4/10 had culture-confirmed multidrug-resistant Mycobacterium tuberculosis CONCLUSION: We detected a high prevalence of TB in children who live with DR-TB patients, regardless of the age of the child. Child contacts of DR-TB patients are a high-yield population for detecting TB cases.

Application of low-background gamma-ray spectrometry to monitor radioactivity in the environment and food.

The results are described of an upgrade of the low-background gamma-ray spectrometry laboratory at New York State Department of Health by acquiring sensitivity to low-energy gamma rays. Tuning of the spectrometer and its low-energy response characteristics are described. The spectrometer has been applied to monitor the environment by measuring aerosols and water in New York State contaminated by the 2011 Fukushima accident plume. In addition, the spectrometer has been used to monitor radioactivity in food by performing a study of cesium in Florida milk.

Basal subtype, as approximated by triple-negative phenotype, is associated with locoregional recurrence in a case-control study of women with 0-3 positive lymph nodes after mastectomy.

PURPOSE: Basal subtype, as approximated by the triple-negative phenotype (ER-PR-Her2-), has correlated with higher LRR in recent studies. Indications for postmastectomy RT (PMRT) in women with 0-3 positive lymph nodes remain unclear. We evaluated the importance of biologic subtype in a cohort of women with LRR after mastectomy. METHODS: We identified 22 women with 0-3 positive lymph nodes at our institution who were initially treated with mastectomy (without post-mastectomy radiation), suffered LRRs, and had paraffin-embedded tissue blocks from the primary mastectomy specimen available for staining. None of these women received PMRT. We case-control matched these to 29 women with 0-3 positive nodes who had mastectomy (no PMRT) and remained without evidence of disease at last follow-up and had available primary specimens for processing. We matched controls for age (±3 years) and follow-up duration (<5 year vs. more). Paraffin-embedded specimens were used to construct a triple-redundant tissue microarray. We used conditional logistic regressions to study the association between each predictor and LRR. Results were summarized based on odds ratio (OR). RESULTS: On univariate analysis, ER+, PR+, or the combination was strongly associated with lower odds of LRR. Basal subtype, as approximated by ER-PR-Her2- (TN), was associated with higher LRR (OR 8.5, p = 0.048). Use of chemotherapy also was associated with lower LRR (OR 0.126, p = 0.0073). CONCLUSIONS: Our data are concordant with reports from others demonstrating that TN phenotype is associated with higher LRR and can be considered along with other predictors of LRR when selecting women for PMRT.

Identification of Chili leaf curl virus Causing Leaf Curl Disease of Petunia in Oman.

Petunias (Petunia × hybrida) are the most important ornamental plants in Oman. In 2012, petunias were observed in public parks and airport landscape in Dhofar region with symptoms of upward leaf curling, yellowing and vein clearing, and size reduction in leaves. Almost all plants in the surveyed landscape showed high infestation of Bemisia tabaci and symptoms that suggested infection with a begomovirus. Six symptomatic samples were collected from three different sites. All symptomatic samples were found PCR-positive with diagnostic primers for begomovirus (3) when DNA extracted from infected leaves was used as template. Nucleic acids extracted from the symptomatic leaves were used to amplify circular DNA molecules by rolling circle amplification method. The amplified concatameric products were digested with restriction enzyme PstI, which yielded a product ∼2.8 kb in size. The putative begomovirus fragment was cloned and sequenced in both orientations. Partial sequences of six clones were 99 to 100% similar and thus only two clones, PT-2 and PT-3, were fully sequenced. The whole genomes of both clones were 2,761 bp, and both were deposited in GenBank under accession numbers HF968755 and HF968756 for the isolates PT-2 and PT-3, respectively. Both sequences had six open reading frames; Rep, TrAP, REn, and C4 genes in complementary sense; and CP and V2 genes in virion-sense, typical of the begomovirus genome organization. Upon alignment, the two sequences showed 99.4% nucleotide identity with each other, thus representing isolates of a single begomovirus species. BlastN comparison showed PT-2 and PT-3 from petunia were 94 to 95% identical to the sequences of ChCLV from Oman (JN604490 to JN604500), which were obtained from other hosts. ClustalV multiple sequence alignment showed that isolates PT-2 and PT-3 shared maximum sequence identity of 93.3 and 92.8%, respectively, with an isolate of ChLCV-OM (JN604495). According to ICTV rules for begomoviruses, PT-3 should be considered to be a new strain of ChLCV-OM and PT-2 a variant of the already existing ChLCV-OM strain. We propose the name for this new strain as the "Petunia strain" of Chili leaf curl virus (ChLCV-Pet). Two infectious clones were constructed from the PT-2 and PT-3 sequences, clones as 1.75-genome sequences in a binary vector, suitable for agroinfection to confirm their infectivity. Both clones, PT-2 and PT-3, produced typical leaf curl disease symptoms upon inoculation on petunia 18 days post inoculation. The presence of the same virus in symptomatic field infected and inoculated petunia was confirmed by Southern blot using 650 bp DIG labeled probe prepared from CP region of PT-3 isolate. ChLCV-OM, a monopartite begomovirus, is widely associated with leaf curl disease of tomato and pepper in Oman, with its origin traced to the Indian subcontinent (2). Identification of a new strain of ChLCV from petunia provides evidence of an ongoing rapid evolution of begomoviruses in this region. Although petunia has been tested as an experimental host for some begomoviruses (1,4), this is the first report of petunia as natural host for ChLCV, a begomovirus previously reported in tomato and pepper in Oman. References: (1) Cui et al. J. Virol. 78:13966, 2004. (2) Khan et al. Virus Res. 177:87, 2013. (3) Khan et al. Plant Dis. 97:1396, 2013. (4) Urbino et al. Arch. Virol. 149:417, 2003.