The Role of Trimethoprim/Sulfamethoxazole in the Treatment of Infections Caused by Carbapenem-Resistant Enterobacteriaceae

In the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE), trimethoprim-sulfamethoxazole (TMP-SMX) had a limited role in the treatment of less severe carbapenem-resistant Enterobacteriaceae (CRE) infections, especially urinary tract infections. Of tested CRE, only 29% were susceptible to TMPSMX. Development of resistance further limits the use of TMPSMX in CRE infections

Which came first: validity or clinical testing? The example of long QT genes

Aim: To investigate the potential relationship between the strength of evidence for a gene-disease association and inclusion of the gene on a targeted, indication-based gene panel test for hereditary long QT syndrome (LQTS) and to explore factors that may influence laboratory decisions about the inclusion or exclusion of genes from these clinical tests.Methods: A comprehensive literature search was performed to quantify existing evidence supporting putative LQTS gene-disease associations. This evidence included the year that the gene was first implicated in LQTS, the total number of published cases of LQTS attributed to the gene, and the presence of published segregation and functional data for the gene. To explore the possible relationship between the published evidence for clinical validity of each gene and availability of clinical genetic testing, semi-structured interviews were conducted with key laboratory stakeholders. Representatives from nine US laboratories offering clinical LQTS gene testing agreed to be interviewed regarding decision-making about when and why genes comprising their clinical LQTS test offerings were added.Results: Genes associated with LQTS before 2006 generally had more reported cases of LQTS and the greatest amount of supporting segregation and functional data prior to being offered as a clinical test. For genes first linked to LQTS after 2006, these trends are less linear and the timeframe between initial report and inclusion on clinical test menus decreased substantially. Advances in technology, lifting of patents, clinician request, and literature searches were cited as the main factors that influence composition of LQTS gene panel tests. Paradoxically, one lab director noted that it may require more evidence to remove a gene than to add a gene to a clinical test panel.Conclusion: Our evaluation of the LQTS genes illustrates the nuanced relationship between published evidence supporting a gene-disease association and availability of clinical testing. Expert assessment of clinical validity of gene-disease associations may help laboratories to determine gene panel content. The ultimate impact of such information on the composition of clinical gene tests as well as their utilization by clinicians and coverage by health insurance policies remains to be seen

"When a man drinks alcohol it's cool but when a woman drinks she is a hoe": A qualitative exploration of alcohol, gender, stigma, and sexual assault in Moshi, Tanzania.

Alcohol's ever-increasing global use poses a distinct threat to human well-being, with intake and associated burdens rising especially quickly in low- and middle-income countries like Tanzania. Prior research has shown alcohol use and related consequences differ by gender in Moshi, Tanzania, with important implications for both clinical care and future alcohol-reduction interventions. This study builds upon this knowledge by providing a deeper understanding of how gender differences affect alcohol-related stigma and sexual assault among Emergency Department (ED) and Reproductive Health Center (RHC) patients at Kilimanjaro Christian Medical Center (KCMC) in Moshi. In-depth interviews were conducted among ED and RHC KCMC patients (n = 19) selected for participation via purposive sampling. A mix of inductive and deductive coding schemes was used to identify themes and subthemes. All data were analyzed through a grounded theory approach. Gender roles that linked men with financial responsibilities and women with child caretaking led to different expectations on alcohol intake, with alcohol use encouraged for men but vilified for women. Women who drank, for example, were deemed poor mothers and undesirable spouses. Patients likewise emphasized that both alcohol-related stigma and sexual violence disproportionately impacted women, the latter fueled through alcohol use, with serious and lasting acts of discrimination and isolation from community members seen among women alcohol users but not for men. Women alcohol users in Moshi are subject to severe social consequences, facing disproportionate stigma and sexual violence as compared to men. Alcohol-related treatment for women should be mindful of the disproportionate burdens present in this context while treatment for men should be cognizant of the social pressures to drink. Strategies to address and/or mitigate these factors should be incorporated in subsequent care and interventions

Cross-Cultural Adaptation and Psychometric Properties of the SF-8 Questionnaire in Tanzanian Swahili for Injury Population

Background: There is a lack of tools to screen for health-related quality of life (HRQoL) in acute injury patients, despite the critical need for having a good understanding of the characteristics of mental health during the rehabilitation process. The SF-8 instrument, a shorter version of the SF-36, is the most widely used patient-based assessment of HRQoL. The aim of this research is to adapt the psychometric properties of the SF-8 to Swahili. Methods: This study is a secondary data analysis of previously collected and psychometric evaluation of the culturally adapted and translated SF-8. A cross-cultural adaptation committee carried out the process of translation to provide validity evidence based on test content. Confirmatory factor analysis was used to test the internal structure-based evidence. The validity based on relation to other variables (discriminant evidence) was tested using polychoric correlation with PHQ-2 (Patient Health Questionnaire-2). The reliability was tested using Cronbach’s alpha, Omega McDonald, and Composite Reliability. Results: 1434 adults who suffered an acute injury and presented to the emergency department between April 2018 and August 2020 were included in the study. The instrument demonstrated language clarity and domain coherence, showing validity evidence based on test content. The CFA (Confirmatory Factor Analysis) analysis showed good fit indices for both models (one- and two-factor models) of the SF-8. The discriminant evidence showed that SF-8 scores correlate strongly with the PHQ-2 instrument. These results supported the validity evidence in relation to other variables. All analyses of reliability were considered adequate with values above 0.90 for both models of the SF-8. Conclusions: The results show that the SF-8 instrument can provide relevant information about the health-related quality of life of acute injury patients, and allow practitioners to gain a better understanding of mental health, improving the treatment and follow-up of injury patients within Tanzanian culture

Alcohol use among emergency medicine department patients in Tanzania: A comparative analysis of injury versus non-injury patients.

BackgroundAlcohol is a leading behavioral risk factor for death and disability worldwide. Tanzania has few trained personnel and resources for treating unhealthy alcohol use. In Emergency Medicine Departments (EMDs), alcohol is a well-known risk factor for injury patients. At Kilimanjaro Christian Medical Center (KCMC) in Moshi, Tanzania, 30% of EMD injury patients (IP) test positive for alcohol upon arrival to the ED. While the IP population is prime for EMD-based interventions, there is limited data on if non-injury patients (NIP) have similar alcohol use behavior and potentially benefit from screening and intervention as well.MethodsThis was a secondary analysis of a systematic random sampling of adult (≥18 years old), KiSwahili speaking, KCMC EMD patients surveyed between October 2021 and May 2022. When medically stable and clinically sober, participants provided informed consent. Information on demographics (sex, age, years of education, type of employment, income, marital status, tribe, and religion), injury status, self-reported alcohol use, and Alcohol Use Disorder (AUD) Identification Test (AUDIT) scores were collected. Descriptive statistics were analyzed in RStudio using frequencies and proportions.ResultsOf the 376 patients enrolled, 59 (15.7%) presented with an injury. The IP and NIP groups did not differ in any demographics except sex, an expected difference as females were intentionally oversampled in the original study design. The mean [SD] AUDIT score (IP: 5.8 [6.6]; NIP: 3.9 [6.1]), drinks per week, and proportion of AUDIT ≥8 was higher for IP (IP:37%; NIP: 21%). However, alcohol preferences, drinking quantity, weekly expenditure on alcohol, perceptions of unhealthy alcohol use, attempts and reasons to quit, and treatment seeking were comparable between IPs and NIPs.ConclusionOur data suggests 37% of injury and 20% of non-injury patients screen positive for harmful or hazardous drinking in our setting. An EMD-based alcohol treatment and referral process could be beneficial to reduce this growing behavioral risk factor in non-injury as well as injury populations

Clinical evaluation of the alcohol use disorders identification test (AUDIT) in Moshi, Tanzania.

BackgroundAlcohol use disorder is a major cause of morbidity and mortality in low- and middle-income countries. Alcohol screening using a validated tool is a useful way to capture high-risk patients and engage them in early harm reduction interventions. Our objectives were to 1) evaluate the psychometric evidence the Alcohol Use Disorders Identification Test (AUDIT) and its subscales in the general population of Moshi, Tanzania, and 2) evaluate the usefulness of the tool at predicting alcohol-related harms.MethodsTwo hundred and fifty-nine adults living in Moshi, Tanzania were included in the study. We used the AUDIT and its subscales to determine the classification of harmful and hazardous drinking. To analyze the internal structure of AUDIT and the model adequacy we used Confirmatory Factor Analysis (CFA). The reliability of AUDIT was analyzed for Cronbach's alpha, Omega 6 and Composite Reliability. The optimal cut off point for the AUDIT was determined by the receiver operating characteristic (ROC) curve, using the Youden approach to maximize sensitivity and specificity.ResultsThe median score of the AUDIT was 1 (inter-quartile range: 0-7). The internal structure of the AUDIT showed factor loadings ranging from 0.420 to 0.873. Cronbach's alpha, Omega and Composite Reliability produced values above 0.70. The Average Variance Extracted was 0.530. For the AUDIT, a score of 8 was identified as the ideal cut-off value in our population.ConclusionsThis study validates AUDIT in the general population of Moshi and is one of the only studies in Africa to include measures of the internal structure of the AUDIT and its subscales

Effectiveness of a Brief Negotiational Intervention and Text-Based Booster to Reduce Harmful and Hazardous Alcohol Use in the Emergency Department of a Low-Resource Setting: A Pragmatic Randomized Adaptive Clinical Trial in Moshi, Tanzania

Background: Alcohol use contributes to over 3 million deaths annually. In Tanzania, similar to other low- and middle-income countries, there are no evidence-based culturally adapted interventions to address harmful alcohol use behaviors. We aim to determine the effectiveness of a culturally adapted brief intervention, “Punguza Pombe Kwa Afya Yako/Reduce Alcohol for your Health”, with mobile health-based boosters in reducing alcohol use and consequences at 3 months after discharge for adult acute injury patients presenting for care. Methods: We are conducting a pragmatic adaptive randomized control trial with two distinct stages, of which we are reporting only Stage 1. Stage 1 is a superiority trial comparing a culturally adapted brief intervention with short-message-service (SMS) text boosters versus usual care. Participants eligible for enrollment are adult injury patients (≥18 years of age), who sought care for an acute injury (<24 hours) at the Kilimanjaro Christian Medical Centre Emergency Department. Alcohol-related criteria for inclusion comprise self-disclosed alcohol use prior to the injury, scoring ≥8 on the Alcohol Use Disorder Identification Test (AUDIT), and/or testing positive (>0.0 g/dL) by alcohol breathalyzer. For all stages, the primary outcome was the number of binge drinking days in the previous 4 weeks. Results: During the trial period, 448 patients met inclusion criteria and consented to participate in the study. Of these, 148 were randomized to usual care, and 300 were randomized to the intervention arms. At the 3-month follow-up, significant differences were observed between the intervention arm and the usual care group. In the primary outcome, the intervention arm showed a notable reduction in mean predicted binge drinking days by 2.03 days (95% CI: -3.53 to -0.86; p=0.0035). Additionally, significant reductions were seen in secondary outcomes for the intervention group: the mean predicted number of drinking days (reduction of 1 day; 95% CI: -2.71 to 0.82; p=0.0005), and the predicted mean difference in the number of drinks (-12.22 drinks; 95% CI: -29.5 to 3.32; p=0.0024). However, no significant differences were found between the two groups in terms of drinking-related consequences or depression. Discussion: When compared to the usual care arm, Punguza Pombe Kwa Afya Yako with text booster significantly reduces binge drinking days, binge drinking episodes, and mean number of drinks consumed. These reductions in alcohol use at 3-month follow-up suggest our culturally adapted intervention is effective for alcohol harm reduction in acute injury patients in Tanzania