Excess natural-cause mortality in US counties and its association with reported COVID-19 deaths.

In the United States, estimates of excess deaths attributable to the COVID-19 pandemic have consistently surpassed reported COVID-19 death counts. Excess deaths reported to non-COVID-19 natural causes may represent unrecognized COVID-19 deaths, deaths caused by pandemic health care interruptions, and/or deaths from the pandemic's socioeconomic impacts. The geographic and temporal distribution of these deaths may help to evaluate which explanation is most plausible. We developed a Bayesian hierarchical model to produce monthly estimates of excess natural-cause mortality for US counties over the first 30 mo of the pandemic. From March 2020 through August 2022, 1,194,610 excess natural-cause deaths occurred nationally [90% PI (Posterior Interval): 1,046,000 to 1,340,204]. A total of 162,886 of these excess natural-cause deaths (90% PI: 14,276 to 308,480) were not reported to COVID-19. Overall, 15.8 excess deaths were reported to non-COVID-19 natural causes for every 100 reported COVID-19 deaths. This number was greater in nonmetropolitan counties (36.0 deaths), the West (Rocky Mountain states: 31.6 deaths; Pacific states: 25.5 deaths), and the South (East South Central states: 26.0 deaths; South Atlantic states: 25.0 deaths; West South Central states: 24.2 deaths). In contrast, reported COVID-19 death counts surpassed estimates of excess natural-cause deaths in metropolitan counties in the New England and Middle Atlantic states. Increases in reported COVID-19 deaths correlated temporally with increases in excess deaths reported to non-COVID-19 natural causes in the same and/or prior month. This suggests that many excess deaths reported to non-COVID-19 natural causes during the first 30 mo of the pandemic in the United States were unrecognized COVID-19 deaths.

Improving forensic perpetrator identification with Super-Recognizers.

About a decade ago, Super-Recognizers (SRs) were first described as individuals with exceptional face identity processing abilities. Since then, various tests have been developed or adapted to assess individuals' abilities and identify SRs. The extant literature suggests that SRs may be beneficial in police tasks requiring individual identification. However, in reality, the performance of SRs has never been examined using authentic forensic material. This not only limits the external validity of test procedures used to identify SRs, but also claims concerning their deployment in policing. Here, we report the first-ever investigation of SRs' ability to identify perpetrators using authentic case material. We report the data of 73 SRs and 45 control participants. These include (a) performance on three challenging tests of face identity processing recommended by Ramon (2021) for SR identification; (b) performance for perpetrator identification using four CCTV sequences depicting five perpetrators and police line-ups created for criminal investigation purposes. Our findings demonstrate that the face identity processing tests used here are valid in measuring such abilities and identifying SRs. Moreover, SRs excel at perpetrator identification relative to control participants, with more correct perpetrator identifications, the better their performance across lab tests. These results provide external validity for the recently proposed diagnostic framework and its tests used for SR identification (Ramon, 2021). This study provides the first empirical evidence that SRs identified using these measures can be beneficial for forensic perpetrator identification. We discuss theoretical and practical implications for law enforcement, whose procedures can be improved via a human-centric approach centered around individuals with superior abilities.

Co-Circulating Monkeypox and Swinepox Viruses, Democratic Republic of the Congo, 2022.

In September 2022, deaths of pigs manifesting pox-like lesions caused by swinepox virus were reported in Tshuapa Province, Democratic Republic of the Congo. Two human mpox cases were found concurrently in the surrounding community. Specific diagnostics and robust sequencing are needed to characterize multiple poxviruses and prevent potential poxvirus transmission.

Interventional Study of Nonpharmaceutical Measures to Prevent COVID-19 Aboard Cruise Ships.

Cruise ships carrying COVID-19-vaccinated populations applied near-identical nonpharmaceutical measures during July-November 2021; passenger masking was not applied on 2 ships. Infection risk for masked passengers was 14.58 times lower than for unmasked passengers and 19.61 times lower than in the community. Unmasked passengers' risk was slightly lower than community risk.

Genome-wide investigation of the LARP gene family: focus on functional identification and transcriptome profiling of ZmLARP6c1 in maize pollen.

BACKGROUND: The La-related proteins (LARPs) are a superfamily of RNA-binding proteins associated with regulation of gene expression. Evidence points to an important role for post-transcriptional control of gene expression in germinating pollen tubes, which could be aided by RNA-binding proteins. RESULTS: In this study, a genome-wide investigation of the LARP proteins in eight plant species was performed. The LARP proteins were classified into three families based on a phylogenetic analysis. The gene structure, conserved motifs, cis-acting elements in the promoter, and gene expression profiles were investigated to provide a comprehensive overview of the evolutionary history and potential functions of ZmLARP genes in maize. Moreover, ZmLARP6c1 was specifically expressed in pollen and ZmLARP6c1 was localized to the nucleus and cytoplasm in maize protoplasts. Overexpression of ZmLARP6c1 enhanced the percentage pollen germination compared with that of wild-type pollen. In addition, transcriptome profiling analysis revealed that differentially expressed genes included PABP homologous genes and genes involved in jasmonic acid and abscisic acid biosynthesis, metabolism, signaling pathways and response in a Zmlarp6c1::Ds mutant and ZmLARP6c1-overexpression line compared with the corresponding wild type. CONCLUSIONS: The findings provide a basis for further evolutionary and functional analyses, and provide insight into the critical regulatory function of ZmLARP6c1 in maize pollen germination.

Ethnicity and outcomes for patients with gastrointestinal disorders attending an emergency department serving a multi-ethnic population.

BACKGROUND: Ethnic inequalities in acute health acute care are not well researched. We examined how attendee ethnicity influenced outcomes of emergency care in unselected patients presenting with a gastrointestinal (GI) disorder. METHODS: A descriptive, retrospective cohort analysis of anonymised patient level data for University Hospitals of Leicester emergency department attendees, from 1 January 2018 to 31 December 2021, receiving a diagnosis of a GI disorder was performed. The primary exposure of interest was self-reported ethnicity, and the two outcomes studied were admission to hospital and whether patients underwent clinical investigations. Confounding variables including sex and age, deprivation index and illness acuity were adjusted for in the analysis. Chi-squared and Kruskal-Wallis tests were used to examine ethnic differences across outcome measures and covariates. Multivariable logistic regression was used to examine associations between ethnicity and outcome measures. RESULTS: Of 34,337 individuals, median age 43 years, identified as attending the ED with a GI disorder, 68.6% were White. Minority ethnic patients were significantly younger than White patients. Multiple emergency department attendance rates were similar for all ethnicities (overall 18.3%). White patients had the highest median number of investigations (6, IQR 3-7), whereas those from mixed ethnic groups had the lowest (2, IQR 0-6). After adjustment for age, sex, year of attendance, index of multiple deprivation and illness acuity, all ethnic minority groups remained significantly less likely to be investigated for their presenting illness compared to White patients (Asian: aOR 0.80, 95% CI 0.74-0.87; Black: 0.67, 95% CI 0.58-0.79; mixed: 0.71, 95% CI 0.59-0.86; other: 0.79, 95% CI 0.67-0.93; p < 0.0001 for all). Similarly, after adjustment, minority ethnic attendees were also significantly less likely to be admitted to hospital (Asian: aOR 0.63, 95% CI 0.60-0.67; Black: 0.60, 95% CI 0.54-0.68; mixed: 0.60, 95% CI 0.51-0.71; other: 0.61, 95% CI 0.54-0.69; p < 0.0001 for all). CONCLUSIONS: Significant differences in usage patterns and disparities in acute care outcomes for patients of different ethnicities with GI disorders were observed in this study. These differences persisted after adjustment both for confounders and for measures of deprivation and illness acuity and indicate that minority ethnic individuals are less likely to be investigated or admitted to hospital than White patients.

A novel hybridization capture method for direct whole genome sequencing of clinical specimens to inform Legionnaires' disease investigations.

The unprecedented precision and resolution of whole genome sequencing (WGS) can provide definitive identification of infectious agents for epidemiological outbreak tracking. WGS approaches, however, are frequently impeded by low pathogen DNA recovery from available primary specimens or unculturable samples. A cost-effective hybrid capture assay for Legionella pneumophila WGS analysis directly on primary specimens was developed. DNA from a diverse range of sputum and autopsy specimens PCR-positive for L. pneumophila serogroup 1 (LPSG1) was enriched with this method, and WGS was performed. All tested specimens were determined to be enriched for Legionella reads (up to 209,000-fold), significantly improving the discriminatory power to compare relatedness when no clinical isolate was available. We found the WGS data from some enriched specimens to differ by less than five single-nucleotide polymorphisms (SNPs) when compared to the WGS data of a matched culture isolate. This testing and analysis retrospectively provided previously unconfirmed links to environmental sources for clinical specimens of sputum and autopsy lung tissue. The latter provided the additional information needed to identify the source of these culture-negative cases associated with the South Bronx 2015 Legionnaires' disease (LD) investigation in New York City. This new method provides a proof of concept for future direct clinical specimen hybrid capture enrichment combined with WGS and bioinformatic analysis during outbreak investigations.IMPORTANCELegionnaires' disease (LD) is a severe and potentially fatal type of pneumonia primarily caused by inhalation of Legionella-contaminated aerosols from man-made water or cooling systems. LD remains extremely underdiagnosed as it is an uncommon form of pneumonia and relies on clinicians including it in the differential and requesting specialized testing. Additionally, it is challenging to obtain clinical lower respiratory specimens from cases with LD, and when available, culture requires specialized media and growth conditions, which are not available in all microbiology laboratories. In the current study, a method for Legionella pneumophila using hybrid capture by RNA baiting was developed, which allowed us to generate sufficient genome resolution from L. pneumophila serogroup 1 PCR-positive clinical specimens. This new approach offers an additional tool for surveillance of future LD outbreaks where isolation of Legionella is not possible and may help solve previously unanswered questions from past LD investigations.

Thinking Beyond the Device: An Overview of Human- and Equity-Centered Approaches for Health Technology Design.

A shift in the traditional technocentric view of medical device design to a human-centered one is needed to bridge existing translational gaps and improve health equity. To ensure the successful and equitable adoption of health technology innovations, engineers must think beyond the device and the direct end user and must seek a more holistic understanding of broader stakeholder needs and the intended context of use early in a design process. The objectives of this review article are (a) to provide rationale for the need to incorporate meaningful stakeholder analysis and contextual investigation in health technology development and biomedical engineering pedagogy, (b) to review existing frameworks and human- and equity-centered approaches to stakeholder engagement and contextual investigation for improved adoption of innovative technologies, and (c) to present case studyexamples of medical device design that apply these approaches to bridge the gaps between biomedical engineers and the contexts for which they are designing.

Experiences of Physicians Investigated for Professionalism Concerns: a Narrative Review.

Growing attention is being paid to physician health and behavior, including the occurrence of mental health issues and burnout in medical providers, physician impairment, and alleged disruptive behavior in physicians. In any of these areas, a physician may become the subject of an investigation. Studying the experience of investigated physicians is important to identify and mitigate any potential adverse personal and practice impacts, which in turn can hinder patient care. The purpose of this review is to (1) summarize the published scientific literature to date regarding the experiences of physicians who have been investigated, and (2) based on these findings consider strategies to mitigate any adverse effects of the investigatory process for physicians. A search of the databases PubMed and Ovid MEDLINE was conducted in June 2023 using relevant search terms. After reviewing titles, abstracts, full-length articles, and reference lists, 16 articles were identified and reviewed. Physicians in multiple countries who had been investigated commonly described short-term (feelings of anger, depression, anxiety, shame, powerlessness, isolation, being betrayed, less confidence in clinical decision-making) and long-term (increase in defensive practice, retiring early) impacts of the investigatory process. Physicians found the most difficult aspects of the investigation process to be the length of time involved, lack of transparency/communication regarding the process, feelings of isolation, and dealing with vexatious complaints. While complaints about physicians have the potential to portend constructive individual practice and systemic changes, research suggests that the investigatory process for physicians is associated with negative short- and long-term emotional and practice impacts. Strategies to mitigate the unintended adverse effects of investigatory processes are proposed. Further research is warranted to clarify the investigation experience for physicians, including physicians underrepresented in medicine, and to systematically assess the effectiveness of strategies to mitigate unhealthy or disruptive components of the investigatory process.

The treatment pattern of advanced HR-positive and HER2-negative breast cancer in central southern China: a hospital-based cross-sectional study.

AIMS: This investigation aims to elucidate the treatment status of advanced HR+/HER2- breast cancer patients in Hunan Province of Central Southern China from November 2021 to December 2022. METHODS: Data from 301 patients with advanced HR+/HER2- breast cancer were collected from the breast cancer investigation project in Hunan under the guidance of the Chinese Society of Clinical Oncolfogy (CSCO). The data included the clinical characteristics of patients and the status of first-line and second-line rescue treatment. RESULTS: First-line chemotherapy and endocrine therapy for mBC accounted for 40% (121/301) and 60% (180/301) of treatments, respectively. AI (21%), AI plus CDK4/6 inhibitor (28%), and fulvestrant (24%) or fulvestrant plus CDK4/6 inhibitor (18%) were the most common first-line endocrine therapies. Taxane-based chemotherapy was the most common first-line chemotherapy (59%). Second-line chemotherapy and endocrine therapy for mBC accounted for 43% (72/166) and 57% (94/166) of treatments, respectively. Fulvestrant (23%) or fulvestrant plus CDK4/6 inhibitor (29%) were the most common second-line endocrine therapies. The prevalences of AI and AI plus CDK4/6 inhibitor decreased to 19% and 11%, respectively. T (taxane)-based chemotherapy was still the most common chemotherapy regimen (46%). Third-line chemotherapy was more prevalent than endocrine therapy (57% vs. 41%). T (taxane)-based chemotherapy was still the most common chemotherapy regimen (46%). Fulvestrant plus CDK4/6 inhibitor was the most common endocrine therapy (33%). AI, AI plus CDK4/6 inhibitor, and fulvestrant accounted for 21%, 12% and 18% of third-line endocrine therapies, respectively. CONCLUSIONS: Compared to chemotherapy, endocrine therapy was a more favorable choice for first-line and second-line treatment for HR+/HER2- advanced breast cancer patients in Hunan Province.

Intermittent investigations on attenuation mechanism of rechargeable zinc-air batteries during charge/discharge cycles.

Rechargeable zinc-air batteries (RZABs) are an ideal substitute for energy storage, but the short cycle longevity during long-term charge/discharge operation is one of the bottleneck factors that seriously restrict commercial application. Herein, the FeCo alloy/N, S co-doped carbon aerogel (NSCA/FeCo) were prepared as catalysts of cathode for RZABs. We investigated the polarization and impedance on long-term cycles during the battery operation to explore the attenuation mechanism. The results indicated that the roundtrip efficiency of batteries during charge/discharge cycles reduced fast initially and then slow. Besides, the comparative experiment was tested through the replacement of a new electrolyte and a zinc sheet. It is manifested that the failure of the battery is mainly due to the attenuation of the air cathode performance. Therefore, to further disclose the influencing factors and internal mechanisms of air cathode performance degradation, we conducted a series of characterization and testing, including the hydrophilicity, surface morphology, elemental composition, and electrochemical performance of three-electrode systems at different cycle times. This work not only provides a theoretical basis for deeply comprehending the attenuation mechanism of the cathode but also serves a reference for the material design and operating condition optimization of RZABs.

Prolactin promotes the recruitment of main olfactory bulb cells and enhances the behavioral exploration toward a socio-sexual stimulus in female mice.

Olfactory communication is triggered by pheromones that profoundly influence neuroendocrine responses to drive social interactions. Two principal olfactory systems process pheromones: the main and the vomeronasal or accessory system. Prolactin receptors are expressed in both systems suggesting a participation in the processing of olfactory information. We previously reported that prolactin participates in the sexual and olfactory bulb maturation of females. Therefore, we explored the expression of prolactin receptors within the olfactory bulb during sexual maturation and the direct responses of prolactin upon pheromonal exposure. Additionally, we assessed the behavioral response of adult females exposed to male sawdust after prolactin administration and the consequent activation of main and accessory olfactory bulb and their first central relays, the piriform cortex and the medial amygdala. Last, we investigated the intracellular pathway activated by prolactin within the olfactory bulb. Here, prolactin receptor expression remained constant during all maturation stages within the main olfactory bulb but decreased in adulthood in the accessory olfactory bulb. Behaviorally, females that received prolactin actively explored the male stimulus. An increased cFos activation in the amygdala and in the glomerular cells of the whole olfactory bulb was observed, but an augmented response in the mitral cells was only found within the main olfactory bulb after prolactin administration and the exposure to male stimulus. Interestingly, the ERK pathway was upregulated in the main olfactory bulb after exposure to a male stimulus. Overall, our results suggest that, in female mice, prolactin participates in the processing of chemosignals and behavioral responses by activating the main olfactory system and diminishing the classical vomeronasal response to pheromones.

The impact of an antibody investigation algorithm emphasizing specificity on reducing potential false-positive warm autoantibody detection at a Canadian tertiary care centre.

BACKGROUND AND OBJECTIVES: To reduce potential false-positive warm autoantibody (WAA) by solid-phase red cell adherence assay (SPRCA), our centre implemented a new antibody investigation algorithm (AIA) by classifying cases with panreactive SPRCA but negative saline-indirect antiglobulin test as 'antibody of undetermined significance' (AUS) after excluding clinically significant antibodies. We assessed the effects of the new AIA and subsequent alloantibody formation in patients with AUS. MATERIALS AND METHODS: Samples from patients with positive SPRCA screens between 1 September 2017 and 31 August 2021 were selected for the study. Frequencies of antibodies classified by the old and new AIAs were compared using Fisher's exact test. Patient demographics, transfusion history and antibody formation in cases of AUS were collected. RESULTS: A significant reduction in potential WAA frequencies from 127/1167 (11%) to 53/854 (6%) was observed (p < 0.001) when compared between the old and new AIAs among 2021 positive SPRCA antibody screens. While no patients with AUS later transitioned to potential WAA using the new AIA, four patients developed alloantibodies, including anti-E, anti-C, both anti-C and anti-E, and anti-Wra . CONCLUSION: A significant reduction in the frequencies of potential false-positive WAA detection at our centre was observed after implementing the new AIA, leading to less resource and phenotypically matched red blood cell (RBC) use. Some patients still developed subsequent RBC alloimmunization, so clinically relevant alloantibodies should be carefully excluded before determining AUS, taking forming or evanescent antibodies into consideration.

Shedding light on vitamin D in tuberculosis: A comprehensive review of clinical trials and discrepancies.

Over the past few decades, there has been extensive research on the use of vitamin D as an adjunctive therapy in the treatment and prevention of tuberculosis. In vitro studies have provided valuable insights into the mechanisms by which vitamin D activates the immune response to combat Mycobacterium tuberculosis. These encouraging findings have spurred clinical investigations globally to assess the effectiveness of vitamin D as a preventive measure and as an adjunctive treatment for tuberculosis. However, the results from these clinical studies have been contradictory, with some demonstrating clear efficacy while others report only modest or no activity. In this review, we aim to analyze the clinical studies on vitamin D and examine the possible discrepancies observed in their outcomes.

Bridging the gap between decomposition theory and forensic research on postmortem interval.

Knowledge of the decomposition of vertebrate animals has advanced considerably in recent years and revealed complex interactions among biological and environmental factors that affect rates of decay. Yet this complexity remains to be fully incorporated into research or models of the postmortem interval (PMI). We suggest there is both opportunity and a need to use recent advances in decomposition theory to guide forensic research and its applications to understanding the PMI. Here we synthesise knowledge of the biological and environmental factors driving variation in decomposition and the acknowledged limitations among current models of the PMI. To guide improvement in this area, we introduce a conceptual framework that highlights the multiple interdependencies affecting decay rates throughout the decomposition process. Our framework reinforces the need for a multidisciplinary approach to PMI research, and calls for an adaptive research cycle that aims to reduce uncertainty in PMI estimates via experimentation, modelling, and validation.

Spatial relationships among offender, knife, and victim during slashing attacks: implications for crime scene reconstruction.

BACKGROUND: The offender-victim spatial relationship is crucial in reconstructing a crime scene. The study aims to evaluate the spatial relationship of performing slashing attacks on a dummy using a Chinese kitchen knife, and thus to establish a scientific basis for crime scene reconstruction. METHODS: Twenty-four participants (12 males and 12 females) slashed a dummy's neck or chest using a kitchen knife, and the kinematic data were obtained using a three-dimensional motion capture system. The spatial relationships among offender, knife, and victim during slashing attacks were analyzed. RESULTS: Slashing distance and occupancy area are significantly influenced by gender (all P < 0.05), with males having higher values than females. Body parts significantly influence bevel angle, offender and victim azimuth angles, slashing distance, relative slashing distance, and occupancy area (all P < 0.01), with slashing the chest resulting in larger values than slashing the neck. CONCLUSION: Gender and body position significantly influence the spatial relationships of slashing action. Our data indicate that males stand farther away and occupy a larger area during slashing attacks. When the chest is slashed, the wound orientation is more diagonal, the offender's standing position and slashing distance are farther, and the occupancy area is larger compared to the neck. The findings could help identify the spatial relationships among offender, knife, and victim, providing a scientific basis for criminal investigations and court trials.

Accelerating evidence synthesis for safety assessment through ClinicalTrials.gov platform: a feasibility study.

BACKGROUND: Standard systematic review can be labor-intensive and time-consuming meaning that it can be difficult to provide timely evidence when there is an urgent public health emergency such as a pandemic. The ClinicalTrials.gov provides a promising way to accelerate evidence production. METHODS: We conducted a search on PubMed to gather systematic reviews containing a minimum of 5 studies focused on safety aspects derived from randomized controlled trials (RCTs) of pharmacological interventions, aiming to establish a real-world dataset. The registration information of each trial from eligible reviews was further collected and verified. The meta-analytic data were then re-analyzed by using 1) the full meta-analytic data with all trials and 2) emulated rapid data with trials that had been registered and posted results on ClinicalTrials.gov, under the same synthesis methods. The effect estimates of the full meta-analysis and rapid meta-analysis were then compared. RESULTS: The real-world dataset comprises 558 meta-analyses. Among them, 56 (10.0%) meta-analyses included RCTs that were not registered in ClinicalTrials.gov. For the remaining 502 meta-analyses, the median percentage of RCTs registered within each meta-analysis is 70.1% (interquartile range: 33.3% to 88.9%). Under a 20% bias threshold, rapid meta-analyses conducted through ClinicalTrials.gov achieved accurate point estimates ranging from 77.4% (using the MH model) to 83.1% (using the GLMM model); 91.0% to 95.3% of these analyses accurately predicted the direction of effects. CONCLUSIONS: Utilizing the ClinicalTrials.gov platform for safety assessment with a minimum of 5 RCTs holds significant potential for accelerating evidence synthesis to support urgent decision-making.

Sexual dimorphism and topological variability in fingerprint ridge density in a north-west Indian population.

The science of fingerprints is very crucial in criminal investigation as it helps identify perpetrators or victims of a crime. Fingerprint ridge density (FPRD), which refers to the number of ridges within a specific area on the epidermal skin layer of the distal phalanges in humans, has been found to differ between males and females. This study attempts to estimate the sex from FPRD and evaluates the diversity in FPRD across several topological areas. The study involves 208 participants (120 males, 88 females) between the ages 18 to 25 years from a North-west Indian population. Fingerprints were collected, and FPRD was accessed in radial, ulnar, and proximal areas as recommended by Gutierrez-Redomero et al. (Forensic Sci Int 180(1):17-22, 2008). FPRD has been quantified using the techniques described by Acree (Forensic Sci Int 102(1):35-44, 1999). When evaluating FPRD in the lateral pocket loops and twin loops, the proximal-side core was considered. The study reveals that males have a mean fingerprint ridge density of 12.82 ridges/25 mm2 while females have 13.01 ridges/25 mm2. Females have higher fingerprint ridge density solely in the proximal area; males have higher fingerprint ridge density in both radial and ulnar areas. In conclusion, this research underscores the potential of fingerprint ridge density as a parameter for investigating population variations and individual identification. Future studies on fingerprint ridge density in India's diverse population will help establish reference ranges, allowing for sex and likely population group estimation, making it a valuable tool for preliminary examinations and exclusion criteria for sex estimation in crime scene investigations.

The yield of tuberculosis contact investigation on relapsed TB patients and analysis of associated risk factors: Singapore's experience.

The yield of contact investigation on relapsed tuberculosis (TB) cases can guide strategies and resource allocation in the TB control programme. We conducted a retrospective cohort study to review the yield of contact investigation in relapsed TB cases and identify factors associated with TB infection (TBI) among close contacts of relapsed TB cases notified between 2018 and 2022 in Singapore. TB infection positivity was higher among contacts of relapsed cases which were culture-positive for Mycobacterium tuberculosis complex compared to those who were only polymerase chain reaction (PCR)-positive (14.8% vs. 12.3%). On multivariate analysis, after adjusting for age and gender of the index, gender, and existing comorbidities of contacts, factors independently associated with TBI were culture and smear positivity of the index (AOR 1.41, 95%CI 1.02-1.94), higher odds with every 10 years of increase in age compared to contacts below aged 30, contacts who were not Singapore residents (AOR 2.09, 95%CI 1.46-2.97), and household contacts (AOR 2.19, 95%CI 1.44-3.34). Although the yield of screening was higher for those who were culture-positive compared to only PCR-positive relapsed cases, contact tracing for only PCR-positive cases may still be important in a country with moderate TB incidence, should resources allow.

Health worker perspectives on barriers and facilitators of tuberculosis investigation coverage among index case contacts in rural Southwestern Uganda: a qualitative study.

BACKGROUND: In 2012, the World Health Organization recommended screening and investigation of contacts of index tuberculosis patients as a strategy to accelerate detection of tuberculosis (TB) cases. Nine years after the adoption of this recommendation, coverage of TB contact investigations in Uganda remains low. The objective of this study was to examine health care providers' perceptions of factors influencing coverage of TB contact investigations in three selected rural health facilities in Mbarara district, southwestern Uganda. METHODS: This study identified provider opinions on the barriers and facilitators to implementation of TB contact investigation using the Consolidated Framework for Implementation Research. Using an exploratory qualitative study design, semi-structured interviews with 19 health workers involved in the TB program at district, health facility and community levels were conducted from April 2020 and July 2020. Analysis was conducted inductively using reflexive thematic analysis in six iterative steps: familiarizing with the data, creating initial codes, searching for themes, reviewing themes, developing theme definitions, and writing the report. RESULTS: Nineteen health care workers participated in this study which translates to a 100% response rate. These included two district TB and leprosy supervisors, five nurses, five clinical officers, six village health team members and one laboratory technician. The three themes that emerged from the analysis were intervention-related, health system and contextual factors. Health system-related barriers included inadequate or delayed government funding for the TB program, shortage of human resources, insufficient personal protective equipment, and a stock-out of supplies such as Xpert MTB cartridges. Contextual barriers included steep terrain, poverty or low income, and the stigma associated with TB and COVID-19. Facilitators comprised increased knowledge and understanding of the intervention, performance review and on-the-job training of health workers. CONCLUSIONS: This study found that most of the factors affecting TB contact investigations in this rural community were related to health system constraints such as inadequate or delayed funding and human resource shortages. This can be addressed by strengthening the foundational elements of the health system - health financing and human resources - to establish a comprehensive TB control program that will enable the efficient identification of missing TB patients.