Lost in Follow-Up: Predictors of Patient No-Shows to Clinic Follow-Up After Abdominal Injury.

BACKGROUND: The aim of this study is to evaluate risk factors for non-attendance to post-discharge, hospital follow-up appointments for traumatically injured patients who underwent exploratory laparotomy. METHODS: This is a retrospective chart review of patients who underwent exploratory laparotomy for traumatic abdominal injury at an urban, Midwestern, level I trauma center with clinic follow-up scheduled after discharge. Clinically, relevant demographic characteristics, patients' distance from hospital, and the presence of staples, sutures, and drains requiring removal were collected. Descriptive statistics of categorical variables were calculated as totals and percentages and compared with a chi-squared test or Fisher's exact when appropriate. RESULTS: The sample included 183 patients who were largely assaultive trauma survivors (68%), male (80%), and black (53%) with a mean age of 35.4 ± 14.9 years. Overall, 18.5% no-showed for their follow-up appointment. On multivariate analysis for clinic no-show; length of stay (odds ratio = 0.92 [0.84-0.99], P = 0.04) and the need for suture, staple, or drain removal were protective for clinic attendance (odds ratio = 5.59 [1.07-7.01], P = 0.04). Overall, 12 patients (6.4%) were readmitted. Forty patients (18.3%) had their follow-up in the emergency department (ED). On multivariate regression of risk factors for ED visits, the only statistically significant factors (P < 0.05) were clinic appointment no-show (OR = 2.81) and self-pay insurance (OR = 4.78). CONCLUSIONS: Abdominal trauma patients are at high risk of no-show for follow-up appointments and no-show visits are associated with ED visits. Future work is needed evaluating interventions to improve follow-up.

Complications from Needle Thoracostomy: Penetration of the Myocardium.

We report a rare but serious complication of needle thoracostomy, penetration of the myocardium. Needle thoracostomy is typically performed in the prehospital setting or upon arrival in the emergency department for suspected tension pneumothorax. Needle decompression is generally taught and done anteriorly, in the 2nd intercostal space on the midclavicular line (MCL). An alternative approach is laterally, along the anterior axillary line (AAL) in the 4th intercostal space. Our case supports prior literature that the anterior MCL location has a low rate of efficacy to decompress the chest, as well as a high rate of complications. We recommend performing needle decompression laterally at the AAL whether in the field or in the emergency department.

Nonrestorative sleep scale: a reliable and valid short form of the traditional Chinese version.

PURPOSE: Previous research has suggested the essential unidimensionality of the 12-item traditional Chinese version of the Nonrestorative Sleep Scale (NRSS). This study aimed to develop a short form of the traditional Chinese version of the NRSS without compromising its reliability and validity. METHODS: Data were collected from 2 cross-sectional studies with identical target groups of adults residing in Hong Kong. An iterative Wald test was used to assess differential item functioning by gender. Based on the generalized partial credit model, we first obtained a shortened version such that further shortening would result in substantial sacrifice of test information and standard error of measurement. Another shortened version was obtained by the optimal test assembly (OTA). The two shortened versions were compared for test information, Cronbach's alpha, and convergent validity. RESULTS: Data from a total of 404 Chinese adults (60.0% female) who had completed the Chinese NRSS were gathered. All items were invariant by gender. A 6-item version was obtained beyond which the test performance substantially deteriorated, and a 9-item version was obtained by OTA. The 9-item version performed better than the 6-item version in test information and convergent validity. It had discrimination and difficulty indices ranging from 0.44 to 2.23 and - 7.58 to 2.13, respectively, and retained 92% of the test information of the original 12-item version. CONCLUSION: The 9-item Chinese NRSS is a reliable and valid tool to measure nonrestorative sleep for epidemiological studies.

Nonrestorative sleep scale: reliable and valid for the Chinese population.

PURPOSE: To conduct a linguistic and psychometric evaluation of a Chinese version of the Nonrestorative Sleep Scale (NRSS). METHODS: The Chinese NRSS was created from a standard forward-backward translation and trialed on 10 Chinese adults. Telephone interviews were then conducted with 100 adults, who completed the Chinese NRSS, the Pittsburgh Sleep Quality Index (PSQI), the Athens Insomnia Scale (AIS), the Center for Epidemiological Studies Depression Scale (CES-D), and the Toronto Hospital Alertness Test (THAT). A household survey was conducted with 20 subjects, followed by a confirmatory factor analysis (CFA), and a bifactor model was developed to evaluate the reliability and validity of the NRSS. RESULTS: The bifactor model had the root mean square error of approximation (RMSEA), standardized root mean square residual (SRMR), and comparative fit index (CFI) of 0.06, 0.06, and 0.97, respectively. Convergent validity was shown from the moderate associations with PSQI (r = - 0.66, P < 0.01), AIS (r = - 0.65, P < 0.01), CES-D (r = - 0.54, P < 0.01), and THAT (r = 0.68, P < 0.01). The coefficient omega (0.92), omega hierarchical (0.81), factor determinacy (0.93), H value (0.91), explained common variance (0.63), and percentage of uncontaminated correlations (0.80) derived from the bifactor CFA supported the essential unidimensionality of NRSS. CONCLUSIONS: The Chinese NRSS is a valid and reliable essential unidimensional tool for the assessment of nonrestorative sleep in the Chinese population.

Pelvic organ prolapse: An unusual cause of small bowel obstruction.

We present the rare case of a small bowel obstruction secondary to pelvic organ prolapse (POP). A 77-year-old female presented with four days of abdominal pain, nausea, and vomiting. She had a history of abdominal hysterectomy with bilateral salpingo-opherectomy and a mildly symptomatic cystocele. She was found to have an enterocele causing small bowel obstruction. The enterocele was manually reduced and subsequently managed non-operatively with a pessary. Prior case reports of small bowel obstructions secondary to POP required emergent surgical intervention. Post-menopausal women should be asked about symptoms or presence of pelvic organ prolapse and in the correct patient population, pelvic examination can be important for diagnosis and treatment of small bowel obstruction. If the enterocele is manually reduced non-operative management can be safe and effective.

Epidemiological features of influenza in Canadian adult intensive care unit patients.

To identify predictive factors and mortality of patients with influenza admitted to intensive care units (ICU) we carried out a prospective cohort study of patients hospitalized with laboratory-confirmed influenza in adult ICUs in a network of Canadian hospitals between 2006 and 2012. There were 626 influenza-positive patients admitted to ICUs over the six influenza seasons, representing 17·9% of hospitalized influenza patients, 3·1/10,000 hospital admissions. Variability occurred in admission rate and proportion of hospital influenza patients who were admitted to ICUs (proportion range by year: 11·7-29·4%; 21·3% in the 2009-2010 pandemic). In logistic regression models ICU patients were younger during the pandemic and post-pandemic period, and more likely to be obese than hospital non-ICU patients. Influenza B accounted for 14·2% of all ICU cases and had a similar ICU admission rate as influenza A. Influenza-related mortality was 17·8% in ICU patients compared to 2·0% in non-ICU patients.

Patient-reported outcomes in routine cancer clinical practice: a scoping review of use, impact on health outcomes, and implementation factors.

BACKGROUND: This review focused on the identification of patient-reported outcome measures (PROMs) used in routine cancer clinical practice, the impact on patient, provider, and system outcomes, and the implementation factors influencing uptake. METHODS: A scoping review of the published health literature was conducted using empirical databases, namely, Ovid Medline (2003 to September 2013), CINAHL (2003-2013) and PsycINFO (2003-2013). Scoping reviews are systematic literature reviews in a broad topic area that provide relevant and quantified results about the knowledge available on a particular topic and aim to rapidly map and synthesize the evidence to emphasize what is known. RESULTS: From a total of 2447 unique publications, 30 articles that met eligibility criteria were reviewed. PRO use appears to be acceptable to patients, enables earlier detection of symptoms and may improve communication between clinicians and patients. However, the impact of routine PROMs collection on health outcomes is less clear and high-quality research is still warranted. CONCLUSION: PROMs use in routine cancer clinical practice is growing with improvements on essential care processes shown but a number of implementation barriers must still be addressed. The lack of standardization in PROMs used in cancer organizations may make it difficult to use these data for quality monitoring in the future.

Insulin resistance, and not ß-cell impairment, mediates association between Mycobacterium tuberculosis sensitization and type II diabetes mellitus among US adults.

Type 2 diabetes mellitus (T2DM) may be a long-term sequela of infection with Mycobacterium tuberculosis (M.tb) by mechanisms that remain to be fully explained. We evaluated association between M.tb sensitization and T2DM among U.S adults and, via formal mediation analysis, the extent to which this association is mediated by insulin resistance and/or ß-cell failure. These evaluations accounted for demographic, socio-economic, behavioral and clinical characteristics. T2DM was assessed by fasting plasma glucose, 2-hour oral glucose tolerance testing and HbA1c; homoeostasis model assessment 2 (HOMA2) was used to estimate ß-cell dysfunction (HOMA2-B) and insulin resistance (HOMA2-IR); while M.tb sensitization status was ascertained by tuberculin skin testing (TST). Exposure to M.tb was associated with increased risk for T2DM, likely driven by an increase in insulin resistance. Definitive prospective studies examining incident T2DM following tuberculosis are warranted. Research in Context: What is already known about this subject?: Accumulating evidence suggests that pre-diabetes and new-onset type 2 diabetes mellitus (T2DM) may be a long-term complication of exposure to Mycobacterium tuberculosis ( M.tb ) via mechanisms that remain to be unraveled What is the key question?: To what extent do insulin resistance and ß-cell failure mediate the association between M.tb sensitization with T2DM among US adults? What are the new findings?: M.tb sensitization is characterized by distinct glucose metabolic disturbances manifesting as increased risk of T2DM and isolated impaired fasting glucose (IFG) Insulin resistance, and not ß-cell impairment, likely independently mediate the observed diabetogenic effects of M.tb sensitization How might this impact on clinical and/or public health practice in the foreseeable future?: If corroborated by prospective studies, both TB programs and individual clinical care must incorporate monitoring of serum glucose and long-term metabolic outcomesThis will be particularly urgent in sub-Saharan Africa and South-East Asia where scarce health resources coincide with overlapping endemic TB and epidemic T2DM.

Human genes containing polymorphic trinucleotide repeats.

Expansions of trinucleotide repeats within gene transcripts are responsible for fragile X syndrome, myotonic dystrophy and spinal and bulbar muscular atrophy. To identify other human genes with similar features as candidates for triplet repeat expansion mutations, we screened human cDNA libraries with repeat probes and searched databases for transcribed genes with repeats. From both strategies, 40 genes were identified and 14 characterized. Five were found to contain repeats which are highly polymorphic including the N-cadherin, BCR, glutathione-S-transferase and Na+/K+ ATPase (beta-subunit) genes. These data demonstrate the occurrence of other human loci which may undergo this novel mechanism of mutagenesis giving rise to genetic disease.

Time toxicity associated with early phase clinical trial participation.

BACKGROUND: Early phase cancer clinical trials (EPCTs) involve experimental drugs being used for the first time in humans. These studies are designed for dose determination and safety, and represent the most time intensive of all clinical trials for both clinicians and patients. We sought to quantify the amount of patient time consumed through EPCT participation. PATIENTS AND METHODS: A retrospective audit of patients treated in the EPCT unit at Liverpool Hospital, Sydney was carried out from 2013 to 2023. We defined 'time toxicity' (TT) as a composite measure where time-toxic days were considered days with any health care system contact, including clinic visits, infusions, procedures or blood work. RESULTS: A total of 219 patients across 36 EPCTs were included. The median age was 65 years (range 31-81 years). Patients spent a median of 29% (range 4%-100%) of their days in direct contact with the health care system during their study. Protocol-specified visits accounted for the greatest contribution to total TT in 101 (46%) patients. In 7% (n = 16) of patients, unscheduled visits due to either adverse events or cancer-related symptoms accounted for the greatest TT. TT reduced as patients completed additional cycles of treatment. Patients who completed >10 cycles spent 14% of their days interacting with health care systems compared with 35% for those who completed ≤2 cycles. No statistically significant difference in TT was noted between dose-expansion and dose-escalation studies or trials focusing on immune-oncology versus targeted therapy. CONCLUSIONS: Our study is the first to report TT in EPCTs with an extended follow-up. Clinicians should be aware of TT when discussing risks and benefits. TT also may not be the appropriate term when describing the time patients invest during EPCTs. Toxicity implies a negative impact, but for many patients, trial participation would be seen as positive. There should be efforts to streamline health care visits to limit TT in EPCTs.

Elevated plasma matrix metalloproteinases associate with Mycobacterium tuberculosis blood stream infection and mortality in HIV-associated tuberculosis.

Mortality from HIV-associated tuberculosis (HIV-TB) is high, particularly among hospitalised patients. In 433 people living with HIV admitted to hospital with symptoms of TB, we investigated plasma matrix metalloproteinases (MMP) and matrix-derived biomarkers in relation to TB diagnosis, mortality and Mycobacterium tuberculosis (Mtb) blood stream infection (BSI). Compared to other diagnoses, MMP-8 was elevated in confirmed TB and in Mtb-BSI, positively correlating with extracellular matrix breakdown products. Baseline MMP-3, -7, -8, -10 and procollagen III N-terminal propeptide (PIIINP) associated with Mtb-BSI and 12-week mortality. These findings implicate MMP dysregulation in pathophysiology of advanced HIV-TB and support MMP inhibition as a host-directed therapeutic strategy for HIV-TB.

Interferon release does not add discriminatory value to smear-negative HIV-tuberculosis algorithms.

Clinical algorithms for evaluating HIV-infected individuals for tuberculosis (TB) prior to isoniazid preventive therapy (IPT) perform poorly, and interferon-γ release assays (IGRAs) have moderate accuracy for active TB. It is unclear whether, when used as adjunct tests, IGRAs add any clinical discriminatory value for active TB diagnosis in the pre-IPT assessment. 779 sputum smear-negative HIV-infected persons, established on or about to commence combined antiretroviral therapy (ART), were screened for TB prior to IPT. Stepwise multivariable logistic regression was used to develop clinical prediction models. The discriminatory ability was assessed by receiver operator characteristic area under the curve (AUC). QuantiFERON-TB Gold in-tube (QFT-GIT) was evaluated. The prevalence of smear-negative TB by culture was 6.4% (95% CI 4.9-8.4%). Used alone, QFT-GIT and the tuberculin skin test (TST) had comparable performance; the post-test probability of disease based on single negative tests was 3-4%. In a multivariable model, the QFT-GIT test did not improve the ability of a clinical algorithm, which included not taking ART, weight <60 kg, no prior history of TB, any one positive TB symptom/sign (cough ≥ 2 weeks) and CD4+ count <250 cells per mm(3), to discriminate smear-negative culture-positive and -negative TB (72% to 74%; AUC comparison p=0.33). The TST marginally improved the discriminatory ability of the clinical model (to 77%, AUC comparison p=0.04). QFT-GIT does not improve the discriminatory ability of current TB screening clinical algorithms used to evaluate HIV-infected individuals for TB ahead of preventive therapy. Evaluation of new TB diagnostics for clinical relevance should follow a multivariable process that goes beyond test accuracy.

Hypercytokinaemia accompanies HIV-tuberculosis immune reconstitution inflammatory syndrome.

Increased access to combination antiretroviral therapy in areas co-endemic for tuberculosis (TB) and HIV-1 infection is associated with an increased incidence of immune reconstitution inflammatory syndrome (TB-IRIS) whose cause is poorly understood. A case-control analysis of pro- and anti-inflammatory cytokines in TB-IRIS patients sampled at clinical presentation, and similar control patients with HIV-TB prescribed combined antiretroviral therapy who did not develop TB-IRIS. Peripheral blood mononuclear cells were cultured in the presence or absence of heat-killed Mycobacterium tuberculosis for 6 and 24 h. Stimulation with M. tuberculosis increased the abundance of many cytokine transcripts with interleukin (IL)-1ß, IL-5, IL-6, IL-10, IL-13, IL-17A, interferon (IFN)-γ, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumour necrosis factor (TNF) being greater in stimulated TB-IRIS cultures. Analysis of the corresponding proteins in culture supernatants, revealed increased IL-1ß, IL-2, IL-6, IL-8, IL-10, IL-12p40, IFN-γ, GM-CSF and TNF in TB-IRIS cultures. In serum, higher concentrations of TNF, IL-6, and IFN-γ were observed in TB-IRIS patients. Serum IL-6 and TNF decreased during prednisone therapy in TB-IRIS patients. These data suggest that cytokine release contributes to pathology in TB-IRIS. IL-6 and TNF were consistently elevated and decreased in serum during corticosteroid therapy. Specific blockade of these cytokines may be rational approach to immunomodulation in TB-IRIS.

Effect of heating and aging of poultry litter on the persistence of enteric bacteria.

Food-borne illnesses have rarely been associated with the reuse of poultry litter as an organic fertilizer and soil amendment in agriculture. Yet farming practices in many countries have come under increased scrutiny because of heightened consumer awareness of food safety and environmental issues. This study was conducted to determine whether simple on-farm management practices could improve the microbiological safety of poultry litter. First, the effects of heat and moisture on the survival of Escherichia coli and Salmonella enterica serovar Typhimurium in poultry litter were investigated under laboratory conditions. Second, the persistence and regrowth of enteric bacteria were examined in poultry litter that had been aged for up to 12 wk in either a turned or static (unturned) windrow. Escherichia coli and Salmonella counts in poultry litter were reduced by >99% in 1 h at 55 or 65°C under laboratory conditions. At 35°C, both persisted longer under moist (65% wt/wt, wet basis) than dry (30% wt/wt) conditions. Poultry litter aged for 3 wk in a turned windrow, and up to 6 wk in a static windrow, supported increased E. coli densities when incubated in the laboratory at 37°C for 21 d. Peak temperatures >65°C were observed in both windrows within the first 3 wk of aging; after this point, the turned windrow was more consistently exposed to temperatures >45°C than the static windrow. By 12 wk, however, E. coli counts were very similar (3 to 3.6 log(10)) in the outside edge of both windrows. This study highlights the need for a better understanding of the interrelationship between spontaneous heating in organic waste streams, organic matter stabilization, and pathogen reduction.

The geometry of the toxicity of silver nanoparticles to freshwater mussels.

The question about the influence of the geometry of silver nanoparticle (nAg) towards toxicity in aquatic organisms is largely unanswered. The purpose of this study was to examine if different geometries of nAg could initiate biophysical stress in the soft tissues of mussels. Freshwater Dreissenna bugensis mussels were exposed for 48 h at 15 °C to 10 and 50 µg/L of ionic Ag and to 3 forms of polyvinylpyrrolidone (PVP)-coated nAg of similar size: sphere, cube and prism. At the end of the exposure period, mussels were allowed to depurate overnight and the post-mitochondrial fraction of the soft tissues were analyzed for the levels of liquid crystals (LCs), changes in the activity and fractal dimensions of pyruvate kinase-lactate dehydrogenase (PK-LDH), F-actin and protein-ubiquitin (UB) levels. The data revealed that exposure to nAg forms lead to increased formation of LCs in increasing order of intensity: prismatic > cubic > spherical nAg. The activity in PK-LDH was decreased by all forms of nAg but not by ionic Ag+ (as with the following effects). Fractal kinetics of the PK-LDH system revealed that the nAg forms increased the spectral dimension (sD) in increasing order: spherical > cubic > prismatic nAg. A decrease in the fractal diffusion rate (fDR) with small changes in the fractal dimension (fD) was also obtained. The levels of F-actin and protein-UB were significantly affected for most forms of nAg and followed a pattern similar to LCs levels. In conclusion, the geometry of nAg could influence the formation of LCs, alter the fractal kinetics of the PK-LDH system, F-actin levels and protein damage in the soft tissues of freshwater mussels.

A realist evaluation of a collaborative model to support research co-production in long-term care settings in England: the ExCHANGE protocol.

BACKGROUND: Collaborative working between academic institutions and those who provide health and social care has been identified as integral in order to produce acceptable, relevant, and timely research, and for outputs to be useful and practical to implement. The ExCHANGE Collaboration aims to bring together researchers and people working, living in and visiting care homes to build capacity, share and mobilise knowledge, and identify key areas for future research. This paper describes an embedded, formative, realist and theory-driven evaluation which aims to gather information about how successful the ExCHANGE Collaboration is perceived to be in achieving its aims. An existing realist programme theory from the literature - Closer Collaboration - will be supplemented by two substantive theories: Co-production and Knowledge Brokering. This will result in an initial programme theory which will be tested by this formative evaluation to refine understanding of how the ExCHANGE Collaboration works. METHODS: The evaluation will employ mixed qualitative methods, including: analysis of documents such as feedback forms, Knowledge Broker journal/diary, event attendance records, risk and issues logs and other relevant paperwork gathered as part of project delivery; observations of events/activities; and interviews with care home providers and staff, care home residents, residents' family members, and researchers who are involved in the project (both project design/delivery, and also attendance or involvement in project activities/events). Framework Analysis will be used to interpret the data collected; analysis will be strategic, by focusing on particular key areas of importance in the developing theory of how the ExCHANGE Collaboration might achieve change. RESULTS: The results of this study are expected to be published in 2022. DISCUSSION: This evaluation will investigate how successful the ExCHANGE Collaboration is perceived to be in achieving its aims, in what way, in which contexts, and how this may differ for those involved. It will do this by testing an initial programme theory about how the collaboration works, for whom, under which circumstances, and in what way. Findings will be shared through written publication, an end of project learning event for those involved/interested in the project, and a lay summary to be made publically available.

The longitudinal relationship between child emotional disorder and parental mental health in the British Child and Adolescent Mental Health surveys 1999 and 2004.

BACKGROUND: Research suggests parental psychopathology has an adverse effect on child mental health. However, due to the interactional nature of parent-child relationships and with a high rate of emotional disorders reported in school-age children, it is important to know whether the effect is reciprocal. METHODS: We explored the longitudinal relationship between child and parent mental health in the British Child and Adolescent Mental Health Surveys (N=7,100 child-parent dyads) and their three-year follow-ups. The Development and Well-Being Assessment with DSM-IV diagnostic criteria was used to measure child psychiatric diagnoses, while parental mental health was assessed using the General Health Questionnaire. Multivariable logistic regression was used to explore the longitudinal association between child emotional disorder and parent mental health. RESULTS: Parents of children who had an emotional disorder at baseline were more likely to have poor mental health three years later compared with parents whose children had no psychiatric diagnosis (33.3% versus 16.7%; crude odds ratio=2.52; adjusted odds ratio=2.19, 95% CI=1.58 to 3.05, p<0.001). Children of parents with poor mental health at baseline were more likely to develop an emotional disorder three years later compared with children whose parents had good mental health (5.2% versus 2.5%; crude odds ratio=2.08; adjusted odds ratio=1.63, 95% CI=1.18 to 2.25, p=0.003). LIMITATIONS: The findings of this research are limited by the survey data collected, the measures used and survey dropout. CONCLUSIONS: We detected a bi-directional relationship between child and parent mental health, suggesting that effective intervention for one individual may benefit other family members.

Enhanced diagnosis of HIV-1-associated tuberculosis by relating T-SPOT.TB and CD4 counts.

The sensitivity of the tuberculin skin test is impaired in HIV-1-infected persons. Enzyme-linked immunospot-based detection of immune sensitisation may be less affected. Furthermore, the quantitative response can be related to the CD4 count, potentially improving specificity for active disease. The T-SPOT.TB assay was performed on HIV-1-infected participants, 85 with active tuberculosis (TB) and 81 healthy patients (non-TB). The ratio of the sum of the 6-kDa early secretory antigenic target and culture filtrate protein 10 response to the CD4 count (spot-forming cell (SFC)/CD4) was calculated. Using the manufacturer's guidelines, active TB was diagnosed with 76% sensitivity and 53% specificity. Using an SFC/CD4 ratio of 0.12, sensitivity (80%) and specificity (62%) improved. The quantitative T-cell response increased with increasing smear-positivity in the active TB group (p = 0.0008). In the non-TB group, the proportion of persons scored positive by T-SPOT.TB assay was lower in the group with a CD4 count of <200 cells·mm(-3) (p = 0.029). The ratio of the summed T-cell response to CD4 count improved the diagnostic accuracy of the T-SPOT.TB assay in HIV-1-infected persons, and a ratio of SFC/CD4 of >0.12 should prompt investigation for active disease. A strong association between the degree of sputum positivity and T-SPOT.TB score was found. The sensitivity of the T-SPOT.TB assay in active disease may be less impaired by advanced immunosuppression.

Association between Gc genotype and susceptibility to TB is dependent on vitamin D status.

Group-specific component (Gc) variants of vitamin D binding protein differ in their affinity for vitamin D metabolites that modulate antimycobacterial immunity. We conducted studies to determine whether Gc genotype associates with susceptibility to tuberculosis (TB). The following subjects were recruited into case-control studies: in the UK, 123 adult TB patients and 140 controls, all of Gujarati Asian ethnic origin; in Brazil, 130 adult TB patients and 78 controls; and in South Africa, 281 children with TB and 182 controls. Gc genotypes were determined and their frequency was compared between cases versus controls. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were obtained retrospectively for 139 Gujarati Asians, and case-control analysis was stratified by vitamin D status. Interferon (IFN)-gamma release assays were also performed on 36 Gujarati Asian TB contacts. The Gc2/2 genotype was strongly associated with susceptibility to active TB in Gujarati Asians, compared with Gc1/1 genotype (OR 2.81, 95% CI 1.19-6.66; p = 0.009). This association was preserved if serum 25(OH)D was <20 nmol.L(-1) (p = 0.01) but not if serum 25(OH)D was > or =20 nmol.L(-1) (p = 0.36). Carriage of the Gc2 allele was associated with increased PPD of tuberculin-stimulated IFN-gamma release in Gujarati Asian TB contacts (p = 0.02). No association between Gc genotype and susceptibility to TB was observed in other ethnic groups studied.