Lipoarabinomannan in sputum to detect bacterial load and treatment response in patients with pulmonary tuberculosis: Analytic validation and evaluation in two cohorts.

BACKGROUND: Lipoarabinomannan (LAM) is a major antigen of Mycobacterium tuberculosis (MTB). In this report, we evaluated the ability of a novel immunoassay to measure concentrations of LAM in sputum as a biomarker of bacterial load prior to and during treatment in pulmonary tuberculosis (TB) patients. METHODS AND FINDINGS: Phage display technology was used to isolate monoclonal antibodies binding to epitopes unique in LAM from MTB and slow-growing nontuberculous mycobacteria (NTM). Using these antibodies, a sandwich enzyme-linked immunosorbent assay (LAM-ELISA) was developed to quantitate LAM concentration. The LAM-ELISA had a lower limit of quantification of 15 pg/mL LAM, corresponding to 121 colony-forming units (CFUs)/mL of MTB strain H37Rv. It detected slow-growing NTMs but without cross-reacting to common oral bacteria. Two clinical studies were performed between the years 2013 and 2016 in Manila, Philippines, in patients without known human immunodeficiency virus (HIV) coinfection. In a case-control cohort diagnostic study, sputum specimens were collected from 308 patients (aged 17-69 years; 62% male) diagnosed as having pulmonary TB diseases or non-TB diseases, but who could expectorate sputum, and were then evaluated by smear microscopy, BACTEC MGIT 960 Mycobacterial Detection System (MGIT) and Lowenstein-Jensen (LJ) culture, and LAM-ELISA. Some sputum specimens were also examined by Xpert MTB/RIF. The LAM-ELISA detected all smear- and MTB-culture-positive samples (n = 70) and 50% (n = 29) of smear-negative but culture-positive samples (n = 58) (versus 79.3%; 46 positive cases by the Xpert MTB/RIF), but none from non-TB patients (n = 56). Among both LAM and MGIT MTB-culture-positive samples, log10-transformed LAM concentration and MGIT time to detection (TTD) showed a good inverse relationship (r = -0.803, p < 0.0001). In a prospective longitudinal cohort study, 40 drug-susceptible pulmonary TB patients (aged 18-69 years; 60% male) were enrolled during the first 56 days of the standard 4-drug therapy. Declines in sputum LAM concentrations correlated with increases of MGIT TTD in individual patients. There was a 1.29 log10 decrease of sputum LAM concentration, corresponding to an increase of 221 hours for MGIT TTD during the first 14 days of treatment, a treatment duration often used in early bactericidal activity (EBA) trials. Major limitations of this study include a relatively small number of patients, treatment duration up to only 56 days, lack of quantitative sputum culture CFU count data, and no examination of the correlation of sputum LAM to clinical cure. CONCLUSIONS: These results indicate that the LAM-ELISA can determine LAM concentration in sputum, and sputum LAM measured by the assay may be used as a biomarker of bacterial load prior to and during TB treatment. Additional studies are needed to examine the predictive value of this novel biomarker on treatment outcomes.

Preventing Diabetes in the Workplace: Effects of Coaching and Monetary Incentives.

OBJECTIVE: Prevention of diabetes demonstrated in the diabetes prevention program has not been thoroughly evaluated in workplace settings. METHODS: Glycemic control was assessed by glycated hemoglobin (HbA1c) and its impact on 5-year incidence of diabetes and prediabetes prevalence, in wellness program participants (WPP) of (Group A, with) or (Group B, without) health coaching and monetary incentives. RESULTS: HbA1c fell in Group A WPP (5.52 ±â€Š0.60 vs 5.58 ±â€Š0.36 SD, P = 0.04) as did prediabetes. Incident diabetes was less than expected (24 vs 74, P < 0.001). HbA1c increased in Group B WPP (5.37 ±â€Š0.40 SD vs 5.58 ±â€Š0.54, P < 0.001) and prediabetes increased from 28 to 36 (P < 0.001). CONCLUSIONS: Health coaching and monetary incentives improved glycemic control over 5 years, an improvement not observed in WPP without these interventions.

Preliminary inter-rater reliability of the wheelchair components questionnaire for condition.

PURPOSE: The Wheelchair Components Questionnaire for Condition (WCQ-C) enables the collection of data on wheelchair maintenance condition and durability in resource-limited environments. It can be used in large studies to indicate typical patterns of wear at a location, or for a type of wheelchair. It can also be used in clinical settings as an evidence based indication that a wheelchair may need repair or replacement. This type of data can enable effective use of limited funds by wheelchair providers, manufacturers and users. The goal of this study was to investigate the inter-rater reliability of the WCQ-C. METHODS: Two therapists from North America who have worked extensively in low-resource areas used the WCQ-C to independently evaluate 46 wheelchairs at a primary school for children with disabilities in Kenya. RESULTS: Mean scores of ratings for each wheelchair by the two raters were used to calculate a two-way random interclass correlation coefficient. A value of 0.82 with a 95% confidence interval of 0.67-0.89 indicated good preliminary reliability. CONCLUSION: Preliminary results indicate that the WCQ-C is a reliable method of assessment. Additional studies are needed with larger and more diverse groups of raters. Because WCQ-C findings are specific to wheelchair wear and maintenance at each location, studies at other locations are also needed. Implications for rehabilitation The importance of inter-rater reliability testing in confirming the reliability of an assessment tool such as the WCQ-C. The use of the WCQ-C to monitor wheelchair condition in low-resource settings and other field settings. If used at regular interval can produce data that can be used to describe typical changes over time at each individual setting. This could enable proactive planning at that setting to avoid typical breakdowns and the injuries or clinical complications that could result. The use of the WCQ-C to monitor the condition of groups of wheelchairs of the same type. It can describe typical patterns of wear and failure in a way that enables responsive change by manufacturers and designers. This enables more effective use of limited funds. On an individual basis, the use of the WCQ-C to alert users and health professionals of a need for repair or replacement. This could minimize the clinical problems and accidents that can result from wheelchair breakdown. Assessment of a wheelchair using the WCQ-C could provide evidence based data to insurance companies or wheelchair providers which indicates a need for wheelchair repair or replacement.

A thermal stress treadmill walk for clinic evaluation of candidates for hazardous materials (HazMat) duty.

UNLABELLED: U.S. guidance for examining hazmat workers recommends stress testing be considered when heat stress is expected. However, the most common stress test-Bruce protocol treadmill electrocardiography (BPTE) wearing gym clothes-creates little thermal stress. OBJECTIVE: Evaluate a novel thermal stress treadmill walk (TSTW). METHODS: Body temperatures and heart rates during BPTE in 93 current and potential hazmat workers wearing gym clothes were compared with later values in 35 of these subjects while they were wearing thermally-restrictive "sauna suits" during a 45-min TSTW. Physiological strain index (PSI) was calculated from temperature and heart rate changes and compared with PSI values from hazmat simulations and climatic chamber exercises. RESULTS: Tympanic temperature (TT) rose 0.5°C (SD 0.5) during BPTE lasting 12.4 min (SD 2.9). PSI reached 6.0 (SD 1.3). TT rose 1.0°C (SD 0.5) during TSTW, p < .01. PSI averaged 6.6 (SD 1.9) in 29 subjects who completed TSTW, versus 5.7 (SD 5.7) in the 6 subjects who did not. Ingested thermistor temperatures increased more than did TT during TSTW, yielding PSI of 7.0 (SD 1.5), equal to PSI values from climatic chamber exercises, i.e., 7.0 (SD 1.0). CONCLUSION: TSTW increased body temperature and PSI in 29 of the 35 subjects who completed it to levels matching those of operational simulations in climatic chambers and during hazmat exercises. This TSTW may be useful for evaluating candidates for hazmat duty.

Feasibility, diagnostic accuracy, and effectiveness of decentralised use of the Xpert MTB/RIF test for diagnosis of tuberculosis and multidrug resistance: a multicentre implementation study.

BACKGROUND: The Xpert MTB/RIF test (Cepheid, Sunnyvale, CA, USA) can detect tuberculosis and its multidrug-resistant form with very high sensitivity and specificity in controlled studies, but no performance data exist from district and subdistrict health facilities in tuberculosis-endemic countries. We aimed to assess operational feasibility, accuracy, and effectiveness of implementation in such settings. METHODS: We assessed adults (≥18 years) with suspected tuberculosis or multidrug-resistant tuberculosis consecutively presenting with cough lasting at least 2 weeks to urban health centres in South Africa, Peru, and India, drug-resistance screening facilities in Azerbaijan and the Philippines, and an emergency room in Uganda. Patients were excluded from the main analyses if their second sputum sample was collected more than 1 week after the first sample, or if no valid reference standard or MTB/RIF test was available. We compared one-off direct MTB/RIF testing in nine microscopy laboratories adjacent to study sites with 2-3 sputum smears and 1-3 cultures, dependent on site, and drug-susceptibility testing. We assessed indicators of robustness including indeterminate rate and between-site performance, and compared time to detection, reporting, and treatment, and patient dropouts for the techniques used. FINDINGS: We enrolled 6648 participants between Aug 11, 2009, and June 26, 2010. One-off MTB/RIF testing detected 933 (90·3%) of 1033 culture-confirmed cases of tuberculosis, compared with 699 (67·1%) of 1041 for microscopy. MTB/RIF test sensitivity was 76·9% in smear-negative, culture-positive patients (296 of 385 samples), and 99·0% specific (2846 of 2876 non-tuberculosis samples). MTB/RIF test sensitivity for rifampicin resistance was 94·4% (236 of 250) and specificity was 98·3% (796 of 810). Unlike microscopy, MTB/RIF test sensitivity was not significantly lower in patients with HIV co-infection. Median time to detection of tuberculosis for the MTB/RIF test was 0 days (IQR 0-1), compared with 1 day (0-1) for microscopy, 30 days (23-43) for solid culture, and 16 days (13-21) for liquid culture. Median time to detection of resistance was 20 days (10-26) for line-probe assay and 106 days (30-124) for conventional drug-susceptibility testing. Use of the MTB/RIF test reduced median time to treatment for smear-negative tuberculosis from 56 days (39-81) to 5 days (2-8). The indeterminate rate of MTB/RIF testing was 2·4% (126 of 5321 samples) compared with 4·6% (441 of 9690) for cultures. INTERPRETATION: The MTB/RIF test can effectively be used in low-resource settings to simplify patients' access to early and accurate diagnosis, thereby potentially decreasing morbidity associated with diagnostic delay, dropout and mistreatment. FUNDING: Foundation for Innovative New Diagnostics, Bill & Melinda Gates Foundation, European and Developing Countries Clinical Trials Partnership (TA2007.40200.009), Wellcome Trust (085251/B/08/Z), and UK Department for International Development.

Prolonged respiratory illness after single overnight continuous positive airway pressure humidification: endotoxin as the suspect.

A patient developed a prolonged respiratory illness after a single overnight use of tap water to humidify air supplied by a constant positive airway pressure (CPAP) device, which she had previously used for six years without difficulty. During those years, she used only distilled water for this purpose, as instructed by her sleep specialist. Analysis of the well water supplying her home showed no microorganisms, metals or other analytes likely to have caused her illness, but endotoxin was found at concentrations well above that recommended by the U.S. Pharmacopeia, as a maximum in water which may be inhaled as an aerosol.

Nurse practitioner services: three-year impact on health care costs.

OBJECTIVE: In 2005, our initial analysis of the impact on health care costs (HCC) of providing on-site Nurse Practitioner (NP) services showed favorable results. METHODS: We measured the effects of the NP program on HCC in two ways. Method 1 compared actual HCC for 2005 to 2007 versus projected HCC, the latter based on medical payments in 2002 to 2004, before the NP intervention. Method 2 was a microanalytic comparison of the HCC of nine Major Diagnostic Categories responsible for 88.5% of all conditions treated by the NP from July 2005 to December 2006. RESULTS: Annualized cost of the NP program was $124,750. Savings in HCC using the first method were $1,089,466 per year, yielding a benefit-to-cost ratio of 8.7 to 1. Savings in HCC using the second method reflected a ratio of 2.0 to 1. In addition, method 1 reflects HCC savings which may be due to the addition of a 24/7 Nurse Help Line. CONCLUSIONS: This 3-year analysis confirms our preliminary findings that an on-site NP has a favorable benefit-to-cost function. Longer-term analyses are needed to confirm these findings.

Inguinal phlegmon and positive serology for syphilis after penile bite laceration: true, true and unrelated.

Among many causes of penile injury, sexual activity is infrequently reported. The present case involved delay in recognition, which led to development of a phlegmon near major vascular structures. Positive serologic evidence of syphilis was an incidental finding.