Geospatial cluster analyses of pneumonia-associated hospitalisations among adults in New York City, 2010-2014.

Pneumonia is a leading cause of death in New York City (NYC). We identified spatial clusters of pneumonia-associated hospitalisation for persons residing in NYC, aged ⩾18 years during 2010-2014. We detected pneumonia-associated hospitalisations using an all-payer inpatient dataset. Using geostatistical semivariogram modelling, local Moran's I cluster analyses and χ2 tests, we characterised differences between 'hot spots' and 'cold spots' for pneumonia-associated hospitalisations. During 2010-2014, there were 141 730 pneumonia-associated hospitalisations across 188 NYC neighbourhoods, of which 43.5% (N = 61 712) were sub-classified as severe. Hot spots of pneumonia-associated hospitalisation spanned 26 neighbourhoods in the Bronx, Manhattan and Staten Island, whereas cold spots were found in lower Manhattan and northeastern Queens. We identified hot spots of severe pneumonia-associated hospitalisation in the northern Bronx and the northern tip of Staten Island. For severe pneumonia-associated hospitalisations, hot-spot patients were of lower mean age and a greater proportion identified as non-Hispanic Black compared with cold spot patients; additionally, hot-spot patients had a longer hospital stay and a greater proportion experienced in-hospital death compared with cold-spot patients. Pneumonia prevention efforts within NYC should consider examining the reasons for higher rates in hot-spot neighbourhoods, and focus interventions towards the Bronx, northern Manhattan and Staten Island.

Formulation and Characterization of Pyrazinamide Polymeric Nanoparticles for Pulmonary Tuberculosis: Efficiency for Alveolar Macrophage Targeting.

Pyrazinamide, a highly specific agent against Mycobacterium tuberculosis is used as first-line drug to treat tuberculosis. The current work aims to formulate polymeric nanoparticles based drug delivery system to sustain the release profile and reduce the dosing frequency of pyrazinamide. Further aim was to target the macrophages within body fluid. These polymeric nanoparticles were prepared by simultaneous double-emulsion (W/O/W) solvent evaporation/diffusion technique. The prepared dispersions were characterized for various biopharmaceutical parameters such as particle size, zeta potential, polydispersity index, drug loading capacity, entrapment efficiency and targeting to alveolar macrophages. The formulated polymeric nanoparticles were in the particle size range of 45.51 to 300.4 nm with a maximum drug entrapment efficiency of 80.9%. The stability study of optimized batch conducted at 40±2°/75±5% relative humidity showed no significant changes up to 90 days. X-Ray Diffraction spectrum exhibits the transformation of crystalline form of drug to amorphous in the formulation. Scanning Electron Microscope image showed nanoparticles spherical in shape with smooth surface. In vitro release profiles were biphasic in nature with burst release followed by controlled release over a period of 24 h obeying diffusion mechanism. In vivo and ex vivo studies results of the study show significant uptake of the nanoparticles by alveolar macrophages through fluorescent micrograph. Polymeric nanoparticles formulation of pyrazinamide could encompass significant uptake by alveolar macrophages, the high first-pass metabolism, sustain the release of drug leading to reduction in dose, toxicity and improvement of patient compliance.

Regional variations in home canning practices and the risk of foodborne botulism in the Republic of Georgia, 2003.

Foodborne botulism is a severe, paralytic illness caused by ingestion of preformed neurotoxins produced by Clostridium botulinum. In 2003, we conducted a population-based household survey of home canning practices to explore marked regional variations in botulism incidence in the Republic of Georgia (ROG). We designed a cluster sampling scheme and subdivided each of the 10 regions of the ROG into a variable number of strata. Households were selected from each stratum using a two-step cluster sampling methodology. We administered a questionnaire about home canning practices to household members responsible for food preparation. Using multivariate logistic regression analysis, we modeled high (eastern ROG) against low (western ROG) incidence areas. Overall, we surveyed 2,742 households nationwide. Home canning with a capping device hermetically sealing the lid covering the jar was practiced by 1,909 households (65.9%; 95% confidence interval [CI]: 59.8 to 72.1%). Canning was more prevalent in regions of low botulism incidence (34 versus 32%; P < 0.01). When compared with low-botulism areas, the following practices were associated with an increased risk in high-botulism areas: ≥ 6 months between canning vegetables and consuming them (adjusted odds ratio [aOR] = 2.1; 95% CI: 1.3 to 3.5) and adding any of the following ingredients to the jar at time of preparation: >1 tablespoon of salt per liter (aOR = 5.1; 95% CI: 1.2 to 22.6); vinegar (aOR = 2.2; 95% CI: 1.3 to 3.7), and greens (aOR = 5.6; 95% CI: 1.7 to 18.2). The following practices were associated with a decreased risk in high-botulism areas: >57 jars canned per household annually (aOR = 0.5; 95% CI: 0.3 to 0.9), covering or immersing vegetables in boiling water before placing them into the jar (aOR = 0.3 95% CI: 0.2 to 0.6), covering or immersing vegetables in boiling water after placing them into the jar (aOR = 0.4; 95% CI: 0.2 to 0.9), or adding garlic (aOR = 0.2; 95% CI: 0.1 to 0.5) or aspirin (aOR = 0.1; 95% CI: 0.1 to 0.2) to the jar at the time of preparation.

Formulation, characterization and ex vivo studies of terbinafine HCl liposomes for cutaneous delivery.

BACKGROUND: The goal of effective treatment for dermal fungal infections could be highly beneficial by the delivery of antifungal drugs on skin from liposomal application. Topical delivery involves minimizing the flux of the drug through the skin while maximizing its retention on the skin. The aim of the present work was the investigation of the effects of lipids and cholesterol for the development of liposomal formulations as potential carriers for antifungal agent terbinafine HCl. Phospholipon 90H (hydrogenated phosphatidylcholine) and dimyristoylglycero-3-phosphocholine (DMPC) along with cholesterol were used for preparation of liposomes by ethanol injection method and characterized for drug content, entrapment efficiency, size, zetapotential, vesicle morphology, stability, FTIR, in vitro and ex vivo drug retention studies. RESULTS: Drug entrapment ranged between 39.46±0.91% to 70.39±0.71%. Vesicles showed good morphological characters with a narrow size distribution, in the size range of 206.9 to 344.8 nm. Gum karaya gel loaded with liposomal dispersion showed prolonged drug retention on the rat skin during ex vivo studies compared to liposomal dispersion and gum karaya plain gel loaded with drug. CONCLUSION: The prolonged retention of drug by the gum karaya gel loaded with liposomal dispersion could effectively exhibit the antifungal activity for prolonged periods for cutaneous delivery.

The utility of stool cultures for diagnosing tuberculosis in people living with the human immunodeficiency virus.

BACKGROUND: Delayed diagnosis of tuberculosis (TB) increases mortality. OBJECTIVE: To evaluate whether stool culture improves the diagnosis of TB in people living with the human immunodeficiency virus (PLHIV). DESIGN: We analysed cross-sectional data of TB diagnosis in PLHIV in Cambodia, Thailand and Viet Nam. Logistic regression was used to assess the association between positive stool culture and TB, and to calculate the incremental yield of stool culture. RESULTS: A total of 1693 PLHIV were enrolled with a stool culture result. Of 228 PLHIV with culture-confirmed TB from any site, 101 (44%) had a positive stool culture; of these, 91 (90%) had pulmonary TB (PTB). After adjusting for confounding factors, a positive stool culture was associated with smear-negative (odds ratio [OR] 26, 95% confidence interval [CI] 12-58), moderately smear-positive (OR 60, 95%CI 23-159) and highly smear-positive (OR 179, 95%CI 59-546) PTB compared with no PTB. No statistically significant association existed with extra-pulmonary TB compared with no extra-pulmonary TB (OR 2, 95%CI 1-5). The incremental yield of one stool culture above two sputum cultures (5%, 95%CI 3-8) was comparable to an additional sputum culture (7%, 95%CI 4-11). CONCLUSION: Nearly half of the PLHIV with TB had a positive stool culture that was strongly associated with PTB. Stool cultures may be used to diagnose TB in PLHIV.

Pre-operative gastric emptying time correlates with clinical response to gastric electrical stimulation in the treatment of gastroparesis.

BACKGROUND: Gastric electrical stimulation (GES) may be of benefit in cases of gastroparesis that fail to respond to standard medical therapy. Response to this treatment is varied and prediction of clinical improvement is difficult. METHODS: This was a retrospective review and symptom questionnaire survey for all patients who underwent GES insertion in a single institution from November 2008 until May 2010 using the gastroparesis cardinal symptom index (GCSI). RESULTS: 14 out of 17 patients who had GES insertion responded to telephone or postal questionnaire. Mean pre-operative gastric emptying time was 151 min (median 146 min, range 18-318). Median follow up was 14 months (range 7-25 months). The mean reduction in GCSI score after GES insertion was 51% (13.4 vs 6.4, Z = 0.0013). Percentage reduction in GCSI correlated with pre-operative solid gastric emptying time (p = 0.0086). Two patients who responded to questionnaire required device removal, one due to a gastric perforation and the other for discomfort related to the implant and a poor clinical response. CONCLUSIONS: GES significantly improves symptoms of gastroparesis on the GCSI score. Not all patients respond equally to GES, and response may be predicted by pre-operative solid gastric emptying times.

Risk factors associated with tuberculosis infection among health care workers in Inner Mongolia, China.

SETTING: Health care workers (HCWs) are at increased risk for tuberculosis (TB) infection. In China, surveys examining TB infection among HCWs have not studied general health care facilities, compared tuberculin tests conducted using local protocols against an internationally accepted test or characterised risk factors. OBJECTIVE: To measure the prevalence of and risk factors for TB infection among HCWs in Inner Mongolia, China. DESIGN: Between April and August 2010, we administered QuantiFERON®-TB Gold In-Tube (QFT-GIT) tests, skin tests using Chinese tuberculin (TST) and surveys among HCWs at an infectious diseases hospital and a general medical hospital. We assessed whether demographic characteristics, personal exposure and work exposure were associated with QFT-GIT and TST positivity, and assessed agreement between test results. RESULTS: Of 999 HCWs, 683 (68%) were QFT-GIT-positive, which was associated with greater age, longer HCW career, TB disease in a co-worker and greater daily patient exposure using multivariable analysis. TST reactions ≥ 5 mm occurred in 69% of the HCWs; agreement between test results was low ( 0.22). CONCLUSIONS: The prevalence of TB infection among HCWs in Inner Mongolia is high; infection was associated with occupational exposure. Results from locally conducted TST are difficult to interpret. In China, TB infection control in health care facilities should be strengthened.

Epidemiological and molecular analysis of a waterborne outbreak of norovirus GII.4.

Contaminated water is one of the main sources of norovirus (NoV) gastroenteritis outbreaks globally. Waterborne NoV outbreaks are infrequently attributed to GII.4 NoV. In September 2009, a NoV outbreak affected a small school in Guangdong Province, China. Epidemiological investigations indicated that household use water, supplied by a well, was the probable source (relative risk 1·9). NoV nucleic acid material in concentrated well-water samples was detected using real-time RT-PCR. Nucleotide sequences of NoV extracted from diarrhoea and well-water specimens were identical and had the greatest sequence identity to corresponding sequences from the epidemic strain GII.4-2006b. Our report documents the first laboratory-confirmed waterborne outbreak caused by GII.4 NoV genotype in China. Our investigations indicate that well water, intended exclusively for household use but not for consumption, caused this outbreak. The results of this report serve as a reminder that private well water intended for household use should be tested for NoV.

Feasibility and safety of elective transradial coronary intervention in Asian females.

BACKGROUND: Transradial access for angioplasty and percutaneous intervention (PCI) has become more popular across the world due to lower risk of bleeding and better patient comfort. It has been shown to be effective and feasible in the Western population. However, there is a relative paucity of similar data for small-statured females, especially from Asian countries. Given the increased theoretical risk of local complications due to smaller-sized radial arteries in such females, feasibility and safety of transradial PCI (rPCI) needs to be better established in this group. METHODS: We present observational data for rPCI from a 3-year period at a single tertiary care center in South Asia. Data were collected on all female patients who underwent rPCI from January 2005 to December 2007. Primary outcomes assessed were procedure failure rate and complication rate. Secondary outcomes included death, recurrence of myocardial infarction, anginal symptoms or other complaints. Outcomes were recorded post-procedurally in the hospital and after discharge for up to 6 months. RESULTS: A total of 93 patients were included for final data analysis. Average patient age was 57.5 ± 10.3 years, with average height of 151.7 ± 8.4 cm and average weight of 58.1 ± 12.5 kg. Seventy patients (75.3%) underwent angioplasty or percutaneous intervention (PCI) for ACS and 23 (24.7%) for chronic stable angina refractory to medical therapy. A total of 118 lesions were treated in 90 patients. Ninety-one lesions (77.1%) were classified as Type B2 and Type C according to modified American College of Cardiology/American Heart Association lesion morphology criteria. Three cases of procedure failure accounted for a failure rate of 3.23%. No specified complications were noted in any of the patients. At 6-month follow-up, no deaths were observed. Two patients developed acute myocardial infarction and 16 patients (17.7%) had recurrence of anginal symptoms. CONCLUSION: Radial artery angioplasty and stenting is feasible and safe in Asian females. Increased theoretical risk of complication due to small-sized radial arteries in this subgroup is unlikely to be true. Success rates are likely to be good even with complex coronary inventions performed with transradial access.

Barriers to human immunodeficiency virus testing of tuberculosis patients in Thailand, 2004-2007.

SETTING: Tuberculosis (TB) clinics in five provinces and one national referral hospital in Thailand. OBJECTIVE: To identify risk factors for TB patients not receiving human immunodeficiency virus (HIV) pre-test counseling and testing in Thailand. DESIGN: We collected data on TB patients treated at participating facilities from 2004 to 2007. Patients with known HIV status at the time of TB diagnosis were excluded from the analysis. We performed multivariate logistic regression to determine patient and facility characteristics associated with HIV counseling and testing. RESULTS: Of 15 903 TB patients, HIV pre-test counseling was provided to 13 604 (86%). HIV testing was provided to 11 702 (86%) of those counseled. Of 6141 patients with unknown HIV status, 2323 (38%) were treated in facilities that provide HIV testing in TB clinics compared with 6412 (58%) of 11 003 non-HIV-infected and 3814 (62%) of 6121 HIV-infected patients (P < 0.05). In multivariate analysis, patients treated in facilities in which HIV testing of TB patients was performed somewhere other than the TB clinic were significantly less likely to undergo HIV pre-test counseling (adjusted OR 1.55, 95%CI 1.28-1.86). CONCLUSION: In Thailand, providing HIV testing directly in TB clinics, rather than in other settings, may increase the proportion of TB patients with known HIV status.

Tuberculosis services and treatment outcomes in private and public health care facilities in Thailand, 2004-2006.

BACKGROUND: The World Health Organization recommends that national tuberculosis (TB) programs encourage public and private providers to follow the 'International standards for tuberculosis care'. We assessed services and treatment outcomes in TB patients in public and private facilities to inform public-private mix scale-up in Thailand. METHODS: We prospectively collected data on TB patients in four provinces and the national infectious diseases hospital during 2004-2006. We analyzed services and outcomes among new pulmonary TB patients according to facility type. RESULTS: Of 7526 patients, 4539 (60%) were treated in small public facilities, 2275 (30%) in large public facilities and 712 (10%) in private facilities. Compared with the private sector, more public sector patients had at least two sputum smears examined, were prescribed a standard anti-tuberculosis regimen and received directly observed therapy; however, public sector facilities also performed suboptimally. Treatment outcomes were unsuccessful for 237 (33%) patients in private facilities, and for respectively 1018 (23%) and 655 (29%) patients in small and large public facilities. CONCLUSIONS: TB diagnostic and treatment services and outcomes should be enhanced in both public and private facilities in Thailand. Initiatives are needed to improve treatment outcomes and increase the use of microscopy, standardized TB regimens, and directly observed therapy in the public and private sectors.

Association between distance to HIV testing site and uptake of HIV testing for tuberculosis patients in Cambodia.

SETTING: Banteay Meanchey Province, Cambodia. OBJECTIVE: Cambodia has the highest incidence of tuberculosis (TB) in Asia. Not all TB patients are tested for human immunodeficiency virus (HIV). We assessed the association between distance to HIV testing facility and HIV testing rates. METHODS: We analyzed data on TB patients from 11 clinics to determine the proportion tested for HIV infection. We categorized each TB clinic as having a voluntary confidential counseling and testing (VCCT) center onsite, or being at <15 min, 15-30 min or >30 min driving distance to the nearest VCCT. RESULTS: Of 1017 TB patients not previously tested for HIV, 708 (70%) were tested. Of 481 TB patients without onsite VCCT, 297 (62%) were tested, compared to 410 (77%) of 535 TB patients with onsite VCCT (RR 0.6, 95%CI 0.5-0.7). When the VCCT site was >15 min from the TB clinic, HIV testing occurred only half as frequently as when onsite VCCT was available. CONCLUSION: TB patients treated at clinics without onsite or nearby HIV testing are less commonly tested for HIV infection. Making HIV testing available to TB patients without the necessity of traveling to a distant HIV testing site is likely to increase HIV testing rates.

Directly observed treatment is associated with reduced default among foreign tuberculosis patients in Thailand.

SETTING: Thailand's Tuberculosis (TB) Active Surveillance Network in four provinces in Thailand. OBJECTIVE: As treatment default is common in mobile and foreign populations, we evaluated risk factors for default among non-Thai TB patients in Thailand. DESIGN: Observational cohort study using TB program data. Analysis was restricted to patients with an outcome categorized as cured, completed, failure or default. We used multivariate analysis to identify factors associated with default, including propensity score analysis, to adjust for factors associated with receiving directly observed treatment (DOT). RESULTS: During October 2004-September 2006, we recorded data for 14359 TB patients, of whom 995 (7%) were non-Thais. Of the 791 patients analyzed, 313 (40%) defaulted. In multivariate analysis, age>or=45 years (RR 1.47, 95%CI 1.25-1.74), mobility (RR 2.36, 95%CI 1.77-3.14) and lack of DOT (RR 2.29, 95%CI 1.45-3.61) were found to be significantly associated with default among non-Thais. When controlling for propensity to be assigned DOT, the risk of default remained increased in those not assigned DOT (RR 1.99, 95%CI 1.03-3.85). CONCLUSION: In non-Thai TB patients, DOT was the only modifiable factor associated with default. Using DOT may help improve TB treatment outcomes in non-Thai TB patients.

Validation of the line-probe assay for rapid detection of rifampicin-resistant Mycobacterium tuberculosis in Vietnam.

BACKGROUND: Delays in identifying multidrug-resistant tuberculosis (MDR-TB) contribute to higher TB morbidity and mortality, and ongoing transmission. The line-probe assay (LiPA) is a rapid, commercially available polymerase chain reaction based assay that detects most mutations in the rpoB gene for rifampicin (RMP) resistance. We validated and compared this assay with conventional drug susceptibility testing (DST). METHODS: We re-cultured a random sample of stored isolates known to be either RMP-resistant or RMP-susceptible according to DST (proportion method). We performed a blinded comparison between LiPA and conventional DST. Genetic sequencing of the rpoB gene was performed on RMP-resistant isolates and discordant results. RESULTS: We tested 79 RMP-resistant and 64 RMP-susceptible strains. Concordance of LiPA with DST was 94%. For detecting RMP resistance, LiPA sensitivity was 90% and specificity was 100%. Molecular analysis of possible false-negative isolates by LiPA revealed an absence of mutations in the rpoB gene. RMP resistance was a good proxy for MDR-TB, as 66 (93%) of 71 RMP-resistant isolates were also isoniazid-resistant. CONCLUSION: The LiPA provided rapid results that were highly predictive of RMP resistance and MDR-TB. False-negatives occurred, but only among isolates with mutations in regions not assessed by LiPA. Performance and cost-effectiveness should be evaluated in patients during routine program conditions.

Fluorescence microscopy is less expensive than Ziehl-Neelsen microscopy in Thailand.

Ziehl-Neelsen (ZN) microscopy is the primary method for acid-fast bacilli examination in resource-limited settings, including Thailand. Despite its considerably improved diagnostic performance, conventional fluorescent microscopy (FM) is rarely used due to its perceived high cost. An evaluation in Thailand found that the total cost of FM operated in the National Tuberculosis Reference Laboratory (NTRL) in Bangkok, Thailand, is similar to that of ZN performed in the NTRL and in four regional Thai laboratories. FM is therefore a cost-effective alternative to ZN in resource-limited settings.

Monitoring the performance of mycobacteriology laboratories: a proposal for standardized indicators.

SETTING: Thailand Tuberculosis (TB) Active Surveillance Network: Bangkok, Chiang Rai, Phuket, Tak and Ubon-Ratchathani, Thailand. BACKGROUND: Mycobacteriology laboratories in resource-limited, high TB burden settings are expanding to perform conventional solid media culture and broth-based mycobacteriology culture. Indicators that measure how well a laboratory performs sputum microscopy have been developed and broadly implemented. Routine monitoring of sputum culture performance, however, is not as common. DESIGN: We implemented indicators for monitoring the quality of laboratory services in five province-level mycobacteriology culture facilities in Thailand. These indicators were derived from literature review, consultation with subject matter experts and our program experience. CONCLUSIONS: We believe that an international consensus document providing monitoring guidelines for mycobacteriology laboratories is urgently needed.

Provider-initiated diagnostic HIV counselling and testing in tuberculosis clinics in Thailand.

SETTINGS: Twelve large public hospitals geographically distributed in Thailand. OBJECTIVES: To assess the uptake of diagnostic human immunodeficiency virus (HIV) counselling and testing (DCT), HIV prevalence in tuberculosis (TB) patients and HIV services provided to newly diagnosed HIV-infected TB patients. METHOD: We provided DCT in TB clinics to newly registered TB patients. Post-test counselling was provided at TB clinics for non-HIV-infected patients and at HIV voluntary counselling and testing centres for HIV-infected patients. HIV-infected patients were referred for HIV-related care during TB treatment. RESULTS: From July to October 2006, 8% of 1086 new TB patients were known to be HIV-infected at the time of TB diagnosis. Of 1000 patients with unknown HIV status, 93% were tested: HIV infection was diagnosed in 11%. Including patients with previously diagnosed HIV infection, 17% of all TB patients were HIV-infected. Of 99 newly diagnosed HIV patients, 36% received cotrimoxazole prophylaxis. Of 41 with CD4 < 200 cells/microl, 42% began antiretroviral treatment during TB treatment. CONCLUSION: The acceptance of DCT was high, but the provision of HIV services was disappointingly low. Increased staff capacity building, stronger coordination with the acquired immune-deficiency syndrome programme and better field supervision are needed to achieve universal access to care for HIV-infected TB patients.

Validity of segmental transit studies used in routine clinical practice, to characterize defaecatory disorder in patients with functional constipation.

OBJECTIVE: Segmental colonic transit can be determined by performing regional counts of radio-opaque markers on an abdominal radiograph. It has been claimed that the pattern of markers can be used to characterize the type of constipation, with a concentration of markers seen in the rectosigmoid region in patients with defaecatory disorders. The aim of our study was to examine this hypothesis in a cohort of patients with functional constipation. METHOD: Consecutive patients presenting to a specialist constipation clinic and satisfying inclusion criteria were studied. All patients had the following assessments: radio-opaque marker study performed according to a standard protocol; proforma-based symptom assessment using Likert scoring; and radioisotope defaecating proctogram. Transit study data included total transit time, rectosigmoid transit time and geometric mean of markers. Symptom scores were recorded for straining, incomplete evacuation and digitation, together with a cumulative symptom score. Evidence of outlet obstruction from the proctogram included four previously described parameters. RESULTS: A total of 108 patients with functional constipation according to the Rome criteria with a median age of 41 years were studied. Neither rectosigmoid transit time nor the geometric centre of markers could differentiate patients with a functional defaecatory disorder (FDD). There was no correlation between the pattern of marker distribution and any of the parameters denoting outlet obstruction. CONCLUSION: Our data do not support the hypothesis that assessment of segmental transit, using standard methods applicable to routine clinical practice can determine the type of constipation. In particular, patients exhibiting evidence of FDD are no more likely to have recto-sigmoid retention of markers than those without.