Emerging novel sequence types of Staphylococcus aureus in Pakistan.

BACKGROUND: Despite an increasing incidence of Staphylococcus aureus infection and dissemination in Pakistan, the epidemiology of different Staphylococcus aureus research clones has been the subject of only a small number of investigations. By analyzing the collected data sequence, this study was designed to study the epidemiology of Staphylococcus aureus in the area using multilocus sequence typing (MLST). METHODS: A total of 1015 staphylococcus strains collected from the city's tertiary care facilities were biochemically screened, followed by antimicrobial susceptibility testing against a panel of 13 antibiotics. Analyzed methicillin-resistant Staphylococcus aureus (MRSA) was subjected to molecular characterization using multilocus sequence typing (MLST), clonal complex analysis, recombination testing, and phylogenetic analysis. RESULTS: Approximately 421 bacteria were verified as Staphylococcus aureus by biochemical analysis. 57% of the isolates exhibited multidrug resistance, of which 89% were found to be methicillin-resistant Staphylococcus aureus (MRSA). MLST results in a total of 39 sequence types (ST) and 5 clonal complexes (CC), out of which twenty-two STs were newly documented worldwide. The most common CC identified was CC8. The direct sequencing data also revealed significant shifts at MLST loci, with point mutations resulting in the aroE-343 and tpi-278 alleles. CONCLUSIONS: This study concludes that there is high diversity in the locally circulating clones of Staphylococcus aureus present in nature and that they are defined by their geographic epidemiology. These findings have practical implications for public health, including the need for tailored infection control strategies, antibiotic stewardship, global surveillance, and a deeper understanding of bacterial evolution.

Blood Eosinophils and Outcomes in Severe Hospitalized Exacerbations of COPD.

BACKGROUND: Patients with moderate exacerbations of COPD and the eosinophilic phenotype have better outcomes with prednisolone. Whether this outcome is similar in patients hospitalized with a severe exacerbation of COPD is unclear. We investigated the rate of recovery of eosinophilic and noneosinophilic exacerbations in patients participating in a multicenter randomized controlled trial assessing health outcomes in hospitalized exacerbations. METHODS: Patients were recruited at presentation to the hospital with an exacerbation of COPD. They were stratified into groups according to eosinophilic exacerbations if the peripheral blood eosinophil count on admission was ≥ 200 cells/µL and/or ≥ 2% of the total leukocyte count. Admission details, serum C-reactive protein levels, length of stay, and subsequent rehospitalization data were compared between groups. RESULTS: A total of 243 patients with COPD (117 men) with a mean age of 71 years (range, 45-93 years) were recruited. The inpatient mortality rate was 3% (median time to death, 12 days; range, 9-16 days). The median absolute eosinophil count was 100 cells/µL (range, 10-1,500 cells/µL), and 25% met our criteria for an eosinophilic exacerbation; in this population, the mean length of stay (in days) was shorter than in patients with noneosinophilic exacerbations (5.0 [range, 1-19] vs 6.5 [range, 1-33]; P = .015) following treatment with oral corticosteroids and independent of treatment prior to admission. Readmission rates at 12 months were similar between groups. CONCLUSIONS: The study patients presenting to the hospital with a severe eosinophilic exacerbation of COPD had a shorter length of stay. The exacerbations were usually not associated with elevated C-reactive protein levels, suggesting that better treatment stratification of exacerbations can be used. TRIAL REGISTRY: http://www.isrctn.com/ISRCTN05557928.

An early rehabilitation intervention to enhance recovery during hospital admission for an exacerbation of chronic respiratory disease: randomised controlled trial.

OBJECTIVE: To investigate whether an early rehabilitation intervention initiated during acute admission for exacerbations of chronic respiratory disease reduces the risk of readmission over 12 months and ameliorates the negative effects of the episode on physical performance and health status. DESIGN: Prospective, randomised controlled trial. SETTING: An acute cardiorespiratory unit in a teaching hospital and an acute medical unit in an affiliated teaching district general hospital, United Kingdom. PARTICIPANTS: 389 patients aged between 45 and 93 who within 48 hours of admission to hospital with an exacerbation of chronic respiratory disease were randomised to an early rehabilitation intervention (n=196) or to usual care (n=193). MAIN OUTCOME MEASURES: The primary outcome was readmission rate at 12 months. Secondary outcomes included number of hospital days, mortality, physical performance, and health status. The primary analysis was by intention to treat, with prespecified per protocol analysis as a secondary outcome. INTERVENTIONS: Participants in the early rehabilitation group received a six week intervention, started within 48 hours of admission. The intervention comprised prescribed, progressive aerobic, resistance, and neuromuscular electrical stimulation training. Patients also received a self management and education package. RESULTS: Of the 389 participants, 320 (82%) had a primary diagnosis of chronic obstructive pulmonary disease. 233 (60%) were readmitted at least once in the following year (62% in the intervention group and 58% in the control group). No significant difference between groups was found (hazard ratio 1.1, 95% confidence interval 0.86 to 1.43, P=0.4). An increase in mortality was seen in the intervention group at one year (odds ratio 1.74, 95% confidence interval 1.05 to 2.88, P=0.03). Significant recovery in physical performance and health status was seen after discharge in both groups, with no significant difference between groups at one year. CONCLUSION: Early rehabilitation during hospital admission for chronic respiratory disease did not reduce the risk of subsequent readmission or enhance recovery of physical function following the event over 12 months. Mortality at 12 months was higher in the intervention group. The results suggest that beyond current standard physiotherapy practice, progressive exercise rehabilitation should not be started during the early stages of the acute illness.Trial registration Current Controlled Trials ISRCTN05557928.

In vivo needle-based electromechanical reshaping of pinnae: New Zealand White rabbit model.

IMPORTANCE: Electromechanical reshaping (EMR) is a low-cost, needle-based, and simple means to shape cartilage tissue without the use of scalpels, sutures, or heat that can potentially be used in an outpatient setting to perform otoplasty. OBJECTIVES: To demonstrate that EMR can alter the shape of intact pinnae in an in vivo animal model and to show that the amount of shape change and the limited cell injury are proportional to the dosimetry. DESIGN, SETTING, AND SPECIMENS: In an academic research setting, intact ears of 18 New Zealand white rabbits underwent EMR using 6 different dosimetry parameters (4 V for 5 minutes, 4 V for 4 minutes, 5 V for 3 minutes, 5 V for 4 minutes, 6 V for 2 minutes, and 6 V for 3 minutes). A custom acrylic jig with 2 rows of platinum needle electrodes was used to bend ears at the middle of the pinna and to perform EMR. Treatment was repeated twice per pinna, in proximal and distal locations. Control pinnae were not subjected to current application when being bent and perforated within the jig. Pinnae were splinted for 3 months along the region of the bend using soft silicon sheeting and a cotton bolster. MAIN OUTCOMES AND MEASURES: The ears were harvested the day after splints were removed and before euthanasia. Photographs of ears were obtained, and bend angles were measured. Tissue was sectioned for histologic examination and confocal microscopy to assess changes to microscopic structure and cellular viability. RESULTS: Treated pinnae were bent more and retained shape better than control pinnae. The mean (SD) bend angles in the 7 dosimetry groups were 55° (35°) for the control, 60° (15°) for 4 V for 4 minutes, 118° (15°) for 4 V for 5 minutes, 88° (26°) for 5 V for 3 minutes, 80° (17°) for 5 V for 4 minutes, 117° (21°) for 6 V for 2 minutes, and 125° (18°) for 6 V for 3 minutes. Shape change was proportional to electrical charge transfer, which increased with voltage and application time. Hematoxylin-eosin staining of the pinnae identified localized areas of cell injury and fibrosis in the cartilage and in the surrounding soft tissue where the needle electrodes were inserted. This circumferential zone of injury (range, 1.5-2.5 mm) corresponded to dead cells on cell viability assay, and the diameter of this region increased with total electrical charge transfer to a maximum of 2.5 mm at 6 V for 3 minutes. CONCLUSIONS AND RELEVANCE: Electromechanical reshaping produced shape change in intact pinnae of rabbits in this expanded in vivo study. A short application of 4 to 6 V can achieve adequate reshaping of the pinnae. Tissue injury around the electrodes increases with the amount of total current transferred into the tissue and is modest in spatial distribution. This study is a critical step toward evaluation of EMR in clinical trials. LEVEL OF EVIDENCE: NA.

In vivo electromechanical reshaping of ear cartilage in a rabbit model: a minimally invasive approach for otoplasty.

OBJECTIVE: To report the first successful study to date of in vivo electromechanical reshaping of ear cartilage in a rabbit model. METHODS: Ears of New Zealand white rabbits were reshaped using percutaneous needle electrode electromechanical reshaping (5 V for 4 minutes) and were then bolstered for 4 weeks. Ten ears were treated, with 2 undergoing sham procedures and serving as controls. The treatment was performed using a platinum array of electrodes consisting of 4 parallel rows of needles inserted across the region of flexures in the ear. After 4 weeks, the animals were killed, and the ears were photographed and sectioned for conventional light microscopy and confocal microscopy (live-dead fluorescent assays). RESULTS: Significant shape change was noted in all the treated ears (mean, 102.4°; range, 87°-122°). Control ears showed minimal shape retention (mean, 14.5°; range, 4°-25°). Epidermis and adnexal structures were preserved in reshaped ears, and neochondrogenesis was noted in all the specimens. Confocal microscopy demonstrated a localized zone of nonviable chondrocytes (<2.0 mm in diameter) surrounding needle sites in all the treated ears. CONCLUSIONS: Electromechanical reshaping can alter the shape of the rabbit auricle, providing good creation and retention of shape, with limited skin and cartilage injury. Needle electrode electromechanical reshaping is a viable technique for minimally invasive tissue reshaping, with potential applications in otoplasty, septoplasty, and rhinoplasty. Further studies to refine dosimetry parameters will be required before clinical trials.

Risk factors for multidrug-resistant tuberculosis in urban Pakistan: A multicenter case-control study.

OBJECTIVE: To evaluate risk factors for multidrug-resistant tuberculosis (MDR-TB) in an urban setting of Pakistan. DESIGN AND METHODS: In this multicenter case-control study, patients aged 15years old or older with sputum culture and sensitivity (C/S) diagnosed with pulmonary MDR-TB were defined as cases, whereas patients aged 15years old or older with sputum C/S diagnosed and susceptible to pulmonary TB were regarded as controls. Fifty cases and 75 controls were enrolled from three tertiary-care hospitals in Karachi. RESULTS: Multivariable logistic regression models showed that cases were more likely to have had a TB patient in the house prior to the diagnosis of MDR-TB (adjusted odds ratio [ORadj]=3.1, 95% confidence interval [CI]: 1.2, 8.3) or had a history of prior TB treatment (ORadj=4.2, 95% CI: 1.1, 15.4). Furthermore, cases compared with controls tended to be male (ORadj=3.6, 95% CI: 1.4, 9.7), 15-25years of age (ORadj=3.7, 95% CI: 1.2, 11.3), of Sindhi ethnicity (adjusted OR=9.1, 95% CI: 1.9, 43.4) or with low educational attainment (ORadj OR=5.5, 95% CI: 1.7-17.6, for no formal schooling; ORadj=3.8, 95% CI: 1.1-14.1, 1 for 1-5 school years). CONCLUSIONS: A TB patient in the house or a history of prior TB treatment was strongly associated with MDR-TB in this study. Furthermore, younger age, male gender, Sindhi ethnicity and poor educational attainment entailed a high risk for MDR-TB. Targeted educational intervention for patients and their contacts may minimize the noncompliance with prescribed TB treatment and lessen MDR-TB magnitude in settings like Karachi.

A randomized trial of auto-titrating CPAP and fixed CPAP in the treatment of obstructive sleep apnea-hypopnea.

BACKGROUND: Continuous positive airway pressure (CPAP) remains the treatment of choice for obstructive sleep apnea hypopnea (OSAH). Auto-titrating CPAP (APAP) devices automatically adjust pressure and may improve treatment compliance compared to fixed CPAP (F-CPAP). METHODS: Randomized, prospective, single-blind, crossover trial to compare efficacy, side effects, compliance, patient satisfaction and preference between APAP and F-CPAP therapy in patients with moderate to severe OSAH. There were two treatment periods of 4 weeks each (APAP and F-CPAP), separated by a 2-week washout period. RESULTS: Ten CPAP-naive OSAH patients (9 males) completed the study. They had Mean +/- SD age of 44.9 +/- 9.7 years; body mass index of 35.9 +/- 12.9 kg/m2 and apnea/hypopnea index (AHI) of 47.2 +/- 35.6. Both forms of therapy were equally effective in improving the symptoms and in reducing the AHI. Both forms of therapy were associated with frequent side effects and had similar patient compliance. At the end of the study, more patients (6-1) preferred F-CPAP to A-CPAP therapy. CONCLUSION: A-PAP was as effective as F-CPAP in the treatment of OSAH but was not associated with fewer side effects, better compliance, better satisfaction or increased patient preference.