Pharmacokinetics of First-Line Antituberculosis Drugs in HIV-Infected Children with Tuberculosis Treated with Intermittent Regimens in India

The objective of this report was to study the pharmacokinetics of rifampin (RMP), isoniazid (INH), and pyrazinamide (PZA) in HIV-infected children with tuberculosis (TB) treated with a thrice-weekly anti-TB regimen in the government program in India. Seventy-seven HIV-infected children with TB aged 1 to 15 years from six hospitals in India were recruited. During the intensive phase of TB treatment with directly observed administration of the drugs, a complete pharmacokinetic study was performed. Drug concentrations were measured by high-performance liquid chromatography. A multivariable regression analysis was done to explore the factors impacting drug levels and treatment outcomes. The proportions of children with subnormal peak concentrations (C_max) of RMP, INH, and PZA were 97%, 28%, and 33%, respectively. Children less than 5 years old had a lower median C_max and lower exposure (area under the time-concentration curve from 0 to 8 h [AUC_0–8]) of INH (C_max, 2.5 versus 5.1 μg/ml, respectively [P = 0.016]; AUC_0–8, 11.1 versus 22.0 μg/ml · h, respectively [P = 0.047[) and PZA (C_max, 34.1 versus 42.3 μg/ml, respectively [P = 0.055]; AUC_0–8, 177.9 versus 221.7 μg/ml · h, respectively [P = 0.05]) than those more than 5 years old. In children with unfavorable versus favorable outcomes, the median C_max of RMP (1.0 versus 2.8 μg/ml, respectively; P = 0.002) and PZA (31.9 versus 44.4 μg/ml, respectively; P = 0.045) were significantly lower. Among all factors studied, the PZA C_max influenced TB treatment outcome (P = 0.011; adjusted odds ratio, 1.094; 95% confidence interval, 1.021 to 1.173). A high proportion of children with HIV and TB had a subnormal RMP C_max. The PZA C_max significantly influenced treatment outcome. These findings have important clinical implications and emphasize that drug doses in HIV-infected children with TB have to be optimized.     

A comparative evaluation of dermatoglyphics in different classes of malocclusion

Aim

To study associations of dermatoglyphic features with malocclusion in Indian children.

Materials and methods

A total of 237 children aged 12–16 years, who attended our outpatient clinic in a government medical college, were selected. Finger and palm prints were collected, and fingertip pattern frequencies, total ridge counts (TRCs), and atd angles (formed by the triradii below the first and last digits and that in the hypothenar region of the palm) were calculated. These parameters were analyzed with their Angle’s class of malocclusion using appropriate statistical tests. Dermatoglyphic parameters were examined and asymmetry analysis was conducted in subjects with different occlusion patterns.

Results

Although no fingerprint pattern was found to be specific for a particular class of occlusion, increased tendencies toward high frequencies of whorls in subjects with class II malocclusion and plain arches in those with class III malocclusion were observed. Significant differences in atd angle and TRC were observed among malocclusion types (p = 0.0001). Asymmetry scores did not differ significantly.

Conclusion

Dermatoglyphic analysis can be used as an indicator of malocclusion at an early age, thereby aiding the development of treatments aiming to establish favorable occlusion. Inheritance and twin studies, as well as those conducted in different ethnic groups, are required to examine these relationships further.     

Compression screw fixation without bone grafting for scaphoid fibrous nonunion

Purpose

Bone graft is often recommended as an adjuvant for treatment of scaphoid nonunions. However, recent literature has suggested that fibrous nonunion may be suited to treatment with rigid fixation without bone grafting. This work reported on outcomes of compression screw fixation for established scaphoid fibrous nonunions without bone graft.

Methods

Fourteen patients underwent surgical compression screw fixation without bone grafting of scaphoid fibrous nonunion between January 1, 2000, and December 31, 2012, with minimum follow-up until the time of clinical and radiographic healing. Fibrous nonunion of the scaphoid was defined as a scaphoid fracture with all of the following features: (1) persistent tenderness, (2) incomplete trabecular bridging on three X-ray views, (3) injury that had occurred at a minimum of 6 months prior to surgery, and (4) identification of fibrous union at the time of surgery. Outcomes were assessed with range of motion assessment, Disability of the Arm, Shoulder and Hand (DASH) scores, and plain radiographs.

Results

Twelve of the 14 patients healed successfully, while two patients required secondary vascularized bone grafting. Both unhealed patients sustained proximal pole fractures and had a duration of ≥1 year from injury to surgery. Average time to healing was 4.4 ± 2.0 months. Average flexion was 73 ± 22° and average extension was 66 ± 22° postoperatively. Average grip strength was 90 ± 25 lbs on the operative side. Mean postoperative pain score was 1.4 (range, 0 to 7). Mean postoperative DASH score was 10.2 (range, 0 to 52). Increasing age and an interval from injury to surgery of >1 year correlated with worse DASH and pain scores.

Conclusions

Patients with fibrous scaphoid nonunion demonstrated good results with rigid fixation without bone grafting. Increasing age and >1-year interval between injury and surgery resulted in lower self-assessed outcomes.

Level of Evidence

Therapeutic Level IV, retrospective case series     

Control of hospital acquired infections in the ICU: A?service perspective

Background

The service setting has some unique strengths and weaknesses that must be kept in mind when organizing Hospital acquired infections (HAI) prevention interventions.

Methods

Following an initial study to gather data regarding HAI in the Surgical intensive care unit (ICU) we put into place various infection control interventions. The present study was carried out to analyse the effect of these interventions on the incidence of HAI in the ICU.

Results

The total admissions to the ICU were 253 patients. Eighty eight patients (34.78%) were admitted for more than 48 hr, 165 patients stayed for less than 48 h. The frequency of HAI was 7.95% (95% CI 3.54, 15). Hospital acquired pneumonia was observed in 2 of the 88 patients (2.27%) (95% CI 0.38, 7.30) which amounted to 9.70 infections per 1000 ventilator days. Bloodstream infection was detected in 3 out of 88 patients (3.4%) (95% CI 0.87, 8.99) amounting to 6.54 fresh infections per 1000 Central Venous Catheter days. Urinary tract infection was observed in 2 (2.27%) (95% CI 0.38, 7.30) at 2.86 fresh infections per 1000 catheter days. As compared to the previous study we found that there was a decline of HAI ranging from 60 to 70%.

Conclusion

Our study demonstrated that by meticulously following infection control protocols especially tailored to the service setting the incidence of HAI''s can be reduced. However, the challenge is in maintaining the gains achieved since there is a rapid turnover of manpower in the ICU and a lack of a structured ICU design model.     

Acute pulmonary embolism in elderly: clinical characteristics and outcome

OBJECTIVE: To evaluate the clinical characteristics and outcome of acute pulmonary embolism in elderly in comparison to the younger patients. METHODS: Study population consisted of 136 patients with a confirmed diagnosis of acute pulmonary embolism. Clinical characteristics and thromboembolic risk factors were analyzed between the elderly (> or =65 years of age) and the younger (<65 years of age) patients. In-hospital mortality was used as a measure of outcome. RESULTS: Elderly group consisted of 70 patients (age 76.4+/-8.3 years, range 65-96 years; females 58%) and younger group of 66 patients (age 48.5+/-12 years, range 18-64 years, females 59%). Syncope was more frequent in elderly group (19% vs. 6%, P=0.03) but the symptoms of shortness of breath and pleuritic chest pain were not significantly different between groups. Malignancy was the most common risk factor for thrombo-embolism, but immobilization predominated among patients in elderly group (21% vs. 6%, P=0.01). Tachycardia was common in younger patients compared to the elderly. Ventilation-perfusion scan was used more commonly in younger patients (76% vs. 57%, P=0.02), whereas, helical computed-tomography scan was used equally in both groups. Most of the patients had lower extremity duplex study (97% in each group). Inferior vena cava filter placement was common and thrombolytic therapy rare among elderly patients. Patients in elderly group had higher in-hospital mortality (17% vs. 5%, P=0.02). CONCLUSIONS: Syncope is a more frequent presenting symptom and immobilization a common risk factor in elderly patients with acute pulmonary embolism. In addition, they have higher in-hospital mortality.     

Study of Efficacy and the Comparison Between 2.0?mm Locking Plating System and 2.0?mm Standard Plating System in Mandibular Fractures

Purpose

The purpose of this study was to evaluate the efficacy and comparison between 2.0 mm locking plate system and 2.0 mm Champy’s titanium mini plating system in mandible fractures.

Materials and Methods

A total of 20 patients with mandibular fractures were selected and divided into two groups A and B on randomized basis. Group A was treated with open reduction internal fixation using 2.0 mm locking plates and group B with 2.0 mm Champy’s titanium miniplates. All patients were followed up for 12 weeks postoperatively.

Results

Results of the study show less screw loosening, less precision in plate adaptation and less alteration of the osseous or occlusal relationship upon screw tightening in group A. Chi square test was applied to compare the results between the two groups. Statistical analysis did not show significant difference of incidence of malocclusion between the two groups (p value = 0.606). Statistical analysis using un-paired t test showed significant difference of working time between the two groups (p value = 0.00296). When comparing the overall complication rates according to plates used, the χ² test showed no statistically significant difference between the locking and nonlocking plates (p > 0.05).

Conclusion

It is observed in our study that the locking plate/screw system offers significant advantages over the conventional plating system. The precise adaptation required for using conventional plates is not needed when this locking plate/screw system is used. Locking plate/screw system provides better stability than the conventional plate/screw system.     

High Recovery of Functional Islets Stored at Low and Ultralow Temperatures

BACKGROUND: Poor recovery of islets upon cryopreservation is the main hurdle in islet banking. Pancreatic islets have a poor antioxidative defense mechanism, and exposure of islets to low temperature leads to oxidative stress. AIM: We aimed to investigate whether known compounds such as metformin, γ aminobutyric acid (GABA), docosahexanoic acid (DHA), or eicosapentaenoic acid (EPA) alone or in combination are capable of reducing oxidative stress for better islet recovery upon storage at suboptimal temperatures. METHODS: Islets isolated from mouse pancreas were stored at low temperature (4°C) for 15 days and at ultralow temperature (-196°C) for 30 days with or without additives. After revival from cold storage, islets were assessed by using three methods: (1) specificity by dithizone (DTZ), (2) viability by fluorescein diacetate/propidium iodide (FDA/PI) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetra-zolium bromide (MTT) assay, and (3) functionality by glucose-stimulated insulin secretion (GSIS). The oxidative status of the islets stored at suboptimal temperatures was determined by both intracellular free radical release (fluorometric analysis) and lipid peroxidation (enzymatic determination). RESULTS: Supplementation with additives led to an improvement in islet survival upon storage at suboptimal temperatures, without depletion of insulin secretory activity, which was comparable to that of controls. The additives acted as cryoprotectants and antioxidants as revealed by high recovery of viable islets and reduction in total reactive oxygen species (ROS) and malonidealdehyde (MDA), respectively. CONCLUSIONS: Our results demonstrate for the first time that supplementation with EPA, DHA, and metformin may lead to higher islet recovery from -196°C storage, enabling proper islet banking.     

Airway management in inhalation injury: a case series

Inhalation injury is a serious consequence of a fire or an explosion, with potential airway compromise and respiratory complications. We present a case series of five patients with inhalational burns who presented to Singapore General Hospital and discuss our approach to their early management, including early evaluation and planning for the upper and lower airway, coexisting cutaneous burns, and monitoring their ICU (intensive care unit) severity of illness, sepsis and acute respiratory distress syndrome. All five patients suffered various grades of inhalation injury. The patients were initially assessed by nasolaryngoscopy, and three patients were prophylactically intubated before being sent to the emergency operating theatre for definitive airway and burns management with fibreoptic bronchoscopy. All patients were successfully extubated and discharged stable. Various complications can arise as a result of an inhalation injury. Based on our cases and literature review, we propose a standardised workflow for patients with inhalation injury.     

Association Between Alcohol Use and HIV-Related Sexual Risk Behaviors Among Men Who Have Sex with Men (MSM): Findings from a Multi-Site Bio-Behavioral Survey in India

This paper examines the association between alcohol use and HIV-related sexual risk behaviors among men who have sex with men (MSM). A cross-sectional bio-behavioral survey was conducted among 3,880 MSM, recruited using time-location cluster sampling from cruising sites in three Indian states. Nearly three-fifths of the participants reported alcohol use. Among frequent users (40 % of the sample), defined as those who consumed alcohol daily or at least once a week, 66 % were aged 25 years and above, 53 % self-identified as kothi (feminine/receptive), and 63 % consistently used condoms with male paying partners. Multivariate logistic regression demonstrated that frequent users were more likely to be aged 25 years and above, less likely to self-identify as kothi, and less likely to consistently use condoms with male paying (AOR = 0.7; 95 % CI 0.5–0.9) and male regular (AOR = 0.7; 95 % CI 0.6–0.9) partners. HIV prevention interventions for MSM need to provide tailored information on alcohol use-related sexual risk, especially for MSM in sex work and MSM with male regular partners.