Effectiveness of 3-day amoxycillin vs. 5-day co-trimoxazole in the treatment of non-severe pneumonia in children aged 2-59 months of age: a multi-centric open labeled trial

This cluster randomized, open labeled trial was conducted to compare the effectiveness of 3 days of oral amoxycillin and 5 days of co-trimoxazole treatment in terms of clinical failure in children with World Health Organization (WHO) defined non-severe pneumonia in primary health centers in rural India. Participants were children aged 2-59 months with WHO defined non-severe pneumonia, with or without wheeze, who were accessible to follow up. From seven primary health centers in each arm, 2009 cases were randomized, 993 and 1016 in treatment with amoxycillin and co-trimoxazole, respectively. Fever was present in 1247 (62.1%) and wheeze in 443 (22.1%). There was good adherence and low loss to follow-up. Clinical failure on amoxycillin and co-trimoxazole on intention to treat analysis was 137 and 97, respectively (absolute difference = 0.04, 95% confidence interval: - 0.035-0.12). We conclude that there was no difference in effectiveness of oral co-trimoxazole or amoxycillin in treating non-severe pneumonia.     

A demographic study to profile non-attenders at a gynaecology outpatient clinic

Missed outpatient appointments result in the inefficient utilisation of resources and have secondary effects on the health of the non-attenders, as well as on other patients who have to wait longer for their appointments. The first part of the study involved retrospective analysis of trends of non-attendance based on a computerised database of all gynaecology appointments over 12 months. The second comprised a prospective case-control study in which women who missed their gynaecology outpatient appointments (index cases) over 2 months were compared with patients who attended the same clinics matched for indication for referral (control cases). The overall non-attendance rate over 12 months was 16.1%, of whom 42% were recurrent non-attenders. Data from 105 defaulters were compared with 105 non-defaulters who attended the same clinics. Defaulters were significantly younger, single or separated and were more likely to be 'follow-ups' rather than new cases (all p < 0.05). Longer intervals between the appointment letter and actual appointment date was significantly related to non-attendance (p = 0.01) and there was a trend to a greater degree of smoking and alcohol ingestion in the defaulter group (p = 0.059). Comparison of other variables such as severity of symptoms, parity, source of referral and fluency of English did not reach statistical significance (p > 0.05). This prospective study has demonstrated certain profiles which are common to defaulters and which can be used to develop strategies to minimise non-attendance. Examples include reducing the time interval between sending the appointment letter and actual appointment date and selectively over-booking younger, single women who smoke.     

Factors associated with sustained virological response in liver transplant recipients with recurrent hepatitis C

Background

Antiviral therapy has achieved sustained virological response (SVR) in less than one third of orthotopic liver transplantation (OLT) patients with recurrent hepatitis C.

Aim

The aim of this study was to identify predictors of SVR in OLT patients treated with pegylated interferon and ribavirin (PEG+RBV) for recurrent hepatitis C virus (HCV).

Methods

We analyzed data from our transplantation database for 62 subjects treated with PEG+RBV between August 2001 and September 2008. After univariate examination for factors known to be associated with SVR, significant associations (P < .05) were probed using multivariate logistic regression. Kaplan-Meier patient and graft survival analyses were compared between patients with (n = 19; 30.6%) versus without SVR.

Results

On univariate analysis, longer duration of therapy, low pretreatment HCV RNA (<1 million IU/mL), and early virological response (EVR) were associated with SVR. On multivariate analysis, only low pretreatment HCV RNA predicted SVR. Patient survival was significantly higher in the SVR group.

Conclusions

Covariates associated with SVR among OLT patients with recurrent HCV were similar to the pretransplantation group. Potentially modifiable risk factors, such as obesity, diabetes mellitus, and metabolic syndrome, were not significant predictors of treatment response. Patient survival was associated with SVR, highlighting the impact of successful HCV therapy on long-term post-OLT outcomes.     

Serous borderline tumor of the fallopian tube in a patient with Klippel-Trenaunay syndrome

We describe a case of a 3-year-old girl with Klippel-Trenaunay syndrome who presented with an enlarging abdominal mass caused by a serous borderline tumor of the fallopian tube. This case is notable for the rarity of this neoplasm in a premenarchal patient as well as the association with this syndrome. We briefly review these entities and the significance of malignancy in Klippel-Trenaunay syndrome.     

Protective effects of 'Khamira Abresham Hakim Arshad Wala', a unani formulation against doxorubicin-induced cardiotoxicity and nephrotoxicity

Doxorubicin is one of the most active cytotoxic agents in current use. The clinical usefulness of the doxorubicin has been precluded by its marked cardiotoxicity. The aim of the present study was to investigate the effect of Khamira Abresham Hakim Arshadwala, a well known unani cardiac tonic formulation, pre-treatment on doxorubicin-induced cardiotoxicity, and nephrotoxicity in rats. Twenty-four Wistar albino rats, divided into four groups, were used. Khamira Abresham Hakim Arshadwala was administered daily, for 7 days, and a single dose of doxorubicin (10 mg/kg, i.v.) on day 5. After 48 h of doxorubicin injection, animals were sacrificed. Lactate dehydrogenase (LDH), aspartate transaminase (AST), blood urea nitrogen (BUN), and creatinine were estimated in the serum. Heart specimens were used for biochemical estimations of lipid peroxides (MDA), reduced glutathione (GSH), catalase, and for microscopic examination of histopathological changes. Doxorubicin showed cardiotoxicity and nephrotoxicity, as evidenced by elevated activities of AST, LDH, BUN, creatinine, and MDA, depletion in GSH level, and catalase activity. Histopathological studies showed disruption of cardiac tissues in doxorubicin groups. Khamira Abresham Hakim Arshadwala pre-treatment showed a protective effect against the enzymatic changes in serum as well as cardiac and kidney tissue damage, significantly. The present findings suggest that Khamira Abresham Hakim Arshadwala significantly (p < 0.01) improved the state of markers for cardiac and kidney damage investigated in this model of doxorubicin-induced experimental cardiotoxicity and nephrotoxicity; indicating its potential in limiting doxorubicin toxicity.     

Population pharmacodynamic model of the longitudinal FEV<Subscript>1</Subscript> response to an inhaled long-acting anti-muscarinic in COPD patients

The precise assessment of the dose–response to bronchodilators in the treatment of chronic obstructive pulmonary disease is hindered by the low signal to noise ratio of the typical clinical endpoint FEV₁. Kinetic-pharmacodynamic (K-PD) models which use time course of response over a range of doses are in principle suited for the assessment of the dose response relationship of pulmonary administered drugs. A K-PD model was successfully developed using the longitudinal FEV1 data collected in the clinical study for a novel bronchodilator X. A superposition of two cosine functions was selected to describe the circadian variability in FEV₁ at baseline. The onset (ka) and offset (kde) of drug action were described with first-order rate constants of 0.214/h and 0.141/h, respectively. Drug potency, EKD_50, was estimated as 6.56 μg/h, and the maximum response, Emax as 0.631 L. Between-subject variability for kde, EKD₅₀ and Emax were 65, 84.7 or 34.4% (expressed as coefficient variation). The model-based simulation predicted that for the same total daily dose of once-daily and twice-daily regimens, the trough FEV₁ response to a twice-daily regimen was higher, and the maximum FEV₁ response to once-daily regimen was higher, while the predicted average FEV₁ response was about the same.     

Lack of Bactericidal Antagonism or Synergism In Vitro between Oxacillin and Vancomycin against Methicillin-Susceptible Strains of Staphylococcus aureus

With the current high prevalence of infection caused by methicillin-resistant Staphylococcus aureus (MRSA) strains but in light of the general belief that β-lactam antibiotics are more effective than vancomycin against infections caused by methicillin-susceptible S. aureus (MSSA) isolates, clinicians may utilize antistaphylococcal penicillins in combination with vancomycin for the empirical treatment of S. aureus infections. Vancomycin is considered to kill MSSA more slowly than oxacillin. Thus, we sought to evaluate the interaction of the combination of oxacillin and vancomycin on bacterial killing in vitro. Ten clinical isolates of MSSA isolated in the year 2000 were investigated. The killing observed at 24 h by vancomycin at 20 μg/ml, oxacillin at 16 μg/ml, or the combination did not differ (approximately 2.5 to 3.5 log₁₀ CFU/ml). In a separate experiment, we assessed bacterial killing in a dynamic model simulating the free plasma concentration profiles expected following the administration of a combination of vancomycin at 1 g every 12 h and oxacillin at 1 g every 6 h. The time-kill profiles of these regimens against S. aureus ATCC 29213 were comparable to those observed in the fixed-concentration experiments. Using these methods, we found no evidence that vancomycin antagonized the bactericidal effect of oxacillin or that there was any benefit from use of the combination.In many clinical settings, methicillin-resistant Staphylococcus aureus (MRSA) strains comprise such a high proportion of the S. aureus isolates that empirical treatment with vancomycin is begun when a staphylococcal infection is suspected (10, 18). However, several studies have reported that for infections due to methicillin-susceptible S. aureus (MSSA) strains, treatment with β-lactam antibiotics results in clinical outcomes better than those achieved with vancomycin (15, 18). For this reason, some clinicians use vancomycin and a β-lactam together as empirical treatment, both to provide adequate coverage for MRSA and in the belief that the β-lactam would provide superior antimicrobial activity should the organism prove to be methicillin susceptible.Small and Chambers (17) reported that vancomycin killed MSSA more slowly than nafcillin when they used time-kill methods. This observation suggests that when the antibiotics are used together, the more slowly acting bactericidal agent, vancomycin, may have the potential to antagonize the more rapid bactericidal effect of oxacillin, negating the anticipated benefit of the β-lactam. Such in vitro antagonism has been demonstrated when ß-lactams are combined with bacteriostatic agents such as erythromycin (8). In the present study, we sought to evaluate the interactions between vancomycin and oxacillin against clinical isolates of MSSA.(Part of the data presented here were presented at the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, CA, 12 to 15 September 2009 [abstr. E-1452].)     

Pulmonary Sarcomatoid Carcinoma: An Analysis of the National Cancer Data Base

Introduction

Pulmonary sarcomatoid carcinoma (PSC) is a grouping of 5 rare non–small-cell lung cancer (NSCLC) subtypes. We studied the clinical characteristics and outcomes of PSC utilizing the National Cancer Data Base (NCDB), an oncology outcomes database.