Efficacy and safety of metronidazole for pulmonary multidrug-resistant tuberculosis.

Pulmonary lesions from active tuberculosis patients are thought to contain persistent, nonreplicating bacilli that arise from hypoxic stress. Metronidazole, approved for anaerobic infections, has antituberculosis activity against anoxic bacilli in vitro and in some animal models and may target persistent, nonreplicating bacilli. In this double-blind, placebo-controlled trial, pulmonary multidrug-resistant tuberculosis subjects were randomly assigned to receive metronidazole (500 mg thrice daily) or placebo for 8 weeks in addition to an individualized background regimen. Outcomes were measured radiologically (change on high-resolution computed tomography [HRCT]), microbiologically (time to sputum smear and culture conversion), and clinically (status 6 months after stopping therapy). Enrollment was stopped early due to excessive peripheral neuropathies in the metronidazole arm. Among 35 randomized subjects, 31 (15 metronidazole, 16 placebo) were included in the modified intent-to-treat analysis. There were no significant differences by arm in improvement of HRCT lesions from baseline to 2 or 6 months. More subjects in the metronidazole arm converted their sputum smear (P = 0.04) and liquid culture (P = 0.04) to negative at 1 month, but these differences were lost by 2 months. Overall, 81% showed clinical success 6 months after stopping therapy, with no differences by arm. However, 8/16 (50%) of subjects in the metronidazole group and 2/17 (12%) of those in the placebo group developed peripheral neuropathy. Subjects who received metronidazole were 4.3-fold (95% confidence interval [CI], 1.1 to 17.1) more likely to develop peripheral neuropathies than subjects who received placebo. Metronidazole may have increased early sputum smear and culture conversion but was too neurotoxic to use over the longer term. Newer nitroimidazoles with both aerobic and anaerobic activity, now in clinical trials, may increase the sterilizing potency of future treatment regimens.

Identifying priority medicines policy issues for Qatar: exploring perspectives and experiences of healthcare professionals through a qualitative study.

OBJECTIVES: To identify priority medicines policy issues, including the 'use' and 'access to medicines' in Qatar. DESIGN: In this qualitative study, general inductive method was used and semi-structured exploratory interviews conducted. SETTING: Stakeholders from a broad range of academic and healthcare practitioners in Qatar. PARTICIPANTS: Exploratory, semi-structured interviews were conducted with 21 stakeholders throughout Qatar. The inclusion criteria include (a) participants working or involved in the Qatar's healthcare system, (b) participants having experience or working knowledge of medicine policy documents, different facets of it, use of medicines and access to medicines, (c) as well as participants well versed in the English language. It was intended to cover stakeholders from a broad range of healthcare and policy institutions in Qatar. PRIMARY AND SECONDARY OUTCOME MEASURES: All participants were involved in semi-structured, audio-recorded interviews, which were then transcribed verbatim, coded into NVivo V.12 and followed by thematic analysis to identify the common themes. Perceptions, experiences and opinions regarding Qatar's medicines policy issues were recorded. RESULTS: This study found challenges related to the availability of pharmaceuticals in Qatar, including medicines registration process. There is no comprehensive national medicines policy in Qatar, however, there are a number of rules, regulations, policies and procedures in place. The community pharmacy services provided are mostly 'traditional' with less emphasis on pharmacists' extended roles and/or cognitive services. The study identifies several areas for improvement including extending the role of the pharmacist, improve the prescribing of antibiotics, medicines compliance and counselling for consumers, pharmacovigilance, implementation of generic medicines policies, as well as the need for a national health record database. CONCLUSIONS: The findings suggest that in the last 20 years, Qatar has moved towards advancing healthcare; however, there are gaps and opportunities. The strategies need to be developed to resolve access to medicines issues, the priority being medicines registration, import and so on. With the rise of chronic diseases and a growing population, there is also a need to work to improve medicines adherence among patients.A national medicines policy should be developed through a consultative broad-based process in which prescribers, physicians, pharmacists and healthcare professionals be given a chance to contribute.

Comparison of forced expiratory volume in one second (FEV1) among asymptomatic smokers and non-smokers.

OBJECTIVE: To compare the forced expiratory volume in first second (FEV1) among asymptomatic smokers and non-smokers for evaluating the effect of cigarette smoking on healthy subjects. METHODS: This was a Comparative cross-sectional study done at military hospital Rawalpindi from June 2006 till June 2007. Two hundred male subjects, 100 smokers and 100 non-smokers were included using non-probability convenience sampling. SCHILLER SPIROMETER (SP-1A) was used to measure forced expiratory volume in one second in all individuals. Best FEV1 was obtained after three efforts. RESULTS: FEV1 was measured in a population of male smokers less than 45 years of age, and compared with a matched group of non smokers, mean age being 35.08 +/- 4.73 years (n=200) and mean height of 170.73 +/- 5.76 cm (n=200). The prevalence rates of previously undetected airflow obstruction were studied according to the British Thoracic Society (BTS) criteria. This study showed that 16 out of 100 smokers had mild airway obstruction while only 01 non smoker out of 100 had FEV1 levels below 80%. The prevalence rate of airway obstruction was associated with age and the number of pack years of smoking. CONCLUSION: The prevalence of undetected airflow obstruction is high among asymptomatic smokers. Targeted screening therefore, especially in smokers needs to be considered. Since lung function declines with time, therefore best time to prevent morbidity and mortality from smoking-related illness should be early in life.

Gated MIBI myocardial SPECT showing balanced ischemia and global hypokinesia in patient having thrombus in basal segment of dominant circumflex system blocking both left anterior descending and circumflex artery.

Myocardial perfusion imaging (MPI) is a powerful diagnostic and prognostic tool for evaluating coronary artery disease (CAD). Gating myocardial perfusion gives important diagnostic and prognostic information. This 43 years old patient was referred for cardiac scan. Exercise stress test showed > 2 mm horizontal ST segment depression. Cardiac scan was normal except for left ventricular cavity dilatation on stress images. Gated images showed global hypokinesia and increased end-diastolic volume. Patient was suspected to have balanced ischemia and was referred for Angiography. Angiography showed total occlusion with no flow in proximal Left Anterior Descending Artery and distal circumflex artery. It is very important to evaluate symptomatic patients and patients with risk factors carefully with normal myocardial perfusion scan.

Diagnostic evaluation of patients presenting with bleeding per rectum by colonoscopy.

BACKGROUND: Rectal bleeding is a manifestation of lower gastrointestinal bleed, which means bleeding from a site distal to ligament of Treitz. Annual incidence of this problem has been estimated to be 20% and mortality as 11%. Patients complaining of haematochezia are suspected of having lower GI bleeding and proctosigmoidoscopy followed by colonoscopy is the examination of choice for diagnosis and treatment. Previous evidence suggested that in our country, frequencies of different aetiologies of lower GI bleed are different from the West. This study validated the previous findings. The Objective of this study was to determine the causes of rectal bleeding in adult patients at Military Hospital, Rawalpindi. METHODS: One hundred and five adult patients with visible rectal bleed, irrespective of their gender were selected by non-probability convenient sampling from general medical OPD and general medical wards. Patients with suspected upper GI source of bleeding; haemorrhoidal bleed and acute infectious diarrhoea were excluded from the study. All patients were subjected to fibre-optic colonoscopy after necessary preparation and findings were recorded. Biopsies taken from suspected lesions were clinically indicated. Diagnosis was based on colonoscopic and histopathologic findings. RESULTS: A total of 105 patients (77 male and 28 female) with mean age 41.04 yrs were part of the study. Colonoscopy showed abnormal findings in 85 (84%) patients. The commonest diagnosis was ulcerative colitis, which was found in 48 (46%) patients. It was followed by colorectal carcinoma, 11 (10%) patients, and non-specific colitis, 9 (8%) patients. Other less frequent findings were colonic diverticuli, 7 (6%) patients, solitary rectal ulcer, 5 (4%) patients, colonic polyps in 3 (2.5%) patients and one case each of telangiectasia and Crohn's disease. CONCLUSION: Colonoscopy has very high diagnostic yield and would be recommended in the workup of patients presenting with bleeding per rectum. Ulcerative colitis was the leading cause of bleeding per rectum in this study; while infrequent findings of Crohn's disease, polyps and diverticuli indicate that these are uncommon in this region.

Dual phase MIBI scintigraphy in diagnosis of parathyroid adenoma followed by ultrasound guided percutaneous alcoholic ablation.

Primary Hyperparathyroidism (HPT) is an inappropriate hyper secretion of parathyroid hormone (PTH). Primary HPT is caused by parathyroid adenoma in 80-85% of patients. Clinical manifestations are kidney stones, abdominal groans, painful bones, psychic moans, and fatigue overtones. Ultrasonography is widely used in suspected cases for localization of parathyroid adenoma. There is considerable intra-observer variation and it is difficult for ultrasound alone to differentiate parathyroid lesion form that of thyroid. Dual phase Tc-99m MIBI scinitigraphy for detection of parathyroid adenomas has sensitivity and specificity values ranging from 82% to 100% and from 89% to 100%, respectively. Percutaneous ethanol injection for parathyroid glands can be applied effectively in selected cases when surgery is unadvisable either for technical reasons (e.g., recurrence ofhyperplastic glands in the neck after subtotal surgery or intrathyroideal parathyroid tumors or the poor clinical state of the patient.

PET/CT imaging correlates with treatment outcome in patients with multidrug-resistant tuberculosis.

Definitive clinical trials of new chemotherapies for treating tuberculosis (TB) require following subjects until at least 6 months after treatment discontinuation to assess for durable cure, making these trials expensive and lengthy. Surrogate endpoints relating to treatment failure and relapse are currently limited to sputum microbiology, which has limited sensitivity and specificity. We prospectively assessed radiographic changes using 2-deoxy-2-[(18)F]-fluoro-D-glucose (FDG) positron emission tomography/computed tomography (PET/CT) at 2 and 6 months (CT only) in a cohort of subjects with multidrug-resistant TB, who were treated with second-line TB therapy for 2 years and then followed for an additional 6 months. CT scans were read semiquantitatively by radiologists and were computationally evaluated using custom software to provide volumetric assessment of TB-associated abnormalities. CT scans at 6 months (but not 2 months) assessed by radiologist readers were predictive of outcomes, and changes in computed abnormal volumes were predictive of drug response at both time points. Quantitative changes in FDG uptake 2 months after starting treatment were associated with long-term outcomes. In this cohort, some radiologic markers were more sensitive than conventional sputum microbiology in distinguishing successful from unsuccessful treatment. These results support the potential of imaging scans as possible surrogate endpoints in clinical trials of new TB drug regimens. Larger cohorts confirming these results are needed.