Fluoroquinolone consumption and -resistance trends in Mycobacterium tuberculosis and other respiratory pathogens: Ecological antibiotic pressure and consequences in Pakistan, 2009-2015.

OBJECTIVE/BACKGROUND: Fluoroquinolones (FQs) are important anti-tuberculous drugs for the treatment of multidrug-resistant (MDR) tuberculosis. Resistance to FQs leads to fewer options for treatment of tuberculosis (TB), and infection with such strains may also require longer treatment duration. Trends of resistance in Mycobacterium tuberculosis (MTB) are indicators of MTB-resistance evolution. Drivers of such resistance need to be understood and studied to inform preventive strategies. METHODS: Here, we present FQ-resistance rates and trends in Pakistan from 2010 to 2015 and compare rates with FQ-consumption data and rates in other community pathogens. RESULTS: Our results reveal a recent decrease in FQ-resistance rates in MTB, but an increase in resistance for Haemophilus influenzae and Shigella spp. Correlation of FQ resistance with FQ consumption at the population level was weak for MTB, although strong associations were noted for H. influenzae and Shigella spp. CONCLUSION: We discuss the possible reasons for the decrease in resistance rates in TB, putative drivers of resistance other than volume of FQ consumption, and the possible impact of the National Tuberculosis Programme and drug regulatory activities.

Use of Xpert(®) MTB/RIF assay in the first national anti-tuberculosis drug resistance survey in Pakistan.

SETTING: The first national anti-tuberculosis drug resistance survey in Pakistan, a high tuberculosis (TB) and low human immunodeficiency virus (HIV) burden country. OBJECTIVE: To determine the proportion of patients with multidrug-resistant TB (MDR-TB) and to compare the performance of Xpert(®) MTB/RIF with conventional phenotypic drug susceptibility testing (DST). METHODS: Sputum samples were collected from 1972 consecutively enrolled pulmonary TB patients from 40 clusters. Phenotypic DST was performed in parallel with Xpert. RESULTS: The proportion of MDR-TB patients was 3.7% (95%CI 2.5-5.0) among new and 18.1% (95%CI 13.0-23.4) among previously treated cases. A valid rifampicin (RMP) testing result was available from substantially more cases with Xpert (n = 1809) than with phenotypic DST (n = 1592). Among strains with discordant results, rpoB sequencing revealed only one false-resistant result (new TB case) with Xpert and 7.7% (8/104) of RMP-resistant cases missed with Xpert against 3.8% (4/14) by phenotypic DST. This difference was not significant. CONCLUSIONS: This survey provides the first representative data for Pakistan on its MDR-TB burden. The Xpert assay had nearly 100% specificity, even in a low MDR-TB prevalence setting. The use of this assay greatly simplifies survey logistics, making it a feasible option for survey implementation, especially in resource-constrained settings.

The ultraviolet photochemistry of phenylacetylene and the enthalpy of formation of 1,3,5-hexatriyne.

The ultraviolet photochemistry of phenylacetylene was studied in a molecular beam at 193 nm. The only primary photofragments observed were HCCH (acetylene) and C(6)H(4). Some of the C(6)H(4) molecules were found to decompose to 1,3,5-hexatriyne and molecular hydrogen. An enthalpy of formation of DeltaH(f) < or = 160 +/- 4 kcal mol(-1) was determined for 1,3,5-hexatriyne from the energetic threshold for this process. This experimentally determined value agrees well with our ab initio calculations performed at the G2 level of theory. Angular distribution measurements for the HCCH + C(6)H(4) channel yielded an isotropic distribution and were attributed to a long-lived intermediate and ground-state dissociation. An exhaustive search yielded no evidence for the phenyl + ethynyl or the atomic hydrogen elimination channels even though these were observed in the pyrolytic studies of phenylacetylene [Hofmann, J.; Zimmermann, G.; Guthier, K.; Hebgen, P.; Homann, K. H. Liebigs Ann. 1995, 631, 1995. Guthier, K.; Hebgen, P.; Hofmann, K. H.; Zimmermann, G. Liebigs Ann. 1995, 637, 1995].

Analysis of known risk factors for bladder cancer in Pakistani population.

The association of aetiological agents incriminated for bladder cancer are well recognised. They are divided into two groups, occupational and non-occupational. The commonest occupational agents are 2-naphthylamine, benzidine, aminobiphenyl, dichlorobenzidine, orthodianisidine and orthotolidine. Recognised non-occupational agents include tobacco, recurrent chronic bladder infection/infestation, coffee and drugs. This study was conducted to evaluate these factors in patients with bladder cancer in our population. Of 250 cases studied, 203 were males and 47 females with a male to female ratio of 4.3:1. In 13.6% cases occupational factors were established with an average duration of exposure of 12 years. Majority (68%) of patients had smoking as the predominant non-occupational factor. In this group average cigarettes smoked per day was 23 with a range of 15 to 90. The duration of smoking ranged between 5 to 55 years with an average of 26 years. Sixty patients (24%) were neither smokers nor had any associated high risk occupation.

Action myoclonus after cerebral anoxia.

Intention or kinesogenic myoclonus is uniquely one of many different movement disorders that if recognized and treated, early or late, responds to treatment. Posthypoxic intention myoclonus appears to be a syndrome associated with a variety of interacting biochemical mechanisms.

Psychosocial aspects of dialysis and renal transplant.

Keeping in view our socio cultural millieu, the psychological aspects of twenty renal transplants recipients and equal number of patients on dialysis were studied. Socio psychiatric profile in the dialysis and transplanted patients revealed that the frequency of anxiety, depression and hypochondriasis was significantly less (P less than 0.01) in the transplanted group. On Bender Gestalt Scale the transplanted group achieved normal status in significantly higher (P less than 0.05) number compared to the dialysis patients. It was concluded that transplanted patients showed marked improvement in social functioning, psychological symptoms and enduring personality traits compared to patients on maintenance dialysis.