A community-based, time-matched, case-control study of respiratory viruses and exacerbations of COPD

Respiratory viruses are associated with severe acute exacerbations of chronic obstructive pulmonary disease (COPD) in hospitalized patients. However, exacerbations are increasingly managed in the community, where the role of viruses is unclear. In community exacerbations, the causal association between viruses and exacerbation maybe confounded by random fluctuations in the prevalence of circulating respiratory viruses. Therefore, to determine whether viral respiratory tract infections are causally associated with community exacerbations, a time-matched case-control study was performed. Ninety-two subjects (mean age 72 yrs), with moderate to severe COPD, (mean FEV(1) 40% predicted), were enrolled. Nasopharyngeal swabs for viral multiplex polymerase chain reaction and atypical pneumonia serology were obtained at exacerbation onset. Control samples were collected in synchrony, from a randomly selected stable patient drawn from the same cohort. In 99 weeks of surveillance, there were 148 exacerbations. Odds of viral isolation were 11 times higher in cases, than their time-matched controls (34 discordant case-control pairs; in 31 pairs only the case had virus and in three pairs only control). Picornavirus (26), influenza A (3), parainfluenza 1,2,3 (2), respiratory syncytial virus (1), and adenovirus (1) were detected in cases while adenovirus (1) and picornavirus (2) were detected in controls. In patients with moderate or severe COPD the presence of a virus in upper airway secretions is strongly associated with the development of COPD exacerbations. These data support the causative role of viruses in triggering COPD exacerbations in the community.     

More than a drink: A rare anaphylactic reaction to sparkling water

Anaphylaxis is a potentially life threatening, type I hypersensitivity reaction which can occur within seconds to minutes after exposure to an allergen. Sulfites have been implicated in causing such reactions with symptoms ranging from mild to potentially life threatening. Here we present a patient who had an anaphylactic reaction secondary to exposure to sulfites found in sparkling water.     

Clinical and microbiological observational study on AmpC β-lactamase-producing Enterobacteriaceae in a hospital of Nepal

Limited information is available regarding AmpC β-lactamase (ABL)-producing Enterobacteriaceae compared to extended-spectrum β-lactamase-producing enterobacteria. Since ABL-producing organisms are often resistant to multiple antimicrobial agents, therapeutic options against these pathogens are limited. Among 230 clinical Enterobacteriaceae isolates, 64 (27.8%) were found to produce ABL in our study. Escherichia coli (83.9%) was a predominant pathogen, followed by Citrobacter freundii (5.2%). A significant proportion of ABL-producing isolates (81.3%) were found to be multidrug resistant against commonly used antibiotics. Univariate analysis showed that prior history of taking antibiotics (odds ratio [OR], 5.278; confidence interval [CI], 2.838–9.817; p < 0.001) and being inpatients (OR, 4.587; CI, 2.132–9.9; p < 0.001) were associated with ABL positivity. Regular antimicrobial resistance surveillance for ABL-producing Enterobacteriaceae is warranted for proper antimicrobial treatment strategy and policy making due to ABL-positive infections.     

Health improvement for disadvantaged people in Nepal – an evaluation

Background

Diarrhoea is the second leading cause of death in children under five accounting for 1.8 million deaths yearly. Despite global efforts to reduce diarrhoea mortality through promotion of proper case management, there is still room for ample improvement. In order to seek options for such improvements this study explored the knowledge and practices of diarrhoea case management among health care providers at health centres and drug shops in Uganda.

Methods

Records were reviewed for case management and structured interviews concerning knowledge and practices were conducted with the staff at all health centres and at all identified drug shops in the rural district of Namutumba, Uganda.

Results

There was a significant gap between knowledge and documented practices among staff. Antibiotics, antimalarials and antipyretics were prescribed or recommended as frequently as Oral Rehydration Solution (ORS). In almost a third of the health facilities, ORS was out of stock. 81% of staff in health centres and 87% of staff in drug shops stated that they prescribed antibiotics for common diarrhoea. Zinc was not prescribed or recommended in any case.

Conclusions

The findings indicate that many children presenting with diarrhoea are inadequately treated. As a result they may not get the rehydration they need and are at risk of potential side effects from unjustified usage of antibiotics. Practices must be improved at health centres and drug shops in order to reduce childhood mortality due to diarrhoeal diseases.     

同期化放疗在局部晚期鼻咽癌治疗中的作用:一项关于Ⅲ期随机对照试验的荟萃分析

目的本项荟萃分析的主要目的是通过比较鼻咽癌病人同期化放疗与单纯放疗的总生存、疾病的局部控制率及远处转移率的差异从而确定同期化放疗在局部晚期鼻咽癌中的作用。次要目的是比较鼻咽癌病人同期化放疗和同期化放疗联合辅助化疗与单纯放疗的生存差别。病人和方法按照预先设计荟萃分析的方案，选择已发表的Ⅲ期随机对照临床研究。临床研究的入选标准包括：①所有人组的鼻咽癌病人随机分为单纯放疗组或同期化放疗组；②临床研究中的病人必须是经组织学证实为鼻咽癌（WHO分型Ⅰ-Ⅲ型）；③所有人组的病人都必须接受原发病灶至少为64Gy的足够剂量的常规分割放疗。结果本项荟萃分析共包括了7个临床研究中的1630名病人。与单纯放疗相比，同期化放疗组病人的2年、3年和5年总生存风险比值分别为0．54（95％置信区间0．41-0．70）、0．54（95％置信区间0．37—0．78）和0．49（95％置信区间0．28—0．84），而其相应的2年、3年和5年绝对生存获益分别为9％、10％和13％。同期化放疗组与单纯放疗组的局部复发率及远处转移率也是可比的，并且同期化放疗组可见到明显的生存获益，其5年局部复发率及远处转移率的风险比值分别为0．49（95％置信区间0．30。0．78）和0．59（95％置信区间0．46—0．76）。同期化放疗加辅助化疗与单纯放疗对比的生存获益（包括总生存、局部控制率和远处转移率）比单用同期化放疗与单纯放疗对比的生存获益有所改善，但这种改善差异没有统计学意义。结论本研究结果表明同期化放疗是改善鼻咽癌患者总生存最有效的方法。辅助化疗的确切作用尚不是非常明确．还需要进行更多的研究明确其作用。     

Second Primary Malignancies in Chronic Myeloid Leukemia

Survival of patients with chronic myeloid leukemia (CML) has improved with the use of imatinib and other tyrosine kinase inhibitors. There is limited data on second primary malignancies (SPM) in CML. We analyzed the SPMs rates among CML patients reported to Surveillance, Epidemiology, and End Results (SEER) database during pre-(1992–2000) and post-(2002–2009) era. We used SEER Multiple Primary-Standardized Incidence Ratio session to calculate standardized incidence ratios (SIRs). Among 8,511 adult CML patients, 446 patients developed 473 SPMs. The SIR for SPMs in CML patients was significantly higher with observed/expected ratio:1.27, P < 0.05 and absolute excess risk of 32.09 per 10,000 person years compared to general population. The rate of SPMs for cancers of all sites in post-imatinib era were significantly higher compared to pre-imatinib era with observed/expected ratio of 1.48 versus 1.06, P = 0.03. This study showed that risk of SPMs is higher among CML patients. The risk of SPMs is significantly higher in post-imatinib era compared to pre-imatinib era.     

Equity and Coverage in the Continuum of Reproductive,Maternal, Newborn and Child Health Services in Nepal-Projecting the Estimates on Death Averted Using the LiST Tool

Introduction

The third Sustainable Development Goal, focused on health, includes two targets related to the reduction in maternal, newborn and under-five childhood mortality. We found it imperative to examine the equity and coverage of reproductive, maternal, newborn and child health (RMNCH) interventions from 2001 to 2016 in Nepal; and the death aversion that will take place during the SDG period.

Methods

We used the datasets from the Nepal Demographic Health Surveys (NDHS) 2001, 2006, 2011 and 2016. We calculated the coverage and equity for RMNCH interventions and the composite coverage index (CCI). Based on the Annualized Rate of Change (ARC) in the coverage for selected RMNCH indicators, we projected the trend for the RMNCH interventions by 2030. We used the Lives Saved Tools (LiST) tool to estimate the maternal, newborn, under-five childhood deaths and stillbirths averted. We categorised the interventions into four different patterns based on coverage and inequity gap.

Results

Between 2001 and 2016, a significant improvement is seen in the overall RMNCH intervention coverage-CCI increasing from 46 to 75%. The ARC was highest for skilled attendance at birth (11.7%) followed by care seeking for pneumonia (8.2%) between the same period. In 2016, the highest inequity existed for utilization of the skilled birth attendance services (51%), followed by antenatal care (18%). The inequity gap for basic immunization services reduced significantly from 27.4% in 2001 to 5% in 2016. If the current ARC continues, then an additional 3783 maternal deaths, 36,443 neonatal deaths, 66,883 under-five childhood deaths and 24,024 stillbirths is expected to be averted by the year 2030.

Conclusion

Nepal has experienced an improvement in the coverage and equity in RMNCH interventions. Reducing inequities will improve coverage for skilled birth attendants and antenatal care. The current annual rate of change in RMNCH coverage will further reduce the maternal, neonatal, under-five childhood deaths and stillbirths.

     

Change in mRNA Expression after Atenolol, a Beta-adrenergic Receptor Antagonist and Association with Pharmacological Response

Aims.  Genetic determinants of variability in response to β-blockers are poorly characterized. We defined changes in mRNA expression after a β-blocker to identify novel genes that could affect response and correlated these with inhibition of exercise-induced tachycardia, a measure of β-blocker sensitivity.
Methods.  Nine subjects exercised before and after a single oral dose of 25mg atenolol and mRNA gene expression was measured using an Affymetrix GeneChip Human Gene 1.0 ST Array. The area under the heart rate-exercise intensity curve (AUC) was calculated for each subject; the difference between post- and pre-atenolol AUCs (Δ AUC), a measure of β-blocker response, was correlated with the fold-change in mRNA expression of the genes that changed more than 1.3-fold.
Results.  Fifty genes showed more than 1.3-fold increase in expression; 9 of these reached statistical significance ( P  < 0.05). Thirty-six genes had more than 1.3-fold decrease in expression after atenolol; 6 of these reached statistical significance ( P  < 0.05). Change in mRNA expression of FGFBP2 and Probeset ID 8118979 was significantly correlated with atenolol response ( P  = 0.03 and 0.02, respectively).
Conclusion.  The expression of several genes not previously identified as part of the adrenergic signaling pathway changed in response to a single oral dose of atenolol. Variation in these genes could contribute to unexplained differences in response to β-blockers.     

Tuberculosis and other clinical presentation of HIV/AIDS in patients with or without undergoing antiretroviral therapy in Kathmandu

Objectives: To screen tuberculosis (TB) and examine the clinical presentation of AIDS in HIV sero-positive persons. Methods: A Cross-sectional study was designed. One hundred HIV infected persons were randomly selected from different parts of the country visiting Tribhuvan University, Teaching Hospital, Kathmandu and different HIV/AIDS care centres. After taking informed consent, questionnaires were filled and three sputum specimens from each person were collected to investigate tuberculosis by Ziehl-Neelsen staining and culture. Data generated were entered into SPSS 11.5 and relevant statistical tools were applied. Results: Among 100 HIV infected cases, 66 (66%) were males and 34 (34%) were females. Sixty percent of the cases were in the age group of 21-30 years. Majority of them were Smokers (41%), alcoholics (34%), illiterates (54%) and unemployed (59%). Heterosexual activity (51%) was found to be the major risk factor for HIV infection. Of the 100 HIV cases, 23 (23%) were co-infected with tuberculosis of which 18(78%) were sputum smear negative tuberculosis, mostly developed in late stage of HIV infection. Weight loss (54%) and diarrhoea (43%) were the major clinical presentations of AIDS. Antiretro-viral therapy non-receiver were more likely to suffer with various clinical disorders/TB as compared to ARV therapy receiver but the values were statistically insignificant, 2 values ranging from 0.003 to 2.24, p>0.05. Conclusion: Prevalence of tuberculosis was still high in HIV/AIDS patients, and specifically, sputum smear negative tuberculosis cases constituted the significant proportion, particularly in late stage of HIV infection. Weight loss and diarrhoea were found to be the major clinical presentation of AIDS. Illiterate and unemployed young adults involved in unsafe sexual practice and drug addiction were high risk of acquiring HIV infection. Key words: Clinical features, HIV/AIDS, Kathmandu; Smear Negative Tuberculosis.