Estimation of Reduction in Influenza Vaccine Effectiveness Due to Egg-Adaptation Changes-Systematic Literature Review and Expert Consensus.

BACKGROUND: Influenza vaccines are the main tool to prevent morbidity and mortality of the disease; however, egg adaptations associated with the choice of the manufacturing process may reduce their effectiveness. This study aimed to estimate the impact of egg adaptations and antigenic drift on the effectiveness of trivalent (TIV) and quadrivalent (QIV) influenza vaccines. METHODS: Nine experts in influenza virology were recruited into a Delphi-style exercise. In the first round, the experts were asked to answer questions on the impact of antigenic drift and egg adaptations on vaccine match (VM) and influenza vaccine effectiveness (IVE). In the second round, the experts were presented with the data from a systematic literature review on the same subject and aggregated experts' responses to round one questions. The experts were asked to review and confirm or amend their responses before the final summary statistics were calculated. RESULTS: The experts estimated that, across Europe, the egg adaptations reduce, on average, VM to circulating viruses by 7-21% and reduce IVE by 4-16%. According to the experts, antigenic drift results in a similar impact on VM (8-24%) and IVE (5-20%). The highest reduction in IVE was estimated for the influenza virus A(H3N2) subtype for the under 65 age group. When asked about the frequency of the phenomena, the experts indicated that, on average, between the 2014 and 19 seasons, egg adaptation and antigenic drift were significant enough to impact IVE that occurred in two and three out of five seasons, respectively. They also agreed that this pattern is likely to reoccur in future seasons. CONCLUSIONS: Expert estimates suggest there is a potential for 9% on average (weighted average of "All strains" over three age groups adjusted by population size) and up to a 16% increase in IVE (against A(H3N2), the <65 age group) if egg adaptations that arise when employing the traditional egg-based manufacturing process are avoided.

Factors Influencing the Generation of Evidence from Simple Data Held in International Rare Disease Patient Registries.

BACKGROUND: Rare diseases (defined as affecting < 1 in 2000 Europeans) may collectively affect up to approximately 8% of the population. The low prevalence of individual diseases limits patient studies and data collection is a key challenge; international rare disease patient registries are essential for optimal data collection and research. Registry data achieves value when research conducted on them are published-this is termed evidence generation. OBJECTIVE: The aim of this study was to examine selected factors and their association with evidence generation, via scientific publication, from international rare disease patient registry data. METHODS: All international rare disease patient registries listed in the Orphanet 2018 report were analysed. Rates of scientific publications were compared by funding stream, disease area and registry size using multivariable regression analyses. Publication characteristics, such as novelty of findings, were also compared by registry funding stream, disease area and duration of operation. RESULTS: Privately funded registries had approximately two to four times higher rates of scientific publication compared with publically funded registries, with adjusted rate ratios of 1.85 (95% confidence interval [CI] 1.07-3.22) and 4.18 (95% CI 2.54-6.87) for private not-for-profit and private for-profit funding, respectively. The inclusion of outcomes, use of pharmaceutical medicines, novel findings and citation rate for publications generated from patient registries with any private funding was not significantly different from those attributed to only publicly funded registries. CONCLUSION: The results of this study indicate that privately funded international rare disease patient registries produce significantly more evidence than their publicly funded counterparts. Examination of the quality indicators of these publications showed they were of the same high quality as those generated from publicly funded patient registry data.

Immune checkpoints indoleamine 2,3-dioxygenase 1 and programmed death-ligand 1 in oral mucosal dysplasia.

BACKGROUND: Oral mucosal dysplasia is a histologic feature of potentially malignant disorders that is associated with the risk of transformation to carcinoma. Dysplastic cells use many strategies during their transformation to cancer, including escape from the immune mediated destruction. We hypothesized that adaptive immunity is inhibited by activation of distinct immune checkpoint molecules, such as indoleamine 2,3-dioxygenase 1 (IDO1) and programmed death-ligand 1 (PD-L1). METHODS: We collected 63 oral dysplasia samples from 47 patients. Nine biopsies from alveolar mucosa were taken during wisdom teeth extractions were used as healthy controls. Tissue samples were stained and scored for IDO1 and PD-L1. Additionally, dysplasia grades and inflammatory cell infiltration were evaluated. Eight patients were followed up to 36 months to evaluate dysplasia progression, inflammation, and immune checkpoint molecules expression. RESULTS: Dysplastic epithelium had significantly lower IDO1 expression than that of healthy controls. PD-L1 positive cells in the lamina propria were mainly in dysplastic samples and seldom in healthy controls. Dysplasia grade was associated negatively with epithelium IDO1 and positively with IDO1 and PD-L1 expression in the lamina propria. There was a positive association between dysplasia grade and level of inflammatory cell infiltration. During follow-up, dysplasia grade, inflammatory cell infiltration, and the immune checkpoint expression fluctuated over time. CONCLUSIONS: Immune checkpoint molecules IDO1 and PD-L1 are modulated during oral epithelial dysplastic changes, and their expression is associated with inflammatory cell infiltration in the lamina propria. As immune checkpoint molecules expression fluctuates over time, these molecules are not useful as biomarkers for oral mucosal dysplasia progression.

Pioglitazone and cause-specific risk of mortality in patients with type 2 diabetes: extended analysis from a European multidatabase cohort study.

OBJECTIVES: Describe and compare the risk of cardiovascular and non-cardiovascular mortality in patients whose antidiabetic therapy is modified to include pioglitazone compared with an alternative antidiabetic medication at the same stage of disease progression. RESEARCH DESIGN AND METHODS: This exploratory linked database cohort analysis used pooled health and mortality data from three European countries: Finland, Sweden and the UK. Propensity score together with exact matching was used to match 31 133 patients with type 2 diabetes first prescribed pioglitazone from 2000 to 2011, to 31 133 patients never prescribed pioglitazone. Exact matching variables were treatment stage, history of diabetes, diabetes complications and cardiovascular disease, and year of cohort entry. Mean follow-up time was 2.60 (SD 2.00) and 2.69 (SD 2.31) years in the pioglitazone and non-pioglitazone-exposed groups, respectively. Crude cause-specific mortality rates were ascertained. Association with pioglitazone use was estimated using Cox proportional hazards models adjusted a priori for country, age, sex, the propensity score quintile and time-dependent variables representing use of antidiabetic drugs. Stepwise testing identified no additional confounders to include in adjusted models. RESULTS: The crude mortality rate was lower in the pioglitazone-exposed group than the non-exposed group for both cardiovascular and non-cardiovascular mortality. Adjusted HRs comparing pioglitazone to alternative antidiabetic exposure were 0.58 (95% CI 0.52 to 0.63) and 0.63 (95% CI 0.58 to 0.68) for cardiovascular and non-cardiovascular mortality, respectively. A protective effect associated with pioglitazone was also found for all specific cardiovascular causes. CONCLUSIONS: This analysis suggests that pioglitazone is associated with a decrease in both cardiovascular and non-cardiovascular mortality. Results should be interpreted with caution due to the potential for residual confounding in this exploratory analysis. Further studies, specifically designed to test the association between pioglitazone use and patient-focused outcomes, are suggested. STUDY REGISTRATION NUMBER: European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP; EUPAS3626).

Pioglitazone and risk of mortality in patients with type 2 diabetes: results from a European multidatabase cohort study.

OBJECTIVES: Estimate and compare the risk of mortality in patients whose antidiabetic therapy is modified to include pioglitazone compared with an alternative antidiabetic medication at the same stage of disease progression. DESIGN: Retrospective cohort study. SETTING: Pooled analysis of clinical data collected from primary and/or secondary care settings in four European countries: Finland, The Netherlands, Sweden and the UK . PARTICIPANTS: 56 337 patients with type 2 diabetes mellitus first prescribed pioglitazone between 2000 and 2011, and 56 337 patients never prescribed pioglitazone matched by treatment stage, history of diabetes, diabetes complications and cardiovascular disease, and year of cohort entry using exact and propensity score matching. Patients were followed-up for a mean of 2.90 (SD 2.21) and 2.83 (SD 2.37) years in the pioglitazone-exposed and non-pioglitazone-exposed groups, respectively. OUTCOMES: All-cause mortality ascertained from clinical or registry data. Mortality was a planned secondary outcome in a study primarily studying the association of pioglitazone use with bladder cancer risk. RESULTS: The crude overall mortality rate per 10 000 patient years was 206 (95% CI 199 to 213) in the pioglitazone-exposed group and 448 (95% CI 438 to 458) in the non-pioglitazone-exposed group. The crude HR comparing pioglitazone to alternative antidiabetic exposure was 0.46 (95% CI 0.45 to 0.48). This reduced in magnitude to 0.67 (95% CI 0.64 to 0.70) following further adjustment for matching variables, propensity scores, age, gender and time-dependent variables representing use of alternative antidiabetic drugs. CONCLUSIONS: In this large observational cohort study of patients with type 2 diabetes, pioglitazone exposure was associated with a statistically significant decrease in the risk of all-cause mortality across four European countries. Results should be interpreted with caution due to the potential for residual confounding. PROTOCOL REGISTRATION: European Network of Centres for Pharmacoepidemiology and Pharmacovigilance.

Pioglitazone use and risk of bladder cancer in patients with type 2 diabetes: retrospective cohort study using datasets from four European countries.

OBJECTIVE:  To evaluate the association between pioglitazone use and bladder cancer risk in patients with type 2 diabetes. DESIGN:  Retrospective cohort study using propensity score matched cohorts. SETTINGS:  Healthcare databases from Finland, the Netherlands, Sweden, and the United Kingdom. Data comprised country specific datasets of linked records on prescriptions, hospitals, general practitioners, cancer, and deaths. PARTICIPANTS:  Patients with type 2 diabetes who initiated pioglitazone (n=56 337) matched with patients with type 2 diabetes in the same country exposed to diabetes drug treatments other than pioglitazone (n=317 109). Two matched cohorts were created, using a 1:1 fixed ratio (nearest match cohort) and a 1:10 variable ratio (multiple match cohort). Patients were matched on treatment history and propensity scores accounting for several variables associated with pioglitazone initiation. MAIN OUTCOME MEASURES:  Hazard ratios and 95% confidence intervals were estimated by Cox's proportional hazards model with adjustments for relevant confounders. To assess the robustness of the findings, several sensitivity and stratified analyses were performed. RESULTS:  In the cohort exposed to pioglitazone treatment, 130 bladder cancers occurred over a mean follow-up time of 2.9 years. In the nearest match and multiple match cohorts not exposed to pioglitazone treatment, 153 and 970 bladder cancers were recorded, with a mean follow­up time of 2.8 and 2.9 years, respectively. With regards to bladder cancer risk, the adjusted hazard ratio for patients ever exposed versus never exposed to pioglitazone was 0.99 (95% confidence interval 0.75 to 1.30) and 1.00 (0.83 to 1.21) in the nearest and multiple match cohorts, respectively. Increasing duration of pioglitazone use and increasing cumulative dose were not associated with risk of bladder cancer (>48 months of pioglitazone use, adjusted hazard ratio 0.86 (0.44 to 1.66); >40 000 mg cumulative dose, 0.65 (0.33 to 1.26) in the nearest match cohort). CONCLUSIONS:  This study shows no evidence of an association between ever use of pioglitzone and risk of bladder cancer compared with never use, which is consistent with results from other recent studies that also included a long follow-up period. TRIAL REGISTRATION:  Registered to the European Union electronic register of post-authorisation studies (EU PAS register no EUPAS3626).

All-Cause and Cause-Specific Mortality among Users of Basal Insulins NPH, Detemir, and Glargine.

BACKGROUND: Insulin therapy in type 2 diabetes may increase mortality and cancer incidence, but the impact of different types of basal insulins on these endpoints is unclear. Compared to the traditional NPH insulin, the newer, longer-acting insulin analogues detemir and glargine have shown benefits in randomized controlled trials. Whether these advantages translate into lower mortality among users in real life is unknown. OBJECTIVE: To estimate the differences in all-cause and cause-specific mortality rates between new users of basal insulins in a population-based study in Finland. METHODS: 23 751 individuals aged ≥40 with type 2 diabetes, who initiated basal insulin therapy in 2006-2009 were identified from national registers, with comprehensive data for mortality, causes of death, and background variables. Propensity score matching was performed on characteristics. Follow-up time was up to 4 years (median 1.7 years). RESULTS: 2078 deaths incurred. With NPH as reference, the adjusted HRs for all-cause mortality were 0.39 (95% CI, 0.30-0.50) for detemir, and 0.55 (95% CI, 0.44-0.69) for glargine. As compared to glargine, the HR was 0.71 (95% CI, 0.54-0.93) among detemir users. Compared to NPH, the mortality risk for both cardiovascular causes as well as cancer were also significantly lower for glargine, and especially for detemir in adjusted analysis. Furthermore, the results were robust in various sensitivity analyses. CONCLUSION: In real clinical practice, mortality was substantially higher among users of NPH insulin as compared to insulins detemir or glargine. Considering the large number of patients who require insulin therapy, this difference in risk may have major clinical and public health implications. Due to limitations of the observational study design, further investigation using an interventional study design is warranted.

Entacapone and prostate cancer risk in patients with Parkinson's disease.

BACKGROUND: The association between Parkinson's disease (PD) and prostate cancer, both common in elderly men, is disputable. In the STRIDE-PD study, prostate cancer developed in 9 patients (3.7%) receiving levodopa/carbidopa with entacapone, a catechol-O-methyltransferase inhibitor, versus 2 cases (0.9%) without entacapone. The current pharmacoepidemiological study aimed to determine whether entacapone increases prostate cancer incidence or mortality in PD patients and whether cumulative exposure affects these rates. METHODS: We performed a retrospective cohort study using population-wide health care registers with patient-level linkage. Prostate cancer incidence and mortality were modeled by Cox's proportional hazards models. RESULTS AND CONCLUSIONS: Use of entacapone with l-dopa/dopa decarboxylase inhibitor caused no increased risk of prostate cancer incidence (hazard ratio [HR]: 1.05; 95% confidence interval: 0.76-1.44) or mortality (0.93; 0.43-1.98). The HR for cumulative entacapone use of >360 days versus never-use was 0.82 (0.56-1.18) for prostate cancer incidence and 1.27 (0.60-2.72) for prostate cancer mortality.

Can symptom relief be provided in the home to palliative care cancer patients by the primary caregivers? An Indian study.

BACKGROUND: A large proportion of cancer deaths occur in the developing world, with limited resources for palliative care. Many patients dying at home experience difficult symptoms. OBJECTIVE: The objective of this study was to assess the feasibility of a structured training program on symptom management along with an acute symptom management kit for primary caregivers of cancer patients receiving home care. METHODS: Descriptive design was used. Thirty primary caregivers of cancer patients attending the palliative care clinic in Vellore, South India, were provided training on the administration of drugs for acute symptoms. A plastic box with partitions for drugs specific to symptom was provided. On follow-up visits, the usage of the kit, drugs used, and routes of administration were noted. A structured questionnaire with a 4-point scale was used to assess primary caregiver views and satisfaction. RESULTS: Of primary caregivers, 96.7% used a kit. The common medications used were morphine, metoclopramide, dexamethasone, and benzodiazepines. Seventy-three percent of primary caregivers administered subcutaneous injections at home. Hospital visits for acute symptoms reduced by 80%; 90% were satisfied with the training received; 73% stated it was not a burden to treat the patient at home. CONCLUSION: The training program and acute symptom management kit were favorably received and appropriately used by caregivers of diverse backgrounds. Rural backgrounds and illiteracy were not barriers to acceptance. IMPLICATION FOR PRACTICE: Healthcare professionals should train caregivers during hospital visits, empowering them to manage acute symptoms and provide simple nursing care. This is doubly important in countries where resources are limited and palliative care facilities scarce.

Diet and Physical Activity Among Women in Urban and Rural Areas in South India: A Community Based Comparative Survey.

INTRODUCTION: Noncommunicable diseases (NCDs) such as diabetes, hypertension, and heart diseases are increasing in India. There is a clear need to study risk factors for NCDs in various population groups in the country. MATERIALS AND METHODS: This community based cross-sectional survey was conducted to study the diet and physical activity of women in urban and rural areas in Vellore district. Dietary data was collected using 24-h dietary recall and physical activity was collected using the International Physical Activity Questionnaire (IPAQ). Sociodemographic variables were collected to assess the risk factors for unfavorable diet and physical activity. RESULTS: The odds of the rural women engaging in high physical activity are 3.61 times greater than urban women (95% confidence interval (CI) = 2.36-5.54). The odds of the urban women consuming a high calorie diet are 1.923 times that of the rural women (95% CI = 1.282-2.857). The odds of the urban women being overweight/obese are 5.555 times than that of the urban women (95% CI = 3.333-10). Women who were housewives and not doing household work were significantly less physically active, took higher calorie diet, and were more overweight and obese compared to women who were involved in active household work. CONCLUSIONS: Urban women had unfavorable diet and physical activity levels compared to rural women. They also had higher levels of overweight and obesity. There is a need for targeted NCD prevention interventions among urban women.

Born with low birth weight in rural Southern India: what are the metabolic consequences 20 years later?

OBJECTIVE: Low birth weight (LBW) is common in the Indian population and may represent an important predisposing factor for type 2 diabetes (T2D) and the metabolic syndrome. Intensive metabolic examinations in ethnic LBW Asian Indians have been almost exclusively performed in immigrants living outside India. Therefore, we aimed to study the metabolic impact of being born with LBW in a rural non-migrant Indian population. SUBJECTS AND METHODS: One hundred and seventeen non-migrant, young healthy men were recruited from a birth cohort in a rural part of south India. The subjects comprised 61 LBW and 56 normal birth weight (NBW) men, with NBW men acting as controls. Subjects underwent a hyperinsulinaemic euglycaemic clamp, i.v. and oral glucose tolerance tests and a dual-energy X-ray absorptiometry scan. The parents' anthropometric status and metabolic parameters were assessed. RESULTS: Men with LBW were shorter (167±6.4 vs 172±6.0 cm, P<0.0001), lighter (51.9±9 vs 55.4±7 kg, P=0.02) and had a reduced lean body mass (42.1±5.4 vs 45.0±4.5 kg, P=0.002) compared with NBW controls. After adjustment for height and weight, the LBW subjects had increased diastolic blood pressure (77±6 vs 75±6 mmHg, P=0.01). Five LBW subjects had impaired glucose tolerance. In vivo insulin secretion and peripheral insulin action were similar in both the groups. Mothers of the LBW subjects were 3 cm shorter than the control mothers. CONCLUSION: Only subtle features of the metabolic syndrome and changes in body composition among LBW rural Indians were found. Whether other factors such as urbanisation and ageing may unmask more severe metabolic abnormalities may require a long-term follow-up.

Mortality predictors of snake bite envenomation in southern India--a ten-year retrospective audit of 533 patients.

Snake bite incidence is highest in Asia and sub-Saharan Africa. This retrospective audit of 533 adult patients, who had presented to the Emergency Department, collates clinical features, effect of pharmacologic interventions and the risk factors that influence morbidity and mortality. Dual toxicity, neurological and haematological, was observed in 30.4% of patients. Laboratory evidence of haematotoxicity was demonstrated in 314 (58.9%) and 40% demonstrated clinical evidence of bleeding. However, 7.3% of these patients did not have laboratory evidence of bleeding disorder (p < 0.001). Conversely, 60% did not have clinical evidence of bleeding, but demonstrated laboratory evidence of abnormal parameters. Acute kidney injury (AKI) was evident in 28% of patients and 15.3% required haemodialysis. About 25% with no haematotoxicity showed evidence of AKI. The majority received 6-12 vials of poly-valent anti-snake venom. Hypersensitivity reaction rate was 8% and predominantly anaphylactoid in nature. The length of hospital stay ranged from 2 to 28 days and 20% required mechanical ventilation. Overall mortality rate was 7.5% with significant association to AKI, haematotoxicity and assisted ventilation. The mortality rate was 18% in patients with pre-hospital delay more than 24 h, as against 5% when admitted within the above specified period (p = <0.001). The strength of this study is the accrued information of over a period of 10 years of snake-bite management through the Emergency Department of a university hospital setting. The limitations are the retrospective study design and the rejection percentage of 15.5% due to insufficient information from the total chart pool.

Transmission dynamics of methicillin-resistant Staphylococcus aureus in a medical intensive care unit in India.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a global pathogen and an important but seldom investigated cause of morbidity and mortality in lower and middle-income countries where it can place a major burden on limited resources. Quantifying nosocomial transmission in resource-poor settings is difficult because molecular typing methods are prohibitively expensive. Mechanistic statistical models can overcome this problem with minimal cost. We analyse the transmission dynamics of MRSA in a hospital in south India using one such approach and provide conservative estimates of the organism's economic burden. METHODS AND FINDINGS: Fifty months of MRSA infection data were collected retrospectively from a Medical Intensive Care Unit (MICU) in a tertiary hospital in Vellore, south India. Data were analysed using a previously described structured hidden Markov model. Seventy-two patients developed MRSA infections and, of these, 49 (68%) died in the MICU. We estimated that 4.2% (95%CI 1.0, 19.0) of patients were MRSA-positive when admitted, that there were 0.39 MRSA infections per colonized patient month (0.06, 0.73), and that the ward-level reproduction number for MRSA was 0.42 (0.08, 2.04). Anti-MRSA antibiotic treatment costs alone averaged $124/patient, over three times the monthly income of more than 40% of the Indian population. CONCLUSIONS: Our analysis of routine data provides the first estimate of the nosocomial transmission potential of MRSA in India. The high levels of transmission estimated underline the need for cost-effective interventions to reduce MRSA transmission in hospital settings in low and middle income countries.

Human papillomavirus types 16 and 18 mRNA levels and not DNA levels may be associated with advancing stages of cervical cancer.

OBJECTIVE: Human papillomavirus (HPV) contributes to the development of cervical cancer. We hypothesize that HPV DNA and messenger RNA (mRNA) levels may be associated with increasing stages of cervical cancer. MATERIALS AND METHODS: In this study, we measured DNA and mRNA viral loads of the most common high-risk HPV-16 and HPV-18 in cervical biopsy tissue of women with cervical neoplasia using real-time polymerase chain reaction. RESULTS: Median HPV-16 and HPV-18 DNA viral loads were 58,342 copies and 71,367 per 5000 cells, respectively. We found that HPV-16 and HPV-18 DNA levels did not correlate with advancing tumor stage (P = 0.977 and P = 0.263). Messenger RNA transcripts were detected in 81 (86%) of HPV-16 DNA-positive women and in 16 (84.2%) of HPV-18-positive women. Median HPV-16 and HPV-18 transcript copy numbers were 5964 and 6158, respectively. In women with squamous cell carcinoma, HPV-16 mRNA loads showed an increasing but not statistically significant trend with advancing disease stage (rho = 0.231, P = 0.058). CONCLUSIONS: We conclude that HPV mRNA levels and not DNA levels may be associated with advancing stages of cervical cancer.

Quality of life assessment after central corpectomy for cervical spondylotic myelopathy: comparative evaluation of the 36-Item Short Form Health Survey and the World Health Organization Quality of Life-Bref.

OBJECT: In this study, the authors assessed the construct validity and the reliability of the World Health Organization Quality of Life-Bref (WHOQOL-Bref) questionnaire in patients with cervical spondylotic myelopathy (CSM) and compared the performance of the WHOQOL-Bref and the 36-Item Short Form Health Survey (SF-36) in assessing quality of life (QOL) in patients with CSM. METHODS: In this prospective study, 70 patients with CSM were assessed preoperatively and again 1 year after central corpectomy using the Nurick scale, the SF-36, and the WHOQOL-Bref. Construct validity and reliability of the WHOQOL-Bref, its responsiveness compared with that of the SF-36, and the correlations between the 2 scales were studied. RESULTS: The WHOQOL-Bref was found to be valid (p < 0.001, Cuzick test for trend between the physical domain of the WHOQOL-Bref and Nurick grade) and reliable (Cronbach alpha > 0.7). It had smaller floor and ceiling effects (ranges 1.4-7.1% and 0-7.1%, respectively) than the SF-36 (ranges 2.9-71.4% and 0-14.1%, respectively). There was significant postoperative improvement in patient scores on all the SF-36 scales (p < 0.001) and the physical, psychological, and environment domains of the WHOQOL-Bref (p < 0.001). The SF-36 scales were more responsive to change (relative efficiency range 0.24-1) than the WHOQOL-Bref domains (relative efficiency range 0.002-0.73). Among scales measuring similar concepts, only the physical functioning and bodily pain scales of the SF-36 had a moderate correlation (r = 0.57 and 0.53, respectively; p < 0.001) with the physical domain of WHOQOL-Bref. Many of the scales of these 2 QOL instruments unexpectedly had a fair correlation with one another (r range = 0.2-0.4). CONCLUSIONS: The WHOQOL-Bref, like the SF-36, is valid and reliable in assessing outcome in patients with CSM. It measures impairment in CSM in a more uniform manner than the SF-36, but its domains are less responsive to postoperative changes. Because the WHOQOL-Bref measures different constructs and has additive value, it should be used along with the SF-36 for QOL assessment in patients with CSM.

Nitric oxide production in acute gastroenteritis in Indian children.

This study compared nitric oxide (NO) levels in 110 children with, and 110 children without, infectious gastroenteritis. Post-infection intestinal function was assessed in a subset. At least one pathogen was identified in 47.2% of cases. The most common diarrhoeal pathogens were rotavirus (22.7%) and norovirus genogroup II (11.8%). The levels of NO measured by median urinary nitrite:creatinine ratio were significantly higher in children with diarrhoea [23.6; interquartile range (IQR) 12.3-46.7] than without diarrhoea (7.8; IQR 4.1-13.2), P<0.001. The ratio was not significantly different between diarrhoeal cases with and without pathogens (P=0.148). Six of twelve children tested had intestinal dysfunction.

Why does size matter for viruses--a new paradigm on viral size.

Size and shape are the two immutable laws that govern all life forms including viruses. In this study we postulate and evaluate the hypothesis that there exists a strong association between viral geometry and features of viral disease outbreaks. Data on viral disease outbreaks were retrieved from WHO and CDC public domains for a period of twelve years to assess the relationship between viral size and epidemiological factors such as number of outbreaks, case fatality rate, proportion of emerging infectious diseases and transmission routes. We observed a significant correlation between viral size and frequency of disease outbreaks (rho=-0.82, p=0.004), case fatality rate (rho=0.48, p=0.03) and genome size (r=0.79, p<0.001). Viral sizes were significantly different among diverse transmission routes (p<0.001). The proportion of emerging infectious diseases were significantly different between viruses with size <10(5) and >or=10(5)nm(3) (21% vs 64%, p=0.046). In conclusion, this preliminary evidence shows that viral size plays a substantial role in the epidemiology of viral diseases. Our data suggests that small size viruses are associated with more number of outbreaks than large size viruses. Large size viruses are associated with high case fatality rate and can be potential emerging pathogens. Viral size may be crucial for niche selection and specified transmission routes in the susceptible host. Hence, viral geometry should not be neglected in epidemiology and modeling of viral diseases, and planning vaccine strategies.

An evaluation of the role of noninvasive positive pressure ventilation in the management of acute respiratory failure in a developing country.

OBJECTIVE: Noninvasive positive pressure ventilation (NIPPV) has been shown to decrease the need for invasive mechanical ventilation (MV) in patients presenting with acute respiratory failure (ARF). We conducted a prospective study to assess if NIPPV use, in a developing country, was associated with clinical and physiological improvements. DESIGN: Prospective observational study. MATERIALS AND METHODS: Forty patients admitted to a medical intensive care unit during a 2-year period who fulfilled criteria for inclusion formed the study cohort to receive NIPPV. FINDINGS: Baseline (mean +/- SD) pH, PaCO 2 and PaO 2 were 7.25 +/- 0.08, 76.6 +/- 20.9 and 79.18 +/- 40.56 mmHg respectively. The primary indication for NIPPV was hypercapnic respiratory failure (n = 36, 90%). The success rate with NIPPV was 85%, with 34 of 40 patients weaned successfully. Significant improvements were observed at 1 hour following institution of NIPPV in pH (7.31 +/- 0.09, P 2 (65 +/- 17.9, P 2 54.7 +/- 20) and maintained (within 12 h) postweaning from the ventilator (pH 7.39 +/- 0.08, PaCO 2 51.9 +/- 12.4). No significant change in the PaO 2 was observed during NIPPV; PaO 2 after 1 h, prior to weaning and after weaning was 90.53 +/- 42.85, 84.80 +/- 33.76, 78.71 +/- 43.81 respectively. CONCLUSION: This study has demonstrated benefits of NIPPV in avoiding the need for invasive MV in patients presenting with ARF of diverse etiology, with results comparable to developed nations. Increased use of NIPPV in ARF is likely to impact favorably in nations with limited resources.