Ibuprofen Compared to Acetazolamide for the Prevention of Acute Mountain Sickness: A Randomized Placebo-Controlled Trial.

INTRODUCTION: Acetazolamide is recommended for the prevention of acute mountain sickness (AMS); however, its use is limited in some areas because of side effects. Previous studies report ibuprofen to be similar to or slightly inferior to acetazolamide. This randomized, triple-blinded, parallel-group, placebo-controlled trial was designed to compare ibuprofen with acetazolamide for the prevention of AMS. METHODS: Four hundred forty-three healthy Asian Indian men with a mean age of 29 (range: 20-49) years were randomized into three groups A, B, and P at 350m (SL). Acetazolamide (A): 85 mg; ibuprofen (B): 600 mg; or placebo (P): calcium carbonate was administered thrice daily, starting one day prior and continuing for three days after arrival at 3500m (HA). Participants were evaluated for AMS using the Lake Louise Questionnaire and for pulse, BP, SpO2, and respiratory rate twice daily for the first two days during rest and once a day for days three to six at HA. RESULTS: Of the 443 participants recruited at SL, 139 could not be airlifted due to logistical limitations, and 304 were available for follow-up at HA. Among these, 254 had ascended as per protocol. By intent to treat (IT) (N = 304; A = 99, B = 102, P = 103), the incidence of AMS (LLQS>/=3) was 12%, 5%, and 13%, and the incidence of severe AMS was 1%, 2%, and 6%, in groups A, B, and P, respectively. Using per protocol analysis (PP) (N = 254; A = 83, B = 87, P = 84), the incidence of AMS was 12%, 6%, and 13% in groups A, B, and P, respectively. The relative risk for developing AMS vs. placebo was A-0.96 (CI:0.46-2.0, p=0.91), B-0.39 (CI:0.14-1.04, p=0.06), A-0.94 (CI:0.42-2.1, p=0.88), and B-0.45 (0.16-1.24, p=0.12) by IT and PP, respectively. CONCLUSION: Ibuprofen is effective in males for the prevention of AMS with rapid ascent to 3500 m-rest for the first two days. Acetazolamide was superior to ibuprofen in the prevention of moderate-to-severe AMS.

Risk factors for cardiovascular disease in a healthy young population: Family matters.

Background: India faces an epidemic of cardiovascular disease (CVD). This study sought the effect of family history of CVD and/or its risk factors (CVD-risk) on the presence of risk factors for CVD, in a healthy young college population. Methods: Blood pressure (BP), heart rate (HR), anthropometric variables, fasting blood sugar and lipid fractions were measured in two hundred healthy individuals (163 men and 37 women), aged 17-22 years. Data were analysed to elicit effect of CVD-risk on measured parameters. Results: All but one subject, had family history of a CVD-risk. Men with family history of coronary heart disease had higher diastolic BP (79.24 ± 7.7 vs 75.99 ± 7.49 mmHg, p = 0.007) and triglycerides (118.66 ± 57.98 vs 85.82 ± 50.89 mg/dL, p < 0.0001) compared with those without similar family history. Men with family history of hypertension (HTN) had higher diastolic BP (78.75 ± 7.15 vs 75.84 ± 8.37 mmHg, p = 0.019) and low-density lipoprotein (86.24 ± 25.38 vs 78.21 ± 17.93 mg/dL, p = 0.019), as well as lower high-density lipoprotein (50.27 ± 8.4 vs 53.96 ± 10.38 mg/dL, p = 0.019). Women with family history of diabetes mellitus had lower high-density lipoproteins (49.89 ± 8.05 vs 59.53 ± 11.44, p = 0.006). Family history of dyslipidaemia was associated with significantly higher triglycerides (146.14 ± 46.19 vs 98.44 ± 56.19 mg/dL, p = 0.002) in men and in subjects across sex. HDL was contrarily higher, in women with family history of cerebrovascular accident/HTN and men with family history of coronary heart disease/HTN. The proportion of pre-HTN, overweight/obese, impaired fasting glucose and borderline high triglycerides was 88.3%, 36.8%, 11% and 38.7% in men and 64.9%, 37.8%, 18.9% and 48.7% in female subjects. Conclusion: Young adults with a family history of CVD-risk already have an incomplete/atypical CVD risk profile.

Epidemiological correlates of hepatitis C infection- A case control analysis from a tertiary care hospital.

Background: Hepatitis C virus (HCV) infection is considered one of the growing public health problems. Identification of HCV-associated risk factors is pivotal for developing appropriate prevention strategies. Objectives: To determine the epidemiological variables of HCV infection in a tertiary care hospital. Methods: This hospital-based case-control study was conducted in a tertiary care hospital in Punjab on 320 subjects, including 160 cases and controls each. Cases and controls were matched by age (±5 years), gender, and residence. A patient ≥18 years of age fulfilling the biomarker criteria with or without clinical criteria diagnosed in the last 1 month was considered as a case. The information on socio-demographic characteristics and previous exposures to selected risk factors was collected through detailed interviews of the subjects. Analysis was performed using SPSS 20 statistical software. Odds ratio (OR) with 95% confidence interval (CI) was calculated to measure the strength of association between cases and controls for each risk factor. Results: Odds of having HCV infection was significantly higher among those with a history of blood transfusion (OR: 2.30, 95%CI: 1.14-4.63), dental procedure (OR: 4.82, 95%CI: 2.38-9.77) and intravenous injection/infusion from quacks (OR: 3.26, 95%CI: 1.47-7.19), injectable drug use (OR: 26.69, 95%CI: 3.55-200.24), non-injectable drug use (OR: 2.37, 95%CI: 1.44-3.90), tattooing (OR: 7.91, 95%CI: 2.31-27.08), and piercing from street hawkers (OR: 2.25, 95%CI: 1.18-4.29). Multivariate analysis identified history of blood transfusion, dental procedure, intravenous injection/infusion from quacks, injecting drug use, and piercing as independent risk factors for HCV infection. Conclusion: The study identified multiple risk factors for acquiring HCV infection and suggest appropriate interventions targeting high-risk populations.

From rapid antigen testing for COVID-19 to final outcome: An experience from industrial city of Ludhiana.

Context: The ongoing corona pandemic has created medical crises all over the world. An increased surge in the number of COVID-19 cases was observed in the month of August, September and October 2020. Punjab has around 10 Lakh migrant workers. Intensive rapid antigen testing was done during this surge among factory workers. With this background, the study aims to find out the positivity rate of rapid antigen testing and to find out the final outcome of the COVID positive cases in terms of morbidity. Materials and methods: Screening of factory workers working in various factories was done for COVID-19 by rapid antigen testing from 26th august to 31st October 2020. Those who tested positive were clinically examined, counseled, and followed up telephonically to get information regarding their course of illness. The collected information was entered in Microsoft excel sheet and analyzed using SPSS. Results: A total of 11045 factory workers were screened using the rapid antigen test. The mean age of subjects was 33.37 ± 10.97 years. The majority of them were males (88.3%) and migrants (who did not belong to Punjab) (97.3%). The majority of the subjects (97.3%) had no symptoms at the time of screening. COVID-19 positivity rate increased with age, was found to be higher in males (2.3%) as compared to females. Conclusion: The positivity rate was higher in asymptomatic males and local resident workers. Rapid antigen testing is an important public health measure to prevent the further spread of the disease during a pandemic due to its quick results and detection of asymptomatic patients.

Epidemiology and pathophysiology of vascular thrombosis in acclimatized lowlanders at high altitude: A prospective longitudinal study.

Background: Previous literature suggests that thrombosis is more common in lowlanders sojourning at high altitude (HA) compared to near-sea-level. Though the pathophysiology is partly understood, little is known of its epidemiology. To elucidate this, an observational prospective longitudinal study was conducted in healthy soldiers sojourning for months at HA. Methods: A total of 960 healthy male subjects were screened in the plains, of which 750 ascended, to altitudes above 15,000ft (4,472m). Clinical examination, haemogram, coagulogram, markers of inflammation and endothelial dysfunction, were studied at three time points during ascent and descent. The diagnosis of thrombosis was confirmed radiologically in all cases where a thrombotic event was suspected clinically. Subjects developing thrombosis at HA were labelled as Index Cases (ICs) and compared to a nested cohort of the healthy subjects (comparison group,(CG)) matched for altitude of stay. Findings: Twelve and three subjects, developed venous (incidence: 5,926/105 person-years) and arterial (incidence: 1,482/105 person-years) thrombosis at HA, respectively. The ICs had enhanced coagulation (FVIIa: p<0.001; FXa: p<0.001) and decreased levels of natural anticoagulants (thrombomodulin, p=0.016; tissue factor pathway inhibitor [TFPI]: p<0.001) and a trend to dampened fibrinolysis (tissue plasminogen activator tPA; p=0.078) compared to CG. ICs also exhibited statistically significant increase in the levels of endothelial dysfunction and inflammation markers (vascular cell adhesion molecule-1[VCAM-1], intercellular adhesion molecule-1 [ICAM-1], vascular endothelial growth factor receptor 3 [VEGFR-3], P-Selectin, CD40 ligand, soluble C-reactive protein and myeloperoxidase: p<0.001). Interpretation: The incidence of thrombosis in healthy subjects at HA was higher than that reported in literature at near sea-level. This was associated with inflammation, endothelial dysfunction, a prothrombotic state and dampened fibrinolysis. Funding: Research grants from the Armed Forces Medical Research Committee, Office of the Director General of Armed Forces Medical Services (DGAFMS) & Defence Research and Development Organization (DRDO), Ministry of Defence, India.

Multifactorial Landscape Parses to Reveal a Predictive Model for Knee Osteoarthritis.

The present study attempted to investigate whether concerted contributions of significant risk variables, pro-inflammatory markers, and candidate genes translate into a predictive marker for knee osteoarthritis (KOA). The present study comprised 279 confirmed osteoarthritis patients (Kellgren and Lawrence scale >2) and 287 controls. Twenty SNPs within five genes (CRP, COL1A1, IL-6, VDR, and eNOS), four pro-inflammatory markers (interleukin-6 (IL-6), interleuin-1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), and high sensitivity C-reactive protein (hsCRP)), along with significant risk variables were investigated. A receiver operating characteristic (ROC) curve was used to observe the predictive ability of the model for distinguishing patients with KOA. Multivariable logistic regression analysis revealed that higher body mass index (BMI), triglycerides (TG), poor sleep, IL-6, IL-1ß, and hsCRP were independent predictors for KOA after adjusting for the confounding from other risk variables. Four susceptibility haplotypes for the risk of KOA, AGT, GGGGCT, AGC, and CTAAAT, were observed within CRP, IL-6, VDR, and eNOS genes, which showed their impact in recessive ß(SE): 2.11 (0.76), recessive ß(SE): 2.75 (0.59), dominant ß(SE): 1.89 (0.52), and multiplicative modes ß(SE): 1.89 (0.52), respectively. ROC curve analysis revealed the model comprising higher values of BMI, poor sleep, IL-6, and IL-1ß was predictive of KOA (AUC: 0.80, 95%CI: 0.74-0.86, p< 0.001), and the strength of the predictive ability increased when susceptibility haplotypes AGC and GGGGCT were involved (AUC: 0.90, 95%CI: 0.87-0.95, p< 0.001).This study offers a predictive marker for KOA based on the risk scores of some pertinent genes and their genetic variants along with some pro-inflammatory markers and traditional risk variables.

Genetic Scores of eNOS, ACE and VEGFA Genes Are Predictive of Endothelial Dysfunction Associated Osteoporosis in Postmenopausal Women.

The present study aimed to examine the participation and contribution of endothelial nitric oxide synthase (eNOS), angiotensin converting enzyme (ACE) and vascular endothelial growth factor (VEGFA) genes for the risk of endothelial dysfunction (ED)-associated osteoporosis risk in postmenopausal women of Punjab, India. Women with ED were categorized into women with osteoporosis (n = 346) and women without osteoporosis (n = 330). They were examined for selected SNPs within eNOS, ACE and VEGFA genes. Linear regression analysis revealed a positive association of ED with bone mineral densities (BMDs) at femoral neck (r2 = 0.78, p < 0.001) and lumbar spine (r2 = 0.24, p = 0.001) after Bonferroni correction. Three susceptibility haplotypes were exposed within eNOS (CTAAAT), ACE (ACDG) and VEGFA (GATA) genes. Bearers of CTAAAT (OR 2.43, p = 0.007), ACDG (OR 2.50, p = 0.002) and GATA (OR 2.10, p = 0.009) had substantial impact for osteoporosis after correcting the effects with traditional risk factors (TRD).With uncertainty measure (R2h) and Akaike information criterion (AIC), best fit models showed that CTAAAT manifested in multiplicative mode (ß ± SE: 2.19 ± 0.86, p < 0.001), whereas ACDG (ß ± SE: 1.73 ± 0.54, p = 0.001) and GATA (ß ± SE: 3.07 ± 0.81, p < 0.001) expressed in dominant modes. Area under receiver operating characteristic curve using weighted risk scores (effect estimates) showed substantial strength for model comprising TRD + GATA (AUC = 0.8, p < 0.001) whereas, model comprising TRD + GATA + CTAAAT exhibited excellent ability to predict osteoporosis (AUC = 0.824, p < 0.001).

Investigation of eNOS gene polymorphism exposes a genetic association between endothelial dysfunction and osteoporosis in postmenopausal women.

OBJECTIVES: To investigate the association of genetic polymorphisms of endothelial nitric oxide synthase (eNOS) gene with endothelial dysfunction associated osteoporosis in postmenopausal women of Punjab, India. METHODS: The study involved 456 postmenopausal women having endothelial dysfunction categorized according to women with (n = 236) and without osteoporosis (n = 220). Bone mineral density (BMD) and reactive hyperemia index (RHI) were evaluated together with six single-nucleotide polymorphisms (SNPs) within the eNOS gene (rs2070744, rs1799983, rs1800780, rs3918181, rs891512, and rs1808593). RESULTS: A moderate association between RHI and BMD at femoral neck (r = 0.213, P = 0.002) and lumbar spine (r = 0.267, P < 0.001) was observed. Minor alleles C and T of SNPs rs2070744 and rs1799983 were associated with chances of osteoporosis in both co-dominant (odds ratio [OR] 2.13, P = 0.017; OR 2.77, P = 0.009) and dominant (OR 2.10, P = 0.011; OR 2.45, P = 0.007) modes, whereas minor allele A of SNP rs891512 showed marginal probability in dominant model (OR 1.68, P = 0.047). A susceptibility haplotype (CTAAAT) was observed within the eNOS gene which conferred 2.32 times higher chances of osteoporosis (OR 2.32, 95% confidence interval 1.18-4.54, P = 0.021) after adjusting for the effect of confounders. Genetic model analysis revealed that each copy of susceptibility haplotype increased the possibility of osteoporosis by a factor of 2.11 ±â€Š0.63 (P < 0.001). RHI was significantly associated with susceptibility haplotype CTAAAT in a dose-dependent manner, whereby the severity of endothelial dysfunction increased significantly in women having two copies over women having one copy or no copy (ß = 2.13, P < 0.001) of susceptibility haplotype. CONCLUSION: A susceptibility haplotype CTAAAT within the eNOS gene is associated with double the possibility of endothelial dysfunction affiliated osteoporosis in postmenopausal women of Punjab, India.

Promoter polymorphisms in IL-6 gene influence pro-inflammatory cytokines for the risk of osteoarthritis.

BACKGROUND: Interleukin-6 (IL-6) gene regulates IL-6 levels, interplay of which has been found to influence pathophysiology of osteoarthritis (OA). Polymorphism within promoter region of IL-6 gene and its association with plasma levels of pro-inflammatory cytokines; IL-6, interleukin 1-beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) remained to be investigated in Punjab region of India, where OA is highly prevalent. METHODS: Six single nucleotide polymorphisms (SNPs) in the promoter region of IL-6 gene; rs1800795 (-174G/C), rs1800796 (-572G/C), rs1800797 (-597G/A), rs2069827 (-1363G/T), rs12700386 (-2954G/C) and rs10499563 (-6331G/T) were investigated by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 279 confirmed osteoarthritis patients and 287 controls. Plasma levels of pro-inflammatory cytokines; IL-6, IL-1ß and TNF-α were measured by sandwich Enzyme Linked Immunosorbent Assay (ELISA). RESULTS: Allele frequency spectrum after adjusting the effect of systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low density lipoprotein (LDL), triglycerides (TG) and body mass index (BMI) revealed that major allele G of rs1800795 and T of rs10499563 were significantly associated with increased risk of OA (P < 0.01) in all the three genetic models; co-dominant (OR 4.08 & 4.12, P < 0.001), recessive (OR 3.00 & 2.51, P < 0.001) and dominant (OR 2.56 & 3.09, P < 0.05). Major allele G of rs1800796 and rs1800797 was observed to enhance OA risk in recessive mode (OR 1.75, P < 0.001 & 1.62, P = 0.01 respectively). Disease risk analysis after adjusting the effect of confounders exposed a susceptibility haplotype GGGGCT, which increased the OA risk by 2.27 times (OR 2.27, 95%CI: 1.26-4.10, P = 0.009) and a protective haplotype CGAGGC which significantly reduced the OA risk (OR 0.47, 95%CI 0.27-0.92, P = 0.031). Both of these haplotypes manifested in the recessive mode of inheritance. Subjects who had one copy of the susceptibility haplotype had lower values of IL-6 (3.6 pg/ml) and IL-1ß levels (3.2 pg/ml) than those who had 2 copies of it (4.4 pg/ml & 4.2 pg/ml respectively). IL-6 and IL-1ß levels were observed to be negatively associated with protective haplotype CGAGGC (P < 0.05). Carriers of 1 copy of this haplotype showed decreased IL-1ß levels than those who had none (1.00 pg/ml vs. 1.3 pg/ml respectively) which further decreased to 0.9 pg/ml in those subjects who carried two copies of protective haplotype. CONCLUSION: The present study discovered susceptibility (GGGGCT) and protective (CGAGGC) haplotypes within promoter region of IL-6 gene which influenced the plasma levels of IL-6 and IL-1ß for the risk of osteoarthritis in the population of Punjab, India.

Reproductive behavior of newly married women in rural Punjab, India: A longitudinal study.

INTRODUCTION: In India, little is known about the reproductive behavior during earlier years of married life of women, when they are more vulnerable to reproductive ill health and early child bearing with very few interventions available. OBJECTIVE: The objective of this study is to follow a cohort of newly married women immediately after marriage until their first pregnancy outcome to gain an insight into their reproductive behavior so that important opportunities could be identified for intervention. SUBJECTS AND METHODS: A community-based longitudinal study was carried out in 15 villages of Ludhiana District under the Rural Health Training Centre of Department of Community Medicine, Dayanand Medical College and Hospital, Ludhiana, Punjab. All marriages of the male residents that took place in these villages from January 1, 2013, to December 31, 2013 were enrolled. Thus, a cohort of 195 newly married women was identified over a period of 1 year and followed every month till first pregnancy outcome. The analysis was performed using SPSS version 20 statistical software. RESULTS: Mean age at marriage for newly married women was 22.9 ± 3.0 years. Majority of them conceived within 1st year of marriage (79.5%) while 10.8% of women did not conceive till the end of follow-up period. Mean age at first pregnancy was 23.4 ± 3.1 years with mean interval between marriage and first pregnancy of 5.4 ± 6.1 months. Nearly, three-fourth of pregnancies resulted in live births while adverse pregnancy outcome including still births and abortions was seen in 15.9% of the study cohort. CONCLUSIONS: Overall findings indicate optimistic picture for married young women, but critical opportunities should be utilized to promote health of these women in a journey toward safe motherhood.

Managing High-Altitude Pulmonary Edema with Oxygen Alone: Results of a Randomized Controlled Trial.

Yanamandra, Uday, Velu Nair, Surinderpal Singh, Amul Gupta, Deepak Mulajkar, Sushma Yanamandra, Konchok Norgais, Ruchira Mukherjee, Vikrant Singh, Srinivasa A. Bhattachar, Sagarika Patyal, and Rajan Grewal. High-altitude pulmonary edema management: Is anything other than oxygen required? Results of a randomized controlled trial. High Alt Med Biol. 17:294-299, 2016.-Treatment strategies for management of high-altitude pulmonary edema (HAPE) are mainly based on the observational studies with only two randomized controlled trials, thus the practice is very heterogeneous and individualized as per the choice of treating physician. To compare the response to different modalities of therapy in patients with HAPE in a randomized controlled manner. We conducted an open-label, randomized noninferiority trial to compare three modalities of therapy (Therapy 1: supplemental O2 with oral dexamethasone 8 mg q8 hours [n = 42], Therapy 2: supplemental O2 with sustained release oral nifedipine 20 mg q8 hours [n = 41], and Therapy 3: only supplemental O2 [n = 50]). Bed rest was mandated in all patients. The study was conducted in a cohort of previously healthy young lowlander males at an altitude of 3500 m. Baseline characteristics of the patients were comparable in the study arms. Complete response was defined as clinical and radiological resolution of features of HAPE, no oxygen dependency, a normal 6-minute walk test (6MWT) on 2 consecutive days, and normal two-dimensional echocardiography. Results were compared by analysis of variance using SPSS version 16.0. There was no statistical difference in duration of therapy to complete response between the three groups (Therapy 1: 8.1 ± 4.0 days, Therapy 2: 6.7 ± 3.9 days, Therapy 3: 6.8 ± 3.2 days; p = 0.15). There were no deaths in any of the groups. We conclude that oxygen and bed rest alone are adequate therapy for HAPE and that adjuvant pharmacotherapy with either dexamethasone or nifedipine does not hasten recovery.

Audiological Evaluation of Patients Taking Kanamycin for Multidrug Resistant Tuberculosis.

INTRODUCTION: The incidence of multidrug resistant tuberculosis is increasing in developing countries. Aminoglycosides are an integral part of second-line drugs, however ototoxicity is a major limitation for their use. This study aims to determine the extent of hearing loss in patients taking one of the commonly prescribed drugs for Multidrug resistant tuberculosis (MDR-TB), Kanamycin, at a Government Medical College, Patiala, Punjab, India, which is a 1200 bed tertiary care hospital. MATERIALS AND METHODS: A total of 100 patients (68 males and 32 females) with confirmed diagnosis of MDR-TB were included in this study conducted between January 2012 and February 2014. Subjects were between 15 to 60 years of age, with a mean age of 37.46 ± 10.1. Pure tone audiometry (PTA) was performed before the start of the therapy, as a baseline, and was repeated after 1 week and 6 weeks of Kanamycin use to assess hearing loss as an effect of therapy. RESULTS: Of the 100 patients examined, ototoxicity was found in 18 subjects post therapy. Incidence of high frequency hearing loss was 2% at week 1, and 12% after 6 weeks of follow up. However, 4% of the cases developed flat loss at week 6. The hearing loss was bilateral in 13 patients and unilateral in 5 patients. Ototoxicity was more common in males (66.67%) compared to females (33.3%). Maximum cases were found in the age group of 36 to 45 years (36.8%), the majority being from a rural background (83.3%). The association with socioeconomic status (P=0.024) and co-morbid conditions like diabetes and hypertension (P=0.001) reached statistical significance. CONCLUSION: Lack of specific guidelines to monitor patients taking aminoglycosides makes ototoxicity a major adverse effect of their use in MDR-TB. More studies are mandated to study the risk factors associated with the development of ototoxicity and for the development of alternate drugs for the treatment of MDR-TB.

Retinal vein occlusion in high altitude.

Staying at high altitude has been reported to be associated with thrombosis in lowlanders. We report 3 cases of retinal vein occlusion in high altitude. Two were males 31 and 37 years of age, who developed nonischemic central retinal vein occlusion while staying at high altitude. The former developed central retinal vein occlusion after 90 days at 6309 m, while the latter was affected at an altitude of 3353 m where he had been for the past 1 year and had recurrence of central retinal vein occlusion in the other eye on re-entry to the same altitude. The third case is that of a 40-year-old female who developed inferotemporal branch retinal vein occlusion on the second day after entry into high altitude (3353 m) by air, while ascending further in a vehicle at an altitude of approximately 4572 m. All three did not have any systemic disease and showed complete recovery on descent to a lower altitude.