Acute paraquat poisoning in an adolescent with compromised outcome: A case report.

Paraquat, a highly toxic herbicide, accounts for a substantial number of poisoning-related fatalities, primarily prevalent in agricultural regions. The ingestion gives rise to severe complications affecting various organs, including the lungs, gastrointestinal tract, kidneys and liver. This report details the case of an 18-year-old male who had been using cannabis for a year and inadvertently ingested paraquat. He presented at the emergency room exhibiting symptoms of vomiting characterized by hematemesis and regurgitated food particles, along with heartburn, dysphagia and reduced urine output. Given the absence of a specific antidote, the prognosis for paraquat poisoning remains generally unfavourable. Diagnosis relies on circumstantial evidence and clinical manifestations, necessitating a focus on supportive care. Presently, no specific antidote for paraquat poisoning is available. Efforts should concentrate on preventive measures, efficient decontamination strategies and vigilant stabilization protocols in instances of exposure.

Antiretroviral drug use and the risk of falls in people living with HIV: a systematic review and meta-analysis.

Objective: The risk of falls in people living with HIV (PLHIVs) on antiretroviral therapy (ART) has received little attention in the literature. The aim of the meta-analysis is to quantify the association between fall risk and various categories of drugs used in ART. Material and Methods: PubMed, Google Scholar, Embase, and the Cochrane Central Register of Controlled Trials were systematically searched from inception to January 2023. Any observational study or controlled trial that reported on the relationship of at least one antiretroviral drug with falls in PLHIVs was included. Data on the frequency of single fallers, multiple fallers (≥2 falls), and non-fallers were extracted and studied for each drug and drug category. The pooled results were reported as an odds ratio (OR) with a 95% confidence interval (CI). Results: A total of five observational studies (51 675 participants) were included out of 414 articles obtained through a literature review. Stavudine use was found to be associated with an increased risk of single falls in PLHIVs (OR: 1.69, 95% CI: 1.08-2.66, P=0.02). However, efavirenz (OR: 0.82, 95% CI=0.76-0.89, P<0.001) and zidovudine (OR: 0.82, 95% CI=0.77-0.92, P<0.001) were found protective against the single falls. Didanosine had no significant association with fall risk (OR: 1.23, 95% CI: 0.78-1.93, P=0.37). Likewise, protease inhibitors, integrase inhibitors, nucleoside reverse transcriptase inhibitors, and non-nucleoside reverse transcriptase inhibitors were discovered to have no significant association with fall risk. Conclusion: Most drug categories of ART have no significant association with the risk of falls in PLHIVs. However, certain drugs, such as didanosine and stavudine, which have the inherent effect of causing balance deficits and neuropathy, should be used cautiously.

Burden of tuberculosis and hepatitis co-infection among people living with HIV in Nepal: a systematic review and meta-analysis.

People living with HIV (PLHIV) are prone to tuberculosis (TB) and hepatitis co-infections, which cause substantial burden on morbidity and mortality. However, data on the burden of HIV co-infection from a specific low- and middle-income country are limited. To address this gap in evidence, a meta-analysis of published literature and country surveillance report was conducted to estimate the burden of TB, hepatitis B (HBV) and hepatitis C (HCV) co-infection among PLHIV in Nepal. Twenty-three studies, including 5900 PLHIV, were included in the meta-analysis. The pooled prevalence of HIV-TB, HIV-HBV and HIV-HCV co-infection was 19% (95% CI, 10-28%), 3% (2-5%) and 19% (4-33%), respectively. Low CD4 cell count (pooled odds ratio [OR] 4.38, 95% CI 1.11-17.25), smoking (3.07, 1.48-6.37) and alcohol drinking (3.12, 1.52-6.43) were significantly correlated with HIV-TB co-infection. The odds of HCV co-infection was greater in PLHIV, who were male (5.39, 1.54-18.89) and drug users (166.26, 15.94-1734.44). PLHIV who were on antiretroviral therapy had a reduced risk of HCV co-infection (0.49, 0.36-0.66) than the general PLHIV population. The burden of TB and hepatitis co-infection among PLHIV in Nepal was high. Regular screening of PLHIV for co-infections and prompt initiation of treatment are essential to reduce the transmission of infection and improve quality of life.

Potential Drug-drug Interaction among the Patients Admitted in Intensive Care Units of a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: Drug interactions are one of the major contributors to increase hospital stay, inflate health care expenses, and cause serious adverse events and end-organ damage. Patients admitted to the intensive care unit are already critically sick and are at greater risk of these adverse outcomes. The study aimed to find out the prevalence of potential drug-drug interactions in the Intensive Care Units of a tertiary care centre. Methods: A descriptive cross-sectional study was conducted among the patients admitted in the Intensive Care Unit of a tertiary care hospital from April-June 2019. Ethical approval was taken from the Institutional Review Board at the institute (Reference number: 399). Convenience sampling method was used. Data was collected using proforma and potential drug-drug interactions were identified using Lexicomp® drug-interactions version 1.1 (Wolters Kluwer). All the drug interactions identified were classified and the severity scale of interactions was also defined. Statistical Package for the Social Sciences version 17.0 was used for data analysis. Point estimate at 95% Confidence Interval was calculated along with frequency, percentage, mean, standard deviation, and mode. Results: Out of 101 patients, the prevalence of the drug-drug interaction was found to be 90 (89.11%) (83.04-95.18 at 95% Confidence Interval). A total of 490 drug-drug interactions were identified. In severity scale, it was seen that 311 (63.46%) were of moderate severity and 303 (61.83%) of drug interactions were categorised as category C in risk rating. Conclusions: Prevalence of potential drug-drug interactions was higher compared to similar published literature. The most common drug with potential interaction was fentanyl and among pairs was fentanyl plus paracetamol. Keywords: drug interactions; intensive care units; Nepal; software.

Intentional pesticide poisoning and pesticide suicides in Nepal.

INTRODUCTION: Intentional pesticide poisoning is a major clinical and public health problem in agricultural communities in low and middle income countries like Nepal. Bans of highly hazardous pesticides (HHP) reduce the number of suicides. We aimed to identify these pesticides by reviewing data from major hospitals across the country and from forensic toxicology laboratories. METHODS: We retrospectively reviewed medical records of 10 hospitals for pesticide poisoned patients and two forensic laboratories of Nepal from April 2017 to February 2020. The poison was identified from the history, referral note, and clinical toxidrome in the hospitals and from gas chromatography analysis in the laboratories. Data on demographics, poison, and patient outcome were recorded on a data collection sheet. Simple descriptive analysis was performed. RESULTS: Among hospital cases (n = 4148), the commonest form of poisoning was self-poisoning (95.8%) while occupation poisoning was rare (0.03%). Case fatality was 5.3% (n = 62). Aluminum phosphide (n = 38/62, 61.3%) was the most commonly identified lethal pesticide for deaths. Forensic toxicology laboratories reported 2535 deaths positive for pesticides, with the compounds most commonly identified being organophosphorus (OP) insecticides (n = 1463/2535; 57.7%), phosphine gas (n = 653/2535; 25.7%; both aluminum [11.8%] and zinc [0.4%] phosphide) and organochlorine insecticides (n = 241/2535; 9.5%). The OP insecticide most commonly identified was dichlorvos (n = 273/450, 60.6%). CONCLUSION: The data held in the routine hospital medical records were incomplete but suggested that case fatality in hospitals was relatively low. The pesticides identified as causing most deaths were dichlorvos and aluminum phosphide. Since this study was completed, dichlorvos has been banned and the most toxic formulation of aluminum phosphide removed from sale. Improving the medical record system and working with forensic toxicology laboratories will allow problematic HHPs to be identified and the effects of the bans in reducing deaths monitored.

Fear, Risk Perception, and Engagement in Preventive Behaviors for COVID-19 during Nationwide Lockdown in Nepal.

The world has faced huge negative effects from the COVID-19 pandemic between early 2020 and late 2021. Each country has implemented a range of preventive measures to minimize the risk during the COVID-19 pandemic. This study assessed the COVID-19-related fear, risk perception, and preventative behavior during the nationwide lockdown due to COVID-19 in Nepal. In a cross-sectional study, conducted in mid-2021 during the nationwide lockdown in Nepal, a total of 1484 individuals completed measures on fear of COVID-19, COVID-19 risk perception, and preventive behavior. A multiple linear regression analysis was used to identify factors associated with COVID-19 fear. The results revealed significant differences in the fear of COVID-19 in association with the perceived risk of COVID-19 and preventive behaviors. Age, risk perception, preventive behavior, and poor health status were significantly positively related to fear of COVID-19. Perceived risk and preventive behaviors uniquely predicted fear of COVID-19 over and above the effects of socio-demographic variables. Being female and unmarried were the significant factors associated with fear of COVID-19 among study respondents. Higher risk perception, poor health status, and being female were strong factors of increased fear of COVID-19. Targeted interventions are essential to integrate community-level mental health care for COVID-19 resilience.

Safety and efficacy of interleukin-6-receptor inhibitors in the treatment of neuromyelitis optica spectrum disorders: a meta-analysis.

BACKGROUND: Interleukin-6-receptor inhibitors like Tocilizumab and Satralizumab are showing promising results in the treatment of Neuromyelitis Optica spectrum disorder (NMOSD). We aimed to investigate the efficacy and safety of various Interleukin-6-receptor inhibitors in the management of NMO/NMOSD. METHODS: PubMed, Embase, and The Cochrane Library were systematically searched for suitable studies. Change in Annualized Relapse Ratio (ARR), Change in Extended Disability Status Scale (EDSS) s, the proportion of relapse-free patients and proportion of patients with adverse events, including serious adverse events and mortality were the parameters considered for the meta-analysis for Tocilizumab. Mean difference (MD) with 95% CI was used to quantify the change in ARR and change in EDSS before and after treatment. A forest plot was prepared to indicate the efficacy and adverse effects outcomes. The results were compared with those of Satralizumab included in two trials. RESULTS: A total of nine studies with 202 patients were included in our study. Tocilizumab found a good proportion (76.95% CI: 0.61-0.91; p < 0.001) of relapse free patients at follow up. It also significantly reduced mean ARR (mean difference: -2.6, 95% CI: - 2.71 to - 1.68; p < 0.001) and but did not show significant difference in change in EDSS score (mean difference = - 0.79, 95% CI: - 1.89 to - 0.31; p = 0.16). Also, the toxicity profile of Tocilizumab was acceptable considering the proportions of patients with adverse events 56% (95% C.I.;0.27-0.85, I2 = 88.95%, p < 0.001), proportions of patients with serious adverse events 11% (95% C.I.; 0.05 to 0.17, I2 = 0%, p < 0.001) and zero treatment related deaths. SAkura studies for Satralizumab showed similar relapse free patients (70% to 80%) and reduction of ARR and EDSS from baseline. Some studies of Tocilizumab have shown to reduce pain and fatigue while trials of Satralizumab had non-significant findings. CONCLUSION: Interleukin-6-receptor inhibitors therapy showed a promising result with good efficacy and acceptable adverse events profile for treatment of NMOSD.

Efficacy and Safety of Paromomycin for Visceral Leishmaniasis: A Systematic Review.

Visceral leishmaniasis, also known as kala-azar is one of the most commonly neglected tropical diseases affecting a large number of rural and resource-limited people in South Asia, Africa, and South America. Paromomycin, an aminoglycoside drug, is frequently used for the treatment of visceral leishmaniasis. Despite limited therapies for visceral leishmaniasis and emerging drug resistance, a proper review on the action of paromomycin for kala-azar is lacking. This systematic review aims to look for the efficacy and safety aspects of paromomycin for the treatment of visceral leishmaniasis.

Suicide by pesticide ingestion in Nepal and the impact of pesticide regulation.

BACKGROUND: Nepal recorded 5754 suicides in 2018-19 - a high number for a relatively small country. Over 24% of these suicides were by poisoning, most by ingestion of highly concentrated agricultural pesticides. Nepal has actively regulated pesticides to reduce their health impacts since 2001. We aimed to analyse Nepal's history of pesticide regulation, pesticides responsible for poisonings, and relate them to national suicide rates. METHODS: Information on pesticide regulation was collected from the Plant Quarantine and Pesticide Management Centre of the Ministry of Agriculture and Livestock Development. National data on suicides from 1980 to 2019 were obtained from the National Statistical Bureau and Nepal Police. Data on the pesticides responsible for self-poisoning and pesticide suicides over time were obtained from a systematic literature review. RESULTS: As of June 2020, 171 pesticides were registered for use in Nepal, of which one was extremely hazardous (WHO Class Ia), one other highly hazardous (WHO Class Ib), and 71 moderately hazardous (WHO Class II). Twenty-four pesticides have been banned since 2001, with eight (including five WHO Class I compounds) banned in 2019. Although the suicide rate has increased more than twelve-fold since 1980, particularly for hanging (15-fold increase from 1980 to 2018), fatal pesticide self-poisoning has increased by 13-fold. Methyl-parathion is reported to be the key pesticide responsible for pesticide self-poisoning in Nepal, despite being banned in 2006. CONCLUSION: The full effect of the recent pesticide policy reform in Nepal remains to be seen. Our analysis shows a continuing increase in suicide numbers, despite bans of the most important pesticide in 2006. This may indicate smuggling across the border and the use of the brand name (Metacid) for pesticides in general making it difficult to identify the responsible pesticide. More information is required from forensic toxicology labs that identify the individual compounds found. The effect of recent bans of common suicide pesticides needs to be monitored over the coming years. Evidence from other Asian countries suggests that HHPs bans will lead to a marked reduction in suicides, as well as fewer cases of occupational poisoning.

Prescribers Perception on Drug Promotional Literatures in A Tertiary Care Hospital in Nepal.

BACKGROUND: Drug promotional literatures can often be misleading and have biased information and can contribute to irrational use of medicines. Thus, it is necessary that prescribers critically analyze the drug promotional literatures presented to them. This study attempts to understand if the prescribers at Tribhuvan University Teaching Hospital are aware about the necessary information that should be present in a drug promotional literature. METHODS: A descriptive cross-sectional study was conducted over six months in which prescribers at Tribhuvan University Teaching Hospital were provided with the self-administered questionnaire and were requested to submit the filled in questionnaire. Prescribers presently working at Tribhuvan University Teaching Hospital, attending out patient department services and had received drug promotional literatures within last six months were included in this study. RESULTS: During the study, 163 of the received questionnaires met the inclusion criteria and were utilized for analysis. Advertisement, reminder items and others type of drug promotional literatures were commonly received by prescribers included in our study. Higher proportion of faculties (35.29%) preferred reprint type of drug promotional literatures. Most of the participants (47.85%) searched for 5-8 WHO-Ethical Criteria for Medicinal Drug Promotion criteria when referring a drug promotional literature. It was seen that 42.94% of prescribers realised that at least two out of four types of information related to negative attribute of the promoted medicines were missing. CONCLUSIONS: The prescribers with least duration of clinical exposure are more likely to always prescribe the medicines promoted to them. Prescribers were more confident on claims made in drug promotional literatures if they were supported using scientific evidences.

Methicillin-resistant Staphylococcus aureus in Nepal: A systematic review and meta-analysis.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a significant health threat and public burden worldwide, particularly in developing countries, including Nepal, due to its low healthcare standards and irrational use of antibiotics. It is evident that MRSA strains are frequently detected in Nepalese hospitals; however, they remain underreported. Therefore, to provide a comprehensive and clear understanding of MRSA infection at the national level, this systematic review and meta-analysis evaluated the prevalence and antimicrobial susceptibility patterns of MRSA in Nepal. METHODS: PubMed, EMBASE, Cochrane CENTRAL, Google scholar, and Nepalese databases were searched for studies published between 1st January 2008 and 31st August 2020. A total of 26 original articles were selected for quantitative analysis. Data extraction was accomplished by three authors independently and meta-analysis was performed using MedCalc Version 19.5.1 and Comprehensive Meta-Analysis (CMA) software v.3.0. RESULT: The pooled prevalence of MRSA infections among 5951 confirmed S. aureus isolates was 38.2% (95% CI, 31.4%-45.2%). We found a significant heterogeneity (I2 = 96.7% for resistance proportion), and no evidence of publication bias (p = 0.256) among studies. MRSA strains showed a high level of resistance to beta-lactam antibiotics and the highest susceptibility profile was noted in vancomycin 98.0% followed by chloramphenicol 91.0%. CONCLUSION: The analysis revealed that the overall MRSA burden in Nepal is considerably high and the prevalence of MRSA infections is in the increasing trend. Sound legislation, definite antibiotic policy, and implementations of control interventions are indispensable for tackling MRSA infection and antimicrobial resistance as a whole.

Efficacy and safety of inhaled budesonide on prevention of acute mountain sickness during emergent ascent: a meta-analysis of randomized controlled trials.

BACKGROUND: Acute Mountain Sickness (AMS) is a pathophysiologic process that occurs in non-acclimated susceptible individuals rapidly ascending to high-altitude. Barometric pressure falls at high altitude and it translates to a decreased partial pressure of alveolar oxygen (PAO2) and arterial oxygen (PaO2). A gradual staged ascent with sufficient acclimatization can prevent AMS but emergent circumstances requiring exposure to rapid atmospheric pressure changes - such as for climbers, disaster or rescue team procedures, and military operations - establishes a need for effective prophylactic medications. This systematic review and meta-analysis aim to analyze the incidence of AMS during emergent ascent of non-acclimatized individuals receiving inhaled budesonide compared to placebo. METHODS: This current meta-analysis was conducted according to the guidance of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. We searched PubMed, Google Scholar and Embase for relevant studies. The efficacy of budesonide in reducing incidence of AMS was evaluated by calculating the pooled ORs and 95% CIs. The efficacy of budesonide in maintaining hemoglobin-oxygen saturation was evaluated by calculating standard mean difference (SMD) and 95% confidence intervals. RESULTS: We found that at high altitude, inhaled budesonide was effective in reducing the incidence of mild AMS [OR: 0.37; 95% CI, 0.14 to 0.9, p = 0.042] but was ineffective in reducing the incidence of severe AMS [OR: 0.46; 95% CI, 0.14 to 1.41, p = 0.17]. Inhaled budesonide was also effective in maintaining SpO2 (SMD: 0.47; 95% CI, 0.09 to 0.84, p = 0.014) at high altitude. However, it was not effective in maintaining or improving pulmonary function at high altitude. Systematic-review found no adverse effects of budesoide in the dose used for prophylaxis of AMS. CONCLUSIONS: Our systematic review showed that prophylactic inhaled budesonide is effective in preventing mild AMS during emergency ascent but not effective in preventing severe AMS. Though statistically significant, authors recommend caution in interpretation of data and questions for further well designed randomized studies to evaluate the role of budesonide in prophylaxis of AMS during an emergent ascent.

The Efficacy of Pralidoxime in the Treatment of Organophosphate Poisoning in Humans: A Systematic Review and Meta-analysis of Randomized Trials.

Introduction The benefits of atropine in the treatment of acute organophosphate (OP) poisoning has been well established, while that of oximes is still uncertain. Pralidoxime is the most often used oxime worldwide. In vitro experiments have consistently shown that oximes are effective reactivators of human acetylcholinesterase enzyme, inhibited by OP compounds. However, the clinical benefit of pralidoxime is still unclear. A recent meta-analysis has found that pralidoxime provides no significant improvement in outcome and rather may cause harm while increasing the economic burden in low-income communities where its use is the most prevalent. Objectives This study aimed to provide an updated evaluation of the efficacy of pralidoxime in addition to atropine alone in the treatment of patients with acute OP poisoning in terms of mortality, need for ventilator support, and the incidence of intermediate syndrome. The intermediate syndrome is a clinical syndrome that occurs 24 to 96 hours after the ingestion of an OP compound and is characterized by prominent weakness of neck flexors, muscles of respiration, and proximal limb muscles.  Materials and methods We searched MEDLINE, EMBASE, CENTRAL, and ClinicalTrials.gov databases until January 2019 for randomized controlled trials (RCTs) in the English language that evaluated the use of pralidoxime in individuals of any age, gender or nationality presenting with an alleged history of OP intake. The primary outcome was mortality. Secondary outcomes were the need for ventilator support and the incidence of intermediate syndrome. The risk of bias in included studies was assessed using the tool recommended by the Cochrane Handbook of Systematic Review of Interventions. Treatment/control differences in these outcomes across included studies were combined using risk ratios (RR). Results Six randomized controlled trials (n = 646) fulfilled the inclusion criteria, including one further trial missed from the most recent systematic review. The risk of bias varied across studies, with Eddleston 2009 being of the lowest risk and Cherian 2005 being of high risk. The risk of mortality (RR = 1.53, 95% confidence interval (CI) 0.97 to 2.41, P = 0.07) and the need for ventilator support (RR = 1.29, 95% CI 0.97 to 1.71, P = 0.08) were not significantly different between the pralidoxime and the control group. There was a significant increase in the incidence of intermediate syndrome in the pralidoxime group (RR = 1.63; 95% CI 1.01 to 2.62, P = 0.04). Conclusions Based on our meta-analysis of the available RCTs, pralidoxime was not shown to be beneficial in patients with acute OP poisoning. Our findings are consistent with the other literature.

Adherence of Drug Promotional Literatures Distributed by Pharmaceutical Companies to World Health Organization Ethical Criteria for Medicinal Drug Promotion.

BACKGROUND: Drug Promotional Literatures are usually relied upon for drug promotion, however studies have shown them to contain several pitfalls. World Health Organization has time and often revised the guideline to address the issue and World Health Organization Ethical Criteria for Medicinal Drug Promotion was established. Based on this guideline, several regional as well as national guidelines have been formulated. Though laws to regulate drug promotion is existent, studies have shown problems with drug promotional literatures in Nepal also. This study was carried out to analyse the drug promotional literatures distributed by pharmaceutical companies in Nepal as per World Health Organization Ethical Criteria for Medicinal Drug Promotion. METHODS: A cross-sectional study over a period of one year was conducted at our department. Pharmaceutical companies registered in Department of Drug Administration, Kathmandu and consenting for the study were requested to provide ten unique drug promotional literatures of their products. Collected drug promotional literatures were analysed for inclusion of essential information as per World Health Organization Ethical Criteria for Medicinal Drug Promotion, level of biasness. Different drug promotional literatures were also classified and compared for these aspects. RESULTS: A total of 48 pharmaceutical companies were included in the study. Drug promotional literatures (n = 372) were analysed during the study. Adherence to criteria concerned with positive attributes of the promoted medicine was found to be higher, most of the drug promotional literatures adhered to 5-8 criteria of World Health Organization Ethical Criteria for Medicinal Drug Promotion and were categorised into grade B. Difference in adherence as well as number of biased drug promotional literatures was also seen when drug promotional literatures were compared on different basis. CONCLUSIONS: Adherence to World Health Organization Ethical Criteria for Medicinal Drug Promotion was found to vary when drug promotional literatures were classified as per pharmaceutical company, type of formulation being promoted, type of drug promotional literatures.