Physiological Effects of Sildenafil Versus Placebo at High Altitude: A Systematic Review.

Poudel, Sangeeta, Sandesh Gautam, Purushottam Adhikari, and Ken Zafren. Physiological effects of sildenafil versus placebo at high altitude: a systematic review. High Alt Med Biol. 25:16-25, 2024. Introduction: High altitude pulmonary edema (HAPE), a life-threatening condition that affects individuals ascending to high altitude, requires the development of pulmonary hypertension. Sildenafil can be used to prevent and treat HAPE, presumably by decreasing pulmonary artery pressure (PaP). We compared the physiological effects of sildenafil versus placebo at high altitude (above 2,500 m), including the effects on PaP. Methods: We performed a systematic search of PubMed, EMBASE, and Cochrane CENTRAL for randomized controlled studies of the physiological effects of sildenafil in hypoxia in healthy individuals. We conducted a systematic review of all studies meeting our criteria. Results: Of the 14 studies that met the inclusion criteria, 8 were hypobaric hypoxia studies. Six studies reported data at rest at altitudes from 3,650 to 5,245 m. Two were simulations reporting exercise data at equivalent altitudes of 2,750-5,000 m. Nine studies used normobaric hypoxia corresponding to altitudes between 2,500 and 6,400 m. One reported only rest data, two reported rest and exercise data, and the others reported only exercise data. Sildenafil significantly reduced PaP at rest and exercise in hypobaric or normobaric hypoxia. There were no significant differences between arterial oxygen saturation (SpO2) with sildenafil in hypobaric or normobaric hypoxia at rest or exercise. There were no significant differences in heart rate or mean arterial pressure (MAP) at rest or exercise and cardiac output during exercise in hypobaric or normobaric hypoxia. Conclusions: Sildenafil significantly reduces PaP at rest and exercise in normobaric or hypobaric hypoxia. Sildenafil has no significant effects on SpO2, heart rate, cardiac output (during exercise), or MAP at rest or exercise in hypobaric or normobaric hypoxia.

Clinicopathological Profile of Dengue Infection in a Tertiary Care Centre in Nepal.

BACKGROUND: Dengue is a mosquito-borne viral disease with a wide spectrum of presentations ranging from subclinical disease to severe dengue. Dengue is endemic to the Terai of Nepal. Interestingly, an increasing incidence has been reported from hilly areas like Kathmandu valley. This study explored the clinicopathological profile of dengue infection. METHODS: A total of 84 serologically confirmed dengue cases from September to November 2019 at KIST Medical College were recruited in a cross-sectional study after obtaining ethical approval. Dengue was categorized as dengue without warning signs, dengue with warning signs, and severe dengue. Clinicopathological information was recorded in the proforma by reviewing patients' records. A descriptive statistical tool and chi-square test were carried out. RESULTS: Out of 84 patients, 76% (64) were dengue without warning signs, 21.4% (18) were dengue with warning signs and 2.4% (2) were severe dengue. About 97.6% (82) presented with fever. During the course of illness, anemia was identified in 38.1% (32), thrombocytopenia in 65.5% (55), hemoconcentration in 6% (5), and leucopenia in 82.1% (69). Similarly, elevated aspartate transaminase and alanine transaminase (ALT) was observed in 67.7% (42) and 53.2% (33) respectively. The severity of dengue on presentation to hospital was significantly associated with thrombocytopenia, leucopenia, and elevated ALT. Similarly, the severity during course of illness in hospital was significantly associated with hemoconcentration, thrombocytopenia, leucopenia, and elevated ALT. CONCLUSIONS: Most common presentation of dengue infection was fever. The most common laboratory abnormalities were leucopenia, thrombocytopenia, hemoconcentration, anemia, and elevated liver enzymes. Awareness of these clinical and laboratory parameters is important for the prompt diagnosis, severity estimation, and overall management of dengue infection.

Effectiveness of Clinical Presentation (CP) Curriculum in teaching clinical medicine to undergraduate medical students: A cross-sectional study.

Introduction: The Clinical Presentation (CP) curriculum was first formulated in 1990 at the University of Calgary, Canada. Since then, it has been adopted at various medical schools, including Patan Academy of Health Sciences (PAHS), a state-funded medical school in a low-income country (LIC), Nepal. This study aims to evaluate the perceived effectiveness of the CP curriculum by students and faculty at PAHS, and test knowledge retention through a surprise non-routine exam administered to students.  Method: This is a cross-sectional study to evaluate the efficacy of the CP curriculum in teaching clinical medicine to the first batch of MBBS students of PAHS School of Medicine. Ethical approval was obtained from the Institutional Review Committee (IRC)-PAHS (Ref no std1505911069). Perceived effectiveness was evaluated using a set of questionnaires for faculty and students. A total of 33 students and 34 faculty filled the perception questionnaires. Subsequently, a questionnaire consisting of 50 Multiple Choice Questions (MCQs) from different clinical medicine disciplines was administered to test students' knowledge retention. Out of 49 students, 38 participated in the surprise non-routine exam.   Result: A significantly higher number of faculty preferred the CP curriculum compared to the traditional system of teaching clinical medicine (16 vs 11, Kruskal Wallis: 0.023, ie. P-value < 0.05). A significantly higher number of the students liked and recommended CP curriculum in the clinical year of medical education (20 vs. 13 with p-value < 0.05). In the non-routine surprise exam, two thirds of the students scored 60% or above.  Conclusion: Both faculty and students perceive that the CP curriculum system is an effective teaching and learning method in medical education, irrespective of their different demographic and positional characteristics. The students' overall performance was good in surprise, non-routine exams taken without scheduling or reminders.

Performance and preference of problem-based learning (PBL) and lecture-based classes among medical students of Nepal.

Background: PBL (problem based learning) is new active learning educational strategy that has been extensively tested and used in recent years. Patan Academy of Health Sciences (PAHS) is one of medical schools from Nepal, a Low Income Country (LIC) implementing PBL for undergraduate medical education. This study aims to compare PAHS students' understanding and knowledge retention when taught through PBL and lecture-based classes and compare students' perceptions of PBL and lectures in medical education. Methods: This is a cross-sectional study of medical students of a PBL based medical school in Nepal, a non-Western low-income country. Ethical approval was given by the institutional research committee of the Patan Academy of Health Sciences. Understanding and knowledge retention was assessed with 50 vignette-based multiple-choice questions, half of which were taught through PBL sessions, and the remaining half were taught in didactic lectures during basic science years of medical school. A separate pre-validated perception questionnaire was used to assess students' preferences regarding PBL and lectures. Results: Out of 107 students, 99 participated in the understanding and knowledge retention questionnaires and 107 completed perception questionnaires. Understanding and knowledge retention of students was found to be the same for topics taught by PBL and lectures, with median scores of 17 and s16, respectively. PBL were mostly preferred for the physiology (59.81%), pathology (51.40%) and pharmacology (53.27%) concepts, and lectures were mostly preferred for the anatomy (78.50%), biochemistry (45.79%), and microbiology (42.99%) topics. Students wanted the same concepts to be taught through both PBL and lectures, especially for anatomy. Conclusions: Understanding and knowledge retention is the same for topics taught by either PBL or lectures during the basic science years of undergraduate medical education. Students prefer PBL for physiology, pathology, and pharmacology-related concepts, conventional didactic lecture for physiology and microbiology, and a combination of lecture and PBL sessions for anatomy.

Unilateral Facial Palsy at High Altitude: A Case Report.

Poudel Sangeeta, Bibechan Thapa, Saroj Adhikari Yadav, and Brenton Systermans. Unilateral facial palsy at high altitude: a case report. High Alt Med Biol. 22:426-428, 2021.-The facial nerve has a long and tortuous route predisposing it to palsy or paresis. Bell's palsy is the most common cause of facial nerve palsy. Most often Bell's palsy is self-limited but it is very crucial to rule out other causes and provide prompt treatment accordingly. Some causes of facial palsy that are specific to high altitude include hypoxia, cold weather, vitamin D deficiency, and high-altitude cerebral edema. Health facilities and diagnostic tools are compromised in resource-limited settings such as at high altitudes. This leads to a diagnostic dilemma, possibly delaying targeted treatment, and resulting in poorer outcomes. Clinical diagnosis plays an important role in such settings. The immediate descent and initiation of steroids improve the condition in many cases. In this article, we discuss the case of a Sherpa who presented to the Everest emergency clinic during the 2021 climbing season with unilateral facial palsy.

Diploma in Mountain Medicine: A Perspective of a Female Doctor from Nepal.

Poudel, Sangeeta. Diploma in mountain medicine: a perspective of a female doctor from Nepal. High Alt Med Biol. 22:417-419, 2021.-Mountaineering is an alluring recreation receiving increasing global attention. With increasing adventure activities in the mountain, the risk of mishaps is high. Each year many trekkers, athletes, pilgrims, and porters are significantly affected and some even lose their lives due to a lack of knowledge in identification and management of altitude illness and other traumatic injuries. The diploma in mountain medicine (DiMM) trains participants in high-altitude environments to access area safety, diagnose, treat, and evacuate victims using available resources, improvised techniques, and rope skills. Doctors willing to work in the wilderness have to work in austere medical clinics, participate in search and rescues, volunteer at sporting events, or work on an expedition often being the only available doctor. Despite challenges, mountain doctors work in the wilderness as a hobby and some make a career of it, as in certain countries mountain medicine is now recognized as a subspeciality. As it becomes more accessible, the mountain medicine course is becoming increasingly popular, with the course in Nepal being no exception. It is developed as a specialty in developed countries, whereas in developing countries it will soon reach maturity. This is a personal report of a young female doctor taking part in a DiMM course in 2019 from Nepal.

Pharmacotherapies in Heart Failure With Preserved Ejection Fraction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Heart failure (HF) with preserved ejection fraction (HFpEF) causes significant cardiovascular morbidity and mortality. It is a growing problem in the developed world, especially, in the aging population. There is a paucity of data on the treatment of patients with HFpEF. We aimed to identify pharmacotherapies that improve peak oxygen consumption (peak VO2), cardiovascular mortality, and HF hospitalizations in patients with HFpEF. METHODS: We conducted a systematic literature search for English studies in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, Scopus, and Google scholar. We searched databases using terms relating to or describing HFpEF, stage C HFpEF, and diastolic HF and included only randomized controlled trials (RCTs). RevMan 5.4 (The Cochrane Collaboration, 2020, London, UK) was used for data analysis, and two independent investigators performed literature retrieval and data-extraction. We used PRISMA guidelines to report the outcomes. We included 14 articles in our systematic review and six studies in meta-analysis. RESULTS: We calculated the pooled mean difference (MD) of peak VO2 between placebo and pharmacotherapies. Our meta-analysis showed that the peak VO2 was comparable between pharmacotherapies and placebo in HFpEF (MD = 0.09, 95% CI: -0.11, 0.30, I2 =28%). Our systematic review highlights that statins and spironolactone use should be further studied in larger RCTs due to their potential beneficial effect on all-cause mortality and hospitalizations, respectively. CONCLUSION: Compared to placebo, none of the pharmacotherapies significantly improved peak VO2 in HFpEF except ivabradine. In our meta-analysis, the pooled improvement in peak VO2 is non-significant. This needs validation with larger studies. We are lacking larger studies on pharmacotherapies that improve peak VO2 in HFpEF. Statin and spironolactone should be further studied in patients with HFpEF as few trials have shown improvement in all-cause mortality and reduction in HF hospitalizations in selected patients, respectively.