Effectiveness of nirmatrelvir/ritonavir (Paxlovid®) in preventing hospitalisation and death among COVID-19 patients: a prospective cohort study.

INTRODUCTION: Previous trials and real-world studies have shown that nirmatrelvir/ritonavir (Paxlovid®) reduces hospitalisation and deaths in symptomatic, high-risk, nonsevere COVID-19 patients. However, there was a scarcity of data on its effectiveness in the local setting. This study aimed to determine the effectiveness of Paxlovid® in reducing hospitalisation and mortality among COVID-19 patients and to identify the types of adverse events that occur after taking Paxlovid®. MATERIALS AND METHODS: A two-arm prospective cohort study was conducted among adult patients with COVID-19 categories 2 and 3 treated with Paxlovid® and a matched control group. A standard risk-stratified scoring system was used to establish Paxlovid® eligibility. All patients who were prescribed Paxlovid® and took at least one dose of Paxlovid® were included in the study. The control patients were selected from a centralised COVID-19 patient registry and matched based on age, gender and COVID-19 stage severity. RESULTS: A total of 552 subjects were included in the study and evenly allocated to the treatment and control groups. There was no statistically significant difference in 28-day hospitalisation after diagnosis [Paxlovid®: 26 (9.4%), Control: 34 (12.3%), OR: 0.74; 95%CI, 0.43-1.27; p=0.274] or all-cause death [Paxlovid®: 2 (0.7%), Control: 3 (1.1%), OR 1.51; 95%CI, 0.25-9.09; p=0.999]. There was no significant reduction in hospitalisation duration, intensive care unit admission events or supplementary oxygen requirement in the treatment arm. Ethnicity, COVID-19 severity at diagnosis, comorbidities and vaccination status were predictors of hospitalisation events. CONCLUSION: In this two-arm study, Paxlovid® did not significantly lower the incidence of hospitalisation, all-cause death and the need for supplemental oxygen. Adverse effects were frequent but not severe. Paxlovid® efficacy varied across settings and populations, warranting further real-world investigations.

Cardiovascular risk factors and LDL subfraction profile in Type 2 diabetes mellitus subjects with good glycaemic control.

OBJECTIVES: To compare cardiovascular risk factors and LDL particle size in well-controlled Type 2 diabetes mellitus and normal subjects. METHODS: Ninety-three Type 2 diabetic males and 186 age-matched, male controls were studied. Glycaemic control was stable for at least 3 months prior to recruitment. None were on insulin or lipid lowering therapy. Anthropometric indices, blood pressure, lipids, glucose, insulin, apolipoprotein A1 and B, LDL subfraction by density ultracentrifugation were obtained after an overnight fast of 10 h. RESULTS: Diabetic subjects (mean HbA(1c) 6.6%+/-0.10) did not differ from controls in total cholesterol levels (5.04+/-0.08 vs. 5.16+/-0.05 mmol/l, respectively) but had lower serum HDL cholesterol (0.98+/-0.03 vs. 1.12+/-0.02 mmol/l, P<0.001), higher serum triglyceride (2.38+/-0.16 vs. 1.80+/-0.08 mmol/l, P<0.001), lower LDL(1) and LDL(2) and higher LDL(3) concentration. An LDL(3) concentration exceeding 100 mg/dl was found in 59.1% of diabetics and 39.1% of non-diabetics (P<0.001). Diabetic subjects also had higher body mass index, waist to hip ratio and insulin resistance (HOMA). Difference in LDL subfraction between groups disappeared after adjustments were made for either triglyceride or HDL cholesterol. CONCLUSION: Well controlled Type 2 diabetes mellitus subjects exhibit an increased cardiovascular burden through low HDL cholesterol and predominance of small, dense LDL particles.

Benefits of micronised Fenofibrate in type 2 diabetes mellitus subjects with good glycemic control.

AIMS: To determine the effects of micronised fenofibrate on lipids and low density lipoprotein (LDL) subfraction in well-controlled diabetic subjects with mild elevations in cholesterol levels. METHODS: Thirty-five male type 2 diabetic subjects with LDL(3) greater than 100 mg/dl and good glycemic control (mean HbA1c 6.7%) were treated with micronised fenofibrate in an open labeled study for 6 months. Anthropometric indices, blood pressure, lipids, glucose, insulin, apolipoprotein A-I and B, and LDL subfraction by density ultracentrifugation were obtained after an overnight fast of 10 h, at the beginning and end of the 6 months treatment period. RESULTS: The blood pressure, waist to hip ratio, body mass index and glycemic control remained unchanged throughout the 6 months study period. Mean serum triglyceride fell from 2.49 to 1.72 mmol/l (33%) whilst HDL cholesterol increased from 0.88 to 0.96 mmol/l (10.8%). There were no significant changes in total or LDL cholesterol. Both LDL(1) and LDL(2) rose significantly whilst the dense LDL(3) fell from a mean of 148 to 85 mg/dl (43% reduction). Fenofibrate changed the LDL subfraction distribution from dense LDL(3) particles towards buoyant LDL(1) and LDL(2) particles in 63% of the subjects. No subjects had elevations in transaminases greater than three-fold or creatine kinase greater than ten-fold from pre-treatment levels. CONCLUSION: Diabetic subjects with mild hypercholesterolemia and good glycemic control may benefit from therapy with micronised fenofibrate because of the reduction in serum triglyceride, elevation in HDL cholesterol and a shift in LDL subfraction towards a non-atherogenic form.

High prevalence of psychiatric morbidity in a medical intensive care unit.

This study seeks to determine the prevalence of psychiatric morbidity within a medical intensive care unit, examine its correlation with the various physiological parameters and delineate any clinical predictors for psychiatric morbidity. Seventy-seven patients who gave informed consent were administered the General Health Questionnaire (GHQ), Acute Physiological And Chronic Health Evaluation II (APACHE II) and thyroid function tests were performed. A high prevalence of psychiatric morbidity was found (36.4%). However, no statistically significant association was found between psychiatric morbidity and gender, age, APACHE II scores and thyroid function indices. Nevertheless, it is hoped that the index of suspicion for psychiatric morbidity can be raised in order to optimise the clinical management of patients within this setting.

Hypertension in the young adult--come feel the pulse.

Hypertension occurring in teenagers and young adults is uncommon. Though the most common form is still essential hypertension, secondary causes are more commonly found here than in older adults. Renal, cardiovascular and endocrine diseases constitute most of these causes. Coarctation of the aorta is the most common cardiovascular cause of hypertension, and its importance lies in the fact that it is correctable, and that its persistence often leads to dangerous complications and early death. The cardinal sign of differential pulse and blood pressures between the upper and lower limbs can be detected clinically. Hence, the importance of a detailed physical examination in all young hypertensives, including palpation of all the pulses, cannot be overemphasized. We present 2 hypertensive young men who were found to have isolated coarctation of the aorta. The lesion in the first patient was located postductally just distal to the left subclavian artery. This area has been found to be the most common site of coarctation. The second patient had an unusual mid-thoracic coarctation. The clinical and radiological features as well as complications are highlighted. In young hypertensive patients, a high index of suspicion may enable the physician to make a timely diagnosis and hence avert the potentially disastrous complications that may arise in undetected cases.

A rational alternative for the diagnosis of diabetes mellitus in high risk individuals.

INTRODUCTIONS: To facilitate early, accurate diagnosis, tests should be easy, cheap and reproducible. We studied volunteers with an increased risk of developing diabetes mellitus (DM) to see if HbA1c levels could replace the oral glucose tolerance test (OGTT) in diagnosing DM. MATERIALS AND METHOD: One hundred and eleven individuals were studied, using the standard oral glucose tolerance test, and simultaneous measurement of HbA1c levels. Receiver operator characteristic (ROC) analysis was performed to assess the sensitivity and specificity of various HbA1c cut-off levels for diagnosing DM. The relationship between fasting plasma glucose (FPG) and DM diagnosis was also investigated. RESULTS: The majority of DM and impaired glucose tolerance (IGT) cases were diagnosed on the basis of two-hour OGTT glucose values. If FPG alone had been used, 29% of the study population with DM or IGT would have been missed. HbA1c cut-off of 6.2% or 6.3% gives the optimal sensitivity and specificity. In linear regression analysis, FPG was found to be a significant predictor of 2-hour OGTT, but only accounted for 45% of the variability of 2-hour OGTT glucose value. CONCLUSIONS: Our data support the view that although HbA1c alone cannot replace the OGTT in the diagnosis of DM, it can still provide a useful guide to rational, cost-effective screening for diabetes mellitus.

The effect of fenofibrate on insulin sensitivity and plasma lipid profile in non-diabetic males with low high density lipoprotein/dyslipidaemic syndrome.

Non-diabetic males, particularly those with very low levels of high density lipoprotein (HDL) type cholesterol and high levels of very low density type lipoprotein (VLDL), are associated with insulin resistance and decreased insulin sensitivity. The evidence that elevation of HDL cholesterol and diminution of triglycerides with drugs, with improvement in insulin sensitivity is still lacking. In the treatment of the dyslipidaemic syndromes with hypolipidaemic drugs, the associated metabolic abnormality of insulin resistance/sensitivity has to be addressed. We investigated the degree of decreased insulin sensitivity in 23 patients with low HDL and/or raised triglycerides by measuring the fasting, first and second hour insulin levels during an oral glucose tolerance test (OGTT) and repeated the measurements after a 6-month course of fenofibrate. The insulin levels were correlated with the OGTT, blood pressure, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides measured before and at the end of the trial. The serum insulin at the second hour of the OGTT fell from 100.79 +/- 42.79 mU/l to 54.56 +/- 25.43 mU/l (P < 0.0005) even though there was no change in the blood glucose level at this point. Our study shows that fenofibrate (Lipanthyl) 300 mg daily significantly raises the pretreatment low HDL cholesterol (from 0.64 +/- 0.1 mmol/l to 0.99 +/- 0.2 mmol/l) as well as lowers the triglyceride level (from 2.17 +/- 1.1 mmol/l to 1.43 +/- 0.64 mmol/l) in patients with low HDL/dyslipidaemic syndrome. The data also support the conclusion that treatment with fenofibrate increases insulin sensitivity as measured by the corresponding insulin levels of the OGTT in the study subjects who presented with very low HDL cholesterol level. There was also a decrease in blood pressure readings in our study subjects. Throughout the trial, there was no significant change in body weight or exercise level in the subjects studied.

Radioiodine (I-131) therapy and the incidence of hypothyroidism.

Radioiodine (I-131) is one of the accepted forms of treatment for thyrotoxicosis. The major drawback of this treatment is the definite incidence of hypothyroidism, which is either early or late, and is cumulative. We set out to analyse the local incidence of this outcome. Patients with hyperthyroidism, treated with radioiodine from 1984 to end of 1989, and still on follow-up with the Department of Nuclear Medicine, Singapore General Hospital were analysed for the incidence of hypothyroidism. Three hundred and eighty-two patients were analysed (305 females, 77 males). Their ages ranged from 14 to 85 years (mean 48.2, SD 11.1 years). The doses of radioiodine ranged from 4 to 18 mCi (mean 7.6 mCi, SD 1.8 mCi). Two hundred and sixty-two patients who received I-131 only required a single dose, while 87 needed one repeated dose of I-131, and 33 needed more than 2 doses. Of the 382 patients, 271(70.9%) became clinically hypothyroid, 6 (1.6%) were subclinically hypothyroid, 100 (26.7%) were euthyroid and 3 (0.8%) remained hyperthyroid. One hundred and eighty-one patients (47.4%) were clinically hypothyroid at the end of 1 year, and an average rise of 4.8% per year was observed from the second to the fifth year. From the sixth year onwards, the average incidence of hypothyroidism was 1% per year. I-131 is indeed an effective means of controlling thyrotoxicosis (99.2% were no longer hyperthyroid). The main problem with this treatment is hypothyroidism, and this is easily managed with L-thyroxine.

Carbimazole-induced agranulocytosis--a report of 2 recent cases.

Carbimazole is a useful antithyroid drug with a rare potentially fatal complication of agranulocytosis. We report 2 cases presenting with this problem. One was treated supportively with barrier nursing and broad spectrum antibiotics, and the other needed use of a haemopoietic growth factor, granulocyte colony stimulating factor (G-CSF). As it is indeed possible for thyrotoxic patients who developed agranulocytosis with carbimazole to have the same complication with propylthiouracil, once agranulocytosis had resolved, both patients were treated with radioiodine to maintain euthyroidism. Carbimazole-induced agranulocytosis usually spontaneously resolves within 1 to 2 weeks of stopping the drug. The use of haemopoietic growth factors to stimulate the proliferation and differentiation of progenitor cells, accelerates neutrophil recovery, as in our first case discussed. We recognise that agranulocytosis from carbimazole is a rare, life-threatening complication. Instead of awaiting spontaneous recovery, the use of haemopoietic growth factors certainly seems a justifiable option, with a promise of a reduction in morbidity and mortality.

Mortality of patients while on treatment for active tuberculosis.

In the era of effective antituberculous chemotherapy, some patients with tuberculosis still die while on treatment. The aim of this study was to review deaths occurring in patients while on treatment for active tuberculosis in Alexandra Hospital during the 4-year period from 1991 to 1994. Medical records of 30 such patients were reviewed retrospectively. Twenty-one patients were certified as dying from tuberculosis; in the remaining 9 patients, the principal cause of death was other than tuberculosis. Of the patients who died of tuberculosis, 7 (33.3%) died within a week and 19 (90.5%) died within a month of initiation of antituberculous treatment. Seventeen (81%) were males and 15 (71%) were smokers. All the 21 patients had pulmonary involvement and in 4 patients, there was disseminated disease. Chest roentgenographic findings of bilateral involvement were seen in 16 (76.2%) patients and of cavitary disease in 15 (71.4%) patients. Eighteen (86%) had a positive sputum smear result. Seven patients received corticosteroid cover. In 14 patients who had their weights recorded at initiation of antituberculous treatment, the mean weight was 36.3 kg (range 25.5k g-47k g). Notable biochemical derangements included hyponatraemia (86%) and hypoalbuminaemia (95%). Plasma cortisol and/or Synacthen stimulation test were performed in 4 patients; none was indicative of adrenal hypofunction. We conclude that death attributed to tuberculosis in patients while on treatment occurs early and is largely due to advanced disease.

Simulated bleeding--a forgotten disease in a land of plenty.

The human body is unable to synthesise Vitamin C and a diet deficient in Vitamin C leads to scurvy. Scurvy may mimic other medical conditions, like bleeding diasthesis or deep vein thrombosis, leading to delay in diagnosis and treatment, thus prolonging sufferings of patients. Often, scurvy could have been diagnosed if it is thought of and features of scurvy carefully looked for. Scurvy is easily treated with high dose of oral vitamin C. Recurrences may occur. Education of care providers cannot be overemphasised. We report three local cases of scurvy to highlight the existence of the disease in our modern society.

Malaria: an audit of 56 cases admitted to a hospital.

A 2-year prospective audit on the profile and outcome of malaria cases admitted to a general hospital was performed. Fifty-six cases were seen from January 1991 to December 1992, 52 of which were due to monoinfections with Plasmodium vivax. The main presenting complaints were fever, chills, sweats, myalgia, dry cough and headache. A significant percentage had anaemia (64.3%), thrombocytopaenia (57.1%), hyponatraemia (42.9%), and liver dysfunction (44.7%). Diagnosis rests on the demonstration of parasites in stained peripheral blood smears. None of the patients developed major complications. A high index of suspicion of malaria must be maintained in the medical evaluation of all patients and in particular, of returning travellers.

Cervicofacial actinomycosis with paravertebral spread: a case report.

We report a case of cervicofacial actinomycosis with paravertebral extension in a 60-year-old man who presented with recurrent neck masses. Diagnosis was confirmed on culture and histology of pus and debris obtained from surgical drainage. He improved only after lengthy in-hospital high dose penicillin therapy. He is currently well and is on maintenance doxycycline therapy for 6 months following the high dose penicillin therapy.

Massive pleural effusion in pancreatitis: 2 case reports.

We report 2 patients with left-sided pleural effusion occurring in the setting of acute pancreatitis. Both patients had a strong history of alcohol consumption. In each case the pleural fluid amylase was markedly elevated, higher than that in the serum. The effusions resolved with closed chest tube drainage and the pancreatitis subsided with conservative therapy. In patients presenting with significant pleural effusions and acute upper abdominal symptoms, a thoracentesis with determination of the amylase titre may provide a quick means of diagnosing acute pancreatitis.

Management of hyperlipidaemia.

Recent community-based studies have shown that hypercholesterolaemia is common in Singapore. High low-density lipoprotein (LDL) cholesterol, low high-density lipoprotein (HDL) cholesterol as well as hypertriglyceridaemia are associated with higher prevalence of cardiovascular disease. The aim of this article is to discuss the clinical management of adult patients with hyperlipidaemia. For practical purposes, the hyperlipidaemias can be divided into four patterns: 1) hypercholesterolaemia with normal triglyceride, 2) moderate hypertriglyceridaemia with normal cholesterol, 3) combined moderate hypercholesterolaemia and hypertriglyceridaemia, and 4) severe hypertriglyceridaemia with moderate hypercholesterolaemia. Each pattern can be attributed primarily to genetic conditions or secondarily to common diseases. It is important to attempt aetiopathogenetic diagnosis for each hyperlipidaemic patient as treatment of an underlying condition may sometimes reverse the hyperlipidaemia eg hypothyroidism and hypercholesterolaemia. In general, a low cholesterol and low fat (particularly saturated fat) diet is useful in patients with all four patterns of hyperlipidaemia. Patients with severe hypertriglyceridaemia and moderate hypercholesterolaemia may benefit from a further drastic reduction in fat intake. Pharmacological therapy is required for patients who do not achieve target lipid levels after diet modification. The choice of drug therapy is, to a large extent, dependent on the pattern of hyperlipidaemia. In some situations, combination drug therapy may be required. Caution is required in combining hypolipidaemic drugs as the side-effects of individual drugs may be potentiated when used in combination.

Metabolic abnormalities in young non-obese males with hypertension.

Essential hypertension has been shown by various studies to be an insulin-resistant state. However, most of these studies have included obese and elderly patients. We were interested to know the extent of insulin resistance in a group of young, non-obese patients with hypertension. A total of 59 male patients with essential hypertension and 31 controls matched for age, sex and body mass index were studied. All the subjects were under 35 years old and had a body mass index of less than 27 kg/m2. Our results showed that such patients with hypertension had significantly higher fasting insulin, total insulin after glucose challenge, insulin/glucose ratio and higher triglycerides than the control subjects.

Massive haemothorax as a complication of primary lung cancer--a case report.

A 58-year-old man was admitted with a massive haemothorax. At thoracotomy, the cause was found to be due to a bleeding primary lung cancer, the cell type of which was adenocarcinoma. A literature search revealed that this complication of lung cancer has not previously been described. Reasons as to the infrequency of this complication are discussed.

Diabetic ketoacidosis--a study of 33 episodes.

Twenty-six patients presenting with 33 episodes of Diabetic Ketoacidosis (DKA) and managed on a protocol oriented system were analysed. Diabetes mellitus was newly diagnosed at presentation in 18% of the 33 episodes. The presenting symptoms were polyuria and polydipsia (58%), nausea and vomiting (52%), change in sensorium (24%), hyperventilation (24%), and abdominal pain (18%). The main clinical findings at admission were dehydration (97%), acidotic respiration (67%), coma and confusion (61%), a clinically detectable source of sepsis (49%), fever (33%) and hypotension (9%). Blood sugar levels at admission ranged between 351 mg/dl and 1200 mg/dl (mean = 633 mg/dl). The mean serum potassium at diagnosis was 5.1 mmol/l and the mean calculated serum osmolality was 320 mOsm/kg. The mean serum osmolality was higher in those with disturbed conscious level. Infections, particularly those of the urogenital tract, were the main precipitating cause for the DKA. Only 12 of the 19 patients with sepsis had fever. Eight of the episodes were attributed to patients' non-compliance with insulin. Four patients died during the 33 hospitalisations, giving a mortality rate of 10%. Death occurred despite glucose control and stabilisation of the ketoacidotic state and was due to uncontrolled septicaemia. The mean duration of hospitalisation was 11 days. The ketoacidosis state was reversed after a mean duration of 9.5 hours, with an average soluble insulin requirement per patient of 52.4 units.

Pasteurella multocida septicaemia following a dog bite.

Bite wounds are often mistakenly considered innocuous. However, they are frequently complicated by infection which may be serious. We describe a case of Pasteurella multocida septicaemia with myopericarditis following a dog bite. Treatment of the infection as well as active support of myocardial function led to a successful outcome.