Efficacy and safety of ivermectin in patients with mild COVID-19 in Japan and Thailand.

BACKGROUND: Ivermectin is an antiparasitic drug administered to hundreds of millions of people worldwide. Fundamental research suggests that ivermectin is effective against coronavirus disease 2019 (COVID-19); therefore, we investigated the efficacy and safety of ivermectin as a COVID-19 treatment option. METHODS: This multi-regional (Japan and Thailand), multicenter, placebo-controlled, randomized, double-blind, parallel-group, Phase III study evaluated the efficacy and safety of ivermectin in patients with mild COVID-19 (IVERMILCO Study). The participants took a specified number of the investigational product (ivermectin or placebo) tablets of, adjusted to a dose of 0.3-0.4 mg/kg, orally on an empty stomach once daily for three days. The primary efficacy endpoint was the time at which clinical symptoms first showed an improving trend by 168 h after investigational product administration. RESULTS: A total of 1030 eligible participants were assigned to receive the investigational product; 502 participants received ivermectin and 527 participants received a placebo. The primary efficacy endpoint was approximately 96 h (approximately four days) for both ivermectin and placebo groups, which did not show statistically significant difference (stratified log-rank test, p = 0.61). The incidence of adverse events and adverse drug reactions did not show statistically significant differences between the ivermectin and placebo groups (chi-square test, p = 0.97, p = 0.59). CONCLUSIONS: The results show that ivermectin (0.3-0.4 mg/kg), as a treatment for patients with mild COVID-19, is ineffective; however, its safety has been confirmed for participants, including minor participants of 12 years or older (IVERMILCO Study ClinicalTrials.gov number, NCT05056883.).

Clinical analysis of adult-onset spinocerebellar ataxias in Thailand.

BACKGROUND: Non-ataxic symptoms of spinocerebellar ataxias (SCAs) vary widely and often overlap with various types of SCAs. Duration and severity of the disease and genetic background may play a role in such phenotypic diversity. We conducted the study in order to study clinical characteristics of common SCAs in Thailand and the factors that may influence their phenotypes. METHODS: 131 (49.43%) out of 265 Thai ataxia families with cerebellar degeneration had positive tests for SCA1, SCA2, Machado-Joseph disease (MJD) or SCA6. The study evaluated 83 available families including SCA1 (21 patients), SCA2 (15), MJD (39) and SCA6 (8). Comparisons of frequency of each non-ataxic sign among different SCA subtypes were analysed. Multivariate logistic regression analyses were undertaken to analyze parameters in association with disease severity and size of CAG repeat. RESULTS: Mean ages at onset were not different among patients with different SCAs (40.31 ± 11.33 years, mean ± SD). Surprisingly, SCA6 patients often had age at onset and phenotypes indistinguishable from SCA1, SCA2 and MJD. Frequencies of ophthalmoparesis, nystagmus, hyperreflexia and areflexia were significantly different among the common SCAs, whilst frequency of slow saccade was not. In contrast to Caucasian patients, parkinsonism, dystonia, dementia, and facial fasciculation were uncommon in Thai patients. Multivariate logistic regression analysis demonstrated that ophthalmoparesis (p < 0.001) and sensory impairment (p = 0.025) were associated with the severity of the disease. CONCLUSIONS: We described clinical characteristics of the 4 most common SCAs in Thailand accounting for almost 90% of familial spinocerebellar ataxias. There were some different observations compared to Caucasian patients including earlier age at onset of SCA6 and the paucity of extrapyramidal features, cognitive impairment and facial fasciculation. Severity of the disease, size of the pathological CAG repeat allele, genetic background and somatic heterogeneity of pathological alleles may influence clinical expressions of these common SCAs.

Hypokalemic periodic paralysis as a manifestation of thyrotoxicosis.

OBJECTIVE: To study the clinical characteristics of patients who suffer from hypokalemic periodic paralysis, as the presenting symptoms of thyrotoxicosis. MATERIAL AND METHOD: A retrospective review of 29 patients who presented with the syndrome of hypokalemic periodic paralysis as the symptom of thyrotoxicosis at Ratchaburi Hospital between January 1,1995 and December 31, 2007. Patients'data, diagnosis, blood chemistry, and thyroid function test were collected from medical records. RESULTS: All patients exhibited muscle weakness for a duration of one to two days, while all patients with hypokalemic periodic paralysis were determined to have high serum thyroid hormone and diagnosed with thyrotoxicosis. Patients with hypokalemic periodic paralysis were the first symptom leading to diagnosis of thyrotoxicosis. The attack of weakness occurred during the night in all patients. The patients, 96.6% being male, showed improvement of their symptoms through potassium replacement and thyrotoxicosis treatment using propylthiouracil and non selective beta adrenergic blocker All patients recovered and did not demonstrate reoccurring hypokalemic periodic paralysis. The degree of muscle weakness was found to correlate significantly (p < 0.05) with level of serum potassium, magnesium, and duration of weakness. CONCLUSION: It is important to determine blood thyroid hormone in all patients with hypokalemic periodic paralysis.

Epilepsia partialis continua as a manifestation of hyperglycemia.

A review of 22 patients who presented with the syndrome of epilepsia partialis continua as symptoms of hyperglycemia and occurred during the phase of hyponatremia and mild hyperosmolality. Epilepsia partialis continua persisted for an average of 9 days,and its duration correlated with the degree of hyponatremia, low blood urea nitrogen(BUN) and measured serum osmolality. In all patients, epilepsia partialis continua was the first symptom leading to the diagnosis of diabetes mellitus. The epilepsia partialis continua ceased by normalization of blood glucose level. All patients survived and did not have any complications. The majority of the patients had evidence of a localized structural brain lesions and low serum sodium. Metabolic abnormalities including hyperglycemia,mild hyperosmolality and hyponatremia contribute to the development of epilepsiapartialis continua in an area of focal brain damage. It is important to determine blood glucose levels in all cases of epilepsia partialis continua.

Prognosis in hypoxic ischemic encephalopathy.

A retrospective review of survivors of cardiopulmonary arrest included 56 patients. Twenty two had a good outcome and thirty four were seriously impaired. Depth and duration of post arrest coma correlated significantly with poor neurologic outcome. Seventy percent of the seriously impaired patients never regained consciousness and non emerged from coma within five days; all of the patients with good outcome were alert within twenty hours after resuscitation. Coma, motor unresponsiveness, absent brainstem reflexes were closely associated with dismal prognosis for neurologic outcome. This study cannot provide a basis for discontinuation of life support at any specific time.

Outcome after transsternal radical thymectomy for myasthenia gravis: 14-year review at Ratchaburi Hospital.

OBJECTIVE: To determine predictability factors, clinical features and outcome in the patients after transsternal radical thymectomy (TRT) for Myasthenia Gravis (MG). METHOD: A 14-year retrospective review (1990-2004) and analysis of medical data on 32 patients with MG who underwent TRT. Two patients were lost to follow-up. Preoperative medication included anticholinesterase drugs and steroids. Plasmaphereses were used in 2 cases before operation. The modified Osserman clinical classification (Table 1) was used to define disease severity. The status of the patients was evaluated as follows: A (remission), B (improvement), C (no change), D (deterioration), E (death due to myasthenia gravis). Using univariate analysis, sex, age, onset, Osserman class and pathology correlated with outcome and statistical significance is defined as P < 0.05. RESULTS: Among the 30 patients in the present study with MG who underwent TRT women comprised 70% (21 of 30 patients), and mean age was 42.87 +/- 12.16 year (19-65 years). The preoperative duration of the disease ranged from 0.5 to 120 months (mean = 25.72 +/- 30.68 months). Clinical statuses of patients as assessed on initial evaluation were 13 patients (43.3%) were in class IIA, 6 (20%) in class IIB, and 11 (36.7%) in class III. (Table 2) The histology of thymus glands consisted of hyperplasia in 22 patients, normal in 2, atrophic thymus in 3, thymomas in 3, (2 were malignant thymomas). Hospital mortality was 0, but 9-month mortality was 3.33% (1 of 30 patients). The mean follow-up period was 41.80 +/- 53.89 months. Complete remission (A) was achieved in 40% of patients (12 of 30), and marked improvement (B) of MG in 40% (12 of 30), for a total benefit rate of 80%. 6.7% (2 of 30) were unchanged (C), 10% (3 of 30) were worse (D) and 3.3% died because of MG (E). Using univariate analysis on sex, clinical status by Osseman classification, and histopathology correlated significantly with outcome (P < 0. 05); 95.2% of women (20 of 21) benefited from the procedure, versus 44.4% of men (4 of 9). 100% (19 of 19) of patients in class IIA and IIB benefited from the procedure, versus 45.5% (4 of 9) of patients in class III. All patients with thymoma presented a less favorable outcome (deteriorated in 2, and died in 1) versus 11.1% (3 of 24) of patients without thymomas were deteriorated. CONCLUSION: The remission and improvement in 80% of patients suggested that adequate thymic tissue were removed with radical thymectomy. Female, absence of thymoma, thymic hyperplasia, patients in class IIA, and IIB (non-respiratory involvement) are favorable predictability prognostic factors.