OBJECTIVES: This study aimed to investigate the genetic architecture of EOPD in a multi-ethnic Malaysian cohort.
METHODS: 161 index patients with PD onset ≤50 years were recruited from multiple centers across Malaysia. A two-step approach to genetic testing was used, combining a next-generation sequencing-based PD gene panel and multiplex ligation-dependent probe amplification (MLPA).
RESULTS: Thirty-five patients (21.7%) carried pathogenic or likely pathogenic variants involving (in decreasing order of frequency): GBA1, PRKN, PINK1, DJ-1, LRRK2, and ATP13A2. Pathogenic/likely pathogenic variants in GBA1 were identified in thirteen patients (8.1%), and were also commonly found in PRKN and PINK1 (11/161 = 6.8% and 6/161 = 3.7%, respectively). The overall detection rate was even higher in those with familial history (48.5%) or age of diagnosis ≤40 years (34.8%). PRKN exon 7 deletion and the PINK1 p.Leu347Pro variant appear to be common among Malay patients. Many novel variants were found across the PD-related genes.
CONCLUSIONS: This study provides novel insights into the genetic architecture of EOPD in Southeast Asians, expands the genetic spectrum in PD-related genes, and highlights the importance of diversifying PD genetic research to include under-represented populations.
METHODS: Parameters influencing corticosteroid (CS) dosing were identified (step 1). Data from children with proliferative LN were used to generate patient profiles (step 2). Physicians rated changes in renal and extrarenal childhood-onset SLE activity between 2 consecutive visits and proposed CS dosing (step 3). The SSR was developed using patient profile ratings (step 4), with refinements achieved in a physician focus group (step 5). A second type of patient profile describing the course of childhood-onset SLE for ≥4 months since kidney biopsy was rated to validate the SSR-recommended oral and intravenous (IV) CS dosages (step 6). Patient profile adjudication was based on majority ratings for both renal and extrarenal disease courses, and consensus level was set at 80%.
RESULTS: Degree of proteinuria, estimated glomerular filtration rate, changes in renal and extrarenal disease activity, and time since kidney biopsy influenced CS dosing (steps 1 and 2). Considering these parameters in 5,056 patient profile ratings from 103 raters, and renal and extrarenal course definitions, CS dosing rules of the SSR were developed (steps 3-5). Validation of the SSR for up to 6 months post-kidney biopsy was achieved with 1,838 patient profile ratings from 60 raters who achieved consensus for oral and IV CS dosage in accordance with the SSR (step 6).
CONCLUSION: The SSR represents an international consensus on CS dosing for use in patients with childhood-onset SLE and proliferative LN. The SSR is anticipated to be used for clinical care and to standardize CS dosage during clinical trials.
METHODS: This study encompassed children born in the Auckland region (New Zealand) with a newborn screen TSH level of 8 to 14 mIU/L blood, age 6.9 to 12.6 years at assessment, and their siblings. Thyroid function tests (serum TSH and free thyroxine) and neurocognitive assessments were performed, including IQ via the Wechsler Intelligence Scale for Children, fourth edition.
RESULTS: Ninety-six mTSHe individuals were studied, including 67 children recruited with 75 sibling controls. Mean mTSHe newborn TSH level was 10.1 mIU/L blood and 2.4 mIU/L at assessment (range, 0.8-7.0 mIU/L, serum). Although higher newborn TSH levels in the mTSHe group correlated with lower full-scale IQ scores (r = 0.25; P = .040), they were not associated with the magnitude of the IQ difference within sibling pairs (P = .56). Cognitive scores were similar for mTSHe and controls (full-scale IQ 107 vs 109; P = .36), with a minor isolated difference in motor coordination scores.
CONCLUSIONS: Our data do not suggest long-term negative effects of neonatal mild TSH elevation. TSH elevation below the screen threshold appears largely transient, and midchildhood neurocognitive performance of these children was similar to their siblings. We propose that associations between neonatal mild TSH elevation and IQ are due to familial confounders. We caution against the practice of reducing screening CH cutoffs to levels at which the diagnosis may not offer long-term benefit for those detected.
CASE REPORT: A 91 year old lady presented with an acute manic relapse for the past 2 weeks. She was previously on oral Sodium Valproate, and during this current admission was augmented with oral Quetiapine IR 100 mg bd. She remained unwell and was planned for right unilateral ECT with age-based dosing stimuli. After only 4 sessions, she showed complete resolution of her manic symptoms.
RESULT: In our case study, the patient showed rapid response to right unilateral ECT. Even though the Post Suppression Index (PSI) was not significant, there is some evidence that in elderly patients, burst suppression (not measured in this case) may be more accurate measure of ECT efficacy. The transient treatment emergent delirium was short lived and ECT was very tolerated in this patient.
CONCLUSION: Clinicians should not delay ECT in old-old patients who do not respond to pharmacologic treatment, as early switch to ECT results in rapid response with good safety profile.
MATERIALS AND METHODS: A retrospective review of patients who underwent horizontal strabismus surgery between 2013 and 2017 in Hospital Universiti Sains Malaysia was conducted. Surgery was considered successful if the post-operative deviation was within 10 prism diopters at 6 months' postoperative period. Factors influencing the outcome of surgery at 6 months were identified. Chi-square and Fisher's exact tests were used in data analysis.
RESULTS: Ninety-eight patients were included. Both genders were equally affected. Exotropia (58.2%) was the most common type. About 65.3% of patients had alternating strabismus, while 51% had an angle of deviation of more than 45 prism diopters. Amblyopia was documented in 14.3% of patients. Those operated on below 10 years of age comprised 64.3%. Ninety-four patients completed follow-ups at 6 months after the surgery. The success rate was 81.6%. Approximately 92% of the patients had best-corrected visual acuities of 6/12 and better at 6 months' postoperative period. There was no significant association between age of onset, gender, presence of amblyopia, type of deviation, amount of deviation, and postoperative best-corrected visual acuity with surgical outcome at 6 months' postoperative period (P > 0.05).
CONCLUSION: The success rate was good. Postoperative best-corrected visual acuity was promising. Age of onset, gender, presence of amblyopia, type of deviation, amount of deviation, and postoperative best-corrected visual acuity did not influence the outcome of horizontal strabismus surgery in our review.
SUMMARY: This study examined country-specific prevalence and incidence data of youth-onset T2D published between 2008 and 2019, and searched for national guidelines to expand the understanding of country-specific similarities and differences. Of the 1,190 articles and 17 congress abstracts identified, 58 were included in this review. Our search found the highest reported prevalence rates of youth-onset T2D in China (520 cases/100,000 people) and the USA (212 cases/100,000) and lowest in Denmark (0.6 cases/100,000) and Ireland (1.2 cases/100,000). However, the highest incidence rates were reported in Taiwan (63 cases/100,000) and the UK (33.2 cases/100,000), with the lowest in Fiji (0.43 cases/100,000) and Austria (0.6 cases/100,000). These differences in epidemiology data may be partly explained by variations in the diagnostic criteria used within studies, screening recommendations within national guidelines and race/ethnicity within countries. Key Messages: Our study suggests that published country-specific epidemiology data for youth-onset T2D are varied and scant, and often with reporting inconsistencies. Finding optimal diagnostic criteria and screening strategies for this disease should be of high interest to every country.
TRIAL REGISTRATION: Not applicable.
OBJECTIVE: This study aims to (1) measure the cost of health resources utilization by MS patients and (2) to examine the difference in utilization and its attributed costs amongst patients who may have a different course of MS and expanded disability status scale (EDSS) scores.
METHODS: A cross-sectional study using Kuwait National MS registry was conducted to estimate the costs of utilization of resources from 2011 to 2015.
RESULTS: Between the period 2011-2015, 1344 MS patients were included in the registry. The average annual cost per MS patient has increased from $10,271 in 2011 to $17,296 in 2015. Utilization of disease-modifying therapies (DMTs) was the main driver of costs reaching 89.9% in 2015. Throughout the five-year period, the occurrence of relapses decreased from 21.8% to 12.2% (p <0.0001). During this same period, ambulatory relapse treatment increased by 5.8% while hospitalizations decreased by 2.6%. Patients with a moderate EDSS score (3.5-6) had the highest average cost (p<0.0001) compared to mild and severe EDSS scores.
CONCLUSIONS: Multiple sclerosis has been a significant economic burden on the Kuwait healthcare system. DMTs are the main driver of cost.
METHODS: This was a cross-sectional study carried out from September 2016 to August 2017 at three tertiary hospitals in Northern Peninsular Malaysia.
RESULTS: A total of 62 patients were recruited, 83.9% of whom were male. The mean age was 29.2 with the median age of onset at 18 years old. The median duration of delay in diagnosis was 3 years. A quarter of them had positive family history. Nearly three-quarters were overweight and obese. About 12/62 (19.4%) had MetS, and it was comparable to healthy controls (15/62, 24.2%). HS patients had a significant higher risk of low-high-density lipoprotein (HDL) and obesity. Based on Hurley staging, 15/62 (24.2%) were in stage I, 38/62 (61.3%) and 9/62 (14.5%) in stages II and III, respectively. However, sonographic scoring showed 50% had severe stage of disease, and 56.9% of the patients had subclinical lesions. There was only a fair agreement between ultrasonography and Hurley staging of disease severity (k = 0.25; P = 0.004).
CONCLUSION: There was a male preponderance among HS patients in Northern Peninsular Malaysia with early age of onset and more severe disease. Only one-fifth had MetS, but they had significantly higher risks of obesity and low HDL. Ultrasonography examination was useful to detect subclinical lesions and providing a better understanding on disease severity.