Mitochondrial diseases in Hong Kong: prevalence, clinical characteristics and genetic landscape.

OBJECTIVE: To determine the prevalence of mitochondrial diseases (MD) in Hong Kong (HK) and to evaluate the clinical characteristics and genetic landscape of MD patients in the region. METHODS: This study retrospectively reviewed the phenotypic and molecular characteristics of MD patients from participating public hospitals in HK between January 1985 to October 2020. Molecularly and/or enzymatically confirmed MD cases of any age were recruited via the Clinical Analysis and Reporting System (CDARS) using relevant keywords and/or International Classification of Disease (ICD) codes under the HK Hospital Authority or through the personal recollection of treating clinicians among the investigators. RESULTS: A total of 119 MD patients were recruited and analyzed in the study. The point prevalence of MD in HK was 1.02 in 100,000 people (95% confidence interval 0.81-1.28 in 100,000). 110 patients had molecularly proven MD and the other nine were diagnosed by OXPHOS enzymology analysis or mitochondrial DNA depletion analysis with unknown molecular basis. Pathogenic variants in the mitochondrial genome (72 patients) were more prevalent than those in the nuclear genome (38 patients) in our cohort. The most commonly involved organ system at disease onset was the neurological system, in which developmental delay, seizures or epilepsy, and stroke-like episodes were the most frequently reported presentations. The mortality rate in our cohort was 37%. CONCLUSION: This study is a territory-wide overview of the clinical and genetic characteristics of MD patients in a Chinese population, providing the first available prevalence rate of MD in Hong Kong. The findings of this study aim to facilitate future in-depth evaluation of MD and lay the foundation to establish a local MD registry.

Effect of rehabilitation on biologic and transcriptomic responses after hospital-acquired deconditioning: a prospective longitudinal feasibility study.

PURPOSE: The objective of this study is to explore the transcriptomic and biologic variables characterizing the longitudinal rehabilitation intervention of patients with hospital-acquired deconditioning (HAD). METHODS: This prospective clinical trial recruited HAD patients (n = 10) who spent ≥3 weeks hospitalized and then received inpatient rehabilitation. Functional improvement was measured using the Functional Independence Measure (FIM). Transcriptomic and biological variables were recorded at rehabilitation admission and 1, 2, 4, and 6 weeks post-admission. RNA sequencing studied the temporal changes of gene expression in leukocytes. Between-subject transcriptome comparisons were performed using principle component analysis. Within-subject changes in gene expression were analyzed using a gene ontology hierarchical clustering to identify common biological terms. Heart rate, weight, albumin, creatinine, and complete blood counts were analyzed. RESULTS: Patients average age was 50.6 ± 7.2, FIM increased during inpatient rehabilitation (p = 0.01), weight increased (p = 0.01), lymphocytes decreased (p = 0.05), neutrophil increased (0.03) and red cell distribution width decreased (p = 0.05). The temporal profiles of gene expression revealed within-patient homogeneity and between-patients heterogeneity. The biological terms "bone morphogenesis" and "muscle cell development" were the most significantly enriched differentially expressed genes. CONCLUSION: Transcriptomic and biologic markers paralleled the functional improvements of HAD patients during inpatient rehabilitation. Transcriptomic analyses were consistent with the cohort heterogeneity. Enrichment of the biological pathways bone morphogenesis and muscle cell development constituted evidence at the gene expression level of the effect of rehabilitation. Larger studies of various rehabilitation patient groups may increase gene expression profile homogeneity. Objective transcriptomic and biologic markers have the potential to improve the rehabilitation of HAD patients.IMPLICATIONS FOR REHABILITATIONNovel gene expression methods are increasingly being integrated into clinical practice and may apply to rehabilitation.Patients with hospital-acquired deconditioning (HAD) enriched gene expression of pathways targeted by inpatient rehabilitation such as bone morphogenesis and muscle cell development.The gene expression paralleled functional improvement of HAD patients.These data demonstrated the feasibility of molecular methods to identify markers of rehabilitation success in HAD patients.

Determinants of Poor Glycemic Control in Patients with Kidney Transplants: A Single-Center Retrospective Cohort Study in Canada.

BACKGROUND: Kidney transplant immunosuppressive medications are known to impair glucose metabolism, causing worsened glycemic control in patients with pre-transplant diabetes mellitus (PrTDM) and new onset of diabetes after transplant (NODAT). OBJECTIVES: To determine the incidence, risk factors, and outcomes of both PrTDM and NODAT patients. DESIGN: This is a single-center retrospective observational cohort study. SETTING: The Ottawa Hospital, Ontario, Canada. PARTICIPANT: A total of 132 adult (>18 years) kidney transplant patients from 2013 to 2015 were retrospectively followed 3 years post-transplant. MEASUREMENTS: Patient characteristics, transplant information, pre- and post-transplant HbA1C and random glucose, follow-up appointments, complications, and readmissions. METHODS: We looked at the prevalence of poor glycemic control (HbA1c >8.5%) in the PrTDM group before and after transplant and compared the prevalence, follow-up appointments, and rate of complications and readmission rates in both the PrTDM and NODAT groups. We determined the risk factors of developing poor glycemic control in PrTDM patients and NODAT. Student t-test was used to compare means, chi-squared test was used to compare percentages, and univariate analysis to determine risk factors was performed by logistical regression. RESULTS: A total of 42 patients (31.8%) had PrTDM and 12 patients (13.3%) developed NODAT. Poor glycemic control (HbA1c >8.5%) was more prevalent in the PrTDM (76.4%) patients compared to those with NODAT (16.7%; P < .01). PrTDM patients were more likely to receive follow-up with an endocrinologist (P < .01) and diabetes nurse (P < .01) compared to those with NODAT. There were no differences in the complication and readmission rates for PrTDM and NODAT patients. Receiving a transplant from a deceased donor was associated with having poor glycemic control, odds ratio (OR) = 3.34, confidence interval (CI = 1.08, 10.4), P = .04. Both patient age, OR = 1.07, CI (1.02, 1.3), P < .01, and peritoneal dialysis prior to transplant, OR = 4.57, CI (1.28, 16.3), P = .02, were associated with NODAT. LIMITATIONS: Our study was limited by our small sample size. We also could not account for any diabetes screening performed outside of our center or follow-up appointments with family physicians or community endocrinologists. CONCLUSION: Poor glycemic control is common in the kidney transplant population. Glycemic targets for patients with PrTDM are not being met in our center and our study highlights the gap in the literature focusing on the prevalence and outcomes of poor glycemic control in these patients. Closer follow-up and attention may be needed for those who are at risk for worse glycemic control, which include older patients, those who received a deceased donor kidney, and/or prior peritoneal dialysis.

CONTEXTE: Les médicaments immunosuppresseurs prescrits à la suite d'une transplantation rénale sont connus pour altérer le métabolisme du glucose, rendant plus difficile le contrôle de la glycémie chez les patients diabétiques avant l'intervention (DbAvT ­ diabétiques avant la transplantation) et chez les patients devenus diabétiques après l'intervention (NDbApT ­ nouveaux diabétiques après la transplantation). OBJECTIF: Déterminer l'incidence d'un contrôle de la glycémie déficient, les facteurs de risque et les résultats chez les patients DbAvT et NDbApT. TYPE D'ÉTUDE: Il s'agit d'une étude de cohorte rétrospective et observationnelle qui s'est tenue dans un seul center. CADRE: L'hôpital d'Ottawa (Ontario), au Canada. SUJETS: Les adultes receveurs d'une greffe rénale entre 2013 et 2015 (n=132) ont été suivis rétrospectivement sur une période de trois ans post-transplantation. MESURES: Les caractéristiques des patients, les informations relatives à la greffe, les taux d'HbA1C et la glycémie pré- et post-transplantation, les rendez-vous de suivi, les complications et les réadmissions. MÉTHODOLOGIE: Nous nous sommes d'abord penchés sur la prévalence d'un contrôle glycémique déficient (HbA1c >8,5 %) dans le groupe DbAvT avant et après la greffe, puis nous avons comparé la prévalence, les rendez-vous de suivi et les taux de complications et de réadmission pour les deux groupes. Nous avons déterminé les facteurs de risque d'un mauvais contrôle glycémique chez les patients DbAvT et NDbApT. Les moyennes ont été comparées à l'aide du test t de Student, et le test du chi carré a servi à comparer les pourcentages. L'analyze univariée pour déterminer les facteurs de risque a été effectuée par régression logistique. RÉSULTATS: Parmi les 132 patients étudiés, 42 (31,8 %) étaient DbAvT et 12 (13,3 %) le sont devenus après l'intervention (NDbApT). La prévalence d'un mauvais contrôle de la glycémie (HbA1c >8,5 %) était plus élevée chez les patients DbAvT que chez les patients NDbApT (76,4 % contre 16,7 %; p<0,01). Les patients DbAvT étaient plus susceptibles d'être suivis par un endocrinologue (p<0.01) et une infirmière spécialisée en diabète (p<0.01) comparativement aux patients NDbApT. Aucune différence n'a été observée entre les deux groupes pour les taux de complications et de réadmission. Un greffon provenant d'un donneur décédé a été associé à un contrôle glycémique déficient (RC=3,34; IC 95 :1,08-10,4; p=0,04). Le développement d'un NDbApT a été associé à la fois à l'âge du patient (RC=1,07 IC 95: 1,02-1,3; p<0,01) et à un traitement de dialyze péritonéale (OR=4,57; IC 95: 1,28-16,3; p=0,02) avant la greffe. LIMITES: Nos résultats sont limités par la faible taille de l'échantillon. Nous n'avons pu rendre compte des dépistages effectués hors de notre center ni des rendez-vous de suivi avec un médecin de famille ou un endocrinologue dans la communauté. CONCLUSION: Un contrôle glycémique déficient est fréquent chez les patients greffés d'un rein. Les cibles glycémiques des patients DbAvT ne sont pas rencontrées dans notre center et notre étude met en lumière les lacunes de la littérature sur la prévalence et les résultats d'un mauvais contrôle glycémique chez ces patients. Un suivi plus étroit et une plus grande attention pourraient être nécessaires pour les patients susceptibles de voir leur contrôle glycémique se détériorer, notamment les personnes âgées, les receveurs d'un rein provenant d'un donneur décédé et les patients traités par dialyze péritonéale avant l'intervention.

New insights in post-traumatic headache with cluster headache phenotype: a cohort study.

OBJECTIVES: To define the characteristics of post-traumatic headache with cluster headache phenotype (PTH-CH) and to compare these characteristics with primary CH. METHODS: A retrospective study was conducted of patients seen between 2007 and 2017 in a headache centre and diagnosed with PTH-CH that developed within 7 days of head trauma. A control cohort included 553 patients with primary CH without any history of trauma who attended the headache clinic during the same period. Data including demographics, attack characteristics and response to treatments were recorded. RESULTS: Twenty-six patients with PTH-CH were identified. Multivariate analysis revealed significant associations between PTH-CH and family history of CH (OR 3.32, 95% CI 1.31 to 8.63), chronic form (OR 3.29, 95% CI 1.70 to 6.49), parietal (OR 14.82, 95% CI 6.32 to 37.39) or temporal (OR 2.04, 95% CI 1.10 to 3.84) location of pain, and presence of prominent cranial autonomic features during attacks (miosis OR 11.24, 95% CI 3.21 to 41.34; eyelid oedema OR 5.79, 95% CI 2.57 to 13.82; rhinorrhoea OR 2.65, 95% CI 1.26 to 5.86; facial sweating OR 2.53, 95% CI 1.33 to 4.93). Patients with PTH-CH were at a higher risk of being intractable to acute (OR 12.34, 95% CI 2.51 to 64.73) and preventive (OR 16.98, 95% CI 6.88 to 45.52) treatments and of suffering from associated chronic migraine (OR 10.35, 95% CI 3.96 to 28.82). CONCLUSION: This largest series of PTH-CH defines it as a unique entity with specific evolutive profile. Patients with PTH-CH are more likely to suffer from the chronic variant, have marked autonomic features, be intractable to treatment and have associated chronic migraine compared with primary CH.

Feasibility of incorporating functionally relevant virtual rehabilitation in sub-acute stroke care: perception of patients and clinicians.

PURPOSE: To determine user satisfaction and safety of incorporating a low-cost virtual rehabilitation intervention as an adjunctive therapeutic option for cognitive-motor upper limb rehabilitation in individuals with sub-acute stroke. METHODS: A low-cost upper limb virtual rehabilitation application incorporating realistic functionally-relevant unimanual and bimanual tasks, specifically designed for cognitive-motor rehabilitation was developed for patients with sub-acute stroke. Clinicians and individuals with stroke interacted with the intervention for 15-20 or 20-45 minutes, respectively. The study had a mixed-methods convergent parallel design that included a focus group interview with clinicians working in a stroke program and semi-structured interviews and standardized assessments (Borg Perceived Exertion Scale, Short Feedback Questionnaire) for participants with sub-acute stroke undergoing rehabilitation. The occurrence of adverse events was also noted. RESULTS: Three main themes emerged from the clinician focus group and patient interviews: Perceived usefulness in rehabilitation, satisfaction with the virtual reality intervention and aspects to improve. All clinicians and the majority of participants with stroke were highly satisfied with the intervention and perceived its usefulness to decrease arm motor impairment during functional tasks. No participants experienced major adverse events. CONCLUSIONS: Incorporation of this type of functional activity game-based virtual reality intervention in the sub-acute phase of rehabilitation represents a way to transfer skills learned early in the clinical setting to real world situations. This type of intervention may lead to better integration of the upper limb into everyday activities. Implications for Rehabilitation • Use of a cognitive-motor low-cost virtual reality intervention designed to remediate arm motor impairments in sub-acute stroke is feasible, safe and perceived as useful by therapists and patients for stroke rehabilitation. • Input from end-users (therapists and individuals with stroke) is critical for the development and implementation of a virtual reality intervention.