Assessment of health professional education across five Asian countries-a protocol.

BACKGROUND: There is an increasing consensus globally that the education of health professionals is failing to keep pace with scientific, social, and economic changes transforming the healthcare environment. This catalyzed a movement in reforming education of health professionals across Bangladesh, China, India, Thailand, and Vietnam who jointly volunteered to implement and conduct cooperative, comparative, and suitable health professional education assessments with respect to the nation's socio-economic and cultural status, as well as domestic health service system. METHODS: The 5C network undertook a multi-country health professional educational study to provide its countries with evidence for HRH policymaking. Its scope was limited to the assessment of medical, nursing, and public health education at three levels within each country: national, institutional, and graduate level (including about to graduate students and alumni). RESULTS: This paper describes the general issues related to health professional education and the protocols used in a five-country assessment of medical, nursing, and public health education. A common protocol for the situation analysis survey was developed that included tools to undertake a national and institutional assessment, and graduate surveys among about-to-graduate and graduates for medical, nursing, and public health professions. Data collection was conducted through a mixture of literature reviews and qualitative research. CONCLUSIONS: The national assessment would serve as a resource for countries to plan HRH-related future actions.

Attitude towards working in rural area and self-assessment of competencies in last year medical students: A survey of five countries in Asia.

BACKGROUND: Five countries in Asia including Bangladesh, China, India, Thailand and Vietnam formed a network called Asia-Pacific Network for Health Professional Education Reforms (ANHER). This network collectively conducted a survey at the national level and at the institutional level (for medical, nursing and public health education). We also undertook an assessment of final year graduates from these schools on their attitudes, competencies and willingness to work in rural areas. METHODS: Pretested anonymous questionnaire comprised of four sections including demographic data, attitudes towards working in rural area, where to work after graduation and perception about competency of respondents was used. Descriptive and analytical statistics were used for data analyses. RESULTS: About 60 % of students from Bangladesh and Thailand had positive attitude towards working in rural area, 50 % in both China and India and only 33 % in Vietnam. Students' positive attitudes towards their school in terms of preparing or inspiring them to work in rural areas were low across all five countries. Upon graduation and in the next five years, majority of students wanted to work in public sectors. Interestingly confidence about overall competency was quite low. DISCUSSION: Positive attitude towards working in rural areas varied significantly across five countries in Asia. Medical schools should improve the preparation and inspiration towards working in rural areas for their students. CONCLUSION: Medical schools should put more effort in improving students' attitude towards working in rural areas.

Diagnostic value of visual evoked potentials for clinical diagnosis of multiple sclerosis.

PURPOSE: Prolonged latency of visual evoked potentials (VEP) has been used to identify clinically silent lesions in multiple sclerosis (MS) suspects. The objective of this study was to determine the reliability of VEP to predict the development of MS in MS suspects. METHODS: Retrospective hospital records of MS suspects were evaluated. VEP was analyzed together with subsequent diagnostic confirmation of MS by McDonald diagnostic criteria for MS-2005. RESULTS: MS developed in 12 of 35 patients (34 %) and 23 (66 %) failed to exhibit diagnostic characteristics. P100 latencies and interocular latency differences were longer in clinically definite multiple sclerosis (CDMS) than non-CDMS patients (p = 0.002, 0.001, respectively). All patients in the subsequent MS group had P100 latencies longer than102 ms, a mean of our MS-free subjects thus providing 100 % of sensitivity. No patient developed MS with a P100 latency <102 ms. Brain MRI lesions associated significantly with developing CDMS (p = 0.001). Predictability of developing CDMS was highest when criteria for P100 latency, interocular latency difference, and brain MRI lesions were combined. CONCLUSION: MS suspects with a P100 latency longer than mean of MS-free subjects are more likely to develop MS than those with lower values. VEP latency combined with MRI could improve the accuracy of MS prediction.

The prone position in COVID-19 impacts the thickness of peripapillary retinal nerve fiber layers and macular ganglion cell layers.

The prone position reduces mortality in severe cases of COVID-19 with acute respiratory distress syndrome. However, visual loss and changes to the peripapillary retinal nerve fiber layer (p-RNFL) and the macular ganglion cell layer and inner plexiform layer (m-GCIPL) have occurred in patients undergoing surgery in the prone position. Moreover, COVID-19-related eye problems have been reported. This study compared the p-RNFL and m-GCIPL thicknesses of COVID-19 patients who were placed in the prone position with patients who were not. This prospective longitudinal and case-control study investigated 15 COVID-19 patients placed in the prone position (the "Prone Group"), 23 COVID-19 patients not in the prone position (the "Non-Prone Group"), and 23 healthy, non-COVID individuals without ocular disease or systemic conditions (the "Control Group"). The p-RNFL and m-GCIPL thicknesses of the COVID-19 patients were measured at 1, 3, and 6 months and compared within and between groups. The result showed that the Prone and Non-Prone Groups had no significant differences in their p-RNFL thicknesses at the 3 follow-ups. However, the m-GCIPL analysis revealed significant differences in the inferior sector of the Non-Prone Group between months 1 and 3 (mean difference, 0.74 µm; P = 0.009). The p-RNFL analysis showed a significantly greater thickness at 6 months for the superior sector of the Non-Prone Group (131.61 ± 12.08 µm) than for the Prone Group (118.87 ± 18.21 µm; P = 0.039). The m-GCIPL analysis revealed that the inferior sector was significantly thinner in the Non-Prone Group than in the Control Group (at 1 month 80.57 ± 4.60 versus 83.87 ± 5.43 µm; P = 0.031 and at 6 months 80.48 ± 3.96 versus 83.87 ± 5.43 µm; P = 0.044). In conclusion, the prone position in COVID-19 patients can lead to early loss of p-RNFL thickness due to rising intraocular pressure, which is independent of the timing of prone positioning. Consequently, there is no increase in COVID-19 patients' morbidity burden.

Identification of the variants in PARL, the nuclear modifier gene, responsible for the expression of LHON patients in Thailand.

The present study explored variation in the PARL gene as one of the potential nuclear modifiers in the pathogenesis of Leber hereditary optic neuropathy (LHON). Ten exons, their franking introns and 3' UTR of the PARL gene were analysed. Seventeen SNPs detected were investigated in 83 affected and 53 unaffected individuals from 47 independent Thai LHON pedigrees using MQLS statistics in order to minimize the influence of the family background. Three intronic SNPs (rs953419, rs3749446 and rs1402000) showed statistically significant results. Joint haplotypes were constructed based on the genotypes at 3 SNPs and 7 possible haplotypes were observed in the 136 subjects. Our findings that the frequency of the haplotype AAC, and AAT were significantly higher in the unaffected cases and the frequencies of haplotype GGT were significantly higher in LHON cases, indicate that it might have a role in the penetrance of this mitochondrial disease.

Plasma exchange for acute optic neuritis in neuromyelitis optica or neuromyelitis optica spectrum disorder: a systematic review.

OBJECTIVES: To appraise whether plasma exchange (PLEX) effectively improves visual function for acute optic neuritis (ON) in neuromyelitis optica (NMO) or neuromyelitis optica spectrum disorder (NMOSD). METHODS AND ANALYSIS: We searched Medline, Embase, Cochrane Library, ProQuest Central, and Web of Science to identify relevant articles published between 2006 and 2020.Eligible studies were in English and evaluated visual outcomes for people with acute ON in NMO or NMOSD treated with PLEX. They also had adequate pre- and posttreatment data. Excluded were studies with 1 or 2 case reports, or incomplete data. RESULTS: Twelve studies were qualitatively synthesized (1 RCT; 1 controlled NRSI; 10 observational studies). Five before-and-after observational studies were used for quantitative synthesis. The PLEX in the 5 studies (3 to 7 cycles over 2 to 3 weeks) was performed as second-line or adjunctive therapy for acute ON in NMO/NMOSD.The qualitative synthesis revealed that visual-acuity recovery occurred between one day and 6 months after the first PLEX cycle completion. Thirty-two of 48 participants in the 5 quantitative-synthesis studies received PLEX. Relative to pre-PLEX values, visual-acuity improvements were nonsignificant at these post-PLEX time points: 1 day (SMD 0.611; 95% CI -0.620 to 1.842); 2 weeks (SMD 0.0214; 95% CI -1.250 to 1.293); 3 months (SMD 1.014; 95% CI -0.954 to 2.982); and 6 months (SMD 0.450; 95% CI -2.643 to 3.543). CONCLUSIONS: There were inadequate data to determine whether PLEX effectively treats acute ON in NMO/NMOSD.

Aggregate current data of this systematic review is insufficient to definitively conclude whether therapeutic PLEX is effective in improving VA in cases of NMO or NMOSD.

Clinical expression and mitochondrial deoxyribonucleic acid study in twins with 14484 Leber's hereditary optic neuropathy: A case report.

BACKGROUND: This study aimed to explore clinical and molecular factors that cause discordance for clinical expression of Leber's hereditary optic neuropathy (LHON) in a pair of identical twins with the 14484 point mutation. CASE SUMMARY: Twin patients with the 14484 point mutation were studied for zygosity by using the Short Tandem Repeats Typing system. For the monozygotic twins, the radioactive restriction and densitometric analyses were used to quantitate the heteroplasmy level for the 14484 point mutation. The mitochondrial genome was analyzed to determine influential factors by mitochondrial deoxyribonucleic acid (DNA) sequencing, denaturing high-performance liquid chromatography and next generation sequencing. For the dizygotic twins, the nuclear DNA was analyzed. The twins with 14484 LHON were monozygotic with homoplasmy. No difference in the point mutation in mitochondrial DNA was found. No modifying genes that potentially influenced the disparity in phenotypic expression of LHON were detected in these twins. CONCLUSION: This 11-year follow-up of monozygotic twins showed additional genetic modifications and epigenetic factors are possibly associated with discordance for LHON.

The epidemiology and mutation types of Leber's hereditary optic neuropathy in Thailand.

PURPOSE: Leber's hereditary optic neuropathy (LHON), the most common mitochondrial optic neuropathy, causes visual loss, especially in young adults. Due to the absence of epidemiological data in Southeast Asia, we aimed to determine Thai LHON patients' characteristics (demographic data, mutation types, and prognoses) as the first study in this region. METHODS: This retrospective chart review enrolled all Thai LHON patients confirmed by three mitochondrial DNA mutations (G11778A, T14484C, and G3460A) between January 1997 and December 2016. Patients with more than one year of follow-up were included in a visual progression analysis. The Mann-Whitney U-test was applied to compare groups, and prognosis-associated factors were analysed with the generalized estimating equation. RESULTS: In all, 229 patients were enrolled, with only nineteen females. Most mutations were of the G11778A type (91%), with T14484C accounting for the remainder. The age at onset of G11778A (21.9 years; interquartile range [IQR] 14.9, 33.5) was younger than that of T14484C (33.0 years; IQR 19.4, 37.5). Of 45 patients, the T14484C group demonstrated good vision recovery, whereas the G11778A group did not improve (difference in logMAR -0.7 and IQR -1.5, -0.2 versus logMAR 0.0 and IQR -0.3, 0.2, respectively; P value .001). The G11778A mutation, male, and older age were related to poor prognoses. CONCLUSIONS: The leading mutation in Thai LHON patients is the G11778A missense, followed by T14484C, while G3460A was not detected. The vast majority of patients were young adult males. The G11778A mutation, older age, and male gender are associated with poor vision outcomes. Key messageThe G11778A missense mutation is the most common among Thai LHON patients, followed by T14484C, while G3460A was not found. The G11778A mutation, older age, and male gender are associated with poor vision outcomes.

Clinical profiles of Thai patients with ocular myasthenia gravis in Siriraj Hospital.

Ninety-six patients with ocular myasthenia gravis (OMG) seen at Siriraj Hospital during 1994 to 2004 were retrospectively reviewed. There were 59 female (61.5%) and 37 (38.5%) male patients with mean ages of 39.5 and 33.8 years, respectively Patients presented with initial symptoms of only ptosis in 46.9%, only diplopia in 13.5% and both ptosis and diplopia in 39.6%. However, diplopia alone is uncommon in childhood OMG. Fifteen percent developed systemic symptoms within two years of diagnosis. Thyroid function test was abnormal in 27.5% of investigated patients. Most abnormalities were hyperthyroidism. Thymoma associated with OMG is a rare condition. Most purely OMG patients can control the disease by pyridostigmine, prednisolone or immunosuppressive drugs.

Genome-wide linkage scan and association study of PARL to the expression of LHON families in Thailand.

Leber hereditary optic neuropathy (LHON) is the most common mitochondrially inherited disease causing blindness, preferentially in young adult males. Most of the patients carry the G11778A mitochondrial DNA (mtDNA) mutation. However, the marked incomplete penetrance and the gender bias indicate some additional genetic and/or environmental factors to disease expression. Herein, we first conducted a genome-wide linkage scan with 400 microsatellite markers in 9 large Thai LHON G11778A pedigrees. Using an affecteds-only nonparametric linkage analysis, 4 regions on chromosomes 3, 12, 13 and 18 showed Zlr scores greater than 2 (P < 0.025), which is consistently significant across several linkage statistics. The most suggestive marker D3S1565 (Zlr > 2 in 10 of 16 allele sharing models tested) was then expanded to include the region 3q26.2-3q28 covering SLC7A14 (3q26.2), MFN1 (3q26.32), MRPL47 (3q26.33), MCCC1 (3q27.1), PARL (3q27.1) and OPA1 (3q28-q29). All of these candidate genes were selected from the Maestro database and had known to be localized in mitochondria. Sixty tag SNPs were genotyped in 86 cases, 211 of their relatives and 32 unrelated Thai controls, by multiplex-PCR-based Invader assay. Analyses using a powerful association testing tool that adjusts for relatedness (the M(QLS) statistic) showed the most evidence of association between two SNPs, rs3749446 and rs1402000 (located in PARL presenilins-associated rhomboid-like) and LHON expression (both P = 8.8 x 10(-5)). The mitochondrial PARL protease has been recently known to play a role with a dynamin-related OPA1 protein in preventing apoptotic events by slowing down the release of cytochrome c out of mitochondrial cristae junctions. Moreover, PARL is required to activate the intramembranous proteolyses resulting in the degradation of an accumulated pro-apoptotic protein in the outer mitochondrial membrane. Under these circumstances, variants of PARL are suggested to influence cell death by apoptosis which has long been believed to intrigue the neurodegeneration of LHON.

Factors associated with insensitivity to pyridostigmine therapy in Thai patients with ocular myasthenia gravis.

The objective of this study was to determine factors associated with pyridostigmine therapy in patients with ocular myasthenia gravis (OMG). This retrospective study included eighty-five patients with OMG who have been treated with pyridostigmine. Patients were excluded if they were diagnosed as generalized myasthenia gravis within a month after diagnosis or were treated with other medications. Forty-two patients responded to pyridostigmine and 43 patients did not. There were no significant differences in gender, age, the duration of symptoms before treatment, the dosage of pyridostigmine, and the initial presentations of ptosis or diplopia between the two groups. However, an initial presentation of concurrent ptosis and diplopia and the presence of systemic involvement after follow up were significant factors associated with an insensitivity to pyridostigmine in patients with OMG (p = 0.001 and p = 0.01, respectively). Determining these factors could help predict the pyridostigmine response in patients with OMG.

Orbital pseudotumor: clinical features and outcomes.

To describe the clinical characteristics of orbital pseudotumor, a retrospective analysis was performed on patients with orbital pseudotumor at Siriraj Hospital for ten years. Forty-nine patients (24 males and 25 females; 62 eyes) with a mean age of 43.75 years were included (a mean follow-up of 25 months). Thirty-six patients (73.5%) had unilateral disease. The clinical features were proptosis (79.6%), ocular motor deficit (61.2%), pain (51%), lid swelling or lid mass (44.9%), ptosis (24.5%), and chemosis (18.4%). The most common presenting sign was proptosis (49%). All were treated with corticosteroids with clinical improvement in 40 (81.6%) patients. Ten (83.3%) of 12 patients with visual loss improved with mean recovery time of 10.3 days. Ocular motility recovered in 24 (80%) patients, occurring an average of 17.8 days after initiation of therapy. It is concluded that the clinical features of orbital pseudotumor are varied. Most patients were improved with corticosteroids treatment.

A comparative study of visual evoked potentials in optic neuritis and optic neuritis with multiple sclerosis.

OBJECTIVE: To compare the visual evoked potentials (VEP) in patients with acute optic neuritis, recurrent optic neuritis, and optic neuritis with multiple sclerosis. MATERIAL AND METHOD: The authors retrospectively reviewed VEP latency records of the patients with optic neuritis in Siriraj Hospital from 1995 to 2005 and divided them into three groups, acute optic neuritis, recurrent optic neuritis, and optic neuritis with multiple sclerosis (ON/MS). The patients with non-recordable VEP in the analysis were excluded. Comparison of the mean latency of the VEP in affected eyes among the three groups was statistically analyzed by a nonparametric independent sample test. RESULTS: Twenty-two patients with acute optic neuritis, 8 patients with recurrent optic neuritis, and 22 patients with ON/MS participated in this study. The mean age among the three groups was not statistically significant. The median value of the latency of flash VEP (fVEP) and pattern reversal VEP (PRVEP) in the acute optic neuritis group was shorter than that of the recurrent optic neuritis group, and statistically significant (fVEP p = 0.012; PRVEP, p = 0.004). The median value of the latency of PRVEP in the acute optic neuritis group was shorter than that of the ON/MS group, and statistically significant (PRVEP p = 0.002). The median value of the latency of both fVEP and PRVEP in the recurrent optic neuritis group and ON/MS group were delayed with no statistical significance (fVEP p = 0.458; PRVEP, p = 0.403). CONCLUSION: The VEP can be used to demonstrate the demyelinating mechanism of optic neuritis and optic neuritis with multiple sclerosis, but cannot determine the susceptibility of the patients with acute ON to become MS. The significantly delayed latency of VEP in recurrent optic neuritis is possibly caused by severe damage of the optic nerve conduction from recurrent attacks.

Diurnal changes in retinal nerve fiber layer thickness with obstructive sleep apnea/hypopnea syndrome.

AIM: To compare the retinal nerve fiber layer (RNFL) thickness in the morning and evening in Thai patients with varying degrees of obstructive sleep apnea/hypopnea syndrome (OSAHS). METHODS: In this cross-sectional study, potential OSAHS patients at Siriraj Hospital underwent polysomnography to determine the severity of OSAHS and an eye examination (including best corrected visual acuity, slit-lamp examination, and Goldmann applanation tonometry). RNFL thickness was recorded once in the morning and once in the evening, using spectral domain optical coherence tomography. Thickness was expressed as an average and given for each quadrant. Patients with ocular or systemic diseases that might affect RNFL thickness were excluded. RESULTS: Forty-one eyes of 41 patients were classified into 4 OSAHS groups. The average and mean RNFL thickness in most of the four quadrants of the severe OSAHS group trended toward being less than those in the comparable quadrants of the other groups in both the morning and evening. In the moderate OSAHS group, the average RNFL thickness and temporal and superior quadrant thickness in the morning were significantly higher than in the evening (P=0.01, P=0.01, and P=0.03, respectively). In the severe OSAHS group, the inferior quadrant thickness in the morning was significantly higher than in the evening (P=0.03). CONCLUSION: The RNFL thickness in the morning was higher than in the evening in moderate OSAHS.

Case report: A Thai patient with Leber's hereditary optic neuropathy linked to mitochondrial DNA 14484 mutation.

A young Thai male presented with bilateral visual loss and disc pallor. The 14484 mutation responsible for Leber's hereditary optic neuropathy (LHON) was identified on blood mitochondrial analysis. His visual loss was more severe than the visual loss described in Caucasian and Japanese patients and showed no improvement. He had no other identifiable mutations related to LHON nor any associated neurological disorder. This is the first case report of LHON with the 14484 mutation in a Thai patient.

Botulinum toxin treatment for upper lid retraction of dysthyroidism.

Six patients with upper eyelid retraction due to dysthyroidism at Siriraj Hospital received subcutaneous botulinum toxin treatment at a dosage of 5-20 units per injection. Five patients experienced an improvement in the lid retraction lasting at least 40 months and 3 patients required more than one injection. Botulinum toxin injection is an alternative treatment for the upper eyelid retraction of dysthyroidism, which is effective and causes minimal side effects, particularly in patients with euthyroid status.

A prospective randomized trial of megadose methylprednisolone and high dose dexamethasone for traumatic optic neuropathy.

PURPOSE: To determine whether the improvement in visual acuity obtained when using high dose dexamethasone in the treatment of traumatic optic neuropathy was comparable to that of megadose methylprednisolone. METHOD: A total of forty-four patients with traumatic optic neuropathy were prospectively randomized and selected to receive intravenous high dose dexamethasone or megadose methylprednisolone within 2 weeks of injury. Age, gender, cause of injury, interval from injury to treatment, initial, post-pulse, and final visual acuity were analysed statistically to compare the dexamethasone and methylprednisolone groups. RESULTS: The mean interval to treatment was not significantly different (p=0.28) for the dexamethasone group at 5.5 days compared to the methylprednisolone group at 4.1 days. Visual improvement of at least two lines of the Snellen chart or two levels of unmeasured visual acuity was shown in 9 patients (37.5%) of the dexamethasone group and 10 patients (50%) of the methylprednisolone group. There was no statistically significant difference between the initial and post-pulse visual acuity (p=1.0) and the initial and final visual outcome (p=0.60) in the dexamethasone group compared with the methylprednisolone group. CONCLUSION: There was no significant difference in the visual acuity obtained after treatment with intravenous dexamethasone or methylprednisolone for traumatic optic neuropathy.

Optic neuritis: characteristics and visual outcome.

OBJECTIVE: To determine clinical characteristics of patients with optic neuritis and visual outcome after intravenous methylprednisolone treatment. METHOD: A total of 81 patients with optic neuritis were reviewed retrospectively with regard to their clinical characteristics by dividing into two groups as follows: group I had isolated optic neuritis and group II had optic neuritis with demyelinative disease. The visual outcome in these patients before and after intravenous methylprednisolone treatment was analyzed. RESULTS: Of 81 patients with optic neuritis, 63 patients (77.8%) had isolated optic neuritis and 18 (22.2%) patients were optic neuritis with demyelinative disease. The ages of the patients ranged from 16 to 59 years (mean = 35.3 years) in patients with isolated optic neuritis and from 16 to 73 years of age (mean = 35.8 years) in patients with optic neuritis with demyelinative disease. After treatment, 45 patients (52 eyes) with isolated optic neuritis and 14 patients (25 eyes) with optic neuritis with demyelinative disease who were followed-up for more than 10 days were studied. After treatment, 60 per cent of the isolated optic neuritis patients and 24 per cent of the optic neuritis patients with demyelinative disease had a visual acuity of 6/12 or better respectively. The isolated optic neuritis who had an onset interval to treatment of less than 8 days had a visual acuity better than 6/9 in 75 per cent. CONCLUSION: The final visual outcome in patients with isolated optic neuritis who received earlier treatment was better than those who received treatment later.

Profiling the mitochondrial proteome of Leber's Hereditary Optic Neuropathy (LHON) in Thailand: down-regulation of bioenergetics and mitochondrial protein quality control pathways in fibroblasts with the 11778G>A mutation.

Leber's Hereditary Optic Neuropathy (LHON) is one of the commonest mitochondrial diseases. It causes total blindness, and predominantly affects young males. For the disease to develop, it is necessary for an individual to carry one of the primary mtDNA mutations 11778G>A, 14484T>C or 3460G>A. However these mutations are not sufficient to cause disease, and they do not explain the characteristic features of LHON such as the higher prevalence in males, incomplete penetrance, and relatively later age of onset. In order to explore the roles of nuclear encoded mitochondrial proteins in development of LHON, we applied a proteomic approach to samples from affected and unaffected individuals from 3 pedigrees and from 5 unrelated controls. Two-dimensional electrophoresis followed by MS/MS analysis in the mitochondrial lysate identified 17 proteins which were differentially expressed between LHON cases and unrelated controls, and 24 proteins which were differentially expressed between unaffected relatives and unrelated controls. The proteomic data were successfully validated by western blot analysis of 3 selected proteins. All of the proteins identified in the study were mitochondrial proteins and most of them were down regulated in 11778G>A mutant fibroblasts. These proteins included: subunits of OXPHOS enzyme complexes, proteins involved in intermediary metabolic processes, nucleoid related proteins, chaperones, cristae remodelling proteins and an anti-oxidant enzyme. The protein profiles of both the affected and unaffected 11778G>A carriers shared many features which differed from those of unrelated control group, revealing similar proteomic responses to 11778G>A mutation in both affected and unaffected individuals. Differentially expressed proteins revealed two broad groups: a cluster of bioenergetic pathway proteins and a cluster involved in protein quality control system. Defects in these systems are likely to impede the function of retinal ganglion cells, and may lead to the development of LHON in synergy with the primary mtDNA mutation.