Anxiety, Depression and Functional Impairment among Health Care Workers during COVID-19 Pandemic: A Crosssectional Online Survey.

Background COVID-19 is an infectious disease caused by a newly discovered coronavirus. The number of cases and dramatic loss of human life worldwide created psychological problems among general public, including health care workers. Objective To determine the burden of anxiety, depression, and functional impairment among health care workers in the early days of lockdown during the first wave of COVID-19 outbreak in Nepal. Method A hospital-based cross-sectional study was carried out among all the employees of Hospital for Children Eye ENT and Rehabilitation Services, Bhaktapur during the COVID-19 pandemic lockdown from April 3, 2020 to May 2, 2020 using an online questionnaire. The tools used were adopted from Nepali version of Hospital Anxiety and Depression scale (HADS) and Nepali version of WHO Disability Assessment Schedule (WHODAS 2.0). Result The mean age (SD) of the participants (n=86) was 32.53 (7.92) years. Male and female participants were equal in number. The point prevalence of anxiety and depression was 25.6% and 14.0%, respectively. Females had a higher prevalence of both anxiety (39.5% vs 11.6%, p < 0.01) and depression (18.6% vs 9.3%, p=0.351). Clinical and nonclinical staff both had a higher prevalence of both anxiety (31.0% and 20.5%, p=0.265) and depression (16.7% and 11.4%, p=0.478). The mean functional impairment score (WHODAS 2.0) among all participants and participants with anxiety and depression was 19.47 (95% CI: 18.13-20.80), 21.27 (95% CI: 18.08-24.46), and 19.92 (95% CI: 15.28- 24.56), respectively. Conclusion Anxiety and depression during the first lockdown due to COVID-19 pandemic were highly prevalent in clinical and non-clinical employees. Besides controlling the outbreak, special consideration should be given to mental health.

Genome re-sequencing to identify single nucleotide polymorphism markers for muscle color traits in broiler chickens.

OBJECTIVE: Meat quality including muscle color in chickens is an important trait and continuous selective pressures for fast growth and high yield have negatively impacted this trait. This study was conducted to investigate genetic variations responsible for regulating muscle color. METHODS: Whole genome re-sequencing analysis using Illumina HiSeq paired end read method was performed with pooled DNA samples isolated from two broiler chicken lines divergently selected for muscle color (high muscle color [HMC] and low muscle color [LMC]) along with their random bred control line (RAN). Sequencing read data was aligned to the chicken reference genome sequence for Red Jungle Fowl (Galgal4) using reference based genome alignment with NGen program of the Lasergene software package. The potential causal single nucleotide polymorphisms (SNPs) showing non-synonymous changes in coding DNA sequence regions were chosen in each line. Bioinformatic analyses to interpret functions of genes retaining SNPs were performed using the ingenuity pathways analysis (IPA). RESULTS: Millions of SNPs were identified and totally 2,884 SNPs (1,307 for HMC and 1,577 for LMC) showing >75% SNP rates could induce non-synonymous mutations in amino acid sequences. Of those, SNPs showing over 10 read depths yielded 15 more reliable SNPs including 1 for HMC and 14 for LMC. The IPA analyses suggested that meat color in chickens appeared to be associated with chromosomal DNA stability, the functions of ubiquitylation (UBC) and quality and quantity of various subtypes of collagens. CONCLUSION: In this study, various potential genetic markers showing amino acid changes were identified in differential meat color lines, that can be used for further animal selection strategy.

Characterization and evaluation of lactic acid bacteria candidates for intestinal epithelial permeability and Salmonella Typhimurium colonization in neonatal turkey poults.

The present study evaluated the microbiological properties of three probiotic candidate strains of lactic acid bacteria (LAB) (128; 131; CE11_2), their effect on intestinal epithelial permeability, and their ability to reduce intestinal colonization of Salmonella Typhimurium (ST) individually or as a batch culture in neonatal turkey poults. Isolates were characterized morphologically and identified using 16S rRNA sequence analyses. Each isolate was evaluated for tolerance and resistance to acidic pH, high osmotic NaCl concentrations, and bile salts in broth medium. In vitro assessment of antimicrobial activity against different enteropathogenic bacteria was determined using an overlay technique. In vitro intestinal permeability was evaluated using a stressed Caco-2 cell culture assay treated with/without the probiotic candidates. The in vivo effect of the selected LAB strains on ST cecal colonization was determined in two independent trials with neonatal turkey poults. The results obtained in this study demonstrate the tolerance of LAB candidates to pH 3, a NaCl concentration of 6.5%, and high bile salts (0.6%). All strains evaluated exhibited in vitro antibacterial activity against Salmonella Enteritidis, ST, and Campylobacter jejuni. Candidates 128 and 131 exhibited a coccus morphology and were identified as Enterococcus faecium, and bacterial strain CE11_2 exhibited clusters of cocci-shaped cells and was identified as Pediococcus parvulus. All three candidate probiotics significantly (P < 0.05) increased transepithelial electrical resistance (TEER) in Caco-2 cells following a 3-h incubation period with hydrogen peroxide compared to control and blank groups. The combination of all three candidates as a batch culture exhibited significant efficacy in controlling intestinal colonization of ST in neonatal turkey poults. Evaluation of the combination of these selected LAB strains according to performance and intestinal health parameters of chickens and turkeys are currently in process.

Effect of prior treatment status and reasons for discontinuation on the efficacy and safety of fingolimod vs. interferon ß-1a intramuscular: Subgroup analyses of the Trial Assessing Injectable Interferon vs. Fingolimod Oral in Relapsing-Remitting Multiple Sclerosis (TRANSFORMS).

BACKGROUND: Fingolimod demonstrated superior efficacy compared with interferon ß-1a intramuscular in relapsing multiple sclerosis. The impact of treatment history on fingolimod efficacy is unknown. OBJECTIVES: This post-hoc analysis of phase 3 TRANSFORMS data compared the efficacy and safety of fingolimod and interferon ß-1a intramuscular among patient subgroups defined by prior treatment history. METHODS: Annualized relapse rate and safety of once-daily oral fingolimod 0.5mg, 1.25mg, or once-weekly interferon ß-1a 30µg intramuscular for 12 months were analyzed in 1292 patients with relapsing multiple sclerosis according to prior disease-modifying therapy, reason for prior disease-modifying therapy discontinuation (adverse events or unsatisfactory therapeutic effect), and prior disease-modifying therapy duration. RESULTS: Compared with interferon ß-1a intramuscular, fingolimod 0.5mg significantly reduced annualized relapse rate in patients who were treatment naive, received prior interferon-ß treatment, discontinued prior disease-modifying therapy for unsatisfactory therapeutic effect, or had prior disease-modifying therapy duration of ≥1 year (P≤0.05, all comparisons). Similar trends were observed in patients with prior glatiramer acetate treatment. Significant reductions were also seen with fingolimod 1.25mg for treatment-naive and prior interferon-ß-treated patients. CONCLUSIONS: This analysis demonstrates superiority of fingolimod over interferon ß-1a intramuscular regardless of prior (interferon-ß) treatment and prior treatment efficacy and duration. ClinicalTrials.gov identifier: NCT00340834.

The burden of dengue infection in some vulnerable regions of Nepal.

Dengue is an emerging mosquito borne disease of public health importance in Nepal. A descriptive cross sectional study was carried out to estimate sero-prevalence and distribution pattern of dengue in certain vulnerable regions of Nepal from June to September 2009. A total of 460 venous blood samples were collected from individuals experiencing a febrile illness clinically consistent with dengue infection visiting nearby hospitals of Kanchanpur, Kailali, Banke, Dang and Chitwan districts. The sero-prevalence of dengue virus specific IgM was determined by enzyme linked immunosorbent assay (ELISA) kit. The anti-dengue IgM positivity was found to be 12.17%. The higher frequency of positive cases (16.4%) were from age group 20-40 years followed by < 20 years age group with 9.7% and 5.3% from > 40 years age group. The association between dengue infection and age is found to be statistically significant (p < 0.05). The male:female ratio was determined as 1.3:1 in IgM positive population. Among sampling areas, Kanchanpur showed highest prevalence of dengue infection (15.5%) followed by Chitwan (11.7%), Kailai (11.1%), Banke (10.7%) and Dang (8.3%). Similarly, 94.6% of the positive cases were indigeneous and had no history of travel to other countries. Dengue is firmly established in terai region with increasing trends of infection and expansion into newer areas raising a public health threat. Regular epidemiological studies are suggested which could further reveal the contributing factors associated with dengue virus infection and help in formulating strategies in reducing the transmission rate and control of the infection.

Etiology and antimicrobial susceptibility pattern of bacterial pathogens from urinary tract infection.

Urinary tract infection (UTI) is the most common infection in both community and hospital patients. In majority of the cases, empirical antimicrobial treatment is practiced before the laboratory results of urine culture. Thus, antibiotic resistance may increase in urinary bacterial pathogens due to improper use of drugs. This study was designed to find out the etiological agents of UTI and their prevalence, and to determine the antimicrobial susceptibility pattern of the bacterial pathogens isolated from urine culture. This study was conducted in Kathmandu Model Hospital, Kathmandu, Nepal from April to October, 2009. Midstream Urine samples from 1323 patients suspected of UTI were analyzed by microscopy, and conventional semi-quantitative culture technique for the significant growth. Antimicrobial susceptibility test was performed for the isolates by Modified Kirby-Bauer disk diffusion method. Data were analyzed using SPSS software window version 16. The overall prevalence of UTI was found to be 18.89%. The most frequent causative organisms isolated were Escherichia coli (82.30%), Enterococcus faecalis (5.60%), Citrobacter freundii (3.60%), Enterobacter aerogenes (2.40%), Coagulase Negative Staphylococci (2.40%), Pseudomonas aeruginosa (1.20%), Proteus mirabilis (0.8%), Klebsiella pneumoniae (0.4%), and Staphylococcus aureus (0.4%). Nitrofurantoin and Amoxycillin were found to be the most effective antibiotic against gram negative and gram positive isolates respectively. E. coli was found to be the most common etiological agent of UTI and Nitrofurantoin was the most effective drug among the isolates.

Effect of plasma exchange in accelerating natalizumab clearance and restoring leukocyte function.

BACKGROUND: Accelerating the clearance of therapeutic monoclonal antibodies (mAbs) from the body may be useful to address uncommon but serious complications from treatment, such as progressive multifocal leukoencephalopathy (PML). Treatment of PML requires immune reconstitution. Plasma exchange (PLEX) may accelerate mAb clearance, restoring the function of inhibited proteins and increasing the number or function of leukocytes entering the CNS. We evaluated the efficacy of PLEX in accelerating natalizumab (a therapy for multiple sclerosis [MS] and Crohn disease) clearance and alpha4-integrin desaturation. Restoration of leukocyte transmigratory capacity was evaluated using an in vitro blood-brain barrier (ivBBB). METHODS: Twelve patients with MS receiving natalizumab underwent three 1.5-volume PLEX sessions over 5 or 8 days. Natalizumab concentrations and alpha4-integrin saturation were assessed daily throughout PLEX and three times over the subsequent 2 weeks, comparing results with the same patients the previous month. Peripheral blood mononuclear cell (PBMC) migration (induced by the chemokine CCL2) across an ivBBB was assessed in a subset of six patients with and without PLEX. RESULTS: Serum natalizumab concentrations were reduced by a mean of 92% from baseline to 1 week after three PLEX sessions (p < 0.001). Although average alpha4-integrin saturation was not reduced after PLEX, it was reduced to less than 50% when natalizumab concentrations were below 1 mug/mL. PBMC transmigratory capacity increased 2.2-fold after PLEX (p < 0.006). CONCLUSIONS: Plasma exchange (PLEX) accelerated clearance of natalizumab, and at natalizumab concentrations below 1 mug/mL, desaturation of alpha4-integrin was observed. Also, CCL2-induced leukocyte transmigration across an in vitro blood-brain barrier was increased after PLEX. Therefore, PLEX may be effective in restoring immune effector function in natalizumab-treated patients.

Leprosy affects the tibial nerves diffusely from the middle of the thigh to the sole of the foot, including skip lesions.

This study investigated where leprosy affects the posterior tibial nerve and whether neurolysis is beneficial. Nine patients with bilateral posterior tibial leprous neuropathy with no sensorimotor recovery were studied. Preoperative sensory-muscle and nerve conduction velocity testing revealed the tarsal tunnel to be the site of a severe lesion in all cases. During surgery, the most proximal site of the nerve lesion was detected by electrically stimulating the spinal roots from the second lumbar nerve to the fourth sacral nerve, evoking efferent mixed nerve compound action potentials that were recorded from the exposed tibial nerve. In all patients, the nerve compound action potentials became normal only proximal to the sciatic nerve bifurcation. Epineuriotomy within these seemingly unaffected segments revealed fibrosis of the interfascicular epineurium. Interfascicular neurolysis was performed on all affected segments. A 2-year follow-up showed an increase in girth of the proximal calf musculature in six of eight patients (the ninth patient had no recordable nerve conduction velocity). It was concluded that (1) leprosy affects the tibial nerves in a scattered way from the sciatic nerve main trunk distally to the exit of the tarsal tunnel; and (2) interfascicular, microsurgical neurolysis is beneficial provided that it is performed on all affected nerve segments.

Therapeutic apheresis in multiple sclerosis and other central nervous system disorders.

Although the cause of multiple sclerosis (MS) remains unknown, the recent advances in research and the use of immunomodulating therapies have revolutionalized the way this disease is now approached. Apheresis is but one of the various immunomodulating therapies successfully used in MS. Pilot and double-blind randomized controlled studies, long-term follow-up studies, and the possible mechanism of action of therapeutic apheresis in MS are discussed. Based on our current knowledge, as well as on the available published data, it is concluded that apheresis is an effective therapy in severely progressive MS (both acute and chronic) when conventional therapies have failed.

Use of Van Nes rotationplasty to manage a burnt knee.

An 11 month old child sustained a deep burn injury to the left knee causing total destruction and sequestration of the knee epiphyses. The ensuing leg length discrepancy with growth was managed by a Van Nes rotationplasty at age four with a good immediate functional result using a below 'knee' prosthesis and the prospect of continuing ambulation as he grows. The surgical options for managing this problem are discussed.

A 3 year prospective audit of burns patients treated at the Western Regional Hospital of Nepal.

Burns in Nepal cause an estimated 1700 deaths per year and much suffering. We carried out a prospective 3 year audit of 237 burns patients admitted to the Western Regional Hospital in Pokhara. The aims were to assess the profile of burns injuries and what could be achieved in local conditions to guide colleagues in developing countries with limited medical facilities. The majority of burns occurred at home and were largely preventable. 61 per cent of patients were children under 15 years of age. There were more female patients and females had more severe burns. No patients with greater than 40 per cent body surface area burns of any age group survived. Public education on burns prevention is needed but poverty, ignorance and a fatalistic attitude are difficult underlying causes to change.

Quantitative MR in the diagnosis of multiple sclerosis.

In patients with multiple sclerosis (MS), the apparently uninvolved cerebral white matter between demyelinated plaques may have biochemical abnormalities. To what degree the changes in the white matter contribute to symptomatology in MS is unknown. In 39 patients with multiple sclerosis, and in 39 age-matched nondiseased volunteers, T1 and T2 were calculated from spin-echo images in four regions of apparently uninvolved white matter. In three of four white matter areas, the average T1 and T2 were significantly longer in the patients than in the controls. The T1 correlated with the disability, measured by the Kurtzke Extended Disability Status Scale, although the correlation was marginally significant. The results suggest that in patients with MS, white matter disease that is not visualized in MR as distinct foci of abnormal signal intensity may contribute to disease burden and disability.

Plasma exchange in chronic progressive multiple sclerosis: a long-term study.

Plasma exchange (PE) was shown in a previous double-blind randomized controlled study to confer significant additional benefit at 1 year upon patients with chronic progressive multiple sclerosis (CPMS) treated with immunosuppressive drug therapy (ISDT). Efficacy over an extended term, indications for retreatment, and long-term toxicity are dealt with in this analysis of a larger number of patients. During the past 7 years, 200 patients with CPMS have been treated with PE and low-dose ISDT at this center. Improvement on the Kurtzke Disability Status Scale by one or more steps post-therapy and at 3-year follow-up is significant by comparison with pre-PE disability status. Clinical improvement was maintained in the majority of patients, reaching as far as a 6-year follow-up. Major life-threatening complications attributable to this combined therapy were not observed.

Treatment of multiple sclerosis with hyperbaric oxygen. Results of a national registry.

Three hundred twelve patients were entered into a long-term study of effects of hyperbaric oxygen on multiple sclerosis. The protocol called for an initial 20 treatments in either the monoplace or multiplace chamber on a daily basis followed by monthly booster treatments for 2 years. One hundred seventy neurologists and 22 institutions provided data for this study. There was no control group, but the study was based on Schumacher's postulation that a scientifically valid study to test the efficacy of a new therapy was possible by choosing patients who were definitively diagnosed with multiple sclerosis and following them up for 2 years after the imposed treatment. If the overwhelming majority of the subjects failed to get worse over the 2-year observation period, the efficacy of the treatment would be manifest. The expanded Kurtzke Disability Status Scale (EDSS) was used to assess the severity of the disease state. The dropout rate was high with only 76% (237 of 312 patients) finishing the initial 20 treatments. Twenty-two percent (69 of 312) finished 1 year of booster therapy, and 9% (28 of 312) completed 2 years of monthly boosters. The mean deterioration on the Kurtzke EDSS score was 0.93 or almost a full step from the beginning of treatment until the last evaluation. There was no difference in outcome between those who had the shortest and longest periods of time between onset of symptoms and hyperbaric oxygen treatment. Treatment pressure made no difference in outcome. Changes in the Kurtzke EDSS score bore no relationship to the use of booster treatment. Patients who were reasonably well off at the onset of treatment with initial Kurtzke EDSS scores of 1 or 2 (n = 21) deteriorated by an average of 1.7 Kurtzke points. Those patients whose initial Kurtzke EDSS scores were greater than 2 (n = 164) deteriorated on an average of 0.82 points. Of interest was that 19.5% (39 of 200) of the patients reported a temporary improvement in bladder function, but improvement was maintained in only 11 patients (5.5%) at 2-year follow-up. Fifteen patients (7.5%) indicated long-term worsening. There was no significant change in the working status of the patients following hyperbaric oxygen treatment. Although this study treated the patients in accordance with protocols reported to produce a benefit in multiple sclerosis, we were unable to substantiate any useful long-term effect of hyperbaric oxygen therapy.

Plasmapheresis with acute inflammatory polyneuropathy.

Eleven children with acute inflammatory polyneuropathy were treated with a short course of intensive plasmapheresis. The 5 males and 6 females ranged in aged from 19 months to 16 years (mean: 7.8 years). The interval from disease onset to the initiation of plasmapheresis therapy was less than 7 days in 5 patients and less than 2 weeks in the others. At the time of the first plasmapheresis, 3 patients were on respirators (Grade 5 on the Guillain-Barré syndrome scale 0-6); 7 were bedridden (Grade 4); and 1 required assisted ambulation (Grade 3). One week after the last plasmapheresis, all but 1 patient had improved by 1 or more grades on the Guillain-Barré syndrome scale. At subsequent examination 6 months later, all patients were ambulatory and 9 of 11 had no significant neurologic findings. Electrophysiologic studies performed shortly before treatment initiation revealed predominant demyelinating neuropathy in 9 and axonal changes in 2. During the 76 plasmapheresis procedures, no severe complications were encountered. Although the number of patients treated is small, the clinical response observed would indicate plasmapheresis to be a safe and effective therapy in children with acute inflammatory polyneuropathy.