Genitourinary Symptoms Associated with Chlamydia trachomatis and Neisseria gonorrhoeae Infections in a Tertiary Care Hospital in Oman.

Objectives: This study aimed to determine the pattern of clinical presentations associated with Chlamydia trachomatis and Neisseria gonorrhoeae infections. Methods: A retrospective cohort study was conducted between 2015 and 2020 and included patients attending Sultan Qaboos University Hospital, Muscat, Oman, who were tested for these infections using nucleic acid amplification. Results: A total of 408 women and 89 men were included. A total of 11 infections were identified in women (n = 11, 2.7%) and 14 in men (n = 14, 15.7%). Chlamydia accounted for almost all infections in women (n = 10, 90.9%), commonly presenting with lower abdominal pain or abnormal vaginal bleeding. In men, urethral discharge/dysuria syndrome was the most common presentation and chlamydia was identified in eight men and gonorrhoea in six; a majority of all infections were seen in patients ≤35 years old. Conclusion: The relative prevalence of two common sexually transmitted infections (STIs) among patients with genitourinary symptoms at a tertiary referral hospital have been described. The pattern of their presentations will inform the design of prospective studies to improve surveillance and guide public health policy in Oman. This study highlights the need for a multi-sectoral approach involving all providers to enable comprehensive STI surveillance.

Retention in HIV care and factors associated with loss to follow-up in Oman: a countrywide study from the Middle East.

We conducted a cross-sectional analysis to determine the rate of retention in HIV care and the factors associated with loss to follow-up (LTFU) among Omani adults living with HIV who were linked to care as of 31 December 2019. Patients (n = 1610) were identified from a central national HIV surveillance dataset. The majority (68.3%) of patients were male, and the median age was 39 years (IQR, 31-48 years). A total of 1480 patient (91.9%) were retained in care. On multivariate analysis, compared to those who received antiretroviral therapy (ART), patients who had never been on ART were 6.8 (95% CI: 3.05-15.16) times more likely to be lost to follow-up. Patients who had a latest HIV viral load (VL) of 200-999 copies/ml (adjusted odds ratio [aOR]: 4.92, 95% CI: 2.27-10.69) and ≥ 1000 copies/ml (aOR: 15.03, 95% CI: 8.31-27.19) compared to those who had a latest HIV VL of <200 copies/ml had higher odds of loss to follow-up. Moreover, patients who were divorced or widowed were 2.64 (95% CI: 1.14-6.07) times more likely to disengage from HIV services, compared to those who were married. These findings will be invaluable in developing targeted interventions that further improve patients' retention in HIV care in Oman.

Predictors of late presentation and advanced HIV disease among people living with HIV in Oman (2000-2019).

BACKGROUND: The aim of this study was to determine the proportions and predictors of late presentation (LP) and advanced HIV disease (AD) in Oman. LP and AD were defined as presenting with a baseline CD4 count of < 350 and < 200 cells/mm3, respectively. METHODS: We conducted a retrospective database analysis of the National HIV Surveillance System to identify Omani people (≥ 13 years old) who were diagnosed with HIV in the period between January 2000 and December 2019 and had a documented baseline CD4 cell count. We calculated the rates and trend over time of LP and AD. A logistic regression was carried out to determine the predictors of LP and AD. RESULTS: A total of 1418 patients, who were diagnosed with HIV in the period from January 2000 to December 2019, were included; 71% were male and 66% were heterosexuals. The median (IQR) age at diagnosis was 33 (25-39) years. Overall, 71% (95% CI: 68-73) and 46% (95% CI: 44-49) of patients had LP and AD at presentation, respectively. The LP percentage decreased from 76% in 2000-2004 to 69% in 2015-2019; AD percentage decreased from 57 to 46% over the same period. The proportions of men with LP and AD were higher than women (74% vs. 62 and 50% vs. 36%, respectively). The percentages of persons with LP among people aged 13-24, 25-49, and ≥ 50 years were 65, 71, and 84%, respectively. The proportions of persons with AD among people aged 13-24, 25-49, and ≥ 50 years were 39, 46, and 65%, respectively. Logistic regression showed that male sex, older age, having an "unknown" HIV risk factor, and living outside Muscat were independent predictors of AD. Male sex also independently predicted LP. CONCLUSIONS: This analysis indicates that a significant proportion of new HIV cases in Oman continue to present late. This study identified patient subgroups at greatest risk of late HIV diagnosis such as men and older people. Targeted interventions and greater efforts to scale up HIV testing services in Oman are needed.

Elimination of mother-to-child transmission of HIV in Oman: a success story from the Middle East.

BACKGROUND: In January 2016, the National AIDS Programme (NAP) in Oman introduced a package of interventions, including capacity building for service providers, to improve the quality of HIV services. AIMS: To report the impact of these interventions on the rate of vertical HIV transmission in the period from January 2016 to December 2019. We also describe the virological and obstetric outcomes for HIV-infected pregnant women. METHODS: This was a medical record review of 94 HIV-positive pregnant women (median age 32 years; interquartile range 25-34 years) reported to NAP in 2016-2019. RESULTS: There were 110 pregnancies in 94 women. The majority (75.3%, 61/81) of women were diagnosed with HIV infection from routine antenatal screening, with 60% (66/110) of pregnancies occurring in women who knew their HIV status at conception. Caesarean section was the most common (50%) mode of delivery. The preterm labour and low birth weight rates were 21.2% and 15.9%, respectively. The antiretroviral coverage during pregnancy was 95.5%, with most (87.8%) women reporting excellent or good adherence. The majority (81.6%) of women achieved HIV viral load of < 400 copies/ml at or near delivery. Almost all infants (99%) were given prophylactic antiretrovirals. The rate of mother-to-child transmission of HIV was 1%. CONCLUSION: The obstetric and virological outcomes for HIV-infected pregnant women delivered in 2016-2019 were favourable, with a low rate of mother-to-child transmission of HIV. Oman is now in the process of finalizing application of World Health Organization validation of elimination of mother-to-child transmission of HIV.

Effectiveness of Intrathecal Baclofen for Intractable Stiffperson Syndrome: a Case Report.

BACKGROUND: Intrathecal baclofen is considered an adjuvant therapy for patients with intractable spasms due to stiff-person syndrome. There is increasing evidence to support the use of intrathecal baclofen in the management of symptomatic stiffperson syndrome, with improvement in function. CASE REPORT: A 38-year-old woman with stiff- person syndrome initially presented to inpatient rehabilitation for intractable muscle spasms. The symptoms made her non-ambulatory and limited her tolerance to wheelchair use for mobility. The patient underwent up-titration of oral baclofen and diazepam, with concurrent intravenous immunoglobulin cycles, leading to transient symptom relief. She agreed to explore intrathecal baclofen therapy. An initial trial of a single bolus of 50 µg intrathecal baclofen resulted in a significant decrease in spontaneous spasms, enabling modified independence in transfers and ambulation. The patient was subsequently implanted with a permanent intrathecal delivery system. To date, the intrathecal baclofen had been titrated to 186 µg per day with simple continuous delivery. The patient was weaned off oral baclofen. She attained complete functional independence with ambulation without the need for assistive devices, and has had no lasting post-procedural complications to date. CONCLUSION: This case report adds to the increasing evidence of cases of refractory stiff-person syndrome managed successfully using intrathecal baclofen therapy.

Acceptability and feasibility of testing for sexually transmitted infections among pregnant women in Muscat, Sultanate of Oman.

There are currently no reliable epidemiological data for estimating the burden of sexually transmitted infections (STIs) in Oman. STIs such as gonorrhoea and chlamydia are often asymptomatic and associated with sexual and reproductive morbidity. An exploratory study was conducted in an antenatal clinic in Muscat, Oman, to assess the acceptability and feasibility of testing for gonorrhoea and chlamydia. Two hundred and twenty-one women were recruited over 14 weeks between July and October 2020. There were three cases of chlamydia (3/221, 1.36%); no cases of gonorrhoea were identified. Acceptability and feasibility for testing in this cohort of pregnant women were good despite anticipated cultural sensitivities surrounding sexually transmitted infections.

Predictors of virologic failure among people living with HIV in Oman: a national study from the Middle East.

We conducted a cross-sectional analysis to determine HIV virologic failure and its associated factors among Omani people living with HIV who are on ART for > 6 months. Patients (n = 1427) were identified from a central national HIV surveillance dataset. Two-thirds (67%) of patients were male, and the median age was 39 years (IQR, 32-48 years). Out of 1427 patients, 14.4% had virologic failure (HIV viral load [VL] ≥ 200 copies/ml). The multivariate analysis showed that patients aged 25-49 years (adjusted odds ratio [aOR]: 1.76, 95% CI: 1.01-3.08) were significantly more likely to fail treatment, compared to those aged ≥ 50 years. Besides, having "Other" HIV risk factor (compared to heterosexuals, aOR: 1.82, 95% CI: 1.02-3.24) and receiving HIV care outside the capital Muscat (compared to those cared for in Muscat, aOR: 1.73, 95% CI: 1.11-2.7) were independently associated with virologic failure. HIV viral suppression (85.6%) in Oman is encouraging; however, further strategies, mainly targeting patients who are young (<50 years), those not disclosing their HIV risk factor and those attending HIV treatment centres outside Muscat, are required to enhance HIV treatment outcome in Oman.

The Epidemiology of HIV in Oman, 1984-2018: A Nationwide Study from the Middle East.

We used population-based data on all diagnosed people living with Human Immunodeficiency (HIV) reported to the National AIDS Programme in 1984-2018 to describe the HIV epidemiology in Oman. A total of 3060 Omanis were diagnosed with HIV from 1984 to 2018. The proportions of new infections attributed to sexual contact accounted for 56.3% (376/668) in 1984-1996 compared with 80.7% (630/780) in 2013-2018. Of 1417 patients with a documented CD4 count at the entry of care, 45.3% had a baseline CD4 count of <200 cells/mm3. Compared with heterosexuals, homosexuals had higher rates of advanced HIV disease [42.7% (388/908) vs 50.4% (136/270), respectively]. Rates of advanced disease and death within a year of HIV diagnosis rose consistently with age at diagnosis. Approximately half (48.8%) of the patients diagnosed in 1984-2018 had died by December 2018. The majority (85.6%; 572/668) of people who were diagnosed in 1984-1997 had died compared with 12.7% (99/780) of those diagnosed in 2013-2018. However, people died more recently had a higher proportion of death within a year of HIV diagnosis [74.7% (74/99) in 2013-2018 compared with 13.8% (79/572) in 1984-1996]. This study shows that the HIV epidemic in Oman is a low-prevalence one. Of concern, a large proportion of new HIV diagnoses continued to present late, which has resulted in a substantial increase in short-term mortality over the past 20 years. Nevertheless, we observed a remarkable decline in overall mortality over time, which may be explained by the improvement in the quality of HIV care in Oman.

The cascade of HIV care in Oman, 2015-2018: A population-based study from the Middle East.

OBJECTIVE: To evaluate the cascade of HIV care in Oman in 2018 and the longitudinal change in each step from 2015 to 2018. METHODS: Population-based data on all diagnosed people living with HIV reported to the National AIDS Programme in 1984-2018 were used. RESULTS: As of December 31, 2018, the estimated number of people living with HIV in Oman was 3030; 1532 (50.6%) were aware of their infection. Of the diagnosed patients, 95.9% were linked to care, 85.8% were retained in care, and 84.3% were on ART. The proportions of patients with viral suppression out of all people with HIV, the diagnosed persons, and those on ART were 37.3%, 73.7%, and 87.5%, respectively. The proportion of patients linked to care increased from 72.6% in 2015 to 95.6% in 2018 (p < 0.001). Only 57% (947/1661) were retained in care in 2015, which increased to 76.9% (1193/1552) in 2017 and 85.8% (1314/1532) in 2018 (p < 0.001). Viral suppression increased from 75.7% (672/888) in 2015 to 84.5% (859/1017) in 2016 and 87.5% (1129/1291) in 2018 (p < 0.001). CONCLUSIONS: A sustained improvement in linkage to care, retention in care, ART coverage, and viral suppression was observed amongst people living with HIV in Oman in 2015-2018.

Role of Diet and Nutritional Supplements in Parkinson's Disease Progression.

OBJECTIVES: The goal of this study is to describe modifiable lifestyle variables associated with reduced rate of Parkinson's disease (PD) progression. METHODS: The patient-reported outcomes in PD (PRO-PD) were used as the primary outcome measure, and a food frequency questionnaire (FFQ) was used to assess dietary intake. In this cross-sectional analysis, regression analysis was performed on baseline data to identify the nutritional and pharmacological interventions associated with the rate of PD progression. All analyses were adjusted for age, gender, and years since diagnosis. RESULTS: 1053 individuals with self-reported idiopathic PD were available for analysis. Foods associated with the reduced rate of PD progression included fresh vegetables, fresh fruit, nuts and seeds, nonfried fish, olive oil, wine, coconut oil, fresh herbs, and spices (P < 0.05). Foods associated with more rapid PD progression include canned fruits and vegetables, diet and nondiet soda, fried foods, beef, ice cream, yogurt, and cheese (P < 0.05). Nutritional supplements coenzyme Q10 and fish oil were associated with reduced PD progression (P = 0.026 and P = 0.019, resp.), and iron supplementation was associated with faster progression (P = 0.022). DISCUSSION: These are the first data to provide evidence that targeted nutrition is associated with the rate of PD progression.

Use of a self-rating scale of the nature and severity of symptoms in Parkinson's Disease (PRO-PD): Correlation with quality of life and existing scales of disease severity.

A self-rating scale was developed to permit patient-reported, remote assessment of Parkinson's disease symptom severity. The goal was to create a continuous outcome measure that does not require a clinical exam, does not fluctuate in response to dopaminergic medications, takes only a few minutes to complete, allows for stratification by symptom(s), and captures both motor and non-motor Parkinson's disease symptoms, major contributors to quality of life. The Patient Reported Outcomes in Parkinson's Disease (PRO-PD) is the cumulative score of 32 slider bars, each evaluating a common Parkinson's disease symptom. The PRO-PD has been used as an outcome measure in three studies. The baseline data from each of these studies were pooled for this analysis. Symptom frequency and severity are described, as well as correlation coefficients with existing measures of Parkinson's disease severity. Data on 1031 participants with Parkinson's disease were available for analysis. Fatigue, impaired handwriting, daytime sleepiness, slowness, tremor, muscle cramps, and forgetfulness were the most frequently reported symptoms. Persons with a relatively long duration of Parkinson's disease tended to report more, and more severe, symptoms. The PRO-PD was most highly correlated with the Parkinson's Disease Questionaire-39 (r = 0.763, P < 0.000) and Patient-Reported Outcome Measurement Information System Global quality of life (r = -0.7293, P < 0.000), other patient-reported quality of life measures. The PRO-PDnon-motor subset was highly correlated with the Non-Motor Symptom Score (r = 0.7533, P < 0.000). There was a moderate correlation seen with Hoehn & Yahr (r = 0.5922, P < 0.000), total Unified Parkinson's disease Rating Scale (r = 0.4724, P < 0.000), and the Timed-Up-&-Go (r = 0.4709, P < 0.000). The PRO-PD may have utility for patients, providers, and researchers as a patient-centered measure of Parkinson's disease symptom severity. Further PRO-PD validation efforts are warranted.

Phase IIb Study of Intranasal Glutathione in Parkinson's Disease.

BACKGROUND: Reduced glutathione (GSH) is an endogenously synthesized tripeptide depleted early in the course of Parkinson's disease (PD) and GSH augmentation has been proposed as a therapeutic strategy in PD. OBJECTIVE: This Phase IIb study was designed to evaluate whether a Phase III study of intranasal GSH, (in)GSH, for symptomatic relief is warranted and to determine the most appropriate trial design for a disease-modification study. METHODS: This was a double-blind, placebo-controlled trial of 45 individuals with Hoehn & Yahr Stage 1-3 PD. Participants were randomized to receive intranasal placebo (saline), 100 mg GSH, or 200 mg GSH thrice daily for three months, and were observed over a one-month washout period. RESULTS: All cohorts improved over the intervention period, including placebo. The high-dose group demonstrated improvement in total Unified PD Rating Scale (UPDRS) (-4.6 (4.7), P = 0.0025) and UPDRS motor subscore (-2.2 (3.8), P = 0.0485) over baseline, although neither treatment group was superior to placebo. One participant in the high-dose GSH cohort developed cardiomyopathy. CONCLUSIONS: Although predicted improvements in PD total and motor scores were observed, these data do not suggest (in)GSH is superior to placebo after a three month intervention. The symptomatic effects are sufficient to warrant a delayed-start or wash-out design study for disease-modification trials. Whether long-term use of (in)GSH leads to clinical improvements that are sustained and significantly different than placebo will require appropriately-powered longer-duration studies in larger cohorts. The improvement in the placebo arm was more robust than has been observed in previous PD studies and warrants further investigation.

A Rare Case of Digital Ischemia and Gangrene in ANCA-Associated Vasculitis with Review of the Literature.

This paper describes one patient with Antineutrophil Cytoplasmic Antibody- (ANCA-) associated vasculitis who initially presented with multiple ischemic fingers and toes. On further evaluation, the patient was also found to have pulmonary-renal involvement and episcleritis. The diagnosis was supported with a positive cANCA (anti-proteinase 3) and a bronchoscopy consistent with diffuse alveolar hemorrhage. Although the patient refused a tissue biopsy, clinical presentation including nasal ulceration, sinus congestion, and epistaxis and anti-proteinase 3 antibody were more consistent with Granulomatosis with Polyangiitis (GPA) rather than Microscopic Polyangiitis (MPA) or Eosinophilic Granulomatosis with Polyangiitis (EGPA) based on the recently presented ACR/EULAR Provisional 2017 Classification Criteria for GPA (Luqmani et al., 2016). The patient responded well to therapy including high dose steroids and cyclophosphamide, with improvement of all organs involved and had no further digital ischemia or gangrene on follow-up. We include a review of the English literature summarizing presentation, management, and outcome of 16 similar cases.

Lipid Flippase Subunit Cdc50 Mediates Drug Resistance and Virulence in Cryptococcus neoformans.

UNLABELLED: Cryptococcus neoformans is a human fungal pathogen and a major cause of fungal meningitis in immunocompromised individuals. Treatment options for cryptococcosis are limited. Of the two major antifungal drug classes, azoles are active against C. neoformans but exert a fungistatic effect, necessitating long treatment regimens and leaving open an avenue for emergence of azole resistance. Drugs of the echinocandin class, which target the glucan synthase and are fungicidal against a number of other fungal pathogens, such as Candida species, are ineffective against C. neoformans Despite the sensitivity of the target enzyme to the drug, the reasons for the innate resistance of C. neoformans to echinocandins remain unknown. To understand the mechanism of echinocandin resistance in C. neoformans, we screened gene disruption and gene deletion libraries for mutants sensitive to the echinocandin-class drug caspofungin and identified a mutation of CDC50, which encodes the ß-subunit of membrane lipid flippase. We found that the Cdc50 protein localized to membranes and that its absence led to plasma membrane defects and enhanced caspofungin penetration into the cell, potentially explaining the increased caspofungin sensitivity. Loss of CDC50 also led to hypersensitivity to the azole-class drug fluconazole. Interestingly, in addition to functioning in drug resistance, CDC50 was also essential for fungal resistance to macrophage killing and for virulence in a murine model of cryptococcosis. Furthermore, the surface of cdc50Δ cells contained increased levels of phosphatidylserine, which has been proposed to act as a macrophage recognition signal. Together, these results reveal a previously unappreciated role of membrane lipid flippase in C. neoformans drug resistance and virulence. IMPORTANCE: Cryptococcus neoformans is a fungal pathogen that is the most common cause of fungal meningitis, causing over 620,000 deaths annually. The treatment options for cryptococcosis are very limited. The most commonly used drugs are either fungistatic (azoles) or highly toxic (amphotericin B). Echinocandins are the newest fungicidal drug class that works well in treating candidiasis and aspergillosis, yet they are ineffective in treating cryptococcosis. In this study, we showed that the regulatory subunit of the lipid translocase (flippase), a protein that regulates the asymmetrical orientation of membrane lipids, is required for C. neoformans resistance to caspofungin, as well as for virulence during infection. This discovery identifies lipid flippase as a potential C. neoformans drug target, which plays an important role in the innate resistance of C. neoformans to echinocandins and in fungal virulence.

Fever, Myositis, and Paralysis: Is This Inflammatory Myopathy or Neuroinvasive Disease?

West Nile virus (WNV) is a mosquito-borne RNA Flavivirus which emerged in North America in 1999. Most patients present with a febrile illness but a few develop WNV neuroinvasive disease. Myopathy is an uncommon manifestation. We describe a case of a 42-year-old male from Los Angeles who presented with 8 days of fever and muscle pain. Initial physical exam was normal except for 4/5 muscle strength testing in his extremity proximal muscles. Laboratory revealed a creatine kinase of 45,000 and a urinalysis with large blood but no red blood cells, suggesting rhabdomyolysis. The patient's condition declined despite aggressive supportive care and hydration, and on hospital day #6 he developed severe altered mental status and progressed to complete right arm paralysis and 2/5 muscle strength in bilateral legs. EMG/NCS showed sensorimotor axonal polyneuropathy and the cerebrospinal fluid was positive for IgM and IgG WNV antibodies. The patient was diagnosed with WNV neuroinvasive disease, poliomyelitis (and encephalitis) type with myopathy/muscle involvement. He was treated supportively and his muscle and neurologic disease gradually improved. At 12-month follow-up his muscle enzymes had normalized and his weakness had improved to 5/5 strength in bilateral legs and 3/5 strength in the right arm.