Modeling the health impact of increasing vaccine coverage and nonpharmaceutical interventions against coronavirus disease 2019 in Ghana.

Seroprevalence studies assessing community exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Ghana concluded that population-level immunity remained low as of February 2021. Thus, it is important to demonstrate how increasing vaccine coverage reduces the economic and public health impacts associated with SARS-CoV-2 transmission. To that end, this study used a Susceptible-Exposed-Presymptomatic-Symptomatic-Asymptomatic-Recovered-Dead-Vaccinated compartmental model to simulate coronavirus disease 2019 (COVID-19) transmission and the role of public health interventions in Ghana. The impact of increasing vaccination rates and decline in transmission rates due to nonpharmaceutical interventions (NPIs) on cumulative infections and deaths averted was explored under different scenarios. Latin hypercube sampling-partial rank correlation coefficient (LHS-PRCC) was used to investigate the uncertainty and sensitivity of the outcomes to the parameters. Simulation results suggest that increasing the vaccination rate to achieve 50% coverage was associated with almost 60,000 deaths and 25 million infections averted. In comparison, a 50% decrease in the transmission coefficient was associated with the prevention of about 150,000 deaths and 50 million infections. The LHS-PRCC results indicated that in the context of vaccination rate, cumulative infections and deaths averted were most sensitive to vaccination rate, waning immunity rates from vaccination, and waning immunity from natural infection. This study's findings illustrate the impact of increasing vaccination coverage and/or reducing the transmission rate by NPI adherence in the prevention of COVID-19 infections and deaths in Ghana.

Effects of Educational Interventions in Facilitating Mammography Screening Among Asian American Women: A Meta-Analysis.

PROBLEM IDENTIFICATION: This meta-analysis evaluated the effects of various types of educational interventions on increasing breast cancer screening uptake among Asian American women. LITERATURE SEARCH: Web of Science, MEDLINE®, PubMed®, and Cochrane Library were searched for randomized controlled trials published from 2010 to 2020 of interventions developed to promote mammography uptake among Asian American women. DATA EVALUATION: A random-effects model was used to estimate pooled effect sizes using relative risk measures. A funnel plot was used to assess publication bias. SYNTHESIS: Seven studies were included in this review. Educational interventions identified were primarily culturally sensitive approaches combined with access-enhancing, individually tailored, or group-based approaches. The interventions were effective at increasing the receipt of mammography. IMPLICATIONS FOR NURSING: This review provides insight into the importance of combining other approaches with educational interventions to increase their effectiveness for Asian American women. Future interventions can incorporate various approaches to enhance the ability of Asian American women to overcome barriers to breast cancer screening.

Age-Stratified Model to Assess Health Outcomes of COVID-19 Vaccination Strategies, Ghana.

We assessed the effect of various COVID-19 vaccination strategies on health outcomes in Ghana by using an age-stratified compartmental model. We stratified the population into 3 age groups: <25 years, 25-64 years, and ≥65 years. We explored 5 vaccination optimization scenarios using 2 contact matrices, assuming that 1 million persons could be vaccinated in either 3 or 6 months. We assessed these vaccine optimization strategies for the initial strain, followed by a sensitivity analysis for the Delta variant. We found that vaccinating persons <25 years of age was associated with the lowest cumulative infections for the main matrix, for both the initial strain and the Delta variant. Prioritizing the elderly (≥65 years of age) was associated with the lowest cumulative deaths for both strains in all scenarios. The consensus between the findings of both contact matrices depended on the vaccine rollout period and the objective of the vaccination program.

Transmission Dynamics of COVID-19 in Ghana and the Impact of Public Health Interventions.

This study characterized COVID-19 transmission in Ghana in 2020 and 2021 by estimating the time-varying reproduction number (Rt) and exploring its association with various public health interventions at the national and regional levels. Ghana experienced four pandemic waves, with epidemic peaks in July 2020 and January, August, and December 2021. The epidemic peak was the highest nationwide in December 2021 with Rt ≥ 2. Throughout 2020 and 2021, per-capita cumulative case count by region increased with population size. Mobility data suggested a negative correlation between Rt and staying home during the first 90 days of the pandemic. The relaxation of movement restrictions and religious gatherings was not associated with increased Rt in the regions with fewer case burdens. Rt decreased from > 1 when schools reopened in January 2021 to < 1 after vaccination rollout in March 2021. Findings indicated most public health interventions were associated with Rt reduction at the national and regional levels.

The use of digital technology to improve and monitor handwashing among children 12 years or younger in educational settings: a scoping review.

Our scoping review aimed to identify and describe the application of digital technology in hand hygiene research among children in educational settings. We searched for articles in PubMed, IEEE Xplore, and Web of Science. Original hand hygiene research with a form of digital technology used among children ≤12 years in educational settings was eligible for inclusion. Twelve studies met the eligibility criteria and the data were extracted by two teams of independent co-authors for narrative synthesis. Ten studies used digital technology as an intervention tool and two for monitoring purposes. Three main digital technologies were identified including computer games (n = 2), videos (n = 8), and video cameras (n = 2). Digital technologies found in our scoping review were reported to be effective in hand hygiene studies over short temporal periods especially when used in combination with other measures. Future research may demonstrate the effectiveness of digital technology in helping children develop sustainable handwashing behaviors.

Double-blind, randomized and controlled trial of EPI-743 in Friedreich's ataxia.

AIM: To evaluate the safety and clinical effects of EPI-743 in Friedreich's ataxia patients. EPI-743 is a compound that targets oxidoreductase enzymes essential for redox control of metabolism. METHODS: We conducted a multicenter trial that evaluated EPI-743 during a 6-month placebo-controlled phase, followed by an 18-month open-label phase. End points included low-contrast visual acuity and the Friedreich's Ataxia Rating Scale. RESULTS/CONCLUSION: EPI-743 was demonstrated to be safe and well tolerated. There were no significant improvements in key end points during the placebo phase. However, at 24 months, EPI-743 treatment was associated with a statistically significant improvement in neurological function and disease progression relative to a natural history cohort (p < 0.001).

Comprehensive systematic review summary: Treatment of cerebellar motor dysfunction and ataxia: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology.

OBJECTIVE: To systematically review evidence regarding ataxia treatment. METHODS: A comprehensive systematic review was performed according to American Academy of Neurology methodology. CONCLUSIONS: For patients with episodic ataxia type 2, 4-aminopyridine 15 mg/d probably reduces ataxia attack frequency over 3 months (1 Class I study). For patients with ataxia of mixed etiology, riluzole probably improves ataxia signs at 8 weeks (1 Class I study). For patients with Friedreich ataxia or spinocerebellar ataxia (SCA), riluzole probably improves ataxia signs at 12 months (1 Class I study). For patients with SCA type 3, valproic acid 1,200 mg/d possibly improves ataxia at 12 weeks. For patients with spinocerebellar degeneration, thyrotropin-releasing hormone possibly improves some ataxia signs over 10 to 14 days (1 Class II study). For patients with SCA type 3 who are ambulatory, lithium probably does not improve signs of ataxia over 48 weeks (1 Class I study). For patients with Friedreich ataxia, deferiprone possibly worsens ataxia signs over 6 months (1 Class II study). Data are insufficient to support or refute the use of numerous agents. For nonpharmacologic options, in patients with degenerative ataxias, 4-week inpatient rehabilitation probably improves ataxia and function (1 Class I study); transcranial magnetic stimulation possibly improves cerebellar motor signs at 21 days (1 Class II study). For patients with multiple sclerosis-associated ataxia, the addition of pressure splints possibly has no additional benefit compared with neuromuscular rehabilitation alone (1 Class II study). Data are insufficient to support or refute use of stochastic whole-body vibration therapy (1 Class III study).

Longitudinal gait and balance decline in Friedreich's Ataxia: A pilot study.

INTRODUCTION: Friedreich's Ataxia (FA) is a devastating, progressive, neurodegenerative disease. Objective measures that detect changes in neurological function in FA patients are needed to facilitate therapeutic clinical trials. The purpose of this pilot study was to analyze longitudinal changes in gait and balance in subjects with FA using the GAITRite Walkway System® and Biodex Balance System™, respectively, and to test the ability of these measures to detect change over time compared to the Friedreich's Ataxia Rating Scale (FARS). METHODS: This was a 24-month longitudinal study comparing ambulatory FA subjects with age- and gender-matched, healthy controls. Eight FA subjects and 8 controls were tested at regular intervals using the GAITRite and Biodex Balance systems and the FARS. RESULTS: In the FA group, comfortable and fast gait velocity declined 8.0% and 13.9% after 12 months and 24.1% and 30.3% after 24 months, respectively. Postural stability indices increased in FA subjects an average of 41% from baseline to 24 months, representing a decline in balance. Subjects with FA also demonstrated a 17.7% increase in FARS neurological exam scores over 24 months. There were no changes in gait or balance variables in controls. In the FA group, multiple gait and balance measures correlated significantly with FARS neurological exam scores. CONCLUSIONS: The GAITRite and Biodex Balance systems provided objective and clinically relevant measures of functional decline in subjects with FA that correlated significantly with performance measures in the FARS. Gait velocity may be an important objective measure to identify disease progression in adults with FA.

The association between arthritis and depression is intensified by excessive body weight: Findings from a US national survey, 2005-2012.

OBJECTIVE: Obesity and arthritis are leading chronic conditions, but comorbidity of these conditions and their interaction leading to depression have not been fully investigated. The purpose of this study is to determine the degree to which excess body weight effect-modifies the relationship between arthritis and depressive symptoms. METHODS: We used the data of 8677 men and 8820 women aged 20 or older, who completed a depression screening and general medical condition interview as a part of the National Health and Nutrition Examination Survey, 2005-2012. Depression was ascertained using the Patient Health Questionnaire-9 (PHQ-9); a PHQ-9 score of 15 or higher was defined as indicative of depression. RESULTS: Arthritis was reported in 26.5% (SE=0.9) of men and 36.9% (SE=1.4) of women. The association between depression and arthritis was not significant among healthy weight women, but significant among overweight and obese women. The prevalence ratios (PRs) of depression among arthritis-free women were 1.00 (reference) for healthy weight, 1.43 (0.85-2.42) for overweight, and 1.99 (1.23-3.23) for obese women. For women with arthritis, the PRs were 1.16 (0.63-2.12) for healthy weight, 3.80 (2.24-6.45) for overweight and 3.73 (2.30-6.05) for obese women. The intensifying effect from excessive body weight on the association between arthritis and depression was less salient among men than women. CONCLUSIONS: The association between arthritis and depression is intensified significantly by increased body weight, in particular, among women.

Occupational Characteristics and Patterns as Risk Factors for Parkinson's Disease: A Case Control Study.

BACKGROUND: Associations have been reported between the risk of Parkinson's disease (PD) and employment in certain fields. Most studies have focused on toxic exposures as potential causal explanations. However, PD also has been associated with personality characteristics that may influence occupational choices and patterns. OBJECTIVE: This study evaluates the role of personality as indicated by occupational choices and employment patterns in the risk for PD. METHODS: In-person interviews were conducted to assess occupational histories and early-adult personality indicators among 89 PD patients and 99 controls. RESULTS: PD cases had fewer lifetime jobs than controls (mean for cases = 4.38 ± 2.20; mean for controls = 5.00 ± 2.26; p = 0.03). Among women, PD was positively associated with more complex work with people (OR = 1.45, 95% CI 1.12-1.89), representing a 95% increased risk for PD comparing women with the greatest complexity of work with those requiring the least complexity of work with people. Women PD cases also performed less complex work with things compared with controls (OR = 0.69 (95% CI 0.53-0.90)), translating into a 13-fold increased risk for PD among women whose work involved the least complex work with things compared with the most. The numbers of jobs and job types were associated with taking more activity risks as a young-adult (r = 0.19, p = 0.02; r = 0.26, p = 0.001, respectively). CONCLUSIONS: Cases with PD held fewer lifetime jobs compared with controls. Occupational complexity was associated with the risk for PD among women, but not men. Further consideration of the possible influence of personality on occupational choices is warranted.

Randomized, controlled pilot trial of solifenacin succinate for overactive bladder in Parkinson's disease.

OBJECTIVE: To evaluate the efficacy of solifenacin succinate in Parkinson's disease (PD) patients suffering from overactive bladder (OAB). BACKGROUND: Urinary dysfunction is a commonly encountered non-motor feature in PD that significantly impacts patient quality of life. DESIGN/METHODS: This was a double-blind, randomized, placebo-controlled, 3-site study with an open label extension phase to determine the efficacy of solifenacin succinate in idiopathic PD patients with OAB. Patients were randomized to receive solifenacin succinate 5-10 mg daily or placebo for 12 weeks followed by an 8-week open label extension. The primary outcome measure was the change in the mean number of micturitions per 24 h period. Secondary outcome measures included the change in the mean number of urinary incontinence episodes and the mean number of nocturia episodes. RESULTS: Twenty-three patients were randomized in the study. There was no significant improvement in the primary outcome measure in the double-blind phase, but there was an improvement in the number of micturitions per 24 h period in the solifenacin succinate group compared to placebo at a mean dose of 6 mg/day (p = 0.01). In the open label phase, the mean number of urinary incontinence episodes per 24 h period decreased (p = 0.03), as did the number of nocturia episodes per 24 h period (p = 0.01). Adverse events included constipation and xerostomia, which resolved after treatment was discontinued. CONCLUSIONS: In this pilot trial, solifenacin succinate treatment led to an improvement in urinary incontinence, despite persistence in other OAB symptoms.

Accelerated Resolution Therapy for treatment of pain secondary to symptoms of combat-related posttraumatic stress disorder.

BACKGROUND: As many as 70% of veterans with chronic pain treated within the US Veterans Administration (VA) system may have posttraumatic stress disorder (PTSD), and conversely, up to 80% of those with PTSD may have pain. We describe pain experienced by US service members and veterans with symptoms of PTSD, and report on the effect of Accelerated Resolution Therapy (ART), a new, brief exposure-based therapy, on acute pain reduction secondary to treatment of symptoms of PTSD. METHODS: A randomized controlled trial of ART versus an attention control (AC) regimen was conducted among 45 US service members/veterans with symptoms of combat-related PTSD. Participants received a mean of 3.7 sessions of ART. RESULTS: Mean age was 41.0 + 12.4 years and 20% were female. Most veterans (93%) reported pain. The majority (78%) used descriptive terms indicative of neuropathic pain, with 29% reporting symptoms of a concussion or feeling dazed. Mean pre-/post-change on the Pain Outcomes Questionnaire (POQ) was -16.9±16.6 in the ART group versus -0.7±14.2 in the AC group (p=0.0006). Among POQ subscales, treatment effects with ART were reported for pain intensity (effect size = 1.81, p=0.006), pain-related impairment in mobility (effect size = 0.69, p=0.01), and negative affect (effect size = 1.01, p=0.001). CONCLUSIONS: Veterans with symptoms of combat-related PTSD have a high prevalence of significant pain, including neuropathic pain. Brief treatment of symptoms of combat-related PTSD among veterans by use of ART appears to acutely reduce concomitant pain.

Metal stopping reagents facilitate discontinuous activity assays of the de novo purine biosynthesis enzyme PurE.

The conversion of 5-aminoimidazole ribonucleotide (AIR) to 4-carboxy-AIR (CAIR) represents an unusual divergence in purine biosynthesis: microbes and nonmetazoan eukaryotes use class I PurEs while animals use class II PurEs. Class I PurEs are therefore a potential antimicrobial target; however, no enzyme activity assay is suitable for high throughput screening (HTS). Here we report a simple chemical quench that fixes the PurE substrate/product ratio for 24h, as assessed by the Bratton-Marshall assay (BMA) for diazotizable amines. The ZnSO4 stopping reagent is proposed to chelate CAIR, enabling delayed analysis of this acid-labile product by BMA or other HTS methods.

Randomized controlled trial of accelerated resolution therapy (ART) for symptoms of combat-related post-traumatic stress disorder (PTSD).

OBJECTIVES: Therapies for post-traumatic stress disorder (PTSD) endorsed by the Department of Defense and Veterans Administration are relatively lengthy, costly, and yield variable success. We evaluated Accelerated Resolution Therapy (ART) for the treatment of combat-related psychological trauma. METHODS: A randomized controlled trial of ART versus an Attention Control (AC) regimen was conducted among 57 U.S. service members/veterans. After random assignment, those assigned to AC were offered crossover to ART, with 3-month follow-up on all participants. Self-report symptoms of PTSD and comorbidities were analyzed among study completers and by the intention-to-treat principle. RESULTS: Mean age was 41 ± 13 years with 19% female, 54% Army, and 68% with prior PTSD treatment. The ART was delivered in 3.7 ± 1.1 sessions with a 94% completion rate. Mean reductions in symptoms of PTSD, depression, anxiety, and trauma-related guilt were significantly greater (p < 0.001) with ART compared to AC. Favorable results for those treated with ART persisted at 3 months, including reduction in aggression (p < 0.0001). Adverse treatment-related events were rare and not serious. CONCLUSIONS: ART appears to be a safe and effective treatment for symptoms of combat-related PTSD, including refractory PTSD, and is delivered in significantly less time than therapies endorsed by the Department of Defense and Veterans Administration.

Function and X-ray crystal structure of Escherichia coli YfdE.

Many food plants accumulate oxalate, which humans absorb but do not metabolize, leading to the formation of urinary stones. The commensal bacterium Oxalobacter formigenes consumes oxalate by converting it to oxalyl-CoA, which is decarboxylated by oxalyl-CoA decarboxylase (OXC). OXC and the class III CoA-transferase formyl-CoA:oxalate CoA-transferase (FCOCT) are widespread among bacteria, including many that have no apparent ability to degrade or to resist external oxalate. The EvgA acid response regulator activates transcription of the Escherichia coli yfdXWUVE operon encoding YfdW (FCOCT), YfdU (OXC), and YfdE, a class III CoA-transferase that is ~30% identical to YfdW. YfdW and YfdU are necessary and sufficient for oxalate-induced protection against a subsequent acid challenge; neither of the other genes has a known function. We report the purification, in vitro characterization, 2.1-Å crystal structure, and functional assignment of YfdE. YfdE and UctC, an orthologue from the obligate aerobe Acetobacter aceti, perform the reversible conversion of acetyl-CoA and oxalate to oxalyl-CoA and acetate. The annotation of YfdE as acetyl-CoA:oxalate CoA-transferase (ACOCT) expands the scope of metabolic pathways linked to oxalate catabolism and the oxalate-induced acid tolerance response. FCOCT and ACOCT active sites contain distinctive, conserved active site loops (the glycine-rich loop and the GNxH loop, respectively) that appear to encode substrate specificity.

Evidence-based guideline: treatment of tardive syndromes: report of the Guideline Development Subcommittee of the American Academy of Neurology.

OBJECTIVE: To make evidence-based recommendations regarding management of tardive syndromes (TDS), including tardive dyskinesias (TDD), by addressing 5 questions: 1) Is withdrawal of dopamine receptor blocking agents (DRBAs) an effective TDS treatment? 2) Does switching from typical to atypical DRBAs reduce TDS symptoms? 3) What is the efficacy of pharmacologic agents in treating TDS? 4) Do patients with TDS benefit from chemodenervation with botulinum toxin? 5) Do patients with TDS benefit from surgical therapy? METHODS: PsycINFO, Ovid MEDLINE, EMBASE, Web of Science, and Cochrane were searched (1966-2011). Articles were classified according to a 4-tiered evidence-rating scheme; recommendations were tied to the evidence. RESULTS AND RECOMMENDATIONS: Clonazepam probably improves TDD and ginkgo biloba probably improves TDS (both Level B); both should be considered as treatment. Risperidone may improve TDS but cannot be recommended as treatment because neuroleptics may cause TDS despite masking symptoms. Amantadine and tetrabenazine might be considered as TDS treatment (Level C). Diltiazem should not be considered as TDD treatment (Level B); galantamine and eicosapentaenoic acid may not be considered as treatment (Level C). Data are insufficient to support or refute use of acetazolamide, bromocriptine, thiamine, baclofen, vitamin E, vitamin B6, selegiline, clozapine, olanzapine, melatonin, nifedipine, fluperlapine, sulpiride, flupenthixol, thiopropazate, haloperidol, levetiracetam, quetiapine, ziprasidone, sertindole, aripiprazole, buspirone, yi-gan san, biperiden discontinuation, botulinum toxin type A, electroconvulsive therapy, α-methyldopa, reserpine, and pallidal deep brain stimulation as TDS treatments (Level U). Data are insufficient to support or refute TDS treatment by withdrawing causative agents or switching from typical to atypical DRBA (Level U).

Update on treatment of essential tremor.

OPINION STATEMENT: Essential tremor is one of the most common movement disorders in the world. Although millions of people worldwide are affected by ET, only one medication, propranolol, is approved by the United States Food and Drug Administration to treat it. None of the medications currently used as ET therapy were developed specifically for this purpose, and select antihypertensive and antiepileptic medications remain at the forefront of ET therapy. Propranolol and primidone are considered "effective" agents that treat ET; topiramate, atenolol, and alprazolam are "probably effective", and nimodipine, nadolol, and clonazepam are "possibly effective". Medications that probably do not adequately treat ET include levetiracetam and pregabalin. Gabapentin appears to improve ET when used as monotherapy, but not when used as adjunct therapy. Sotalol has been found to be "probably effective" in treating ET in previous reviews, but it may be associated with arrhythmias and should not be routinely recommended. Botulinum toxin A may reduce limb tremor, but may cause dose dependent weakness. Deep brain stimulation (DBS) of the VIM is used as an alternative to pharmacological therapy of ET in patients who fail to adequately respond to medical therapy. The magnitude of effect from DBS is greater than from medical management, but more severe side effects are possible with surgery. Future treatment options for ET will depend on valid animal models, and a better understanding of its pathophysiology.