Effects of a Remote Multimodal Intervention Involving Diet, Walking Program, and Breathing Exercise on Quality of Life Among Newly Diagnosed People with Multiple Sclerosis: A Quasi-Experimental Non-Inferiority Pilot Study.

Background: Interventions involving diet, physical activity, and breathing exercises are shown to be beneficial in managing both fatigue and quality of life (QoL) related to MS; however, the impact of such interventions among people newly diagnosed with clinically isolated syndrome (CIS) or relapsing-remitting multiple sclerosis (RRMS) who decline disease-modifying therapies (DMTs) is unknown. Methods: A 12-month prospective quasi-experimental non-inferiority trial recruited people newly diagnosed with CIS or RRMS who voluntarily declined DMTs (health behavior group; HB, n = 29) or followed standard of care (SOC, n = 15). Participants in the HB group were remotely coached on the study diet, moderate-intensity walking, and breathing exercises. All participants completed questionnaires validated to assess MS symptoms, including perceived mental and physical QoL (MSQOL54); fatigue (Fatigue Severity Scale, FSS; and Modified Fatigue Impact Scale, MFIS); mood (Hospital Anxiety and Depression Scale, HADS); and cognitive function (Perceived Deficits Questionnaire, PDQ). Results: During the 12 months, the HB group experienced improvement in scores for mental QoL (MSQOL54 - Mental, 0.24, 95% CI 0.01, 0.47; p = 0.04), fatigue (Total MFIS, -7.26, 95% CI -13.3,-1.18; p = 0.02), and perceived cognitive function (Total PDQ, PDQ-Attention, PDQ-Promemory, and PDQ-Planning, p ≤ 0.03 for all). A between-group difference was observed only for PDQ-Planning (p = 0.048). Non-inferiority analysis revealed that the 12-month changes in means for the HB group were not worse than those for the SOC group with respect to fatigue (FSS, p = 0.02), mood (HDS-Anxiety, p = 0.02; HADS-Depression, p < 0.0001), physical QoL (MSQOL54 - Physical, p = 0.02), or cognitive dysfunction (Total PDQ, p = 0.01). Conclusion: The multimodal lifestyle intervention for individuals newly diagnosed with CIS or RRMS, who voluntarily decline DMTs, did not yield patient-reported outcomes worse than those observed in the SOC group regarding perceived mental quality of life, mood, fatigue, and cognitive function. Trial Registration: clinicaltrials.gov identifier: NCT04009005.

Diet-induced changes in functional disability are mediated by fatigue in relapsing-remitting multiple sclerosis: A secondary analysis of the WAVES randomized parallel-arm trial.

Background: People with multiple sclerosis (MS) often report dietary modifications; however, evidence on functional outcomes remains sparse. Objective: Evaluate the impact of the low-saturated fat (Swank) and modified Paleolithic elimination (Wahls) diets on functional disability among people with relapsing-remitting MS. Methods: Baseline-referenced MS functional composite (MSFC) scores were calculated from nine-hole peg-test (NHPT), timed 25-foot walk, and oral symbol digit modalities test (SDMT-O) collected at four study visits: (a) run-in, (b) baseline, (c) 12 weeks, and (d) 24 weeks. Participants were observed at run-in and then randomized at baseline to either the Swank (n = 44) or Wahls (n = 43) diets. Results: Among the Swank group, MSFC scores significantly increased from -0.13 ± 0.14 at baseline to 0.10 ± 0.11 at 12 weeks (p = 0.04) and 0.14 ± 0.11 at 24 weeks (p = 0.02). Among the Wahls group, no change in MSFC scores was observed at 12 weeks from 0.10 ± 0.11 at baseline but increased to 0.28 ± 0.13 at 24 weeks (p = 0.002). In both groups, NHPT and SDMT-O z-scores increased at 24 weeks. Changes in MSFC and NHPT were mediated by fatigue. Discussion: Both diets reduced functional disability as mediated by fatigue. Trial Registration: Clinicaltrials.gov Identifier: NCT02914964.

Neurologic Complications of COVID-19.

OBJECTIVE: This article describes the spectrum of neurologic complications occurring in acute or postacute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as well as the neurologic risks and benefits of vaccination against SARS-CoV-2. LATEST DEVELOPMENTS: Early in the COVID-19 pandemic, reports of neurologic complications of COVID-19 began to surface. A variety of neurologic conditions have since been reported in association with COVID-19. Understanding of the underlying mechanism of COVID-19 neurologic involvement continues to evolve; however, the evidence seems to suggest that aberrant inflammatory responses may play a role. In addition to neurologic symptoms in acute COVID-19, neurologic post-COVID-19 conditions are increasingly recognized. The development of COVID-19 vaccines has been essential in preventing the spread of COVID-19. With increasing numbers of vaccine doses administered, various neurologic adverse events have been reported. ESSENTIAL POINTS: Neurologists must be aware of the potential acute, postacute, and vaccine-associated neurologic complications associated with COVID-19 and be poised to serve as integral members of multidisciplinary care teams for patients with COVID-19-related conditions.

The COVID-19 pandemic's impact on all-cause mortality disparities in Medicare: By race, income, chronic health, mental/behavioral health, disability.

BACKGROUND: The Medicare-enrolled population is heterogeneous across race, ethnicity, age, dual eligibility, and a breadth of chronic health, mental and behavioral health, and disability-related conditions, which may be differentially impacted by the COVID-19 pandemic. OBJECTIVE: To quantify changes in all-cause mortality prior-to and in the first year of the COVID-19 pandemic across Medicare's different sociodemographic and health-condition subpopulations. METHODS: This observational, population-based study used stratified bivariate regression to investigate Medicare fee-for-service subpopulation differences in pre-pandemic (i.e., 2019 versus 2016) and pandemic-related (2020 versus 2019) changes in all-cause mortality. RESULTS: All-cause mortality in the combined Medicare-Advantage (i.e., managed care) and fee-for-service beneficiary population improved by a relative 1% in the ten years that preceded the COVID-19 pandemic, but then escalated by a relative 15.9% in 2020, the pandemic's first year. However, a closer look at Medicare's fee-for-service subpopulations reveals critical differences. All-cause mortality had actually been worsening prior to the pandemic among most psychiatric and disability-related condition groups, all race and ethnicity groups except White Non-Hispanic, and Medicare-Medicaid dual-eligible (i.e., low-income) beneficiaries. Many of these groups then experienced all-cause mortality spikes in 2020 that were over twice that of the overall Medicare fee-for-service population. Of all 61 chronic health conditions studied, beneficiaries with schizophrenia were the most adversely affected, with all-cause mortality increasing 38.4% between 2019 and 2020. CONCLUSION: This analysis reveals subpopulation differences in all-cause mortality trends, both prior to and in year-one of the COVID-19 pandemic, indicating that the events of 2020 exacerbated preexisting health-related inequities.

Severe Arboviral Neuroinvasive Disease in Patients on Rituximab Therapy: A Review.

With increasing use of rituximab and other B-cell depleting monoclonal antibodies for multiple indications, infectious complications are being recognized. We summarize clinical findings of patients on rituximab with arboviral diseases identified through literature review or consultation with the Centers for Disease Control and Prevention. We identified 21 patients on recent rituximab therapy who were diagnosed with an arboviral disease caused by West Nile, tick-borne encephalitis, eastern equine encephalitis, Cache Valley, Jamestown Canyon, and Powassan viruses. All reported patients had neuroinvasive disease. The diagnosis of arboviral infection required molecular testing in 20 (95%) patients. Median illness duration was 36 days (range, 12 days to 1 year), and 15/19 (79%) patients died from their illness. Patients on rituximab with arboviral disease can have a severe or prolonged course with an absence of serologic response. Patients should be counseled about mosquito and tick bite prevention when receiving rituximab and other B-cell depleting therapies.

Experience of a systematic approach to care and prevention of fragility fractures in New Zealand.

This narrative review describes efforts to improve the care and prevention of fragility fractures in New Zealand from 2012 to 2022. This includes development of clinical standards and registries to benchmark provision of care, and public awareness campaigns to promote a life-course approach to bone health. PURPOSE: This review describes the development and implementation of a systematic approach to care and prevention for New Zealanders with fragility fractures, and those at high risk of first fracture. Progression of existing initiatives and introduction of new initiatives are proposed for the period 2022 to 2030. METHODS: In 2012, Osteoporosis New Zealand developed and published a strategy with objectives relating to people who sustain hip and other fragility fractures, those at high risk of first fragility fracture or falls and all older people. The strategy also advocated formation of a national fragility fracture alliance to expedite change. RESULTS: In 2017, a previously informal national alliance was formalised under the Live Stronger for Longer programme, which includes stakeholder organisations from relevant sectors, including government, healthcare professionals, charities and the health system. Outputs of this alliance include development of Australian and New Zealand clinical guidelines, clinical standards and quality indicators and a bi-national registry that underpins efforts to improve hip fracture care. All 22 hospitals in New Zealand that operate on hip fracture patients currently submit data to the registry. An analogous approach is ongoing to improve secondary fracture prevention for people who sustain fragility fractures at other sites through nationwide access to Fracture Liaison Services. CONCLUSION: Widespread participation in national registries is enabling benchmarking against clinical standards as a means to improve the care of hip and other fragility fractures in New Zealand. An ongoing quality improvement programme is focused on eliminating unwarranted variation in delivery of secondary fracture prevention.

Enterovirus A71 causing meningoencephalitis and acute flaccid myelitis in a patient receiving rituximab.

We present the case of a young woman being treated with rituximab for rheumatoid arthritis who developed a severe enteroviral meningoencephalitis and acute flaccid myelitis (AFM). Cerebrospinal fluid (CSF) and stool reverse transcription-polymerase chain reaction (RT-PCR) testing confirmed the diagnosis and additional sequencing studies performed at the CDC further characterized the enterovirus as enterovirus A71 (EV-A71). After treatment with intravenous immunoglobulin (IVIg) and fluoxetine (based on previous reports of possible efficacy) the patient experienced a remarkable improvement over time. This case highlights the importance of considering enteroviral infection in patients treated with rituximab, depicts a possible clinical course of enteroviral meningoencephalitis and AFM, and illustrates the importance of testing multiple sites for enterovirus infection (CSF, stool, nasopharyngeal swab, blood). Here we present the case with a brief review of the literature pertaining to EV-A71.

Usutu virus disease: a potential problem for North America?

Usutu virus is an emerging mosquito-borne flavivirus initially identified in South Africa in 1959 that is now circulating throughout parts of Africa, Europe, and the Middle East. It is closely related to West Nile virus, and has similar vectors, amplifying bird hosts, and epidemiology. Usutu virus infection can occur in humans and may be asymptomatic or cause systemic (e.g., fever, rash, and hepatitis) or neuroinvasive (e.g., meningitis and encephalitis) disease. Given few reported cases, the full clinical spectrum is not known. No anti-viral treatment is available, but it can be largely prevented by avoiding mosquito bites. Because of similar mosquitoes, birds, and climate to Europe, the potential for introduction to North America is possible.

Red Blood Cell Product Transfusion Thresholds and Clinical Outcomes.

OBJECTIVE: To determine whether patients transfused red blood cell (RBC) products according to guideline-specified pretransfusion hemoglobin (Hb) concentrations or for other reasons were more likely to survive their intensive care unit (ICU) stay. DESIGN: An observational study of 375 478 episodes of ICU care, over 5 years, was performed with ICU survival as the primary outcome. Outcomes were analyzed as a function of pretransfusion Hb concentration for groups with distinct transfusion indications while adjusting for potential confounders. SETTING AND PATIENTS: This study included all adult patients discharged from 1 of 203 adult ICUs from 32 US health-care systems. The patients were from community hospitals, tertiary, and academic medical centers. INTERVENTION: Transfusion of allogenic packed RBCs or whole blood was prescribed at the discretion of the treating clinicians. MEASUREMENTS AND MAIN RESULTS: We found that 15% of adult ICU patients are transfused RBC products, and most transfusions for hemodynamically stable patients are administered above the guideline-specified pretransfusion Hb threshold of 7 g/dL. Hemodynamically stable patients transfused below this threshold were significantly more likely to survive their ICU stay than those not transfused (odds ratio [OR] 0.59, 95% confidence interval [CI], 0.43-0.81; P = .001), and patients transfused at thresholds above 9 g/dL were less likely to survive their ICU stay than those not transfused. Patients of the acute blood loss group who were transfused appeared to benefit or were not harmed by transfusion. CONCLUSION: Conservative RBC product transfusion practices for groups that are targeted by guidelines are justified by outcomes observed in clinical practice. This study provides evidence for the liberal administration of RBC products to critically ill adults with acute blood loss based on association with lower risk of mortality.

Five Emerging Neuroinvasive Arboviral Diseases: Cache Valley, Eastern Equine Encephalitis, Jamestown Canyon, Powassan, and Usutu.

There are many arthropod-borne viruses (arboviruses) capable of neuroinvasion, with West Nile virus being one of the most well known. In this review, we highlight five rarer emerging or reemerging arboviruses capable of neuroinvasion: Cache Valley, eastern equine encephalitis, Jamestown Canyon, Powassan, and Usutu viruses. Cache Valley and Jamestown Canyon viruses likely circulate throughout most of North America, while eastern equine encephalitis and Powassan viruses typically circulate in the eastern half. Usutu virus is not currently circulating in North America, but has the potential to be introduced in the future given similar climate, vectors, and host species to Europe (where it has been circulating). Health care providers should contact their state or local health departments with any questions regarding arboviral disease surveillance, diagnosis, treatment, or prevention. To prevent neuroinvasive arboviral diseases, use of insect repellent and other mosquito and tick bite prevention strategies are key.

Maryland Multipayor Patient-centered Medical Home Program: A 4-Year Quasiexperimental Evaluation of Quality, Utilization, Patient Satisfaction, and Provider Perceptions.

OBJECTIVE: To evaluate impact of the Maryland Multipayor Patient-centered Medical Home Program (MMPP) on: (1) quality, utilization, and costs of care; (2) beneficiaries' experiences and satisfaction with care; and (3) perceptions of providers. DESIGN: 4-year quasiexperimental design with a difference-in-differences analytic approach to compare changes in outcomes between MMPP practices and propensity score-matched comparisons; pre-post design for patient-reported outcomes among MMPP beneficiaries. SUBJECTS: Beneficiaries (Medicaid-insured and privately insured) and providers in 52 MMPP practices and 104 matched comparisons in Maryland. INTERVENTION: Participating practices received unconditional financial support and coaching to facilitate functioning as medical homes, membership in a learning collaborative to promote education and dissemination of best practices, and performance-based payments. MEASURES: Sixteen quality, 20 utilization, and 13 cost measures from administrative data; patient-reported outcomes on care delivery, trust in provider, access to care, and chronic illness management; and provider perceptions of team operation, team culture, satisfaction with care provided, and patient-centered medical home transformation. RESULTS: The MMPP had mixed impact on site-level quality and utilization measures. Participation was significantly associated with lower inpatient and outpatient payments in the first year among privately insured beneficiaries, and for the entire duration among Medicaid beneficiaries. There was indication that MMPP practices shifted responsibility for certain administrative tasks from clinicians to medical assistants or care managers. The program had limited effect on measures of patient satisfaction (although response rates were low) and on provider perceptions. CONCLUSIONS: The MMPP demonstrated mixed results of its impact and indicated differential program effects for privately insured and Medicaid beneficiaries.

Decision support during electronic prescription to stem antibiotic overuse for acute respiratory infections: a long-term, quasi-experimental study.

BACKGROUND: Interventions to support decision-making can reduce inappropriate antibiotic use for acute respiratory infections (ARI), but they may not be sustainable. The objective of the study is to evaluate the long-term effectiveness of a clinical decision-support system (CDSS) interposed at the time of electronic (e-) prescriptions for selected antibiotics. METHODS: This is a retrospective, observational intervention study, conducted within a large, statewide Veterans Affairs health system. Participants are outpatients with an initial visit for ARI. A CDSS was deployed upon e-prescription of selected antibiotics during the study period. From 01/2004 to 05/2006 (pre-withdrawal period), the CDSS targeted azithromycin and the fluoroquinolone gatifloxacin. From 05/2006 to 12/2011 (post-withdrawal period), the CDSS was retained for azithromycin but withdrawn for the fluoroquinolone. A manual record review was conducted to determine concordance of antibiotic prescription with ARI treatment guidelines. RESULTS: Of 1131 included ARI visits, 380 (33.6%) were guideline-concordant. For azithromycin, concordance did not change between the pre- and post-withdrawal periods, and adjusted odds of concordance was 8.8 for the full study period, compared to unrestricted antibiotics. For fluoroquinolones, guideline concordance decreased from 88.6% (39 of 44 visits) to 51.3% (59 of 115 visits), pre- vs. post-withdrawal periods (p < 0.005). The adjusted odds of concordance compared to "All Other Antibiotics" visits decreased from 24.4 (95% CI 9.0-66.3) pre-withdrawal to 5.5 (95% CI 3.5-8.8) post-withdrawal (p = .008). Concordance did not change between those same time periods for antibiotics that were never subjected to the intervention ("All Other Antibiotics"). CONCLUSIONS: A CDSS interposed at the time of e-prescription of selected antibiotics can shift their use toward ARI treatment guidelines, and this effect can be maintained over the long term as long as the CDSS remains in place. Removal of the CDSS after 3.5 years of implementation resulted in a rise in guideline-discordant antibiotic use.