Subjective Cognitive Complaints in Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Subjective cognitive complaints (SCCs) in Parkinson's disease (PD) are reported frequently, but their prevalence and association with changes on objective testing are not fully known. OBJECTIVE: We aimed to determine the prevalence, clinical correlates, and predictive value of SCCs in PD. METHODS: We conducted a systematic review and meta-analysis. From 204 abstracts, we selected 31 studies (n = 3441 patients), and from these, identified the prevalence, clinical features, associations with neuropsychiatric symptoms, and predictive values of SCCs in PD. RESULTS: The meta-analysis showed an SCC prevalence of 36%. This prevalence, however, was significantly moderated by study heterogeneity regarding female sex, disease severity, levodopa equivalent daily dosage, exclusion from the overall sample of patients with objective cognitive impairment, and measurement instrument. SCC prevalence did not differ between de novo and treated PD patients. SCCs were weakly and negligibly associated with cognitive changes on objective testing in cross-sectional studies. However, in cognitively healthy patients, SCCs had a risk ratio of 2.71 for later cognitive decline over a mean follow-up of 3.16 years. Moreover, SCCs were moderately related to co-occurring symptoms of depression, anxiety, or apathy and were more strongly related to these neuropsychiatric symptoms than objective cognitive functioning. CONCLUSION: Our analyses suggest that SCCs in patients with and without objective cognitive impairment are frequent, occurring in more than one third of PD patients. Establishing uniform measurement instruments for identifying PD-related SCCs is critical to understand their implications. Even in cases lacking evidence of objective cognitive impairment and where SCCs might reflect underlying neuropsychiatric symptoms, the possibility of later cognitive deterioration should not be excluded. Therefore, SCCs in PD patients warrant close monitoring for opportunities for targeted and effective interventions. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Engaging School Communities During COVID-19: The Role of School Nurses.

We explored the role of school nurses during the COVID-19 pandemic by conducting interviews and focus groups with them in 2022 and 2023 in an urban public school district. Findings indicated that school nurses played an essential public health role in engaging the school community, overseeing COVID-19 testing, and enforcing risk mitigation strategies during the pandemic. Our results contribute to understanding school nurses' experiences during the pandemic and highlight the need for training and support for their vital role. (Am J Public Health. 2024;114(S5):S402-S404. https://doi.org/10.2105/AJPH.2024.307591).

Simultaneous Free Flap Breast Reconstruction Combined With Contralateral Mastopexy or Breast Reduction: A Propensity-Matched National Surgical Quality Improvement Program Study on Postoperative Outcomes.

BACKGROUND: Simultaneous free flap breast reconstruction combined with contralateral mastopexy or breast reduction can increase patient satisfaction and minimize the need for a second procedure. Surgeon concerns of increases in operative time, postoperative complications, and final breast symmetry may decrease the likelihood of these procedures being done concurrently. This study analyzed postoperative outcomes of simultaneous contralateral mastopexy or breast reduction with free flap breast reconstruction. METHODS: By using the American College of Surgeons National Surgical Quality Improvement Program database (2010-2020), we analyzed 2 patient cohorts undergoing (A) free flap breast reconstruction only and (B) free flap breast reconstruction combined with contralateral mastopexy or breast reduction. The preoperative variables assessed included demographic data, comorbidities, and perioperative data. Using a neighbor matching algorithm, we performed a 1:1 propensity score matching of 602 free flap breast reconstruction patients and 621 with concurrent contralateral operation patients. Bivariate analysis for postoperative surgical and medical complications was performed for outcomes in the propensity-matched cohort. RESULTS: We identified 11,308 cases who underwent microsurgical free flap breast reconstruction from the American College of Surgeons National Surgical Quality Improvement Program database from the beginning of 2010 to the end of 2020. A total of 621 patients underwent a free flap breast reconstruction combined with contralateral mastopexy or breast reduction. After propensity score matching, there were no significant differences in patient characteristics, perioperative variables or postoperative medical complications between the 2 cohorts. CONCLUSIONS: Simultaneous free flap breast reconstruction combined with contralateral mastopexy or breast reduction can be performed safely and effectively without an increase in postoperative complication rates. This can improve surgeon competence in offering this combination of procedures as an option to breast cancer survivors, leading to better patient outcomes in terms of symmetrical and aesthetically pleasing results, reduced costs, and elimination of the need for a second operation.

Pen needle use patterns in an insured population with diabetes: US retrospective claims analysis.

BACKGROUND: People with diabetes who inject insulin with pen devices may reuse the pen needles (PNs), a practice that can cause PN tip deformity, breakage, and contamination, and that is associated with lipohypertrophy and injection-related pain. OBJECTIVE: This retrospective study aimed to estimate the extent of PN reuse among people with diabetes in two insured populations in the United States. METHODS: Using claims data for Commercial Fully Insured (CFI) and Medicare Advantage (MA) populations from 1-Oct-2018 to 31-Dec-2022, we identified adults with type 1 or type 2 diabetes (T1D/T2D) who had ≥1 claim for PNs and ≥2 claims for insulin from 1-Jan-2019 to 31-Dec-2021, with continuous medical/pharmacy eligibility for 3 months before first claim and 1 year after (follow-up). Those receiving hospice or palliative care or using mail-order prescriptions were excluded. We compared actual annual fill rate of PNs with expected fill rate (assuming single use) according to prescribed insulin regimen. Whether the annual actual-to-expected ratio for PN numbers equaled 1 was evaluated using sign tests with 2-sided p-values. RESULTS: Median annual actual-to-expected ratios ranged from 0.41 (T1D basal+prandial cohort) to 0.82 (T2D basal cohort; all p<0.001) in the CFI population (N=10,854), and from 0.55 (TID basal+prandial) to 1.10 (T2D basal and basal+prandial; p=0.382 to <0.001) in the MA population (N=32,495); medians were 0.34 and 0.55 for four expected T2D basal+prandial injections/day in CFI and MA populations, respectively (p<0.001). Annual actual-to-expected ratios were <1 for 62% and 47% of CFI and MA populations, respectively. An estimated 2-27% and 0-17%, respectively, depending on insulin regimen, had inadequate supplies of PNs suggesting that PNs could have been used ≥5 times. CONCLUSIONS: These findings highlight the need for educating people with diabetes about reasons for avoiding PN reuse and the key role that pharmacists can play in providing this information and adequate supplies of PNs.

Guideline-Concordant Antiviral Treatment in Children at High Risk for Influenza Complications.

BACKGROUND: National guidelines recommend antiviral treatment for children with influenza at high risk for complications regardless of symptom duration. Little is known about concordance of clinical practice with this recommendation. METHODS: We performed a cross-sectional study of outpatient children (aged 1-18 years) at high risk for complications who were diagnosed with influenza during the 2016-2019 influenza seasons. High-risk status was determined using an existing definition that includes age, comorbidities, and residence in a long-term care facility. The primary outcome was influenza antiviral dispensing within 2 days of influenza diagnosis. We determined patient- and provider-level factors associated with guideline-concordant treatment using multivariable logistic regression. RESULTS: Of the 274 213 children with influenza at high risk for influenza complications, 159 350 (58.1%) received antiviral treatment. Antiviral treatment was associated with the presence of asthma (aOR, 1.13; 95% confidence interval [CI], 1.11-1.16), immunosuppression (aOR, 1.10; 95% CI, 1.05-1.16), complex chronic conditions (aOR, 1.04; 95% CI, 1.01-1.07), and index encounter in the urgent care setting (aOR, 1.3; 95% CI, 1.26-1.34). Factors associated with decreased odds of antiviral treatment include age 2-5 years compared with 6-17 years (aOR, 0.95; 95% CI, .93-.97), residing in a chronic care facility (aOR, .61; 95% CI, .46-.81), and index encounter in an emergency department (aOR, 0.66; 95% CI, .63-.71). CONCLUSIONS: Among children with influenza at high risk for complications, 42% did not receive guideline-concordant antiviral treatment. Further study is needed to elucidate barriers to appropriate use of antivirals in this vulnerable population.

Pharmacokinetics and safety of a single dose of telavancin in pediatric subjects 2-17 years of age.

Antimicrobial resistance increases infection morbidity in both adults and children, necessitating the development of new therapeutic options. Telavancin, an antibiotic approved in the United States for certain bacterial infections in adults, has not been examined in pediatric patients. The objectives of this study were to evaluate the short-term safety and pharmacokinetics (PK) of a single intravenous infusion of telavancin in pediatric patients. Single-dose safety and PK of 10 mg/kg telavancin was investigated in pediatric subjects >12 months to ≤17 years of age with known or suspected bacterial infection. Plasma was collected up to 24-h post-infusion and analyzed for concentrations of telavancin and its metabolite for noncompartmental PK analysis. Safety was monitored by physical exams, vital signs, laboratory values, and adverse events following telavancin administration. Twenty-two subjects were enrolled: 14 subjects in Cohort 1 (12-17 years), 7 subjects in Cohort 2 (6-11 years), and 1 subject in Cohort 3 (2-5 years). A single dose of telavancin was well-tolerated in all pediatric age cohorts without clinically significant effects. All age groups exhibited increased clearance of telavancin and reduced exposure to telavancin compared to adults, with mean peak plasma concentrations of 58.3 µg/mL (Cohort 1), 60.1 µg/mL (Cohort 2), and 53.1 µg/mL (Cohort 3). A 10 mg/kg dose of telavancin was well tolerated in pediatric subjects. Telavancin exposure was lower in pediatric subjects compared to adult subjects. Further studies are needed to determine the dose required in phase 3 clinical trials in pediatrics.

Definition and Clinical Evaluation for Trimethoprim-Sulfamethoxazole Severe Acute Respiratory Failure.

OBJECTIVES: Trimethoprim-sulfamethoxazole (TMP-SMX)-associated severe acute respiratory distress syndrome (ARDS) has gone underrecognized. We propose the first disease definition and clinical evaluation for a novel adverse drug reaction (ADR) based on a series of recently identified rare cases of life-threatening ADRs. DESIGN: A retrospective study was conducted. All medical records were evaluated. Available pathology samples were sent to Massachusetts General for clinical consultation. Blood samples from surviving patients were obtained and human leukocyte antigen (HLA) analysis was performed by the Children's Mercy Hospital Genomic Center and Vanderbilt University Medical Center. SETTING: U.S. ICUs, 1996-2021. PATIENTS: Nineteen young patients (10-37) were identified. Patients were previously healthy, with no preexisting pulmonary disease, no other cause for respiratory failure, and no chronic history of smoking/vaping. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Through our retrospective analysis, we analyzed clinical characteristics associated with TMP-SMX. Pathology samples were reviewed, and HLA analysis was performed on available samples by the study team or as standard of care at treatment hospitals in some cases. In 19 critically ill patients, we identified a pattern of severe respiratory failure requiring ICU admission, mechanical ventilation, and frequent extracorporeal membrane oxygenation use. We describe the first three-part clinical diagnosis and evaluation strategy: 1) Clinical definition: Unexplained severe respiratory failure in a patient receiving greater than or equal to 6 days of TMP-SMX at treatment dose (not prophylaxis). TMP-SMX ARDS is a diagnosis of exclusion. 2) Genetic association: One hundred percent of currently available TMP-SMX respiratory failure patient genomic data, ( n = 11) have been carriers of both HLA-B*07:02 and HLA-C*07:02 alleles. HLA allele evaluation could be considered in patients with suspected TMP-SMX respiratory failure. 3) Lung pathology: A unique pulmonary pathologic pattern of lung injury termed diffuse alveolar injury with delayed epithelialization has been observed in these cases. In suspected cases, surgical lung biopsy early in the clinical course could be considered. CONCLUSIONS: TMP-SMX is a commonly prescribed antibiotic. However, we find it imperative to share this relatively rare but life-threatening condition with clinicians as the mortality rate approaches 40%.

Memory Phenotypes In Early, De Novo Parkinson's Disease Patients with Mild Cognitive Impairment.

BACKGROUND: Memory deficits in mild cognitive impairment related to Parkinson's disease (PD-MCI) are quite heterogeneous, and there is no general agreement on their genesis. OBJECTIVES: To define memory phenotypes in de novo PD-MCI and their associations with motor and non-motor features and patients' quality of life. METHODS: From a sample of 183 early de novo patients with PD, cluster analysis was applied to neuropsychological measures of memory function of 82 patients with PD-MCI (44.8%). The remaining patients free of cognitive impairment were considered as a comparison group (n = 101). Cognitive measures and structural magnetic resonance imaging-based neural correlates of memory function were used to substantiate the results. RESULTS: A three-cluster model produced the best solution. Cluster A (65.85%) included memory unimpaired patients; Cluster B (23.17%) included patients with mild episodic memory disorder related to a "prefrontal executive-dependent phenotype"; Cluster C (10.97%) included patients with severe episodic memory disorder related to a "hybrid phenotype," where hippocampal-dependent deficits co-occurred with prefrontal executive-dependent memory dysfunctions. Cognitive and brain structural imaging correlates substantiated the findings. The three phenotypes did not differ in terms of motor and non-motor features, but the attention/executive deficits progressively increased from Cluster A, through Cluster B, to Cluster C. This last cluster had worse quality of life compared to others. CONCLUSIONS: Our results demonstrated the memory heterogeneity of de novo PD-MCI, suggesting existence of three distinct memory-related phenotypes. Identification of such phenotypes can be fruitful in understanding the pathophysiological mechanisms underlying PD-MCI and its subtypes and in guiding appropriate treatments. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Validation of the Rainbow Model of Integrated Care Measurement Tool in Parkinson's Disease.

BACKGROUND: Integrated care is essential for improving the management and health outcomes for people with Parkinson's disease (PD); reliable and objective measures of care integration are few. OBJECTIVE: The aim of this study was to test the psychometric properties of the Rainbow Model of Integrated Care Measurement Tool (RMIC-MT, provider version) for healthcare professionals involved in PD care. METHODS: A cross-sectional survey was administered online to an international network representing 95 neurology centers across 41 countries and 588 healthcare providers. Exploratory factor analysis with principal axis extraction method was used to assess construct validity. Confirmatory factor analysis was used to evaluate model fit of the RMIC-MT provider version. Cronbach's alpha was used to assess the internal consistency reliability. RESULTS: Overall, 371 care providers (62% response rate) participated in this study. No item had psychometric sensitivity problems. Nine factors (professional coordination, cultural competence, triple aims outcome, system coordination, clinical coordination, technical competence, community-centeredness, person-centeredness, and organizational coordination) with 42 items were determined by exploratory factor analysis. Cronbach's alpha ranged from 0.76 (clinical coordination) to 0.94 (system coordination) and showed significant correlation among all items in the scale (>0.4), indicating good internal consistency reliability. The confirmatory factor analysis model passed most goodness-of-fit tests, thereby confirming the factor structure of nine categories with a total of 40 items. CONCLUSIONS: The results provide evidence for the construct validity and other psychometric properties of the provider version of the RMIC-MT to measure integrated care in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Research Priorities of Individuals and Caregivers With Lewy Body Dementia: A Web-based Survey.

INTRODUCTION: Lewy body dementia (LBD) is common, yet under-recognized and under-researched. To plan studies with the highest impact, engagement of the community personally affected by these conditions is essential. METHODS: A web-based survey of people living with LBD and current and former caregivers of people with LBD queried research priorities through forced ranking and exploration of burden of LBD symptoms. Specific caregiving needs in LBD and perceptions of research participation were also investigated. RESULTS: Between April 7, 2021 and July 1, 2021, 984 responses were recorded. Top research priorities included disease-modifying therapies and improved disease detection and staging. People with LBD were interested in pathophysiology and more bothered by motor symptoms; caregivers were interested in risk factors and symptomatic therapies and more bothered by neuropsychiatric symptoms. Few available LBD treatments and resources were rated as helpful, and many valuable services were never received. Previous participation in LBD research was infrequent, but interest was high. DISCUSSION: People with LBD and caregivers highlighted the need for research across all aspects of LBD, from pathophysiology and disease modification to prognosis, education, symptomatic treatments, and caregiver support. Funders should increase support for all aspects of LBD research to target the many needs identified by individuals and families living with LBD.

Activity Monitoring in Parkinson Disease: A Qualitative Study of Implementation Determinants.

BACKGROUND AND PURPOSE: There is interest in incorporating digital health technology in routine practice. We integrate multiple stakeholder perspectives to describe implementation determinants (barriers and facilitators) regarding digital health technology use to facilitate exercise behavior change for people with Parkinson disease in outpatient physical therapy. METHODS: The purposeful sample included people with Parkinson disease (n = 13), outpatient physical therapists (n = 12), and advanced technology stakeholders including researchers and reimbursement specialists (n = 13). Semistructured interviews were used to elicit implementation determinants related to using digital health technology for activity monitoring and exercise behavior change. Deductive codes based on the Consolidated Framework for Implementation Research were used to describe implementation determinants. RESULTS: Key implementation determinants were similar across stakeholder groups. Essential characteristics of digital health technology included design quality and packaging, adaptability, complexity, and cost. Implementation of digital health technology by physical therapists and people with Parkinson disease was influenced by their knowledge, attitudes, and varied confidence levels in using digital health technology. Inner setting organizational determinants included available resources and access to knowledge/information. Process determinants included device interoperability with medical record systems and workflow integration. Outer setting barriers included lack of external policies, regulations, and collaboration with device companies. DISCUSSION AND CONCLUSIONS: Future implementation interventions should address key determinants, including required processes for how and when physical therapists instruct people with Parkinson disease on digital health technology, organizational readiness, workflow integration, and characteristics of physical therapists and people with Parkinson disease who may have ingrained beliefs regarding their ability and willingness to use digital health technology. Although site-specific barriers should be addressed, digital health technology knowledge translation tools tailored to individuals with varied confidence levels may be generalizable across clinics.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content available at: http://links.lww.com/JNPT/A436 ).

Real-World Persistence, Adherence, Hypoglycemia, and Health Care Resource Utilization in People With Type 2 Diabetes Who Continued With the Second-Generation Basal Insulin Analog Insulin Glargine 300 Units/mL or Switched to a First-Generation Basal Insulin (Insulin Glargine 100 Units/mL or Detemir 100).

People with type 2 diabetes receiving a second-generation basal insulin (BI) analog may be switched to a first-generation formulation for financial reasons or changes in health insurance. However, because second-generation BI analogs have more even pharmacokinetic profiles, longer durations of action (>24 vs. ≤24 hours), and more stable action profiles than first-generation BI analogs, such a change may result in suboptimal treatment persistence and/or adherence. This study compared treatment persistence, treatment adherence, rates of hypoglycemia, and health care resource utilization outcomes in people with type 2 diabetes who either continued treatment with the second-generation BI Gla-300 or switched to a first-generation BI. The study showed that continuing with Gla-300 was associated with a lower risk of discontinuing therapy, fewer emergency department visits, and lower hypoglycemia event rates than switching to a first-generation BI.

Survey Reveals Patient and Health Care Provider Experiences and Challenges With the Use of High Doses of Basal Insulin.

Type 2 diabetes is a chronic, progressive disease, and its management results in a high emotional burden on patients. Eventually many patients require and can benefit from the use of insulin. This article reports results of a survey of patients and health care providers regarding their experiences of and challenges with the use of basal insulin. Health care providers can play a key role in helping people with type 2 diabetes overcome the challenges associated with the use of basal insulin, including connecting with their emotional needs and understanding the stressors associated with managing diabetes.

HLA-B*07:02 and HLA-C*07:02 are associated with trimethoprim-sulfamethoxazole respiratory failure.

We have identified an underrecognized severe adverse drug reaction (ADR) of trimethoprim-sulfamethoxazole (TMP-SMX) associated respiratory failure in previously healthy children and young adults. We investigated potential genetic risk factors associated with TMP-SMX induced respiratory failure in a cohort of seven patients. We explored whole genome sequence among seven patients representing nearly half of all reported cases worldwide and 63 unrelated control individuals in two stages: (1) human leukocyte antigen (HLA) locus variation as several other ADRs have been associated HLA genetic variants and (2) coding variation to catalog and explore potential rare variants contributing to this devastating reaction. All cases were either heterozygous (carriers) or homozygous for the common HLA-B*07:02-HLA-C*07:02 haplotype. Despite the small sample size, this observation is statistically significant both in conservative comparison to maximum reported population frequencies (binomial P = 0.00017 for HLA-B and P = 0.00028 for HLA-C) and to our control population assessed by same HLA genotyping approach (binomial P = 0.000001 for HLA-B and P = 0.000018 for HLA-C). No gene elsewhere in the genome harnessed shared rare case enriched coding variation. Our results suggests that HLA-B*07:02 and HLA-C*07:02 are necessary for a patient to develop respiratory failure due to TMP-SMX.

Precision dosing of vancomycin: in defence of AUC-guided therapy in children.

In 2020, new vancomycin guidelines were released, recommending the transition from trough-based to AUC24 monitoring for adult and paediatric patients. Given the resources required to achieve this transition, there has been debate about the costs and benefits of AUC24-based monitoring. A recent narrative review of vancomycin therapeutic drug monitoring in paediatrics claims to have uncovered the methodological weaknesses of the data that informed the guidelines and advises against premature adoption of AUC24-guided monitoring. In this article, we present supporting arguments for AUC24-guided monitoring in children, which include that: (i) troughs alone are inadequate surrogates for AUC24; (ii) vancomycin-associated nephrotoxicity has significant consequences that warrant optimization of dosing; (iii) a substantial portion of children receiving vancomycin are at high risk for poor outcomes and deserve targeted monitoring; and (iv) limited efficacy data in support of AUC24 is not a justification to revert to a less supported monitoring approach.

Oral Superabsorbent Hydrogel (Plenity) for Weight Management.

OBJECTIVE: To describe the mechanism, clinical trial data, adverse effects, and potential role in therapy of an oral superabsorbent hydrogel (OSH) for weight management. DATA SOURCES: A literature search was completed using MEDLINE and Google Scholar using the following search terms: oral superabsorbent hydrogel, Plenity, and Gelesis100 (September 1999 to July 2020). Abstracts and posters were identified from relevant scientific congress archives and published supplements. STUDY SELECTION AND DATA EXTRACTION: All available studies were considered. Only human studies were used for drug interaction, efficacy, and safety data. DATA SYNTHESIS: OSH is a first-in-class, nonsystemic agent for weight management. It is indicated for use in patients with a body mass index (BMI) of 25 to 40 kg/m2 regardless of comorbidity status. OSH functions primarily through space occupancy in the stomach and small intestine. Studies have demonstrated that OSH has modest weight loss efficacy and a favorable safety profile, with no significant difference in overall adverse events compared with placebo. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: OSH is one of the only prescription antiobesity therapeutics (AOTs) that can be utilized in overweight patients with BMI equal to 25 to 30 kg/m2, regardless of comorbidity status. Given its nonsystemic mechanism of action and safety profile, OSH may help shift the focus of weight management toward patients with a lower BMI. CONCLUSIONS: OSH offers a nonsystemic approach to weight management for patients who are diagnosed with overweight or obesity. As an alternative option to current pharmacological AOTs, OSH may address an existing clinical gap in weight management.

Frameworks for Parkinson's Disease Rehabilitation Addressing When, What, and How.

PURPOSE OF REVIEW: This review summarizes the evidence on rehabilitation for people with Parkinson's disease, including when to refer, what rehabilitation professionals should address, and how to deliver rehabilitation care. RECENT FINDINGS: Clinical practice guidelines support physical therapy, occupational therapy, and speech-language pathology for Parkinson's disease. However, integrating guidelines into practice may be difficult. Implementation studies take into account patient and clinician perspectives. Synthesizing guidelines with implementation research can improve local delivery. There is moderate to strong evidence supporting physical therapy, occupational therapy, and speech-language pathology soon after diagnosis and in response to functional deficits. We propose a framework of three pathways for rehabilitation care: (1) consultative proactive rehabilitation soon after diagnosis for assessment, treatment of early deficits, and promotion meaningful activities; (2) restorative rehabilitation to promote functional improvements; and (3) skilled maintenance rehabilitation for long-term monitoring of exercise, meaningful activities, safety, contractures, skin integrity, positioning, swallowing, and communication.

Cholinergic Switch between Two Types of Slow Waves in Cerebral Cortex.

Sleep slow waves are known to participate in memory consolidation, yet slow waves occurring under anesthesia present no positive effects on memory. Here, we shed light onto this paradox, based on a combination of extracellular recordings in vivo, in vitro, and computational models. We find two types of slow waves, based on analyzing the temporal patterns of successive slow-wave events. The first type is consistently observed in natural slow-wave sleep, while the second is shown to be ubiquitous under anesthesia. Network models of spiking neurons predict that the two slow wave types emerge due to a different gain on inhibitory versus excitatory cells and that different levels of spike-frequency adaptation in excitatory cells can account for dynamical distinctions between the two types. This prediction was tested in vitro by varying adaptation strength using an agonist of acetylcholine receptors, which demonstrated a neuromodulatory switch between the two types of slow waves. Finally, we show that the first type of slow-wave dynamics is more sensitive to external stimuli, which can explain how slow waves in sleep and anesthesia differentially affect memory consolidation, as well as provide a link between slow-wave dynamics and memory diseases.

COVID-19 infection among first responders in Broward County, Florida, March-April 2020.

BACKGROUND: First responders (FRs) may have a significant risk of coronavirus 19 (COVID-19) infection than the general population due to job-related exposures. We aimed to determine the prevalence and exposure patterns of COVID-19 among FRs. METHODS: Between March and April 2020, FRs in Broward County, Florida, were screened for COVID-19 infection by real-time reverse transcription polymerase chain reaction assay using nasopharyngeal swabs. Demographics and COVID-19 positive rate of the FRs were summarized. RESULTS: A total of 3375 FRs were screened for COVID-19 infection. The median age of FRs tested was 42 years (IQR 33-52 years), and 1464 (43.4%) were men. A total of 2902 (85.9%) were asymptomatic, and 473 (14.1%) reported symptoms associated with COVID-19. Overall, 289 (8.6%) were positive, with the highest rates among the age between 25 and 49 years. Of those testing positive, 235 (81.3%) were asymptomatic. Fourteen days after their first positive test, 81 (69.8%) of the 116 asymptomatically infected FRs were negative, and 35 (30.2%) remained positive and asymptomatic. CONCLUSIONS: The FRs in Broward County, FL, had an overall infection rate of 8.6% at the time of COVID-19 testing, and asymptomatic FRs accounted for 81.3% of infection. Active surveillance should be focused on the asymptomatic FRs with COVID-19.

Peripheral electrical stimulation to reduce pathological tremor: a review.

Interventions to reduce tremor in essential tremor (ET) and Parkinson's disease (PD) clinical populations often utilize pharmacological or surgical therapies. However, there can be significant side effects, decline in effectiveness over time, or clinical contraindications for these interventions. Therefore, alternative approaches must be considered and developed. Some non-pharmacological strategies include assistive devices, orthoses and mechanical loading of the tremorgenic limb, while others propose peripheral electrical stimulation. Specifically, peripheral electrical stimulation encompasses strategies that activate motor and sensory pathways to evoke muscle contractions and impact sensorimotor function. Numerous studies report the efficacy of peripheral electrical stimulation to alter tremor generation, thereby opening new perspectives for both short- and long-term tremor reduction. Therefore, it is timely to explore this promising modality in a comprehensive review. In this review, we analyzed 27 studies that reported the use of peripheral electrical stimulation to reduce tremor and discuss various considerations regarding peripheral electrical stimulation: the stimulation strategies and parameters, electrodes, experimental designs, results, and mechanisms hypothesized to reduce tremor. From our review, we identified a high degree of disparity across studies with regard to stimulation patterns, experimental designs and methods of assessing tremor. Having standardized experimental methodology is a critical step in the field and is needed in order to accurately compare results across studies. With this review, we explore peripheral electrical stimulation as an intervention for tremor reduction, identify the limitations and benefits of the current state-of-the-art studies, and provide ideas to guide the development of novel approaches based on the neural circuitries and mechanical properties implied in tremor generation.