ObjectiveFriedreich ataxia (FRDA) is a progressive neurodegenerative disorder of adults and children. This study analyzed neurological outcomes and changes to identify predictors of progression and generate power calculations for clinical trials.MethodsEight hundred and twelve subjects in a natural history study were evaluated annually across 12 sites using the Friedreich Ataxia Rating Scale (FARS), 9‐Hole Peg Test, Timed 25‐Foot Walk, visual acuity tests, self‐reported surveys and disability scales. Cross‐sectional outcomes were assessed from recent visits, and longitudinal changes were gaged over 5 years from baseline.ResultsCross‐sectional outcomes correlated with measures of disease severity. Age, genetic severity (guanine‐adenine‐adenine [GAA] repeat length), and testing site predicted performance. Serial progression was relatively linear using FARS and composite measures of performance, while individual performance outcomes were nonlinear over time. Age strongly predicted change from baseline until removing the effects of baseline FARS scores, when GAA becomes a more important factor. Progression is fastest in younger subjects and subjects with longer GAA repeats. Improved coefficients of variation show that progression results are more reproducible over longer assessment durations.InterpretationWhile age predicted progression speed in simple analyses and may provide an effective way to stratify cohorts, separating the effects of age and genetic severity is difficult. Controlling for baseline severity, GAA is the major determinant of progression rate in FRDA. Clinical trials will benefit from enrollment of younger subjects, and sample size requirements will shrink with longer assessment periods. These findings should prove useful in devising gene therapy trials in the near future.

Angelman syndrome (AS) is a neurogenetic disorder. The goal of this study was to investigate the primary health issues affecting adults with AS and to further characterize the natural history and genotype-phenotype correlations. Standardized phone interviews with caregivers for 110 adolescents and adults with AS were conducted. The impact of age, gender, and genotype on specific outcomes in neurology, orthopedics, internal medicine, and psychiatry were investigated. The mean age of individuals with AS was 24 years (range 16–50y). Active seizures were present in 41% of individuals, and 72% had sleep dysfunction. Significant constipation was present in 85%, and 32% were overweight or obese, with obesity disproportionately affecting women. Scoliosis affected 50% with a mean age at diagnosis of 12 years, and 24% of those diagnosed with scoliosis required surgery, an intervention disproportionately affecting men. Sixty-eight percent were able to walk independently, and 13% were able to speak 5 or more words. Self-injurious behavior was exhibited in 52% of individuals. The results of this study indicate that epilepsy severity may assume a bimodal age distribution: seizures are typically most severe in early childhood but may recur in adulthood. While late-adolescent and adult sleep patterns were improved when compared to the degree of sleep dysfunction present during infancy and childhood, the prevalence of poor sleep in adults remained quite high. Primary areas of clinical management identified include the following: seizures, sleep, aspiration risk, GERD, constipation, dental care, vision, obesity, scoliosis, bone density, mobility, communication, behavior, and anxiety.

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Massive unemployment during the COVID-19 pandemic could result in an eviction crisis in US cities. Here we model the effect of evictions on SARS-CoV-2 epidemics, simulating viral transmission within and among households in a theoretical metropolitan area. We recreate a range of urban epidemic trajectories and project the course of the epidemic under two counterfactual scenarios, one in which a strict moratorium on evictions is in place and enforced, and another in which evictions are allowed to resume at baseline or increased rates. We find, across scenarios, that evictions lead to significant increases in infections. Applying our model to Philadelphia using locally-specific parameters shows that the increase is especially profound in models that consider realistically heterogenous cities in which both evictions and contacts occur more frequently in poorer neighborhoods. Our results provide a basis to assess eviction moratoria and show that policies to stem evictions are a warranted and important component of COVID-19 control.

Massive unemployment during the COVID-19 pandemic could result in an eviction crisis in US cities. Here we model the effect of evictions on SARS-CoV-2 epidemics, simulating viral transmission within and among households in a theoretical metropolitan area. We recreate a range of urban epidemic trajectories and project the course of the epidemic under two counterfactual scenarios, one in which a strict moratorium on evictions is in place and enforced, and another in which evictions are allowed to resume at baseline or increased rates. We find, across scenarios, that evictions lead to significant increase in infections. Applying our model to Philadelphia using locally-specific parameters shows that the increase is especially profound in models that consider realistically heterogenous cities in which both evictions and contacts occur more frequently in poorer neighborhoods. Our results provide a basis to assess municipal eviction moratoriums and show that policies to stem evictions are a warranted and important component of COVID-19 control.

Congenital lymphedema has been described as a possible rare association of tuberous sclerosis complex (TSC), with only six previous cases reported in the literature. TSC is an autosomal dominant, multisystem disorder connected to aberrant regulation of the mammalian target of rapamycin (mTOR) pathway. The aim of this study is to review cases of lymphedema in a large cohort of TSC patients. The medical records of 268 patients seen at The Herscot Center for Children and Adults with Tuberous Sclerosis Complex at the Massachusetts General Hospital from 2002 to 2012 were retrospectively reviewed for reports of lymphedema or edema of unknown etiology. Genotypic and phenotypic data were collected in accordance with institutional review board (IRB) approval. This cohort presents two new cases of congenital lymphedema in TSC patients and acquired lymphedema was found in eight additional cases. Thus, we report 10 new cases of lymphedema in TSC (4%). The two patients with congenital lymphedema were female, as were the previous six reported cases. The frequency of lymphedema reported here (4%) is higher than the estimated prevalence in the general population (0.133-0.144%), suggesting a higher frequency of lymphedema in TSC. This study shows that patients with TSC and lymphedema are more likely to be females with renal AMLs and suggests that congenital lymphedema is a gender-specific (female) manifestation of TSC. Exploration of the potential role of mTOR antagonists may be important in treatment of lymphedema in TSC patients.

u t n e e d e d h e lp w ith m a n y d a ily a c tiv itie s . T he m a jo r ity (82%) h a d e p ile p t ic seizu res. A b n o rm a l E E G -a ctiv ity c o n s is t in g o f 2-3/s r h y th m ic tr ip h a s ic w a v e s o f h ig h a m p litu d e w ith a m a x im u m o v e r th e fr o n ta l reg io n s, w h ic h h IN T R O D U C T IO NSince the first description of A ngelm an syndrom e (AS) by A ngelm an [1965], m ore th a n 400 cases have been reported. M ost stu d ies h av e described AS in in fancy or childhood, an d only a few have m entioned ad u lt AS p a tien ts [W illiam s a n d F rias, 1982; B jerre et al., 1984; W illiam s e t a lM 1989; G anji and D uncan, 1989; M agenis e t al., 1990; Im aizu m i et al., 1990; K irkilionis et al., 1991; J a y e t al., 1991; M atsum oto e t al., 1992; C layton-Sm ith, 1993; S m ith e t al., 1994; B untinx et al,, 1995], L ittle is know n about the evolu tion of the clinical sym ptom s into adulthood. H ere we Received for publication November 27, 1995; revision received March 22, 1996. Address reprint requests to L.A

BackgroundDespite impressive reductions in infectious disease burden within Sub-Saharan Africa (SSA), half of the top ten causes of poor health or death in SSA are communicable illnesses. With emerging and re-emerging infections affecting the region, the possibility of healthcare-acquired infections (HAIs) being transmitted to patients and healthcare workers, especially nurses, is a critical concern. Despite infection prevention and control (IPC) evidence-based practices (EBP) to minimize the transmission of HAIs, many healthcare systems in SSA are challenged to implement them. The purpose of this review is to synthesize and critique what is known about implementation strategies to promote IPC for nurses in SSA.MethodsThe databases, PubMed, Ovid/Medline, Embase, Cochrane, and CINHAL, were searched for articles with the following criteria: English language, peer-reviewed, published between 1998 and 2018, implemented in SSA, targeted nurses, and promoted IPC EBPs. Further, 6241 search results were produced and screened for eligibility to identify implementation strategies used to promote IPC for nurses in SSA. A total of 61 articles met the inclusion criteria for the final review. The articles were evaluated using the Joanna Briggs Institute’s (JBI) quality appraisal tools. Results were reported using PRISMA guidelines.ResultsMost studies were conducted in South Africa (n = 18, 30%), within the last 18 years (n = 41, 67%), and utilized a quasi-experimental design (n = 22, 36%). Few studies (n = 14, 23%) had sample populations comprising nurses only. The majority of studies focused on administrative precautions (n = 36, 59%). The most frequent implementation strategies reported were education (n = 59, 97%), quality management (n = 39, 64%), planning (n = 33, 54%), and restructure (n = 32, 53%). Penetration and feasibility were the most common outcomes measured for both EBPs and implementation strategies used to implement the EBPs. The most common MAStARI and MMAT scores were 5 (n = 19, 31%) and 50% (n = 3, 4.9%) respectively.ConclusionsAs infectious diseases, especially emerging and re-emerging infectious diseases, continue to challenge healthcare systems in SSA, nurses, the keystones to IPC practice, need to have a better understanding of which, in what combination, and in what context implementation strategies should be best utilized to ensure their safety and that of their patients. Based on the results of this review, it is clear that implementation of IPC EBPs in SSA requires additional research from an implementation science-specific perspective to promote IPC protocols for nurses in SSA.