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OBJECTIVE: Although typically serving higher income and younger demographic groups, meal-kit subscription services have the potential to improve food availability and dietary quality in communities experiencing low food access due to systemic discrimination. This study describes the development and characteristics of a pilot community-led meal-kit service (SouthEats) and evaluates key implementation outcomes of adoption, acceptability, and feasibility among households experiencing less income. DESIGN: We utilised a mixed methods study design, including data from administrative records, customer surveys and worker interviews. Thematic qualitative analyses and descriptive quantitative analyses were conducted to illuminate the characteristics and extent the pilot meal-kit service was adopted, acceptable, and financially feasible among the target populations. SETTING: The study took place in Washington DC, USA. PARTICIPANTS: Study participants included SouthEats consumers (n 35) and workers (n 3). RESULTS: During the pilot period, sixty-seven community members signed up for the meal-kit service, with 52 % making recurring purchases. Our results suggest that the meal-kit service is acceptable among people living in low food access areas. Our feasibility analysis indicates that, although not without challenges, the SouthEats model could be financially feasible. CONCLUSION: These preliminary insights can inform the scalability and potential replication of this service and provide foundational evidence for an approach that may be used to improve food access.
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Renda , Refeições , Humanos , Estudos de Viabilidade , Inquéritos e Questionários , Projetos de PesquisaRESUMO
OBJECTIVE: To test the hypothesis that monogenic neuropathies such as Charcot-Marie-Tooth disease (CMT) contribute to frequent but often unexplained neuropathies in the elderly, we performed genetic analysis of 230 patients with unexplained axonal neuropathies and disease onset ≥35 years. METHODS: We recruited patients, collected clinical data, and conducted whole-exome sequencing (WES; n = 126) and MME single-gene sequencing (n = 104). We further queried WES repositories for MME variants and measured blood levels of the MME-encoded protein neprilysin. RESULTS: In the WES cohort, the overall detection rate for assumed disease-causing variants in genes for CMT or other conditions associated with neuropathies was 18.3% (familial cases 26.4%, apparently sporadic cases 12.3%). MME was most frequently involved and accounted for 34.8% of genetically solved cases. The relevance of MME for late-onset neuropathies was further supported by detection of a comparable proportion of cases in an independent patient sample, preponderance of MME variants among patients compared to population frequencies, retrieval of additional late-onset neuropathy patients with MME variants from WES repositories, and low neprilysin levels in patients' blood samples. Transmission of MME variants was often consistent with an incompletely penetrant autosomal-dominant trait and less frequently with autosomal-recessive inheritance. CONCLUSIONS: A detectable fraction of unexplained late-onset axonal neuropathies is genetically determined, by variants in either CMT genes or genes involved in other conditions that affect the peripheral nerves and can mimic a CMT phenotype. MME variants can act as completely penetrant recessive alleles but also confer dominantly inherited susceptibility to axonal neuropathies in an aging population.
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Envelhecimento , Neuropatia Hereditária Motora e Sensorial/genética , Neprilisina/genética , Idade de Início , Idoso , Envelhecimento/sangue , Doença de Charcot-Marie-Tooth/sangue , Doença de Charcot-Marie-Tooth/genética , Feminino , Predisposição Genética para Doença/genética , Neuropatia Hereditária Motora e Sensorial/sangue , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Neprilisina/sangue , Sequenciamento do ExomaRESUMO
The use and utility of targeted gene panels for diagnosing the type of Charcot-Marie-Tooth have grown rapidly because commercial gene panels that contain most of the relevant genes are available and affordable for many patients. We used a targeted gene panel to analyze 175 patients who had an unexplained axonal polyneuropathy affecting large myelinated axons, 86 of whom reported a family history of neuropathy, and 89 of whom did not. In patients reporting a family history, the panel identified a pathogenic variant causing the neuropathy in six cases (7%); in patients not reporting a family history, the gene panel identified pathogenic variants causing neuropathy in two patients (2%). Interpretation in a tertiary referral setting, current gene panels identify the genetic cause of neuropathy in a small minority of patients who have an unexplained axonal neuropathy, even in those reporting a family history.
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Doença de Charcot-Marie-Tooth/genética , Predisposição Genética para Doença/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Bacterial resistance to first line antibiotics used to treat community-onset urinary tract infections (UTIs) continues to increase. We sought to create a clinical prediction tool for community-onset UTIs due to extended-spectrum cephalosporin-resistant (ESC-R) Enterobacterales (formerly Enterobacteriaceae, EB). METHODS: A case-control study was performed. The source population included patients presenting to an emergency department (ED) or outpatient practice with an EB UTI between 2010 and 2013. Case patients had ESC-R EB UTIs. Control patients had ESC-susceptible EB UTIs and were matched to cases 1:1 on study year. Multivariable conditional logistic regression was performed to develop the predictive model by maximizing the area under the receiver-operating curve (AUC). Internal validation was performed via bootstrapping. RESULTS: A total of 302 patients with a community-onset EB UTI were included, with 151 cases and 151 controls. After multivariable analysis, we found that presentation with an ESC-R EB community-onset UTI could be predicted by the following: (1) a history of malignancy; (2) a history of diabetes; (3) recent skilled nursing facility or hospital stay; (4) recent trimethoprim-sulfamethoxazole exposure; and (5) pyelonephritis at the time of presentation (AUC 0.73, Hosmer-Lemeshow goodness-of-fit P value 0.23). With this model, each covariate confers a single point, and a patient with ≥ 2 points is considered high risk for ESC-R EB (sensitivity 80%, specificity 54%). The adjusted AUC after bootstrapping was 0.71. CONCLUSIONS: Community-onset ESC-R EB UTI can be predicted using the proposed scoring system, which can help guide diagnostic and therapeutic interventions.
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OBJECTIVE: Charcot-Marie-Tooth (CMT) disease 4B1 and 4B2 (CMT4B1/B2) are characterized by recessive inheritance, early onset, severe course, slowed nerve conduction, and myelin outfoldings. CMT4B3 shows a more heterogeneous phenotype. All are associated with myotubularin-related protein (MTMR) mutations. We conducted a multicenter, retrospective study to better characterize CMT4B. METHODS: We collected clinical and genetic data from CMT4B subjects in 18 centers using a predefined minimal data set including Medical Research Council (MRC) scores of nine muscle pairs and CMT Neuropathy Score. RESULTS: There were 50 patients, 21 of whom never reported before, carrying 44 mutations, of which 21 were novel and six representing novel disease associations of known rare variants. CMT4B1 patients had significantly more-severe disease than CMT4B2, with earlier onset, more-frequent motor milestones delay, wheelchair use, and respiratory involvement as well as worse MRC scores and motor CMT Examination Score components despite younger age at examination. Vocal cord involvement was common in both subtypes, whereas glaucoma occurred in CMT4B2 only. Nerve conduction velocities were similarly slowed in both subtypes. Regression analyses showed that disease severity is significantly associated with age in CMT4B1. Slopes are steeper for CMT4B1, indicating faster disease progression. Almost none of the mutations in the MTMR2 and MTMR13 genes, responsible for CMT4B1 and B2, respectively, influence the correlation between disease severity and age, in agreement with the hypothesis of a complete loss of function of MTMR2/13 proteins for such mutations. INTERPRETATION: This is the largest CMT4B series ever reported, demonstrating that CMT4B1 is significantly more severe than CMT4B2, and allowing an estimate of prognosis. ANN NEUROL 2019.
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Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/genética , Proteínas Tirosina Fosfatases não Receptoras/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: To characterize the phenotype in individuals with OPA3-related autosomal dominant optic atrophy and cataract (ADOAC) and peripheral neuropathy (PN). METHODS: Two probands with multiple affected relatives and one sporadic case were referred for evaluation of a PN. Their phenotype was determined by clinical ± neurophysiological assessment. Neuropathologic examination of sural nerve and skeletal muscle, and ultrastructural analysis of mitochondria in fibroblasts were performed in one case. Exome sequencing was performed in the probands. RESULTS: The main clinical features in one family (n = 7 affected individuals) and one sporadic case were early-onset cataracts (n = 7), symptoms of gastrointestinal dysmotility (n = 8), and possible/confirmed PN (n = 7). Impaired vision was an early-onset feature in another family (n = 4 affected individuals), in which 3 members had symptoms of gastrointestinal dysmotility and 2 developed PN and cataracts. The less common features among all individuals included symptoms/signs of autonomic dysfunction (n = 3), hearing loss (n = 3), and recurrent pancreatitis (n = 1). In 5 individuals, the neuropathy was axonal and clinically asymptomatic (n = 1), sensory-predominant (n = 2), or motor and sensory (n = 2). In one patient, nerve biopsy revealed a loss of large and small myelinated fibers. In fibroblasts, mitochondria were frequently enlarged with slightly fragmented cristae. The exome sequencing identified OPA3 variants in all probands: a novel variant (c.23T>C) and the known mutation (c.313C>G) in OPA3. CONCLUSIONS: A syndromic form of ADOAC (ADOAC+), in which axonal neuropathy may be a major feature, is described. OPA3 mutations should be included in the differential diagnosis of complex inherited PN, even in the absence of clinically apparent optic atrophy.
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We report on two patients, with different POLG mutations, in whom axonal neuropathy dominated the clinical picture. One patient presented with late onset sensory axonal neuropathy caused by a homozygous c.2243G>C (p.Trp748Ser) mutation that resulted from uniparental disomy of the long arm of chromosome 15. The other patient had a complex phenotype that included early onset axonal Charcot-Marie-Tooth disease (CMT) caused by compound heterozygous c.926G>A (p.Arg309His) and c.2209G>C (p.Gly737Arg) mutations.
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Doença de Charcot-Marie-Tooth/diagnóstico , DNA Polimerase gama/genética , Mutação , Condução Nervosa/fisiologia , Doenças do Sistema Nervoso Periférico/diagnóstico , Adolescente , Doença de Charcot-Marie-Tooth/genética , Diagnóstico Diferencial , Eletrodiagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Linhagem , Doenças do Sistema Nervoso Periférico/genética , FenótipoRESUMO
BACKGROUND: Bacterial resistance to first line antibiotics used to treat community-onset urinary tract infections (UTIs) continues to emerge. We sought to determine the association between extended-spectrum cephalosporin resistance (ESC-R) and recurrence among Enterobacteriaceae (EB) UTIs. METHODS: A retrospective cohort study was performed. All patients presenting to the Emergency Departments (EDs) or outpatient practices in a large health system with EB UTIs between 2010 and 2013 were included. Exposed patients had ESC-R EB UTIs. Unexposed patients had ESC-susceptible EB UTIs and were matched to exposed patients 1:1 on study year. Multivariable Cox proportional hazards regression analyses were performed to evaluate the association between ESC-R EB UTI and time to recurrent UTI within 12 months. RESULTS: A total of 302 patients with an index community-onset EB UTI were included, with 151 exposed and 151 unexposed. Overall, 163 (54%) patients experienced a recurrent UTI with a median time to recurrence of 69 days (interquartile range 25-183). On multivariable analyses, ESC-resistance was associated with an increased hazard of recurrent UTI (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.01-1.91, P = 0.04). Other variables that were independently associated with recurrence included a history of UTI prior to the index UTI and presence of a urinary catheter at the time of the index UTI. Secondarily, we found that when the treatment for the index UTI was adjusted for, there was no longer a significant association between ESC-R status and time to recurrent UTI (aHR 1.26, 95% CI 0.91-1.76, P = 0.17). CONCLUSIONS: Community-onset UTI due to EB demonstrating ESC-resistance is associated with a significantly increased hazard of recurrent UTI within 12 months compared to ESC-susceptible EB, even after adjusting for baseline factors that predispose patients to UTI recurrence. This association appears to be driven primarily by delayed or inappropriate treatment for the index ESC-R EB UTI.
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Resistência às Cefalosporinas , Cefalosporinas/uso terapêutico , Infecções Comunitárias Adquiridas , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Infecções Urinárias/epidemiologia , Infecções Urinárias/microbiologia , Adulto , Idoso , Antibacterianos/uso terapêutico , Resistência às Cefalosporinas/efeitos dos fármacos , Resistência às Cefalosporinas/genética , Estudos de Coortes , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Infecções Urinárias/tratamento farmacológico , beta-Lactamases/genéticaRESUMO
Dominant mutations in MFN2 cause a range of phenotypes, including severe, early-onset axonal neuropathy, "classical CMT2", and late-onset axonal neuropathy. We found a novel MFN2 mutation - c.283A>G (p.Arg95Gly) - that results in an axonal neuropathy with variable clinical severity in a multigenerational family. In affected family members, electromyography showed moderate to severe, chronic denervation in distal muscles. Such variable clinical severity highlights the need to do careful assessments of at risk individuals when assessing MFN2 variants.
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Doença de Charcot-Marie-Tooth/diagnóstico , GTP Fosfo-Hidrolases/genética , Proteínas Mitocondriais/genética , Mutação , Adulto , Idoso de 80 Anos ou mais , Doença de Charcot-Marie-Tooth/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo , Índice de Gravidade de Doença , Adulto JovemRESUMO
OBJECTIVE: Resistance to extended-spectrum cephalosporins (ESC) among Enterobacteriaceae (EB) is increasingly prevalent. We sought to determine the clinical outcomes associated with community-onset ESC-resistant (ESC-R) EB urinary tract infections (UTIs) in a US health system. DESIGN: Retrospective cohort study.PatientsAll patients presenting to the emergency departments (EDs) or outpatient practices with EB UTIs between 2010 and 2013 were included. Exposed patients had ESC-R EB UTIs. Unexposed patients had ESC-susceptible EB UTIs and were matched to exposed subjects 1:1 on study year. Multivariable logistic regression analyses were performed to evaluate the association between ESC-R EB UTI and the outcomes of clinical failure and inappropriate initial antibiotic therapy (IIAT). RESULTS: A total of 302 patients with community-onset EB UTI were included, with 151 exposed and unexposed. On multivariable analyses, UTI due to an ESC-R EB was significantly associated with clinical failure (odds ratio [OR], 7.07; 95% confidence interval [CI], 3.16-15.82; P<.01). Other independent risk factors for clinical failure included infection with Citrobacter spp and need for hemodialysis. UTI due to an ESC-R EB was also significantly associated with IIAT (OR, 4.40; 95% CI, 2.64-7.33; P<.01). CONCLUSIONS: Community-onset UTI due to an ESC-R EB organism is significantly associated with clinical failure, which may be due in part to IIAT. Further studies are needed to determine which patients in the community are at high risk for drug-resistant infection to help inform prompt diagnosis and appropriate antibiotic prescribing for ESC-R EB.
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Resistência às Cefalosporinas , Cefalosporinas/uso terapêutico , Infecções Comunitárias Adquiridas/epidemiologia , Infecções por Enterobacteriaceae/epidemiologia , Infecções Urinárias/epidemiologia , Infecções Urinárias/microbiologia , Adulto , Idoso , Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/genética , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/microbiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Análise Multivariada , Pennsylvania/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Infecções Urinárias/tratamento farmacológicoRESUMO
Dominant mutations in MFN2 cause a range of phenotypes, including severe, early-onset axonal neuropathy, "classical CMT2," and late-onset axonal neuropathies. We report a large family with an axonal polyneuropathy, with clinical onset in the 20s, followed by slow progression.