RESUMO
BACKGROUND: Breast cancer is a common cause for central nervous system (CNS) metastasis, resulting in a significant reduction in overall survival. Germline pathogenic variants (PVs) in BRCA1/2 are the most common genetic risk factor for breast cancer, associated with poor prognostic factors. This study sought to explore the patterns and outcome of CNS metastases in breast cancer patients with germline PVs in BRCA1/2 genes. METHODS: A retrospective cohort of 75 breast cancer patients with known BRCA1/2 mutation status, who were diagnosed with CNS metastases in 2006-2021. Histopathology, characteristics of CNS disease, treatments, and survival were compared between BRCA1/2 carriers (n = 25) and non-carriers (n = 50), using propensity score matching (1:2 ratio) to control for the possible influence of tumor receptor status (ER, PR, HER2) and patient age. Pearson chi-square or Fisher exact test and Kaplan-Meier survival curves with log-rank test were used for statistical analyses. RESULTS: Patients with PVs in BRCA1/2 had more high-grade tumors (88% vs. 68%, P = 0.060), were younger at CNS disease diagnosis (median 46.69 vs. 55.02 years, P = 0.003) and had better ECOG performance status (ECOG PS 0 in 20% vs. 2%, P = 0.033), but without significant differences in systemic or CNS-directed treatment approaches. BRCA1/2 mutation was associated with a higher rate of temporal lobe involvement (52% vs. 26%, P = 0.026) and leptomeningeal spread (40% vs. 20%, P = 0.020). Survival after diagnosis of CNS disease was shorter (median 8.03 vs. 28.36 months, P < 0.0001), with no significant differences in time to development of CNS metastases or overall-survival. CONCLUSION: Patients with CNS metastatic breast cancer and PVs in BRCA1/2 showed a higher rate of leptomeningeal and temporal lobe involvement, and a shorter survival with CNS disease. To the best of our knowledge, this is the first study suggesting an exclusive impact of germline BRCA1/2 mutations in CNS metastatic breast cancer.
Assuntos
Proteína BRCA1 , Proteína BRCA2 , Neoplasias da Mama , Neoplasias do Sistema Nervoso Central , Feminino , Humanos , Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/patologia , Sistema Nervoso Central , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/secundário , Células Germinativas/patologia , Mutação em Linhagem Germinativa , Análise por Pareamento , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Previous studies demonstrated a 'weekend effect' and a 'night effect' of increased mortality among patients admitted during weekends or night shifts, presumably due to understaffing. AIMS: To examine whether death during hospitalisation follows a similar effect regardless of admission time. METHODS: A retrospective cohort study among deceased patients hospitalised in the internal medicine wing of a tertiary medical centre in Israel, between 2019 and 2020. Demographic and medical data were retrieved from electronic medical charts. Causes of death were specifically categorised. We applied statistical models to test for differences in mortality using incidence rate ratio (IRR) according to the day, time and cause of death. RESULTS: One thousand, two hundred and seventy-eight deceased patients were included. All-cause mortality was similar between weekends and weekdays. When sepsis was the cause of death, higher IRR were demonstrated on Fridays in comparison with weekdays (IRR 1.4; 95% confidence interval (CI) 1.1-1.9; P < 0.05). Other causes of death were not consistent with a 'weekend effect'. Mortality during night shifts was higher in comparison with the afternoon (IRR 1.5; 95% CI 1.3-4.7) and similar to the morning (IRR 1; 95% CI 0.9-1.2). CONCLUSION: Our study did not find a pattern of 'weekend effect' or 'night effect' on all-cause mortality among hospitalised patients in internal medicine wards. Our findings suggest that perhaps specifically death from sepsis, and not all-cause mortality, can be used as a surrogate for the measurement of understaffing or quality of care in the internal ward.
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Mortalidade Hospitalar , Unidades Hospitalares , Medicina Interna , Admissão do Paciente , Humanos , Mortalidade Hospitalar/tendências , Hospitalização , Estudos Retrospectivos , Fatores de Tempo , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Centros de Atenção Terciária , Israel/epidemiologia , Admissão do Paciente/estatística & dados numéricosRESUMO
OBJECTIVE: Isolation and school closure during the COVID-19 pandemic could decrease human papillomavirus (HPV) vaccination uptake and potentially increase future HPV-related morbidity among unvaccinated populations. The aim of our study was to investigate HPV vaccination rates in Israel during the pandemic. METHODS: The HPV vaccination rates were compared before and during the COVID-19 pandemic years (2020-2021). Data regarding HPV vaccination between 2015 and 2021 were extracted from the Israeli Ministry of Health online reports. Vaccination rates were compared with other childhood vaccines, given at similar ages. Israeli HPV vaccination rates were further compared with England and Australia, which have an established vaccination infrastructure. RESULTS: The average Israeli coverage of first-dose HPV vaccine was 60.2%, with significant variations from 2015 to 2021. During the pandemic years, first-dose vaccine coverage increased compared with the 3 previous years. The pandemic had also no apparent influence on other childhood vaccine uptake, even though adolescents in Israel missed many school days during this time. Average vaccine uptake in England and Australia was significantly higher than Israel ( p = .009); however, first-dose vaccination rates decreased considerably in England during 2020, to a nadir of 59%. The pandemic had little effect on HPV vaccination rates in Australia. CONCLUSIONS: Despite many school days missed, the COVID-19 pandemic did not result in a decrease in HPV vaccine uptake in Israel. The pandemic could prove a good opportunity to further educate the public regarding the importance of whole-population vaccination programs. Implementing catch-up vaccination programs may bridge "vaccination gaps" that may be caused by future pandemics.
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COVID-19 , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Adolescente , Humanos , Criança , Pandemias , Israel/epidemiologia , Papillomavirus Humano , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , COVID-19/epidemiologia , COVID-19/prevenção & controle , VacinaçãoRESUMO
STUDY OBJECTIVE: To evaluate the impact of Asherman syndrome (AS) following hysteroscopic adhesiolysis on reproductive outcomes and the time to achieve pregnancy in women with infertility undergoing in vitro fertilization (IVF) treatment. DESIGN: Case-control study. SETTING: Tertiary university-affiliated medical center. PATIENTS: Fifty-one infertile women who were treated for AS and underwent IVF (study group) matched for age and etiology of infertility with non-AS controls at a 1:1 ratio. INTERVENTIONS: Medical records search, chart review, and phone survey were used to assess reproductive outcomes. MEASUREMENTS AND MAIN RESULTS: A multivariate logistic regression analyses was used to assess live birth, accounting for patient age at stimulation cycle start, parity, number of embryos transferred, and endometrial thickness. A survival analysis was performed to assess the times that had lapsed from interventions to conception. The study group of 51 women included 38 (74.5%) with moderate to severe disease. The mean number of embryo transfers per woman was similar for the study and control groups (4.9 ± 4.6 vs 6.22 ± 4.3, respectively, p = .78). The controls had a significantly higher mean endometrial thickness before embryo transfer (8.7 ± 1.8 mm vs 6.95 ± 1.7 mm, p = .001). The overall time to achieve live birth was significantly longer in women with AS (p = .022). In a logistic regression analysis, the presence of moderate to severe AS was shown to be an independent factor for achieving a live birth (adjusted odds ratio 0.174, 95% confidence interval [CI], 0.032-0.955, p = .004). Women with AS who had live births had a significantly thicker mean endometrial thickness (8.2 ± 1.4 mm vs 6.9 ± 1.2, p = .001). CONCLUSION: Moderate and severe AS has a detrimental effect on reproductive performance in infertile women. Endometrial thickness is an important predictor for live births among women with AS who undergo IVF.
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Ginatresia , Infertilidade Feminina , Gravidez , Humanos , Feminino , Ginatresia/complicações , Ginatresia/cirurgia , Infertilidade Feminina/etiologia , Infertilidade Feminina/terapia , Estudos de Casos e Controles , Estudos Retrospectivos , Fertilização in vitro/efeitos adversos , Nascido Vivo , Prognóstico , Taxa de GravidezRESUMO
BACKGROUND & AIMS: The early stages of Crohn's disease (CD) course are heterogeneous, and it is a challenge to predict the course of disease in patients with new diagnosis. METHODS: We performed an observational longitudinal study of 156 adults (79 male; median age, 27.7 years; 57 treatment naïve) with newly diagnosed CD (within 6 months of enrollment), referred from medical centers and community clinics in Israel from 2013 through 2017. Study participants each received semi-annual scheduled evaluations. Indolent disease was defined as a disease course without need for strict interventions to control complicated course of CD (hospitalization or surgery, or decision to start steroid, immunomodulator, or biologic therapy). Cox regression and receiver operating characteristic analyses were used to identify factors associated with early indolent or complicated course of CD. We validated our findings in an independent cohort of patients with CD from a separate medical center in Israel in 2018. RESULTS: Over a median follow-up period of 17.2 months (interquartile range, 8.8-23.8 months), 52 patients (33.3%) had an indolent course of CD, 29 (18.5%) required hospitalizations, and 75 (48%) were recommended to start steroid, immunomodulator, or biologic therapies. The median time to first intervention was 3.4 months (95% CI, 2.4-4.4). We developed a model based on clinical factors that identified 4 factors associated with complicated course in treatment-naïve patients: body mass index <25 kg/m2 (hazard ratio [HR], 2.45; 95% CI, 1.07-5.43; P = .033), serum level of vitamin B12 <350 pg/mL (HR, 2.78; 95% CI, 1.21-6.41; P = .016), white blood cells ≥7 × 103/µL (HR, 2.419; 95% CI, 1.026-5.703; P = .044), and serum level of ALT ≥25 IU/L (HR, 2.680; 95% CI, 1.186-6.058; P = .018). This model discriminated between patients with vs without a complicated course of disease with 90% and 89% accuracy at 6 and 12 months after diagnosis, respectively. A validation cohort demonstrated a discriminatory ability of 79% at 3 months after diagnosis, and a nomogram was constructed. CONCLUSIONS: In an observational longitudinal study of 156 patients with newly diagnosed CD, we found that one third have an early indolent course of disease. We identified factors that can be measured at diagnosis to identify patients at risk for an early complicated course-these might be used in patient management and selection of treatment.
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Doença de Crohn , Adulto , Estudos de Coortes , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Progressão da Doença , Humanos , Estudos Longitudinais , Masculino , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
PURPOSE: The purpose of this study is to explore differences in the pattern and outcome of central nervous system (CNS) involvement in breast cancer by age at diagnosis. METHODS: A retrospective database of a tertiary cancer center yielded 174 consecutive patients with breast cancer who were diagnosed with CNS metastases in 2006-2019. Data on histopathology, characteristics of CNS involvement, treatments, and survival (at three time points during the disease course) were compared between patients aged ≤ 45 and > 45 years. Pearson Chi-square or Fisher exact test and Kaplan-Meier survival curves with log-rank test were used for statistical analyses. RESULTS: Study population was divided according to age at diagnosis of breast cancer. 65 patients were ≤ 45 years old and 109 patients > 45 years old. The younger group was characterized by longer median overall survival (117.1 months vs 88 months, p = 0.017) and longer interval between breast cancer diagnosis to development of CNS metastases (97.4 months vs 75.9 months, p = 0.026). Median survival after development of CNS disease was not significantly different (18.7 months vs 11.1 months, p = 0.341), although it was significantly longer in younger patients within the subgroup of patients with triple-negative disease (22.5 vs 7.9 months, p = 0.033). There were no between-group differences in number, location, and clinical presentation of CNS metastases or in systemic and CNS-directed treatment approaches. CONCLUSION: While the presentation of CNS involvement was similar between the different age groups, younger patients had significantly longer CNS-free interval and longer overall survival, and for the subgroups of triple-negative patients, younger age at breast cancer diagnosis was associated with longer survival after diagnosis of CNS disease.
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Neoplasias da Mama , Neoplasias do Sistema Nervoso Central , Idoso , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/epidemiologia , Neoplasias do Sistema Nervoso Central/secundário , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVES: The APOE-ε4 genotype has been associated with old-age depression, but this relationship has been rarely investigated in type 2 diabetes (T2D) older adults, who are at significantly increased risk for depression, a major contributor to T2D complications. We examined whether trajectories of depression symptoms over time differ by APOE-ε4 genotype in older adults with T2D. METHODS: Participants (n = 754 [13.1% APOE-ε4 carrier]s) were from the longitudinal Israel Diabetes and Cognitive Decline (IDCD) study. They were initially cognitively normal and underwent evaluations of depression approximately every 18 months using the 15-item version of the Geriatric Depression Scale (GDS) and the depression subscale of the Neuropsychiatric Inventory (NPI). APOE was defined as a dichotomy of ε4 carriers and non-carriers. We used Hierarchical Linear Mixed Models (HLMM) that modeled the effects of APOE status on repeated GDS and NPI-depression scores in an unadjusted model (Model 1), adjusting for demographic factors (Model 2) and additionally adjusting for cardiovascular factors and global cognition (Model 3). RESULTS: Participants' mean age was 71.37 (SD = 4.5); 38.2% female. In comparison to non-carriers, APOE-ε4 carriers had lower mean GDS scores (ß = -0.46, p = 0.018) and lower NPI-depression scores (ß = -0.170, p = 0.038) throughout all study follow period. The groups did not differ in the slope of change over time in GDS (ß = -0.005, p = 0.252) or NPI-depression (ß = -0.001, p = 0.994) scores. Additional adjustment for cardiovascular factors and global cognition did not alter these results. CONCLUSIONS: In older adults with T2D, APOE-ε4 carriers have less depressive symptoms in successive measurements suggesting they may be less susceptible to depression.
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Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Idoso , Apolipoproteína E4/genética , Cognição , Depressão/genética , Diabetes Mellitus Tipo 2/genética , Feminino , Genótipo , Humanos , Masculino , Testes NeuropsicológicosRESUMO
INTRODUCTION: Inflammatory myopathies are treated with glucocorticoids and other immunosuppressive medications. Intravenous immunoglobulin (IVIG) is increasingly used for refractory or severe cases; however, the evidence for their effectiveness is limited. We assessed effectiveness and safety of IVIG when used with other immunomodulatory agents in the treatment of inflammatory myopathies. METHODS: This study reviewed records of patients diagnosed with dermatomyositis or polymyositis and treated with IVIG, from 2009 through 2016 in 1 tertiary medical center. Mixed-effects general linear regression models were applied to determine effectiveness of treatment on muscle strength, creatinine phosphokinase levels, and steroid dosage. RESULTS: Twenty-three patients with dermatomyositis/polymyositis treated with IVIG were followed up for a mean of 31 (SD, ±25) months. During this period, a significant improvement in muscle strength was demonstrated, with a mean increase of 0.92 Medical Research Council scale points (ß = 0.14; confidence interval [CI], 0.136-0.149; p < 0.0001), a significant reduction of creatinine phosphokinase levels and steroid dosage with a mean decrease of 1140 IU/L (ß = -0.274; CI, -0.354 to -0.195; p < 0.0001), and 36 mg/d (ß = -0.008; CI, -0.011 to -0.006; p < 0.0001), respectively. Overall, remission was observed in 10 patients (43.5%), and partial remission in 6 patients (26%), whereas 1 patient (17%) remained refractory to treatment, and 6 patients (27%) were lost to follow-up. CONCLUSIONS: The majority of patients with inflammatory myopathies experienced a clinical and laboratory improvement during IVIG treatment. In addition, a steroid-sparing effect was noticed in most patients. These results encourage the use of IVIG as an alternative treatment option for patients with limited responsiveness to conventional methods.
Assuntos
Dermatomiosite , Miosite , Polimiosite , Dermatomiosite/diagnóstico , Dermatomiosite/tratamento farmacológico , Humanos , Imunoglobulinas Intravenosas , Fatores Imunológicos , Miosite/diagnóstico , Miosite/tratamento farmacológico , Polimiosite/diagnóstico , Polimiosite/tratamento farmacológicoRESUMO
OBJECTIVE: To assess outcomes of ultrasound and physical examination-based cerclage performed at mid to late second trimester and to assess the potential added value of progesterone treatment combined with cerclage for preventing preterm birth. STUDY DESIGN: A retrospective cohort study of women who underwent cerclage in a university-affiliated tertiary medical center (2012-2018). Inclusion criteria included only ultrasound-based cerclage and physical examination-based cerclage. Women who underwent history-based cerclage or multiple gestations were excluded. Study groups were stratified by previous PTB < 37 weeks and other risk factors for PTB. Primary outcome was the incidence of preterm birth < 35 weeks of gestation. Secondary outcomes included the potential added value of progesterone treatment and neonatal outcome. RESULTS: Sixty-nine women underwent cervical cerclage placement between 16-23 weeks of gestation. All women had short cervix (cervical length of < 25 mm) at presentation. Indications for cerclage placement included: 29% previous PTB, 32% prior cervical interventions (history of at least one D&C, hysteroscopy or cold-knife conization in the past), 22% had cervical dilatation > 1 cm at presentation, 12% due to failure of progesterone treatment defined as continued cervical shortening after 14 days of progesterone treatment, and 5% had other indications. Overall, 42 women (61%) gave birth at term. 27 women (39%) delivered prior to 37 weeks of gestation, of them, 20 women (29%) gave birth prior to 35 weeks. Overall median gestational age at delivery was 35 + 5 ± 4.7 weeks. Cervical dilatation at presentation of > 1 cm was associated with an increased risk for PTB < 35 weeks (OR 3.57, CI 1.43-30.81, p = 0.036). Previous PTB, prior cervical interventions and extent of cervical shortening at presentation did not increase the risk of PTB. Progesterone treatment in addition to cerclage did not result in a decreased risk for PTB < 35 weeks of gestation (OR 2.83, CI 0.58-13.89, p = 0.199). CONCLUSION: Late second trimester cerclage is a practical measure for preventing PTB in cases of asymptomatic cervical shortening. Our study did not find adjunctive benefit for progesterone treatment with physical or ultrasound-based cerclage in reducing the rate PTB.
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Cerclagem Cervical/métodos , Nascimento Prematuro/prevenção & controle , Progesterona/uso terapêutico , Adulto , Feminino , Humanos , Gravidez , Progesterona/farmacologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , UltrassonografiaRESUMO
OBJECTIVE: Women with inflammatory bowel disease (IBD) have an increased risk for adverse pregnancy outcome, so as women using assisted reproduction technology (ART). However, data are scarce regarding the risk imposed by the combination of both. Thus, we aimed to assess pregnancy outcome in these women. METHODS: A retrospective case-control study, of women with IBD who conceived using ART due to female infertility. The study group (IBD-ART) was matched using propensity score and compared in a 1:1 ratio with three control groups, IBD patients who conceived spontaneously (IBD-SP), women using ART (H-ART) and women who conceived spontaneously (H-SP). RESULTS: The study group comprised of 49 women with IBD conceived via ART that gave birth at our center during the study period. All studied groups did not differ in demographics and obstetric characteristics. IBD groups (both ART and spontaneous) were comparable in disease status prior and throughout pregnancy. Maternal outcome showed no difference regarding preterm birth and pregnancy complications among all studied groups. Women in the IBD-ART group had decreased rates of vaginal delivery (34.7% vs 57.1%, p = 0.032) and higher rates of elective CS (32.7% vs 14.3%, p = 0.048) in comparison to H-SP group, but comparable rates to both IBD-SP and H-ART groups. Neonatal outcomes were comparable among all studied groups. In a sub-analysis by disease type, a higher rate of gestational diabetes was found among ulcerative colitis patients using ART (29.4% Crohn's vs 6.1% UC, p = 0.025). CONCLUSION: Patients with IBD undergoing ART have comparable pregnancy outcome to women using ART and to patients with IBD with spontaneous pregnancy.
Assuntos
Colite Ulcerativa/complicações , Doença de Crohn/complicações , Infertilidade Feminina/terapia , Doenças Inflamatórias Intestinais/complicações , Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Técnicas de Reprodução Assistida/estatística & dados numéricos , Adulto , Estudos de Casos e Controles , Parto Obstétrico , Diabetes Gestacional/etiologia , Feminino , Humanos , Recém-Nascido , Infertilidade Feminina/etiologia , Gravidez , Complicações na Gravidez/etiologia , Nascimento Prematuro/etiologia , Técnicas de Reprodução Assistida/efeitos adversos , Estudos RetrospectivosRESUMO
PURPOSE: To determine the influence of maternal diets on maternal and umbilical cord blood levels of vitamin B12, folic acid, ferritin, and hemoglobin. METHODS: A prospective observational study on women who maintained the same diet for at least 3 months prior to, and throughout current pregnancy. Women were divided according to their diet. Diet questionnaires were filled in during the 3rd trimester. Blood samples for complete blood counts and levels of ferritin, vitamin B12, folate, and albumin were taken from the women prior to delivery and from the umbilical cord immediately after delivery. RESULTS: The 273 enrolled women included 112 omnivores, 37 pescatarians, 64 vegetarians, and 60 vegans. There were no significant differences in the maternal B12 levels between the study groups (P = 0.426). Vegans had lower maternal ferritin levels compared to pescatarians (27 ± 17 vs 60 ± 74 ng/ml, respectively, P = 0.034), but not compared to vegetarians (P = 0.597), or omnivores (P = 1.000). There were no significant differences in the umbilical cord B12, folate, ferritin, and hemoglobin levels between the study groups. A sub-analysis that compared women who consumed multivitamins, B12 and iron supplements during pregnancy to women who did not, revealed differences in the levels of umbilical-cord B12 (1002 ± 608 vs 442 ± 151 pg/ml, respectively, P = 0.000) and maternal blood B12 (388 ± 209 vs 219 ± 95 pg/ml, respectively, P = 0.030) only among vegans, but not among omnivores. CONCLUSION: Vegan diet does not change the umbilical cord levels of B12, folic acid, ferritin, and hemoglobin. Vegans who do not take any vitamin supplementation are at greater risk for B12 deficiency than omnivores.
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Dieta Vegana/métodos , Ferritinas/sangue , Sangue Fetal/química , Ácido Fólico/sangue , Vitamina B 12/sangue , Adulto , Feminino , Humanos , Masculino , Gravidez , Estudos ProspectivosRESUMO
BACKGROUND: Deep brain stimulation (DBS) is a well-established treatment option for individuals with advanced Parkinson's disease (PD). The potential influence of the LRRK2 p.G2019S or GBA1 variants on its lasting efficacy and adverse effects should be better characterized. METHODS: We conducted a retrospective single-center case-control study involving PD patients who were carriers of a GBA1 variant (GBA1-PD), the LRRK2 p.G2019S variant (LRRK2-PD), and non-carriers (Nc-PD). All participants underwent DBS and were followed up for at least a year. Assessments before surgery and at 1, 2, 3, 5, and 10 years post-DBS included the following: the Movement Disorder Society's Unified PD Rating Scale (MDS-UPDRS) Part III, Hoehn and Yahr scale, Levodopa Equivalent Daily Dose (LEDD) and non-motor symptoms (psychotic episodes, depressive symptoms, and cognitive decline). RESULTS: The sample was composed of 103 patients (72 males, mean age at DBS surgery 61.5 ± 8.7 years, mean postoperative follow-up 7.0 ± 4.1 years). Of these, 19 were LRRK2-PD, 20 GBA1-PD, and 64 were Nc-PD. No significant differences in motor outcomes were observed between the groups. Compared to the Nc-PD patients, the GBA1-PD patients were at increased risk of both psychotic episodes [hazard ratio (HR) 2.76 (95 % CI: 1.12-6.80), p = 0.027], and cognitive decline [HR 2.28 (95 % CI: 1.04-5.00), p = 0.04]. CONCLUSION: LRRK2 and GBA1 variant status did not affect the motor outcomes of DBS in PD patients. However, GBA1-PD patients were at increased risk for psychosis and cognitive decline. Further studies are required to determine the role of genetic stratification in referral to DBS.
Assuntos
Estimulação Encefálica Profunda , Glucosilceramidase , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina , Doença de Parkinson , Humanos , Doença de Parkinson/terapia , Doença de Parkinson/genética , Estimulação Encefálica Profunda/efeitos adversos , Masculino , Feminino , Serina-Treonina Proteína Quinase-2 com Repetições Ricas em Leucina/genética , Glucosilceramidase/genética , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Estudos de Casos e Controles , Resultado do Tratamento , SeguimentosRESUMO
BACKGROUND: We examined the cross-sectional and longitudinal relationships of motor functions with depression in older adults with type 2 diabetes (T2D). METHODS: Participants (n = 984) were from the longitudinal Israel Diabetes and Cognitive Decline (IDCD) study. They were initially cognitively normal and underwent evaluations of motor functions (grip strength and gait speed) and of depression (using the 15-item version of the Geriatric Depression Scale [GDS]) approximately every 18 months. We applied Hierarchical Linear Mixed Models (HLMM) to investigate the associations between motor functions and depression adjusting for sociodemographic, cardiovascular factors, overall cognitive score, and subjective report of exhaustion. RESULTS: Participants' baseline characteristics were 72 (±5) years of age (59.6% males), 13 (±4) years of education, Mini-Mental Status Exam (MMSE) score of 28.01 (±1.78), and a GDS score of (2 ± 2.00), consistent with normal cognitive status and lack of major affective symptomatology. Slower gait speed at baseline was associated with higher GDS scores (p = .001) and with their increase over time (p = .049). A decrease in walking speed from baseline was associated with an increase in GDS scores (p = .015). Lower grip strength at baseline was associated with higher GDS scores (p = .002), but not with trajectories in GDS scores over time. A faster decrease in grip strength from baseline was associated with a faster increase in GDS scores (p = .022). CONCLUSIONS: Both gait speed and grip strength are cross-sectionally associated with depression. However, only gait speed and its decrease over time can potentially be used to predict incident depression symptoms, thus facilitating the introduction of depression prevention strategies.
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Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Masculino , Humanos , Idoso , Feminino , Velocidade de Caminhada , Diabetes Mellitus Tipo 2/complicações , Depressão/epidemiologia , Depressão/diagnóstico , Estudos Transversais , Disfunção Cognitiva/diagnósticoRESUMO
OBJECTIVES: The use of antiplatelet agents is postulated to lead to improved outcomes in sepsis. We aimed to evaluate whether chronic, pre-hospitalization aspirin use leads to improved outcomes in patients with sepsis. METHODS: We conducted an observational cohort study among patients with sepsis, hospitalized in internal medicine wards in a single university-affiliated medical center. A propensity-score model was used to match and compare patients on chronic aspirin use to non-users. Patients with established cardiovascular disease were excluded. The primary outcome was survival rates at 30 days. Secondary outcomes included survival rates at 90 days, days of fever, length of hospital stay, and hospital readmission within 90 days. RESULTS: A total of 1671 patients fulfilled the inclusion criteria. 533 chronic aspirin users were matched to 533 aspirin non-users. Survival rates were significantly higher among patients on chronic aspirin use (hazard ratio (HR) 0.67; 95% CI, 0.51-0.89)). This effect was highlighted in several subgroups of patients, as patients with chronic obstructive pulmonary disease (COPD) or those with chronic use of beta blockers showed the greatest survival benefit with aspirin use. Patients in the aspirin group also showed significantly higher 90 days survival rates (HR 0.69; 95% CI, 0.57-0.92; p = 0.006) and experienced less days of fever in comparison to the control group. DISCUSSION: Pre-hospitalization treatment with aspirin for patients without established cardiovascular disease may be associated with mortality reduction, as shown in this is hypothesis-generating single center observational study.
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Doenças Cardiovasculares , Sepse , Aspirina/uso terapêutico , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/tratamento farmacológico , Estudos de Coortes , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate the impact of prolonged exposure to meconium-stained amniotic fluid (MSAF), in women with term pre-labor spontaneous rupture of membranes (PROM), on pregnancy outcome. METHODS: A retrospective cohort study of women who gave birth in a single university-affiliated tertiary medical center (2011-2019). Eligibility was limited to singleton pregnancies at term who presented with PROM. Women with MSAF were immediately induced and were compared to low-risk pregnant women with clear amniotic fluid (CAF) at admission who underwent induction of labor 24 h after rupture of membranes. All women were stratified into 4-time frame groups from rupture of membranes to delivery: T0: 0-7 h, T1: 8-13 h, T2: 14-18 h, and T3: > 18 h for the MSAF group. The time frames for the CAF were: T0 - 24-31 h, T1: 32-38 h, T2: 40-44 h, and T3: > 44 h. The maternal adverse composite outcome included any of the following: intrapartum fever (IPF), prolonged second stage (PSS), need for manual removal of suspected retained placenta, postpartum hemorrhage, and readmission within 45 days after delivery. The adverse composite neonatal outcome included one or more of the following: meconium aspiration syndrome, neonatal asphyxia, need for respiratory support, and intracranial hemorrhage. RESULTS: Overall, 1631 women met the inclusion criteria (536 in the MSAF and 1095 in the CAF group). Both groups showed a gradual decrease in the rate of vaginal delivery over time, the vaginal delivery rate in the MSAF group was 75.7% at T0 in comparison to 61.6% at T3 (p < .001). In the CAF group, the vaginal delivery rate was 84.5% at T0 in comparison to 68.8% at T3 (p < .001). This decrease was in concomitance with an increase in the rates of prolonged second-stage and intrapartum fever. There were no significant differences in the rates of postpartum hemorrhage, suspected retained placenta, or readmission within 45 days between women with either MSAF or CAF. There was a significant gradual increase in the adverse composite neonatal outcome in the MSAF group (1.9% at T0, 5.2% at T1, 6.0% at T2, and 8.2% at T3. p = .038). No similar increase was found in the CAF group (2.5% at T0, 4.1% at T1, 2.6% at T2, and 4.1% at T3. p = .449). CONCLUSION: Prolonged rupture of membranes in the presence of meconium does not affect maternal outcomes, however, prolonged exposure to meconium lead to an increased adverse neonatal outcome.
Assuntos
Doenças do Recém-Nascido , Síndrome de Aspiração de Mecônio , Placenta Retida , Hemorragia Pós-Parto , Complicações na Gravidez , Nascimento Prematuro , Gravidez , Feminino , Humanos , Recém-Nascido , Mecônio , Resultado da Gravidez/epidemiologia , Estudos Retrospectivos , Ruptura Espontânea , Síndrome de Aspiração de Mecônio/epidemiologia , Líquido AmnióticoRESUMO
OBJECTIVE: Cefazolin is a widely used antimicrobial prophylactic agent, however the appropriate dosage, timing, pharmacology and microbial coverage have not been well-established for gynecologic procedures. We aimed to describe serum concentrations and pharmacokinetics of Intravenous cefazolin given to women prior to scheduled minimally invasive gynecologic surgeries, and to determine whether appropriate antimicrobial coverage had been achieved in short time from prophylactic administration to surgical start time. METHODS: A prospective cohort analysis study, using a resampled dataset, of women undergoing scheduled gynecological surgeries in a university affiliated tertiary medical center. IV cefazolin (1 or 2 gr) was administered prior to incision to women weighing <80 kg (Group A) and ≥80 kg (Group B), respectively. Cefazolin serum levels were obtained at the time of skin incision (Time 0) and 30 min later (Time 30), measured by high-pressure liquid chromatography (HPLC). Appropriate antimicrobial coverage was defined when cefazolin serum levels were above minimal inhibitory concentrations (MIC) for Enterobacteriaceae. RESULTS: Overall, 21 women were included. The mean time interval between drug administration and incision did not differ between the two groups (18 ± 10 min vs. 11 ± 10 min, respectively, p = .0.25). A hierarchical mixed linear regression model, using a simulation of multiple random bootstrap resampling (n = 1,000), revealed that cefazolin serum levels exceeded MIC, regardless of the timing of administration in the sampling intervals. Mean cefazolin serum levels in time 0 and time 30 min were not affected by BMI in patients receiving 1 gr. CONCLUSION: A single dose of IV cefazolin given shortly prior to skin incision provides serum concentrations above minimal inhibitory concentrations for susceptible pathogens in most women undergoing scheduled minimally invasive gynecologic surgery.
Assuntos
Antibioticoprofilaxia/métodos , Cefazolina/administração & dosagem , Cefazolina/farmacocinética , Procedimentos Cirúrgicos em Ginecologia/métodos , Adulto , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Estudos Prospectivos , Tempo para o TratamentoRESUMO
OBJECTIVE: To determine the effect of a maternal vegan diet on pregnancy outcome. STUDY DESIGN: This is a prospective observational study. Women with a singleton pregnancy who maintained the same diet prior to, and throughout current pregnancy were enrolled. Stratification was performed according to diet type: vegans, lacto-ovo-vegetarians, fish-eaters, and omnivores. RESULTS: Overall, 273 women were enrolled, of them, 112 omnivores, 37 fish-eaters, 64 lacto-ovo-vegetarians, and 60 vegans. The vegan diet was significantly associated with an increased risk of small-for-gestational-age newborns compared only to an omnivore diet (RR = 5.9, 95% CI, 1.2-21.8). The incidence of preterm birth was similar in all groups. Vegans had lower birthweight compared to lacto-ovo-vegetarians (3015 ± 420 g vs. 3285 ± 482 g, P = 0.004), and to omnivores (3328 ± 495 g, P < 0.001), but not to fish-eaters. Vegans also had a lower mean gestational weight gain compared only to omnivores (11.6 ± 4.2 kg vs. 14.3 ± 4.6 kg, P = 0.001). CONCLUSION: The vegan diet is associated with an increased risk for small-for-gestational-age newborns and lower birthweight.
Assuntos
Dieta Vegana , Nascimento Prematuro , Animais , Dieta , Dieta Vegetariana , Feminino , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez/epidemiologia , VegetarianosRESUMO
BACKGROUND: Paleolithic diet has recently gained popularity due to its presumed health benefits. The favorable metabolic effects of this diet were assessed in non-pregnant population but its impact during pregnancy remains to be evaluated. STUDY DESIGN: A retrospective cohort study comparing two groups. Group A comprised of women with singleton low-risk pregnancy adherent to paleolithic diet throughout gestation (nâ¯=â¯37). Group B comprised low risk pregnant women on a regular diet (nâ¯=â¯39). Women were excluded if they had low adherence to diet, started paleolithic diet during pregnancy, and had pre-gestational diabetes mellitus or other types of metabolic syndrome such as pre gestational hyperlipidemia, hypertension or BMI > 35. Blood indices such as Glucose challenge test scores, hemoglobin, ferritin, and TSH levels were compared. Other pregnancy factors such as maternal weight gain, rest days during gestation and pregnancy complications such as IUGR, GDM or preeclampsia were compared. Lastly, obstetrical outcomes such as mode of delivery and complications such as high-grade tears, as well as neonatal factors such as birth weight and pH were compared between the two groups. RESULTS: General maternal characteristics such as age, BMI and parity were comparable between the two groups. Women who maintained a paleolithic diet had a significant decrease in glucose challenge test scores (95.8â¯mg/dL vs. 123.1â¯mg/dL, pâ¯<â¯0.01) and increase in hemoglobin levels (12.1â¯g/dL vs. 11.05â¯g/dL pâ¯<â¯0.01) and Ferritin (32.1 vs 21.3â¯mg/mL, pâ¯=â¯0.03) compared to women maintaining regular diet. Maternal pregnancy weight gain was also slightly decreased in group A (9.3Kg vs. 10.8â¯kg, pâ¯=â¯0.03). Birthweights were lower in group A (3098â¯g Vs.3275â¯g, pâ¯=â¯0.046) with no difference in adverse neonatal outcomes. We found no differences in other pregnancy complications or labor outcomes such as mode of delivery, shoulder dystocia or high grade perineal tears. CONCLUSION: Paleolithic diet maintained during pregnancy may have a beneficial effect on the glucose tolerance. It also may increase iron stores and hemoglobin levels. Neonates of women maintaining paleolithic diet are slightly lighter but appropriate for gestational age with no difference in neonatal outcomes.