Natural selection at the RASGEF1C (GGC) repeat in human and divergent genotypes in late-onset neurocognitive disorder.

Expression dysregulation of the neuron-specific gene, RASGEF1C (RasGEF Domain Family Member 1C), occurs in late-onset neurocognitive disorders (NCDs), such as Alzheimer's disease. This gene contains a (GGC)13, spanning its core promoter and 5' untranslated region (RASGEF1C-201 ENST00000361132.9). Here we sequenced the (GGC)-repeat in a sample of human subjects (N = 269), consisting of late-onset NCDs (N = 115) and controls (N = 154). We also studied the status of this STR across various primate and non-primate species based on Ensembl 103. The 6-repeat allele was the predominant allele in the controls (frequency = 0.85) and NCD patients (frequency = 0.78). The NCD genotype compartment consisted of an excess of genotypes that lacked the 6-repeat (divergent genotypes) (Mid-P exact = 0.004). A number of those genotypes were not detected in the control group (Mid-P exact = 0.007). The RASGEF1C (GGC)-repeat expanded beyond 2-repeats specifically in primates, and was at maximum length in human. We conclude that there is natural selection for the 6-repeat allele of the RASGEF1C (GGC)-repeat in human, and significant divergence from that allele in late-onset NCDs. STR alleles that are predominantly abundant and genotypes that deviate from those alleles are underappreciated features, which may have deep evolutionary and pathological consequences.

Spectrum and Antifungal Resistance of Candidemia in Neonates With Early- and Late-Onset Sepsis in Pakistan.

BACKGROUND: Neonatal candidemia leads to high morbidity and mortality in developing countries. We studied the trends, spectrum and antifungal resistance in neonatal candidemia isolates from the year 2014 to 2019. METHODS: This was a cross-sectional study conducted at the Aga Khan University, Pakistan. Neonates with positive blood cultures with Candida species were retrospectively identified from the laboratory database (2014-2018) and prospectively in 2019 where clinical information was also collected as part of routine laboratory reporting. RESULTS: We identified 669 neonates with Candida species in blood cultures. Three hundred forty-six neonates had early-onset disease (EOD age ≤7 days) and 323 had late-onset disease (LOD age >7 days). Non-albicans Candida species (86.7%) were predominant versus C. albicans (13.3%; P-value 0.024) with Candida tropicalis being most common in both EOD and LOD. Candida pelliculosa and Candida guilliermondii were associated with EOD and C. albicans with LOD. Isolation of fluconazole nonsusceptible non-albicans Candida species was significantly higher in early-onset (5.9%) versus late-onset (2%) neonatal candidemia (P-value 0.005; crude odds ratio [COR] 2.73, 95% CI: 1.34-5.53). LOD in neonates was more likely associated with the use of vancomycin (COR 3.89, 95% CI: 1.39-10.89). EOD was more likely seen in patients with vaginal delivery (COR 4.16, 95% CI: 1.42-12.23) and in neonates with respiratory distress leading to intensive care unit admission (COR 3.31, 95% CI: 1.05-10.42). CONCLUSIONS: Non-albicans Candida species were increasingly isolated from neonates with candidemia during recent years from Pakistan. Amphotericin remains first-line option for neonatal candidemia in our setting as fluconazole nonsusceptible Candida species are commonly isolated.

Sleep disorders and late-onset epilepsy of unknown origin: Understanding new trajectories to brain amyloidopathy.

The intertwining between epilepsy, sleep disorders and beta amyloid pathology has been progressively highlighted, as early identification and stratification of patients at high risk of cognitive decline is the need of the hour. Modification of the sleep-wake activity, such as sleep impairment or excessive daytime sleepiness, can critically affect cerebral beta amyloid levels. Both mice models and human studies have demonstrated a substantial increase in the burden of beta amyloid pathology after sleep-deprivation, with potential negative effects partially restored by sleep recovery. The accumulation of beta amyloid has been shown to be an early event in the course of Alzheimer's disease dementia. Beta amyloid accumulation has been linked to epileptic seizures epileptic seizures, with beta amyloid being itself pro-epileptogenic in mice models already at oligomeric stage, well before plaque deposition. Further supporting a potential relationship between beta amyloid and epilepsy: i) seizures happen in 1 out of oofut 10 patients with Alzheimer's disease in the prodromal stage, ii) epileptic activity accelerates cognitive decline in Alzheimer's disease, iii) people with late-onset epilepsy present a critically high risk of developing dementia. In this Review we highlight the role of beta amyloid as a potential shared mechanisms between sleep disorders, late-onset epilepsy, and cognitive decline.

Late-onset Neonatal Infections 1997 to 2017 Within a Cohort in Western Sweden-The Last 21 Years of a 43-Year Surveillance.

BACKGROUND: The objective of the study was to assess the epidemiology of late-onset (LO) neonatal invasive infections with surveillance covering 43 years, starting from 1975. METHODS: Observational epidemiologic, retrospective study including a cohort of infants born in western Sweden in 1997-2017, who had a positive blood and cerebral spinal fluid culture between 3 and 120 days of age. A comparison was made of the incidence between 1997-2007 and 2008-2017. Data on LO infections during 3-27 days of life were assessed from 1975. RESULTS: A total of 473 cases of LO infections were registered in 437 patients. The incidence increased from 2.0 to 3.1/1000 live births (LB) between 1997-2007 and 2008-2017 (P < 0.001). The increase in incidence was most pronounced among infants born <28 weeks gestation (from 255 to 398/1000 LB, P < 0.001). The most frequent pathogens were Staphylococcus aureus (25%), coagulase-negative staphylococci (17%), and Escherichia coli (13%). Infections due to group B Streptococci rose from 0.16/1000 LB to 0.33 (P = 0.03). During the whole surveillance period from 1975 to 2017, there were 579 cases between 3 and 27 days of life. Although the incidence increased in 2008-2017 to 1.9/1000 LB after first declining in 1997-2007, the case-fatality rate continued to decline from 27/284 (9.5%) between 1975 and 1996 to 6/182 (3.3%) in 2008 and 2017 (P = 0.01). CONCLUSIONS: The incidence of LO neonatal invasive infections increased during the study period (1997-2017), but the case-fatality rate remained lower than in the previous surveillance period (1975-1996). Further surveillance and interventions with focus on prevention is critical to counteract the increasing incidence among high-risk infants.

Differential Expression of PEG10 Contributes to Aggressive Disease in Early Versus Late-Onset Colorectal Cancer.

BACKGROUND: Colorectal cancer is a leading cause of cancer-related death. Early onset colorectal cancer (age ≤45 y) is increasing and associated with advanced disease. Although distinct molecular subtypes of colorectal cancer have been characterized, it is unclear whether age-related molecular differences exist. OBJECTIVE: We sought to identify differences in gene expression between early and late-onset (age ≥65 y) colorectal cancer. DESIGN: We performed a review of our institution's colorectal cancer registry and identified patients with colorectal cancer with tissue specimens available for analysis. We used the Cancer Genome Atlas to initially identify differences in gene expression between early and late-onset colorectal cancer. In vitro experiments were performed on 2 colorectal cancer cell lines. SETTINGS: The study was conducted at a tertiary medical center. PATIENTS: Patients with early onset (n = 28) or late onset (age ≥65 y; n = 38) at time of diagnosis were included. MAIN OUTCOME MEASURES: The primary outcome was differential gene expression in patients with early versus late-onset colorectal cancer. The secondary outcome was patient mortality. RESULTS: Seven genes had increased expression in younger patients using The Cancer Genome Atlas. Only PEG10 was sufficiently expressed with quantitative polymerase chain reaction and had increased expression in our early onset group. Multivariable linear regression analysis identified age as a significant independent predictor of increased PEG10 expression. Outcomes data from The Cancer Genome Atlas suggests that PEG10 is associated with poor overall survival. In vitro studies in HCT-116 and HT-29 cell lines showed that PEG10 contributes to cellular proliferation and invasion in colorectal cancer. LIMITATIONS: Tissue samples were from formalin-fixed, paraffin-embedded sections. Many patients did not have mutational status for review. CONCLUSIONS: PEG10 is differentially expressed in early onset colorectal cancer and may functionally contribute to tumor cell proliferation and invasion. An increase in PEG10 expression correlates with decreased overall survival. See Video Abstract at http://links.lww.com/DCR/B343. LA EXPRESIÓN DIFERENCIAL DE PEG10 CONTRIBUYE A LA ENFERMEDAD AGRESIVA EN EL CÁNCER COLORRECTAL DE INICIO TEMPRANO VERSUS INICIO TARDÍO: El cáncer colorrectal es una de las principales causas de muerte relacionada con el cáncer. El cáncer colorrectal de inicio temprano (edad ≤45 años) está en aumento y asociado con enfermedad avanzada. Aunque se han caracterizado distintos subtipos moleculares del cáncer colorrectal, no está claro si existen diferencias moleculares relacionadas con la edad.Se buscó identificar diferencias en la expresión génica entre el cáncer colorrectal de inicio temprano y tardío (edad ≥ 65 años).Realizamos una revisión del registro de cáncer colorrectal de nuestra institución e identificamos pacientes con cáncer colorrectal con muestras de tejido disponibles para su análisis. Utilizamos el Atlas del Genoma del Cáncer para identificar inicialmente las diferencias en la expresión génica entre el cáncer colorrectal de inicio temprano y de inicio tardío. Se realizaron experimentos in vitro en dos líneas celulares de cáncer colorrectal.El estudio se realizó en un centro médico de tercer nivel.Se incluyeron pacientes con inicio temprano (n = 28) e inicio tardío (edad ≥65 años, n = 38) al momento del diagnóstico.El resultado primario fue la expresión diferencial de genes en pacientes con cáncer colorrectal de inicio temprano versus tardío. El resultado secundario fue la mortalidad de los pacientes.Siete genes aumentaron su expresión en pacientes más jóvenes usando el Atlas del Genoma del Cáncer. Solo PEG10 se expresó suficientemente con la reacción en cadena de la polimerasa cuantitativa y tuvo una mayor expresión en nuestro grupo de inicio temprano. El análisis de regresión lineal multivariable identificó la edad como un predictor independiente significativo del aumento de la expresión de PEG10. Los datos de resultados de el Atlas del Genoma del Cáncer sugieren que PEG10 está asociado con una pobre supervivencia general. Los estudios in vitro en líneas celulares HCT-116 y HT-29 mostraron que PEG10 contribuye a la proliferación e invasión celular en el cáncer colorrectal.Las muestras de tejido fueron de portaobjetos embebidos en parafina fijados con formalina. Muchos pacientes no tenían el estado de mutación para su revisión.El PEG10 se expresa diferencialmente en el cáncer colorrectal de inicio temprano y puede contribuir funcionalmente a la proliferación e invasión de células tumorales. El aumento en la expresión de PEG10 se correlaciona con la disminución de la supervivencia general. Consulte Video Resumen en http://links.lww.com/DCR/B343.

Limbic-predominant age-related TDP-43 encephalopathy in Black and White decedents.

OBJECTIVE: The association of limbic-predominant age-related transactive response DNA-binding protein 43 encephalopathy neuropathologic change (LATE-NC) with cognition and dementia was assessed in community-dwelling Black elders, and racial differences in these associations were tested. METHODS: Black (n = 76) and White (n = 152) decedents from 4 longitudinal clinical pathologic studies of aging were matched 2 to 1 by age at death, sex, years of education, dementia status, and follow-up time. LATE-NC detected by immunohistochemistry was dichotomized into none/mild and moderate/severe groups. Distribution and clinical and pathologic characteristics of LATE-NC and its association with cognitive profiles and odds of dementia were determined in Black decedents, and racial differences in these associations were assessed. RESULTS: The overall frequency of LATE-NC in Black and White decedents was similar (40.8% vs 45.4%). Black decedents with moderate/severe LATE-NC were older, had significantly lower global cognition scores, particularly in memory domains, and had higher frequency of Alzheimer disease, hippocampal sclerosis, and cerebral amyloid angiopathy than the LATE-NC none/mild group. LATE-NC in Black decents was independently associated with impaired global cognition, episodic and semantic memory, and visuospatial abilities. There were no racial differences in clinical features or pathologic distribution of LATE-NC except for a significant increase in the mean cytoplasmic inclusions in the entorhinal and mid temporal cortices in White compared to Black decedents. In addition, no racial differences in the cognitive profiles or the odds of dementia were observed in Black vs White decedents. CONCLUSIONS: Consistent with findings in White decedents, LATE-NC in Black decedents is associated with impaired cognition, including memory domains.

Gestational weight gain and rate of late-onset preeclampsia: a retrospective analysis on 57 000 singleton pregnancies in Reunion Island.

OBJECTIVES: To investigate in singleton term pregnancies (≥37 weeks gestation) if applying optimal gestational weight gains (optGWG) on our population could have an effect on the incidence of late-onset preeclampsia (LOP). DESIGN: 18.5-year-observational cohort study (2001-2019). SETTINGS: Centre Hospitalier Universitaire Hospitalier Sud Reunion's maternity (French overseas department, Indian Ocean), the only maternity providing services to take care of all preeclamptic cases in an area with approximately 360 000 inhabitants. MAIN OUTCOMES AND MEASURES: Simulation rates of LOP between women achieving optimal versus inappropriate GWG (insufficient and excessive) in the non-overweight, overweight and class I-III obesity categories. RESULTS: Among 66 373 singleton term pregnancies with a live birth, and 716 LOP (≥37 weeks, LOP37), the GWG could be determined in 87% of cases. In a logistic regression model validating the independent association of optGWG, maternal ages and body mass index (BMI), primiparity, smoking habit, chronic hypertension with term preeclampsia, optGWG reduced the risk of LOP37, aOR 0.74, p=0.004. Primiparity, higher maternal BMI, chronic hypertension and higher maternal age increased the risk of LOP37. The 'protective' effect of optGWG appeared stronger in patients with overweight and obesity in a linear manner: 0.57% versus 1.07% (OR 0.53, p=0.003), overweight; class I obese (30-34.9 kg/m²), 0.70% vs 1.56% (OR 0.44, p=0.01); severe obesity (≥35 kg/m²) 0.86% vs 2.55% (OR 0.33, p=0.06). All patients with overweight/obesity together, OR 0.42, p<0.0001. CONCLUSIONS: Overweight and obesity may not result in a higher risk of developing LOP at term when a optGWG is achieved. The results of this large retrospective population cohort study suggest that targeted and strictly monitored interventions on achieving an optGWG might represent an effective method to reduce the rate of LOP and would have the potential to halve its rate in women with overweight/obesity. These findings suggest a potentially achievable pathway to actively counterbalance the morbid effects of high BMIs, so we solicit adequately powered prospective trials.

Epidemiological characteristics of subsyndromal depression in late life.

OBJECTIVES: Subsyndromal depression is prevalent and associated with poor outcomes in late life, but its epidemiological characteristics have barely been investigated. The aim of this prospective cohort study is to compare the prevalence, incidence and risk factors of subsyndromal depression with those of syndromal depression including major and minor depressive disorders in community-dwelling elderly individuals. METHODS: In a nationwide community-based study of randomly sampled Korean elderly population aged 60 years or older (N = 6640), depression was assessed with standardized diagnostic interviews. At baseline and at 2-year and 4-year follow-ups, the authors diagnosed subsyndromal depression by the operational criteria and syndromal depression by the Diagnostic and Statistical Manual of Mental Disorders (4th ed.) diagnostic criteria. Multivariate logistic regression analyses were conducted to identify the risk factors for incident depression. RESULTS: The age- and gender-adjusted prevalence rate of subsyndromal depression was 9.24% (95% confidence interval = [8.54, 9.93]), which was 2.4-fold higher than that of syndromal depression. The incidence rate of subsyndromal depression was 21.70 per 1000 person-years (95% confidence interval = [19.29, 24.12]), which was fivefold higher than that of syndromal depression. The prevalence to incidence ratio of subsyndromal depression was about half that of syndromal depression. The risk for subsyndromal depression was associated with female gender, low socioeconomic status, poor social support and poor sleep quality, while that of syndromal depression was associated with old age and less exercise. CONCLUSION: Subsyndromal depression should be validated as a clinical diagnostic entity, at least in late life, since it has epidemiological characteristics different from those of syndromal depression.

Late-onset unexplained epilepsy: What are we missing?

With the aging of the US population, the incidence of epilepsy will increase, with 25 to 50% of new cases with no identifiable etiology diagnosed as late-onset unexplained epilepsy (LOUE). In the current targeted review, we discuss the possible role of cerebral small vessel ischemic disease, accumulation of amyloidß and hyperphosphorylated tau, and sleep apnea as potential pathophysiologic mechanisms explaining LOUE. We highlight the impact of these processes on cognition and avenues for diagnosis and treatment.

Late-onset sepsis and mortality among neonates in a Brazilian Intensive Care Unit: a cohort study and survival analysis.

A cohort study was performed from January 2014 to December 2016 in a Brazilian neonatal intensive care unit, including neonates with high risk for infection and death. We estimated bloodstream infection (BSI) incidence and conducted a survival analysis, considering the time to death and to the first episode of BSI as outcomes, comparing very low birth weight (VLBW) neonates with the remaining neonates. An extended Cox model was performed and the hazard ratio (HR) was calculated for different time periods. The study had 1560 neonates included, the incidence and the incidence density of BSI was 22% and 18.6 per 1000 central venous catheter-days, respectively. Considering VLBW neonates as the reference group, the HR for time to death was 4.06 (95% CI 2.75-6.00, P < 0.01) from day 0 to 60 and for time to the first episode of BSI was 1.76 (95% CI 1.31-2.36, P < 0.01) from day 0 to 36. Having the heavier neonates group as reference, the HR for time to the first episode of BSI was 2.94 (95% CI 1.92-4.34, P < 0.01) from day 37 to 90. Late-onset neonatal sepsis prevention measures should consider the differences in risk during time, according to neonates' birth weight.

Interventions to improve adherence to surveillance guidelines in survivors of childhood cancer: a systematic review.

PURPOSE: Many survivors of childhood cancer are at high risk of late effects of their cancer therapy, including cardiac toxicity and subsequent malignant neoplasms (SMN). Current North American guidelines recommend periodic surveillance for these late effects. We conducted a systematic review of the literature to estimate rates of adherence to recommended surveillance and summarize studies evaluating interventions intended to increase adherence. METHODS: We searched MEDLINE, Embase, Web of Science, and the Cumulative Index of Nursing and Allied Health Literature (CINAHL) for articles published between January 2000 and September 2018 that reported adherence to surveillance for cardiac toxicity and SMN (breast and colorectal cancer) and interventions implemented to improve completion of recommended testing. Risk of bias was assessed using relevant Cochrane checklists. Due to heterogeneity and overlapping study populations, we used narrative synthesis to summarize the findings. This review was registered in PROSPERO: CRD42018098878. RESULTS: Thirteen studies met our inclusion criteria for assessing adherence to surveillance, while five assessed interventions to improve rates of surveillance. No studies met criteria for low risk of bias. Completion of recommended surveillance was lowest for colorectal cancer screening (11.5-30.0%) followed by cardiomyopathy (22.3-48.1%) and breast cancer (37.0-56.5%). Factors such as patient-provider communication, engagement with the health care system, and receipt of information were consistently reported to be associated with higher rates of surveillance. Of five randomized controlled trials aimed at improving surveillance, only two significantly increase completion of recommended testing-one for echocardiography and one for mammography. Both involved telephone outreach to encourage and facilitate these tests. CONCLUSION: The majority of childhood cancer survivors at high risk of cardiac toxicity or SMN do not receive evidence-based surveillance. There is paucity of rigorous studies evaluating interventions to increase surveillance in this population. IMPLICATIONS FOR CANCER SURVIVORS: Robust trials are needed to assess whether tailored interventions, designed based on unique characteristics and needs of each survivor population, could improve adherence.

Adjuvant carboplatin therapy in patients with clinical stage 1 testicular seminoma: is long-term morbidity increased?

PURPOSE: Clinical stage (CS) 1 testicular seminoma is cured in almost 100% of cases following either retroperitoneal radiotherapy, carboplatin monotherapy, or surveillance strategies. Little is known about potential long-term effects of carboplatin. We, therefore, examined late sequelae of this drug in seminoma patients. PATIENTS AND METHODS: We retrospectively identified 451 patients with CS1 testicular seminoma treated between 1994 and 2014, of whom 243 underwent carboplatin therapy [median follow-up (F/U) 96 months], 81 received radiotherapy (median F/U 142 months), and 127 underwent surveillance (median F/U 40 months). Satisfaction regarding management, as well as the following events during F/U, were analysed by questionnaire: subsequent malignant neoplasms (SMNs), cardiovascular events, arterial hypertension, peptic ulcer, tinnitus, peripheral neuropathy, hypogonadism, and infertility. The relative frequencies of the events were analysed using descriptive statistics. The frequency of observed SMNs was compared with the expected number. RESULTS: Patients receiving carboplatin tolerated the treatment less well (71.2%) than those under surveillance (81.9%). After carboplatin, 12 SMNs (5.0%) were noted vis-a-vis 5.0 expected. There were three cases of prostatic cancer and 3 melanomas among the SMNs. Half of these SMNs occurred early after treatment. Among the other health events, only reported hypogonadism (13.2%) appeared to be marginally increased in frequency. CONCLUSIONS: This study found a 2.4-fold higher than expected rate of SMN-and a slightly increased rate of hypogonadism-in the long-term period following carboplatin treatment. Although further studies are needed to confirm these preliminary findings, these results are probably informative for clinicians caring for seminoma patients.

Long-term Follow-up of Partial Bleb Excision in Late-onset Bleb-related Complications by a Single Surgeon Using Conjunctival Advancement.

PURPOSE: The purpose of this study was to describe the long-term results of partial bleb excision in late-onset bleb-related complications by a single experienced surgeon using the same surgical technique. PATIENTS AND METHODS: This was a retrospective study of 21 eyes of 11 women and 10 men aged 34 to 87 years (mean 64±12.8 y) who underwent first repair of late-onset bleb leaks with or without numerical hypotony (NH) and dysesthesia. The surgical technique consists of removing nonviable conjunctiva until the functional tissue becomes visible, thus adapting to individual conditions, and later conjunctival advancement. Complete success was defined as maintenance of intraocular pressure control without additional bleb revision, surgery, or glaucoma medications. Qualified success met these criteria, but with glaucoma medications. RESULTS: The mean follow-up was 5.6±4.4 years (1 to 17 years). Sixty-two percent of the cases were considered complete success, and a moderate number of cases (19%) needed glaucoma medication for achieving qualified success at the end of the follow-up period. Interestingly, bleb leak with NH seems to have long-term outcomes, like the other bleb-related complications (in terms of success and failures), with a significant intraocular pressure increase at 1 month after revision that tended to remain within normal values and lead to visual acuity recovery without recurrent NH. CONCLUSIONS: Partial bleb excision seems to be a good technique for different late-onset bleb-related complications. Bleb leak with NH showed a good long-term response, like the other bleb revision indications.

Late-Life Depressive and Anxiety Symptoms Following Rehabilitation Services in Medicare Beneficiaries.

OBJECTIVE: The aim of this study was to determine whether patients who received rehabilitation services had an increased risk of having late-life depressive or anxiety symptoms within the year following termination of services. METHODS: The National Health and Aging Trends Study (NHATS) is a population-based, longitudinal cohort survey of a nationally representative sample of Medicare beneficiaries aged 65years and older. This study involved 5,979 participants from the 2016 NHATS survey. The Patient Health Questionnaire-2 and Generalized Anxiety Disorder 2-item assessed for clinically significant depressive and anxiety symptoms. RESULTS: The prevalence of depressive and anxiety symptoms was higher in older adults who had received rehabilitation services in the year prior and varied by site: no rehabilitation (depressive and anxiety symptoms): 10.4% and 8.8%; nursing home or inpatient rehabilitation: 38.8% and 23.8%; outpatient rehabilitation: 8.6% and 5.5%; in-home rehabilitation: 35.3% and 20.5%; multiple rehabilitation sites: 20.3% and 14.4%; and any rehabilitation site: 18.4% and 11.8%. In multiple logistic regression analyses, nursing home and inpatient and in-home rehabilitation services, respectively, were associated with an increased risk of having subsequent depressive symptoms (odds ratio: 3.51; 95% confidence interval [CI]: 1.85-6.63; OR: 2.15; 95% CI: 1.08-4.30) but not anxiety symptoms. CONCLUSION: Older adults who receive rehabilitation services are at risk of having depressive and anxiety symptoms after these services have terminated. As mental illness is associated with considerable morbidity and may affect rehabilitation outcomes, additional efforts to identify and treat depression and anxiety in these older adults may be warranted.

Clinical and demographic features of chronic progressive external ophthalmoplegia in a large adult-onset cohort.

Chronic progressive external ophthalmoplegia (CPEO) is a common mitochondrial disease. We evaluated the impact of sex and smoking status upon knee extension strength and the phenotypic spectrum of disease in a large cohort of adult-onset CPEO patients (N=116) using retrospective chart analysis. The CPEO patients showed significantly lower knee extension strength as compared to the age- and sex-matched control population (-37%, P<0.05). Smoking also negatively impacted knee extension strength only in women with CPEO (-26%, P<0.05). We conclude that smoking and female sex interact negatively in CPEO patients.

The Incidence of Nonaffective, Nonorganic Psychotic Disorders in Older People: A Population-based Cohort Study of 3 Million People in Sweden.

BACKGROUND: There are limited data on the epidemiology of very late-onset schizophrenia-like psychosis (VLOSLP) and how this relates to potential risk factors including migration, sensory impairment, traumatic life events, and social isolation. METHODS: We followed up a cohort of 3 007 378 people living in Sweden, born 1920-1949, from their 60th birthday (earliest: January 15, 1980) until December 30 2011, emigration, death, or first recorded diagnosis of nonaffective psychosis. We examined VLOSLP incidence by age, sex, region of origin, income, partner or child death, birth period, and sensory impairments. RESULTS: We identified 14 977 cases and an overall incidence of 37.7 per 100 000 person-years at-risk (95% CI = 37.1-38.3), with evidence that rates increased more sharply with age for women (likelihood ratio test: χ2(6) = 31.56, P < .001). After adjustment for confounders, rates of VLOSLP were higher among migrants from Africa (hazard ratio [HR] = 2.0, 95% CI = 1.4-2.7), North America (HR = 1.4, 95% CI = 1.0-1.9, P = .04), Europe (HR = 1.3, 95% CI = 1.2-1.4), Russian-Baltic regions (HR = 1.6, 95% CI = 1.4-1.9), and Finland (HR = 1.6, 95% CI = 1.5-1.7). VLOSLP risk was highest for those in the lowest income quartile (HR = 3.1, 95% CI = 2.9-3.3). Rates were raised in those whose partner died 2 years before cohort exit (HR = 1.1, 95% CI = 1.0-1.3, P = .02) or whose child died in infancy (HR = 1.2, 95% CI = 1.0-1.4, P = .05), those without a partner (HR = 1.9, 95% CI = 1.8-1.9) or children (HR = 2.4, 95% CI = 2.3-2.5), and those whose child had a psychotic disorder (HR = 2.4, 95% CI = 2.2-2.6). INTERPRETATION: We identified a substantial burden of psychosis incidence in old age, with a higher preponderance in women and most migrant groups. Life course exposure to environmental factors including markers of deprivation, isolation, and adversity were associated with VLOSLP risk.

Recurrent, late-onset pleural effusions in elderly patients receiving pacemaker therapy.

Late-onset pacemaker-related pleural effusions (PEs) are rare and are often misdiagnosed with other entities. Our study aimed to detail the clinical features and management of PEs long after pacemaker insertion.We conducted a review of 6 consecutive elderly patients with PEs, who had undergone a new pacemaker insertion from September 2014 to January 2017. Also, the clinical characteristics and therapeutic courses of PEs were summarized.Two cases involved fluids after the first implantations, with pacing durations of 3 and 7 months. Two other cases developed PEs 3 or 4 months after the first replacement, with pacing durations of 6 and 11 years. Another 2 cases developed PEs 3 or 5 months following the second replacement, with total pacing durations of 16 and 18 years, respectively. The average interval was 4.17 months for the 6 cases from the time of the new pacemaker insertion to the occurrence of PEs. During the course, they had to be hospitalized repeatedly for thoracenteses because conventional treatments had only short-term effects. After the pacing settings were adjusted, PEs in all cases disappeared gradually. No patients were readmitted for PEs during the median follow-up period of 13 months.For elderly patients following implantation of a new pacemaker, PEs should be considered due to improper pacing settings, and corresponding adjustments to the device should be made.

Association of vitamin D deficiency with an increased risk of late-onset neonatal sepsis.

BACKGROUND: Vitamin D deficiency in mothers and neonates is being recognised increasingly as a leading cause of many adverse health effects in the newborn infant, including sepsis. METHODS: A prospective observational study was conducted at a tertiary care Paediatric teaching hospital in northern India to assess vitamin D deficiency as a possible risk factor for late-onset sepsis (LOS) in term and late preterm neonates and also to examine the correlation between maternal and infant vitamin D levels during the neonatal period. Late-onset sepsis (LOS) was defined as the development of signs and symptoms of severe sepsis after 72 h of life and a positive sepsis screen. All term and late preterm neonates admitted with LOS between September 2015 and February 2016 who had not been previously admitted for >48 h and had not been prescribed antibiotics or vitamin D were included in the study. Matched controls were recruited from otherwise healthy neonates admitted with physiological hyperbilirubinaemia. Serum 25(OH) vitamin D was assessed in neonates in both groups and their mothers. RESULTS: A total of 421 neonates were admitted to the neonatal intensive care unit during the study period, 120 of whom satisfied the inclusion criteria, and 60 were recruited as cases. Sixty neonates were recruited as controls who were similar in gender, gestational age, age at admission and anthropometry. The study group had significantly lower mean (SD) vitamin D levels [15.37 ng/ml (10.0)] than the control group [21.37 ng/ml (9.53)] (p = 0.001). The odds ratio was 1.7 (95% CI 0.52-5.51) for LOS in vitamin D-deficient neonates. Mothers of septic neonates also had significantly lower mean (SD) vitamin D levels [17.87 (11.89)] than the mothers of non-septic neonates [23.65 ng/ml (9.55)] (p = 0.004). Maternal vitamin D levels strongly correlated to neonatal vitamin D levels in both groups. CONCLUSION: Neonates with vitamin D deficiency are at greater risk of LOS than those with sufficient vitamin D levels.

Late development of hepatocellular carcinoma after viral clearance in patients with chronic hepatitis C: A need for continual surveillance.

OBJECTIVE: Eradication of chronic hepatitis C (CHC) infection decreases the incidence of hepatocellular carcinoma (HCC), but a risk remains. We aimed to investigate HCC development-associated factors in CHC patients with sustained virological response (SVR) after antiviral therapies. METHODS: We compared CHC patients achieving SVR from 1996-2016 who did and did not develop HCC. Their median follow-up period was 8.01 years. RESULTS: Compared with 164 non-HCC SVR patients, 22 who developed HCC were older at SVR (P = 0.032), had a higher incidence of diabetes (P = 0.013) and higher pre-antiviral treatment alpha-fetoprotein (AFP) levels (P = 0.016), more had fibrosis stage 3 and cirrhosis (P = 0.0009) and hepatitis B core antibody (anti-HBc) positivity (P = 0.006). Eight and seven of 22 patients, respectively, developed HCC at 4-10 years and 10 years after SVR. The longest duration from SVR to HCC was 18.7 years. Independent factors associated with HCC development were anti-HBc positivity (hazard ratio [HR] 5.57, P = 0.012), age at SVR (HR 1.08, P = 0.014), higher pre-antiviral treatment AFP levels (HR 1.01, P = 0.01) and Hispanic ethnicity (HR 12.9, P = 0.002). HCC risk was significantly less in genotype 2 patients (HR 0.2, P = 0.02) or in those with higher pre-antiviral treatment albumin levels (HR 0.33, P = 0.04). CONCLUSIONS: The risk for HCC exists in a subset of CHC patients after SVR and may occur up to 18 years after viral clearance. Indefinite HCC surveillance is necessary in SVR patients with other risk factors.