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People with focal epilepsies are known to under-document their seizures, but there is no data on self-documentation in adults with genetic (idiopathic) generalized epilepsy (GGE/IGE). We assessed the accuracy of self-evaluation of typical absences (TA) or myoclonic seizures (MS) in adults with IGE based on home video-EEG telemetry (HVET). Patients' own estimates were compared to the objective count of definite TA and MS, performed visually. We considered definite TA as generalized spike-wave discharges (GSWD) that met any of the following criteria: 1) coinciding with clear behavioural arrest on video, 2) followed after a few seconds by positive indication that an absence occurred, or 3) in the absence of video, consistently coinciding with clear motor arrest, as evidenced by interruption of continuous muscle activity. For each patient, we also classified probable TA as GSWDs that were longer than those corresponding to the shortest definite TA on HVET or based on the most recent sleep-deprived EEG (SDEEG). From the first 300 consecutive adults who had HVET, 24 had IGE with TA and / or MS; 23 were women. Only one patient had newly diagnosed IGE. Erroneous self-assessment of TA and MS was noted in 16/24 patients (66.7%). Seizures were overestimated in nine (37.5%) and underestimated in seven (29.2%). Only one patient (4.2%) documented all her TA and MS without false-positive estimates. Overestimation (but not underestimation) of TA on HVET could be predicted when patients reported daily or multiple weekly TA and a recent SDEEG was either normal or contained only subclinical GSWD (p=0.0095). Under- and over-self-documentation of TA and MS occurred in two thirds of adults with GGE/IGE, with substantial impact on their outpatient management and treatment. Diagnostic HVET is a useful tool for the detection of erroneous self-evaluation in these patients.

Background/Aims: Maternal and fetal outcomes in pregnant patients with Non-alcoholic fatty liver disease (NAFLD) have been largely unexplored. To determine the level of evidence associated with maternal and fetal outcomes in pregnant women with NAFLD.Methods: We conducted a comprehensive literature search. The studies included pregnant patients with a previous, current or subsequent diagnosis of NAFLD. We used a random-effects model using odds ratios (OR) with 95% confidence intervals (CI).Results: Twenty-two studies, with 13,641 female NAFLD patients were reviewed. The results highlight that NAFLD patients had a statistically significant increased likelihood of baseline diabetes mellitus (OR, 6.00; 95% CI, 2.21–16.31; P0.05).Conclusions: This meta-analysis provides pooled evidence that NAFLD is associated with a substantial increase in maternal diabetic and hypertensive complications and multiple adverse fetal outcomes. This data is important for clinicians managing these patients before, during and after pregnancy.

Acral melanomas are a unique subset of melanomas occurring on the palms, soles, and nails. There is poor prognosis with surgery alone and no specific guidelines for the treatment of metastatic acral melanoma. This meta-analysis explored the systemic therapy outcomes for metastatic acral melanoma. Medline, Pubmed, EMBASE, and the grey literature were searched from 2010 to August 2020 for studies specifying the treatment outcome of metastatic acral melanoma. Studies were assessed by two investigators. A random-effects meta-analysis was performed and pooled Kaplan-Meier curves for progression-free survival and overall survival were created. Critical appraisal was performed using the Newcastle-Ottawa Scale. Nineteen nonrandomized studies were included, comprising 646 patients with acral melanomas and 1609 patients with nonacral melanomas treated with systemic therapy including chemotherapy, KIT-targeted drugs, as well as anti-CTLA-4 and anti-PD-1 checkpoint inhibitor therapy. Thirteen studies included Kaplan-Meier curves for progression-free survival or overall survival and 11 studies reported treatment responses. Patients with acral melanomas had worse prognosis than nonacral cutaneous melanoma (acral overall survival: median 15 months, 95% CI, 13.7-16.3 months; nonacral cutaneous: median 24 months, 95% CI, 22.6-25.4 months, P

Given a national push toward bundled payment models, the purpose of this study was to examine the prevalence as well as the effect of smoking on early inpatient complications and cost following elective total knee arthroplasty (TKA) in the United States across multiple years. Using the nationwide inpatient sample, all primary elective TKA admissions were identified from 2012 to 2014. Patients were stratified by smoking status through a secondary diagnosis of “tobacco use disorder.” Patient characteristics as well as prevalence, costs, and incidence of complications were compared. There was a significant increase in the rate of smoking in TKA from 17.9% in 2012 to 19.2% in 2014 (p

BACKGROUND Patients with typical biliary pain, no gallstones on ultrasound and low gallbladder ejection fraction (GBEF) on cholescintigraphy (gallbladder dyskinesia) may be considered for a laparoscopic cholecystectomy. However, some studies have suggested that symptoms alone are an adequate indication for laparoscopic cholecystectomy. The aim was to determine the role of cholescintigraphy in predicting outcomes of cholecystectomy in patients with typical and atypical biliary symptoms and normal biliary ultrasound. METHODS Meta-analysis using Preferred Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines of published literature using several electronic databases. RESULTS Twenty-four articles were selected with a total of 1710 patients. The majority (n = 1633, 94.4%) of patients had typical biliary symptoms. A total of 1047 patients with typical symptoms and a reduced GBEF had a cholecystectomy with 852 (81.4%) having complete resolution of symptoms. A total of 148 with typical symptoms and normal GBEF had a cholecystectomy with 103 (69.5%) having complete resolution, which was significantly less than those with a reduced GBEF (odds ratio 1.65, confidence interval 1.08-2.05, P = 0.01). Forty-five patients with atypical symptoms and a reduced GBEF had a cholecystectomy with 31 (68.9%) having complete resolution of symptoms, which is significantly lower than those with typical symptoms (odds ratio 1.97, confidence interval 0.95-3.90, P = 0.05). CONCLUSION Cholescintigraphy improved the predication of outcome of cholecystectomy in biliary dyskinesia by 10%. However, the presence of typical symptoms does predict an effective response in 70% of patients. Atypical symptoms predict a poorer response.

Background Exploding head syndrome is a rarely reported benign sensory parasomnia that may nonetheless have significant impact on patients’ quality of life and their perceived well-being. To date, the mechanisms underlying attacks, characterised by a painless perception of abrupt, loud noises at transitional sleep-wake or wake-sleep states, are by and large unclear. Methods and results In order to address the current gap in the knowledge of potential underlying pathophysiology, a retrospective case-control study of polysomnographic recordings of patients presenting to a tertiary sleep disorders clinic with exploding head syndrome was conducted. Interictal (non-attack associated) electroencephalographic biomarkers were investigated by performing macrostructural and event-related dynamic spectral analyses of the whole-night EEG. In patients with exploding head syndrome, additional oscillatory activity was recorded during wakefulness and at sleep/wake periods. This activity differed in its frequency, topography and source from the alpha rhythm that it accompanied. Conclusion Based on these preliminary findings, we hypothesise that at times of sleep-wake transition in patients with exploding head syndrome, aberrant attentional processing may lead to amplification and modulation of external sensory stimuli.

Maternal and fetal outcomes in pregnant patients with autoimmune hepatitis (AIH) has been largely unexplored.This meta-analysis aims to determine the level of evidence associated with both maternal and fetal outcomes in patients with AIH.We conducted a comprehensive literature search. The studies included AIH patients who had at least one pregnancy with a previously known or index presentation diagnosis of AIH. We used a random-effects model using odds ratios (OR) with 95% confidence intervals (CI).Fourteen studies with 1452 AIH patients and with a total of 1556 gestations were included. Analysis revealed statistically significant increased likelihood of diabetes mellitus in the AIH group (OR: 5.73, 95% CI: 2.73-12.02;This meta-analysis provides the first pooled evidence that autoimmune hepatitis is associated with a substantial increase in maternal Pre-pregnancy and gestational diabetes mellitus, and that AIH females are more likely to have premature births, small for gestational age (SGA) births, and low birth weight (LBW) babies and a substantial decrease in full term birth compared to normal controls. This data is important for clinicians managing these patients before, during and after pregnancy.

Vagus nerve stimulation (VNS) is a neuromodulatory therapeutic option for drug-resistant epilepsy. In randomised controlled trials, VNS implantation has resulted in over 50% reduction in seizure frequency in 26%–40% of patients within 1 year. Long-term uncontrolled studies suggest better responses to VNS over time; however, the assessment of other potential predictive factors has led to contradictory results. Although initially designed for managing focal seizures, its use has been extended to other forms of drug-resistant epilepsy. In this review, we discuss the evidence supporting the use of VNS, its impact on seizure frequency and quality of life, and common adverse effects of this therapy. We also include practical guidance for the approach to and the management of patients with VNS in situ.

Background Minor cranial sutural synostosis is currently regarded as a rare diagnosis. As clinical awareness grows, a greater number of cases are being documented. This study aims to describe the variants of unicoronal synostosis with regard to major and minor sutural involvement and secondary effects on cranial and orbital morphology. The information is aimed to improve clinical diagnosis and management. Methods A retrospective study was conducted collecting preoperative computed tomographic scans of patients diagnosed with unicoronal synostosis and listed for surgical interventions, identified from a craniofacial database. Within these patients, different synostotic variants were identified based on which suture was affected. Scans of normal pediatric skulls (trauma) were used for a control group. Computed tomographic scans were analyzed for sutural involvement, cranial base deflection, and ipsilateral and contralateral orbital height and width. One-way analysis of variance was used to detect differences between synostotic variants and controls. Results A total of 57 preoperative computed tomographic scans of patients with unicoronal synostosis were reviewed, in addition to 18 computed tomographic scans of normal skulls (control group). Four variants of unicoronal synostosis were identified: frontoparietal, frontosphenoidal, frontoparietal and frontosphenoidal, and frontosphenoidal and frontoparietal. The last two variants differ in their temporal involvement in the direction of sutural synostosis and ultimately cranial and orbital morphology. Three variants have been previously identified, but the fourth is presented for the first time. Conclusions An understanding of the variants of unicoronal synostosis and their temporal relationships is integral for accurate clinical diagnosis and surgical correction. Recommendations for treatment are based on discrete changes in orbital morphology.

Fecal microbiota transplantation (FMT) represents the most effective means of therapeutically manipulating the gastrointestinal microbiome. Originally employed as a treatment of last-resort in patients with life-threatening Clostridioides difficile infection (CDI), FMT gained widespread acceptance during the CDI epidemic, where it achieved resolution rates approaching 100%. Following our newfound appreciation for the role of the gut microbiome in both health and disease and owing to FMT's unique mechanism/s of action, FMT is rapidly advancing as an effective treatment for a number of conditions in which the gastrointestinal microbiome is thought to play a role. We review the role of FMT from its beginnings in CDI to its expansion into inflammatory bowel disease, irritable bowel syndrome, and colon cancer.

Immunoglobulin G autoantibodies to glycine receptors are found in many patients with progressive encephalomyelitis with rigidity and myoclonus (PERM). Crisp et al. show that purified patient IgGs disrupt inhibitory neurotransmission in cultured motoneurons, and provide evidence for direct antagonistic actions on glycine receptors., Chloride-permeable glycine receptors have an important role in fast inhibitory neurotransmission in the spinal cord and brainstem. Human immunoglobulin G (IgG) autoantibodies to glycine receptors are found in a substantial proportion of patients with progressive encephalomyelitis with rigidity and myoclonus, and less frequently in other variants of stiff person syndrome. Demonstrating a pathogenic role of glycine receptor autoantibodies would help justify the use of immunomodulatory therapies and provide insight into the mechanisms involved. Here, purified IgGs from four patients with progressive encephalomyelitis with rigidity and myoclonus or stiff person syndrome, and glycine receptor autoantibodies, were observed to disrupt profoundly glycinergic neurotransmission. In whole-cell patch clamp recordings from cultured rat spinal motor neurons, glycinergic synaptic currents were almost completely abolished following incubation in patient IgGs. Most human autoantibodies targeting other CNS neurotransmitter receptors, such as N-methyl-d-aspartate (NMDA) receptors, affect whole cell currents only after several hours incubation and this effect has been shown to be the result of antibody-mediated crosslinking and internalization of receptors. By contrast, we observed substantial reductions in glycinergic currents with all four patient IgG preparations with 15 min of exposure to patient IgGs. Moreover, monovalent Fab fragments generated from the purified IgG of three of four patients also profoundly reduced glycinergic currents compared with control Fab-IgG. We conclude that human glycine receptor autoantibodies disrupt glycinergic neurotransmission, and also suggest that the pathogenic mechanisms include direct antagonistic actions on glycine receptors.

Exercise-induced pulmonary hemorrhage (EIPH) occurs commonly in horses undergoing strenuous exercise. Reported risk factors include racing in cold temperatures and wearing of bar shoes. In horses with documented moderate to severe EIPH, increasing the interval between races and adopting a negative race pace strategy may reduce the severity of EIPH in subsequent races. EIPH seems to have an impact on performance only when moderate to severe. This occurs in a small number of starters, approximately 6%. EIPH often is erratic in severity from race to race, although across a population it is weakly progressive over increasing race starts.

Background Anxiety disorders during pregnancy are associated with various adverse outcomes. Previous reviews of anxiety disorders during pregnancy have methodological limitations and were conducted without a meta-analysis. The present study is a systematic review and meta-analysis of the published research on the prevalence, onset and course of all anxiety disorders during pregnancy plus obsessive-compulsive disorder (OCD) and posttraumatic stress disorder. Methods A comprehensive literature search was performed on a wide range of databases. A random effects model was used for the meta-analysis. Results Thirty-six studies were included. Prevalence rates of anxiety disorders during pregnancy varied considerably. The pooled prevalence rate of each disorder during pregnancy was 3%, except for specific phobia, where it was 6%. Between 13% and 39% of pregnant OCD women had the onset of OCD during pregnancy, and this occurred mainly in the 2nd trimester. The onset of panic disorder (PD) was more common in the 1st and 2nd trimesters of pregnancy. Limitations Different designs of the included studies, as well as different assessment tools and assessment times during pregnancy and the paucity of studies of the onset and course, preclude definitive conclusions. Conclusions Anxiety disorders are common during pregnancy. Unlike prevalence rates of other anxiety disorders during pregnancy, prevalence rates of PD and OCD during pregnancy were higher than their lifetime prevalence rates in women in the general population. The onset of OCD during pregnancy is not rare and the course of PD and OCD during pregnancy is highly variable. These findings suggest that pregnancy may be a specific risk factor for the occurrence and/or exacerbation of PD and OCD and underscore the importance of their early diagnosis and management.

Acute pancreatitis (AP) is one of the most common general acute surgical presentations. Current recommendations are that idiopathic acute pancreatitis (IAP) should account for no more than 20% of AP cases. Some studies suggest gallbladder microlithiasis is the aetiology in up to 75% of IAP patients. Endoscopic ultrasound (EUS) has been reported to be effective in the detection of microlithiasis and choledocholithiasis as well as pancreatic parenchymal, ductal and ampullary disorders. The aims of this study were to evaluate the usefulness of EUS in establishing aetiology in IAP patients and to assess if there is a role for EUS in the selection criteria for laparoscopic cholecystectomy to treat a potential biliary cause in IAP patients. A systematic review following PRISMA guideline was performed to gather data on patients with IAP undergoing EUS for further investigation. Three databases (MEDLINE, PubMed, and EMBASE) were searched to 28 July 2018. Our systematic review included 28 studies, comprising 1850 patients with an initial diagnosis of IAP prior to having EUS. Diagnosis of a potential aetiology or associated pancreatic pathology was established in 1095 (62%, p

Warm Modified Circumpolar Deep Water (MCDW) from the Southern Ocean drives rapid basal melt of the Totten Ice Shelf on the Sabrina Coast (East Antarctica), affecting the mass balance of the grounded Totten Glacier. Recent observations show that MCDW intrudes onto the continental shelf through a depression at the shelf break. Here we investigate such intrusions by combining (1) new oceanographic and bathymetric observations collected for two consecutive years by profiling floats in the depression south of the shelf break, (2) oceanographic measurements collected by conductivity‐temperature‐depth‐instrumented seals on continental slope, and (3) an ocean model. The depression provides a pathway for persistent inflow of warm (0‐1°C) MCDW to the inner shelf. In austral autumn and early winter MCDW intrusions were up to 0.5°C warmer and were are ~75 m thicker than in spring and summer. The seasonality of the flow on the continental slope explains the seasonality of the intrusions. The MCDW layer on the continental slope is warmer and thicker to the east of the depression than to the west. In autumn and early winter a strong, top‐to‐bottom westward current (Antarctic Slope Current) transports the warmer and thicker MCDW layer along the slope and is diverted poleward at the eastern entrance of the depression. A bottom‐intensified eastward current (Antarctic Slope Undercurrent) develops in other months, allowing cooler and thinner intrusions to enter the depression from the west. Our study illustrates how circulation on the Antarctic slope regulates the ocean heat delivery to the continental shelf and ultimately to the ice shelves.

Over the last three decades, laparoscopic appendicectomy (LA) has become the routine treatment for uncomplicated acute appendicitis. The role of laparoscopic surgery for complicated appendicitis (gangrenous and/or perforated) remains controversial due to concerns of an increased incidence of post-operative intra-abdominal abscesses (IAA) in LA compared to open appendicectomy (OA). The aim of this study was to compare the outcomes of LA versus OA for complicated appendicitis. A systematic literature search following PRISMA guidelines was conducted using MEDLINE, EMBASE, PubMed and Cochrane Database for randomised controlled trials (RCT) and case–control studies (CCS) that compared LA with OA for complicated appendicitis. Data from three RCT and 30 CCS on 6428 patients (OA 3,254, LA 3,174) were analysed. There was no significant difference in the rate of IAA (LA = 6.1% vs. OA = 4.6%; OR = 1.02, 95% CI = 0.71–1.47, p = 0.91). LA for complicated appendicitis has decreased overall post-operative morbidity (LA = 15.5% vs. OA = 22.7%; OR = 0.43, 95% CI: 0.31–0.59, p

Copyright © 2021 O’Regan, Nesbitt, Biabani, Drakatos, Selsick, Leschziner, Steier, Birdseye, Duncan, Higgins, Kumari, Stokes, Young and Rosenzweig. Background: Following the success of Cognitive Behavioral Therapy (CBT) for insomnia, there has been a growing recognition that similar treatment approaches might be equally beneficial for other major sleep disorders, including non-rapid eye movement (NREM) parasomnias. We have developed a novel, group-based, CBT-program for NREM parasomnias (CBT-NREMP), with the primary aim of reducing NREM parasomnia severity with relatively few treatment sessions. Methods: We investigated the effectiveness of CBT-NREMP in 46 retrospectively-identified patients, who completed five outpatient therapy sessions. The outcomes pre- and post- CBT-NREMP treatment on clinical measures of insomnia (Insomnia Severity Index), NREM parasomnias (Paris Arousal Disorders Severity Scale) and anxiety and depression (Hospital Anxiety and Depression Scale), were retrospectively collected and analyzed. In order to investigate the temporal stability of CBT-NREMP, we also assessed a subgroup of 8 patients during the 3 to 6 months follow-up period. Results: CBT-NREMP led to a reduction in clinical measures of NREM parasomnia, insomnia, and anxiety and depression severities [pre- vs. post-CBT-NREMP scores: P (Insomnia Severity Index) = 0.000054; P (Paris Arousal Disorders Severity Scale) = 0.00032; P (Hospital Anxiety and Depression Scale) = 0.037]. Improvements in clinical measures of NREM parasomnia and insomnia severities were similarly recorded for a subgroup of eight patients at follow-up, demonstrating that patients continued to improve post CBT-NREMP. Conclusion: Our findings suggest that group CBT-NREMP intervention is a safe, effective and promising treatment for NREM parasomnia, especially when precipitating and perpetuating factors are behaviorally and psychologically driven. Future randomized controlled trials are now required to robustly confirm these findings. National Institute for Health Research (NIHR) Biomedical Research Centre at South London; Maudsley NHS Foundation Trust and King's College London; National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London

Kleine-Levin syndrome (KLS) is a rare disorder characterized by severe episodic hypersomnia, with cognitive impairment accompanied by apathy or disinhibition. Pathophysiology is unknown, although imaging studies indicate decreased activity in hypothalamic/thalamic areas during episodes. Familial occurrence is increased, and risk is associated with reports of a difficult birth. We conducted a worldwide case.control genome-wide association study in 673 KLS cases collected over 14 y, and ethnically matched 15,341 control individuals. We found a strong genome-wide significant association (rs71947865, Odds Ratio [OR] = 1.48, P = 8.6 × 10-9) within the 3'region of TRANK1 gene locus, previously associated with bipolar disorder and schizophrenia. Strikingly, KLS cases with rs71947865 variant had significantly increased reports of a difficult birth. As perinatal outcomes have dramatically improved over the last 40 y, we further stratified our sample by birth years and found that recent cases had a significantly reduced rs71947865 association. While the rs71947865 association did not replicate in the entire follow-up sample of 171 KLS cases, rs71947865 was significantly associated with KLS in the subset follow-up sample of 59 KLS cases who reported birth difficulties (OR = 1.54, P = 0.01). Genetic liability of KLS as explained by polygenic risk scores was increased (pseudo R2= 0.15; P < 2.0 ∼ 10-22at P = 0.5 threshold) in the follow-up sample. Pathway analysis of genetic associations identified enrichment of circadian regulation pathway genes in KLS cases. Our results suggest links between KLS, circadian regulation, and bipolar disorder, and indicate that the TRANK1 polymorphisms in conjunction with reported birth difficulties may predispose to KLS.

Obstructive sleep apnea is linked to cardiovascular disease, metabolic disorders and dementia. The precise nature of the association between respiratory events in obstructive sleep apnea, cortical or subcortical arousals, and cognitive, autonomic and oxidative stress consequences remains incompletely elucidated. Previous studies have aimed to understand the relationship between obstructive sleep apnea and arousal patterns, as defined by the cyclic alternating pattern, but results have been inconsistent, in part likely due to the presence of associated comorbidities. To better define this relationship, we analysed cyclic alternating patterns in patients with obstructive sleep apnea without any additional comorbidities. We identified 18 adult male, non-obese subjects with obstructive sleep apnea and no other comorbidities or medication history, who underwent whole-night electroencephalography and polysomnography. Cyclic alternating pattern analysis was performed and verified by certified somnologists. Pairwise linear regression analysis demonstrated an inverse relationship between obstructive sleep apnea severity and cyclic alternating pattern subtype A1, and a direct correlation with cyclic alternating pattern subtype A3. Cyclic alternating pattern subtypes A1 prevail in milder obstructive sleep apnea phenotype, whilst cyclic alternating pattern subtypes A2 and A3 overcome among moderate-to-severe obstructive sleep apnea patients. The milder obstructive sleep apnea group also presented higher sleep efficiency, and increased percentages of non-rapid eye movement stage 3 and rapid eye movement sleep, as well as longer cyclic alternating pattern sequences in N3, while severe obstructive sleep apnea patients spent more time in lighter sleep stages. These results imply/suggest a balance between cyclic alternating pattern's adaptive and maladaptive arousal processes in obstructive sleep apnea of differing severities. In milder obstructive sleep apnea (apnea-hypopnea index < 20), sleep continuity may be reinforced by cyclic alternating pattern subtype A1, whereas in more severe obstructive sleep apnea, decompensation of these sleep-stabilizing mechanisms may occur and more intrusive cyclic alternating pattern fluctuations disrupt sleep circuitry.

Background: Despite the strong evidence on immunological effects of shift work and consequent vulnerability for infection, there is a dearth of evidence on the association between shift work and COVID-19 infection. The main objective of this study is to assess whether shift work, particularly night shift, increases the odds of COVID-19 infection. Methods: This study is based on the data from UK Biobank participants who were tested for COVID-19 infection, covering the period from 16th March to 27th July 2020. Participants were categorised as non-shift workers, day shift workers, mixed shift workers and night shift workers. The prospective association between shift work and COVID-19 infection were explored after controlling for age, gender, ethnic minority status, income, education, Townsend deprivation quintile, sleep duration, sleep problems, daytime sleepiness, overall health and obesity. Findings: Among the 12,428 participants ((13.2% positive cases) around 1 in 6 were frontline health workers (16.2%) with 1 in 5 involved in a shift work-based job (21.2%). Within the shift work-based jobs, people who worked mostly night shift were at the highest risk of COVID-19 infection (23.6%, P-value

Objectives This study aimed to evaluate the impact of different periodontal treatment strategies during pregnancy on perinatal outcomes. Study selection This systematic review and meta-analysis of clinical trials was conducted according to PRISMA guidelines to assess the effect of mouthwash in addition to scaling and root planing (SRPM) on pregnancy outcomes, including preterm birth, low birth weight, gestational age, and birth weight. Pooled risk ratios (RR), mean differences (MD), and 95% confidence intervals (CI) were calculated using the random effect model. Results Twenty trials involving 5938 participants, including thirteen trials comparing scaling and root planing (SRP) and seven trials comparing SRPM with control groups. SRPM was associated with reduced risk of preterm birth (RR=0.37; 95%CI=0.16–0.84; p=0.017; I2=93.26%; p Conclusion Using mouthwash in addition to scaling and root planing (SRPM) for the treatment of periodontal disease during pregnancy significantly improves perinatal outcomes.

BACKGROUND Lobular carcinoma in situ (LCIS) is a known risk factor for breast cancer of unclear significance when detected in association with invasive carcinoma. This meta-analysis aims to determine the impact of LCIS on local recurrence risk for individuals with breast cancer treated with breast conservation therapy to help guide appropriate management strategies. METHODS We identified relevant studies from five electronic databases. Studies were deemed suitable for inclusion where they compared patients with invasive breast cancer and concurrent LCIS to those with breast cancer alone, all patients underwent breast conservation therapy (lumpectomy with adjuvant radiation therapy) and local recurrence was evaluated. Recurrence data were pooled by use of a random-effects model. RESULTS From 1488 citations screened by our search, nine studies were deemed suitable for inclusion. These studies comprised 990 cases and 12 870 controls. Median follow-up time was 104 months. There was a significantly increased risk of overall local recurrence of breast cancer for individuals with LCIS in association with breast cancer following breast conservation therapy (pooled odds ratio (pOR) 1.73; 95% confidence interval (CI) 1.10-2.71; P = 0.018). The risk of local recurrence was not significantly increased at 5 years (pOR 1.00; 95% CI 0.49-2.04; P = 0.995) and 10 years (pOR 1.52; 95% CI 0.72-3.23; P = 0.275). CONCLUSION Individuals with LCIS in association with invasive breast cancer have an increased risk of local recurrence following breast conservation therapy. This supports consideration of increased medical surveillance and exploration of further risk reduction strategies for such patients.

For 27 years, national prospective data on selected rare childhood diseases have been collected monthly by the Australian Paediatric Surveillance Unit (APSU) from paediatricians and other clinical specialists who report cases in children aged up to 16 years. We report here the annual results of APSU surveillance in 2020 for ten rare communicable diseases and complications of communicable diseases, namely: acute flaccid paralysis (AFP); congenital cytomegalovirus (CMV) infection; neonatal herpes simplex virus (HSV) infection; perinatal exposure to human immunodeficiency virus (HIV); paediatric HIV infection; severe complications of seasonal influenza; juvenile onset recurrent respiratory papillomatosis (JoRRP); congenital rubella syndrome; congenital varicella syndrome; and neonatal varicella infection. We describe the results for each disease in the context of the total period of study, including demographics, clinical characteristics, treatment and short-term outcomes. Despite challenges presented by the coronavirus disease 2019 (COVID-19) pandemic in 2020, more than 1,400 paediatricians reported regularly to the APSU and an overall monthly reporting rate of > 90% was achieved. The minimum AFP target of 1 case per 100,000 children aged less than 15 years was achieved and there were few cases of vaccine-preventable diseases (JoRRP, rubella, varicella). However, high cases of congenital CMV, neonatal HSV and perinatal exposure to HIV persist. There were no severe complications of seasonal influenza reported for the first time in 13 years. This is consistent with other surveillance data reporting a decline of influenza and other communicable diseases in 2020, and likely reflects the wider effects of public health measures to reduce transmission of SARS-CoV-2 in the Australian community.

Summary Background Clinical services for Barrett’s esophagus have been rising worldwide including Australia, but little is known of the long-term outcomes of such patients. Retrospective studies using data at baseline are prone to both selection and misclassification bias. We investigated the clinical characteristics and outcomes of Barrett’s esophagus patients in a prospective cohort. Methods We recruited patients diagnosed with Barrett’s esophagus in tertiary settings across Australia between 2008 and 2016. We compared baseline and follow-up epidemiological and clinical data between Barrett’s patients with and without dysplasia. We calculated age-adjusted incidence rates and estimated minimally and fully adjusted hazard ratios (HR) to identify those clinical factors related to disease progression. Results The cohort comprised 268 patients with Barrett’s esophagus (median follow-up 5 years). At recruitment, 224 (84%) had no dysplasia, 44 (16%) had low-grade or indefinite dysplasia (LGD/IND). The age-adjusted incidence of esophageal adenocarcinoma (EAC) was 0.5% per year in LGD/IND compared with 0.1% per year in those with no dysplasia. Risk of progression to high-grade dysplasia/EAC was associated with prior LGD/IND (fully adjusted HR 6.55, 95% confidence interval [CI] 1.96–21.8) but not long-segment disease (HR 1.03, 95%CI 0.29–3.58). Conclusions These prospective data suggest presence of dysplasia is a stronger predictor of progression to cancer than segment length in patients with Barrett’s esophagus.

Study objectives To explore sleep trajectories and identify the risk factors and mediators of poor sleep in middle-aged adults. Methods Group-based multi-trajectory modelling was applied to the three waves of sleep data the from UK Biobank cohort to identify latent trajectories of sleep and group characteristics. Self-reported sleep duration, sleep problems (based on insomnia symptoms, snoring and trouble waking up) and daytime sleepiness (based on daytime tiredness and sleepiness) were included in the trajectory analyses. Multinomial logistic regression and mediation analysis were used to identify the main factors associated with poor sleep. Results Analysis of sleep data from 41,094 participants (51.9% females) with a median age of 57 years (interquartile range 50–62 years) identified three distinct trajectories of sleep: healthy sleepers (40.8%); borderline poor sleepers (31.6%); and poor sleepers (27.6%). Socio-economic disadvantage, ethnic minority background, shift work, unhealthy lifestyle, poor health, depressive symptoms and obesity were the main risk factors associated with poor sleep. Around a third of the total effect of socio-economic deprivation on poor sleep was mediated through depressive symptoms. Conclusions The distinct groups with differential risk for developing sleep issues and stable sleep trajectories highlight the non-transient nature of sleep issues. Early management of depressive symptoms can help in reducing the future burden of poor sleep. Due to the increased risk of poor sleep, people from socio-economically deprived groups, particularly females from ethnic minorities, should be the highest priority for interventions aiming to improve population sleep health.

Sleep complaints are so common in PoTS as to almost constitute part and parcel of the syndrome. However, while unrefreshing sleep is exceedingly frequently described, there are multiple factors that may underlie sleep disturbance. These include other symptoms of PoTS that can impact on sleep quality as well as primary sleep pathologies such as restless legs syndrome. This chapter discusses the range of sleep complaints seen, the importance of differentiating fatigue and sleepiness, and appropriate treatment options.

Background Helicobacter pylori infection has had a major impact on the global health of billions of people. Triple therapy was extensively used in Australia by 1986 for H pylori eradication after its discovery in 1984 and was critical in reducing the morbidity and mortality associated with this infection. Aims This study analyzed hospital admission, mortality, and therapeutic data to determine the economic and clinical impact that antibiotic triple therapy had on peptic ulcer disease (PUD) in Australia. Methods An analysis of indirect and direct cost-savings in Australia between 1990 and 2015 associated with triple therapy and the impact on PUD mortality and hospital admissions. Results The direct and indirect impacts of PUD treated by triple therapy between 1990 and 2015 suggest that triple therapy is likely to have prevented 18 665 deaths, and saved 258 887 life years and 33 776 productive life years. The total savings, over the 26-year period, including direct and indirect costs, are calculated to be $10.03 billion, equating to an average annual saving of $393.419 million. Conclusions This study highlights the enormous benefits to Australia's health care of the discovery of triple therapy, a relatively low-cost antibiotic regimen which brought considerable savings via the reduction in morbidity (hospital admissions) and mortality related to PUD. It is likely that benefits of similar scale occurred internationally.

BackgroundThe impact of CD4+ T-cell count and highly active antiretroviral therapy (HAART) on the rate of surgical site infection (SSI) in patients with human immunodeficiency virus (HIV) undergoing total hip arthroplasty is still unclear. The goals of this study were to assess the rate of perioperative infection at a large tertiary care referral center and to identify risk factors in HIV+ patients undergoing total hip arthroplasty (THA).MethodsThis study was a prospective, observational study at a single medical center from 2000–2017. Patients who were HIV+ and underwent THA were followed from the preoperative assessment period, through surgery and for a 2-year follow-up period.ResultsSixteen of 144 HIV+ patients (11%) undergoing THA developed perioperative surgical site infections. Fourteen patients (10%) required revision THA within a range of 12 to 97 days after the initial surgery. The patients’ mean age was 49.6 ± 4.5 years, and the most common diagnosis prompting THA was osteonecrosis (96%). Patients who developed SSI had a lower waist-hip ratio (0.86 vs. 0.93,p= 0.047), lower high density lipoprotein cholesterol (45.8 vs. 52.5,p= 0.015) and were more likely to have post-traumatic arthritis (12.5% vs. 0%,p= 0.008). Logistic regression analysis demonstrated that current alcohol use and higher waist-hip ratio were significant protectors against infection (p< 0.05). No other demographic, medical, immunologic parameters, or specific HAART regimens were associated with perioperative infection.ConclusionsImmunologic status as measured by CD4+ cell count, HIV viral load, and medical therapy do not appear to influence the development of SSI in HIV+ patients undergoing THA. Metabolic factors and post-traumatic arthritis may influence the increased rate of infection in HIV+ patients following THA.

Unpleasant dreamlike mentation can occur during non-rapid eye movement parasomnias, leading to associated panic attacks. The mentations are rarely remembered and are likely underreported. However, they may lead to significant personal distress and, if not addressed, may contribute to poorer clinical outcomes. Cotard le délire de negation are very rare nihilistic delusions, historically described with psychotic disorders. Their association with a variety of neurologic disorders, including migraine and cluster-headache, has also been reported. Here we present three cases of Cotard parasomnia during which distinct states of consciousness defined by nihilistic ideation occurred. Patients described believing they are dead or dying, while unable to perceive or experience their bodies in whole, or in part, as their own. A source analysis of the electroencephalographic fingerprint of these mentations suggests right-hemispheric hypoactivity subsequent to confusional arousals. Mechanistically, an aberrant activation of two major intrinsic brain networks of wakefulness, the salience network and the default mode network, is argued. CITATION: Gnoni V, Higgins S, Nesbitt AD, et al. Cotard parasomnia: le délire de negation that occur during the sleep-wake dissociation? J Clin Sleep Med. 2020;16(6):971–976.

Danielle Wasserman,1,2,* Dorothea Bindman,1,* Alexander D Nesbitt,1– 3 Diana Cash,4 Milan Milosevic,5 Paul T Francis,6 K Ray Chaudhuri,7 Guy D Leschziner,1,2 Luigi Ferini-Strambi,8 Clive Ballard,9 Amy Eccles,10 Ivana Rosenzweig1,2 1Sleep and Brain Plasticity Centre, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, London, UK; 2Sleep Disorders Centre, Guy’s and St Thomas’ NHS Foundation Trust, London, UK; 3Headache Group, Department of Clinical Neurosciences, King’s College Hospital NHS Foundation Trust, London, UK; 4BRAIN, Department of Neuroimaging, King’s College London, London, UK; 5School of Public Health “Andrija Stampar“, University of Zagreb School of Medicine, Zagreb, Croatia; 6Wolfson Centre for Age-Related Diseases, King’s College London, London, UK; 7Movement Disorders Unit, King’s College Hospital, Department of Clinical and Basic Neurosciences, Institute of Psychiatry, Psychology & Neuroscience, Parkinson Foundation Centre of Excellence, King’s College London, London, UK; 8Sleep Disorders Center, Department of Clinical Neurosciences, Università Vita-Salute San Raffaele, Milan, Italy; 9Medical School, University of Exeter, Exeter, UK; 10Department of Nuclear Medicine, Guy’s and St. Thomas’ NHS Foundation Trust, London, UK*These authors contributed equally to this workCorrespondence: Ivana RosenzweigSleep and Brain Plasticity Centre, Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience (IoPPN), King’s College London, Box 089, De Crespigny Park, London SE5 8AF, UKEmail ivana.1.rosenzweig@kcl.ac.ukIntroduction: Idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) is increasingly recognised as an important precursor disease state of alpha-synucleinopathies. This parasomnia is characterized by a history of recurrent nocturnal dream enactment behaviour, loss of skeletal muscle atonia, and increased phasic muscle activity during REM sleep. Neuroimaging studies of striatal dopamine transporter uptake tracer signaling suggest increasing dopaminergic deficit across the continuum of the alpha-synucleinopathies, with early sleep dysfunction suggestive of early caudate dysfunction. Henceforth, we set out to investigate the relationship between early sleep changes and the striatal dopaminergic availability in iRBD.Methods: Twelve patients with iRBD, who had undergone a video polysomnography and a neuroimaging assessment of striatal dopamine transporter (DaT) uptake tracer signaling, and 22 matched controls who had similarly undergone a video polysomnography were retrospectively identified. Data were statistically analyzed to identify altered sleep parameters and correlate them with striatal dopamine transporter uptake tracer signaling.Results: The iRBD patients exhibited an increased number of periodic limb movements during sleep (P=0.001), compared to 22 age-matched healthy subjects. In addition, several significant links were found between regional DaT-uptakes and sleep architecture. Correlational analyses suggested a strong positive association between sleep fragmentation and dopamine deficiency in left caudate (r=− 0.630, P=0.028), whilst an increased uptake in the whole striatum was strongly linked to the sleep efficiency, and to a lesser degree to the length of sleep duration.Discussion: To the best of our knowledge, this is the first demonstration of a close relationship between dopaminergic availability in striatum and the quality of sleep in iRBD. Taken together, our exploratory findings suggest that subtle but functionally significant striatal changes in early stages of iRBD may contribute to the further shaping of sleep architecture.Keywords: isolated rapid eye movement behaviour disorder, polysomnography, sleep architecture, striatum, striatal dopamine transporter uptake tracer signalling imaging, DaTSCAN

Esophageal cancer (EC) is a highly prevalent malignancy in China. According to the data released by National Cancer Registry Center of China in 2015, the prevalence of EC was 21.17/100,000 in China in 2012, ranking fifth among all malignancies; the mortality rate was 15.58/100,000, ranking fourth. It is expected that there will be 477,900 new EC cases nationwide in 2015, whereas 375,000 people will die from EC (1,2). Worldwide, EC is the 8 th most common malignancy, with 416,000 new cases in 2012 (3). At present, EC treatment is based on multidisciplinary treatment, but surgery remains the most effective therapy in optimizing long-term prognosis in patients without metastatic disease. The ideal surgical approach is a matter of debate.

Background Non-REM parasomnias are not uncommon conditions in the general population. Current treatment options are based on small case series and reports. In this study, we aimed to present the clinical experience from a large cohort of patients. Patients Five hundred and twelve patients with Non-REM parasomnia or parasomnia overlap disorder (POD), who had undergone a video polysomnography and were exposed to treatment, were retrospectively identified. Treatment outcome was assessed based on patients’ reports, and treatment approach on a locally accepted hierarchy of interventions. Results Forty percent of patients were diagnosed with sleepwalking, 23.8% with mixed-phenotype and 10% with POD. Ultimately, 97.2% reported adequate control of their symptoms. Moreover, 60.1% were treated with pharmacotherapy and 32.0% without, consistent across all phenotypes (p = 0.09). Benzodiazepines were the most common drugs prescribed (47.1%, p, Highlights • This study supports a standardised treatment approach in NREM-parasomnias. • Pharmacotherapy alone effectively treated two thirds of the patients. • One third of the patients were effectively treated without pharmacotherapy. • Treatment of sleep apnea and periodic limb movements in sleep is recommended. • Melatonin and psychological therapies are promising treatment options.

Summary Objective Professional singers are more likely to develop laryngeal pathologies and symptoms associated with misuse and overuse of the voice. However, different studies have shown conflicting evidence. We aim to perform a systematic review and quantitative meta-analysis to determine the prevalence and risk of laryngeal pathologies and symptoms among professional singers. Methods Four electronic databases (MEDLINE, PubMed, EMBASE, and CINAHL) were searched, with no language restrictions. From 3368 potential studies, a total of 21 studies met our inclusion criteria. A systematic review of the literature was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. All cohort, case-control, or cross-sectional studies that reported the risk of laryngeal pathologies in singers were included. Data were pooled by a random effects model and the pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results There was a positive relationship between singing and laryngeal pathologies. There was an increased risk of hoarseness (OR: 2.00, 95% CI: 1.61–2.49), gastroesophageal reflux disease (GERD) (OR: 1.45, 95% CI: 1.19–1.77), Reinke edema (OR: 2.15, 95% CI: 1.08–4.30), and polyps (OR: 2.10, 95% CI: 1.06–4.14) in professional singers. Conclusion Professional singers are at an increased risk of laryngeal pathologies and symptoms associated with vocal misuse and overuse, particularly hoarseness, GERD, edema, and polyps.

Background: Serum thyroglobulin (Tg) is used in the follow-up of patients with differentiated thyroid cancers (DTC), but the presence of antithyroglobulin antibodies (TgAbs) makes Tg measurements u...

Intra-abdominal abscess (IAA) post-appendicectomy occurs in 1.4-4.4% of cases. Non-operative management of small (4 cm) post-appendicectomy IAA in children is well established, but minimal evidence exists in adults. Percutaneous catheter drainage is considered standard treatment for IAA, yet outcome data for post-appendicectomy IAA are sparse. The aims of this study were to assess the effectiveness of non-operative management of small (4 cm diameter) IAA and the outcomes of percutaneous drainage for larger (4 cm) IAA post-appendicectomy.A retrospective case note review of a series of patients with a post-appendicectomy IAA between 2006 and 2017 was conducted. IAAs were treated selectively; small (4 cm) IAAs were managed non-operatively and larger IAAs were managed with percutaneous drainage .A total of 4901 patients had an appendicectomy. Forty-two (0.9%) developed a post-operative IAA. Sixteen (38%) had a percutaneous drainage and 26 (62%) had non-operative management. The percutaneous drainage group had a higher proportion of complicated appendicitis (75%) compared to the non-operative group (42%, P = 0.04). The percutaneous drainage group had a significantly higher leucocytosis (P = 0.01) and C-reactive protein (P = 0.02). All patients managed non-operatively resolved without the need for invasive procedures. In the percutaneous drainage group, six had aspiration alone, nine had a percutaneous drain and one was abandoned. Three required repeat percutaneous drainage and four (25%) required operative drainage. Seven patients (34%) of the percutaneous drainage group had grade II or III complications.This case series study provides support that small (4 cm) IAA post-appendicectomy can be safely and effectively managed non-operatively.

Intra-abdominal abscess (IAA) complicates 2–3% of patients having an appendicectomy. The usual management is prolonged antibiotics and drainage of the IAA. From 2006, our unit chose to use early re-laparoscopy and washout in patients with persistent sepsis following appendicectomy. The aims of this study were to assess the outcomes of early laparoscopic washout in patients with features of persistent intra-abdominal sepsis and compare those with percutaneous drainage and open drainage of post-appendicectomy IAA. A retrospective case note review was performed for all patients having a laparoscopic washout, percutaneous drainage or open drainage following appendicectomy between January 2006 and December 2017. During the period, 4901 appendicectomies occurred. Forty-one (0.8%) patients had a laparoscopic washout, 16 (0.3%) had percutaneous drainage, and 6 (0.1%) had an open drainage. The demographics, ASA grade and pathology at initial appendicectomy were similar. The mean time after appendicectomy was significantly shorter for laparoscopic washout (4.1 days vs. 10.1 and 9.0 days, p =

Small bowel obstruction (SBO) due to adhesions is a common acute surgical presentation. Laparoscopic adhesiolysis is being performed more frequently. However, the clear benefits of laparoscopic adhesiolysis (LA) compared with traditional open adhesiolysis (OA) remain uncertain. The aim of this study was to compare the outcomes of LA versus OA for SBO due to adhesions. A systemic literature review was conducted using PRISMA guidelines. A search was conducted using MEDLINE, EMBASE, PubMed and Cochrane Databases of all randomised controlled trials (RCT) and case-controlled studies (CCS) that compared LA with OA for SBO. Data were extracted using a standardised form and subsequently analysed. There were no RCT. Data from 18 CCS on 38,927 patients (LA = 5,729 and OA = 33,389) were analysed. A meta-analysis showed that LA for SBO has decreased overall mortality (LA = 1.6% vs. OA = 4.9%, p

One of the most common acute conditions managed by general surgeons is acute appendicitis. Laparoscopic appendicectomy (LA) is the surgical technique used by many surgeons. The aims of this study were to define our unit’s negative appendicectomy rate and compare the outcomes associated with removal of a normal appendix with those for acute appendicitis in patients having LA. A single-centre retrospective case note review of patients undergoing LA for suspected acute appendicitis was performed. Patients were divided into positive and negative appendicectomy groups based on histology results. The positive group was subdivided into uncomplicated and complicated (perforated and/or gangrenous) appendicitis. Outcomes were compared between groups. There were 1413 patients who met inclusion criteria, 904 in the positive group and 509 in the negative group, an overall negative appendicectomy rate of 36.0%. Morbidity rates (6.3% vs. 6.9%; P = 0.48) and types of morbidity were the same for negative appendicectomy and uncomplicated appendicitis. There was no significant difference in complication severity (all P > 0.17) or length of stay (2.3 vs. 2.6 days; P = 0.06) between negative appendicectomy and uncomplicated appendicitis groups. Patients with complicated appendicitis had a significantly higher morbidity rate compared to negative and uncomplicated groups (20.1% vs. 6.3% and 20.1% vs. 6.9%; both P

Objectives Visible hematuria (VH) is a common urological complaint. A history of initial or terminal VH in men is indicative of a lower urinary tract (LUT) source. A careful clinical history could limit unnecessary extensive upper tract imaging in this group of patients with VH. We conducted a single-center prospective study to examine the usefulness of investigating the upper tract in patients with a history of VH likely from a LUT source (initial and/or terminal VH) with specific reference to the incidence of demonstrable significant upper tract abnormalities. Methods We conducted a single-center prospective study of consecutive male patients presenting with VH over eight months. All patients underwent standard investigations including physical examination, flexible cystoscopy (FC), and radiological imaging (ultrasound scan (USS) and/or computed tomography urogram (CTU)). Those with a clear history of initial or terminal VH were identified for further scrutiny with regards to detectable upper tracts abnormalities. Results In total, 57 patients (aged 23-95 years) with initial or terminal VH were identified. Of these, 56 had FC and nine patients were subsequently diagnosed with a LUT malignancy. With regards to upper urinary tract (UUT), 35 patients (61.4%) had an USS, 46 (80.7%) underwent a CTU, and 25 (43.9%) patients had both. In this group, no UUT malignancy was identified on upper tract imaging. Conclusions Initial or terminal VH patients may not need extensive upper tract imaging. FC is recommended, but a non-invasive USS can be a safe initial investigation for the UUT, with a CTU subsequently considered in those with abnormalities on USS and those with ongoing bleeding. Further combined multicenter analysis will help corroborate these findings and could have several beneficial outcomes including a reduction in investigations cost, patient inconvenience, and ionizing radiation.

Satellite-derived Antarctic sea ice extent has displayed a slight upward since 1979, but with strong temporal and regional variability—the drivers of which are poorly understood. Here, we conduct numerical experiments with a circum-Antarctic ocean–sea ice–ice shelf model driven by realistic atmospheric surface boundary conditions to examine the factors responsible for the temporal and spatial patterns in observed Antarctic sea ice variability. The model successfully reproduces observed seasonal and interannual variability in total sea ice extent and the temporal/spatial patterns of sea ice concentration and seasonality (days of advance and retreat and actual ice days) for 1979–2014. Sensitivity experiments are performed, in which the interannual variability in wind stress or thermodynamic surface forcing is ignored, to delineate their contributions to Antarctic sea ice fields. The results demonstrate that: (1) thermodynamic forcing plays a key role in driving interannual variability in sea ice extent and seasonality in most Antarctic sectors; (2) only in the Ross Sea the wind stress does become the main driver of sea ice extent variability; (3) thermodynamic forcing largely regulates interannual variability in the timing of sea ice advance, while wind stress largely controls the timing of the sea ice retreat; and (4) although both wind stress and thermodynamic forcing contribute to variability in total sea ice volume, the wind stress plays a dominant role in regulating sea ice volume variability in the near-coastal zone.

Benzodiazepine use is highly prevalent in elderly and late middle-aged populations and may be associated with an increased risk of dementia. Observational studies have suggested that benzodiazepine use may increase the risk of dementia, however there have been significant concerns regarding protopathic bias in these studies, precluding conclusive findings. The aim of our study was to investigate the risk of dementia associated with the use of benzodiazepines in elderly patients, after controlling for protopathic bias. We identified observational studies with more than 50 cases, adequate assessment of benzodiazepine exposure, and reliable dementia diagnosis ascertainment, from the MEDLINE, PubMed, EMBASE, CINAHL, LILACS and CENTRAL electronic databases through to 5 June 2018, with no language limits. The association of any current or former use of short- or long-acting benzodiazepines with incident dementia was analysed. A subgroup analysis was performed by the introduction of lag time to assess the effect of protopathic bias. We also performed analyses considering the effect of higher benzodiazepine cumulative doses and adjustment for psychiatric covariates. Study quality was investigated using the Newcastle–Ottawa Scale. We identified 15 studies reported in 14 articles, involving 159,090 cases. Ever use of benzodiazepines was associated with a significantly increased risk of dementia [odds ratio (OR) 1.39, 95% confidence interval (CI) 1.21–1.59]. Those studies that implemented the longest lag times of ≥ 5 years, and hence most likely to overcome protopathic bias, found a risk estimate that was marginally attenuated, but still significant (OR 1.30, 95% CI 1.14–1.48). Long-acting benzodiazepines were associated with a marginally higher magnitude risk (OR 1.21, 95% CI 0.99–1.49) than short-acting benzodiazepines (OR 1.13, 95% CI 1.02–1.26), although the former failed to reach statistical significance (p = 0.059). Our findings indicate that the association between benzodiazepine use and dementia incidence is not purely an artefact due to protopathic bias. Reduction of inappropriate benzodiazepine prescription is likely to attenuate dementia risk.

Case report: A 7-year-old Clydesdale gelding was referred with a history of progressive lethargy and ventral oedema. The horse developed diarrhoea after treatment with antibiotics by the referring veterinarian. History, clinical signs, imaging and laboratory findings were consistent with hypertrophic cardiomyopathy complicated by antibiotic-associated colitis. Progression of clinical signs prompted euthanasia and the antemortem diagnosis of hypertrophic cardiomyopathy was confirmed at postmortem examination. Conclusion: Primary HCM is reported as rare in horses, but specific descriptions are lacking. The history, clinical, laboratory and postmortem findings in this case supported a diagnosis of HCM, complicated by antibiotic-associated colitis.

Background Duchenne Muscular Dystrophy is a paediatric disorder resulting from a defective dystrophin gene. It causes progressive loss of muscle fibres, muscle weakness, and eventually loss of ambulation during adolescence, with death due to respiratory or cardiovascular complications soon afterwards. The drug eteplirsen has received support from medical experts and parents of affected children, but the FDA has delayed their decision for approval of this drug. Objective This study analysed the results of previous studies to assess the safety and efficacy of the eteplirsen, and is the first pooled-analysis of its kind. Methods A literature search of electronic databases was performed. Only human studies using eteplirsen were eligible. Results A total of four relevant clinical studies were identified. A pooled-analysis was performed using data relating to percentage dystrophin-positive fibres obtained from muscle biopsy, and the six-minute walk test (6 MWT). The average increase in percentage dystrophin-positive fibres after treatment with eteplirsen was 24.23% (range −4 to 78; SD 24.44%). The average rate of decline in distance walked was 65 metres (range −335 to 83; SD 100.08 m). Conclusions Whether or not this increase in percentage dystrophin-positive fibres and distance walked is clinically significant is unclear, and there is therefore a need for more clinical trials.

The central hypersomnias encompass a range of conditions causing persisting or intermittent excessive daytime sleepiness (EDS). These conditions therefore present not infrequently in general clinical sleep practice, and remain in the differential for patients presenting with sleepiness. Our understanding of the pathophysiology, diagnosis and management of these conditions has progressed significantly over recent years, and in this article we review this group of disorders, focussing in particular on recent changes in classification and diagnosis, pathophysiological advances, and novel treatment options.

Long term health related quality of life (HRQL) and nutritional outcome of patients following esophagectomy for cancer has become increasingly significant as the 5-year survival rate in this patient group is increasing. This meta-analysis aims to investigate the HRQOL, nutritional impact symptoms and nutritional outcomes of patients following an esophagectomy at greater than 12 months after surgery. In studies reporting on HRQL as an outcome, global QOL score at 6-month compare to greater than 12-month showed no statistically significant difference (65.92 vs. 75.78, p = 0.07). Forty-one percent of patients reported a greater than 10% weight loss at six-month follow-up (95% CI: 20-65%; I2 = 94.27, p0.001), and at the greater than 12-month follow-up, 33% of patients had the greater than 10% weight loss (95% CI: 15-57%; I2 = 96.18, p0.001). At the 12-month or longer post esophagectomy, just over half the patients reported dysphagia (51%, 95% CI: 25-76%; I2 = 95.70, p0.001), nausea was reported by 11% (95% CI: 7-19%; I2 = 59.31, p = 0.09), dumping syndrome reported by 60% (95% CI: 43-76%; I2 = 96.92, p0.001). Symptoms such as dysphagia, diarrhea, reflux, dumping syndrome, and nausea were found to persist following esophagectomy. There were insufficient robust research investigating how these symptoms impact on the adequacy of dietary intake and micronutrient status.

Primary peritonitis in horses attributable to Actinobacillus equuli has been reported in Australia, New Zealand and North America. Published reports describe a rapid response to treatment with appropriate antimicrobial and supportive treatment and an excellent prognosis for survival. To our knowledge, this is the first reported case of Actinobacillus capsulatus in the horse. The case was complicated by the development of an idiopathic chylous abdominal effusion. The report highlights the importance of molecular methods in the correct identification of bacterial species. Prognosis for horses diagnosed with Actinobacillus peritonitis may be guarded given the atypical response to appropriate antimicrobial treatment in this case.

SummaryBackground Non-alcoholic fatty liver disease (NAFLD) is a significant disease burden in obesity. Liver fibrosis is an important prognostic factor in NAFLD, and detection is vital. The pathophysiological changes of obesity can alter the accuracy of non-invasive NAFLD tests. We aimed to review current evidence for common non-invasive tests for NAFLD-related fibrosis in obesity. Methods We systematically searched for studies assessing the diagnostic accuracy of 11 biomarker panels and elastography techniques for NAFLD-related fibrosis in obesity. Meta-analyses were performed where possible. Results Thirty-eight studies were identified assessing the selected tests in obese populations. Simple biomarker panels (e.g. NAFLD fibrosis score) were the most validated. Evidence showed better accuracy of complex biomarker panels (NAFLD fibrosis score: summary receiver operator characteristic [SROC] 0.795–0.813 vs. enhanced liver fibrosis: SROC 0.962); however, these were poorly validated in obesity. Elastography techniques were better studied and had high diagnostic accuracy (transient elastography: SROC 0.859; magnetic resonance elastography: SROC 0.965) but were limited by BMI-dependent failure. Limited evidence was found to validate the accuracy of any test in exclusively obese populations. Conclusion In obese subjects, complex biomarker panels and elastography have been reasonable to good accuracy for NAFLD-related fibrosis; however, these methods have not been well validated. Further study in this high-risk population is needed.

Recent NICE guidelines recommend open surgical approaches for the treatment of primary unilateral inguinal hernias. However, many surgeons perform a laparoscopic approach based on the advantages of less post-operative pain and faster recovery. Our aim was to examine current evidence comparing transabdominal pre-peritoneal (TAPP) laparoscopic repair and open surgical repair for primary inguinal hernias. A systematic search of six electronic databases was conducted for randomised controlled trials (RCTs) comparing TAPP and open repair for primary unilateral inguinal hernia. A random-effects model was used to combine the data. A total of 13 RCTs were identified, with 1310 patients receiving TAPP repair and 1331 patients receiving open repair. There was no significant difference between the two groups for rates of haematoma (RR 0.92; 95% CI 0.49–1.71; P = 0.78), seroma (RR 1.90; 95% CI 0.87–4.14; P = 0.10), urinary retention (RR 0.99; 95% CI 0.36–2.76; P = 0.99), infection (RR 0.61; 95% CI 0.29–1.28; P = 0.19), and hernia recurrence (RR 0.67; 95% CI 0.42–1.07; P = 0.10). TAPP repair had a significantly lower rate of paraesthesia (RR 0.20; 95% CI 0.08–0.50; P = 0.0005), shorter bed stay (2.4 ± 1.4 vs 3.1 ± 1.6 days, P = 0.0006), and shorter return to normal activities (9.5 ± 7.9 vs 17.3 ± 8.4 days, P

Background International post-licensure studies on rotavirus vaccines have identified an increased risk of intussusception in infants after administration. The first developed rotavirus vaccine (Rotashield (RRV-TV)) was suspended post-licensure in 1999 after an association with intussusception was found. The currently available second-generation rotavirus vaccines (Rotateq (RV5) and Rotarix (RV1)), are recommended as a routine vaccine by the World Health Organisation (WHO). Post-licensure studies of these vaccines have shown a smaller but temporal increased risk for developing intussusception. Methods A meta-analysis was performed to summarise available evidence and to give an overall risk of developing intussusception from case-control and cohort studies for all rotavirus vaccines that have been manufactured up to date. A search was conducted on MEDLINE, PubMed, EMBASE and Google Scholar up to May 2017. Eligible studies assessed the relationship between the rotavirus vaccine administration and subsequent development of intussusception both after receiving the first dose and after receiving all doses combined. Data was extracted on study characteristics, methods and outcomes. Results were pooled using the random-effect model. Results Six cohort studies involving 4506265 total first doses and five case-control studies involving a total sample of 9643 children were included in this analysis. The cohort data revealed that there was an associated increased risk of intussusception after the first 7 days post first dose of the vaccine (RR:3.71, 95% CI:1.08–12.69) and after receiving all doses of the rotavirus vaccine (RR:3.47, 95% CI:1.23–9.78). Similarly, the case-control data found an increased risk of intussusception following the first dose (OR: 8.45, 95% CI: 4.08–17.50) and following all doses (OR: 1.59, 95% CI: 1.11–2.27). Conclusions Findings of this meta-analysis suggest that the rotavirus vaccine is associated with an increased risk on the development of intussusception, principally seen after administration of the first dose of vaccine.