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Previous results have been mixed regarding the role of the apolipoprotein E e4 (APOE e4) allele in later-life depression: some studies note that carriers experience greater symptoms and increased risk while others find no such association. However, there are few prospective, population-based studies of the APOE e4-depression association and fewer that examine depressive symptom trajectory and depression risk longitudinally. We examined the association between APOE e4 allele status and longitudinal change in depressive symptoms and depression risk in later-life, over a 12-year follow-up period.
We used data from 690 participants of the Lothian Birth Cohort 1936 who took part in the Scottish Mental Survey 1947 (aged 11) and were followed-up in later-life over five waves from 2004 to 2019 (aged 70–82). We used APOE e4 allele status to predict longitudinal change in depressive symptom scores and risk of depression (defined by a symptom score threshold or use of depression-related medication). Models were adjusted for sex, childhood cognitive ability, childhood social class, education, adult social class, smoking status and functional limitations at baseline.
Depressive symptom scores increased with age. Once adjusted for covariates, APOE e4 allele status did not significantly predict symptom score trajectories or depression risk. Greater functional limitations at baseline significantly predicted poorer symptom score trajectories and increased depression risk (defined by medications). APOE e4 allele status did not significantly moderate the contribution of sex, education or functional limitations.
There was no evidence that APOE e4 carriers experience an increased risk for later-life depression.
Previous evidence confirms a relationship between the timing of food intake and weight loss. We aimed to evaluate the effect of late v. early evening meal (EEM) consumption on weight loss and cardiometabolic risk factors in women during a weight loss programme. Eighty-two healthy women (BMI 27−35 kg/m2; age 18−45 years) were randomly assigned to two groups: EEM group (eating at 19.00−19.30 hours) or late evening meal (LEM) group (eating at 22.30−23.00 hours), for 12 weeks. Compared with the LEM group, the EEM group had a greater mean reduction in weight (EEM: −6·74 (sd 1·92) kg; LEM: −4·81 (sd 2·22) kg; P < 0·001), BMI (EEM: −2·60 (sd 0·71) kg/m2; LEM: −1·87 (sd 0·85) kg/m2; P < 0·001), waist circumference (EEM: −8 (sd 3·25) cm; LEM: −6 (sd 3·05) cm, P = 0·007), total cholesterol (EEM: −0·51 (sd 0·19) mmol/l, LEM: −0·43 (sd 0·19) mmol/l, P = 0·038), TAG (EEM: −0·28 (sd 0·10) mmol/l, LEM: −0·19 (sd 0·10) mmol/l, P < 0·001) and homoeostasis model assessment of insulin resistance (EEM: −0·83 (sd 0·37); LEM: −0·55 (sd 0·28), P < 0·001) after 12 weeks. In conclusion, eating an earlier evening meal resulted in favourable changes in weight loss and plasma cardiometabolic risk markers during a weight loss programme.
Background: Healthcare services are increasingly shifting from inpatient to outpatient settings. Outpatient settings such as emergency departments (EDs), oncology clinics, dialysis clinics, and day surgery often involve invasive procedures with the risk of acquiring healthcare-associated infections (HAIs). As a leading cause of HAI, Clostridioides difficile infection (CDI) in outpatient settings has not been sufficiently described in Canada. The Canadian Nosocomial Infection Surveillance Program (CNISP) aims to describe the epidemiology, molecular characterization, and antimicrobial susceptibility of outpatient CDI across Canada. Methods: Epidemiologic data were collected from patients diagnosed with CDI from a network of 47 adult and pediatric CNISP hospitals. Patients presenting to an outpatient setting such as the ED or outpatient clinics were considered as outpatient CDI. Cases were considered HAIs if the patient had had a healthcare intervention within the previous 4 weeks, and they were considered community-associated if there was no history of hospitalization within the previous 12 weeks. Clostridioides difficile isolates were submitted to the National Microbiology Laboratory for testing during an annual 2-month targeted surveillance period. National and regional rates of CDI were stratified by outpatient location. Results: Between January 1, 2015, and June 30, 2019, 2,691 cases of outpatient-CDI were reported, and 348 isolates were available for testing. Most cases (1,475 of 2,691, 54.8%) were identified in outpatient clinics, and 72.8% (1,960 of 2,691) were classified as community associated. CDI cases per 100,000 ED visits were highest in 2015, at 10.3, and decreased to 8.1 in 2018. Rates from outpatient clinics decreased from 3.5 in 2016 to 2.7 in 2018 (Fig. 1). Regionally, CDI rates in the ED declined in Central Canada and increased in the West after 2016. Rates in outpatient clinics were >2 times higher in the West compared to other regions. RT027 associated with NAP1 was most common among ED patients (26 of 195, 13.3%), whereas RT106 associated with NAP11 was predominant in outpatient clinics (22 of 189, 11.6%). Overall, 10.4% of isolates were resistant to moxifloxacin, 0.5% were resistant to rifampin, and 24.2% were resistant to clindamycin. No resistance was observed for metronidazole, vancomycin, or tigecycline. Compared to CNISP inpatient CDI data, outpatients with CDI were younger (51.8 ± 23.3 vs 64.2 ± 21.6; P < .001), included more females (56.4% vs 50.9%; P < .001), and were more often treated with metronidazole (63.0% vs 56.1%; P < .001). Conclusions: For the first time, CDI cases identified in outpatient settings were characterized in a Canadian context. Outpatient CDI rates are decreasing overall, but they vary by region. Predominant ribotypes vary based on outpatient location. Outpatients with CDI are younger and are more likely female than inpatients with CDI.
Disclosures: Susy Hota reports contract research for Finch Therapeutics.
Background: Carbapenemase-producing Enterobacterales (CPE) have rapidly become a global health concern and are associated with substantial morbidity and mortality due to limited treatment options. Travel to endemic areas, especially healthcare exposure in these areas, is an important risk factor for acquisition. We describe the evolving epidemiology, molecular features, and outcomes of CPE in Canada through surveillance by the Canadian Nosocomial Infection Surveillance Program (CNISP). Methods: CNISP has conducted surveillance for CPE among inpatients and outpatients of all ages since 2010. Participating acute-care facilities submit eligible specimens to the National Microbiology Laboratory for detection of carbapenemase production, and epidemiological data are collected. Incidence rates per 10,000 patient days are calculated based on inpatient data. Results: In total, 59 CNISP hospitals in 10 Canadian provinces representing 21,789 beds and 6,785,013 patient days participated in this surveillance. From 2010 to 2018, 118 (26%) CPE-infected and 547 (74%) CPE-colonized patients were identified. Few pediatric cases were identified (n = 18). Infection incidence rates remain low and stable (0.02 per 10,000 patient days in 2010 to 0.03 per 10,000 patient days in 2018), and colonization incidence rates have increased by 89% over the surveillance period. Overall, 92% of cases were acquired in a healthcare facility: 61% (n = 278) in a Canadian healthcare facility and 31% (n = 142) in a healthcare facility outside Canada. Of the 8% of cases not acquired in a healthcare facility, 50% (16 of 32) reported travel outside of Canada in the 12 months prior to positive culture. The distribution of carbapenemases varied by region; New Delhi metallo-B-lactamase (NDM) was dominant (59%) in western Canada and Klebsiella pneumoniae carbapenemase (KPC) (66%) in central Canada. NDM and class D carbapenemase OXA-48 were more commonly identified among those who traveled outside of Canada, whereas KPC was more commonly identified among patients without travel. In addition, 30-day all-cause mortality was 14% (25 of 181) among CPE infected patients and 32% (14 of 44) among those with bacteremia. Conclusions: CPE rates remain low in Canada; however, national surveillance data suggest that the increase in CPE in Canada is now being driven by local nosocomial transmission as well as travel and healthcare within endemic areas. Changes in screening practices may have contributed to the increase in colonizations; however, these data are currently lacking and will be collected moving forward. These data highlight the need to intensify surveillance and coordinate infection control measures to prevent further spread of CPE in Canadian acute-care hospitals.
Susy Hota reports contracted research for Finch Therapeutics. Allison McGeer reports funds to her institution for projects for which she is the principal investigator from Pfizer and Merck, as well as consulting fees from the following companies: Sanofi-Pasteur, Sunovion, GSK, Pfizer, and Cidara.
Lewy body dementia, consisting of both dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), is considerably under-recognised clinically compared with its frequency in autopsy series.
This study investigated the clinical diagnostic pathways of patients with Lewy body dementia to assess if difficulties in diagnosis may be contributing to these differences.
We reviewed the medical notes of 74 people with DLB and 72 with non-DLB dementia matched for age, gender and cognitive performance, together with 38 people with PDD and 35 with Parkinson's disease, matched for age and gender, from two geographically distinct UK regions.
The cases of individuals with DLB took longer to reach a final diagnosis (1.2 v. 0.6 years, P = 0.017), underwent more scans (1.7 v. 1.2, P = 0.002) and had more alternative prior diagnoses (0.8 v. 0.4, P = 0.002), than the cases of those with non-DLB dementia. Individuals diagnosed in one region of the UK had significantly more core features (2.1 v. 1.5, P = 0.007) than those in the other region, and were less likely to have dopamine transporter imaging (P < 0.001). For patients with PDD, more than 1.4 years prior to receiving a dementia diagnosis: 46% (12 of 26) had documented impaired activities of daily living because of cognitive impairment, 57% (16 of 28) had cognitive impairment in multiple domains, with 38% (6 of 16) having both, and 39% (9 of 23) already receiving anti-dementia drugs.
Our results show the pathway to diagnosis of DLB is longer and more complex than for non-DLB dementia. There were also marked differences between regions in the thresholds clinicians adopt for diagnosing DLB and also in the use of dopamine transporter imaging. For PDD, a diagnosis of dementia was delayed well beyond symptom onset and even treatment.
Mild cognitive impairment (MCI) may gradually worsen to dementia, but often remains stable for extended periods of time. Little is known about the predictors of decline to help explain this variation. We aimed to explore whether this heterogeneous course of MCI may be predicted by the presence of Lewy body (LB) symptoms in a prospectively-recruited longitudinal cohort of MCI with Lewy bodies (MCI-LB) and Alzheimer's disease (MCI-AD).
A prospective cohort (n = 76) aged ⩾60 years underwent detailed assessment after recent MCI diagnosis, and were followed up annually with repeated neuropsychological testing and clinical review of cognitive status and LB symptoms. Latent class mixture modelling identified data-driven sub-groups with distinct trajectories of global cognitive function.
Three distinct trajectories were identified in the full cohort: slow/stable progression (46%), intermediate progressive decline (41%) and a small group with a much faster decline (13%). The presence of LB symptomology, and visual hallucinations in particular, predicted decline v. a stable cognitive trajectory. With time zeroed on study end (death, dementia or withdrawal) where available (n = 39), the same subgroups were identified. Adjustment for baseline functioning obscured the presence of any latent classes, suggesting that baseline function is an important parameter in prospective decline.
These results highlight some potential signals for impending decline in MCI; poorer baseline function and the presence of probable LB symptoms – particularly visual hallucinations. Identifying people with a rapid decline is important but our findings are preliminary given the modest cohort size.
On 29 April 2015, four beacons were deployed onto an ice island in the Strait of Belle Isle to record positional data. The ice island later broke up into many fragments, four of which were tracked by the beacons. The relative influences of wind drag, current drag, Coriolis force, sea surface height gradient and sea-ice force on the drift of the tracked ice island fragments were analyzed. Using atmospheric and oceanic model outputs, the sea-ice force was calculated as the residual of the fragments' net forces and the sum of all other forces. This was compared against the force obtained through ice concentration-dependent relationships when sea ice was present. The sea-ice forces calculated from the residual approach and concentration-dependent relationships were significant only when sea ice was present at medium-high concentrations in the vicinity of the ice island fragments. The forces from ocean currents and sea surface tilt contributed the most to the drift of the ice island fragments. Wind, however, played a minimal role in the total force governing the drift of the four ice island fragments, and Coriolis force was significant when the fragments were drifting at higher speeds.
Psychosocial interventions that mitigate psychosocial distress in cancer patients are important. The primary aim of this study was to examine the feasibility and acceptability of an adaptation of the Mindful Self-Compassion (MSC) program among adult cancer patients. A secondary aim was to examine pre–post-program changes in psychosocial wellbeing.
The research design was a feasibility and acceptability study, with an examination of pre- to post-intervention changes in psychosocial measures. A study information pack was posted to 173 adult cancer patients 6 months–5 years post-diagnosis, with an invitation to attend an eight-week group-based adaptation of the MSC program.
Thirty-two (19%) consented to the program, with 30 commencing. Twenty-seven completed the program (mean age: 62.93 years, SD 14.04; 17 [63%] female), attending a mean 6.93 (SD 1.11) group sessions. There were no significant differences in medico-demographic factors between program-completers and those who did not consent. However, there was a trend toward shorter time since diagnosis in the program-completers group. Program-completers rated the program highly regarding content, relevance to the concerns of cancer patients, and the likelihood of recommending the program to other cancer patients. Sixty-three percent perceived that their mental wellbeing had improved from pre- to post-program; none perceived a deterioration in mental wellbeing. Small-to-medium effects were observed for depressive symptoms, fear of cancer recurrence, stress, loneliness, body image satisfaction, mindfulness, and self-compassion.
Significance of results
The MSC program appears feasible and acceptable to adults diagnosed with non-advanced cancer. The preliminary estimates of effect sizes in this sample suggest that participation in the program was associated with improvements in psychosocial wellbeing. Collectively, these findings suggest that there may be value in conducting an adequately powered randomized controlled trial to determine the efficacy of the MSC program in enhancing the psychosocial wellbeing of cancer patients.
The most frequently asked questions about Chlamydia trachomatis, commonly known as “chlamydia,” are (1) what is it? and (2) where did it come from? The capricious and cryptic nature of genital infections caused by C. trachomatis and the difficulties in isolating the pathogen have led to many misconceptions about its origins and how infection occurs. The first question is now easy to answer. There is no doubt: chlamydiae are not viruses, nor are they protozoan parasites; they are bacteria. However, they are not free-living bacteria and so cannot be cultivated on conventional media such as agar plates. Chlamydiae are highly specialized bacteria, which can be grown only within living cells; thus they are obligate intracellular pathogens.
Chlamydiae also have a complex developmental cycle. The name is derived from Chlamydozoa, which means “cloaked organisms,” because they develop within an inclusion membrane within the cytoplasm of the cell and initially in the infection process are not visible. These gram-negative bacteria have a unique development cycle that includes the repeated division of a replicating stage, called an RB, or reticulate body. RBs increase in number to a point where they can be seen under the microscope as moving specks within a defined membrane structure known as an inclusion in the host cell's cytoplasm. With time the inclusion ruptures out of the cell and releases the smaller nonreplicating infectious forms called “elementary bodies.”
The genus is also known as Chlamydia; it is a proper noun written in italics, with no plural. The genus Chlamydia currently contains nine species and no doubt, more will be added. The species C. trachomatis, the focus of our discussion, is made up of a number of serovars, differentiated by surface antigens that induce specific antibodies. It has four ocular serovars that cause blinding endemic trachoma, A, B, Ba, and C and at least eight serovars, D to K, which typically cause genital tract infections. There are additionally the three L serovars that cause the condition known as lymphogranuloma venerum. Closely related species are C. muridarum, which infects mice and hamsters, and C. suis, which is endemic in pigs.
Whole-grain cereal breakfast consumption has been associated with beneficial effects on glucose and insulin metabolism as well as satiety. Pearl millet is a popular ancient grain variety that can be grown in hot, dry regions. However, little is known about its health effects. The present study investigated the effect of a pearl millet porridge (PMP) compared with a well-known Scottish oats porridge (SOP) on glycaemic, gastrointestinal, hormonal and appetitive responses. In a randomised, two-way crossover trial, twenty-six healthy participants consumed two isoenergetic/isovolumetric PMP or SOP breakfast meals, served with a drink of water. Blood samples for glucose, insulin, glucagon-like peptide 1, glucose-dependent insulinotropic polypeptide (GIP), peptide YY, gastric volumes and appetite ratings were collected 2 h postprandially, followed by an ad libitum meal and food intake records for the remainder of the day. The incremental AUC (iAUC2h) for blood glucose was not significantly different between the porridges (P > 0·05). The iAUC2h for gastric volume was larger for PMP compared with SOP (P = 0·045). The iAUC2h for GIP concentration was significantly lower for PMP compared with SOP (P = 0·001). Other hormones and appetite responses were similar between meals. In conclusion, the present study reports, for the first time, data on glycaemic and physiological responses to a pearl millet breakfast, showing that this ancient grain could represent a sustainable alternative with health-promoting characteristics comparable with oats. GIP is an incretin hormone linked to TAG absorption in adipose tissue; therefore, the lower GIP response for PMP may be an added health benefit.
Background: Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease resulting in muscle weakness, dysarthria and dysphagia, and ultimately respiratory failure leading to death. Half of the ALS patients survive less than 3 years, and 80% of the patients survive less than 5 years. Riluzole is the only approved medication in Canada with randomized controlled clinical trial evidence to slow the progression of ALS, albeit only to a modest degree. The Canadian Neuromuscular Disease Registry (CNDR) collects data on over 140 different neuromuscular diseases including ALS across ten academic institutions and 28 clinics including ten multidisciplinary ALS clinics. Methods: In this study, CNDR registry data were analyzed to examine potential differences in ALS care among provinces in time to diagnosis, riluzole and feeding tube use. Results: Significant differences were found among provinces, in time to diagnosis from symptom onset, in the use of riluzole and in feeding tube use. Conclusions: Future investigations should be undertaken to identify factors contributing to such differences, and to propose potential interventions to address the provincial differences reported.
Dopaminergic imaging has high diagnostic accuracy for dementia with Lewy bodies (DLB) at the dementia stage. We report the first investigation of dopaminergic imaging at the prodromal stage.
We recruited 75 patients over 60 with mild cognitive impairment (MCI), 33 with probable MCI with Lewy body disease (MCI-LB), 15 with possible MCI-LB and 27 with MCI with Alzheimer's disease. All underwent detailed clinical, neurological and neuropsychological assessments and FP-CIT [123I-N-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)] dopaminergic imaging. FP-CIT scans were blindly rated by a consensus panel and classified as normal or abnormal.
The sensitivity of visually rated FP-CIT imaging to detect combined possible or probable MCI-LB was 54.2% [95% confidence interval (CI) 39.2–68.6], with a specificity of 89.0% (95% CI 70.8–97.6) and a likelihood ratio for MCI-LB of 4.9, indicating that FP-CIT may be a clinically important test in MCI where any characteristic symptoms of Lewy body (LB) disease are present. The sensitivity in probable MCI-LB was 61.0% (95% CI 42.5–77.4) and in possible MCI-LB was 40.0% (95% CI 16.4–67.7).
Dopaminergic imaging had high specificity at the pre-dementia stage and gave a clinically important increase in diagnostic confidence and so should be considered in all patients with MCI who have any of the diagnostic symptoms of DLB. As expected, the sensitivity was lower in MCI-LB than in established DLB, although over 50% still had an abnormal scan. Accurate diagnosis of LB disease is important to enable early optimal treatment for LB symptoms.
The accurate clinical characterisation of mild cognitive impairment (MCI) is becoming increasingly important. The aim of this study was to compare the neuropsychiatric symptoms and cognitive profile of MCI with Lewy bodies (MCI-LB) with Alzheimer's disease MCI (MCI-AD).
Participants were ⩾60 years old with MCI. Each had a thorough clinical and neuropsychological assessment and 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single photon emission computed tomography FP-CIT SPECT). MCI-LB was diagnosed if two or more diagnostic features of dementia with Lewy bodies were present (visual hallucinations, cognitive fluctuations, motor parkinsonism, rapid eye movement sleep behaviour disorder or positive FP-CIT SPECT). A Lewy body Neuropsychiatric Supportive Symptom Count (LBNSSC) was calculated based on the presence or absence of the supportive neuropsychiatric symptoms defined by the 2017 DLB diagnostic criteria: non-visual hallucinations, delusions, anxiety, depression and apathy.
MCI-LB (n = 41) had a higher LBNSSC than MCI-AD (n = 24; 1.8 ± 1.1 v. 0.7 ± 0.9, p = 0.001). 67% of MCI-LB had two or more of those symptoms, compared with 16% of MCI-AD (Likelihood ratio = 4.2, p < 0.001). MCI-LB subjects scored lower on tests of attention, visuospatial function and verbal fluency. However, cognitive test scores alone did not accurately differentiate MCI-LB from MCI-AD.
MCI-LB is associated with neuropsychiatric symptoms and a cognitive profile similar to established DLB. This supports the concept of identifying MCI-LB based on the presence of core diagnostic features of DLB and abnormal FP-CIT SPECT imaging. The presence of supportive neuropsychiatric clinical features identified in the 2017 DLB diagnostic criteria was helpful in differentiating between MCI-LB and MCI-AD.
Lewy body dementia (consisting of dementia with Lewy bodies and Parkinson's disease dementia) is a common neurodegenerative disease characterised by visual hallucinations, fluctuating attention, motor disturbances, falls, and sensitivity to antipsychotics. This combination of features presents challenges for pharmacological management. Given this, we sought to review evidence for non-pharmacological interventions with patients with Lewy body dementia and their carers. Bibliographic databases were searched using a wide range of search terms and no restrictions were placed on study design, language, or clinical setting. Two reviewers independently assessed papers for inclusion, rated study quality, and extracted data. The search identified 21 studies including two randomised controlled trials with available subgroup data, seven case series, and 12 case studies. Most studies reported beneficial effects of the interventions used, though the only sizeable study was on dysphagia, showing a benefit of honey-thickened liquids. Given the heterogeneity of interventions and poor quality of the studies overall, no quantitative synthesis was possible. Overall, identified studies suggested possible benefits of non-pharmacological interventions in Lewy body dementia, but the small sample sizes and low quality of studies mean no definite recommendations can be offered. Our findings underscore the clear and urgent need for future research on this topic.
Latrodectism following Black Widow envenomation is rare in Canada. We present the case of a previously healthy 50 year old male who presented with an acute abdomen, hypertension, and urinary retention. After a thorough work up it was determined to be as a result of a Black Widow spider bite. Due to climate change we may see more cases of Latrodectism in the future and it should be considered as a differential diagnosis in anyone presenting with an acute abdomen after an insect bite.
NHS England recently published a national plan to develop community services for people with intellectual disabilities and autism who display challenging behaviour by using resources from the closure of a large number of hospital beds. An ambitious timescale has been set to implement this plan. The bed closure programme is moving ahead rapidly, but there has been little progress in developing community services to support it. This paper discusses the impact of the gap between policy and practice on the care and safety of patients with intellectual disabilities and forensic needs who form a distinct subgroup of the target population and are being disproportionately affected by this government policy.