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Pharmacological treatment options for patients with dementia owing to Alzheimer's disease are limited to symptomatic therapy. Recently, the US Food and Drug Administration approved the monoclonal antibody lecanemab for the treatment of amyloid-positive patients with mild cognitive impairment (MCI) and early Alzheimer´s dementia. European approval is expected in 2024. Data on the applicability and eligibility for treatment with anti-amyloid monoclonal antibodies outside of a study population are lacking.
Aims
This study examined eligibility criteria for lecanemab in a real-world memory clinic population between 1 January 2022 and 31 July 2023.
Method
We conducted a retrospective, single-centre study applying the clinical trial eligibility criteria for lecanemab to out-patients of a specialised psychiatric memory clinic. Eligibility for anti-amyloid treatment was assessed following the phase 3 inclusion and exclusion criteria and the published recommendations for lecanemab.
Results
The study population consisted of 587 out-patients. Two-thirds were diagnosed with Alzheimer's disease (probable or possible Alzheimer's disease dementia in 43.6% of cases, n = 256) or MCI (23%, n = 135), and 33.4% (n = 196) were diagnosed with dementia or neurocognitive disorder owing to another aetiology. Applying all lecanemab eligibility criteria, 11 (4.3%) patients with dementia and two (1.5%) patients with MCI would have been eligible for treatment with this compound, whereas 13 dementia (5.1%) and 14 (10.4%) MCI patients met clinical inclusion criteria, but had no available amyloid status.
Conclusions
Even in a memory clinic with a good infrastructure and sufficient facilities for dementia diagnostics, most patients do not meet the eligibility criteria for treatment with lecanemab.
Previous studies suggest that influenza virus infection may provide temporary non-specific immunity and hence lower the risk of non-influenza respiratory virus infection. In a randomized controlled trial of influenza vaccination, 1 330 children were followed-up in 2009–2011. Respiratory swabs were collected when they reported acute respiratory illness and tested against influenza and other respiratory viruses. We used Poisson regression to compare the incidence of non-influenza respiratory virus infection before and after influenza virus infection. Based on 52 children with influenza B virus infection, the incidence rate ratio (IRR) of non-influenza respiratory virus infection after influenza virus infection was 0.47 (95% confidence interval: 0.27–0.82) compared with before infection. Simulation suggested that this IRR was 0.87 if the temporary protection did not exist. We identified a decreased risk of non-influenza respiratory virus infection after influenza B virus infection in children. Further investigation is needed to determine if this decreased risk could be attributed to temporary non-specific immunity acquired from influenza virus infection.
Specialty on-call clinicians cover large areas and complex workloads. This study aimed to assess clinical communication using the mixed-reality HoloLens 2 device within a simulated on-call scenario.
Method
This study was structured as a randomised, within-participant, controlled study. Thirty ENT trainees used either the HoloLens 2 or a traditional telephone to communicate a clinical case to a consultant. The quality of the clinical communication was scored objectively and subjectively.
Results
Clinical communication using the HoloLens 2 scored statistically higher than telephone (n = 30) (11.9 of 15 vs 10.2 of 15; p = 0.001). Subjectively, consultants judged more communication episodes to be inadequate when using the telephone (7 of 30) versus the HoloLens 2 (0 of 30) (p = 0.01). Qualitative feedback indicates that the HoloLens 2 was easy to use and would add value during an on-call scenario with remote consultant supervision.
Conclusion
This study demonstrated the benefit that mixed-reality devices, such as the HoloLens 2 can bring to clinical communication through increasing the accuracy of communication and confidence of the users.
Given the importance of angiostrongyliasis as an emerging infectious disease of humans, companion animals, and wildlife, the current study focused on the transmission dynamics of first- and third-stage larvae of the parasitic nematode, Angiostrongylus cantonensis. The migration of infective larvae and their subsequent distribution within the Lymnaeidae snail, Bullastra lessoni, were investigated over time using microscopic examination of histological sections and fresh tissue. Snails were divided into four anatomical regions: (i) anterior and (ii) posterior cephalopedal masses, (iii) mantle skirt and (iv) visceral mass. The viability of free-swimming third-stage larvae, after their release from snail tissues, was evaluated in vitro by propidium iodide staining and infectivity by in vivo infection of Wistar rats. Snails were sequentially dissected over time to assess the number and anatomical distribution of larvae within each snail and hence infer their migration pathway. Herein, ongoing larval migratory activity was detected over 28 days post-infection. A comparison of infection rates and the larval distribution within the four designated snail regions demonstrated a significant relationship between anatomical region and density of infective larvae, with larvae mostly distributed in the anterior cephalopedal mass (43.6 ± 10.8%) and the mantle skirt (33.0 ± 8.8%). Propidium iodide staining showed that free-swimming third-stage larvae retained viability for between 4 and 8 weeks when stored under laboratory conditions. In contrast to viability, larval infectivity in rats remained for up to 2 weeks only. Knowledge gained from the current work could provide information on the development of new approaches to controlling the transmission of this parasite.
The COVID-19 pandemic has placed significant strain on emergency departments (EDs) that were not designed to care for many patients who may be highly contagious. This report outlines how a busy urban ED was adapted to prepare for COVID-19 via 3 primary interventions: (1) creating an open-air care space in the ambulance bay to cohort, triage, and rapidly test patients with suspected COVID-19, (2) quickly constructing temporary doors on all open treatment rooms, and (3) adapting and expanding the waiting room. This description serves as a model by which other EDs can repurpose their own care spaces to help ensure safety of their patients and health care workers.
One of the main concerns about the fast spreading coronavirus disease 2019 (Covid-19) pandemic is how to intervene. We analysed severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) isolates data using the multifractal approach and found a rich in viral genome diversity, which could be one of the root causes of the fast Covid-19 pandemic and is strongly affected by pressure and health index of the hosts inhabited regions. The calculated mutation rate (mr) is observed to be maximum at a particular pressure, beyond which mr maintains diversity. Hurst exponent and fractal dimension are found to be optimal at a critical pressure (Pm), whereas, for P > Pm and P < Pm, we found rich genome diversity relating to complicated genome organisation and virulence of the virus. The values of these complexity measurement parameters are found to be increased linearly with health index values.
Preterm birth (delivery <37 weeks of gestation) is associated with impaired glomerular capillary growth in neonates; if this persists, it may be a contributing factor in the increased risk of hypertension and chronic kidney disease in people born preterm. Therefore, in this study, we aimed to determine the long-term impact of preterm birth on renal morphology, in adult sheep. Singleton male sheep were delivered moderately preterm at 132 days (~0.9) of gestation (n = 6) or at term (147 days gestation; n = 6) and euthanised at 14.5 months of age (early adulthood). Stereological methods were used to determine mean renal corpuscle and glomerular volumes, and glomerular capillary length and surface area, in the outer, mid and inner regions of the renal cortex. Glomerulosclerosis and interstitial collagen levels were assessed histologically. By 14.5 months of age, there was no difference between the term and preterm sheep in body or kidney weight. Renal corpuscle volume was significantly larger in the preterm sheep than the term sheep, with the preterm sheep exhibiting enlarged Bowman’s spaces; however, there was no difference in glomerular volume between groups, with no impact of preterm birth on capillary length or surface area per glomerulus. There was also no difference in interstitial collagen levels or glomerulosclerosis index between groups. Findings suggest that moderate preterm birth does not adversely affect glomerular structure in early adulthood. The enlarged Bowman’s space in the renal corpuscles of the preterm sheep kidneys, however, is of concern and merits further research into its cause and functional consequences.
Introduction: The purpose of this study was to identify, through self-assessment, how comfortable rural emergency medicine (EM) practitioners are in treating critically ill trauma patients, the resources available to treat such patients and their comfort with performing trauma procedures. Our goal is to enhance rural trauma care by identifying obstacles rural EM physicians face in Saskatchewan. Methods: This was a cross sectional survey study, emailed to family physicians practicing rural EM in Saskatchewan identified through the Saskatchewan Medical Association database. Inclusion criteria included physicians who are providing EM care currently or within the past year. Rural was assumed to be communities in Saskatchewan that were outside of Saskatoon and Regina. The survey was an anonymous self-assessment regarding demographics, training, hospital resources and comfort. Results: 113 physicians of the 479 rural physicians agreed to participate, 78 met our inclusion criteria. Most (67%) were from communities with less than 10,000 population, 70% had less than 300 ED visits per month. Most (68%) were less than 45 years of age. In terms of training, 57% had completed undergraduate training out of Canada and 63% had completed residency training in Canada. Most had been practicing for more than 2 years (76%). Most (59%) had current ATLS credentials, however only 37% had ever completed the EDE course. Regarding available resources, most centers had plain radiography (99%), POCUS (68%), PRBC (78%) and TXA (93%). However, fresh frozen plasma (41%) and platelets (26%) were not widely available. Comfort was measured on a Likert scale. The types of trauma that respondents were least comfortable with included pediatric (39%), vascular (46%), spine (56%) and genitourinary (60%). The types skills that participants were least comfortable with included pericardiocentesis (19%), and surgical airway (25%). The majority had not performed Pediatric endotracheal tube insertion (79%), surgical airways (99%), pericardiocentesis (99%), central venous line placement (80%) and needle thoracentesis (71%) within the past 12 months. Conclusion: This self-assessment helped us identify aspects of rural trauma medicine that are the most challenging for rural practitioners. Understanding the most difficult challenges in light of the critical resources available to rural trauma medicine providers will inform future professional development initiatives.
The chronic worldwide shortage of psychiatrists has impaired the delivery of first class mental health care (WHO 2008). This international project funded by a World Psychiatric Association grant proposes to examine and compare the effects of country-specific undergraduate and postgraduate factors involved in medical student choice of a psychiatric career. Phase 1 focussed on identifying published proven and novel modifiable factors to improve psychiatric recruitment.
Method
We searched EMBASE, PsychInfo and Medline using the keywords ‘career psychiatry’, ‘medical education’, and ‘career choice’. All 206 papers retrieved using the combined search were reviewed and categorized thematically.
Results
Findings are summarised under three themes:
· Pre-medical school factors: arts & social sciences qualifications, attitudes towards mental illness, high uncertainty tolerance, liberal political views, gender and life goals.
· Medical school factors: availability of psychology/sociology/special-studies modules, electives; length of clinical placement; exposure to motivated patients and effective treatment; quality of teaching and good role models; and conversely negative attitudes from other specialities.
· Post-graduate factors: availability of early clinical posts in psychiatry, work-life balance, remuneration.
Conclusions
· Studies have been limited by small sample sizes, unicentricity, and datedness, given the major reorganisations of mental health services and postgraduate training in many countries.
· During the next stage we will generate the first multicountry comparison, with sufficient power to detect differences in factors influencing a psychiatric career choice at personal, institutional and national level. We will focus on factors that may be modifiable by policy to positively influence career choice towards psychiatry.
Vascular Dementia (VD) patients have increased co-morbidity and higher mortality in comparison to other patients. Neuro-degeneration, cognitive deficits and underlying medical conditions may influence the pattern of co-morbid disorders and their possible effects on mortality in VD.
Aim
To investigate whether the pattern of co-morbidity and its relevance for later death differed between hospitalised VD and elderly controls.
Method
Diseases with a prevalence of more than 1% at hospital admission were compared between 341 hospitalised VD and 72244 control subjects aged above 70 years referred to the University of Birmingham Hospital, UK. Risk factors i.e. co-morbidities that were predictors of mortality within the seven year follow-up were identified using logistic regression and cox regression analyses. Confidence intervals of relative risks were used to compare the relevance of risk factors for later mortality between groups.
Results
Subjects with VD suffer more with peripheral vascular disease, atrial fibrillation, type 2 diabetes mellitus, pneumonia, ischemic stroke and urinary tract infections than other hospitalised elderly patients. In contrast, myocardial infarction was less prevalent in VD subjects in comparison with hospitalised controls. The prevalence of hypertension, ischemic heart disease, angina and heart failure was not statistically different in the two groups.
Conclusion
Patients with Vascular Dementia have a different pattern of co-morbidity, but die from the same diseases as other hospitalised patients. Infections including pneumonia may need special attention in patients with vascular dementia who might not be able to identify or report the early symptoms.
Neurodegeneration and cognitive deficits may influence the pattern of co-morbid disorders and their possible effects on mortality in late-onset Alzheimer's disease (AD). However, subjects with AD have to live long enough to experience and be diagnosed with dementia. We investigated whether the pattern of co-morbidity and its relevance for later death differed between hospitalised AD and elderly controls subjects.
Methods
Diseases with a prevalence of more than 1% were compared between 634 hospitalised AD and 72244 control subjects aged above 70 years referred to the University of Birmimgham NHS Trust. Predictors of mortality within the seven year follow-up were identified using regression regression analyses. Confidence intervals of relative risks were used to compare the relevance of risk factors for later mortality between groups.
Results
Subjects with AD suffer more infections, brain diseases and neck of femur fractures than other hospitalised elderly patients. In contrast, cardiovascular diseases and diabetes mellitus were less prevalent in AD subjects in comparison with hospitalised controls. Diseases that might contribute to later mortality in AD were pneumonia, ischemic heart disease and gastroenteritis, but there were no significant differences in their impact on mortality compared to other hospitalised elderly control subjects.
Conclusions
Patients with Alzheimer's disease have a different pattern of co-morbidity, but die from the same diseases as other hospitalised patients. Infections including pneumonia, and diseases that may occur secondary to neurodegeneration and confusion may need special attention in patients with Alzheimer disease who might not be able to identify or report the early symptoms.
The chronic worldwide shortage of psychiatrists has impaired the delivery of first class mental health care. The WHO produced a report on the Mental Health Gap, showing the high burden of mental health, neurological and substance misuse disorders worldwide, estimating a treatment gap of 75% between need and resources.
Aims and objectives
Research to date has highlighted key areas that influence students' choice of a career in psychiatry. There have been several key literature reviews summarising work in the area since the 1950s. The current study updates literature with a systematic review of the past 10 years.
Methods
A five level search strategy was used.
A standard Critical Appraisal tool was developed based on the one used by the Best Evidence in Medical Education Group in Dundee. Papers were coded and graded using hierarchies of evidence - Sackett Hierarchy of Evidence and Kirkpatrick Hierarchy.
Results & conclusions
The quality of published studies has risen over the past 30 years, with the past decade producing the most robust evidence. However, it is a complex area to research with many potential confounders, and large gaps in knowledge remain.
The aim of this study was to evaluate contact endoscopy in detecting local treatment failures post-radiotherapy in squamous cell carcinoma of the upper aerodigestive tract.
Method
A total of 135 consecutive patients with suspected residual or recurrent cancer after definitive radiotherapy underwent contact endoscopy before biopsy. Contact endoscopy findings were compared with histopathological examination findings. Contact endoscopy could not be completed in 7 patients (5.9 per cent) and histopathological examination was inconclusive in 5 patients (3.7 per cent). The findings of the remaining 123 patients were compared.
Results
The sensitivity, specificity and accuracy of contact endoscopy were 88.75, 88.72 and 86.99 per cent, respectively, with similar results across various sites of upper aerodigestive tract. Inter-observer kappa value was 0.86 (95 per cent confidence interval: 0.79–0.93). The intra-observer kappa value was 0.93 (95 per cent confidence interval: 0.87–1.00) for the first observer and 0.95 (95 per cent confidence interval: 0.90–1.00) for second and third observers.
Conclusion
Contact endoscopy showed the same high sensitivity and specificity with low inter- and intra-observer variability in detecting post-radiotherapy failures in cancer of the upper aerodigestive tract as has been shown in non-irradiated tissues in earlier studies.
Early laryngeal cancer treated with definitive radiotherapy or surgery has a high cure rate. This study evaluated the patterns of treatment failure and long-term results of early laryngeal cancers treated with definitive radiotherapy.
Method
From January 2002 to December 2014, a total of 242 patients with early-stage laryngeal cancers were treated with radical radiotherapy.
Results
All patients had squamous cell carcinoma of the larynx (92 per cent male and 8 per cent female). Median follow-up was 4.5 years. The majority of patients were smokers (57.4 per cent). Local failure was seen in 12.5 per cent of stage I patients and 22.8 per cent of stage II patients. The 5-year overall survival and disease specific survival were 84 per cent and 91 per cent, respectively.
Conclusion
In summary, radiotherapy is a suitable treatment modality for patients with early-stage laryngeal cancer, with an overall locoregional control rate of 84 per cent. Patients who fail radiotherapy may still undergo salvage laryngectomy.
This chapter addresses the challenges of establishing and sustaining governance arrangements conducive to environmental citizenship. The significance of this concern is illustrated by Australian experiences with governance arrangements seeking to promote citizenship among rural landholders in natural resources conservation. The chapter draws from Vincent Ostrom's thinking about polycentric governance, who drew from de Tocqueville. Ostrom identified ‘the way people think and relate to one another’ (corresponding with the meta-constitutional level of analysis in the Institutional Analysis and Development framework) as vital for governance that is capable of promoting citizenship, and the citizenship required to sustain polycentric governance. Progress in empirical investigation of relationships between polycentric governance and environmental citizenship is reviewed. One relationship of this kind is illustrated by policy reform in Australia’s Murray-Darling Basin.
India has the second largest number of people with type 2 diabetes (T2D) globally. Epidemiological evidence indicates that consumption of white rice is positively associated with T2D risk, while intake of brown rice is inversely associated. Thus, we explored the effect of substituting brown rice for white rice on T2D risk factors among adults in urban South India. A total of 166 overweight (BMI ≥ 23 kg/m2) adults aged 25–65 years were enrolled in a randomised cross-over trial in Chennai, India. Interventions were a parboiled brown rice or white rice regimen providing two ad libitum meals/d, 6 d/week for 3 months with a 2-week washout period. Primary outcomes were blood glucose, insulin, glycosylated Hb (HbA1c), insulin resistance (homeostasis model assessment of insulin resistance) and lipids. High-sensitivity C-reactive protein (hs-CRP) was a secondary outcome. We did not observe significant between-group differences for primary outcomes among all participants. However, a significant reduction in HbA1c was observed in the brown rice group among participants with the metabolic syndrome (−0·18 (se 0·08) %) relative to those without the metabolic syndrome (0·05 (se 0·05) %) (P-for-heterogeneity = 0·02). Improvements in HbA1c, total and LDL-cholesterol were observed in the brown rice group among participants with a BMI ≥ 25 kg/m2 compared with those with a BMI < 25 kg/m2 (P-for-heterogeneity < 0·05). We observed a smaller increase in hs-CRP in the brown (0·03 (sd 2·12) mg/l) compared with white rice group (0·63 (sd 2·35) mg/l) (P = 0·04). In conclusion, substituting brown rice for white rice showed a potential benefit on HbA1c among participants with the metabolic syndrome and an elevated BMI. A small benefit on inflammation was also observed.
A cross-sectional study was conducted from 2014 to 2017 in 13 organised pig farms located in eight states of India (Northern, North-Eastern and Southern regions) to identify the risk factors, pathotype and antimicrobial resistance of Escherichia coli associated with pre- and post-weaning piglet diarrhoea. The data collected through questionnaire survey were used to identify the risk factors by univariable analysis, in which weaning status, season, altitude, ventilation in the shed, use of heater/cooler for temperature control in the sheds, feed type, water source, and use of disinfectant, were the potential risk factors. In logistic regression model, weaning and source of water were the significant risk factors. The piglet diarrhoea prevalence was almost similar across the regions. Of the 909 faecal samples collected (North – 310, North-East – 194 and South – 405) for isolation of E. coli, pathotyping and antibiotic screening, 531 E. coli were isolated in MacConkey agar added with cefotaxime, where 345 isolates were extended spectrum β-lactamase (ESBL) producers and were positive for blaCTX-M-1 (n = 147), bla TEM (n = 151), qnrA (n = 98), qnrB (n = 116), qnrS (n = 53), tetA (n = 46), tetB (n = 48) and sul1 (n = 54) genes. Multiple antibiotic resistance (MAR) index revealed that 14 (2.64%) isolates had MAR index of 1. On the virulence screening of E. coli, 174 isolates harboured alone or combination of Stx1, Stx2, eaeA, hlyA genes. The isolates from diarrhoeic and post-weaning samples harboured higher number of virulence genes than non-diarrhoeic and pre-weaning. Alleviating the risk factors might reduce the piglet diarrhoea cases. The presence of multidrug-resistant and ESBL-producing pathogenic E. coli in piglets appears a public health concern.
Nano-patterned surfaces have potential applications in the development of efficient solar cells through multiple internal reflections and may be used to fulfil the energy demand of rural India. Therefore, the basic understanding of growth mechanism of patterns under ion irradiation is much required. Here, the ripple patterns are grown on Si (100) surfaces for two specific ion irradiation conditions. First, the two set of samples (namely set-A and set-B) of Si (100) are irradiated by 50 keVAr+ ion beam at oblique (60°) and normal incidence, respectively, using ion fluence of 5×1016 ions/ cm2. The aim of this first stage irradiation at two different angles is the creation of different depth locations of amorphous/crystalline (a/c) interface while keeping the free surface similar in surface features, which is a crucial parameter in surface growth. Further, the sequential second stage irradiation is carried out at 60° for the same energy of Ar beam for the fluences 3×1017 to 9×1017 ions/cm2 to see the evolution of ripple patterns. Atomic force microscopy (AFM) study shows that the ripple pattern ordering is better in set-A rather than set-B. Lateral correlation length of each ripple structure surface is computed by autocorrelation function while roughness exponent is measured with height-height correlation function. Fractals behaviors of patterned on Si (100) surface are found to be sensitive to the two stage irradiation approach. The understanding of the mechanism of nano-patterns formation may be useful to develop efficient solar systems for the needs of energy in rural India.