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Schizophrenia spectrum disorders are among the most debilitating mental disorders and has complex pathophysiological underpinnings. There is growing evidence that brain-derived neurotrophic factor (BDNF) can play a role in its pathogenesis. The present study investigated the longitudinal variation of serum BDNF levels in a 24-month observational prospective cohort study of Sardinian psychotic patients and its relationship with psychopathological and cognitive changes. Furthermore, we examined whether genetic variation within the BDNF gene could moderate these relationships.
Every 6 months, 105 patients were assessed for their BDNF serum levels, as well as for a series of psychopathological, cognitive, and social measures. We performed a targeted analysis of four tag single nucleotide polymorphisms within the BDNF gene that were selected and analyzed using polymerase chain reaction. Longitudinal data were analyzed using mixed-effects linear regression models.
We observed a declining longitudinal trajectory of BDNF levels in psychotic patients in general, and in relation to the severity of depressive and negative symptoms. BDNF serum levels also declined in patients scoring lower in cognitive measures such as attention and speed of information processing and verbal fluency. The rs7934165 polymorphism moderated the significant association between verbal fluency and BDNF levels.
These findings in patients from real-world settings suggest a plausible role of peripheral BDNF levels as a marker of illness burden in schizophrenia spectrum disorders.
It has been suggested that dysregulation of sex hormones is associated with schizophrenia. However, obesity and metabolic syndrome are very common between schizophrenic patients, and it can also dysregulate sex hormones so they could act as confounders.
To determine if estradiol and progesterone are abnormally elevated regardless of obesity or metabolic syndrome in men with SCZ.
We measured serum levels of progesterone and estradiol in 56 schizophrenic male patients at treatment with a depot antipsychotic. Subsequently, we studied the association or independence of our results with obesity or metabolic syndrome by a Chi Square Test.
66.07% of our patients elevated progesterone levels, 19.64% of our patients elevated estradiol levels, and 16.07% of our patients elevated both, progesterone and estradiol, simultaneously. We found no relationship between increased estradiol and / or progesterone with obesity and / or metabolic syndrome.
Estradiol and progesterone are abnormally elevated regardless of obesity and / or metabolic syndrome in male schizophrenic patients on depot treatment.
Capacity development is critical to long-term conservation success, yet we lack a robust and rigorous understanding of how well its effects are being evaluated. A comprehensive summary of who is monitoring and evaluating capacity development interventions, what is being evaluated and how, would help in the development of evidence-based guidance to inform design and implementation decisions for future capacity development interventions and evaluations of their effectiveness. We built an evidence map by reviewing peer-reviewed and grey literature published since 2000, to identify case studies evaluating capacity development interventions in biodiversity conservation and natural resource management. We used inductive and deductive approaches to develop a coding strategy for studies that met our criteria, extracting data on the type of capacity development intervention, evaluation methods, data and analysis types, categories of outputs and outcomes assessed, and whether the study had a clear causal model and/or used a systems approach. We found that almost all studies assessed multiple outcome types: most frequent was change in knowledge, followed by behaviour, then attitude. Few studies evaluated conservation outcomes. Less than half included an explicit causal model linking interventions to expected outcomes. Half of the studies considered external factors that could influence the efficacy of the capacity development intervention, and few used an explicit systems approach. We used framework synthesis to situate our evidence map within the broader literature on capacity development evaluation. Our evidence map (including a visual heat map) highlights areas of low and high representation in investment in research on the evaluation of capacity development.
Schistosomiasis has been subjected to extensive control efforts in the People's Republic of China (China) which aims to eliminate the disease by 2030. We describe baseline results of a longitudinal cohort study undertaken in the Dongting and Poyang lakes areas of central China designed to determine the prevalence of Schistosoma japonicum in humans, animals (goats and bovines) and Oncomelania snails utilizing molecular diagnostics procedures. Data from the Chinese National Schistosomiasis Control Programme (CNSCP) were compared with the molecular results obtained.
Sixteen villages from Hunan and Jiangxi provinces were surveyed; animals were only found in Hunan. The prevalence of schistosomiasis in humans was 1.8% in Jiangxi and 8.0% in Hunan determined by real-time polymerase chain reaction (PCR), while 18.3% of animals were positive by digital droplet PCR. The CNSCP data indicated that all villages harboured S. japonicum-infected individuals, detected serologically by indirect haemagglutination assay (IHA), but very few, if any, of these were subsequently positive by Kato-Katz (KK).
Based on the outcome of the IHA and KK results, the CNSCP incorporates targeted human praziquantel chemotherapy but this approach can miss some infections as evidenced by the results reported here. Sensitive molecular diagnostics can play a key role in the elimination of schistosomiasis in China and inform control measures allowing for a more systematic approach to treatment.
Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
The assessment of cognitive disorders in schizophrenia is becoming a part of clinical and research practice by using batteries that differ widely in their content. The Brief Assessment of Cognition in Schizophrenia (BACS) was developed to cover the main cognitive deficits of schizophrenia.
The objective of this study was to assess concurrent validity of the Arabic version of the BACS with a standard neurocognitive battery of tests in Lebanese patients with schizophrenia and healthy controls.
A sample of 120 stable inpatients diagnosed with schizophrenia and 60 healthy controls received the Arabic version of the BACS in a first session, and a standard battery in a second session.
The mean duration of completion for the BACS was 31.2 ± 5.4 min in patients with schizophrenia. All tests demonstrated significant differences between controls and patients (p<0.01). A principal components analysis demonstrated that a one-factor solution best fits our dataset (64.8% of the variance). A high Cronbach alpha was found (0.85). The BACS composite scores were significantly correlated with the standard battery composite scores in patients (r=0.78, p < 0.001) and healthy controls (r=0.77, p < 0.001). Also, the correlation analysis between the BACS sub-scores and the standard battery sub-scores showed significant results (p < 0.05). The Arabic-BACS demonstrated high ability to discriminate patients with schizophrenia from healthy controls.
The results showed that the Arabic version of the BACS is a useful tool for assessing cognition in patients with schizophrenia and could be used in clinical practice in Lebanon.
The burden of depression and anxiety is poorly documented in Central African populations.
To present the epidemiology of depressive and anxiety disorders among older people in two Central African countries.
A cross-sectional population-based study was carried out in Republic of Congo (ROC) and Central African Republic (CAR) between 2011 - 2012 among people aged ≥ 65 years (EPIDEMCA study). Data were collected using a standardized questionnaire and participants underwent a brief physical examination. Depression and anxiety symptoms were ascertained using a community version of the Geriatric Mental State (GMS-B3). Probable cases were defined as having a GMS-AGECAT score ≥ 3. Logistic regression models were used to investigate the association between potential risk factors collected and presence of at least one of both symptoms.
Overall 2002 participants were included in the EPIDEMCA study. Median age of the participants was 72 years [interquartile range: 68 – 78 years] and 61.8% were females. Prevalence was 38.1% (95% Confidence Interval: 35.9% - 40.2%) for depression, 7.7% (95% CI: 6.5% - 8.9%) for anxiety. In total 40.1% had least one of both symptoms. In multivariable models, the following factors were associated with the presence of at least one of both symptoms: female sex, residence area, frailty, cognitive disorders, a high happiness score (protective) and hypertension (adjusted Odds Ratios from 1.3 to 1.7; p<0.01).
In light of the high prevalence of both psychiatric symptoms among Central African older people, evidence on their epidemiology is important for better management and policy planning.
Air pollution is linked to mortality and morbidity. Since humans spend nearly all their time indoors, improving indoor air quality (IAQ) is a compelling approach to mitigate air pollutant exposure. To assess interventions, relying on clinical outcomes may require prolonged follow-up, which hinders feasibility. Thus, identifying biomarkers that respond to changes in IAQ may be useful to assess the effectiveness of interventions.
We conducted a narrative review by searching several databases to identify studies published over the last decade that measured the response of blood, urine, and/or salivary biomarkers to variations (natural and intervention-induced) of changes in indoor air pollutant exposure.
Numerous studies reported on associations between IAQ exposures and biomarkers with heterogeneity across study designs and methods. This review summarizes the responses of 113 biomarkers described in 30 articles. The biomarkers which most frequently responded to variations in indoor air pollutant exposures were high sensitivity C-reactive protein (hsCRP), von Willebrand Factor (vWF), 8-hydroxy-2′-deoxyguanosine (8-OHdG), and 1-hydroxypyrene (1-OHP).
This review will guide the selection of biomarkers for translational studies evaluating the impact of indoor air pollutants on human health.
Aggressive behaviour is a highly prevalent and devastating condition in autism spectrum disorder resulting in impoverished quality of life. Gold-standard therapies are ineffective in about 30% of patients leading to greater suffering. We investigated cortical thickness in individuals with autism spectrum disorder with pharmacological-treatment-refractory aggressive behaviour compared with those with non-refractory aggressive behaviour and observed a brain-wide pattern of local increased thickness in key areas related to emotional control and overall decreased cortical thickness in those with refractory aggressive behaviour, suggesting refractoriness could be related to specific morphological patterns. Elucidating the neurobiology of refractory aggressive behaviour is crucial to provide insights and potential avenues for new interventions.
As the primary risk factor for cardiovascular disease (CVD), hypertension is the leading cause of preventable, premature mortality globally. Hypertension, or elevated blood pressure (BP), has a number of well-established risk factors, including genetics. A common C677T polymorphism in the gene encoding the folate metabolising enzyme methylenetetrahydrofolate reductase (MTHFR) affects 10–12% of UK and Irish populations and has been linked with 24–87% increased risk of hypertension globally. Evidence from randomised controlled trials (RCTs) conducted at this Centre has shown BP to be highly responsive (by 5–13 mmHg) to supplementation with riboflavin (MTHFR co-factor), an effect confined to homozygous individuals (TT genotype). To date, our trials have focused on peripheral BP; however, additional measures of vascular health such as central pressure are reported to be more closely correlated with CVD risk. Investigation of central BP, augmentation index (AIx) and pulse pressure amplification (PPA) may thus offer further insight into the role of this gene-nutrient interaction in blood pressure. The present study aims to investigate BP, and measures of vascular health in healthy adults stratified by MTHFR 677 genotype. Apparently healthy adults aged 18–60 years were recruited from workplaces across Northern Ireland and screened for MTHFR genotype via buccal swab. Clinic BP, anthropometry and blood sample were measured in TT individuals (n 209) and age and sex-matched CC (n 98) and CT (n 102) controls. AIx and central BP were assessed using SphygmoCor® (AtCor Medical, Australia). Preliminary results demonstrate higher BP in individuals with the MTHFR 677TT genotype compared to non-TT controls (systolic BP 134.7 ± 13.8 mmHg vs 129.7 ± 12.4 mmHg, P < 0.001; diastolic BP 81.6 ± 9.5 mmHg vs 79.7 mmHg ± 8.9 mmHg, P = 0.023, respectively). The MTHFR 677TT genotype group had significantly higher central systolic BP (119.4 ± 11.8 vs 116.7 ± 10.9 mmHg, P = 0.018), central pulse pressure (P = 0.006) and central mean pressure (P = 0.011) compared to the non-TT group. No significant differences for central diastolic BP, pulse pressure amplification, pulse pressure ratio and augmentation index were observed. This study confirms the phenotype of elevated BP in individuals with the C677T polymorphism in the gene encoding MTHFR. For the first time, this study reports that individuals with the MTHFR 677TT genotype have higher central systolic BP, central mean pressure and pulse pressure. Further investigations through RCTs investigating the effect of the MTHFR cofactor, riboflavin, on central blood pressure in these genetically at-risk adults are warranted.
Vitamin B12 deficiency is common among older adults, even with dietary intakes well in excess of current recommendations. Severe clinical B12 deficiency (i.e. pernicious anaemia) leads to irreversible neurological damage, but once diagnosed, can be treated effectively with B12 injections. A much more common cause of low vitamin B12 status in older adults is food-bound malabsorption owing to atrophic gastritis. This in turn leads to reduced gastric acid secretion, thus limiting B12 absorption from food (given the essential role of gastric acid in releasing B12 from food proteins). Proton pump inhibitor (PPI) drugs reduce gastric acid secretion, similar to atrophic gastritis, thus there is a concern that these medications may lead to vitamin B12 malabsorption. Therefore, the aim of this study was to investigate biomarker status of vitamin B12 in relation to atrophic gastritis and PPI usage. Data were accessed from The Trinity Ulster Department of Agriculture (TUDA) Ageing Cohort Study, a cross-sectional study of community-dwelling adults (n 5186, ≥ 60 years) recruited across Northern Ireland and the Republic of Ireland (2008–2012). TUDA participants were classified into 3 groups; ‘healthy’ controls, atrophic gastritis and PPI users. Vitamin B12 status was assessed using a total of four biomarkers: serum total B12; serum holotranscobalamin, holoTC; plasma methylmalonic acid, MMA; plasma homocysteine. Atrophic gastritis was identified using pepsinogen analysis (via ELISA), with a pepsinogen I : II ratio of < 3 considered indicative of atrophic gastritis. Based on results from all four biomarkers, participants with atrophic gastritis were found to have significantly lower B12 status compared to healthy controls: e.g. mean (95% CI) serum total vitamin B12, 188 (156, 218) pmol/L vs. 262 (252, 272) pmol/L P < 0.001; holoTC, 46.0 (38.1, 53.8) pmol/L vs. 60.3 (57.8, 62.8) pmol/L P < 0.001; plasma MMA, 0.65 (0.52, 0.78) μmol/L vs. 0.37 (0.32, 0.42) μmol/L P = 0.001. No differences in B12 biomarker concentrations were observed between PPI users and healthy controls. Regular consumption of fortified foods (i.e. ≥ 5 portions per week) compared to non-regular consumption (i.e. 0–4 portions per week) impacted positively on B12 biomarker status in all participants. This effect however appeared insufficient to restore normal vitamin B12 status in those with atrophic gastritis. These results show that older adults with atrophic gastritis have significantly lower vitamin B12 biomarker status, particularly in those who did not regularly consume fortified foods. Further investigations of the effect of atrophic gastritis and PPI usage on B12 status are warranted.
Introduction: For rhythm control of acute atrial flutter (AAFL) in the emergency department (ED), choices include initial drug therapy or initial electrical cardioversion (ECV). We compared the strategies of pharmacological cardioversion followed by ECV if necessary (Drug-Shock), and ECV alone (Shock Only). Methods: We conducted a randomized, blinded, placebo-controlled trial (1:1 allocation) comparing two rhythm control strategies at 11 academic EDs. We included stable adult patients with AAFL, where onset of symptoms was <48 hours. Patients underwent central web-based randomization stratified by site. The Drug-Shock group received an infusion of procainamide (15mg/kg over 30 minutes) followed 30 minutes later, if necessary, by ECV at 200 joules x 3 shocks. The Shock Only group received an infusion of saline followed, if necessary, by ECV x 3 shocks. The primary outcome was conversion to sinus rhythm for ≥30 minutes at any time following onset of infusion. Patients were followed for 14 days. The primary outcome was evaluated on an intention-to-treat basis. Statistical significance was assessed using chi-squared tests and multivariable logistic regression. Results: We randomized 76 patients, and none was lost to follow-up. The Drug-Shock (N = 33) and Shock Only (N = 43) groups were similar for all characteristics including mean age (66.3 vs 63.4 yrs), duration of AAFL (30.1 vs 24.5 hrs), previous AAFL (72.7% vs 69.8%), median CHADS2 score (1 vs 1), and mean initial heart rate (128.9 vs 126.0 bpm). The Drug-Shock and Shock only groups were similar for the primary outcome of conversion (100% vs 93%; absolute difference 7.0%, 95% CI -0.6;14.6; P = 0.25). The multivariable analyses confirmed the similarity of the two strategies (P = 0.19). In the Drug-Shock group 21.2% of patients converted with the infusion. There were no statistically significant differences for time to conversion (84.2 vs 97.6 minutes), total ED length of stay (9.4 vs 7.5 hours), disposition home (100% vs 95.3%), and stroke within 14 days (0 vs 0). Premature discontinuation of infusion (usually for transient hypotension) was more common in the Drug-Shock group (9.1% vs 0.0%) but there were no serious adverse events. Conclusion: Both the Drug-Shock and Shock Only strategies were highly effective and safe in allowing AAFL patients to go home in sinus rhythm. IV procainamide alone was effective in only one fifth of patients, much less than for acute AF.
Introduction: Older (age >=65 years) trauma patients suffer increased morbidity and mortality. This is due to under-triage of older trauma victims, resulting in lack of transfer to a trauma centre or failure to activate the trauma team. There are currently no Canadian guidelines for the management of older trauma patients. The objective of this study was to identify modifiers to the prehospital and emergency department (ED) phases of major trauma care for older adults based on expert consensus. Methods: We conducted a modified Delphi study to assess senior-friendly major trauma care modifiers based on national expert consensus. The panel consisted of 24 trauma care providers across Canada, including medical directors, paramedics, emergency physicians, emergency nurses, trauma surgeons and trauma administrators. Following a literature review, we developed an online Delphi survey consisting of 16 trauma care modifiers. Three online survey rounds were distributed and panelists were asked to score items on a 9-point Likert scale. The following predetermined thresholds were used: appropriate (median score 7–9, without disagreement); inappropriate (median score 1–3; without disagreement), and uncertain (any median score with disagreement). The disagreement index (DI) is a method for measuring consensus within groups. Agreement was defined a priori as a DI score <1. Results: There was a 100% response rate for all survey rounds. Three new trauma care modifiers were suggested by panelists. Of 19 trauma care modifiers, the expert panel achieved consensus agreement for 17 items. The prehospital modifier with the strongest agreement to transfer to a trauma centre was a respiratory rate <10 or >20 breaths/minute or needing ventilatory support (DI = 0.24). The ED modifier with the strongest level of agreement was obtaining a 12-lead electrocardiogram following the primary and secondary survey for all older adults (DI = 0.01). Two trauma care modifiers failed to reach consensus agreement: transporting older patients with ground level falls to a trauma centre and activating the trauma team based solely on an age >=65 years. Conclusion: Using a modified Delphi process, an expert panel agreed upon 17 trauma care modifiers for older adults in the prehospital and ED phases of care. These modifiers may improve the delivery of senior-friendly trauma care and should be considered when developing local and national trauma guidelines.
Introduction: Acute heart failure (AHF) is a common emergency department (ED) presentation and may be associated with poor outcomes. Conversely, many patients rapidly improve with ED treatment and may not need hospital admission. Because there is little evidence to guide disposition decisions by ED and admitting physicians, we sought to create a risk score for predicting short-term serious outcomes (SSO) in patients with AHF. Methods: We conducted prospective cohort studies at 9 tertiary care hospital EDs from 2007 to 2019, and enrolled adult patients who required treatment for AHF. Each patient was assessed for standardized real-time clinical and laboratory variables, as well as for SSO (defined as death within 30 days or intubation, non-invasive ventilation (NIV), myocardial infarction, coronary bypass surgery, or new hemodialysis after admission). The fully pre-specified, logistic regression model with 13 predictors (age, pCO2, and SaO2 were modeled using spline functions with 3 knots and heart rate and creatinine with 5 knots) was fitted to the 10 multiple imputation datasets. Harrell's fast stepdown procedure reduced the number of variables. We calculated the potential impact on sensitivity (95% CI) for SSO and hospital admissions and estimated a sample size of 170 SSOs. Results: The 2,246 patients had mean age 77.4 years, male sex 54.5%, EMS arrival 41.1%, IV NTG 3.1%, ED NIV 5.2%, admission on initial visit 48.6%. Overall there were 174 (7.8%) SSOs including 70 deaths (3.1%). The final risk scale is comprised of five variables (points) and had c-statistic of 0.76 (95% CI: 0.73-0.80): 1.Valvular heart disease (1) 2.ED non-invasive ventilation (2) 3.Creatinine 150-300 (1) ≥300 (2) 4.Troponin 2x-4x URL (1) ≥5x URL (2) 5.Walk test failed (2) The probability of SSO ranged from 2.0% for a total score of 0 to 90.2% for a score of 10, showing good calibration. The model was stable over 1,000 bootstrap samples. Choosing a risk model total point admission threshold of >2 would yield a sensitivity of 80.5% (95% CI 73.9-86.1) for SSO with no change in admissions from current practice (48.6% vs 48.7%). Conclusion: Using a large prospectively collected dataset, we created a concise and sensitive risk scale to assist with admission decisions for patients with AHF in the ED. Implementation of this risk scoring scale should lead to safer and more efficient disposition decisions, with more high-risk patients being admitted and more low-risk patients being discharged.
Introduction: An important challenge physicians face when treating acute heart failure (AHF) patients in the emergency department (ED) is deciding whether to admit or discharge, with or without early follow-up. The overall goal of our project was to improve care for AHF patients seen in the ED while avoiding unnecessary hospital admissions. The specific goal was to introduce hospital rapid referral clinics to ensure AHF patients were seen within 7 days of ED discharge. Methods: This prospective before-after study was conducted at two campuses of a large tertiary care hospital, including the EDs and specialty outpatient clinics. We enrolled AHF patients ≥50 years who presented to the ED with shortness of breath (<7 days). The 12-month before (control) period was separated from the 12-month after (intervention) period by a 3-month implementation period. Implementation included creation of rapid access AHF clinics staffed by cardiology and internal medicine, and development of referral procedures. There was extensive in-servicing of all ED staff. The primary outcome measure was hospital admission at the index visit or within 30 days. Secondary outcomes included mortality and actual access to rapid follow-up. We used segmented autoregression analysis of the monthly proportions to determine whether there was a change in admissions coinciding with the introduction of the intervention and estimated a sample size of 700 patients. Results: The patients in the before period (N = 355) and the after period (N = 374) were similar for age (77.8 vs. 78.1 years), arrival by ambulance (48.7% vs 51.1%), comorbidities, current medications, and need for non-invasive ventilation (10.4% vs. 6.7%). Comparing the before to the after periods, we observed a decrease in hospital admissions on index visit (from 57.7% to 42.0%; P <0.01), as well as all admissions within 30 days (from 65.1% to 53.5% (P < 0.01). The autoregression analysis, however, demonstrated a pre-existing trend to fewer admissions and could not attribute this to the intervention (P = 0.91). Attendance at a specialty clinic, amongst those discharged increased from 17.8% to 42.1% (P < 0.01) and the median days to clinic decreased from 13 to 6 days (P < 0.01). 30-day mortality did not change (4.5% vs. 4.0%; P = 0.76). Conclusion: Implementation of rapid-access dedicated AHF clinics led to considerably increased access to specialist care, much reduced follow-up times, and possible reduction in hospital admissions. Widespread use of this approach can improve AHF care in Canada.