Reversal learning in those with early psychosis features contingency-dependent changes in loss response and learning.

INTRODUCTION: People with psychotic disorders commonly feature broad decision-making impairments that impact their functional outcomes. Specific associative/reinforcement learning problems have been demonstrated in persistent psychosis. But these phenotypes may differ in early psychosis, suggesting that aspects of cognition decline over time. METHODS: The present proof-of-concept study examined goal-directed action and reversal learning in controls and those with early psychosis. RESULTS: Equivalent performance was observed between groups during outcome-specific devaluation, and reversal learning at an 80:20 contingency (reward probability for high:low targets). But when the low target reward probability was increased (80:40) those with early psychosis altered their response to loss, whereas controls did not. Computational modelling confirmed that in early psychosis there was a change in punishment learning that increased the chance of staying with the same stimulus after a loss, multiple trials into the future. In early psychosis, the magnitude of this response was greatest in those with higher IQ and lower clinical severity scores. CONCLUSIONS: We show preliminary evidence that those with early psychosis present with a phenotype that includes altered responding to loss and hyper-adaptability in response to outcome changes. This may reflect a compensatory response to overcome the milieu of corticostriatal changes associated with psychotic disorders.

Impairments in goal-directed action and reversal learning in a proportion of individuals with psychosis.

Cognitive impairment in psychosis is one of the strongest predictors of functional decline. Problems with decision-making processes, such as goal-directed action and reversal learning, can reflect cortico-striatal dysfunction. The heterogenous symptoms and neurobiology observed in those with psychosis suggests that specific cognitive phenotypes may reflect differing causative mechanisms. As such, decision-making performance could identify subgroups of individuals with more severe cortico-striatal dysfunction and help to predict their functional decline. The present work evaluated the relationship between goal-directed action, reversal learning, and symptom profiles in those with psychosis. We assessed decision-making processes in healthy controls (N = 34) and those with persistent psychosis (N = 45), subclassifying subjects based on intact/impaired goal-directed action. Compared with healthy controls (<20%), a large proportion (58%) of those with persistent psychosis displayed impaired goal-directed action, predicting poor serial reversal learning performance. Computational approaches indicated that those with impaired goal-directed action had a decreased capacity to rapidly update their prior beliefs in the face of changing contingencies. Impaired decision-making also was associated with reduced levels of grandiosity and increased problems with abstract thinking. These findings suggest that prominent decision-making deficits, indicative of cortico-striatal dysfunction, are present in a large proportion of people with persistent psychosis. Moreover, these impairments would have significant functional implications in terms of planning and abstract thinking.

Predictors of Laryngospasm During 276,832 Episodes of Pediatric Procedural Sedation.

STUDY OBJECTIVE: Laryngospasm is a rare but potentially life-threatening complication of sedation. The objective of this study was to perform a predictor analysis of biologically plausible predictors and the interventions and outcomes associated with laryngospasm. METHODS: Secondary analysis of prospectively collected data from consecutively sedated patients, less than or equal to 22 years of age, at multiple locations at 64 member institutions of the Pediatric Sedation Research Consortium. The primary outcome was laryngospasm. The independent variables in the multivariable model included American Society of Anesthesiologists category, age, sex, concurrent upper respiratory infection, medication regimen, hospital sedation location, whether the procedure was painful, and whether the procedure involved the airway. The analysis included adjusted odds ratios (aORs) and predicted probabilities. RESULTS: We analyzed 276,832 sedations with 913 reported events of laryngospasm (overall unadjusted prevalence 3.3:1,000). A younger age, a higher American Society of Anesthesiologists category, a concurrent upper respiratory infection (aOR 3.94, 2.57 to 6.03; predicted probability 12.2/1,000, 6.3/1,000 to 18.0/1,000), and airway procedures (aOR 3.73, 2.33 to 5.98; predicted probability 9.6/1,000, 5.2/1,000 to 13.9/1,000) were associated with increased risk. Compared with propofol alone, propofol combination regimens had increased risk (propofol+ketamine: aOR 2.52, 1.41 to 4.50; predicted probability 7.6/1,000, 3.1/1,000 to 12/1,000; and propofol+dexmedetomidine: aOR 2.10, 1.25 to 3.52; predicted probability 6.3/1,000, 3.7,/1,000 to 8.9/1,000). Among patients with laryngospasm, the resulting outcomes included desaturation less than 70% for more than 30 seconds (19.7%), procedure not completed (10.6%), emergency airway intervention (10.0%), endotracheal intubation (5.3%), unplanned admission/increase in level of care (2.3%), aspiration (1.1%), and cardiac arrest (0.2%). CONCLUSION: We found increased associations of laryngospasm in pediatric procedural sedation with multiple biologic factors, procedure types, and medication regimens. However, effect estimates showed that the laryngospasm prevalence remained low, and this should be taken into consideration in sedation decisionmaking.

CoMET: a randomised controlled trial of co-commencement of metformin versus placebo as an adjunctive treatment to attenuate weight gain in patients with schizophrenia newly commenced on clozapine.

BACKGROUND: There is limited evidence on interventions to minimise weight gain at clozapine commencement. We compared the effect of adjunctive metformin versus placebo at clozapine initiation. METHODS: People with schizophrenia commencing on clozapine were randomised to either metformin or placebo for 24 weeks. The primary outcome was difference in the change of body weight. Secondary outcomes included comparative rates of weight gain of more than 5%, overall weight gain/loss, and differences in metabolic and psychosis outcomes. RESULTS: The study was closed prematurely in March 2020 due to COVID-19 restrictions. Ten participants were randomised to each of the metformin and placebo groups. Eight metformin group and five placebo group participants completed the trial and were included in the analysis. The study was insufficiently powered to detect difference between the metformin and placebo groups for the primary outcome of change in weight (0.09 kg vs 2.88 kg, p = 0.231). In terms of secondary outcomes, people in the metformin group were significantly less likely to gain >5% of their body weight (12.5% vs 80%, p = 0.015) and were more likely to lose weight (37.5% vs 0% p = 0.024) compared to placebo. There was no difference between the groups in terms of adverse drug reactions (ADRs). CONCLUSION: While limited by the forced premature closure of the trial due to COVID19, the findings from this randomised controlled trial are promising. Clozapine and metformin co-commencement may be a promising treatment to prevent clozapine-associated weight gain, especially given the low rates of ADRs associated with metformin. This supports the consideration of use of metformin to prevent weight gain in people initiated on clozapine; however, further studies are needed to confirm this finding. TRIAL REGISTRATION: ACTRN12617001547336.

Metformin reduces 12-month change in body weight among people newly commenced on clozapine: a retrospective naturalistic cohort study.

BACKGROUND: People with schizophrenia have a 15-20-year reduction in life expectancy, driven in part by the metabolic effects of antipsychotics. Clozapine is associated with the highest rates of weight gain. As clozapine remains the most effective antipsychotic for treatment-resistant schizophrenia (TRS), identifying treatments to ameliorate clozapine-induced weight gain (CIWG) is urgently needed to reduce this morality gap. METHODS: We retrospectively analysed digital health records of patients with TRS aged 18-65 newly initiated on clozapine at four tertiary hospitals in south-east Queensland from 1 March 2017 to 30 June 2019. Our primary outcome was the effect of metformin on change in percentage bodyweight at 12 months after clozapine initiation, with secondary outcome being proportion with >5% or >7% bodyweight change. We also explored impact on bodyweight change of other variables including sex, tobacco smoking, type 2 diabetes (T2DM), age, clozapine level and dose and clozapine/norclozapine ratio. RESULTS: Among 90 patients initiated on clozapine, metformin use (n = 48) was associated with a smaller increase in percentage bodyweight (1.32% versus 5.95%, p = 0.031), lower rates of >7% gain in bodyweight (37.8% versus 63.0%, p = 0.025) but not >5% gain in bodyweight. Age below the median (32.0 years) was associated with greater bodyweight gain (5.55% versus 1.22%, p = 0.046). Sex, tobacco smoking, T2DM, clozapine dose and level and clozapine/norclozapine ratio were not associated with differences in change in bodyweight. CONCLUSION: In this small retrospective cohort study, use of metformin within 12-months of clozapine initiation was associated with a statistically and clinically significant reduction in CIWG. Although there is increasing evidence for the role of metformin to ameliorate bodyweight gain at time of clozapine initiation, our findings need replication and testing in a randomised controlled trial before recommending metformin co-commencement with clozapine as standard clinical practice.

Characterizing T cell subsets in the nasal mucosa of children with acute respiratory symptoms.

BACKGROUND: In infants admitted to an ICU with respiratory failure, there is an association between the ratio of CD8+ to CD4+ T cells within the upper respiratory tract and disease severity. Whether this ratio is associated with respiratory disease severity within children presenting to a pediatric emergency department is not known. METHODS: We studied a convenience sample of 63 children presenting to a pediatric emergency department with respiratory symptoms. T cell subsets in the nasal mucosa were analyzed by flow cytometry. We compared CD4+ and CD8+ T cells subsets in these samples and analyzed the proportion of these subsets that expressed markers associated with tissue residency. RESULTS: We were able to identify major subsets of CD8 and CD4 T cells within the nasal mucosa using flocked swabs. We found no difference in the ratio CD8+ to CD4+ T cells in children with upper or lower respiratory illness. A positive association between tissue-resident memory T cell frequency and patient age was identified. CONCLUSIONS: In our patient populations, the CD8+:CD4+ ratio was not associated with disease severity. The majority of T cells collected on nasal swabs are antigen experienced, and there is an association between the frequency of tissue-resident T cells and age. IMPACT: Immune cell populations from the nasal mucosa can be captured using flocked nasal swabs and analyzed by flow cytometry. Nasal CD8+:CD4+ ratio does not predict respiratory illness severity in children presenting to the emergency department. The frequency of CD8+ and CD4+ resident memory T cells within the nasal mucosa increases with age.

The Administration of Postintubation Sedation in the Pediatric Emergency Department.

BACKGROUND: The administration of postintubation sedation (PIS) is an essential component of postintubation care. Recent studies in the adult emergency medicine literature have highlighted both delays in time to administration of PIS and subtherapeutic dosing of sedative agents in the emergency department. We aimed to investigate the administration of PIS in the pediatric population as this has not been adequately reviewed to date. OBJECTIVES: The aim of this study was to determine the percentage of pediatric emergency department patients who received PIS within an adequate time frame. We also investigated the relationship between this primary outcome and the rapid sequence intubation (RSI) agents used, the reason for intubation, and individual patient characteristics. METHODS: This was a retrospective cohort analysis of all pediatric patients who underwent RSI at a tertiary care pediatric emergency department from July 2007 to January 2016. The primary outcome of "sedation in an adequate time frame" was defined as a time to post-RSI sedative administration that was shorter than the duration of action of the RSI sedative agent used. Logistic regression was performed to identify predictors of adequate sedation. RESULTS: A total of 240 patients were included in the analysis. Of these, 28% (95% confidence interval, 22.7%-34.1%) met the primary outcome of sedation within an adequate time frame; 72.8% (95% confidence interval, 66.8%-78.1%) of patients received some form of PIS during their emergency department stay. Patients receiving long-acting paralytic agents were much less likely to receive PIS with an odds ratio (OR) of 0.16 for meeting the primary outcome (P < 0.001, adjusted OR [AOR] = 0.13, P < 0.001). Children with higher systolic blood pressure were more likely to receive appropriate PIS with an OR of 1.02 for every mm Hg increase in systolic blood pressure (P = 0.006, AOR = 1.02, P = 0.021). Finally, patients who were ultimately admitted to the pediatric intensive care unit (vs the operating room, transfer, or neonatal intensive care unit) were less likely to receive PIS as evidenced by an OR of 0.37 (P = 0.009, AOR = 0.27, P = 0.004). CONCLUSIONS: Most pediatric patients do not receive PIS within an adequate time frame. Patients who receive long-acting paralytic agents are much less likely to be adequately sedated after RSI compared with those receiving succinylcholine.

Co-morbidity between mood and anxiety disorders: A systematic review and meta-analysis.

There is consistent evidence that mood disorders often co-occur with anxiety disorders, however, the strength of the association of these two broad groups of disorders has been challenging to summarize across different studies. The aim was to conduct a meta-analysis of publications reporting on the pairwise comorbidity between mood and anxiety disorders after sorting into comparable study types. We searched MEDLINE, Embase, CINAHL, Web of Science, and the grey literature for publications between 1980 and 2017 regardless of geographical locations and languages. We meta-analyzed estimates from original articles after sorting by: (a) broad or narrow diagnostic criteria, (b) study time-frame, and (c) estimates with or without covariate adjustments. Over 43 000 unique studies were identified through electronic searches, of which 391 were selected for full-text review. Finally, 171 studies were eligible for inclusion, including 53 articles from additional snowball searching. In general, regardless of variations in diagnosis type, study time-frame, temporal order, or use of adjustments, there was substantial comorbidity between mood and anxiety disorders. Based on the entire 90 separate meta-analyses, the median OR was 6.1 (range 1.5-18.7). Of these estimates, all 90 were above 1, and 87 were significantly greater than 1 (i.e., the 95% confidence intervals did not include 1). Fourteen of the 90 pooled estimates had ORs that were greater than 10. This systematic review found robust and consistent evidence of comorbidity between broadly defined mood and anxiety disorders. Clinicians should be vigilant for the prompt identification and treatment of this common type of comorbidity.

Safety and effectiveness of intranasal midazolam and fentanyl used in combination in the pediatric emergency department.

OBJECTIVE: To examine the safety and effectiveness of intranasal midazolam and fentanyl used in combination for laceration repair in the pediatric emergency department. METHODS: We performed a retrospective chart review of a random sample of 546 children less than 18 years of age who received both intranasal midazolam and fentanyl for laceration repair in the pediatric emergency department at a large, urban children's hospital. Records were reviewed from April 1, 2012 to June 31, 2015. The primary outcome measures were adverse events and failed laceration repair. RESULTS: Of the 546 subjects analyzed, 5.1% had multiple lacerations. Facial lacerations were the most common site representing 70.3%, followed by lacerations to the hand (9.9%) and leg (7.0%). The median length of lacerations was 1.5 cm [1.0-2.5]. The median dose of fentanyl was 2.0 µg/kg [1.9-2.0] and midazolam was 0.2 mg/kg [0.19-0.20]. There were no serious adverse events reported. The rate of minor side effects was 0.7% (95% CI 0.2% to 1.9%); 0.5% (95% CI 0.1% to 1.6%) experienced anxiety and 0.2% (95% CI 0.0% to 1.0%) vomited. No patients developed hypotension or hypoxia. Of the 546 patients, 2.4% (95% CI 1.3% to 4.0%) experienced a treatment failure. 2.0% (95% CI 1.3% to 4.0%) required IV sedation and 0.4% (95% CI 0.0% to 1.3%) were repaired in the operating room. CONCLUSIONS: Our results suggest that the combination of INM and INF may be a safe and effective strategy for procedural sedation in young children undergoing simple laceration repair.

Early survival following in utero myocardial infarction.

Intrauterine myocardial infarction is a rare and frequently fatal diagnosis. It has been presented in the literature only as case reports and short series. We present a case report of a coronary occlusive intrauterine myocardial infarction and survival and present a systematic review of the literature. This is the first summative description of current data on intrauterine and perinatal myocardial infarction. We performed the systematic review based on the guidelines established by the PRISMA statement. Our population of intrauterine and perinatal myocardial infarction included published cases who presented as a live birth within the first 28 postnatal days, and had a diagnosis of myocardial infarction. We conducted descriptive statistics and regression analysis on short-term mortality as the primary outcome. After applying exclusion criteria we described 84 individual cases of myocardial infarction from 63 full-text articles including our own case. Presentation within the first 12 hours was associated with mortality (OR 3.90, p=0.004). Treatment modalities were varied and inconsistently recorded. The aetiologies and comorbidities are varied in our systematic review. We would have a low threshold to perform viral testing, consider anticoagulation early and coronary imaging if feasible. The use of extracorporeal membranous oxygenation may serve as a bridge to cardiac recovery.

Improved Diagnosis and Treatment of Bone and Joint Infections Using an Evidence-based Treatment Guideline.

BACKGROUND: Our institution created a multidisciplinary guideline for treatment of acute hematogenous osteomyelitis (AHO) and septic arthritis (SA) in response to updates in evidence-based literature in the field and existing provider variability in treatment. This guideline aims to improve the care of these patients by standardizing diagnosis and treatment and incorporating up to date evidence-based research into practice. The primary objective of this study is to compare cases before versus after the implementation of the guideline to determine concrete effects the guideline has had in the care of patients with AHO and SA. METHODS: This is an Institutional Review Board-approved retrospective study of pediatric patients age 6 months to 18 years hospitalized between January 2009 and July 2016 with a diagnosis of AHO or SA qualifying for the guideline. Cohorts were categorized: preguideline and postguideline. Exclusion criteria consisted of: symptoms >14 days, multifocal involvement, hemodynamic instability, sepsis, or history of immune deficiency or chronic systemic disease. Cohorts were compared for outcomes that described clinical course. RESULTS: Data were included for 117 cases that qualified for the guideline: 54 preguideline and 63 postguideline. Following the successful implementation of the guideline, we found significant decrease in the length of intravenous antibiotic treatment (P<0.001), decrease in peripherally inserted central catheter use (P<0.001), and an increase in bacterial identification (P=0.040). Bacterial identification allowed for targeted antibiotic therapy. There was no change in length of hospital stay or readmission rate after the implementation of the guideline. CONCLUSION: Utilizing an evidence-based treatment guideline for pediatric acute hematogenous bone and joint infections can lead to improved bacterial diagnosis and decreased burden of treatment through early oral antibiotic use. LEVEL OF EVIDENCE: Level III- retrospective comparative study.

The personal and workplace characteristics of uninsured expatriate males in Saudi Arabia.

BACKGROUND: A major concern by the health decision makers in Gulf Cooperative Council (GCC) countries is the burden of financing healthcare. While other GCC countries have been examining different options, Saudi Arabia has endeavoured to reform its private healthcare system and control expatriate access to government resources through the provision of Compulsory Employment-Based Health Insurance (CEBHI). The objective of this research was to investigate, in a natural setting, the characteristics of uninsured expatriates based on their personal and workplace characteristics. METHODS: Using a cross-sectional survey, data were collected from a sample of 4,575 male expatriate employees using a multi-stage stratified cluster sampling technique. Descriptive statistics were used to summarize all variables, and the dependent variable was tabulated by access to health insurance and tested using Chi-square. Logistic analysis was performed, guided by the conceptual model. RESULTS: Of survey respondents, 30% were either uninsured or not yet enrolled in a health insurance scheme, 79.4% of these uninsured expatriates did not have valid reasons for being uninsured, with Iqama renewal accounting for 20.6% of the uninsured. The study found both personal and workplace characteristics were important factors influencing health insurance status. Compared with single expatriates, married expatriates (accompanied by their families) are 30% less likely to be uninsured. Moreover, workers occupying technical jobs requiring high school level of education or above were two-thirds more likely to be insured compared to unskilled workers. With regard to firm size, respondents employed in large companies (more than 50 employees) are more likely to be insured compared to those employed in small companies (less than ten employees). In relation to business type, the study found that compared to workers from the agricultural sector, industrial/manufacturing, construction and trading sectors, workers were, respectively, 76%, 85%, and 60% less likely to be uninsured. CONCLUSION: Although the CEBHI is mandatory, this study found that the characteristics of uninsured expatriates, in respect of their personal and workplace characteristics have similarities with the uninsured from other private employment-sponsored health insurance schemes. Other factors influencing access to health insurance, besides employee and workplace characteristics, include the development and extent of the country's insurance industry.

Financing healthcare in Gulf Cooperation Council countries: a focus on Saudi Arabia.

BACKGROUND: This paper presents an analysis of the main characteristics of the Gulf Cooperation Council's (GCC) health financing systems and draws similarities and differences between GCC countries and other high-income and low-income countries, in order to provide recommendations for healthcare policy makers. The paper also illustrates some financial implications of the recent implementation of the Compulsory Employment-based Health Insurance (CEBHI) system in Saudi Arabia. METHODS: Employing a descriptive framework for the country-level analysis of healthcare financing arrangements, we compared expenditure data on healthcare from GCC and other developing and developed countries, mostly using secondary data from the World Health Organization health expenditure database. The analysis was supported by a review of related literature. RESULTS: There are three significant characteristics affecting healthcare financing in GCC countries: (i) large expatriate populations relative to the national population, which leads GCC countries to use different strategies to control expatriate healthcare expenditure; (ii) substantial government revenue, with correspondingly high government expenditure on healthcare services in GCC countries; and (iii) underdeveloped healthcare systems, with some GCC countries' healthcare indicators falling below those of upper-middle-income countries. CONCLUSION: Reforming the mode of health financing is vital to achieving equitable and efficient healthcare services. Such reform could assist GCC countries in improving their healthcare indicators and bring about a reduction in out-of-pocket payments for healthcare.

Cost-effectiveness of community-based strategies for blood pressure control in a low-income developing country: findings from a cluster-randomized, factorial-controlled trial.

BACKGROUND: Evidence on economically efficient strategies to lower blood pressure (BP) from low- and middle-income countries remains scarce. The Control of Blood Pressure and Risk Attenuation (COBRA) trial randomized 1341 hypertensive subjects in 12 randomly selected communities in Karachi, Pakistan, to 3 intervention programs: (1) combined home health education (HHE) plus trained general practitioner (GP); (2) HHE only; and (3) trained GP only. The comparator was no intervention (or usual care). The reduction in BP was most pronounced in the combined group. The present study examined the cost-effectiveness of these strategies. METHODS AND RESULTS: Total costs were assessed at baseline and 2 years to estimate incremental cost-effectiveness ratios based on (1) intervention cost; (2) cost of physician consultation, medications, diagnostics, changes in lifestyle, and productivity loss; and (3) change in systolic BP. Precision of the incremental cost-effectiveness ratio estimates was assessed by 1000 bootstrapping replications. Bayesian probabilistic sensitivity analysis was also performed. The annual costs per participant associated with the combined HHE plus trained GP, HHE alone, and trained GP alone were $3.99, $3.34, and $0.65, respectively. HHE plus trained GP was the most cost-effective intervention, with an incremental cost-effectiveness ratio of $23 (95 confidence interval, 6-99) per mm Hg reduction in systolic BP compared with usual care, and remained so in 97.7 of 1000 bootstrapped replications. CONCLUSIONS: The combined intervention of HHE plus trained GP is potentially affordable and more cost-effective for BP control than usual care or either strategy alone in some communities in Pakistan, and possibly other countries in Indochina with similar healthcare infrastructure.

Cost of diabetes care in out-patient clinics of Karachi, Pakistan.

BACKGROUND: Diabetes Mellitus (DM) is a growing epidemic and the cost of treating diabetes is largely increasing. The objective of this study was to estimate the cost-of-illness of DM among attendees of out-patient clinics in Karachi, Pakistan. This is the first study conducted from a societal perspective to estimate the cost of managing diabetes in Pakistan. METHODS: A prevalence-based 'Cost-of-Illness' study for diabetes care was conducted in six different out-patient clinics of Karachi, Pakistan from July to September 2006. A pre-tested questionnaire was administered to collect the data from 345 randomly selected persons with diabetes. RESULTS: The annual mean direct cost for each person with diabetes was estimated to be Pakistani rupees 11,580 (US$ 197). Medicines accounted for the largest share of direct cost (46%), followed by laboratory investigations (32%). We found that increased age, the number of complications and longer duration of the disease significantly increase the burden of cost on society (p < 0.001). Comparing cost with family income it was found that the poorest segment of society is spending 18% of total family income on diabetes care. CONCLUSION: This study concluded that substantial expenditure is incurred by people with diabetes; with the implication that resources could be saved by prevention, earlier detection and a reduction in diabetes co-morbidities and complications through improved diabetes care. Large scale and cost-effective prevention programs need to be initiated to maximise health gains and to reverse the advance of this epidemic.

Choosing the best estimate of gestational age from routinely collected population-based perinatal data.

Obtaining gestational data of acceptable validity on whole populations is a considerable challenge, which must be met in order to further epidemiological investigation involving perinatal factors. As the means of estimating gestational duration multiply, routinely available population data pertaining to gestational duration may be conflicting. This exacerbates its reputation for unreliability, which is due primarily to the generally occult nature of conception and secondly to the propensity for data entry errors of the data from which gestational duration is estimated. However, the key to improving reliability may paradoxically lie in the increasing variety of methods for estimating gestational duration, because agreement between independent observations increases the reliability that can be placed on estimates of factors that are inherently difficult to measure. This paper demonstrates that the acceptability of population data for gestational duration can be improved by simple rectification of recurring data entry errors and demanding compatibility of two independent estimates of gestational duration. Compared with the previous algorithm that relied primarily on last menstrual period data, the new algorithm, that considers both antenatal and neonatal indicators of gestational duration, decreased the proportion of births in a geographically defined birth cohort 1986-99 (n=354,216) without a gestational estimate, from 0.5% to 0.03%, halved the number of births of >400 g estimated to occur before 20 weeks, and almost eliminated gestational estimates of >45 weeks.

The threat of climate change to freshwater pearl mussel populations.

Changes in climate are occurring around the world and the effects on ecosystems will vary, depending on the extent and nature of these changes. In northern Europe, experts predict that annual rainfall will increase significantly, along with dramatic storm events and flooding in the next 50-100 years. Scotland is a stronghold of the endangered freshwater pearl mussel, Margaritifera margaritifera (L.), and a number of populations may be threatened. For example, large floods have been shown to adversely affect mussels, and although these stochastic events were historically rare, they may now be occurring more often as a result of climate change. Populations may also be affected by a number of other factors, including predicted changes in temperature, sea level, habitat availability, host fish stocks and human activity. In this paper, we explain how climate change may impact M. margaritifera and discuss the general implications for the conservation management of this species.