Stella M. Gwini

Influenza vaccination, pneumococcal vaccination and risk of acute myocardial infarction: matched case–control study

Background: Previous studies have shown an association between acute myocardial infarction and preceding respiratory infection. Contradictory evidence exists on the influence of influenza vaccination and pneumococcal vaccination in preventing cardiovascular disease. We aimed to investigate the possible association of influenza vaccination and pneumococcal vaccination with acute myocardial infarction. Methods: We used a matched case–control design with data from the United Kingdom General Practice Research Database. Cases were patients who were at least 40 years of age at diagnosis of first acute myocardial infarction recorded from Nov.1, 2001, to May 31, 2007, and were matched for sex, general practice, age and calendar time (i.e., month corresponding to index date of acute myocardial infarction), with up to four controls each. Data were analyzed using conditional logistic regression, adjusted for vaccination target groups, cardiovascular risk factors, treatment medications and attendances at a general practice. Results: We included 78 706 patients, of whom 16 012 were cases and 62 694 were matched controls. Influenza vaccination had been received in the previous year by 8472 cases (52.9%) and 32 081 controls (51.2%) and was associated with a 19% reduction in the rate of acute myocardial infarction (adjusted odds ratio [OR] 0.81, 95% confidence interval [CI] 0.77–0.85). Early seasonal influenza vaccination was associated with a lower rate of acute myocardial infarction (adjusted OR 0.79, 95% CI 0.75–0.83) than vaccination after mid-November (adjusted OR 0.88, 95% CI 0.79–0.97). Pneumococcal vaccination was not associated with a reduction in the rate of acute myocardial infarction (adjusted OR 0.96, 95% CI 0.91–1.02). Interpretation: Influenza vaccination but not pneumococcal vaccination is associated with a reduced rate of first acute myocardial infarction. This association and the potential benefit of early seasonal vaccination need to be considered in future experimental studies.

The effect of influenza vaccination on risk of acute myocardial infarction: self-controlled case-series study.

Acute myocardial infarction (AMI) peaks in winter months, partly linked to epidemic influenza. This implies that influenza vaccination may prevent some cases of AMI. This study investigated the association between influenza vaccination and AMI using the self-controlled case-series method. We identified 8180 cases of first AMI aged 40 years and over at time of diagnosis. The incidence of AMI was significantly reduced in the 60 days following vaccination (compared with the baseline period), ranging from a reduction of 32% (IRR 0.68; 95% CI 0.60-0.78) at 1-14 days after vaccination, to 18% (IRR 0.82; 95% CI 0.75-0.90) at 29-59 days after vaccination. Reductions in AMI incidence were more pronounced for early seasonal vaccinations before mid-November.

Effect of Adjunctive Raloxifene Therapy on Severity of Refractory Schizophrenia in Women: A Randomized Clinical Trial

IMPORTANCE A substantial proportion of women with schizophrenia experience debilitating treatment-refractory symptoms. The efficacy of estrogen in modulating brain function in schizophrenia has to be balanced against excess exposure of peripheral tissue. Raloxifene hydrochloride is a selective estrogen receptor modulator (mixed estrogen agonist/antagonist) with potential psychoprotective effects and fewer estrogenic adverse effects. OBJECTIVE To determine whether adjunctive raloxifene therapy reduces illness severity in women with refractory schizophrenia. DESIGN, SETTING, AND PARTICIPANTS This 12-week, double-blind, placebo-controlled, randomized clinical trial with fortnightly assessments was performed at an urban tertiary referral center and a regional center from January 1, 2006, to December 31, 2014. Participants included 56 women with schizophrenia or schizoaffective disorder and marked symptom severity despite substantial and stable antipsychotic doses. Data were analyzed using intention to treat as the basis. INTERVENTIONS Adjunctive raloxifene hydrochloride, 120 mg/d, or placebo for 12 weeks. MAIN OUTCOMES AND MEASURES The primary outcome was the change in the Positive and Negative Syndrome Scale (PANSS) total score. Clinical response (defined as a ≥20% decrease in PANSS total score from baseline) and change in PANSS subscale scores, mood, cognition, reproductive hormone levels, and adverse events were also assessed. RESULTS Of the 56 participants (mean [SD] age, 53 [7.7] years; age range, 40-70 years; mean [SD] duration of psychotic illness, 24 [11] years), 26 were randomized to raloxifene and 30 were randomized to placebo. Raloxifene produced a greater reduction in the PANSS total score relative to placebo (β = -6.37; 95% CI, -11.64 to -1.10; P = .02) and resulted in an increased probability of a clinical response (hazard ratio, 5.79; 95% CI, 1.46 to 22.97; P = .01). A significant reduction was found in the PANSS general symptom scores for the raloxifene compared with the placebo (β = -3.72; 95% CI, -6.83 to -0.61; P = .02) groups. For patients who completed the full 12-week trial, there was not a statistically significant treatment effect on PANSS positive symptom scores (β for change in raloxifene vs placebo, -1.92; 95% CI, -3.83 to 0.00; P = .05). Change in mood, cognition, and reproductive hormone levels and the rate of adverse events did not differ between groups. CONCLUSIONS AND RELEVANCE Raloxifene hydrochloride, 120 mg/d, reduces illness severity and increases the probability of a clinical response in women with refractory schizophrenia. This large trial of raloxifene in this patient population offers a promising, well-tolerated agent that has potential application in clinical practice. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00361543.

09 Can older people who fall be identified in the ambulance call centre to enable alternative responses or care pathways

Background Older people who fall make up a substantial proportion of the 999 workload. They are a particularly vulnerable group who may benefit from referral to specialised community based falls services. This requires early identification, ideally from dispatch codes assigned in the ambulance call centre. Objective To assess the feasibility of using information given during 999 calls to identify older people who fall and who may benefit from an alternative response. Methods We examined all records of patients aged 65 years and over during 2008 in the Nottinghamshire area and identified those recorded as having fallen by attending crews. Dispatch codes were recorded for all cases and the utility of the dispatch code ‘Fall without priority symptoms’ (AMPDS 17) for identifying older people who had fallen was assessed. Results From 56 584 emergency (999) calls recorded, including 8119 for patients aged 65 years and over, 3246 (40%) cases were recorded as a fall. Of these, 2186 (67%) had been allocated AMPDS code 17 at dispatch (true positives), and 413 (13%) had not (false negatives), with 647 unknowns. Of 4871 cases not categorised as a fall by attending crews, 175 (4%) had been allocated an AMPDS code 17 (false positives), and 3315 (68%) had been given other codes (true negatives), with 1381 unknowns. The dispatch code AMPDS 17 had a sensitivity of 84% and a specificity of 95% for identifying falls compared with categorisation by crews. Limitations Definition of a fall is not always clear and there may be variations in usage of the category by crews. There was a high level of missing data in this study. Conclusion A large majority of older people who fall and for whom a 999 call is made can be identified in the ambulance call centre using dispatch codes. This provides a means for rapid and effective targeting of alternative responses to these patients, thereby potentially improving processes and outcomes of care.

Multisymptom Illness in Gulf War Veterans: A Systematic Review and Meta-Analysis.

Objective: The aim of this study was to conduct a systematic review and meta-analysis of multisymptom illness (MSI) in 1990 to 1991 Gulf/Afghanistan/Iraq War veterans. Methods: Electronic databases were searched from January 1990, June 2014 for studies on MSI prevalence in Gulf/Afghanistan/Iraq War veterans, based on the Centers for Disease Control and Prevention MSI case definition, and which included a military comparison group. Results: Seven studies were identified among US, UK, and Australian Gulf War veterans; no studies were identified in Afghanistan/Iraq War veterans. MSI prevalence in Gulf War veterans and comparison groups ranged from 26 to 65% and from 12 to 37%, respectively. More recent studies were larger, with improved designs. The pooled odds ratio comparing Gulf War veterans to other military groups was 2.74 (95% confidence interval 2.15 to 3.51). Conclusion: The systematic review showed that MSI was most prevalent in Gulf War veterans, emphasizing the health burden of MSI in this veteran population.

Increased symptom reporting persists in 1990–1991 Gulf War veterans 20 years post deployment

BACKGROUND Following the 1990-1991 Gulf War, Gulf War veterans (veterans) reported health symptoms more commonly than non-deployed groups. This article examines symptom persistence, incidence and prevalence 20 years on. METHODS In 2000-2003 and 2011-2012, a 63-item symptom checklist was administered to 697 veterans and 659 comparison group. Symptomatology was compared using log-binomial regression. RESULTS Both veterans and comparison group reported significantly increased prevalence (3-52%) over time in more than half the symptoms, with a similar overall rate of increase. Half the symptoms had higher incidence (risk-ratios ranged 1.43-1.50) and a quarter were more persistent (risk-ratios ranged 1.12-1.20) in veterans than the comparison group. CONCLUSIONS Symptomatology increased in both groups over time, but persisted to a similar extent and had higher incidence among veterans than the comparison group. The gap in symptom prevalence between the two groups remained unchanged. These findings suggest enduring health consequences of Gulf War service.

Traumatic injury and perceived injustice: Fault attributions matter in a “no-fault” compensation state

Background Traumatic injury can lead to loss, suffering and feelings of injustice. Previous research has shown that perceived injustice is associated with poorer physical and mental wellbeing in persons with chronic pain. This study aimed to identify the relative association between injury, compensation and pain-related characteristics and perceived injustice 12-months after traumatic injury. Methods 433 participants were recruited from the Victorian Orthopedic Trauma Outcomes Registry and Victorian State Trauma Registry, and completed questionnaires at 12–14 months after injury as part of an observational cohort study. Using hierarchical linear regression we examined the relationships between baseline demographics (sex, age, education, comorbidities), injury (injury severity, hospital length of stay), compensation (compensation status, fault, lawyer involvement), and health outcomes (SF-12) and perceived injustice. We then examined how much additional variance in perceived injustice was related to worse pain severity, interference, self-efficacy, catastrophizing, kinesiophobia or disability. Results Only a small portion of variance in perceived injustice was related to baseline demographics (especially education level), and injury severity. Attribution of fault to another, consulting a lawyer, health-related quality of life, disability and the severity of pain-related cognitions explained the majority of variance in perceived injustice. While univariate analyses showed that compensable injury led to higher perceptions of injustice, this did not remain significant when adjusting for all other factors, including fault attribution and consulting a lawyer. Conclusions In addition to the “justice” aspects of traumatic injury, the health impacts of injury, emotional distress related to pain (catastrophizing), and the perceived impact of pain on activity (pain self-efficacy), had stronger associations with perceptions of injustice than either injury or pain severity. To attenuate the likelihood of poor recovery from injury, clinical interventions that support restoration of health-related quality of life, and adjustment to the impacts of trauma are needed.

Major depression and depressive symptoms in Australian Gulf War veterans 20 years after the Gulf War.

BACKGROUND Risk of major depression (depression) was elevated in Australias Gulf War veterans in a 2000-2002 (baseline) study. A follow up study has measured the Gulf War-related risk factors for depression, also the current prevalence and severity of depression, use of anti-depressant medication, and persistence, remittance or incidence of depression since baseline in Gulf War veterans and a military comparison group. METHODS Participants completed the Composite International Diagnostic Interview v.2.1, the 9-item Patient Health Questionnaire and the Military Service Experience Questionnaire, and consented to Repatriation Pharmaceutical Benefits Scheme (RPBS) and PBS linkage. RESULTS Prevalence of depression (9.7% Gulf War veterans and 7.7% comparison group; adj RR=1.2, 95% CI 0.8-1.7), and pattern of persistence, remittance and incidence of depression since baseline, were similar in the two groups, however veterans reported slightly more severe symptoms (adj median difference 1, 95% CI 0.26-1.74) and were more likely to have been dispensed anti-depressant medication (adj RR=1.56, 95% CI 1.05-2.32). Depression amongst veterans was associated with self-reported Gulf War-related stressors in a dose-response relationship (adj RR 1.06, 95% CI 1.02-1.09). LIMITATIONS Lower participation rates at follow up resulted in reduced statistical power compared with baseline, Gulf War related stressor data collected at baseline was at risk of recall bias, and RPBS and PBS databases do not capture all dispensed Nervous System medications. CONCLUSIONS More than 20 years after the Gulf War, veterans are experiencing slightly more severe depressive symptoms than a military comparison group, and depression continues to be associated with Gulf War-related stressors.

Exploratory study of factors associated with adverse clinical features in patients presenting with non-fatal drug overdose/self-poisoning to the ambulance service

Aim To investigate the factors associated with adverse clinical features presented by drug overdose/self-poisoning patients and the treatments provided. Methods Historical patient records collected over 3 months from ambulance crews attending non-fatal overdoses/self-poisoning incidents were reviewed. Logistic regression was used to investigate predictors of adverse clinical features (reduced consciousness, obstructed airway, hypotension or bradycardia, hypoglycaemia) and treatment. Results Of 22 728 calls attended to over 3 months, 585 (rate 26/1000 calls) were classified as overdose or self-poisoning. In the 585 patients identified, paracetamol-containing drugs were most commonly involved (31.5%). At least one adverse clinical feature occurred in 103 (17.7%) patients, with higher odds in men and opiate overdose or illegal drugs. Older patients and patients with reduced consciousness were more likely to receive oxygen. The latter also had a greater chance of receiving saline. Conclusion Non-fatal overdose/self-poisoning accounted for 2.6% of patients attended by an ambulance. Gender, illegal drugs or opiates were important predictors of adverse clinical features. The treatments most often provided to patients were oxygen and saline.

Preterm growth restriction and bronchopulmonary dysplasia: the vascular hypothesis and related physiology

Approximately 5–10% pregnancies are affected by fetal growth restriction. Preterm infants affected by fetal growth restriction have a higher incidence of bronchopulmonary dysplasia. The present study is the first to measure pulmonary artery thickness and stiffness. The findings show that impaired vasculogenesis may be a contributory factor in the higher incidence of bronchopulmonary dysplasia in preterm growth restricted infants. The study addresses the mechanistic link between fetal programming and vascular architecture and mechanics.