Patient characteristics in tardive COVID-19 pseudoperniosis: a case series of 16 patients.

BACKGROUND: Acute pseudoperniosis (PP) has a recognized association with COVID-19 and tends to occur without cold precipitation in young, healthy patients, often without a clear history of COVID-19. These lesions usually resolve within 2 weeks and without long-term sequelae. In the early months of 2021, patients with delayed and protracted PP began to emerge. We have called this presentation 'tardive COVID-19 PP (TCPP)'. AIM: To consolidate and expand knowledge on TCPP, we describe the clinical characteristics, treatments and outcomes of 16 patients with TCPP who were reviewed by our outpatient dermatology service. RESULTS: The initial clinical manifestations were erythema, swelling and PP of the fingers in 56.2%, and of the toes in 31.2%, desquamation in 56.2% and acrocyanosis in 12.5%. Ten patients had eventual involvement of all acral sites. The median duration of symptoms was 191 days. Six patients reported close contact with a confirmed or suspected case of COVID-19, but only two had positive COVID-19 tests. Four patients experienced complete or almost complete resolution of symptoms, while the rest remain under active treatment. CONCLUSION: Unlike acute PP, TCPP has a protracted and delayed presentation that is typically associated with profound acrocyanosis. Patients with TCPP represent a new phenomenon that is part of the post-COVID-19 syndrome, with risk factors and pathophysiology that are not yet fully understood. Our data indicate that likely predisposing factors for developing TCPP include young age, a preceding history of cold intolerance and an arachnodactyloid phenotype. Anorexia, connective tissue disorders or sickle cell trait may also predispose to TCPP. In addition, low titre antinuclear antibody positivity, the presence of cryoglobulins, or low complement levels may represent further risk factors. Finally, prolonged low temperatures are also likely to be contributing to the symptoms.

A novel candidate gene in autosomal dominant facial pruritus.

In the clinical investigation of a family with debilitating centrofacial pruritus by exome sequencing, we have observed a clear segregation of the TRPM3 variant outlined, which is highly suggestive of a causal relationship.

Potential methanol toxicity and the importance of using a standardised alcohol-based hand rub formulation in the era of COVID-19.

OBJECTIVES: Hand sanitisers are urgently needed in the time of COVID-19, and as a result of shortages, some people have resorted to making their own formulations, including the repurposing of distilleries. We wish to highlight the importance of those producing hand sanitisers to avoid methylated spirits containing methanol and to follow WHO recommended formulations. METHODS: We explore and discuss reports of methanol toxicity through ingestion and transdermal absorption. We discuss the WHO formulations and explain the rationale behind the chosen ingredients. SHORT CONCLUSION: We advise those producing hand sanitisers to follow WHO recommended formulations, and advise those producing hand sanitisers using methylated spirits, to avoid formulations which contain methanol.

Childhood infections, vaccinations, and tonsillectomy and risk of first clinical diagnosis of CNS demyelination in the Ausimmune Study.

BACKGROUND: The association between childhood vaccinations and infections and risk of multiple sclerosis is unclear; few studies have considered age at vaccination/infection. OBJECTIVE: To explore age-related associations between childhood vaccinations, infection and tonsillectomy and risk of a first clinical diagnosis of CNS demyelination. METHODS: Data on case (n = 275, 76.6% female; mean age 38.6 years) and age- and sex-matched control (n = 529) participants in an incident population-based case-control study included self-reported age at time of childhood vaccinations, infections, and tonsillectomy. Conditional logistic regression models were used to calculate adjusted odds ratios (AOR) and 95% confidence intervals (CI). RESULTS: Poliomyelitis vaccination prior to school-age was associated with increased risk of a first clinical diagnosis of CNS demyelination (AOR = 2.60, 95%CI 1.02-6.68), based on a very small unvaccinated reference group. Late (11-15 years) rubella vaccination (compared to none) was associated with lower odds of being a case (AOR = 0.47, 95%CI 0.27-0.83). Past infectious mononucleosis at 11-15 years (AOR = 2.84, 95%CI 1.0-7.57) and 16-20 years (AOR = 1.92, 95%CI 1.12-3.27) or tonsillectomy in adolescence (11-15 years: AOR = 2.45, 95%CI 1.12-5.35), including after adjustment for IM, were associated with increased risk of a first clinical diagnosis of CNS demyelination. CONCLUSIONS: Age at vaccination, infection or tonsillectomy may alter the risk of subsequent CNS demyelination. Failing to account for age effects may explain inconsistencies in past findings.

Changing trends in the UK management of upper GI bleeding: is there evidence of reduced UK training experience?

OBJECTIVE: The aim of this study was to evaluate UK trainee experience in endoscopy for acute upper gastrointestinal bleeding (AUGIB). METHODS: Data was prospectively collected from all patients presenting to South Yorkshire Hospitals with AUGIB from September 2011 to December 2011 and compared with data from 1996. Concurrently, all gastroenterology trainees registered with the British Society of Gastroenterology were invited to respond to a web-based questionnaire regarding their experience in AUGIB management. RESULTS: 77% (589/766) of the patient cohort underwent endoscopy for AUGIB; 15% (90/589) were performed by trainees. 7.2% (9/125) of the out of hours endoscopy case load was performed by trainees; all were low-risk or medium-risk cases (pre-endoscopy Rockall score ≤4). During the study period, dual therapy was delivered by a trainee on only four occasions. Comparison with the 1996 cohort demonstrated a marked reduction in the number of trainee performed endoscopies (76% vs 15%; p<0.001). Questionnaires were returned by 51% (245/478) of British Society of Gastroenterology trainees. 81% (198/245) thought that <10% of the gastroscopies they had performed involved therapeutic intervention. 23% (57/245) felt they would not be competent in AUGIB endoscopy by completion of specialty training. CONCLUSIONS: This study demonstrates the decline over time in trainee experience in AUGIB endoscopy. It also highlights a lack of trainee exposure to more challenging cases, out of hours endoscopy and therapeutic procedures. Furthermore, trainees are concerned that a level of competency may not be attained during specialty training. We advocate reviewing UK endoscopic training provision for AUGIB to ensure that experienced endoscopists are produced to meet future service needs.

Non-centralised service for palliative stenting of malignant gastric outlet obstruction.

INTRODUCTION: Malignant gastric outlet obstruction (GOO) is a common, debilitating and frequently pre-terminal symptom of intra-abdominal malignancies. Traditional 'gold standard' treatment has been palliative surgical gastro-enterostomy. Over the past two decades, use of self-expanding metallic stents (SEMSs) to relieve malignant GOO has become first-line treatment. We present the results from a single district general hospital in the UK in which malignant GOO was treated with SEMSs over a six-year period. METHODS: All patients who underwent palliative stenting for malignant gastro-duodenal tumours in our centre for six years up to January 2013 were assessed retrospectively. Outcomes were assessed with regard to: technical and clinical success; return to oral nutrition; prevalence of complications and re-intervention; and overall survival. RESULTS: Thirty-two stents were implanted in 29 patients. Technical success was 100%. Clinical success and return to oral nutrition were both 91%. The prevalence of complications was 16%. The prevalence of re-intervention was 13%. Mean survival was 91 (range, 5-392) days. Median wait from decision to implant a stent to stent implantation was 1 (range, 0-14) day. Overall, 25 covered and nine uncovered stents were implanted. CONCLUSION: Stent implantation for GOO in this patient group is an established and preferable alternative to surgical intervention. Much of the treatment for malignancies of the upper gastrointestinal tract has now been centralised. Our data showed comparable results with published data for these procedures, with a high prevalence of success and low prevalence of major complications. It is of considerable benefit to these patients not to have to travel to a regional centre for stent implantation.

Mental health services for children exposed to armed conflict: Médecins Sans Frontières' experience in the Democratic Republic of Congo, Iraq and the occupied Palestinian territory.

BACKGROUND: Armed conflict has broad-ranging impacts on the mental health and wellbeing of children and adolescents. Mental health needs greatly exceed service provision in conflict settings, particularly for these age groups. The provision and targeting of appropriate services requires better understanding of the characteristics and requirements of children and adolescents exposed to armed conflict. METHODS: Routine patient and programme monitoring data were analysed for patients <20 years of age attending mental health services provided by Médecins Sans Frontières (MSF) in three countries affected by armed conflict: the Democratic Republic of Congo (DRC), Iraq and the occupied Palestinian territory (oPt). The demographic characteristics, presenting mental health complaint, attributed precipitating event, services provided and short-term outcomes for mental health services users in each country are described. RESULTS: Between 2009 and 2012, 3025 individuals <20 years of age presented for care in DRC and Iraq, and in 2012 in oPt, constituting 14%, 17.5% and 51%, respectively, of all presentations to MSF mental health services in those three countries. The most common precipitating event was sexual violence in DRC (36.5%), domestic violence in Iraq (17.8%) and incarceration or detention in oPt (33%). Armed conflict-related precipitants were reported by 25.9%, 55.0% and 76.4% of youths in DRC, Iraq and oPt, respectively. The most common presenting complaints in children and adolescents were anxiety-related, followed by mood-related, behaviour-related and somatisation problems; these varied according to country and precipitating event. Although a high proportion (45.7%) left programmes early, 97% of those who completed care self-reported improvement in their presenting complaint. CONCLUSIONS: Brief trauma-focused therapy, the current MSF mental health therapeutic intervention, appears to be effective in reducing symptoms arising from the experience of trauma. Although inferences on outcomes are limited by high default rates, this provides a feasible tool for addressing the mental health needs of children exposed to armed conflict. Priorities for future research include understanding why children and adolescents constitute a small proportion of patients in some programmes, why many leave care early and how to address these issues, but this research must occur within the context of efforts to provide access to mental health services for children.

Early-life hygiene-related factors affect risk of central nervous system demyelination and asthma differentially.

The increasing prevalence of immune-related diseases, including multiple sclerosis, may be partly explained by reduced microbial burden during childhood. Within a multi-centre case-control study population, we examined: (i) the co-morbid immune diseases profile of adults with a first clinical diagnosis of central nervous system demyelination (FCD) and (ii) sibship structure in relation to an autoimmune (FCD) and an allergic (asthma) disease. FCD cases (n = 282) were aged 18-59 years; controls (n = 558) were matched on age, sex and region. Measures include: history of doctor-diagnosed asthma; sibling profile (number; dates of birth); and regular childcare attendance. FCD cases did not differ from controls with regard to personal or family history of allergy, but had a greater likelihood of chronic fatigue syndrome [odds ratio (OR) = 3·11; 95% confidence interval (CI) 1·11, 8·71]. Having any younger siblings showed reduced odds of FCD (OR = 0·68; 95% CI: 0·49, 0·95) but not asthma (OR = 1·47; 95% CI: 0·91, 2·38). In contrast, an increasing number of older siblings was associated with reduced risk of asthma (P trend = 0·04) but not FCD (P trend = 0·66). Allergies were not over-represented among people presenting with FCD. Sibship characteristics influence both FCD and asthma risk but the underlying mechanisms differ, possibly due to the timing of the putative 'sibling effect'.

Occupational exposure and risk of central nervous system demyelination.

Inconsistent evidence exists regarding the association between work-related factors and risk of multiple sclerosis (MS). We examined the association between occupational exposures and risk of a first clinical diagnosis of central nervous system demyelination (FCD), which is strongly associated with progression to MS, in a matched case-control study of 276 FCD cases and 538 controls conducted in Australia (2003-2006). Using a personal residence and work calendar, information on occupational history and exposure to chemicals and animals was collected through face-to-face interviews. Few case-control differences were noted. Fewer cases had worked as professionals (≥6 years) than controls (adjusted odds ratio (AOR) = 0.60, 95% confidence interval (CI): 0.37, 0.96). After further adjustment for number of children, cases were more likely to have ever been exposed to livestock than controls (AOR = 1.54, 95% CI: 1.03, 2.29). Among women, there was an increase in FCD risk associated with 10 or more years of exposure to livestock (AOR = 2.78, 95% CI: 1.22, 6.33) or 6 or more years of farming (AOR = 2.00, 95% CI: 1.23, 3.25; also adjusted for number of children). Similar findings were not evident among men. Thus, farming and exposure to livestock may be important factors in the development of FCD among women, with this finding further revealed after the confounding effect of parity or number of children is considered.

Offspring number, pregnancy, and risk of a first clinical demyelinating event: the AusImmune Study.

OBJECTIVE: To examine the association between past pregnancy, offspring number, and first clinical demyelination risk. METHODS: Cases (n = 282) were aged 18-59 years with a first clinical diagnosis of CNS demyelination (first clinical demyelinating event [FCD]) and resident within 1 of 4 Australian centers (from latitudes 27° south to 43° south) from 2003 to 2006. Controls (n = 542) were matched to cases on age, sex, and study region, without first clinical diagnosis of CNS demyelination. RESULTS: Higher offspring number was associated with FCD risk among women (p < 0.001) but not men (p = 0.71); difference in effect; p = 0.001. Among women, higher parity was associated with reduced risk of FCD (adjusted odds ratio 0.51 [95% confidence interval 0.36, 0.72] per birth) with a similar magnitude of effect observed among classic first demyelinating events (adjusted odds ratio 0.47 [95% confidence interval 0.29, 0.74]). The apparent beneficial effect of higher parity was also evident among parous women only (p < 0.001). Among cases, a clear female excess was evident for those with low but not high (4 or more) offspring number. Factors such as human leukocyte antigen DR15 genotype did not appear to modify the association between higher parity and a reduced FCD risk among women. CONCLUSIONS: These findings are consistent with a cumulative beneficial effect of pregnancy. Temporal changes toward an older maternal age of parturition and reduced offspring number may partly underlie the increasing female excess among MS cases over time.

A review of shoulder replacement surgery.

Shoulder replacement surgery is employed in the treatment of severe shoulder arthritis and following some proximal humeral fractures. Three different replacements are available: hemiarthroplasty (HAS), total shoulder replacement (TSR) and reverse shoulder replacement (RSR). HAS and TSR are indicated in patients with intact rotator cuffs and RSR for cuff deficient older patients. Outcomes are favourable, with the majority of patients having improvements in shoulder pain and function.

Current and past Epstein-Barr virus infection in risk of initial CNS demyelination.

OBJECTIVES: To assess risk of a first clinical diagnosis of CNS demyelination (FCD) in relation to measures of Epstein-Barr virus (EBV) infection within the context of other known risk factors. METHODS: This was a multicenter incident case-control study. FCD cases (n = 282) aged 18-59 years and controls (n = 558, matched on age, sex, and region) were recruited from 4 Australian centers between November 1, 2003, and December 31, 2006. A nested study (n = 215 cases, n = 216 controls) included measurement of whole blood quantitative EBV DNA load and serum EBV-specific antibodies. Conditional logistic regression was used to analyze case-control differences. RESULTS: There were no significant case-control differences in the proportion with detectable EBV DNA (55.8% vs 50.5%, respectively, p = 0.28), or in quantitative EBV DNA load (p = 0.33). Consistent with previous work, higher anti-EBV-specific immunoglobulin G (IgG) titers and a history of infectious mononucleosis were associated with increased FCD risk and there was an additive interaction with HLA-DRB1*1501 status. We found additional interactions between high anti-EBNA IgG titer and SNPs in HLA-A (adjusted odds ratios [AOR] = 19.84 [95% confidence interval (CI) 5.95 to 66.21] for both factors compared to neither) and CTLA-4 genes (AOR = 0.31 [95% CI 0.13 to 0.76] for neither factor compared to both). EBV DNA load was lower at higher serum 25-hydroxyvitamin D concentrations in controls (r = -0.17, p = 0.01). An adverse effect of higher EBV DNA load on FCD risk was increased with higher 25-hydroxyvitamin D concentration (p[interaction] = 0.02). CONCLUSION: Past infection with EBV, but not current EBV DNA load in whole blood, is significantly associated with increased FCD risk. These associations appear to be modified by immune-related gene variants.

Sun exposure and vitamin D are independent risk factors for CNS demyelination.

OBJECTIVES: To examine whether past and recent sun exposure and vitamin D status (serum 25-hydroxyvitamin D [25(OH)D] levels) are associated with risk of first demyelinating events (FDEs) and to evaluate the contribution of these factors to the latitudinal gradient in FDE incidence in Australia. METHODS: This was a multicenter incident case-control study. Cases (n = 216) were aged 18-59 years with a FDE and resident within one of 4 Australian centers (from latitudes 27°S to 43°S), from November 1, 2003, to December 31, 2006. Controls (n = 395) were matched to cases on age, sex, and study region, without CNS demyelination. Exposures measured included self-reported sun exposure by life stage, objective measures of skin phenotype and actinic damage, and vitamin D status. RESULTS: Higher levels of past, recent, and accumulated leisure-time sun exposure were each associated with reduced risk of FDE, e.g., accumulated leisure-time sun exposure (age 6 years to current), adjusted odds ratio (AOR) = 0.70 (95% confidence interval [CI] 0.53-0.94) for each ultraviolet (UV) dose increment of 1,000 kJ/m(2) (range 508-6,397 kJ/m(2)). Higher actinic skin damage (AOR = 0.39 [95% CI 0.17-0.92], highest grade vs the lowest) and higher serum vitamin D status (AOR = 0.93 [95% CI 0.86-1.00] per 10 nmol/L increase in 25(OH)D) were independently associated with decreased FDE risk. Differences in leisure-time sun exposure, serum 25(OH)D level, and skin type additively accounted for a 32.4% increase in FDE incidence from the low to high latitude regions. CONCLUSIONS: Sun exposure and vitamin D status may have independent roles in the risk of CNS demyelination. Both will need to be evaluated in clinical trials for multiple sclerosis prevention.

The influence of weather on community gastroenteritis in Australia.

Infectious gastroenteritis is a common illness in Australia as elsewhere. Data from a year-long national gastroenteritis survey in 2001-2002 showed that gastroenteritis was more common in the northern and hotter part of Australia. These data were used to quantify associations between local weather variables and gastroenteritis in people aged >5 years while controlling for socioeconomic status. A distributed lag model was used to examine the influence of weather over a period of days prior to an event and the maximal effect was found at a lag of 2-5 days. The total effect over the preceding week indicated a relative increase from baseline in the probability of gastroenteritis of 2·48% (95% CI 1·01-3·97) for each degree rise (°C) over that period. Given the very high burden of gastroenteritis, this represents a substantial effect at the population level and has relevance for health predictions due to climate change.

Atrial fibrillation and anticoagulation in a stroke unit population.

BACKGROUND: Atrial fibrillation (AF) is an important predisposing factor for ischaemic stroke. There is evidence to suggest that even in appropriate candidates warfarin therapy is underutilized. We assessed the prevalence of AF in an Australian stroke unit to determine the degree of undertreatment at presentation. METHODS: A retrospective analysis of all patients admitted to our Stroke Unit between October 2004 and September 2006 was carried out. All patients with a diagnosis of AF, either new or old, were then selected from this group to determine the overall prevalence and anticoagulation status. Data regarding prior stroke, stroke severity and discharge anticoagulation status were also determined. RESULTS: Data from a total of 500 patients were analysed. Our results showed that AF-related strokes accounted for a large proportion (28%) of all admissions and were associated with a larger neurological deficit. Most patients (68%) with a prior diagnosis of AF without having obvious contraindications were either not anticoagulated or under-anticoagulated when presenting with an ischaemic stroke or transient ischaemic attack. CONCLUSION: Our results stress the importance of initiating and maintaining anticoagulation in patients with AF and without obvious contraindications to minimize the risk of subsequent stroke.

Observational analytic studies in multiple sclerosis: controlling bias through study design and conduct. The Australian Multicentre Study of Environment and Immune Function.

Rising multiple sclerosis incidence over the last 50 years and geographic patterns of occurrence suggest an environmental role in the causation of this multifactorial disease. Design options for epidemiological studies of environmental causes of multiple sclerosis are limited by the low incidence of the disease, possible diagnostic delay and budgetary constraints. We describe scientific and methodological issues considered in the development of the Australian Multicentre Study of Environment and Immune Function (the Ausimmune Study), which seeks, in particular, to better understand the causes of the well-known MS positive latitudinal gradient. A multicentre, case-control design down the eastern seaboard of Australia allows the recruitment of sufficient cases for adequate study power and provides data on environmental exposures that vary by latitude. Cases are persons with an incident first demyelinating event (rather than prevalent multiple sclerosis), sourced from a population base using a two tier notification system. Controls, matched on sex, age (within two years) and region of residence, are recruited from the general population. Biases common in case-control studies, eg, prevalence-incidence bias, admission-rate bias, non-respondent bias, observer bias and recall bias, as well as confounding have been carefully considered in the study design and conduct of the Ausimmune Study.

Adverse effects of a multicentre system for ethics approval on the progress of a prospective multicentre trial of cancer treatment: how many patients die waiting?

BACKGROUND: As cancer survival is improving approximately by 1-2% per year, delays in the clinical trials that lead to that improvement could cost lives. AIMS: To review the process of ethics committee approval for a multicentre clinical trial of cancer treatment and to estimate the delay it will cause in obtaining the results and the effects of such delays on survival for all cancers in Australia. METHODS: A survey was sent to each of the 15 centres participating in the study to obtain details about submissions they had made to their ethics committees and the replies received from them. RESULTS: The survey response rate was 100%. The average time required to complete an ethics submission was 12 h, and the average length of time for a final reply was 70 days. Wide variation was noted in the replies, 40% were considered constructive. Most centres said the effort in ethics submissions is sufficient to limit participation in other clinical trials that are available. CONCLUSION: The multicentre system of ethics approval has significantly delayed this multicentre trial and may delay advances in cancer care. Extrapolating this delay to determine an influence on improvements in cancer survival suggests that it may be responsible for 60 cancer deaths per year. A method for measuring the effect on the shape of the accrual curve is defined, and the term DIABOLECAL (Delays in Accrual Brought On Largely by Ethics Committee Activity Lag-time) is proposed to describe it. Attempts to overcome this problem have been introduced overseas.

Higher maternal dietary protein intake in late pregnancy is associated with a lower infant ponderal index at birth.

AIM: A high ponderal index at birth has been associated with later obesity and it has been suggested that intervention to prevent obesity and its sequela should consider the antenatal period. In this context, we investigated the association between maternal nutrition and birth anthropometry. DESIGN: We analyzed data on 1040 mother-infant pairs collected during the Tasmanian Infant Health Survey (TIHS), Tasmania, 1988-1989. Maternal dietary intake during pregnancy was measured by food frequency questionnaire (FFQ) applied soon after birth. Outcomes of interest were birth weight, birth length, head circumference, ponderal index, head circumference -to-ponderal index ratio, placenta-to-birth weight ratio and head circumference-to-birth length index. RESULTS: In multiple regression model, an increase of 10 g of absolute protein intake/day was associated with a reduction in birth weight of 17.8 g (95% CI: -32.7, -3.0; P=0.02). Protein intake was also associated negatively with ponderal index (beta=-0.01; 95% CI: -0.02, -0.00; P=0.01). A 1 % increase in carbohydrate intake resulted in a 1% decline in placental weight relative to birth weight. Higher protein intake in the third trimester was associated with a reduced ponderal index among large birth weight infants but not low birth weight infants. CONCLUSIONS: This raises the possibility that any effect of high protein in altering infant anthropometry at birth may involve changes in body composition and future work to examine how a high-protein diet influences body composition at birth is warranted.

Haemophilus influenzae oral whole cell vaccination for preventing acute exacerbations of chronic bronchitis.

BACKGROUND: Acute bronchitis leading to ongoing exacerbations is a serious condition predisposed to by viruses, bacteria or environmental factors. It can be fatal. Antibiotic therapy is not particularly useful. An oral Haemophilus influenzae vaccine has been developed. OBJECTIVES: To assess the effects of an oral, monobacterial whole-cell, killed, nontypeable H. influenzae vaccine in protecting against recurrent acute episodes in chronic bronchitis. SEARCH STRATEGY: In this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006), MEDLINE (1966 to January Week 4 2006), EMBASE (1990 to September 2005) and ISI Current Contents (2004 to May 2006). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the effects of the H. influenzae vaccine on patients with recurrent acute exacerbations of chronic bronchitis were included when there was overt matching of the vaccine and placebo groups on clinical grounds. DATA COLLECTION AND ANALYSIS: Three authors extracted data and assessed trial quality independently from original records and publications for incidence and severity of bronchitis episodes and carriage rate of nontypeable H. influenzae measured in the upper respiratory tract every three months following vaccination. MAIN RESULTS: Six trials were included in the study with a total of 440 participants. The vaccine reduced the incidence of bronchitic episodes at three months after vaccination (rate ratio is 0.69; 95% CI 0.41 to 1.14) and at six months after vaccination (rate ratio 0.82; 95% CI 0.62 to 1.09). If these results been statistically significant, they would have represented a reduction in acute bronchitic attacks for vaccinated individuals of 31% at three months, and 18% at six. The effect had disappeared by nine months. The severity of exacerbations in the treatment group, as measured by requirement to prescribe antibiotics, was likewise reduced by 58% at three months (Peto odds ratio = 0.42; 95% CI 0.16 to 1.13), and by 65% at six months (Peto odds ratio = 0.35; 95% CI 0.16 to 0.75). AUTHORS' CONCLUSIONS: Vaccinating patients with recurrent acute exacerbations of chronic bronchitis in the autumn may reduce the number and severity of exacerbations over the following winter. A large clinical trial is needed.

Age group differences in psychological distress: the role of psychosocial risk factors that vary with age.

BACKGROUND: There is continuing controversy about how age affects depression and anxiety, with a lack of consistent results across studies. Two reasons for this inconsistency are age bias in measures and different patterns of exposure to risk factors across age groups in various studies. METHOD: Data on anxiety and depression symptoms were collected in a community survey of 7485 persons aged 20-24, 40-44 or 60-64 years. These measures were investigated for factorial invariance across age groups. Data were also collected on a wide range of potential risk factors, including social, physical health and personal factors, with the aim of determining whether these factors might partly or wholly account for age group differences. RESULTS: The invariance of correlated latent factors representing anxiety and depression was examined across age groups, and a generalized measure of psychological distress was computed. Depression, anxiety and psychological distress showed a decline across age groups for females and a decline from 40-44 to 60-64 years for males. Some of these age differences were accounted for by other risk factors, with the most important being recent crises at work and negative social relationships with family and friends. CONCLUSION: Psychological distress generally declined across the age range 20-64 years and this was not attributable to measurement bias. Differential exposure to risk factors explained some, but not all, of the age group difference. Therefore other mechanisms that explain the lower level of distress in older age groups remain to be identified.