First Australian estimates of incidence and prevalence of uterine fibroids: a data linkage cohort study 2000-2022.

STUDY QUESTION: What is the estimated prevalence and incidence of uterine fibroids diagnosed in Australian women of reproductive age? SUMMARY ANSWER: An estimated 7.3% of Australian women had a diagnosis of uterine fibroids by the age of 45-49 years, with age-specific incidence highest in women aged 40-44 years (5.0 cases per 1000 person-years). WHAT IS KNOWN ALREADY: Uterine fibroids are associated with a high symptom burden and may affect overall health and quality of life. Studies in different countries show a wide variation in both the prevalence (4.5-68%) and incidence (2.2-37.5 per 1000 person-years) of uterine fibroids, which may be partly explained by the type of investigation, method of case ascertainment, or the age range of the study population, necessitating the reporting of country-specific estimates. STUDY DESIGN, SIZE, DURATION: This observational prospective cohort study using self-report survey and linked administrative data (2000-2022) included 8066 women, born between 1973 and 1978, in the Australian Longitudinal Study on Women's Health. PARTICIPANTS/MATERIALS, SETTING, METHODS: A combination of self-report survey and linked administrative health data (hospital, emergency department, the Medicare Benefits Schedule, and the Pharmaceutical Benefits Scheme) were used to identify women with a report of a diagnosis of uterine fibroids between 2000 and 2022. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 8066 Australian women followed for 22 years, an estimated 7.3% of women (95% CI 6.9, 7.6) had a diagnosis of uterine fibroids by the age of 45-49 years. The incidence increased with age and was highest in women aged 40-44 years (5.0 cases per 1000 person-years, 95% CI 4.3, 5.7 cases per 1000 person-years). Women with uterine fibroids were more likely to experience heavy or painful periods. They were also more likely to report low iron levels, endometriosis, and poor self-rated health and to have two or more annual visits to their general practitioner. LIMITATIONS, REASONS FOR CAUTION: Our estimates are based on self-report of doctor diagnosis or treatment for fibroids and/or data linked to treatment and procedure administrative records. This predominantly captures women with symptomatic fibroids, but has the potential for misclassification of asymptomatic women and an underestimate of overall prevalence and incidence. In addition, questions on fibroids were only asked in surveys when women were 37-42 years of age to 43-48 years of age, so cases at younger ages may have been underestimated (particularly in women with less severe symptoms) as these were only ascertained through data linkage. WIDER IMPLICATIONS OF THE FINDINGS: These are the first population-based estimates of the prevalence and incidence of uterine fibroids in women of reproductive age in Australia. Establishing these first estimates will help inform health policy and health care provision in the Australian context. STUDY FUNDING/COMPETING INTEREST(S): The ALSWH is funded by the Australian Government Department of Health and Aged Care. L.FW. was supported by an Australian National Health and Medical Research Council (NHMRC) Centres for Research Excellence grant (APP1153420) and G.D.M. was supported by an NHMRC Leadership Fellowship (APP2009577). The funding bodies played no role in the design, the collection, analysis or interpretation of data, the writing of the manuscript, or the decision to submit the manuscript for publication. There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Women's interest, knowledge, and attitudes relating to anti-Mullerian hormone testing: a randomized controlled trial.

STUDY QUESTION: What is the impact of co-designed, evidence-based information regarding the anti-Mullerian hormone (AMH) test on women's interest in having the test? SUMMARY ANSWER: Women who viewed the evidence-based information about the AMH test had lower interest in having an AMH test than women who viewed information produced by an online company selling the test direct-to-consumers. WHAT IS KNOWN ALREADY: Online information about AMH testing often has unfounded claims about its ability to predict fertility and conception, and evidence suggests that women seek out and are recommended the AMH test as a measure of their fertility potential. STUDY DESIGN, SIZE, DURATION: An online randomized trial was conducted from November to December 2022. Women were randomized (double-blind, equal allocation) to view one of two types of information: co-designed, evidence-based information about the AMH test (intervention), or existing information about the AMH test from a website which markets the test direct-to-consumers (control). A total of 967 women were included in the final analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were women recruited through an online panel, who were aged 25-40 years, living in Australia or The Netherlands, had never given birth, were not currently pregnant but would like to have a child now or in the future, and had never had an AMH test. The primary outcome was interest in having an AMH test (seven-point scale; 1 = definitely NOT interested to 7 = definitely interested). Secondary outcomes included attitudes, knowledge, and psychosocial and behavioural outcomes relating to AMH testing. MAIN RESULTS AND THE ROLE OF CHANCE: Women who viewed the evidence-based information about the AMH test had lower interest in having an AMH test (MD = 1.05, 95% CI = 0.83-1.30), less positive attitudes towards (MD = 1.29, 95% CI = 4.57-5.70), and higher knowledge about the test than women who viewed the control information (MD = 0.75, 95% CI = 0.71-0.82). LIMITATIONS, REASONS FOR CAUTION: The sample was more highly educated than the broader Australian and Dutch populations and some measures (e.g. influence on family planning) were hypothetical in nature. WIDER IMPLICATIONS OF THE FINDINGS: Women have higher knowledge of and lower interest in having the AMH test when given evidence-based information about the test and its limitations. Despite previous studies suggesting women are enthusiastic about AMH testing to learn about their fertility potential, we demonstrate that this enthusiasm does not hold when they are informed about the test's limitations. STUDY FUNDING/COMPETING INTEREST(S): This project was supported by an NHMRC Emerging Leader Research Fellowship (2009419) and the Australian Health Research Alliance's Women's Health Research, Translation and Impact Network EMCR award. B.W.M. reports consultancy for ObsEva and Merck and travel support from Merck. D.L. is the Medical Director of, and holds stock in, City Fertility NSW and reports consultancy for Organon and honoraria from Ferring, Besins, and Merck. K.H. reports consultancy and travel support from Merck and Organon. K.M. is a director of Health Literacy Solutions that owns a licence of the Sydney Health Literacy Lab Health Literacy Editor. No other relevant disclosures exist. TRIAL REGISTRATION NUMBER: ACTRN12622001136796. TRIAL REGISTRATION DATE: 17 August 2022. DATE OF FIRST PATIENT'S ENROLMENT: 21 November 2022.

Asthma severity and impact on perinatal outcomes: an updated systematic review and meta-analysis.

BACKGROUND: Large-scale studies exploring the associations of asthma severity, exacerbations and medication use with adverse perinatal outcomes have been published in recent years. OBJECTIVES: To update evidence on the associations of asthma severity, exacerbations and medication use with the adverse perinatal outcomes of preterm delivery (PD), low birthweight (LBW) and small-for-gestational-age (SGA). SEARCH STRATEGY: PubMed, Embase, Wanfang, and China National Knowledge Infrastructure (CNKI) from inception to 1 January 2021. SELECTION CRITERIA: Cohort studies comparing the likelihood of adverse perinatal outcomes in groups of asthmatic women stratified by asthma severity, asthma exacerbations or medication use, or comparing the likelihood of adverse perinatal outcomes between non-asthmatic women and asthmatics of various levels of severity and exacerbation. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed risk of bias. Random-effects models were used to meta-analyse the results. MAIN RESULTS: Twenty studies met the inclusion criteria. The odds of delivering SGA babies increased with maternal asthma severity. Pregnant women with an asthma exacerbation had higher odds of delivering LBW babies and SGA babies, compared with pregnant women with asthma but without an exacerbation (pooled adjusted odds ratio [OR] 1.15, 95% CI 1.02-1.29 for LBW; number of studies with adjusted OR 3; I2 = 0%) (pooled adjusted OR 1.13, 95% CI 1.04-1.23 for SGA; number of studies with adjusted OR 4; I2 = 0%) and compared to pregnant women without asthma. Oral corticosteroids use during pregnancy was associated with increased odds of LBW, but not PD. CONCLUSIONS: The available data suggest that maternal asthma severity and exacerbations are associated with increased odds of LBW and SGA babies. TWEETABLE ABSTRACT: A systematic review and meta-analysis found that maternal asthma severity and exacerbations are associated with increased odds of delivering low birthweight and small-for-gestational-age babies.

Delayed diagnosis of endometriosis disadvantages women in ART: a retrospective population linked data study.

STUDY QUESTION: Do the outcomes and use of ART differ between women with and without endometriosis? SUMMARY ANSWER: ART use and outcome do not appear to differ for women with and without endometriosis, as long as endometriosis is diagnosed prior to commencing ART. WHAT IS KNOWN ALREADY: Approximately 40% of women with endometriosis have infertility and ART is the recommended treatment option for these women. However, diagnosis of endometriosis can be complex and lengthy, and a delay in diagnosis can reduce the likelihood of achieving a live birth. STUDY DESIGN, SIZE, DURATION: This retrospective national cohort study used longitudinal self-report data (collected 1996-2018) from women born in 1973-1978 who are participants in the Australian Longitudinal Study on Women's Health (ALSWH). The study also used linked administrative data on Endometriosis (1970-2018), ART (1996-2020) and births (1996-2018). PARTICIPANTS/MATERIALS, SETTING, METHODS: The outcome measures were: age at first ART cycle; use of ART treatments (IVF only; IUI only/and IVF); number of ART cycles (1-3; 4-10; 11-36); and births after first ART (no; yes) (note that births could not be tied to ART). MAIN RESULTS AND THE ROLE OF CHANCE: One in three (34.7%, n = 459/1322) women using ART had endometriosis, with 65.6% of these diagnosed before first ART and 34.4% after. Adjusted regression analyses showed women with endometriosis diagnosed before first ART were not significantly different to women without endometriosis on any outcome. However, women with endometriosis diagnosed after first ART were more likely to use IUI (adjusted odds ratio (aOR) 2.14, 95% CI 1.48, 3.09) and do more cycles (11-36 cycles: aOR 4.09, 95% CI 2.41, 6.95), and less likely to report a birth (aOR 0.67, 95% CI 0.45, 0.99), compared to women without endometriosis, despite no significant difference in starting age (coefficient = -0.62, 95% CI -1.36, 0.13). LIMITATIONS, REASONS FOR CAUTION: We did not have information on the severity of endometriosis, or the reasons for using ART, which can influence treatment and outcomes. We were not able to reliably link births with ART treatment. Finally, it is possible that some of the women in our 'no endometriosis' group did have endometriosis and were unaware of it, although prevalence rates match population estimates. WIDER IMPLICATIONS OF THE FINDINGS: These findings support previous studies that have found no difference in outcome of ART for women with endometriosis, but add the new insight that this is only true if endometriosis is diagnosed prior to commencing ART. A delayed diagnosis can create disadvantage during ART treatment. Early recourse to IVF may be advantageous for pregnancy prospects for women with endometriosis. STUDY FUNDING/COMPETING INTEREST(S): The ALSWH is funded by the Australian Government Department of Health. G.D.M. is supported by an NHMRC Principal Research Fellowship (APP11218449). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Clinicians' perspectives on diagnosing polycystic ovary syndrome in Australia: a qualitative study.

STUDY QUESTION: What are clinicians' views about the diagnosis of polycystic ovary syndrome (PCOS), and how do they handle any complexities and uncertainties in practice? SUMMARY ANSWER: Clinicians have to navigate many areas of complexity and uncertainty regarding the diagnosis of PCOS, related to the diagnostic criteria, limitations in current evidence and misconceptions surrounding diagnosis, and expressed concern about the risk and consequences of both under- and overdiagnosis. WHAT IS KNOWN ALREADY: PCOS is a complex, heterogeneous condition with many areas of uncertainty, raising concerns about both underdiagnosis and overdiagnosis. Quantitative studies with clinicians have found considerable variation in diagnostic criteria used and care provided, as well as a lack of awareness around the breadth of PCOS features and poor uptake of recommended screening for metabolic complications. Clinicians' views about the uncertainties and complexities of diagnosing PCOS have not been explored. STUDY DESIGN, SIZE, DURATION: Semi-structured telephone interviews were conducted with clinicians from September 2017 to July 2018 to explore their perceptions about the diagnosis of PCOS, including how they handle any complexities and uncertainties in practice. PARTICIPANTS/MATERIALS, SETTING, METHODS: A group of 36 clinicians (15 general practitioners, 10 gynaecologists and 11 endocrinologists) currently practicing in Australia, were recruited through advertising via professional organisations, contacting a random sample of endocrine and gynaecology teams across Australia and snowballing. Transcribed audio-recordings were analysed thematically using Framework analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Clinicians expressed a range of uncertainties and complexities regarding the diagnosis of PCOS, which were organised into three areas: (i) establishing diagnosis (e.g. lack of standardisation regarding diagnostic cut-offs, risk of misdiagnosis), (ii) factors influencing the diagnostic process (e.g. awareness of limitations in evidence and consideration of the benefits and harms) and (iii) strategies for handling challenges and uncertainties (e.g. using caution and communication of uncertainties). Clinicians also varied in their concerns regarding under- and overdiagnosis. Overall, most felt the diagnosis was beneficial for women provided that it was the correct diagnosis and time was taken to assess patient expectations and dispel misconceptions, particularly concerning fertility. LIMITATIONS, REASONS FOR CAUTION: There is possible selection bias, as clinicians who are more knowledgeable about PCOS may have been more likely to participate. Clinicians' views may also differ in other countries. WIDER IMPLICATIONS OF THE FINDINGS: These findings underscore the vital need to first consider PCOS a diagnosis of exclusion and use caution before giving a diagnosis in order to reduce misdiagnosis, as suggested by clinicians in our study. Until there is greater standardisation of diagnostic criteria, more transparent conversations with women may help them understand the uncertainties surrounding the criteria and limitations in the evidence. Additionally, clinicians emphasised the importance of education and reassurance to minimise the potential harmful impact of the diagnosis and improve patient-centred outcomes. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the University of Sydney Lifespan Research Network and an NHMRC Program Grant (APP1113532). T.C. is supported by an Australian Government Research Training Program (RTP) Scholarship and a Sydney Medical School Foundation Scholarship, from the The University of Sydney, Australia. B.W.M. reports consultancy for ObsEva, Merck, Merck KGaA and Guerbet. No further competing interests exist. TRIAL REGISTRATION NUMBER: N/A.

A comparison of males and females' temporal patterning to short- and long-term heat acclimation.

The current study assessed sex differences in thermoregulatory and physiological adaptation to short-term (STHA) and long-term heat acclimation (LTHA). Sixteen (eight males; eight females) participants performed three running heat tolerance tests (RHTT), preceding HA (RHTT1), following 5 days HA (RHTT2) and 10 days HA (RHTT3). The RHTT involved 30-min running (9 km/h, 2% gradient) in 40 °C, 40% relative humidity. Following STHA, resting rectal temperature (Trrest ) (males: -0.24 ± 0.16 °C, P ≤ 0.001; females: -0.02 ± 0.08 °C, P = 0.597), peak rectal temperature (Trpeak ) (males: -0.39 ± 0.36 °C, P ≤ 0.001; females -0.07 ± 0.18 °C, P = 0.504), and peak heart rate (males: -14 ± 12 beats/min, P ≤ 0.001; females: -5 ± 3 beats/min, P = 0.164) reduced in males, but not females. Following STHA, sweat rate relative to body surface area (SRBSA ) increased (428 ± 269 g/h/m(2) , P = 0.029) in females, but not males (-11 ± 286 g/h/m(2) , P = 0.029). Following LTHA, Trrest (males: -0.04 ± 0.15 °C, P = 0.459; females: -0.22 ± 0.12 °C, P ≤ 0.01) and Trpeak (males: -0.05 ± 0.26 °C, P = 0.590; females: -0.41 ± 0.24 °C, P ≤ 0.01) reduced in females, but not males. Following LTHA, SRBSA increased in males (308 ± 346 g/h/m(2) , P = 0.029), but not females (44 ± 373 g/h/m(2) , P = 0.733). Males and females responded to STHA; however, females required LTHA to establish thermoregulatory and cardiovascular stability. HA protocols should be designed to target sex differences in thermoregulation for optimal adaptation.

The benefits and harms of receiving a polycystic ovary syndrome diagnosis: a qualitative study of women's experiences.

STUDY QUESTION: What are the benefits and harms of receiving a polycystic ovary syndrome (PCOS) diagnosis in a community sample of women, including impact on psychosocial wellbeing, lifestyle choices and behaviour? SUMMARY ANSWER: Although some women benefit considerably from the diagnosis, such as through increased awareness and reassurance, women with minimal symptoms may experience more harm than benefit, including long-lasting anxiety and altered life plans. WHAT IS KNOWN ALREADY: Disease labels can validate symptoms and play a vital role in understanding and coping with illness; however, they can also cause harm by evoking illness schemas about severity and permanence. Regarding PCOS, the diagnostic criteria have expanded over time to include women with milder phenotypes (such as those without signs of androgen excess). This has occurred despite limited investigation of the benefits and harms of the diagnosis and has increased the number of women diagnosed. STUDY DESIGN SIZE DURATION: Semi-structured interviews were conducted face-to-face or by telephone with 26 participants from April-July 2018 to explore women's experiences with the diagnosis, including the benefits and harms of receiving the diagnosis and the impact on their life. PARTICIPANTS/MATERIALS SETTING METHODS: In total, 26 women in the community self-reporting a diagnosis of PCOS (reporting mild to severe symptoms) made by a medical doctor, aged 18-45 years and living in Australia were recruited through social media. Data were analysed thematically using Framework analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The study identified a range of both positive and negative effects of a PCOS diagnosis in the immediate, short and long-term, which were influenced by symptom severity, expectations and experience. For women with previously unexplained and bothersome symptoms, it was a relief to receive a diagnosis, and this resulted in an increased understanding about the importance of a healthy lifestyle. By contrast, women with milder symptoms often reported feeling shocked and overwhelmed by the diagnosis, consequently experiencing anxiety about the associated long-term risks. The majority of women, regardless of symptom severity, experienced prolonged worry and anxiety about infertility, resulting for some in risk taking with contraception, unintended pregnancies, pressure to conceive early or altered life plans. With time, many women developed positive coping strategies and perceived the diagnosis to be valuable, including those who felt they had experienced minimal benefit or even harm. LIMITATIONS REASONS FOR CAUTION: PCOS diagnosis was self-reported and the sample was highly educated. WIDER IMPLICATIONS OF THE FINDINGS: Fear of infertility was salient for many women, underscoring the need for accurate information, counselling and reassurance of fertility potential. Given the risk of significant consequences, health professionals should use a tailored approach to PCOS diagnosis to increase the benefits of appropriate and timely diagnosis for women affected by significant symptoms, while reducing the harms of unnecessarily labelling healthy women for whom the benefits of a diagnosis are small. STUDY FUNDING/COMPETING INTERESTS: The study was funded by the University of Sydney Lifespan Research Network and an NHMRC Program Grant (APP1113532). B.W.M. reports consultancy for ObsEva, Merck, Merck KGaA and Guerbet. No further competing interests exist. TRIAL REGISTRATION NUMBER: N/A.

Antibiotics for bronchiolitis in children.

BACKGROUND: Bronchiolitis is a serious, potentially life-threatening respiratory illness commonly affecting young babies. It is most often caused by Respiratory Syncytial Virus (RSV). The diagnosis is usually made on clinical grounds (especially tachypnoea and wheezing in a child less than two years of age). Antibiotics are not recommended for bronchiolitis unless there is concern about complications such as secondary bacterial pneumonia. Despite this, they are used at rates of 34 to 99% in uncomplicated cases. OBJECTIVES: To evaluate the use of antibiotics for bronchiolitis. SEARCH STRATEGY: We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL) which includes the Acute Respiratory Infection Groups' specialised register, the Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library Issue 3, 2006); MEDLINE (January 1966 to August Week 2, 2006); EMBASE (1990 to March 2006); and Current Contents (2001 to September 2006). SELECTION CRITERIA: Types of studies: single or double blind randomised controlled trials comparing antibiotics to placebo in the treatment of bronchiolitis. TYPES OF PARTICIPANTS: children under the age of two years diagnosed with bronchiolitis using clinical criteria (including respiratory distress preceded by coryzal symptoms with or without fever). Types of interventions: oral, intravenous, intramuscular or inhaled antibiotics versus placebo. Types of outcome measures: primary clinical outcomes: time for the resolution of symptoms/signs (pulmonary markers: respiratory distress; wheeze; crepitations; oxygen saturation; and fever). SECONDARY OUTCOMES: hospital admissions; time to discharge from hospital; re-admissions; complications/adverse events developed; and radiological findings. DATA COLLECTION AND ANALYSIS: All data were analysed using Review Manager software, version 4.2.7. MAIN RESULTS: One study met our inclusion criteria. It randomised children presenting clinically with bronchiolitis to either ampicillin or placebo. The main outcome measure was duration of illness and death. There was no significant difference between the two groups for length of illness and there were no deaths in either group. AUTHORS' CONCLUSIONS: This review found no evidence to support the use of antibiotics for bronchiolitis. This results needs to be treated with caution given only one RCT justified inclusion. It is unlikely that simple RCTs of antibiotics against placebo for bronchiolitis will be undertaken in future. Research to identify a possible small subgroup of patients presenting with bronchiolitis-like symptoms who may benefit from antibiotics may be justified. Otherwise, research may be better focussed on determining the reasons for clinicians to use antibiotics so readily for bronchiolitis, and ways of reducing their anxiety, and therefore their use of antibiotics for bronchiolitis.

Early invasive versus conservative strategies for unstable angina & non-ST-elevation myocardial infarction in the stent era.

BACKGROUND: In patients with unstable angina and non-ST-elevation myocardial infarction (UA/NSTEMI) two strategies are possible: a routine invasive strategy where all patients undergo coronary angiography shortly after admission and, if indicated, coronary revascularization; or a conservative strategy where medical therapy alone is used initially with selection of patients for angiography based on clinical symptoms or investigational evidence of persistent myocardial ischemia. OBJECTIVES: To determine the benefits of an invasive compared to a conservative strategy for treating UA/NSTEMI in the stent era. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (Issue 3 2005), MEDLINE and EMBASE were searched from 1996 to September 2005 with no language restrictions. SELECTION CRITERIA: Included studies were prospective trials comparing invasive with conservative strategies in UA/NSTEMI. DATA COLLECTION AND ANALYSIS: We identified 5 studies (7818 participants). Using intention-to-treat analysis with random effects models, summary estimates of relative risk (95% confidence interval [CI]) were determined for primary end-points of all-cause death, fatal and non-fatal myocardial infarction; all-cause death or non-fatal myocardial infarction; and refractory angina. Further analysis of included studies was undertaken based on whether glycoprotein IIb/IIIa receptor antagonists were used routinely. Heterogeneity was assessed using chi-square and variance (I(2)) methods. MAIN RESULTS: In the all-study analysis, mortality during initial hospitalization showed a trend to hazard with an invasive strategy; relative risk 1.59 (95% CI 0.96 to 2.64). Mortality and myocardial infarction assessed at 2-5 years in two trials were significantly decreased by an invasive strategy with relative risk of 0.75 (95% CI 0.62 to 0.92) and 0.75 (95% CI 0.61 to 0.91) respectively. The composite end-point of death or non-fatal myocardial infarction was significantly decreased by an invasive strategy at several time points after initial hospitalization. The incidence of early (<4 months) and intermediate (6-12 months) refractory angina were both significantly decreased by an invasive strategy; relative risk 0.47 (95% CI 0.32 to 0.68) and 0.67 (95% CI 0.55 to 0.83) respectively, as were early and intermediate rehospitalization rates with relative risk 0.60 (95% CI 0.41 to 0.88) and 0.67 (95% CI 0.61 to 0.74) respectively. The invasive strategy was associated with a two-fold increase in the relative risk of peri-procedural myocardial infarction (as variably defined) and a 1.7-fold increase in the relative risk of bleeding. AUTHORS' CONCLUSIONS: An early invasive strategy is preferable to a conservative strategy in the treatment of UA/NSTEMI.

Leukocyte Hsp72 mRNA transcription does not differ between males and females during heat acclimation.

Purpose: Thermotolerance is an acquired state of increased cytoprotection achieved following single or repeated exposures to heat stress, in part characterized by changes in the intracellular 72 kda heat shock protein (HSP72; HSPA1A). Females have demonstrated reduced exercise induced HSP72 in comparison to males. This study examined sex differences in heat shock protein 72 messenger ribonucleic acid (Hsp72 mRNA) transcription during heat acclimation (HA) to identify whether sex differences were a result of differential gene transcription. Methods: Ten participants (5M, 5F) performed 10, 90 min controlled hyperthermia [rectal temperature (Tre) ≥ 38.5°C] HA sessions over 12 d. Leukocyte Hsp72 mRNA was measured pre and post D1, D5, and D10, via Reverse transcription polymerase chain reaction (RT-QPCR). Results: HA was evidenced by a reduction in resting Tre (-0.4 ± 0.5°C) and resting heart rate [(HR); -13 ± 7 beats.min-1] following HA (p ≤ 0.05). During HA no difference (p > 0.05) was observed in ΔTre between males (D1 = 1.5 ± 0.2°C; D5 = 1.6 ± 0.4°C; D10 = 1.8 ± 0.3°C) and females (D1 = 1.5 ± 0.5°C; D5 = 1.4 ± 0.2°C; D10 = 1.8 ± 0.3°C). This was also true of mean Tre demonstrating equality of thermal stimuli for mRNA transcription and HA. There were no differences (p > 0.05) in Hsp72 mRNA expression between HA sessions or between males (D1 = +1.8 ± 1.5-fold; D5 = +2.0 ± 1.0 fold; D10 = +1.1 ± 0.4-fold) and females (D1 = +2.6 ± 1.8-fold; D5 = +1.8 ± 1.4-fold; D10 = +0.9 ± 1.9-fold). Conclusions: This experiment demonstrates that there is no difference in Hsp72 mRNA increases during HA between sexes when controlled hyperthermia HA is utilised. Gender specific differences in exercise-induced HSP72 reported elsewhere likely result from post-transcriptional events.

Identifying studies for systematic reviews of diagnostic tests was difficult due to the poor sensitivity and precision of methodologic filters and the lack of information in the abstract.

BACKGROUND AND OBJECTIVES: Methods to identify studies for systematic reviews of diagnostic accuracy are less well developed than for reviews of intervention studies. This study assessed (1) the sensitivity and precision of five published search strategies and (2) the reliability and accuracy of reviewers screening the results of the search strategy. METHODS: We compared the results of the search filters with the studies included in two systematic reviews, and assessed the interobserver reliability of two reviewers screening the list of articles generated by a search strategy. RESULTS: In the first review, the search strategy published by van der Weijden had the greatest sensitivity, and in the second, four search strategies had 100% sensitivity. There was "substantial" agreement between two reviewers, but in the first review each reviewer working on their own would have missed one paper eligible for inclusion in the review. Ascertainment intersection techniques indicate that it is unlikely that further papers have been missed in the screening process. CONCLUSION: Published search strategies may miss papers for reviews of diagnostic test accuracy. Papers are not easily identified as studies of diagnostic test accuracy, and the lack of information in the abstract makes it difficult to assess the eligibility for inclusion in a systematic review.

Vascular correlates of circular type manic-depressive disorder.

An ambulant patient with a regular series of mood changes constantly varying between retarded depression and hypomania on a 32- to 36-day cycle was studied for 39 weeks. The patient completed a daily self-assessment of the 11-point Dorland mood scale each evening. This scale encompasses a range of moods varying from depression through euthymia to mania. Weekly recordings each lasting 65 min were made of resting heart rate, 14 parameters derived from electrical impedance plethysmography of the head together with arterial blood pressures before and after each recording. Results were correlated with the changing mood scores. Time series analysis of the mood scores yielded a recurrent mood cycle of 35 days unchanged by such drug treatments as had been prescribed by the psychiatrist. The mood score correlated positively with the impedance amplitude, inflow angle, and transit times, and negatively with percent rise time, heart rate, and blood pressures. Amplitudes, rise times, and CT2 were independent of heart rate and blood pressures and hence probably related more closely to cerebral blood flow.

Carotid-vertebral artery blood transit time: results in healthy subjects and patients with schizophrenia and brain disease.

Estimation of blood transit time in the neck and the extension of this into the head was made by a method of electrical impedance, over a wide age range, in 159 healthy subjects, 160 schizophrenic patients, and 199 patients with organic brain disease. In each case, the distance between the electrocardiogram and the next succeeding pulse-volume impedance wave was measured and averaged over 30 serial wave forms. Chronological age proved a significant variable, transit times lengthening progressively with the age, but only for measurements extending into the head. Sex and hemispheric laterality played no significant role. With age held constant, mean transit times into the head were significantly prolonged in both groups of patients as compared with controls. No significant differences were found however between means of psychiatric andneurological patients. It is suggested that these results reinforce the organic etiology of schizophrenia.

Maternal effects on progeny in Thymelaea hirsuta.

In the evergreen desert shrub. Thymelaea hirsuta (L.) Endl., three major gender variants produce seed. 'Stable females' produce seed throughout the reproductive life of the individual, whereas the other two variants are dichogamous, producing both pollen and ovules at different limes, as 'protandrous', and 'protogynous' individuals. Seed was collected from individuals of the three maternal gender phenotypes, from six desert habitats in Egypt. Seed and seedling traits (seed mass, germination. Seedling emergence, growth and survival to 30 d, and to 1 yr) Were examined in laboratory and botanic garden experiments. Highly significant effects of maternal habitat were observed for most of these traits. Seedling height after 30 d differed significantly between habitats and maternal gender phenotypes. Plants from saline and non-saline depressions were significantly taller than those from other sites, and progeny of females, overall, were taller than those of protandrous and protogynous seed parents. A significant interaction was observed between maternal habitat and maternal gender phenotype, for progeny height after 30 d and for per cent seed germination. We suggest that the three maternal gender phenotypes might be differentially favoured by selection.

Systematic review: terlipressin in acute oesophageal variceal haemorrhage.

BACKGROUND: Controversy exists surrounding pharmacological therapy in acute variceal bleeding. AIM: To determine the efficacy and safety of terlipressin. METHODS: Randomized trials were identified and duplicate, independent, review identified 20 randomized trials involving 1609 patients that compared terlipressin with placebo, balloon tamponade, endoscopic treatment, octreotide, somatostatin or vasopressin for treatment of acute oesophageal variceal haemorrhage. RESULTS: Meta-analysis showed that compared to placebo, terlipressin reduced mortality (relative risk 0.66, 95% CI 0.49-0.88), failure of haemostasis (relative risk 0.63, 95% CI 0.45-0.89) and the number of emergency procedures per patient required for uncontrolled bleeding or rebleeding (relative risk 0.72, 95% CI 0.55-0.93). When used as an adjuvant to endoscopic sclerotherapy, terlipressin reduced failure of haemostasis (relative risk 0.75, 95% CI 0.58-0.96), and had an effect on reducing mortality that approached statistical significance (relative risk 0.74, 95% CI 0.53-1.04). No significant difference was demonstrated between terlipressin and endoscopic sclerotherapy, balloon tamponade, somatostatin or vasopressin. Haemostasis was achieved more frequently with octreotide compared to terlipressin (relative risk 1.62, 95% CI 1.05-2.50), but this result was based on unblinded studies. Adverse events were similar between terlipressin and the other comparison groups except for vasopressin, which caused more withdrawals due to adverse events. CONCLUSIONS: Terlipressin is a safe and effective treatment for acute oesophageal variceal bleeding, with or without adjuvant endoscopic sclerotherapy. Terlipressin appears to reduce mortality in acute oesophageal variceal bleeding compared to placebo, and is the only pharmacological agent shown to do so. Future studies will be required to detect potential mortality differences between terlipressin and other therapeutic approaches.

Effects of prior heavy exercise on phase II pulmonary oxygen uptake kinetics during heavy exercise.

We tested the hypothesis that heavy-exercise phase II oxygen uptake (VO(2)) kinetics could be speeded by prior heavy exercise. Ten subjects performed four protocols involving 6-min exercise bouts on a cycle ergometer separated by 6 min of recovery: 1) moderate followed by moderate exercise; 2) moderate followed by heavy exercise; 3) heavy followed by moderate exercise; and 4) heavy followed by heavy exercise. The VO(2) responses were modeled using two (moderate exercise) or three (heavy exercise) independent exponential terms. Neither moderate- nor heavy-intensity exercise had an effect on the VO(2) kinetic response to subsequent moderate exercise. Although heavy-intensity exercise significantly reduced the mean response time in the second heavy exercise bout (from 65.2 +/- 4.1 to 47.0 +/- 3.1 s; P < 0.05), it had no significant effect on either the amplitude or the time constant (from 23.9 +/- 1.9 to 25.3 +/- 2.9 s) of the VO(2) response in phase II. Instead, this "speeding" was due to a significant reduction in the amplitude of the VO(2) slow component. These results suggest phase II VO(2) kinetics are not speeded by prior heavy exercise.

Oxygen uptake kinetics during treadmill running in boys and men.

The purpose of this study was to compare the kinetics of the oxygen uptake (VO(2)) response of boys to men during treadmill running using a three-phase exponential modeling procedure. Eight boys (11-12 yr) and eight men (21-36 yr) completed an incremental treadmill test to determine lactate threshold (LT) and maximum VO(2). Subsequently, the subjects exercised for 6 min at two different running speeds corresponding to 80% of VO(2) at LT (moderate exercise) and 50% of the difference between VO(2) at LT and maximum VO(2) (heavy exercise). For moderate exercise, the time constant for the primary response was not significantly different between boys [10.2 +/- 1.0 (SE) s] and men (14.7 +/- 2.8 s). The gain of the primary response was significantly greater in boys than men (239.1 +/- 7.5 vs. 167.7 +/- 5.4 ml. kg(-1). km(-1); P < 0.05). For heavy exercise, the VO(2) on-kinetics were significantly faster in boys than men (primary response time constant = 14.9 +/- 1.1 vs. 19.0 +/- 1.6 s; P < 0.05), and the primary gain was significantly greater in boys than men (209.8 +/- 4.3 vs. 167.2 +/- 4.6 ml. kg(-1). km(-1); P < 0.05). The amplitude of the VO(2) slow component was significantly smaller in boys than men (19 +/- 19 vs. 289 +/- 40 ml/min; P < 0.05). The VO(2) responses at the onset of moderate and heavy treadmill exercise are different between boys and men, with a tendency for boys to have faster on-kinetics and a greater initial increase in VO(2) for a given increase in running speed.

Oxygen uptake kinetics in treadmill running and cycle ergometry: a comparison.

The purpose of the present study was to comprehensively examine oxygen consumption (VO(2)) kinetics during running and cycling through mathematical modeling of the breath-by-breath gas exchange responses to moderate and heavy exercise. After determination of the lactate threshold (LT) and maximal oxygen consumption (VO(2 max)) in both cycling and running exercise, seven subjects (age 26.6 +/- 5.1 yr) completed a series of "square-wave" rest-to-exercise transitions at running speeds and cycling power outputs that corresponded to 80% LT and 25, 50, and 75%Delta (Delta being the difference between LT and VO(2 max)). VO(2) responses were fit with either a two- (LT) exponential model. The parameters of the VO(2) kinetic response were similar between exercise modes, except for the VO(2) slow component, which was significantly (P < 0.05) greater for cycling than for running at 50 and 75%Delta (334 +/- 183 and 430 +/- 159 ml/min vs. 205 +/- 84 and 302 +/- 154 ml/min, respectively). We speculate that the differences between the modes are related to the higher intramuscular tension development in heavy cycle exercise and the higher eccentric exercise component in running. This may cause a relatively greater recruitment of the less efficient type II muscle fibers in cycling.

Effect of endurance training on oxygen uptake kinetics during treadmill running.

The purpose of this study was to examine the effect of endurance training on oxygen uptake (VO(2)) kinetics during moderate [below the lactate threshold (LT)] and heavy (above LT) treadmill running. Twenty-three healthy physical education students undertook 6 wk of endurance training that involved continuous and interval running training 3-5 days per week for 20-30 min per session. Before and after the training program, the subjects performed an incremental treadmill test to exhaustion for determination of the LT and the VO(2 max) and a series of 6-min square-wave transitions from rest to running speeds calculated to require 80% of the LT and 50% of the difference between LT and maximal VO(2). The training program caused small (3-4%) but significant increases in LT and maximal VO(2) (P<0.05). The VO(2) kinetics for moderate exercise were not significantly affected by training. For heavy exercise, the time constant and amplitude of the fast component were not significantly affected by training, but the amplitude of the VO(2) slow component was significantly reduced from 321+/-32 to 217+/-23 ml/min (P<0.05). The reduction in the slow component was not significantly correlated to the reduction in blood lactate concentration (r = 0. 39). Although the reduction in the slow component was significantly related to the reduction in minute ventilation (r = 0.46; P<0.05), it was calculated that only 9-14% of the slow component could be attributed to the change in minute ventilation. We conclude that the VO(2) slow component during treadmill running can be attenuated with a short-term program of endurance running training.

Randomised controlled trial to examine the effects of a GP exercise referral programme in Hailsham, East Sussex, on modifiable coronary heart disease risk factors.

OBJECTIVE: To examine the effects of a GP exercise referral programme on modifiable coronary heart disease risk factors. DESIGN: Randomised controlled trial. A battery of validated measures were carried out at 0, 8, 16, 26, and 37 weeks. SETTING: Two community health centres and a leisure centre in Hailsham, East Sussex. SUBJECTS: 389 patients (smokers, hypertensive or overweight) were selected from medical records, screened for contraindications to exercise and 345 were invited into the study. Of 142 patients randomly allocated, 40 (41%) completed the study in the exercise group and 31 (69%) in the control group. Sixty (35%) invited smokers (48% of non-smokers), 71 (38%) invited hypertensive patients (45% of non-hypertensive patients), and 107 (45%) overweight patients (33% of non-overweight patients) were randomised. Of those randomised, 27 (45%) smokers, 52 (48%) overweight, and 43 (61%) hypertensive patients completed the study. INTERVENTION: The exercise group was offered 20, half price sessions over 10 weeks at a leisure centre. Patients engaged in moderate and vigorous aerobic type activity on various exercise machines, in a semi-supervised, informal environment. RESULTS: 87% of those referred used the prescription and 28% (high adherers)(45% of obese patients) did at least 15 sessions. The exercise group reduced sum of skinfolds by 8.1% (2.9 to 13.3, 95% confidence intervals) more than the control group, up to 16 weeks after baseline. High adherers reduced sum of skinfolds by 9.2% (0.9 to 17.5) more than the control group, up to 26 weeks. High adherers reduced systolic blood pressure by 7.2% (-0.7 to 14.9) (that is, 9 mm Hg) more than low adherers, up to 37 weeks. Non-smokers and obese patients attended more prescribed sessions than smokers and non-overweight patients. CONCLUSIONS: Reduction in sum of skinfolds was maintained up to 26 weeks, among high adherers compared with controls. Reduction in systolic blood pressure was evident up to 37 weeks among high adherers, but only in comparison with low adherers. Selection of appropriate referees and use of other strategies to improve exercise adherence will help to maximise the benefits from GP exercise prescription schemes.