In-vitro fertilization (IVF) is the treatment of choice for unresolved infertility. It comprises a number of key steps, each of which has to be negotiated before the next is attempted, but the ...factors which are associated with failure at each stage have not been reported.
We analyzed anonymised national data on women undergoing their first fresh autologous IVF and intracytoplasmic sperm injection (ICSI) cycle in the United Kingdom between 2000 and 2007 to predict factors associated with overall lack of livebirth as well as the chance of non-progress at different stages of an IVF cycle. A total of 121,744 women were included in this analysis. Multivariable models underlined the importance of increased female age and duration of infertility, lack of previous pregnancy, and a diagnosis of tubal or male factor infertility in predicting the risk of not having a live birth in an IVF treatment. At each stage, a woman's chance of proceeding to the next stage of IVF treatment is affected by increased age and duration of infertility. The intention to use intra-cytoplasmic sperm injection (ICSI) is associated with a decreased risk of treatment failure in women starting an IVF cycle (RR 0.93, 99% CI 0.92, 0.94) but this association is reversed at a later stage once fertilisation has been confirmed (RR=1.01, 99%CI 1.00, 1.03).
Female age is a key predictor of failure to have a livebirth following IVF as well as the risk of poor performance at each stage of treatment. While increased duration of infertility is also associated with worse outcomes at every stage, its impact appears to be less influential. Women embarking on ICSI treatment for male factor infertility have a lower chance of treatment failure but this does not appear to be due to increased chances of implantation of ICSI embryos.
BACKGROUND/OBJECTIVES
Randomized controlled trials are used to inform clinical guidelines on the management of hypertension in older adults, but it is unclear to what extent these trials represent ...the general population attending routine clinical practice. This study aimed to define the proportion and characteristics of patients eligible for hypertension trials conducted in older people.
DESIGN
Cross‐sectional study.
SETTING
A total of 24 general practices in England.
PARTICIPANTS
Anonymized electronic health record data from all individuals aged 80 and older.
MEASUREMENTS
Descriptive statistics were used to define the proportion and characteristics of patients eligible for two previous medication intensification trials (HYVET, SPRINT) and one medication reduction trial (OPTiMISE). A logistic regression model was constructed to estimate predictors of eligibility for each trial.
RESULTS
Of 15,376 patients identified, 268 (1.7%; 95% confidence interval CI = 1.5–2.0%), 5,290 (34.4%; 95%CI = 33.7–35.2%), and 3,940 (25.6%; 95%CI = 24.9–26.3%) were eligible for the HYVET, SPRINT, and OPTiMISE trials, respectively. Between 5.6% and 30.7% of exclusions from each trial were due to eligibility criteria excluding those with high or uncontrolled blood pressure. Frailty (odds ratio OR = .44; 95%CI = .36–.54 OPTiMISE), cardiovascular polypharmacy (OR = .61; 95%CI = .55–.68 SPRINT) and multimorbidity (OR = .72; 95%CI = .64–.82 SPRINT) were associated with a lower likelihood of being eligible for one or more of the trials.
CONCLUSION
A possible unintended consequence of blood pressure criteria used by trials attempting to answer different primary questions is that for many older patients, no trial evidence exists to inform treatment decisions in routine practice. Caution should be exercised when applying results from existing trials to patients with frailty or multimorbidity.
See related editorial by Jeff D. Williamson in this issue.
BackgroundEffective interventions, targeting key contributory causal factors, are needed to prevent the emergence of severe mental health problems in young people. Insomnia is a common clinical issue ...that is problematic in its own right but that also leads to the development and persistence of psychotic experiences. The implication is that treating sleep problems may prevent the onset of psychosis. We collected initial case series data with 12 young people at ultra-high-risk of psychosis. Post-intervention, there were improvements in sleep, depression and psychotic experiences. Now we test the feasibility of a randomised controlled trial, with a clinical aim to treat sleep problems and hence reduce depression, psychotic experiences, and prevent transition to psychosis.Methods and analysisA randomised controlled feasibility trial will be conducted. Forty patients aged 14 to 25 years who are at ultra-high-risk of psychosis and have sleep disturbance will be recruited from National Health Service (NHS) mental health services. Participants will be randomised to receive either a novel, targeted, youth-focussed sleep intervention in addition to usual care or usual care alone. Assessor-blinded assessments will be conducted at baseline, 3 months (post-intervention) and 9 months (follow-up). The eight-session psychological intervention will target the key mechanisms which disrupt sleep: circadian rhythm irregularities, low sleep pressure, and hyperarousal. To gain an in-depth understanding of participants’ views on the acceptability of the intervention and study procedures, 16 participants (n=10 intervention, n=6 control) will take part in qualitative interviews. Analyses will focus on feasibility outcomes (recruitment, retention, and treatment uptake rates) and provide initial CI estimates of intervention effects. Thematic analysis of the qualitative interviews will assess the acceptability of the intervention and trial procedures.Ethics and disseminationThe trial has received ethical approval from the NHS Health Research Authority. Findings will be disseminated through peer-reviewed publications, conference presentations, and lay networks.Trial registration numberISRCTN85601537.
IntroductionNew-onset hypertension affects approximately 10% of pregnancies and is associated with a significant increase in risk of cardiovascular disease in later life, with blood pressure measured ...6 weeks postpartum predictive of blood pressure 5–10 years later. A pilot trial has demonstrated that improved blood pressure control, achevied via self-management during the puerperium, was associated with lower blood pressure 3-4 years postpartum. Physician Optimised Post-partum Hypertension Treatment (POP-HT) will formally evaluate whether improved blood pressure control in the puerperium results in lower blood pressure at 6 months post partum, and improvements in cardiovascular and cerebrovascular phenotypes.Methods and analysisPOP-HT is an open-label, parallel arm, randomised controlled trial involving 200 women aged 18 years or over, with a diagnosis of pre-eclampsia or gestational hypertension, and requiring antihypertensive medication at discharge. Women are recruited by open recruitment and direct invitation around time of delivery and randomised 1:1 to, either an intervention comprising physician-optimised self-management of postpartum blood pressure or, usual care. Women in the intervention group upload blood pressure readings to a ‘smartphone’ app that provides algorithm-driven individualised medication-titration. Medication changes are approved by physicians, who review blood pressure readings remotely. Women in the control arm follow assessment and medication adjustment by their usual healthcare team. The primary outcome is 24-hour average ambulatory diastolic blood pressure at 6–9 months post partum. Secondary outcomes include: additional blood pressure parameters at baseline, week 1 and week 6; multimodal cardiovascular assessments (CMR and echocardiography); parameters derived from multiorgan MRI including brain and kidneys; peripheral macrovascular and microvascular measures; angiogenic profile measures taken from blood samples and levels of endothelial circulating and cellular biomarkers; and objective physical activity monitoring and exercise assessment. An additional 20 women will be recruited after a normotensive pregnancy as a comparator group for endothelial cellular biomarkers.Ethics and disseminationIRAS PROJECT ID 273353. This trial has received a favourable opinion from the London—Surrey Research Ethics Committee and HRA (REC Reference 19/LO/1901). The investigator will ensure that this trial is conducted in accordance with the principles of the Declaration of Helsinki and follow good clinical practice guidelines. The investigators will be involved in reviewing drafts of the manuscripts, abstracts, press releases and any other publications arising from the study. Authors will acknowledge that the study was funded by the British Heart Foundation Clinical Research Training Fellowship (BHF Grant number FS/19/7/34148). Authorship will be determined in accordance with the ICMJE guidelines and other contributors will be acknowledged.Trial registration numberNCT04273854.
Cognitive-behavioural therapy (CBT) for childhood anxiety disorders is associated with modest outcomes in the context of parental anxiety disorder.
This study evaluated whether or not the outcome of ...CBT for children with anxiety disorders in the context of maternal anxiety disorders is improved by the addition of (i) treatment of maternal anxiety disorders, or (ii) treatment focused on maternal responses. The incremental cost-effectiveness of the additional treatments was also evaluated.
Participants were randomised to receive (i) child cognitive-behavioural therapy (CCBT); (ii) CCBT with CBT to target maternal anxiety disorders CCBT + maternal cognitive-behavioural therapy (MCBT); or (iii) CCBT with an intervention to target mother-child interactions (MCIs) (CCBT + MCI).
A NHS university clinic in Berkshire, UK.
Two hundred and eleven children with a primary anxiety disorder, whose mothers also had an anxiety disorder.
All families received eight sessions of individual CCBT. Mothers in the CCBT + MCBT arm also received eight sessions of CBT targeting their own anxiety disorders. Mothers in the MCI arm received 10 sessions targeting maternal parenting cognitions and behaviours. Non-specific interventions were delivered to balance groups for therapist contact.
Primary clinical outcomes were the child's primary anxiety disorder status and degree of improvement at the end of treatment. Follow-up assessments were conducted at 6 and 12 months. Outcomes in the economic analyses were identified and measured using estimated quality-adjusted life-years (QALYs). QALYS were combined with treatment, health and social care costs and presented within an incremental cost-utility analysis framework with associated uncertainty.
MCBT was associated with significant short-term improvement in maternal anxiety; however, after children had received CCBT, group differences were no longer apparent. CCBT + MCI was associated with a reduction in maternal overinvolvement and more confident expectations of the child. However, neither CCBT + MCBT nor CCBT + MCI conferred a significant post-treatment benefit over CCBT in terms of child anxiety disorder diagnoses adjusted risk ratio (RR) 1.18, 95% confidence interval (CI) 0.87 to 1.62, p = 0.29; adjusted RR CCBT + MCI vs. control: adjusted RR 1.22, 95% CI 0.90 to 1.67, p = 0.20, respectively or global improvement ratings (adjusted RR 1.25, 95% CI 1.00 to 1.59, p = 0.05; adjusted RR 1.20, 95% CI 0.95 to 1.53, p = 0.13). CCBT + MCI outperformed CCBT on some secondary outcome measures. Furthermore, primary economic analyses suggested that, at commonly accepted thresholds of cost-effectiveness, the probability that CCBT + MCI will be cost-effective in comparison with CCBT (plus non-specific interventions) is about 75%.
Good outcomes were achieved for children and their mothers across treatment conditions. There was no evidence of a benefit to child outcome of supplementing CCBT with either intervention focusing on maternal anxiety disorder or maternal cognitions and behaviours. However, supplementing CCBT with treatment that targeted maternal cognitions and behaviours represented a cost-effective use of resources, although the high percentage of missing data on some economic variables is a shortcoming. Future work should consider whether or not effects of the adjunct interventions are enhanced in particular contexts. The economic findings highlight the utility of considering the use of a broad range of services when evaluating interventions with this client group.
Current Controlled Trials ISRCTN19762288.
This trial was funded by the Medical Research Council (MRC) and Berkshire Healthcare Foundation Trust and managed by the National Institute for Health Research (NIHR) on behalf of the MRC-NIHR partnership (09/800/17) and will be published in full in Health Technology Assessment; Vol. 19, No. 38.
Deprescribing of antihypertensive medications is recommended for some older patients with polypharmacy and multimorbidity when the benefits of continued treatment may not outweigh the harms.
This ...study aimed to establish whether antihypertensive medication reduction is possible without significant changes in systolic blood pressure control or adverse events during 12-week follow-up.
The Optimising Treatment for Mild Systolic Hypertension in the Elderly (OPTIMISE) study was a randomized, unblinded, noninferiority trial conducted in 69 primary care sites in England. Participants, whose primary care physician considered them appropriate for medication reduction, were aged 80 years and older, had systolic blood pressure lower than 150 mm Hg, and were receiving at least 2 antihypertensive medications were included. Participants enrolled between April 2017 and September 2018 and underwent follow-up until January 2019.
Participants were randomized (1:1 ratio) to a strategy of antihypertensive medication reduction (removal of 1 drug intervention, n = 282) or usual care (control, n = 287), in which no medication changes were mandated.
The primary outcome was systolic blood pressure lower than 150 mm Hg at 12-week follow-up. The prespecified noninferiority margin was a relative risk (RR) of 0.90. Secondary outcomes included the proportion of participants maintaining medication reduction and differences in blood pressure, frailty, quality of life, adverse effects, and serious adverse events.
Among 569 patients randomized (mean age, 84.8 years; 276 48.5% women; median of 2 antihypertensive medications prescribed at baseline), 534 (93.8%) completed the trial. Overall, 229 (86.4%) patients in the intervention group and 236 (87.7%) patients in the control group had a systolic blood pressure lower than 150 mm Hg at 12 weeks (adjusted RR, 0.98 97.5% 1-sided CI, 0.92 to ∞). Of 7 prespecified secondary end points, 5 showed no significant difference. Medication reduction was sustained in 187 (66.3%) participants at 12 weeks. Mean change in systolic blood pressure was 3.4 mm Hg (95% CI, 1.1 to 5.8 mm Hg) higher in the intervention group compared with the control group. Twelve (4.3%) participants in the intervention group and 7 (2.4%) in the control group reported at least 1 serious adverse event (adjusted RR, 1.72 95% CI, 0.7 to 4.3).
Among older patients treated with multiple antihypertensive medications, a strategy of medication reduction, compared with usual care, was noninferior with regard to systolic blood pressure control at 12 weeks. The findings suggest antihypertensive medication reduction in some older patients with hypertension is not associated with substantial change in blood pressure control, although further research is needed to understand long-term clinical outcomes.
EudraCT Identifier: 2016-004236-38; ISRCTN identifier: 97503221.
Design and objective
This paper describes the protocol for a large-scale pragmatic, randomised controlled trial and economic evaluation to investigate the effectiveness and cost-effectiveness of the ...self-directed E-Couch social anxiety module versus a waiting list control condition, for reducing sub-clinical social anxiety symptoms in the general population.
Study population
Community-based adults (aged 18+) with social anxiety symptoms that do not meet the criteria for social anxiety disorder recruited via a direct-to-consumer advertisement on national websites.
Intervention and control
Intervention is the self-guided E-Couch social anxiety module. Control group participants are placed on a waiting list to receive the intervention at the end of the trial. Both groups receive email and text message reminders.
Outcome measures
The primary outcome will be change in self-reported social anxiety score using the Social Phobia Inventory (SPIN). Secondary outcomes will be the changes in the following self-report measures: Brief Fear of Negative Evaluation scale (BFNE-S); depression (CES-D); mental wellbeing (SWEMWEBS); health status (SF36); use of health services; safety events; and adherence, retention, and attrition rates. All measures will be administered at baseline, 6 weeks, and 3, 6 and 12 months.
Analysis
A mixed effects model will be used to analyse the effect of the intervention on the primary and secondary outcomes (intention to treat analysis). Secondary analyses will explore moderators and mediators of effect. A prospective economic evaluation, conducted from a NHS and social care perspective, will provide estimates of cost utility and cost-effectiveness. An interview study will be conducted with 20 participants to explore issues including acceptability, adherence, retention and attrition.
Trial registration numbers
NCT02451878 and ISRCTN15819951
Hypertension affects 1 in 10 pregnancies, often persisting postpartum, when antihypertensive requirements may vary substantially. This unmasked, randomized controlled trial evaluated the feasibility ...and effects on blood pressure (BP) of self-management of postpartum hypertension. Women with gestational hypertension or preeclampsia, requiring postnatal antihypertensive treatment, were randomized to self-management or usual care. Self-management entailed daily home BP monitoring and automated medication reduction via telemonitoring. Women attended 5 follow-up visits during 6 months. The primary outcome was feasibility: specifically recruitment, retention, and compliance with follow-up rates. Secondary outcomes included BP control and safety, analyzed on an intention-to-treat basis. Forty-nine percent (91/186) of those women approached were randomized (45 intervention, 46 control), and 90% (82/91) finished follow-up. The groups had similar baseline characteristics. After randomization, BP was lower in the intervention group, most markedly at 6 weeks: intervention group mean (SD), systolic 121.6 (8.7)/diastolic 80.5 (6.6) mm Hg; control group, systolic 126.6 (11.0)/diastolic 86.0 (9.7) mm Hg; adjusted differences (95% confidence interval), systolic -5.2 (-9.3 to -1.2)/diastolic -5.8 (-9.1 to -2.5) mm Hg. Diastolic BP remained significantly lower in those self-managing to 6 months: adjusted difference -4.5 (-8.1 to -0.8) mm Hg. This is the first randomized evaluation of BP self-management postpartum and indicates it would be feasible to trial this intervention in larger studies. Self-management resulted in better diastolic BP control to 6 months, even beyond medication cessation.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT02333240.
To test the long-term effectiveness of a total diet replacement programme (TDR) for routine treatment of obesity in a primary care setting.
This study was a pragmatic, two-arm, parallel-group, ...open-label, individually randomised controlled trial in adults with obesity. The outcomes were change in weight and biomarkers of diabetes and cardiovascular disease risk from baseline to 3 years, analysed as intention-to-treat with mixed effects models.
The intervention was TDR for 8 weeks, followed by food-reintroduction over 4 weeks. Behavioural support was provided weekly for 8 weeks, bi-weekly for the next 4 weeks, then monthly for 3 months after which no further support was provided. The usual care (UC) group received dietary advice and behavioural support from a practice nurse for up to 3 months.
Outcome measures were collected from 179 (66%) participants. Compared with baseline, at 3 years the TDR group lost -6.2 kg (SD 9.1) and usual care -2.7 kg (SD 7.7); adjusted mean difference -3.3 kg (95% CI: -5.2, -1.5), p < 0.0001. Regain from programme end (6 months) to 3 years was greater in TDR group +8.9 kg (SD 9.4) than UC + 1.2, (SD 9.1); adjusted mean difference +6.9 kg (95% CI 4.2, 9.5) P < 0.001. At 3 years TDR led to greater reductions than UC in diastolic blood pressure (mean difference -3.3 mmHg (95% CI:-6.2; -0.4) P = 0.024), and systolic blood pressure (mean differences -3.7 mmHg (95% CI: -7.4; 0.1) P = 0.057). There was no evidence of differences between groups in the change from baseline to 3 years HbA
(-1.9 mmol/mol (95% CI: -0.7; 4.5; P = 0.15), LDL cholesterol concentrations (0.2 mmol/L (95% CI -0.3, 0.7) P = 0.39), cardiovascular risk score (QRISK2) (-0.37 (95% CI -0.96; 0.22); P = 0.22).
Treatment of people with obesity with a TDR programme compared with support from a practice nurse leads to greater weight loss which persists to at least 3 years, but there was only evidence of sustained improvements in BP and not in other aspects of cardiometabolic risk.
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