Electronic Mapping of a Bacterial Genome with Dual Solid-State Nanopores and Active Single-Molecule Control.

We present an electronic mapping of a bacterial genome using solid-state nanopore technology. A dual-nanopore architecture and active control logic are used to produce single-molecule data that enables estimation of distances between physical tags installed at sequence motifs within double-stranded DNA. Previously developed "DNA flossing" control logic generates multiple scans of each captured DNA.

Postpartum blood pressure self-management following hypertensive pregnancy: protocol of the Physician Optimised Post-partum Hypertension Treatment (POP-HT) trial.

Introduction: New-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.

Testing the short-term effectiveness of primary care referral to online weight loss programmes: A randomised controlled trial.

Guidelines ask health professionals to offer brief advice to encourage weight loss for people living with obesity. We tested whether referral to one of three online programmes could lead to successful weight loss. A total of 528 participants aged ≥18 years with a body mass index of ≥30 kg/m were invited via a letter from their GP.

Extended follow-up of a short total diet replacement programme: results of the Doctor Referral of Overweight People to Low Energy total diet replacement Treatment (DROPLET) randomised controlled trial at 3 years.

Objectives: To test the long-term effectiveness of a total diet replacement programme (TDR) for routine treatment of obesity in a primary care setting.

Methods: 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.

Short-Term Postpartum Blood Pressure Self-Management and Long-Term Blood Pressure Control: A Randomized Controlled Trial.

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The early use of Antibiotics for at Risk CHildren with InfluEnza-like illness (ARCHIE): a double-blind randomised placebo-controlled trial.

Introduction: The UK government stockpiles co-amoxiclav to treat bacterial complications during influenza pandemics. This pragmatic trial examines whether early co-amoxiclav use reduces reconsultation due to clinical deterioration in "at risk" children presenting with influenza-like illness (ILI) in primary or ambulatory care.

Methods: "At risk" children aged from 6 months to 12 years presenting within 5 days of ILI onset were randomly assigned to oral co-amoxiclav 400/57 or a placebo twice daily for 5 days (dosing based on age±weight).

Treating sleep problems in young people at ultra-high-risk of psychosis: study protocol for a single-blind parallel group randomised controlled feasibility trial (SleepWell).

Background: Effective 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.

Generalizability of Blood Pressure Lowering Trials to Older Patients: Cross-Sectional Analysis.

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.

Effect of Antihypertensive Medication Reduction vs Usual Care on Short-term Blood Pressure Control in Patients With Hypertension Aged 80 Years and Older: The OPTIMISE Randomized Clinical Trial.

Importance: 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.

Objective: 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.

Design, Setting, And Participants: 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.

Effectiveness and Cost-Effectiveness of a Self-Guided Internet Intervention for Social Anxiety Symptoms in a General Population Sample: Randomized Controlled Trial.

Background: Many people are accessing digital self-help for mental health problems, often with little evidence of effectiveness. Social anxiety is one of the most common sources of mental distress in the population, and many people with symptoms do not seek help for what represents a significant public health problem.

Objective: This study aimed to evaluate the effectiveness of a self-guided cognitive behavioral internet intervention for people with social anxiety symptoms in the general population.

What the public think about participation in medical research during an influenza pandemic: an international cross-sectional survey.

Objectives: The public and patients are primary contributors and beneficiaries of pandemic-relevant clinical research. However, their views on research participation during a pandemic have not been systematically studied. We aimed to understand public views regarding participation in clinical research during a hypothetical influenza pandemic.

Barriers to a software reminder system for risk assessment of stroke in atrial fibrillation: a process evaluation of a cluster randomised trial in general practice.

Background: Oral anticoagulants reduce the risk of stroke in patients with atrial fibrillation (AF), but are underused. AURAS-AF (AUtomated Risk Assessment for Stroke in AF) is a software tool designed to identify eligible patients and promote discussions within consultations about initiating anticoagulants.

Aim: To investigate the implementation of the software in UK general practice.

OPtimising Treatment for MIld Systolic hypertension in the Elderly (OPTiMISE): protocol for a randomised controlled non-inferiority trial.

Introduction: Recent evidence suggests that larger blood pressure reductions and multiple antihypertensive drugs may be harmful in older people, particularly frail individuals with polypharmacy and multimorbidity. However, there is a lack of evidence to support deprescribing of antihypertensives, which limits the practice of medication reduction in routine clinical care. The aim of this trial is to examine whether antihypertensive medication reduction is possible in older patients without significant changes in blood pressure control at follow-up.

Self-Management of Postnatal Hypertension: The SNAP-HT Trial.

Unlabelled: 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.

Gefitinib and Methotrexate to Treat Ectopic Pregnancies with a Pre-Treatment Serum hCG 1000-10,000 IU/L: Phase II Open Label, Single Arm Multi-Centre Trial.

Background: Ectopic pregnancies are a leading cause of maternal mortality. Most are treated surgically. We evaluated the efficacy and safety of combining oral gefitinib (epidermal growth factor receptor inhibitor) with methotrexate to treat larger ectopic pregnancies.

Mitigating the effect of persistent postnatal depression on child outcomes through an intervention to treat depression and improve parenting: a randomised controlled trial.

Background: Maternal postnatal depression occurs following 10-15% of births and is associated with a range of negative child outcomes. Risks to children are particularly increased when postnatal depression is persistent. We aimed to examine whether a parenting video-feedback therapy (VFT) intervention versus a control treatment of progressive muscle relaxation (PMR), both added to cognitive behavioural therapy (CBT) for persistent postnatal depression, would lead to improved child outcomes at age 2 years.

Effectiveness and cost-effectiveness of a fully self-guided internet-based intervention for sub-clinical social anxiety symptoms: Protocol for a randomised controlled trial.

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.

Automated Software System to Promote Anticoagulation and Reduce Stroke Risk: Cluster-Randomized Controlled Trial.

Background And Purpose: Oral anticoagulants (OAC) substantially reduce risk of stroke in atrial fibrillation, but uptake is suboptimal. Electronic health records enable automated identification of people at risk but not receiving treatment. We investigated the effectiveness of a software tool (AURAS-AF [Automated Risk Assessment for Stroke in Atrial Fibrillation]) designed to identify such individuals during routine care through a cluster-randomized trial.

Cost of fertility treatment and live birth outcome in women of different ages and BMI.

Study Question: What is the impact of different age and BMI groups on total investigation and treatment costs in women attending a secondary/tertiary care fertility clinic?

Summary Answer: Women in their early to mid-30s and women with normal BMI had higher cumulative investigation and treatment costs, but also higher probability of live birth.

What Is Known Already: Female age and BMI have been used as criteria for rationing publically funded fertility treatments. Population-based data on the costs of investigating and treating infertility are lacking.

Factors associated with failed treatment: an analysis of 121,744 women embarking on their first IVF cycles.

Background: 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.

Methods And Findings: 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.

Phase II single arm open label multicentre clinical trial to evaluate the efficacy and side effects of a combination of gefitinib and methotrexate to treat tubal ectopic pregnancies (GEM II): study protocol.

Introduction: Tubal ectopic pregnancy (tEP) is the most common life-threatening condition in gynaecology. tEPs with pretreatment serum human chorionic gonadotrophin (hCG) levels <1000 IU/L respond well to outpatient medical treatment with intramuscular methotrexate (MTX). TEPs with hCG >1000 IU/L take a significant time to resolve with MTX and require multiple outpatient monitoring visits.

A pragmatic RCT of conventional versus increased concentration sucrose in freezing and thawing solutions for human embryos.

Background: Intact frozen-thawed embryos have a greater potential than damaged embryos to establish successful pregnancies. This study aimed to determine whether elevated concentrations of sucrose during freezing would increase the proportion of patients with ≥ 50% of embryos intact after thawing (primary outcome), and improve clinical outcome.

Methods: In a two arm, parallel group, pragmatic trial, IVF/ICSI couples were randomized prospectively to have their supernumerary embryos frozen in a medium containing 0.

Acupuncture for pain relief during induced labour in nulliparae: a randomised controlled study.

Objective: To assess the role of acupuncture for analgesia during labour.

Design: Double-blind study of manual, electro and sham acupuncture, and single-blind study comparing acupuncture with a control group for analgesia for labour induction.

Setting: A major obstetric unit in the UK.

Clomifene citrate and intrauterine insemination as first-line treatments for unexplained infertility: are they cost-effective?

Background: First-line treatments for unexplained infertility traditionally include clomifene citrate (CC) or unstimulated intrauterine insemination (IUI). A recently published randomized controlled trial considered the effectiveness of CC and IUI in patients with unexplained infertility and found that neither treatment offered a superior live birth rate when compared with expectant management (EM). This paper reports the economic evaluation conducted alongside this trial in order to assess whether health care providers are gaining value for money in this clinical area.