NHS programme linked to 20% reduction in risk of Diabetes

An NHS behaviour-change programme has been linked to a significant reduction in the risk of developing Type 2 Diabetes in adults with raised blood sugars | University of Manchester | PLoS Medicine

Analysis carried out by University of Manchester researchers shows that when controlling for the characteristics of participants, the risk of Diabetes progression was 20% lower in people with pre-diabetes referred to the NHS Diabetes Prevention Programme (NDPP) when compared to similar patients not referred to NDPP. The study, funded by the National Institute for Health and Care Research (NIHR), and hosted by Northern Care Alliance NHS Foundation Trust, is published in the journal PLoS Medicine.

The NHS Healthier You Diabetes Prevention Programme in England is offered to non-diabetic adults with raised blood sugars – or pre-diabetes – providing exercise and dietary advice to help reduce people’s risk of developing the disease. Latest data shows that over 1.2 million people have been offered support through the programme.

Full detail: NHS programme linked to 20% reduction in risk of Diabetes

Full research paper: Referral to the NHS Diabetes Prevention Programme and conversion from nondiabetic hyperglycaemia to type 2 diabetes mellitus in England: A matched cohort analysis

See also: NHS scheme reduces chances of Type 2 diabetes for at risk adults | NHS England

A Community-Powered NHS

A Community-Powered NHS: Making prevention a reality | New Local

This report argues for a health care system that is focused as much on preventing illness as treating it. It discusses how working collaboratively with communities as equal partners in the design and delivery of health care could be a way of achieving this.

Full detail: A Community-Powered NHS: Making prevention a reality

See also:

• Executive summary
• Podcast: A Community-Powered NHS: Making prevention a reality

A Cluster-Randomized Trial of Hydroxychloroquine for Prevention of Covid-19

BACKGROUND

Current strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited to nonpharmacologic interventions. Hydroxychloroquine has been proposed as a postexposure therapy to prevent coronavirus disease 2019 (Covid-19), but definitive evidence is lacking.

METHODS

We conducted an open-label, cluster-randomized trial involving asymptomatic contacts of patients with polymerase-chain-reaction (PCR)–confirmed Covid-19 in Catalonia, Spain. We randomly assigned clusters of contacts to the hydroxychloroquine group (which received the drug at a dose of 800 mg once, followed by 400 mg daily for 6 days) or to the usual-care group (which received no specific therapy). The primary outcome was PCR-confirmed, symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, defined by symptoms compatible with Covid-19 or a positive PCR test regardless of symptoms. Adverse events were assessed for up to 28 days.

RESULTS

The analysis included 2314 healthy contacts of 672 index case patients with Covid-19 who were identified between March 17 and April 28, 2020. A total of 1116 contacts were randomly assigned to receive hydroxychloroquine and 1198 to receive usual care. Results were similar in the hydroxychloroquine and usual-care groups with respect to the incidence of PCR-confirmed, symptomatic Covid-19 (5.7% and 6.2%, respectively; risk ratio, 0.86 [95% confidence interval, 0.52 to 1.42]). In addition, hydroxychloroquine was not associated with a lower incidence of SARS-CoV-2 transmission than usual care (18.7% and 17.8%, respectively). The incidence of adverse events was higher in the hydroxychloroquine group than in the usual-care group (56.1% vs. 5.9%), but no treatment-related serious adverse events were reported.

CONCLUSIONS

Postexposure therapy with hydroxychloroquine did not prevent SARS-CoV-2 infection or symptomatic Covid-19 in healthy persons exposed to a PCR-positive case patient. (Funded by the crowdfunding campaign YoMeCorono and others; BCN-PEP-CoV2 ClinicalTrials.gov number, NCT04304053. opens in new tab.)

Reference: N Engl J Med 2021; 384:417-427

A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19

BACKGROUND

Coronavirus disease 2019 (Covid-19) occurs after exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For persons who are exposed, the standard of care is observation and quarantine. Whether hydroxychloroquine can prevent symptomatic infection after SARS-CoV-2 exposure is unknown.

METHODS

We conducted a randomized, double-blind, placebo-controlled trial across the United States and parts of Canada testing hydroxychloroquine as postexposure prophylaxis. We enrolled adults who had household or occupational exposure to someone with confirmed Covid-19 at a distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high-risk exposure) or while wearing a face mask but no eye shield (moderate-risk exposure). Within 4 days after exposure, we randomly assigned participants to receive either placebo or hydroxychloroquine (800 mg once, followed by 600 mg in 6 to 8 hours, then 600 mg daily for 4 additional days). The primary outcome was the incidence of either laboratory-confirmed Covid-19 or illness compatible with Covid-19 within 14 days.

RESULTS

We enrolled 821 asymptomatic participants. Overall, 87.6% of the participants (719 of 821) reported a high-risk exposure to a confirmed Covid-19 contact. The incidence of new illness compatible with Covid-19 did not differ significantly between participants receiving hydroxychloroquine (49 of 414 [11.8%]) and those receiving placebo (58 of 407 [14.3%]); the absolute difference was −2.4 percentage points (95% confidence interval, −7.0 to 2.2; P=0.35). Side effects were more common with hydroxychloroquine than with placebo (40.1% vs. 16.8%), but no serious adverse reactions were reported.

CONCLUSIONS

After high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure. (Funded by David Baszucki and Jan Ellison Baszucki and others; ClinicalTrials.gov number, NCT04308668. opens in new tab.)

Reference: N Engl J Med 2020; 383:517-525

Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 10-year follow-up and registry-based 20-year data in the CAPP2 study

Background

Lynch syndrome is associated with an increased risk of colorectal cancer and with a broader spectrum of cancers, especially endometrial cancer. In 2011, our group reported long-term cancer outcomes (mean follow-up 55·7 months [SD 31·4]) for participants with Lynch syndrome enrolled into a randomised trial of daily aspirin versus placebo. This report completes the planned 10-year follow-up to allow a longer-term assessment of the effect of taking regular aspirin in this high-risk population.

Methods

In the double-blind, randomised CAPP2 trial, 861 patients from 43 international centres worldwide (707 [82%] from Europe, 112 [13%] from Australasia, 38 [4%] from Africa, and four [<1%] from The Americas) with Lynch syndrome were randomly assigned to receive 600 mg aspirin daily or placebo. Cancer outcomes were monitored for at least 10 years from recruitment with English, Finnish, and Welsh participants being monitored for up to 20 years. The primary endpoint was development of colorectal cancer. Analysis was by intention to treat and per protocol. The trial is registered with the ISRCTN registry, number ISRCTN59521990.

Findings

Between January, 1999, and March, 2005, 937 eligible patients with Lynch syndrome, mean age 45 years, commenced treatment, of whom 861 agreed to be randomly assigned to the aspirin group or placebo; 427 (50%) participants received aspirin and 434 (50%) placebo. Participants were followed for a mean of 10 years approximating 8500 person-years. 40 (9%) of 427 participants who received aspirin developed colorectal cancer compared with 58 (13%) of 434 who received placebo. Intention-to-treat Cox proportional hazards analysis revealed a significantly reduced hazard ratio (HR) of 0·65 (95% CI 0·43–0·97; p=0·035) for aspirin versus placebo. Negative binomial regression to account for multiple primary events gave an incidence rate ratio of 0·58 (0·39–0·87; p=0·0085). Per-protocol analyses restricted to 509 who achieved 2 years’ intervention gave an HR of 0·56 (0·34–0·91; p=0·019) and an incidence rate ratio of 0·50 (0·31–0·82; p=0·0057). Non-colorectal Lynch syndrome cancers were reported in 36 participants who received aspirin and 36 participants who received placebo. Intention-to-treat and per-protocol analyses showed no effect. For all Lynch syndrome cancers combined, the intention-to-treat analysis did not reach significance but per-protocol analysis showed significantly reduced overall risk for the aspirin group (HR=0·63, 0·43–0·92; p=0·018). Adverse events during the intervention phase between aspirin and placebo groups were similar, and no significant difference in compliance between intervention groups was observed for participants with complete intervention phase data; details reported previously.

Interpretation

The case for prevention of colorectal cancer with aspirin in Lynch syndrome is supported by our results.

Funding

Cancer Research UK, European Union, MRC, NIHR, Bayer Pharma AG, Barbour Foundation.

Reference: The Lancet, VOLUME 395, ISSUE 10240, P1855-1863, JUNE 13, 2020

Primary Care–Based Interventions to Prevent Illicit Drug Use in Children, Adolescents, and Young Adults

Importance  In 2017, an estimated 7.9% of persons aged 12 to 17 years reported illicit drug use in the past month, and an estimated 50% of adolescents in the US had used an illicit drug by the time they graduated from high school. Young adults aged 18 to 25 years have a higher rate of current illicit drug use, with an estimated 23.2% currently using illicit drugs. Illicit drug use is associated with many negative health, social, and economic consequences and is a significant contributor to 3 of the leading causes of death among young persons (aged 10-24 years): unintentional injuries including motor vehicle crashes, suicide, and homicide.

Objective  To update its 2014 recommendation, the USPSTF commissioned a review of the evidence on the potential benefits and harms of interventions to prevent illicit drug use in children, adolescents, and young adults.

Population  This recommendation applies to children (11 years and younger), adolescents (aged 12-17 years), and young adults (aged 18-25 years), including pregnant persons.

Evidence Assessment  Because of limited and inadequate evidence, the USPSTF concludes that the benefits and harms of primary care–based interventions to prevent illicit drug use in children, adolescents, and young adults are uncertain and that the evidence is insufficient to assess the balance of benefits and harms. More research is needed.

Recommendation  The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of primary care–based behavioral counseling interventions to prevent illicit drug use, including nonmedical use of prescription drugs, in children, adolescents, and young adults. (I statement)

Reference: JAMA. 2020;323(20):2060-2066.

Primary Care Interventions for Prevention and Cessation of Tobacco Use in Children and Adolescents

Importance  Tobacco use is the leading cause of preventable death in the US. An estimated annual 480 000 deaths are attributable to tobacco use in adults, including from secondhand smoke. It is estimated that every day about 1600 youth aged 12 to 17 years smoke their first cigarette and that about 5.6 million adolescents alive today will die prematurely from a smoking-related illness. Although conventional cigarette use has gradually declined among children in the US since the late 1990s, tobacco use via electronic cigarettes (e-cigarettes) is quickly rising and is now more common among youth than cigarette smoking. e-Cigarette products usually contain nicotine, which is addictive, raising concerns about e-cigarette use and nicotine addiction in children. Exposure to nicotine during adolescence can harm the developing brain, which may affect brain function and cognition, attention, and mood; thus, minimizing nicotine exposure from any tobacco product in youth is important.

Objective  To update its 2013 recommendation, the USPSTF commissioned a review of the evidence on the benefits and harms of primary care interventions for tobacco use prevention and cessation in children and adolescents. The current systematic review newly included e-cigarettes as a tobacco product.

Population  This recommendation applies to school-aged children and adolescents younger than 18 years.

Evidence Assessment  The USPSTF concludes with moderate certainty that primary care–feasible behavioral interventions, including education or brief counseling, to prevent tobacco use in school-aged children and adolescents have a moderate net benefit. The USPSTF concludes that there is insufficient evidence to determine the balance of benefits and harms of primary care interventions for tobacco cessation among school-aged children and adolescents who already smoke, because of a lack of adequately powered studies on behavioral counseling interventions and a lack of studies on medications.

Recommendation  The USPSTF recommends that primary care clinicians provide interventions, including education or brief counseling, to prevent initiation of tobacco use among school-aged children and adolescents. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of primary care–feasible interventions for the cessation of tobacco use among school-aged children and adolescents. (I statement)

Reference: JAMA. 2020;323(16):1590-1598.

Application of non-HDL cholesterol for population-based cardiovascular risk stratification

Background

The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment.

Methods

In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol.

Findings

Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7–59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0–20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0–1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6–2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0–1·3 to 2·3, 2·0–2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced.

Interpretation

Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician–patient communication about primary prevention strategies.

Funding

EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research.

Reference: The Lancet, VOLUME 394, ISSUE 10215, P2173-2183, DECEMBER 14, 2019

Polypill for Cardiovascular Disease Prevention in an Underserved Population

BACKGROUND

Persons with low socioeconomic status and nonwhite persons in the United States have high rates of cardiovascular disease. The use of combination pills (also called “polypills”) containing low doses of medications with proven benefits for the prevention of cardiovascular disease may be beneficial in such persons. However, few data are available regarding the use of polypill therapy in underserved communities in the United States, in which adherence to guideline-based care is generally low.

METHODS

We conducted a randomized, controlled trial involving adults without cardiovascular disease. Participants were assigned to the polypill group or the usual-care group at a federally qualified community health center in Alabama. Components of the polypill were atorvastatin (at a dose of 10 mg), amlodipine (2.5 mg), losartan (25 mg), and hydrochlorothiazide (12.5 mg). The two primary outcomes were the changes from baseline in systolic blood pressure and low-density lipoprotein (LDL) cholesterol level at 12 months.

RESULTS

The trial enrolled 303 adults, of whom 96% were black. Three quarters of the participants had an annual income below $15,000. The mean estimated 10-year cardiovascular risk was 12.7%, the baseline blood pressure was 140/83 mm Hg, and the baseline LDL cholesterol level was 113 mg per deciliter. The monthly cost of the polypill was $26. At 12 months, adherence to the polypill regimen, as assessed on the basis of pill counts, was 86%. The mean systolic blood pressure decreased by 9 mm Hg in the polypill group, as compared with 2 mm Hg in the usual-care group (difference, −7 mm Hg; 95% confidence interval [CI], −12 to −2; P=0.003). The mean LDL cholesterol level decreased by 15 mg per deciliter in the polypill group, as compared with 4 mg per deciliter in the usual-care group (difference, −11 mg per deciliter; 95% CI, −18 to −5; P<0.001).

CONCLUSIONS

A polypill-based strategy led to greater reductions in systolic blood pressure and LDL cholesterol level than were observed with usual care in a socioeconomically vulnerable minority population. (Funded by the American Heart Association Strategically Focused Prevention Research Network and the National Institutes of Health; ClinicalTrials.gov number, NCT02278471. opens in new tab.)

Reference N Engl J Med 2019; 381:1114-1123

Effectiveness of polypill for primary and secondary prevention of cardiovascular diseases (PolyIran)

Background

A fixed-dose combination therapy (polypill strategy) has been proposed as an approach to reduce the burden of cardiovascular disease, especially in low-income and middle-income countries (LMICs). The PolyIran study aimed to assess the effectiveness and safety of a four-component polypill including aspirin, atorvastatin, hydrochlorothiazide, and either enalapril or valsartan for primary and secondary prevention of cardiovascular disease.

Methods

The PolyIran study was a two-group, pragmatic, cluster-randomised trial nested within the Golestan Cohort Study (GCS), a cohort study with 50 045 participants aged 40–75 years from the Golestan province in Iran. Clusters (villages) were randomly allocated (1:1) to either a package of non-pharmacological preventive interventions alone (minimal care group) or together with a once-daily polypill tablet (polypill group). Randomisation was stratified by three districts (Gonbad, Aq-Qala, and Kalaleh), with the village as the unit of randomisation. We used a balanced randomisation algorithm, considering block sizes of 20 and balancing for cluster size or natural log of the cluster size (depending on the skewness within strata). Randomisation was done at a fixed point in time (Jan 18, 2011) by statisticians at the University of Birmingham (Birmingham, UK), independent of the local study team. The non-pharmacological preventive interventions (including educational training about healthy lifestyle—eg, healthy diet with low salt, sugar, and fat content, exercise, weight control, and abstinence from smoking and opium) were delivered by the PolyIran field visit team at months 3 and 6, and then every 6 months thereafter. Two formulations of polypill tablet were used in this study. Participants were first prescribed polypill one (hydrochlorothiazide 12·5 mg, aspirin 81 mg, atorvastatin 20 mg, and enalapril 5 mg). Participants who developed cough during follow-up were switched by a trained study physician to polypill two, which included valsartan 40 mg instead of enalapril 5 mg. Participants were followed up for 60 months. The primary outcome—occurrence of major cardiovascular events (including hospitalisation for acute coronary syndrome, fatal myocardial infarction, sudden death, heart failure, coronary artery revascularisation procedures, and non-fatal and fatal stroke)—was centrally assessed by the GCS follow-up team, who were masked to allocation status. We did intention-to-treat analyses by including all participants who met eligibility criteria in the two study groups. The trial was registered with ClinicalTrials.gov, number NCT01271985.

Findings

Between Feb 22, 2011, and April 15, 2013, we enrolled 6838 individuals into the study—3417 (in 116 clusters) in the minimal care group and 3421 (in 120 clusters) in the polypill group. 1761 (51·5%) of 3421 participants in the polypill group were women, as were 1679 (49·1%) of 3417 participants in the minimal care group. Median adherence to polypill tablets was 80·5% (IQR 48·5–92·2). During follow-up, 301 (8·8%) of 3417 participants in the minimal care group had major cardiovascular events compared with 202 (5·9%) of 3421 participants in the polypill group (adjusted hazard ratio [HR] 0·66, 95% CI 0·55–0·80). We found no statistically significant interaction with the presence (HR 0·61, 95% CI 0·49–0·75) or absence of pre-existing cardiovascular disease (0·80; 0·51–1·12; p_interaction=0·19). When restricted to participants in the polypill group with high adherence, the reduction in the risk of major cardiovascular events was even greater compared with the minimal care group (adjusted HR 0·43, 95% CI 0·33–0·55). The frequency of adverse events was similar between the two study groups. 21 intracranial haemorrhages were reported during the 5 years of follow-up—ten participants in the polypill group and 11 participants in the minimal care group. There were 13 physician-confirmed diagnoses of upper gastrointestinal bleeding in the polypill group and nine in the minimal care group.

Interpretation

Use of polypill was effective in preventing major cardiovascular events. Medication adherence was high and adverse event numbers were low. The polypill strategy could be considered as an additional effective component in controlling cardiovascular diseases, especially in LMICs.

Funding

Tehran University of Medical Sciences, Barakat Foundation, and Alborz Darou.

Reference: The Lancet, VOLUME 394, ISSUE 10199, P672-683, AUGUST 24, 2019