The effect of psychiatric decision unit services on inpatient admissions and mental health presentations in emergency departments: an interrupted time series analysis from two cities and one rural area in England.

AIMS: High-quality evidence is lacking for the impact on healthcare utilisation of short-stay alternatives to psychiatric inpatient services for people experiencing acute and/or complex mental health crises (known in England as psychiatric decision units [PDUs]). We assessed the extent to which changes in psychiatric hospital and emergency department (ED) activity were explained by implementation of PDUs in England using a quasi-experimental approach. METHODS: We conducted an interrupted time series (ITS) analysis of weekly aggregated data pre- and post-PDU implementation in one rural and two urban sites using segmented regression, adjusting for temporal and seasonal trends. Primary outcomes were changes in the number of voluntary inpatient admissions to (acute) adult psychiatric wards and number of ED adult mental health-related attendances in the 24 months post-PDU implementation compared to that in the 24 months pre-PDU implementation. RESULTS: The two PDUs (one urban and one rural) with longer (average) stays and high staff-to-patient ratios observed post-PDU decreases in the pattern of weekly voluntary psychiatric admissions relative to pre-PDU trend (Rural: -0.45%/week, 95% confidence interval [CI] = -0.78%, -0.12%; Urban: -0.49%/week, 95% CI = -0.73%, -0.25%); PDU implementation in each was associated with an estimated 35-38% reduction in total voluntary admissions in the post-PDU period. The (urban) PDU with the highest throughput, lowest staff-to-patient ratio and shortest average stay observed a 20% (-20.4%, CI = -29.7%, -10.0%) level reduction in mental health-related ED attendances post-PDU, although there was little impact on long-term trend. Pooled analyses across sites indicated a significant reduction in the number of voluntary admissions following PDU implementation (-16.6%, 95% CI = -23.9%, -8.5%) but no significant (long-term) trend change (-0.20%/week, 95% CI = -0.74%, 0.34%) and no short- (-2.8%, 95% CI = -19.3%, 17.0%) or long-term (0.08%/week, 95% CI = -0.13, 0.28%) effects on mental health-related ED attendances. Findings were largely unchanged in secondary (ITS) analyses that considered the introduction of other service initiatives in the study period. CONCLUSIONS: The introduction of PDUs was associated with an immediate reduction of voluntary psychiatric inpatient admissions. The extent to which PDUs change long-term trends of voluntary psychiatric admissions or impact on psychiatric presentations at ED may be linked to their configuration. PDUs with a large capacity, short length of stay and low staff-to-patient ratio can positively impact ED mental health presentations, while PDUs with longer length of stay and higher staff-to-patient ratios have potential to reduce voluntary psychiatric admissions over an extended period. Taken as a whole, our analyses suggest that when establishing a PDU, consideration of the primary crisis-care need that underlies the creation of the unit is key.

Search for Evidence of Baryogenesis and Dark Matter in B

A new dark sector antibaryon, denoted ψ_{D}, could be produced in decays of B mesons. This Letter presents a search for B^{+}→ψ_{D}+p (and the charge conjugate) decays in e^{+}e^{-} annihilations at 10.58 GeV, using data collected in the BABAR experiment. Data corresponding to an integrated luminosity of 398 fb^{-1} are analyzed. No evidence for a signal is observed. Branching fraction upper limits in the range from 10^{-7}-10^{-5} are obtained at 90% confidence level for masses of 1.0

Enhancing the communication of functional neurological disorder diagnosis: a multidisciplinary education session.

BACKGROUND AND PURPOSE: Functional neurological disorder (FND) is a common diagnosis within neurology. Effective communication of the diagnosis is known to be an important part of treatment and can result in reduction or cessation of symptoms, as well as decreased healthcare utilisation. A single group education session, facilitated by professionals commonly involved in the care of patients with FND, was developed to further enhance patients' and relatives' understanding and acceptance of diagnosis. METHODS: Patients and relatives attending a single education session were asked to complete self-report ratings of understanding of diagnosis, acceptance of diagnosis, belief in treatability and hopefulness regarding recovery, at the beginning and end of the session. Satisfaction data were also collected. RESULTS: Data were obtained from 193 patients and 153 relatives. Patients had experienced a median duration of symptoms of 4 years, and more than 80% of patients reported more than one functional neurological symptom. There were significant increases in terms of understanding, acceptance, belief in treatability and hopefulness for patients and relatives. Effect sizes ranged from large for improved understanding of FND to small-to-medium for increased agreement with FND diagnosis. High levels of satisfaction were also reported. CONCLUSIONS: A multidisciplinary, single group education session is an effective and acceptable method of increasing understanding and acceptance of an FND diagnosis, even for patients with a long duration of symptoms and high symptom burden. It could help improve readiness for further treatment.

Treatment outcomes in mild traumatic brain injury: a systematic review of randomized controlled trials.

OBJECTIVES: Mild traumatic brain injury (mTBI) is a controversial and under-researched area, despite most traumatic brain injuries being classed as mild. Our objective was to review the evidence underpinning these approaches to treat mTBI including educational, psychological, rehabilitative and pharmacological approaches and discuss their efficacy. METHODS: A systematic review of literature was carried out using Web of science, Scopus, Medline, Pubmed, Cinahl, and PsychInfo databases. Randomized Controlled Trials (RCTs) looking at treatment outcome in mTBI for adults were included, published between 1980 and 2019. Methodological quality of the studies was reviewed using the Scottish Intercollegiate Guideline Network (SIGN) checklist for RCTs. RESULTS: Searches identified 3993 studies, of which 25 met inclusion criteria, and a total number of participants of 3213. Mean age was 35, and 59% male. Ten studies had <100 participants, 15 studies 100-395. Studies were grouped into education and early intervention, rehabilitation (8), psychological interventions (4), and pharmacotherapy (4). Inconsistency of definitions and outcome measures used precluded meta-analysis. CONCLUSIONS: Traditional education and reassurance can no longer be recommended as having the best evidence base for efficacy as compared to psychological and rehabilitative approaches, and guidelines should begin to reflect this.

What is the impact of psychiatric decision units on mental health crisis care pathways? Protocol for an interrupted time series analysis with a synthetic control study.

BACKGROUND: The UK mental health system is stretched to breaking point. Individuals presenting with mental health problems wait longer at the ED than those presenting with physical concerns and finding a bed when needed is difficult - 91% of psychiatric wards are operating at above the recommended occupancy rate. To address the pressure, a new type of facility - psychiatric decision units (also known as mental health decision units) - have been introduced in some areas. These are short-stay facilities, available upon referral, targeted to help individuals who may be able to avoid an inpatient admission or lengthy ED visit. To advance knowledge about the effectiveness of this service for this purpose, we will examine the effect of the service on the mental health crisis care pathway over a 4-year time period; the 2 years proceeding and following the introduction of the service. We use aggregate service level data of key indicators of the performance of this pathway. METHODS: Data from four mental health Trusts in England will be analysed using an interrupted time series (ITS) design with the primary outcomes of the rate of (i) ED psychiatric presentations and (ii) voluntary admissions to mental health wards. This will be supplemented with a synthetic control study with the same primary outcomes, in which a comparable control group is generated for each outcome using a donor pool of suitable National Health Service Trusts in England. The methods are well suited to an evaluation of an intervention at a service delivery level targeting population-level health outcome and the randomisation or 'trialability' of the intervention is limited. The synthetic control study controls for national trends over time, increasing our confidence in the results. The study has been designed and will be carried out with the involvement of service users and carers. DISCUSSION: This will be the first formal evaluation of psychiatric decision units in England. The analysis will provide estimates of the effect of the decision units on a number of important service use indicators, providing much-needed information for those designing service pathways. TRIAL REGISTRATION: primary registry: isrctn.com Identifying number: ISRCTN77588384 Link: Date of registration in primary registry: 27/02/2020. PRIMARY SPONSOR: St George's, University of London, Cramner Road, Tooting, SW17 ORE. Primary contact: Joe Montebello.

Staff attitudes to completely smoke-free policies and smoking cessation practices in a mental health setting.

BACKGROUND: Mental health trusts in England were expected to become completely smoke-free and embed smoking cessation practices by 2018. Such policies are fraught with concerns and have received mixed support from mental health staff. Understanding staff attitudes to these practices prior to enforcement of the policy could help design an effective implementation strategy. METHODS: A cross-sectional survey was conducted with clinical and non-clinical staff in a Mental Health Trust to understand smoking cessation practices and attitudes to the implementation of a completely smoke-free policy. RESULTS: There were 631 responses. Most participants disagreed with the policy on wards (59.6%) and throughout all mental health settings (57.4%). Clinicians expressed significantly lower organizational policy support (P = 0.001) than non-clinicians (P = 0.001). Psychiatrists were more supportive of the organizational items than nurses and allied health professionals. Clinicians' attitudes towards smoking cessation practices were less positive for those who were current smokers (P < 0.001), but more positive for clinicians who had received or were interested in attending smoking cessation training (P < 0.001). CONCLUSIONS: Partial and completely smoke-free policies remain unsupported by staff in mental health settings. Smoking cessation training appears to reinforce rather than alter attitudes towards smoking cessation.

Preheart failure comorbidities and impact on prognosis in heart failure patients: a nationwide study.

BACKGROUND: Data regarding the impact of preheart failure (HF) comorbidities on the prognosis of HF are scarce, especially in the younger HF patients. OBJECTIVES: To investigate pre-existing comorbidities in HF patients versus matched controls and to assess their impact on mortality. METHODS: We included all first-time in-hospital and outpatient diagnoses of HF from 1995 to 2017, and comorbidities antedating the HF-diagnosis in the Danish nationwide registries. HF patients were matched with up to five controls. One-year all-cause mortality rates and population attributable risk (PAR) were estimated for three separate age groups (≤50, 51-74 and >74 years). RESULTS: Totally 280 002 patients with HF and 1 166 773 controls were included. Cardiovascular comorbidities, for example, cerebrovascular disease and ischaemic heart disease were more frequent in the oldest (17.9% and 29.7% in HF vs. 9.8% and 10.7% in controls) compared to the youngest age group (3.9% and 15.2% in HF vs. 0.7% and 0.9% in controls). Amongst patients with HF, 1-year mortality rates (per 100 person-years) were highest amongst those with >1 noncardiovascular comorbidity: ≤50 years (10.4; 9.64-11.3), 51-74 years (23.3; 22.9-23.7), >74 years (58.5; 57.9-59.0); hazard ratios 245.18 (141.45-424.76), 45.85 (42.77-49.15) and 24.5 (23.64-25.68) for those ≤50, 51-74 and >74 years, respectively. For HF patients ≤50 years, PAR was greatest for hypertension (17.8%), cancer (14.1%) and alcohol abuse (8.5%). For those aged >74 years, PAR was greatest for hypertension (23.6%), cerebrovascular disease (6.2%) and cancer (7.2%). CONCLUSIONS: Heart failure patients had a higher burden of pre-existing comorbidities, compared to controls, which adversely impacted prognosis, especially in the young.

Extraction of form Factors from a Four-Dimensional Angular Analysis of B[over ¯]→D

An angular analysis of the decay B[over ¯]→D^{*}ℓ^{-}ν[over ¯]_{ℓ}, ℓ∈{e,µ}, is reported using the full e^{+}e^{-} collision data set collected by the BABAR experiment at the ϒ(4S) resonance. One B meson from the ϒ(4S)→BB[over ¯] decay is fully reconstructed in a hadronic decay mode, which constrains the kinematics and provides a determination of the neutrino momentum vector. The kinematics of the semileptonic decay is described by the dilepton mass squared, q^{2}, and three angles. The first unbinned fit to the full four-dimensional decay rate in the standard model is performed in the so-called Boyd-Grinstein-Lebed approach, which employs a generic q^{2} parametrization of the underlying form factors based on crossing symmetry, analyticity, and QCD dispersion relations for the amplitudes. A fit using the more model-dependent Caprini-Lellouch-Neubert (CLN) approach is performed as well. Our form factor shapes show deviations from previous fits based on the CLN parametrization. The latest form factors also provide an updated prediction for the branching fraction ratio R(D^{*})≡B(B[over ¯]→D^{*}τ^{-}ν[over ¯]_{τ})/B(B[over ¯]→D^{*}ℓ^{-}ν[over ¯]_{ℓ})=0.253±0.005. Finally, using the well-measured branching fraction for the B[over ¯]→D^{*}ℓ^{-}ν[over ¯]_{ℓ} decay, a value of |V_{cb}|=(38.36±0.90)×10^{-3} is obtained that is consistent with the current world average for exclusive B[over ¯]→D^{(*)}ℓ^{-}ν[over ¯]_{ℓ} decays and remains in tension with the determination from inclusive semileptonic B decays to final states with charm.

Observation of the Decay D

We report the observation of the rare charm decay D^{0}→K^{-}π^{+}e^{+}e^{-}, based on 468 fb^{-1} of e^{+}e^{-} annihilation data collected at or close to the center-of-mass energy of the ϒ(4S) resonance with the BABAR detector at the SLAC National Accelerator Laboratory. We find the branching fraction in the invariant mass range 0.675

Search for a Stable Six-Quark State at BABAR.

Recent investigations have suggested that the six-quark combination uuddss could be a deeply bound state (S) that has eluded detection so far, and a potential dark matter candidate. We report the first search for a stable, doubly strange six-quark state in ϒ→SΛ[over ¯]Λ[over ¯] decays based on a sample of 90×10^{6}ϒ(2S) and 110×10^{6}ϒ(3S) decays collected by the BABAR experiment. No signal is observed, and 90% confidence level limits on the combined ϒ(2S,3S)→SΛ[over ¯]Λ[over ¯] branching fraction in the range (1.2-1.4)×10^{-7} are derived for m_{S}<2.05 GeV. These bounds set stringent limits on the existence of such exotic particles.

Echocardiographic right ventricular strain from multiple apical views is superior for assessment of right ventricular systolic function.

BACKGROUND: Right ventricular (RV) systolic function is an important determinant of outcome in patients with pulmonary hypertension (PH). Conventional echocardiographic measures of RV are mainly based on longitudinal contractility. Recently, measurement of RV global longitudinal strain derived from multiple windows (RVGLS) has emerged as an option but has not been well evaluated. The aim of the present study was to evaluate which echocardiographic RV function parameter correlates best with RV ejection fraction derived from cardiac magnetic resonance imaging (RVEFCMR ). METHODS AND RESULTS: Fifty-five patients evaluated for PH underwent RV assessment with echocardiography and CMR. Conventional echocardiographic parameters of RV function including tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (S'), RV fractional area change (RVFAC) and RV index of myocardial performance (RIMP). RVGLS was measured from three separate apical views using a 17-segment model and strain from the lateral free wall was calculated separately (RVfree). The study included 55 patients, whereas assessment of RVGLS could be obtained in 29 patients. The Pearson correlation coefficient with RVEFCMR was strong for RVGLS (r = 0·814, P<0·001) and RVfree (r = 0·778, P<0·001), modest for RVFAC (r = 0·681, P<0·001), TAPSE (r = 0·592, P<0·001) and RIMP (r=-0·521, P<0·01), and weak for S' (r = 0·385, P<0·01). CONCLUSION: The echocardiographic RV measures, RVGLS and RVfree correlated well with RVEFCMR , whereas correlation with TAPSE, RIMP and S' was unsatisfactory. Our findings suggest that RVGLS and RVfree are the preferred echocardiographic methods for clinical practice. RVfree is easiest to perform but RVGLS could provide incremental value in selected patients.

Changing face of orofacial pain: The diagnostic impact of working with Neurology on an orofacial pain clinic.

This study assessed the impact of collaborative working with a headache neurologist on diagnoses of patients attending orofacial pain (OFP) clinic. Patient diagnostic data was collected from adult patients attending an Orofacial Pain Service from January 2013 to January 2017. A liaison headache neurologist was appointed late 2015; OFP clinics were co-run with the neurologist specialist thereafter. Overall, 639 patients attended the service; 315 in 2013-2015 and 324 in 2016-2017. Compared to 2013-2015, there were increased rates of diagnoses related to neurovascular (27.5% vs. 19.0%; P=.012) and musculoskeletal pain (36.9% vs. 26.0%; P=.003) in the 2016-2017 cohort and decreased rates of neuropathic (55.6% vs. 70.2%; P<.001) and atypical/idiopathic pain (1.3% vs. 5.4%; P=.003) diagnoses. There was a trend towards an increased rate of comorbid diagnoses (26.3% vs. 20.3%; P=.077), especially those relating to headache conditions. The findings suggest that introduction of a specialist headache neurologist into the OFP clinic widened its remit of assessment, increasing recognition of (co-morbid) neurovascular-related pain and decreasing atypical/idiopathic pain diagnoses in patients with complex OFP. The increase rate of musculoskeletal pain diagnosis in the later cohort is likely attributable to service expansion and normalisation of diagnostics reportedly seen in other OFP services. Statement of clinical relevance: Orofacial pain is a complex diagnosis, it requires a multidisciplinary approach that includes neurological input.

Measurement of the D

We measure the mass difference, Δm_{+}, between the D^{*}(2010)^{+} and the D^{+} using the decay chain D^{*}(2010)^{+}→D^{+}π^{0} with D^{+}→K^{-}π^{+}π^{+}. The data were recorded with the BABAR detector at center-of-mass energies at and near the ϒ(4S) resonance, and correspond to an integrated luminosity of approximately 468 fb^{-1}. We measure Δm_{+}=(140 601.0±6.8[stat]±12.9[syst]) keV. We combine this result with a previous BABAR measurement of Δm_{0}≡m(D^{*}(2010)^{+})-m(D^{0}) to obtain Δm_{D}=m(D^{+})-m(D^{0})=(4824.9±6.8[stat]±12.9[syst]) keV. These results are compatible with and approximately five times more precise than the Particle Data Group averages.

A brief psychological intervention for mothers of children with food allergy can change risk perception and reduce anxiety: Outcomes of a randomized controlled trial.

BACKGROUND: Mothers of children with food allergy have increased anxiety, which may be influenced by healthcare professionals' communication of risk. OBJECTIVE: To evaluate a brief psychological intervention for reducing anxiety in mothers of children with food allergy. METHODS: Two hundred mothers of children with food allergy were recruited from allergy clinics. A computer-generated randomization list was used to allocate participants to a single-session cognitive behavioural therapy intervention including a risk communication module, or standard care. Anxiety and risk perception were assessed at 6 weeks and 1 year. Primary outcome was state anxiety at 6 weeks. Secondary outcomes included state anxiety at 1 year, risk perception at 6 weeks and 1 year, and salivary cortisol response to a simulated anaphylaxis scenario at 1 year. RESULTS: We found no significant difference in the primary outcome state anxiety at 6 weeks, with mean 31.9 (SD 10.2) intervention, 34.0 (10.2) control; mean difference 2.1 (95% CI -0.9, 5.0; P=.17). There was significantly reduced state anxiety at 6 weeks in the intervention group, in the subgroup of participants with moderate/high anxiety at enrolment (103/200, 52%), with mean 33.0 (SD 9.3) intervention, 37.8 (SD 10.0) control; mean difference 4.8 (95% CI 0.9, 8.7; P=.016; Cohen's d effect size 0.50). The psychological intervention also reduced risk perception and salivary cortisol response (P=.032; effect size 0.36). CONCLUSION: We found evidence that a brief psychological intervention which incorporates accurate risk information may impact on anxiety, risk perception and physiological stress response in mothers of children with food allergy.

Search for B

We search for the rare flavor-changing neutral current process B^{+}→K^{+}τ^{+}τ^{-} using data from the BABAR experiment. The data sample, collected at the center-of-mass energy of the ϒ(4S) resonance, corresponds to a total integrated luminosity of 424 fb^{-1} and to 471×10^{6} BB[over ¯] pairs. We reconstruct one B meson, produced in the ϒ(4S)→B^{+}B^{-} decay, in one of many hadronic decay modes and search for activity compatible with a B^{+}→K^{+}τ^{+}τ^{-} decay in the rest of the event. Each τ lepton is required to decay leptonically into an electron or muon and neutrinos. Comparing the expected number of background events with the data sample after applying the selection criteria, we do not find evidence for a signal. The resulting upper limit, at the 90% confidence level, is B(B^{+}→K^{+}τ^{+}τ^{-})<2.25×10^{-3}.

Search for Invisible Decays of a Dark Photon Produced in e

We search for single-photon events in 53 fb^{-1} of e^{+}e^{-} collision data collected with the BABAR detector at the PEP-II B-Factory. We look for events with a single high-energy photon and a large missing momentum and energy, consistent with production of a spin-1 particle A^{'} through the process e^{+}e^{-}→γA^{'}; A^{'}→invisible. Such particles, referred to as "dark photons," are motivated by theories applying a U(1) gauge symmetry to dark matter. We find no evidence for such processes and set 90% confidence level upper limits on the coupling strength of A^{'} to e^{+}e^{-} in the mass range m_{A^{'}}≤8 GeV. In particular, our limits exclude the values of the A^{'} coupling suggested by the dark-photon interpretation of the muon (g-2)_{µ} anomaly, as well as a broad range of parameters for the dark-sector models.

Dental Pulp Cell Behavior in Biomimetic Environments.

There is emerging recognition of the importance of a physiologically relevant in vitro cell culture environment to promote maintenance of stem cells for tissue engineering and regenerative medicine purposes. In vivo, appropriate cellular cues are provided by local tissue extracellular matrix (ECM), and these are not currently recapitulated well in vitro using traditional cultureware. We therefore hypothesized that better replication of the in vivo environment for cell culture and differentiation could be achieved by culturing dental pulp cells with their associated ECM. Primary dental pulp cells were subsequently seeded onto pulp-derived ECM-coated cultureware. While at up to 24 h they exhibited the same level of adherence as those cells seeded on tissue culture-treated surfaces, by 4 d cell numbers and proliferation rates were significantly decreased in cells grown on pulp ECM compared with controls. Analysis of stem cell and differentiation marker transcripts, as well as Oct 3/4 protein distribution, supported the hypothesis that cells cultured on ECM better maintained a stem cell phenotype compared with those cultured on standard tissue culture-treated surfaces. Subsequent differentiation analysis of cells cultured on ECM demonstrated that they exhibited enhanced mineralization, as determined by alizarin red staining and mineralized marker expression. Supplementation of a 3% alginate hydrogel with pulp ECM components and dental pulp cells followed by differentiation induction in mineralization medium resulted in a time-dependent mineral deposition at the periphery of the construct, as demonstrated histologically and using micro-computed tomography analysis, which was reminiscent of tooth structure. In conclusion, data indicate that culture of pulp cells in the presence of ECM better replicates the in vivo environment, maintaining a stem cell phenotype suitable for downstream tissue engineering applications.

Patients' ability to treat anaphylaxis using adrenaline autoinjectors: a randomized controlled trial.

BACKGROUND: Previous work has shown patients commonly misuse adrenaline autoinjectors (AAI). It is unclear whether this is due to inadequate training, or poor device design. We undertook a prospective randomized controlled trial to evaluate ability to administer adrenaline using different AAI devices. METHODS: We allocated mothers of food-allergic children prescribed an AAI for the first time to Anapen or EpiPen using a computer-generated randomization list, with optimal training according to manufacturer's instructions. After one year, participants were randomly allocated a new device (EpiPen, Anapen, new EpiPen, JEXT or Auvi-Q), without device-specific training. We assessed ability to deliver adrenaline using their AAI in a simulated anaphylaxis scenario six weeks and one year after initial training, and following device switch. Primary outcome was successful adrenaline administration at six weeks, assessed by an independent expert. Secondary outcomes were success at one year, success after switching device, and adverse events. RESULTS: We randomized 158 participants. At six weeks, 30 of 71 (42%) participants allocated to Anapen and 31 of 73 (43%) participants allocated to EpiPen were successful - RR 1.00 (95% CI 0.68-1.46). Success rates at one year were also similar, but digital injection was more common at one year with EpiPen (8/59, 14%) than Anapen (0/51, 0%, P = 0.007). When switched to a new device without specific training, success rates were higher with Auvi-Q (26/28, 93%) than other devices (39/80, 49%; P < 0.001). CONCLUSIONS: AAI device design is a major determinant of successful adrenaline administration. Success rates were low with several devices, but were high using the audio-prompt device Auvi-Q.

Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials.

BACKGROUND: Genetic variants have been associated with the risk of coronary heart disease. In this study, we tested whether or not a composite of these variants could ascertain the risk of both incident and recurrent coronary heart disease events and identify those individuals who derive greater clinical benefit from statin therapy. METHODS: A community-based cohort study (the Malmo Diet and Cancer Study) and four randomised controlled trials of both primary prevention (JUPITER and ASCOT) and secondary prevention (CARE and PROVE IT-TIMI 22) with statin therapy, comprising a total of 48,421 individuals and 3477 events, were included in these analyses. We studied the association of a genetic risk score based on 27 genetic variants with incident or recurrent coronary heart disease, adjusting for traditional clinical risk factors. We then investigated the relative and absolute risk reductions in coronary heart disease events with statin therapy stratified by genetic risk. We combined data from the different studies using a meta-analysis. FINDINGS: When individuals were divided into low (quintile 1), intermediate (quintiles 2-4), and high (quintile 5) genetic risk categories, a significant gradient in risk for incident or recurrent coronary heart disease was shown. Compared with the low genetic risk category, the multivariable-adjusted hazard ratio for coronary heart disease for the intermediate genetic risk category was 1·34 (95% CI 1·22-1·47, p<0·0001) and that for the high genetic risk category was 1·72 (1·55-1·92, p<0·0001). In terms of the benefit of statin therapy in the four randomised trials, we noted a significant gradient (p=0·0277) of increasing relative risk reductions across the low (13%), intermediate (29%), and high (48%) genetic risk categories. Similarly, we noted greater absolute risk reductions in those individuals in higher genetic risk categories (p=0·0101), resulting in a roughly threefold decrease in the number needed to treat to prevent one coronary heart disease event in the primary prevention trials. Specifically, in the primary prevention trials, the number needed to treat to prevent one such event in 10 years was 66 in people at low genetic risk, 42 in those at intermediate genetic risk, and 25 in those at high genetic risk in JUPITER, and 57, 47, and 20, respectively, in ASCOT. INTERPRETATION: A genetic risk score identified individuals at increased risk for both incident and recurrent coronary heart disease events. People with the highest burden of genetic risk derived the largest relative and absolute clinical benefit from statin therapy. FUNDING: National Institutes of Health.