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Nasir Hamid
PREDICTING INDIVIDUAL RISK OF MUSCLE DISORDERS IN PATIENTS ELIGIBLE FOR STATIN TREATMENT: STRATIFY-STATINMD MODEL DERIVATION USING DATA FROM ELECTRONIC HEALTH RECORDS
OBJECTIVE: Concerns about muscle-related adverse events have posed a dilemma when considering statin prescription for prevention of cardiovascular disease (CVD). This study aimed to develop a prediction model for an individual's risk of muscle disorders to support clinical decision making in primary care. DESIGN AND METHOD: A prospective cohort design was adopted, using electronic health records from the Clinical Practice Research Datalink in the UK. Males aged over 50 and females aged over 60, who were potentially eligible for statin treatment based on their underlying CVD risk, were followed-up for ten years. The primary outcome was hospitalisation or death in those with a diagnosis of muscle disorders. The Fine-Gray proportional sub-distribution hazards model was fitted to address competing risk of death from other causes. Statin prescriptions within the 12 months before follow up and other predictors were included in the model based on a literature review. RESULTS: The cohort included 1,785,207 patients, with a mean age of 64 and 44% females. Patients prescribed statins were predicted to have a higher risk of muscle disorders (atorvastatin: hazard ratio = 1.77 [95% confidence interval: 1.58 - 1.97]; rosuvastatin: 2.04 [1.58 - 2.63]; simvastatin: 1.58 [1.45 - 1.71]; other statins (fluvastatin/pravastatin): 1.38 [1.14 - 1.68]). Female sex, deprivation, smoking, obesity, frailty, liver or kidney disease, rheumatic arthritis, previous muscle problems, degenerative joint disorders, hypothyroidism, vitamin D or B12 deficiency, and the use of drugs that are potentially myotoxic or interact with statins also increased an individual's risk (Table). An automated risk calculator was developed based on the model (Figure). CONCLUSIONS: This model uses routinely available patient characteristics and medical history to predict an individual's risk of muscle disorders. The calculator may help clinicians and patients communicate the safety concerns and make shared decisions or monitoring strategies on statin treatment. External validation of this model is ongoing to support general application of the risk calculator in clinical practice.
PREDICTING THE RISK OF FALLS IN PATIENTS WITH AN INDICATION FOR ANTIHYPERTENSIVE TREATMENT: DEVELOPMENT AND VALIDATION OF THE STRATIFY-FALLS PREDICTION MODEL
OBJECTIVE: Falls are one of the most common side effects associated with antihypertensive medication. In patients at high risk of falls, the additional risk of harm from medication may outweigh the potential benefits in terms of cardiovascular risk reduction. However, it is currently unclear which patients are at high risk of falls. This study aimed to develop and validate a clinical prediction model for risk of hospitalisation or death from falls in adults eligible for antihypertensive treatment. DESIGN AND METHOD: Eligible patients were aged 40 and above, with at least one blood pressure measurement between 130-179 mm Hg. The outcome was a fall resulting in hospitalisation or death within 10 years of entering the study. Model development was conducted in data from CPRD GOLD using a Fine-Gray approach, accounting for the competing risk of death from other causes, with subsequent recalibration at specific time-points using pseudo-values. External validation was conducted using data from CPRD Aurum, with performance assessed through calibration curves, the Observed/Expected (O/E) ratio, C-statistic, and D-statistic, each pooled across GP practices. RESULTS: Analysis included 1,773,224 patients (62,691 events) for model development, and 3,805,322 (206,956 events) for external validation. Conditional on other variables, increasing age, being female, of white ethnicity, being a heavy drinker and living in an area of high social deprivation were associated with an increased risk of falls. Upon external validation, the re-calibrated model showed good discrimination, with pooled C-statistics of 0.843 (95%CI: 0.841 to 0.844) and 0.833 (95%CI: 0.831 to 0.835) at 5 and 10 years respectively. Original model calibration was poor on visual inspection and whilst this improved with re-calibration, under-prediction of risk remained (Observed/Expected ratio 1.839 at 10 years, 95%CI: 1.811 to 1.865) (Figure 1). CONCLUSIONS: STRATIFY-Falls uses commonly recorded clinical characteristics and shows good discrimination on external validation, accurately distinguishing between patients at high and low risk of falls in the next 5-10 years. This model may be used in routine clinical practice to help identify those at high risk of falls, for whom the benefits of antihypertensive medication may be outweighed by the harms.
Attainment of NICE blood pressure targets among older people with newly diagnosed hypertension: nationwide linked electronic health records cohort study
Background: it is not known if clinical practice reflects guideline recommendations for the management of hypertension in older people and whether guideline adherence varies according to overall health status. Aims: to describe the proportion of older people attaining National Institute for Health and Care Excellence (NICE) guideline blood pressure targets within 1 year of hypertension diagnosis and determine predictors of target attainment. Methods: a nationwide cohort study of Welsh primary care data from the Secure Anonymised Information Linkage databank including patients aged ≥65 years newly diagnosed with hypertension between 1st June 2011 and 1st June 2016. The primary outcome was attainment of NICE guideline blood pressure targets as measured by the latest blood pressure recording up to 1 year after diagnosis. Predictors of target attainment were investigated using logistic regression. Results: there were 26,392 patients (55% women, median age 71 [IQR 68-77] years) included, of which 13,939 (52.8%) attained a target blood pressure within a median follow-up of 9 months. Success in attaining target blood pressure was associated with a history of atrial fibrillation (OR 1.26, 95% CI 1.11, 1.43), heart failure (OR 1.25, 95% CI 1.06, 1.49) and myocardial infarction (OR 1.20, 95% CI 1.10, 1.32), all compared to no history of each, respectively. Care home residence, the severity of frailty, and increasing co-morbidity were not associated with target attainment following adjustment for confounder variables. Conclusions: blood pressure remains insufficiently controlled 1 year after diagnosis in nearly half of older people with newly diagnosed hypertension, but target attainment appears unrelated to baseline frailty, multi-morbidity or care home residence.
Antihypertensive Deprescribing in Older Adults: a Practical Guide
Purpose of Review: To summarise evidence on both appropriate and inappropriate antihypertensive drug withdrawal. Recent Findings: Deprescribing should be attempted in the following steps: (1) identify patients with several comorbidities and significant functional decline, i.e. people at higher risk for negative outcomes related to polypharmacy and lower blood pressure; (2) check blood pressure; (3) identify candidate drugs for deprescribing; (4) withdraw medications at 4-week intervals; (5) monitor blood pressure and check for adverse events. Although evidence is accumulating regarding short-term outcomes of antihypertensive deprescribing, long-term effects remain unclear. Summary: The limited evidence for antihypertensive deprescribing means that it should not be routinely attempted, unless in response to specific adverse events or following discussions between physicians and patients about the uncertain benefits and harms of the treatment. Perspectives: Clinical controlled trials are needed to examine the long-term effects of deprescribing in older subjects, especially in those with comorbidities, and significant functional decline.
PREDICTING THE RISK OF SYNCOPE IN PATIENTS WITH AN INDICATION FOR ANTIHYPERTENSIVE TREATMENT: DEVELOPMENT OF THE STRATIFY-SYNCOPE PREDICTION MODEL
OBJECTIVE: Syncope is one of the most common side effects associated with antihypertensive medication. In patients at increased of syncope, the additional risk of harm from antihypertensive medication may outweigh the potential benefits of treatment in terms of cardiovascular risk reduction. However, it is unclear how to identify patients at most risk of syncope events. This study aimed to develop a clinical prediction model for risk of hospitalisation or death from syncope. DESIGN AND METHOD: This was a cohort study using data from the Clinical Practice Research Datalink (CPRD) in the UK. The electronic health records of patients aged greater than 40, with at least one blood pressure measurement between 130-179 mmHg were included. Outcomes were defined as a syncope event resulting in hospitalisation or death within 10 years of baseline. Predictors of syncope were based on the literature and expert opinion and included patient characteristics, past medical history and prescribed treatment (including antihypertensive prescription). A Fine-Gray model was used to adjust for competing risk of mortality and results are reported as subdistribution hazard ratios (SHR). RESULTS: A total of 1,772,617 patients were eligible for the study, with mean age of 59 and 48% males. Median follow up was 6.2 years with 39898 syncope events (2.3%). The antihypertensive medications most strongly associated with syncope were alpha blockers (SHR: 1.21, 95%CI 1.15 to 1.28) and ACE inhibitors (SHR: 1.19, 95%CI 1.16 to 1.22). Other important predictors included age (Figure 1), male sex, high social deprivation, heavy alcohol consumption, previous syncope, diabetes, dementia, structural cardiac problems, arrhythmias, spinal cord injuries, parkinsonism, cardiopulmonary disease and prescription of antidepressants, antipsychotics and opioids (table 1). CONCLUSIONS: This prediction model identified a number of strong predictors of syncope which are routinely available in an individual's electronic health records. The accuracy of this model will examined in a further ∼3,000,000 patients from a different electronic health record database. If it is found to perform well, such a model could be used to provide personalised estimates of an individual's risk of harm from antihypertensive treatment, thus facilitating more informed treatment choices.
The association between prehospital care and in-hospital treatment decisions in acute stroke: A cohort study
Background: Hospital prealerting in acute stroke improves the timeliness of subsequent treatment, but little is known about the impact of prehospital assessments on in-hospital care. Objective: Examine the association between prehospital assessments and notification by emergency medical service staff on the subsequent acute stroke care pathway. Methods: This was a cohort study of linked patient medical records. Consenting patients with a diagnosis of stroke were recruited from two urban hospitals. Data from patient medical records were extracted and entered into a Cox regression analysis to investigate the association between time to CT request and recording of onset time, stroke recognition (using the Face Arm Speech Test (FAST)) and sending of a prealert message. Results: 151 patients (aged 71±15 years) travelled to hospital via ambulance and were eligible for this analysis. Time of symptom onset was recorded in 61 (40%) cases, the FAST test was positive in 114 (75%) and a prealert message was sent in 65 (44%). Following adjustment for confounding, patients who had time of onset recorded (HR 0.73, 95% CI 0.52 to 1.03), were FAST-positive (HR 0.54, 95% CI 0.37 to 0.80) or were prealerted (HR 0.26, 95% CI 0.18 to 0.38), were more likely to receive a timely CT request in hospital. Conclusions: This study highlights the importance of hospital prealerting, accurate stroke recognition, and recording of onset time. Those not recognised with stroke in a prehospital setting appear to be excluded from the possibility of rapid treatment in hospital, even before they have been seen by a specialist.
Measuring adherence to antihypertensive medication using an objective test in older adults attending primary care: cross-sectional study
Analysis of urine samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS) has previously revealed high rates of non-adherence to antihypertensive medication. It is unclear whether these rates represent those in the general population. This study aimed to investigate whether it is feasible to collect urine samples in a primary care setting and analyse them using LC-MS/MS to detect non-adherence to antihypertensive medication. This study used a prospective, observational cohort design. Consecutive patients were recruited opportunistically from five general practices in UK primary care. They were aged ≥65 years with hypertension and had at least one antihypertensive prescription. Participants were asked to provide a urine sample for analysis of medication adherence. Samples were sent to a laboratory via post and analysed using LC-MS/MS. Predictors of adherence to medication were explored with multivariable logistic regression. Of 349 consecutive patients approached for the study, 214 (61.3%) gave informed consent and 191 (54.7%) provided a valid urine sample for analysis. Participants were aged 76.2 ± 6.6 years and taking a median of 2 antihypertensive medications (IQR 1–3). A total of 27/191 participants (14.2%) reported not taking all of their medications on the day of urine sample collection. However, LC-MS/MS analysis of samples revealed only 4/27 (9/191 in total; 4.7%) were non-adherent to some of their medications. Patients prescribed more antihypertensive medications were less likely to be adherent (OR 0.24, 95%CI 0.09–0.65). Biochemical testing for antihypertensive medication adherence is feasible in routine primary care, although non-adherence to medication is generally low, and therefore widespread testing is not indicated.
Impact of self-monitoring of blood pressure on processes of hypertension care and long-term blood pressure control
BACKGROUND: Self-monitoring of blood pressure (SMBP) improves blood pressure (BP) outcomes at 12-months, but information is lacking on how SMBP affects hypertension care processes and longer-term BP outcomes. METHODS AND RESULTS: We pooled individual participant data from 4 randomized clinical trials of SMBP in the United Kingdom (combined n=2590) with varying intensities of support. Multivariable random effects regression was used to estimate the probability of antihypertensive intensification at 12 months for usual care versus SMBP. Using these data, we simulated 5-year BP control rates using a validated mathematical model. Trial participants were mostly older adults (mean age 66.6 years, SD 9.5), male (53.9%), and predominantly white (95.6%); mean baseline BP was 151.8/85.0 mm Hg. Compared with usual care, the likelihood of antihypertensive intensification increased with both SMBP with feedback to patient or provider alone (odds ratio 1.8, 95% CI 1.2–2.6) and with telemonitoring or self-management (3.3, 2.5–4.2). Over 5 years, we estimated 33.4% BP control (<140/90 mm Hg) with usual care (95% uncertainty interval 27.7%–39.4%). One year of SMBP with feedback to patient or provider alone achieved 33.9% (28.3%–40.3%) BP control and SMBP with telemonitoring or self-management 39.0% (33.1%–45.2%) over 5 years. If SMBP interventions and associated BP control processes were extended to 5 years, BP control increased to 52.4% (45.4%–59.8 %) and 72.1% (66.5%–77.6%), respectively. CONCLUSIONS: One year of SMBP plus telemonitoring or self-management increases the likelihood of antihypertensive intensification and could improve BP control rates at 5 years; continuing SMBP for 5 years could further improve BP control.
Excess mortality in the first COVID pandemic peak: Cross-sectional analyses of the impact of age, sex, ethnicity, household size, and long-term conditions in people of known SARS-CoV-2 status in England
Background The SARS-CoV-2 pandemic has passed its first peak in Europe. Aim To describe the mortality in England and its association with SARS-CoV-2 status and other demographic and risk factors. Design and setting Cross-sectional analyses of people with known SARS-CoV-2 status in the Oxford RCGP Research and Surveillance Centre (RSC) sentinel network. Method Pseudonymised, coded clinical data were uploaded from volunteer general practice members of this nationally representative network (n = 4413734). All-cause mortality was compared with national rates for 2019, using a relative survival model, reporting relative hazard ratios (RHR), and 95% confidence intervals (CI). A multivariable adjusted odds ratios (OR) analysis was conducted for those with known SARSCoV-2 status (n = 56628, 1.3%) including multiple imputation and inverse probability analysis, and a complete cases sensitivity analysis. Results Mortality peaked in week 16. People living in households of ≥9 had a fivefold increase in relative mortality (RHR = 5.1, 95% CI = 4.87 to 5.31, P<0.0001). The ORs of mortality were 8.9 (95% CI = 6.7 to 11.8, P<0.0001) and 9.7 (95% CI = 7.1 to 13.2, P<0.0001) for virologically and clinically diagnosed cases respectively, using people with negative tests as reference. The adjusted mortality for the virologically confirmed group was 18.1% (95% CI = 17.6 to 18.7). Male sex, population density, black ethnicity (compared to white), and people with long-term conditions, including learning disability (OR = 1.96, 95% CI = 1.22 to 3.18, P = 0.0056) had higher odds of mortality. Conclusion The first SARS-CoV-2 peak in England has been associated with excess mortality. Planning for subsequent peaks needs to better manage risk in males, those of black ethnicity, older people, people with learning disabilities, and people who live in multi-occupancy dwellings.
Prospective external validation of the Predicting Out-of-OFfice Blood Pressure (PROOF-BP) strategy for triaging ambulatory monitoring in the diagnosis and management of hypertension: Observational cohort study
Objective To prospectively validate the Predicting Out-of-OFfice Blood Pressure (PROOF-BP) algorithm to triage patients with suspected high blood pressure for ambulatory blood pressure monitoring (ABPM) in routine clinical practice. DeSiGN Prospective observational cohort study. SettiNG 10 primary care practices and one hospital in the UK. ParticiPaNtS 887 consecutive patients aged 18 years or more referred for ABPM in routine clinical practice. All underwent ABPM and had the PROOF-BP applied. MaiN OutcOMe MeaSureS The main outcome was the proportion of participants whose hypertensive status was correctly classified using the triaging strategy compared with the reference standard of daytime ABPM. Secondary outcomes were the sensitivity, specificity, and area under the receiver operator characteristic curve (AUROC) for detecting hypertension. reSultS The mean age of participants was 52.8 (16.2) years. The triaging strategy correctly classified hypertensive status in 801 of the 887 participants (90%, 95% confidence interval 88% to 92%) and had a sensitivity of 97% (95% confidence interval 96% to 98%) and specificity of 76% (95% confidence interval 71% to 81%) for hypertension. The AUROC was 0.86 (95% confidence interval 0.84 to 0.89). Use of triaging, rather than uniform referral for ABPM in routine practice, would have resulted in 435 patients (49%, 46% to 52%) being referred for ABPM and the remainder managed on the basis of their clinic measurements. Of these, 69 (8%, 6% to 10%) would have received treatment deemed unnecessary had they received ABPM. cONcluSiONS In a population of patients referred for ABPM, this new triaging approach accurately classified hypertensive status for most, with half the utilisation of ABPM compared with usual care. This triaging strategy can therefore be recommended for diagnosis or management of hypertension in patients where ABPM is being considered, particularly in settings with limited resources.
The effects of hypocapnia on cardiac electrical activity and heart function and its relevance to the diagnosis of coronary artery disease
Current methods used in the diagnosis of coronary artery disease vary in sensitivity and specificity and have a number of limitations. The aim of this thesis investigation was to explore a new technique for inducing hypocapnia in resting subjects and investigate whether this technique has any clinical applications in the diagnosis of coronary artery disease. In 18 healthy subjects, the effects of hypocapnia, induced by mechanical hyperventilation (in 21% or 15% inspired O\(_2\)), on cardiac electrical activity and heart function were investigated using an electrocardiogram (ECG) and echocardiogram. In addition, a pilot study was conducted to examine the effect of hypocapnia on the ECG of four patients suffering from coronary artery disease with stable angina. Experiments using mechanical hyperventilation showed that the most severe hypocapnia tolerable (PetCO\(_2\) = 20 ± 0mmHg) in normal healthy subjects causes a significant increase in T wave amplitude (increase of up to 0.09 ± 0.02mV, P < 0.01) in the anteroseptal leads (V\({_1-3}\)) of 18 normal subjects but these changes do not exceed the clinical thresholds for hyperacute T wave amplitudes. Hypocapnia did not cause any other significant ECG or echocardiographic ... (continues)
Benefits and Harms of Antihypertensive Treatment in Low-Risk Patients with Mild Hypertension
Importance: Evidence to support initiation of pharmacologic treatment in low-risk patients with mild hypertension is inconclusive, with previous trials underpowered to demonstrate benefit. Clinical guidelines across the world are contradictory. Objective: To examine whether antihypertensive treatment is associated with a low risk of mortality and cardiovascular disease (CVD) in low-risk patients with mild hypertension. Design, Setting, and Participants: In this longitudinal cohort study, data were extracted from the Clinical Practice Research Datalink, from January 1, 1998, through September 30, 2015, for patients aged 18 to 74 years who had mild hypertension (untreated blood pressure of 140/90-159/99 mm Hg) and no previous treatment. Anyone with a history of CVD or CVD risk factors was excluded. Patients exited the cohort if follow-up records became unavailable or they experienced an outcome of interest. Exposures: Prescription of antihypertensive medication. Propensity scores for likelihood of treatment were constructed using a logistic regression model. Individuals treated within 12 months of diagnosis were matched to untreated patients by propensity score using the nearest-neighbor method. Main Outcomes and Measures: The rates of mortality, CVD, and adverse events among patients prescribed antihypertensive treatment at baseline, compared with those who were not prescribed such treatment, using Cox proportional hazards regression. Results: A total of 19143 treated patients (mean [SD] age, 54.7 [11.8] years; 10 705 [55.9%] women; 10 629 [55.5%] white) were matched to 19143 similar untreated patients (mean [SD] age, 54.9 [12.2] years; 10 631 [55.5%] female; 10 654 [55.7%] white). During a median follow-up period of 5.8 years (interquartile range, 2.6-9.0 years), no evidence of an association was found between antihypertensive treatment and mortality (hazard ratio [HR], 1.02; 95% CI, 0.88-1.17) or between antihypertensive treatment and CVD (HR, 1.09; 95% CI, 0.95-1.25). Treatment was associated with an increased risk of adverse events, including hypotension (HR, 1.69; 95% CI, 1.30-2.20; number needed to harm at 10 years [NNH10], 41), syncope (HR, 1.28; 95% CI, 1.10-1.50; NNH10, 35), electrolyte abnormalities (HR, 1.72; 95% CI, 1.12-2.65; NNH10, 111), and acute kidney injury (HR, 1.37; 95% CI, 1.00-1.88; NNH10, 91). Conclusions and Relevance: This prespecified analysis found no evidence to support guideline recommendations that encourage initiation of treatment in patients with low-risk mild hypertension. There was evidence of an increased risk of adverse events, which suggests that physicians should exercise caution when following guidelines that generalize findings from trials conducted in high-risk individuals to those at lower risk.
Association of guideline and policy changes with incidence of lifestyle advice and treatment for uncomplicated mild hypertension in primary care: A longitudinal cohort study in the clinical practice research datalink
Objectives Evidence to support initiation of pharmacological treatment in patients with uncomplicated (low risk) mild hypertension is inconclusive. As such, clinical guidelines are contradictory and healthcare policy has changed regularly. The aim of this study was to determine the incidence of lifestyle advice and drug therapy in this population and whether secular trends were associated with policy changes. Design Longitudinal cohort study. setting Primary care practices contributing to the Clinical Practice Research Datalink in England. Participants Data were extracted from the linked electronic health records of patients aged 18–74 years, with stage 1 hypertension (blood pressure between 140/90 and 159/99 mm Hg), no cardiovascular disease (CVD) risk factors and no treatment, from 1998 to 2015. Patients exited if follow-up records became unavailable, they progressed to stage 2 hypertension, developed a CVD risk factor or received lifestyle advice/treatment. Primary outcome measures The association between policy changes and incidence of lifestyle advice or treatment, examined using an interrupted time-series analysis. results A total of 108 843 patients were defined as having uncomplicated mild hypertension (mean age 51.9±12.9 years, 60.0% female). Patientsspent a median 2.6 years (IQR 0.9–5.5) in the study, after which 12.2% (95% CI 12.0% to 12.4%) were given lifestyle advice, 29.9% (95% CI 29.7% to 30.2%) were prescribed medication and 19.4% (95% CI 19.2% to 19.6%) were given both. The introduction of the quality outcomes framework (QOF) and subsequent changes to QOF indicators were followed by significant increases in the incidence of lifestyle advice. Treatment prescriptions decreased slightly over time, but were not associated with policy changes. Conclusions Despite secular trends that accord with UK guidance, many patients are still prescribed treatment for mild hypertension. Adequately powered studies are needed to determine if this is appropriate.