Large Primary Care Cohort Research Articles

Screening patients in general practice for advanced chronic liver disease using an innovative IT solution: The Liver Toolkit.

Identifying patients with undiagnosed advanced chronic liver disease (ACLD) is a public health challenge. Patients with advanced fibrosis or compensated cirrhosis have much better outcomes than those with decompensated disease and may be eligible for interventions to prevent disease progression. A cloud-based software solution ("the Liver Toolkit") was developed to access primary care practice software to identify patients at risk of ACLD. Clinical history and laboratory results were extracted to calculate aspartate aminotransferase-to-platelet ratio index and fibrosis 4 scores. Patients identified were recalled for assessment, including Liver Stiffness Measurement (LSM) via transient elastography. Those with an existing diagnosis of cirrhosis were excluded. Existing laboratory results of more than 32,000 adults across nine general practices were assessed to identify 703 patients at increased risk of ACLD (2.2% of the cohort). One hundred seventy-nine patients (26%) were successfully recalled, and 23/179 (13%) were identified to have ACLD (LSM ≥10.0kPa) (10% found at indeterminate risk [LSM 8.0-9.9kPa] and 77% low risk of fibrosis [LSM <8.0kPa]). In most cases, the diagnosis of liver disease was new, with the most common etiology being metabolic dysfunction-associated steatotic liver disease (n=20, 83%). Aspartate aminotransferase-to-platelet ratio index ≥1.0 and fibrosis 4 ≥3.25 had a positive predictive value for detecting ACLD of 19% and 24%, respectively. Patients who did not attend recall had markers of more severe disease with a higher median aspartate aminotransferase-to-platelet ratio index score (0.57 vs. 0.46, p=0.041). This novel information technology system successfully screened a large primary care cohort using existing laboratory results to identify patients at increased risk ACLD. More than 1 in 5 patients recalled were found to have liver disease requiring specialist follow-up.

Ambient temperature and kidney function in primary care patients

IntroductionExposure to high ambient temperatures is associated with a risk of acute kidney injury. However, evidence comes from emergency departments or extreme weather exposures. It is unclear whether temperature-related adverse kidney outcomes can also be detected at a community level in a temperate climate zone.MethodsIn a 9.5-year retrospective cohort study we correlated estimated glomerular filtration rate (eGFR) values of Swiss adult primary care patients from the FIRE cohort (Family medicine Research using Electronic medical records) with same-day maximum local ambient temperature data. We investigated 5 temperature groups (< 15 °C, 15–19 °C, 20–24 °C, 25–29 °C and ≥ 30 °C) as well as possible interactions for patients with increased kidney vulnerability (chronic heart failure, diabetes, chronic kidney disease, therapy with renin–angiotensin–aldosterone-system (RAAS) inhibitors, diuretics or non-steroidal anti-inflammatory drugs).ResultsWe included 18,000 primary care patients who altogether provided 132,176 creatinine measurements. In the unadjusted analysis, higher ambient temperatures were associated with lower eGFR across all age and vulnerability groups. In the adjusted models, we did not find a consistent association.The highest ambient temperature differences (> 25 or > 30 versus < 15 °C) were associated with marginally reduced kidney function only in patients with ≥ 3 risk factors for kidney vulnerability, with a maximum estimated glomerular filtration rate reduction of −2.9 ml/min/1.73m2 (SE 1.0), P 0.003.DiscussionIn a large primary care cohort from a temperate climate zone, we did not find an association between ambient temperatures and kidney function. A marginal inverse association in highly vulnerable patients is of unclear clinical relevance.Graphical abstract

Chronic kidney disease in primary care: risk of cardiovascular events, end stage kidney disease and death

BackgroundThe prevalence of chronic kidney disease (CKD) is increasing globally. Early diagnosis in primary care may have a role in ensuring proper intervention. We aimed to determine the prevalence and outcome of CKD in primary care.MethodsWe performed an observational cohort study in primary care in Copenhagen (2001–2015). Outcomes were stroke, myocardial infarction (MI), heart failure (HF), peripheral artery disease (PAD), all-cause- and cardiovascular mortality. We combined individuals with normal kidney function and CKD stage 2 as reference. We conducted cause-specific Cox proportional regressions to calculate the hazard ratios for outcomes according to CKD group. We explored the associations between kidney function and the outcomes examined using eGFR as a continuous variable modelled with penalised splines. All models were adjusted for age, gender, diabetes, hypertension, existing CVD, heart failure, LDL cholesterol and use of antihypertensive treatment.ResultsWe included 171,133 individuals with at least two eGFR measurements of which the majority (n = 157,002) had eGFR > 60 ml/min/1.73m2 at index date, and 0.05% were in CKD stage 5. Event rates were low in eGFR > 60 ml/min/1.73m2 but increased in those with higher stages of CKD. In adjusted analyses we observed an increase in hazard rates for every outcome with every increment in CKD stage. Compared to the reference group, individuals in CKD stage 4 had double the hazard rate of PAD, MI, cardiovascular and all-cause mortality.ConclusionsOur data from a large primary care cohort demonstrate an early increase in the risk of adverse outcomes already at CKD stage 3. This underlines the importance of studying early intervention in primary care.

#2976 CHRONIC KIDNEY DISEASE WITH COMORBIDITY IN PRIMARY CARE: CARDIORENAL TREATMENT, QUALITY OF CARE AND PROGNOSIS

Abstract Background and Aims Diabetes, heart failure, hypertension and cardiovascular disease are common in primary care, and frequently coexist with impaired kidney function (CKD), further increasing risk of cardiovascular- and renal events as well as premature death. These comorbidities therefore call for more complex treatment regimens and monitoring. Our aim was to describe the prevalence, management, and prognosis of individuals with CKD and additional comorbidity in a large primary care cohort. Method Individuals were included from the Copenhagen Primary Care Laboratory (CopLab) Database, which contains 112 million biochemistry results from persons followed in primary care between 2000 and 2015 and divided into three groups based on (CKD-EPI) eGFR (&amp;gt;60 ml/min, 30-59 ml/min and &amp;lt;30 ml/min) with or without comorbidity in the form of diabetes or heart failure. We included all individuals with at least two measurements of creatinine. The date of the second measurement of creatinine was considered index date (baseline). The database has been combined with pharmacological data (The Danish National Prescription Registry), outpatient clinic visits and hospitalizations (The Danish National Patient Registry - NPR), and mortality information (The Danish Civil Registration System). Heart Failure was defined by ICD-codes in NPR from outpatient clinic visits and hospitalizations and we calculated crude event rates for a range of outcomes according to comorbidity. Diabetes was defined as at least one measurement of plasma or serum glucose ≥11 mmol/l or HbA1c ≥48 mmol/mol in CopLab. We evaluated monitoring of eGFR, albuminuria (UACR) and use of guideline-recommended pharmacological therapy (i.e. RAS-blockers and statins) in each group. Results In the total primary care population of 171,134 individuals of which 63.8% were female, 8.3% had impaired kidney function (eGFR&amp;lt;60ml/min). The median follow-up for the three eGFR groups was 8.4, 4.7 and 2.0 years, respectively. Overall, event rates were higher in individuals with impaired kidney function and comorbidity, i.e. mortality in the group with eGFR&amp;lt;30 ml/min with concurrent heart failure; 42.8 per 100 patient-years (PY). Event rates for ESKD were low in general (0.03 to 0.51 per 100 PY) except for individuals with eGFR&amp;lt;30 ml/min (2.1 to 3.5 per 100 PY). Annual monitoring of eGFR was high in all groups (&amp;gt;90%) with increasing frequency in individuals with impaired kidney function, and measurement of UACR was low in groups with non-diabetic CKD (10-30%). Antihypertensive treatment was frequently prescribed in eGFR &amp;lt;30 ml/min; overall 87.6% and 94.8% with coexisting diabetes and 92.8% with coexisting heart failure. The use of RAS inhibition was more used in diabetes and in heart failure (&amp;gt;50%) but less with low eGFR. Statin therapy was used in approximately 50% of individuals with diabetes, regardless of CKD group, but was used to a much less extent in non-diabetic CKD (20-24%). Conclusion Our data from a large primary care cohort demonstrate a high prevalence of coexisting diabetes and/or heart failure with CKD, increasing the risk for adverse outcomes. The quality of CKD care in general practice may be improved, especially in the non-diabetic population.

Clinical relevance of double-arm blood pressure measurement and prevalence of clinically important inter-arm blood pressure differences in Indian Primary Care.

Hypertension guidelines recommend measuring blood pressure (BP) in both arms at least once. However, this is seldom done due to uncertainties regarding measurement procedure and the implications of finding a clinically important inter-arm BP difference (IAD). This study aimed to provide insight into the prevalence of clinically important IADs in a large Indian primary care cohort. A number of 134678 (37% female) unselected Indian primary care participants, mean age 45.2 (SD 11.9) years, had BP measured in both arms using a standardized, triplicate, automated simultaneous measurement method (Microlife WatchBP Office Afib). On average, there were clinically minor differences in right and left arm BP values: systolic BP 134.4 vs. 134.2 mmHg (p<0.01) and diastolic BP 82.7 vs. 82.6 mmHg (p<0.01), respectively. Prevalence of significant mean systolic IAD between 10 and 15 mmHg was 7813 (5.8%). Systolic IAD ≥ 15 mmHg 2980 (2.2%) and diastolic IAD ≥ 10 mmHg 7151 (5.3%). In total, there were 7595 (5.6%) and 8548 (6.3%) participants with BP above the 140/90 mmHg threshold in only the left or right arm, respectively. Prevalence of participants with elevated BP on one arm only was highest in patients with a systolic IAD ≥ 15 mmHg; 19.1% and 13.7%, for left and right arm, respectively. This study shows that a substantial prevalence of IAD exist in Indian primary care patients. BP is above the diagnostic threshold for hypertension in one arm only for 6% of participants. These findings emphasise the importance of undertaking bilateral BP measurement in routine clinical practice. This article is protected by copyright. All rights reserved.

Survival among people with heart failure and atrial fibrillation; a population cohort study

Abstract Background People with chronic heart failure (HF) have a poor prognosis, with survival rates at five year follow-up close to 50%.1 More than half of patients with HF will develop atrial fibrillation (AF). The presence of AF in people with HF has been associated with a poor prognosis, irrespective of left ventricular ejection fraction. 2,3 However, the majority of studies to date have analysed prognosis among secondary care cohorts or randomised trial participants, who may not be representative of patients with chronic HF in the community.2 Purpose To examine the association between survival in patients with HF and AF compared to either condition alone, among a large primary care cohort. Methods We extracted data from the Clinical Practice Research Datalink of primary care records from 1st January 2000 to 31st December 2018 and included all patients aged 45 years and over who were registered at an up-to-standard practice for a minimum of 12 months. Records were linked to Hospital Episode Statistics for secondary care data. The primary outcome was all-cause mortality. Exposure groups were defined as HF+AF, HF or AF, with exposure status treated as a time-varying covariate across follow-up. We used Cumulative Hazard plots to compare survival in people with HF and AF, compared to people with either condition alone or neither. We also report a Cox regression model for risk of all-cause mortality among people with HF and AF, adjusting for age, sex, ethnicity, smoking status and comorbid cardiovascular disease. Results There were 314,042 deaths during the study follow-up. The average age of participants was 58.0 years (SD 10.6) and 51.4% were women. At some point across follow-up, 94,990 people had HF alone, 147,815 had AF alone and 74,470 had both HF and AF. In an unadjusted Cox regression analysis, people with HF and AF were at the greatest risk of death (HR 17.94, 95% CI 17.75 to 18.13), followed by people with HF alone (HR 12.00, 95% CI 11.87 to 12.13), and AF alone (HR 6.14, 95% CI 6.08 to 6.21) compared to people with neither HF nor AF. In the fully adjusted analysis, the risk of death remained highest among people with HF and AF (HR 3.78, 95% CI 3.73 to 3.83), followed by people with HF alone (HR 3.06, 95% CI 3.02 to 3.10), then people with AF alone (HR 1.85, 95%, CI 1.82 to 1.87). In a cumulative hazard plot, the risk of death across follow-up was similar among people with HF and AF, compared to those with HF alone. Conclusion In our large community cohort, we found HF and AF was associated with a worse prognosis than either condition alone. Both HF and AF were also associated with a poor prognosis. These results support the findings of previous secondary care and trial studies regarding the importance of AF as a prognostic indicator among people with HF. Further research could aim to identify preventive strategies that might improve prognosis among this high-risk group of patients. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The study was undertaken as part of NRJ's Doctoral Research Fellowship, supported by the Wellcome Trust (grant number 203921/Z/16/Z), with additional funding for this project from the National Institute for Health Research (NIHR) Collaboration for Applied Health Research (CLAHRC) Oxford at Oxford Health NHS Foundation Trust (P2-001).

Body mass index and survival in people with heart failure

Abstract Background People with obesity are twice as likely to develop heart failure (HF) compared to people with a healthy body mass index (BMI) [1]. However, among people with HF a higher BMI has been linked to a reduced risk of all-cause mortality, a concept known as the “obesity paradox” [2]. Purpose To examine the association between BMI and survival in patients with chronic HF among a large primary care cohort. Methods We extracted data from the Clinical Practice Research Datalink of primary care records from 1st January 2000 to 31st December 2017 and included 47,531 patients with an incident diagnosis of HF, who were aged 45 years and over and who had a recorded BMI. Patients were stratified into categories of baseline BMI as underweight (BMI &amp;lt;18.5 kg/m2), healthy weight (BMI 18.5 to 24.9 kg/m2), overweight (BMI 25.0 to 29.9 kg/m2) or obese, with obesity split into class I (30.0–34.9 kg/m2), class II (35.0–39.9 kg/m2) and class III (40 kg/m2 and over). The primary outcome was all-cause mortality. We used Kaplan-Meier curves and log rank tests to compare survival in people with HF, based on baseline BMI. We also report a Cox regression model for risk of all-cause mortality among people with HF comparing BMI categories. Results There were 25,013 deaths during the study follow-up. The average age of participants was 77.1 years (SD 10.6) and mean BMI was 27.9 (SD 6.1). In an age- and sex-adjusted analysis, people who were underweight were at increased risk of all-cause mortality compared to people with healthy weight (HR 1.52, 95% CI 1.41 to 1.64). People with overweight (HR 0.81, 95% CI 0.79 to 0.84), obesity class I (HR 0.79, 95% CI 0.76 to 0.82) and obesity class II (HR 0.78, 95% CI 0.74 to 0.82) were at decreased risk of all-cause mortality. People with obesity class III had no difference in risk of death compared to people with healthy weight (HR 0.95, 95% CI 0.88 to 1.02). In a Kaplan-Meier analysis, there was an inverse relationship between body weight and risk of death, even within the first year of follow-up. Conclusion In our large community cohort of people with HF, we found an inverse relationship between BMI and survival. Underweight people with HF have the poorest prognosis and should be identified as high-risk. Conversely, people with HF who are overweight or obese (class I and II) are at lower risk of death confirming the obesity paradox in a real-world primary care population. These findings suggest a more cautious approach to weight management in overweight and obese patients may be needed for people with HF in primary care. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The SurviveHF study was funded by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) Oxford at Oxford Health NHS Foundation Trust and the Wellcome Institutional Strategic Fund. The funders did not have any role in the design of the study, analysis and interpretation of the data, or writing of the results for publication.

Clinical relevance of double-arm blood pressure measurement and prevalence of clinically important inter-arm blood pressure differences in Indian primary care.

Hypertension guidelines recommend measuring blood pressure (BP) in both arms at least once. However, this is seldom done due to uncertainties regarding measurement procedure and the implications of finding a clinically important inter‐arm BP difference (IAD). This study aimed to provide insight into the prevalence of clinically important IADs in a large Indian primary care cohort.A number of 134 678 (37% female) unselected Indian primary care participants, mean age 45.2 (SD 11.9) years, had BP measured in both arms using a standardized, triplicate, automated simultaneous measurement method (Microlife WatchBP Office Afib).On average, there were clinically minor differences in right and left arm BP values: systolic BP 134.4 vs 134.2 mmHg (p < .01) and diastolic BP 82.7 vs 82.6 mmHg (p < .01), respectively.Prevalence of significant mean systolic IAD between 10 and 15 mmHg was 7,813 (5.8%). Systolic IAD ≥ 15 mmHg 2,980 (2.2%) and diastolic IAD ≥ 10 mmHg 7,151 (5.3%). In total, there were 7,595 (5.6%) and 8,548 (6.3%) participants with BP above the 140/90 mmHg threshold in only the left or right arm, respectively. Prevalence of participants with elevated BP on one arm only was highest in patients with a systolic IAD ≥ 15 mmHg; 19.1% and 13.7%, for left and right arm, respectively.This study shows that a substantial prevalence of IAD exists in Indian primary care patients. BP is above the diagnostic threshold for hypertension in one arm only for 6% of participants. These findings emphasize the importance of undertaking bilateral BP measurement in routine clinical practice.

MO518: Chronic Kidney Disease in Primary Care and the Risk of Cardiovascular Comorbidity and Mortality

Abstract BACKGROUND AND AIMS The prevalence of chronic kidney disease (CKD) is increasing globally. Often, the condition develops silently over time, with no or only a few symptoms in earlier stages. Therefore, early recognition in primary care may have an important role in ensuring diagnosis and proper intervention. We aimed to determine the prevalence and outcome of CKD in a large primary care cohort in Denmark. METHOD We performed an observational cohort study using data from individuals above age 40 followed in primary care in the greater Copenhagen area between 2000 and 2015 and linked them to Danish health registries. A run-in period of 3 months was included to ensure stable conditions and rule out acute changes in eGFR at baseline. The date of the second measurement of eGFR during the study period was considered the subject's index date (baseline). Outcomes were relevant diagnoses such as stroke, myocardial infarction (MI), hospitalisations for heart failure (HHF) and peripheral artery disease (PAD) (last update 2018), all-cause mortality and cardiovascular mortality. Kidney function (eGFR) was estimated by the CKD-EPI formula based on serum creatinine and expressed in mL/min/1.73 m2. Conventional CKD groups are used with CKD 1 and 2 (normal—eGFR &amp;gt; 60 mL/min/1.73 m2) as reference groups for the hazard ratio estimates. Outcomes were presented as the number of events/100 person-years (PY). We conducted survival (all-cause mortality outcome) and competing risk (rest of the outcomes) analyses using the Cox proportional hazards model to calculate the (cause-specific) hazard ratios for the outcomes according to CKD group. We further explored the continuous associations between kidney function and the outcomes examined by using eGFR as a continuous variable with penalised splines. All models were adjusted for known risk factors (age, gender, diabetes, hypertension, existing CVD, heart failure, LDL cholesterol, use of antihypertensive treatment). RESULTS We included a population of 171 133 individuals. As expected, the majority (n = 157002) was in CKD 1 or 2 at the index date, and only a small proportion (0.05%) was in CKD stage 5. In general, event rates were low in CKD stages 1 and 2 and rose with higher stages of CKD. In the adjusted analyses, we observed a stepwise increase in hazard rates for every outcome with every increment in CKD stage (Fig. 1). This was confirmed by the continuous analysis. Compared with CKD stage 1 + 2, individuals in CKD stage 4 had approximately double the hazard rate of PAD, MI, cardiovascular and all-cause mortality. CONCLUSION Our data from a large primary care cohort demonstrate an early increase in risk for adverse outcomes already at CKD stage 3. This provides the basis and underlines the importance of studying early intervention in primary care.

Achalasia is associated with a higher incidence of depression in outpatients in Germany.

Background and aimAchalasia represents a chronic motility disorder of the esophagus featuring an impaired lower esophageal sphincter relaxation and loss of esophageal peristalsis. By causing dysphagia, regurgitation, aspiration and chest pain, achalasia might tremendously affect life quality of patients. However, the impact of achalasia on the development of mood disorders including depression has largely remained unclear. The aim of this study was to evaluate the incidence of depression in achalasia patients.MethodsWe analyzed a large primary care cohort database in Germany capturing data from 7.49 million patients.ResultsA total of n = 1,057 patients with achalasia diagnosed between January 2005 and December 2018 were matched to a cohort of n = 3,171 patients without achalasia controlling for age, sex, physician, index year, and the Charlson comorbidity index. Interestingly, while the frequency of depression prior to the diagnosis of achalasia was comparable in both groups, new diagnoses of depression were significantly higher within one year after the diagnosis of achalasia compared to the control group, suggesting a direct and previously unrecognized association between achalasia and depression.ConclusionOur data suggest that the clinical management of patients with achalasia should include a careful and structured work-up for mood disorders in order to improve long-term quality of life in these patients.

Predicting cardiovascular disease risk across the atherosclerotic disease continuum.

Cardiovascular disease (CVD) guidelines dichotomize populations into primary and secondary prevention. We sought to develop a risk equation for secondary prevention of CVD that complements existing equations for primary prevention of CVD, and to describe the distributions of CVD risk across the population. Adults aged 30-79 years who had routine CVD risk assessment in 2007-16 were identified from a large primary care cohort (PREDICT) with linkage to national and regional datasets. The 5-year risk of developing CVD among people without atherosclerotic CVD (ASCVD) was calculated using published equations (PREDICT-1°). A new risk equation (PREDICT-2°) was developed from Cox regression models to estimate the 5-year risk of CVD event recurrence among patients with known ASCVD. The outcome for both equations was hospitalization for a CVD event or cardiovascular death. Of the 475 161 patients, 12% (57 061) had ASCVD. For those without ASCVD, median (interquartile range) 5-year risks with the PREDICT-1° score were women 2.2% (1.2-4.2%), men 3.5% (2.0-6.6%), and whole group 2.9% (1.6-5.5%). For those with ASCVD, the 5-year risks with the new PREDICT-2° equation were women 21% (15-33%), men 23% (16-35%), and whole group 22% (16-34%). We developed CVD risk scores for people with ASCVD (PREDICT-2°) to complement the PREDICT-1° scores. Median CVD risk is eight-fold higher among those with ASCVD than those without; however, there was overlap and the widest distribution of CVD risk was among people with ASCVD. This study describes a CVD risk continuum and the limitations of a 'one size fits all' approach to assessing risk in people with ASCVD.

Association of Positional Plagiocephaly and Developmental Delay Within a Primary Care Network.

Previous research has suggested an association between plagiocephaly and developmental delay. However, study samples drawn from children seen in subspecialty clinics increase the potential for selection and referral bias. Our study evaluates the association between plagiocephaly and developmental delay and the timing of these diagnoses in a primary care setting, where plagiocephaly is commonly diagnosed and managed. Our retrospective analysis used electronic medical record data from 45 primary care sites within a children's health system from 1999 to 2017, including children aged 0 to 5 years with diagnoses determined by physician diagnosis codes at primary care visits. Children were classified in the plagiocephaly group if diagnosis occurred by 12 months of age. Primary outcome was any developmental delay. Pearson χ2 test, Fisher exact test, and logistic regression analyses were conducted, with multivariable models adjusted for sex, race, ethnicity, insurance, prematurity status (22-36 weeks' gestation), primary care sites, birth year, and diagnoses of abnormal tone and torticollis. Of 77,108 patients seen by 12 months, 2315 (3.0%) were diagnosed with plagiocephaly, with an increase in diagnosis prevalence over the study time frame. Plagiocephaly was independently associated with an increased odds of any developmental delay diagnosis (adjusted odds ratio 1.50, 95% confidence interval 1.32-1.70). The diagnosis of plagiocephaly was recorded before the diagnosis of developmental delay in most cases when both diagnoses were present (374 of 404, 92.6%). Data from a large primary care cohort demonstrate an association between plagiocephaly and developmental delay, affirming findings in previous subspecialty literature.

Nonalcoholic Fatty Liver Disease Increases the Risk of Anxiety and Depression.

Nonalcoholic fatty liver disease (NAFLD), depression, and anxiety disorders are frequent diseases, and data on mutual influence are inconsistent. The aim of this study was to explore the incidence of depression and anxiety in a large primary care cohort in Germany and to study the impact of NAFLD over a 10‐year time frame. Patients with NAFLD diagnosed between 2010 and 2015 were matched to a cohort without NAFLD controlling for age, sex, physician, index year, and Charlson comorbidity index. The primary outcome of the study was the incidence of depression, anxiety, and first prescription of antidepressant drugs. We compared 19,871 patients with NAFLD to 19,871 matched controls. Within 10 years of the index date, 21.2% of patients with NAFLD and 18.2% of controls were diagnosed with depression (P < 0.001). On regression analysis, the hazard ratio (HR) for incidence of depression was 1.21 (P < 0.001). This association was similar for the endpoint of the first prescription of antidepressant drugs (HR, 1.21; P < 0.001). Anxiety disorders were diagnosed in 7.9% of patients with NAFLD and 6.5% of controls during the observation time (P = 0.003). The HR for incidence of anxiety was 1.23 (P < 0.001). This association remained significant in women (P < 0.001), while there was only a trend in men (HR, 1.15; 95% confidence interval, 0.99‐1.34; P < 0.067). The risk of developing anxiety disorders was higher in younger patients. Conclusion: NAFLD constitutes an independent risk factor for emerging depression and anxiety even after controlling for confounding comorbidities.

Variability in Glycated Hemoglobin and Risk of Poor Outcomes Among People With Type 2 Diabetes in a Large Primary Care Cohort Study.

Diabetes guidelines focus on target glycated hemoglobin (HbA1c) levels. Long-term variability in HbA1c may be predictive of hospitalization or mortality, but its importance at different average levels or trajectories is unclear. Using English primary care data, 58,832 patients with type 2 diabetes had HbA1c average (mean of annual means), variability (coefficient of variation), and trajectory (annual regression slope) estimated during 2006-2009. Hazard ratios (HRs) for mortality and emergency hospitalization during 2010-2015, with adjustment for age, sex, smoking, BMI, duration of diabetes, and deprivation, were estimated using Cox regression. The simultaneous impact of HbA1c average, variability, and trajectory was estimated using percentiles. In mutually adjusted models, HbA1c variability showed a consistent dose-response relationship with all-cause mortality, while average level was only important among individuals in the highest or lowest 10% of the distribution, and trajectory had no independent effect. Individuals with the most unstable HbA1c (top 10%) were almost twice as likely to die (HR 1.93 [95% CI 1.72-2.16]) than were those with the most stable (bottom 10%)-an association attenuated but not explained by hypoglycemia. For emergency hospitalizations, similar trends were seen except for coronary artery disease (CAD) and ischemic stroke (IS), where increasing average rather than variability was predictive. HbA1c variability was strongly associated with overall mortality and emergency hospitalization and not explained by average HbA1c or hypoglycemic episodes. Only for CAD and IS hospitalizations was no association found, with average HbA1c strongly predictive. Targets should focus on both stability and absolute level of HbA1c.

The comorbidity burden of type 2 diabetes mellitus: patterns, clusters and predictions from a large English primary care cohort

BackgroundThe presence of additional chronic conditions has a significant impact on the treatment and management of type 2 diabetes (T2DM). Little is known about the patterns of comorbidities in this population. The aims of this study are to quantify comorbidity patterns in people with T2DM, to estimate the prevalence of six chronic conditions in 2027 and to identify clusters of similar conditions.MethodsWe used the Clinical Practice Research Datalink (CPRD) linked with the Index of Multiple Deprivation (IMD) data to identify patients diagnosed with T2DM between 2007 and 2017. 102,394 people met the study inclusion criteria. We calculated the crude and age-standardised prevalence of 18 chronic conditions present at and after the T2DM diagnosis. We analysed longitudinally the 6 most common conditions and forecasted their prevalence in 2027 using linear regression. We used agglomerative hierarchical clustering to identify comorbidity clusters. These analyses were repeated on subgroups stratified by gender and deprivation.ResultsMore people living in the most deprived areas had ≥ 1 comorbidities present at the time of diagnosis (72% of females; 64% of males) compared to the most affluent areas (67% of females; 59% of males). Depression prevalence increased in all strata and was more common in the most deprived areas. Depression was predicted to affect 33% of females and 15% of males diagnosed with T2DM in 2027. Moderate clustering tendencies were observed, with concordant conditions grouped together and some variations between groups of different demographics.ConclusionsComorbidities are common in this population, and high between-patient variability in comorbidity patterns emphasises the need for patient-centred healthcare. Mental health is a growing concern, and there is a need for interventions that target both physical and mental health in this population.

Brain Natriuretic Peptide in Plasma as Predictor of All-Cause Mortality in a Large Danish Primary Health Care Population Suspected of Heart Failure.

Measurement of B-type natriuretic peptide (BNP) in plasma may have its greatest potential in primary care, as general practitioners need to rapidly identify patients who warrant further medical review. The aim of the present study was to examine the prognostic information of BNP measurement on all-cause mortality in a large Danish primary care cohort. This study covered a cohort of Danish primary care patients (n = 61665) with a median follow-up period of 4.36 years (interquartile range, 2.29-6.62 years). BNP was measured in plasma using the ADVIA Centaur/CentaurXP platform. The association of BNP with mortality was assessed with a hazard ratio for all-cause mortality from a multivariable Cox proportional hazards model. Kaplan-Meier curves showed decreasing survival probability with increasing BNP (P < 0.001). Each doubling of BNP increased mortality by 32.3% (95% CI, 30.8-33.8) when adjusted for sex and age, and by 25.3% (95% CI, 23.8-26.8) when further adjusted for Charlson comorbidity index, hemoglobin, estimated glomerular filtration rate, glycohemoglobin, and thyroid-stimulating hormone. Also, in a subcohort (n = 10824) without biochemical signs of severe kidney failure, anemia, polycythemia, hypothyroidism or hyperthyroidism, or dysregulated diabetes, each doubling of BNP increased mortality by 28.6% (95% CI, 22.8-34.7). Our results show that even in a primary care population, BNP measurements contain prognostic information regarding all-cause mortality.

Glycemic Control and Risk of Infections Among People With Type 1 or Type 2 Diabetes in a Large Primary Care Cohort Study.

Diabetes mellitus (DM) increases the risk of infections, but the effect of better control has not been thoroughly investigated. With the use of English primary care data, average glycated hemoglobin (HbA1c) during 2008-2009 was estimated for 85,312 patients with DM ages 40-89 years. Infection rates during 2010-2015 compiled from primary care, linked hospital, and mortality records were estimated across 18 infection categories and further summarized as any requiring a prescription or hospitalization or as cause of death. Poisson regression was used to estimate adjusted incidence rate ratios (IRRs) by HbA1c categories across all DM, and type 1 and type 2 DM separately. IRRs also were compared with 153,341 age-sex-practice-matched controls without DM. Attributable fractions (AF%) among patients with DM were estimated for an optimal control scenario (HbA1c 6-7% [42-53 mmol/mol]). Long-term infection risk rose with increasing HbA1c for most outcomes. Compared with patients without DM, those with DM and optimal control (HbA1c 6-7% [42-53 mmol/mol], IRR 1.41 [95% CI 1.36-1.47]) and poor control (≥11% [97 mmol/mol], 4.70 [4.24-5.21]) had elevated hospitalization risks for infection. In patients with type 1 DM and poor control, this risk was even greater (IRR 8.47 [5.86-12.24]). Comparisons within patients with DM confirmed the risk of hospitalization with poor control (2.70 [2.43-3.00]) after adjustment for duration and other confounders. AF% of poor control were high for serious infections, particularly bone and joint (46%), endocarditis (26%), tuberculosis (24%), sepsis (21%), infection-related hospitalization (17%), and mortality (16%). Poor glycemic control is powerfully associated with serious infections and should be a high priority.

Identification, risk assessment, and management of patients with atrial fibrillation in a large primary care cohort

BackgroundAtrial fibrillation (AF) is associated with increased risk of cardiovascular disease (CVD) complications including stroke. We investigated the assessment and management of cardiovascular risk among patients with AF aged 35–74years, by ethnic group, in a large cohort of people receiving a CVD risk assessment in primary care (PREDICT). MethodsPREDICT was linked to national dispensing, hospitalisation and mortality records. AF was present if recorded in PREDICT or during a prior hospitalisation; medications were those dispensed ≤6months before or after a PREDICT assessment; the CHA2DS2-VASc score and a New Zealand (NZ) adjusted Framingham CVD risk were calculated. Data were linked to outcomes of stroke or major adverse cardiovascular event (MACE). Results12,739 (2.8%) of 447,020 people aged 35–74years had AF. Māori, the indigenous population of NZ, had the highest proportion of AF, which by age group, was similar to that among Europeans 10years older. 77% were at high stroke risk, of whom 42% received anticoagulation; 54% were at high CVD risk, of whom 67% received both lipid- and blood pressure-lowering medication. Per category of predicted risk, stroke risk was overestimated and risk of MACE was underestimated. ConclusionsThe burden of AF and risk factors differed by ethnic group thus recommendations to screen for AF above a universal age threshold may introduce inequity in the detection and management of associated risk. The high burden of comorbidities at younger ages among many ethnic groups contributes to the poor performance of available risk assessment tools, further compounding potential inequity.

Impact of initial medication non-adherence on use of healthcare services and sick leave: a longitudinal study in a large primary care cohort in Spain.

Initial medication non-adherence is highly prevalent in primary care but no previous studies have evaluated its impact on the use of healthcare services and/or days on sick leave. To estimate the impact of initial medication non-adherence on the use of healthcare services, days of sick leave, and costs overall and in specific medication groups. A 3-year longitudinal register-based study of all primary care patients (a cohort of 1.7 million) who were prescribed a new medication in Catalonia (Spain) in 2012. Thirteen of the most prescribed and/or costly medication subgroups were considered. All medication and medication subgroups (chronic, analgesics, and penicillin) were analysed. The number of healthcare services used and days on sick leave were considered. Multilevel multivariate linear regression was used. Three levels were included: patient, GP, and primary care centre. Initially adherent patients made more use of medicines and some healthcare services than non-adherent and partially adherent patients. They had lower productivity losses, producing a net economic return, especially when drugs for acute diseases (such as penicillins) were considered. Initial medication non-adherence resulted in a higher economic burden to the system in the short term. Initial medication non-adherence seems to have a short-term impact on productivity losses and costs. The clinical consequences and long-term economic consequences of initial medication non-adherence need to be assessed. Interventions to promote initial medication adherence in primary care may reduce costs and improve health outcomes.

Childhood respiratory illness presentation and service utilisation in primary care: a six-year cohort study in Wellington, New Zealand, using natural language processing (NLP) software

ObjectivesTo identify childhood respiratory tract-related illness presentation rates and service utilisation in primary care by interrogating free text and coded data from electronic medical records.DesignRetrospective cohort study. Data interrogation used...