Sex-dependent effect of socioeconomic status on cardiovascular event risk in a population-based cohort of patients with type 2 diabetes.

BACKGROUND: Socioeconomic status (SES) factors often result in profound health inequalities among populations, and their impact may differ between sexes. The aim of this study was to estimate and compare the effect of socioeconomic status indicators on incident cardiovascular disease (CVD)-related events among males and females with type 2 diabetes (T2D). METHODS: A population-based cohort from a southern European region including 24,650 patients with T2D was followed for five years. The sex-specific associations between SES indicators and the first occurring CVD event were modeled using multivariate Fine-Gray competing risk models. Coronary Heart Disease (CHD) and stroke were considered secondary outcomes. RESULTS: Patients without a formal education had a significantly higher risk of CVD than those with a high school or university education, with adjusted hazard ratios (HRs) equal to 1.24 (95%CI: 1.09-1.41) for males and 1.50 (95%CI: 1.09-2.06) for females. Patients with <18 000€ income had also higher CVD risk than those with ≥18 000€, with HRs equal to 1.44 (95%CI: 1.29-1.59) for males and 1.42 (95%CI: 1.26-1.60) for females. Being immigrant showed a HR equal to 0.81 (95%CI: 0.66-0.99) for males and 1.13 (95%CI: 0.68-1.87) for females. Similar results were observed for stroke, but differed for CHD when income is used, which had higher effect in females. CONCLUSION: Socioeconomic inequalities in CVD outcomes are present among T2D patients, and their magnitude for educational attainment is sex-dependent, being higher in females, suggesting the need to consider them when designing tailored primary prevention and management strategies.

Cohort Profile: CArdiovascular Risk in patients with DIAbetes in NAvarra (CARDIANA cohort).

PURPOSE: The CArdiovascular Risk in patients with DIAbetes in Navarra (CARDIANA cohort) cohort was established to assess the effects of sociodemographic and clinical variables on the risk of cardiovascular events in patients with type 1 (T1D) or type 2 (T2D) diabetes, with a special focus on socioeconomic factors, and to validate and develop cardiovascular risk models for these patients. PARTICIPANTS: The CARDIANA cohort included all patients with T1D and T2D diabetes registered in the Public Health Service of Navarra with prevalent disease on 1 January 2012. It consisted of 1067 patients with T1D (ages 2-88 years) and 33842 patients with T2D (ages 20-105 years), whose data were retrospectively extracted from the Health and Administrative System Databases. FINDINGS TO DATE: The follow-up period for wave 1 was from 1 January 2012 to 31 December 2016. During these 5 years, 9 patients (0.8%; 95% CI (0.4% to 1.6%)) in the T1D cohort developed a cardiovascular disease event, whereas for the T2D cohort, 2602 (7.7%; 95% CI (7.4% to 8.0%)) had an event. For the T2D cohort, physical activity was associated with a reduced risk of cardiovascular events, with adjusted estimated ORs equal to 0.84 (95% CI 0.66 to 1.07) for the partially active group and 0.71 (95% CI 0.56 to 0.91) for the active group, compared with patients in the non-active group. FUTURE PLANS: The CARDIANA cohort is currently being used to assess the effect of sociodemographic risk factors on CV risk at 5 years and to externally validate cardiovascular predictive models. A second wave is being conducted in late 2022 and early 2023, to extend the follow-up other 5 years, from 1 January 2016 to 31 December 2021. Periodic data extractions are planned every 5 years.

Blood pressure targets for the treatment of people with hypertension and cardiovascular disease.

BACKGROUND: This is the third update of the review first published in 2017. Hypertension is a prominent preventable cause of premature morbidity and mortality. People with hypertension and established cardiovascular disease are at particularly high risk, so reducing blood pressure to below standard targets may be beneficial. This strategy could reduce cardiovascular mortality and morbidity but could also increase adverse events. The optimal blood pressure target in people with hypertension and established cardiovascular disease remains unknown. OBJECTIVES: To determine if lower blood pressure targets (systolic/diastolic 135/85 mmHg or less) are associated with reduction in mortality and morbidity compared with standard blood pressure targets (140 mmHg to 160mmHg/90 mmHg to 100 mmHg or less) in the treatment of people with hypertension and a history of cardiovascular disease (myocardial infarction, angina, stroke, peripheral vascular occlusive disease). SEARCH METHODS: For this updated review, we used standard, extensive Cochrane search methods. The latest search date was January 2022. We applied no language restrictions. SELECTION CRITERIA: We included randomized controlled trials (RCTs) with more than 50 participants per group that provided at least six months' follow-up. Trial reports had to present data for at least one primary outcome (total mortality, serious adverse events, total cardiovascular events, cardiovascular mortality). Eligible interventions involved lower targets for systolic/diastolic blood pressure (135/85 mmHg or less) compared with standard targets for blood pressure (140 mmHg to 160 mmHg/90 mmHg to 100 mmHg or less). Participants were adults with documented hypertension and adults receiving treatment for hypertension with a cardiovascular history for myocardial infarction, stroke, chronic peripheral vascular occlusive disease, or angina pectoris. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. We used GRADE to assess the certainty of the evidence. MAIN RESULTS: We included seven RCTs that involved 9595 participants. Mean follow-up was 3.7 years (range 1.0 to 4.7 years). Six of seven RCTs provided individual participant data. None of the included studies was blinded to participants or clinicians because of the need to titrate antihypertensive drugs to reach a specific blood pressure goal. However, an independent committee blinded to group allocation assessed clinical events in all trials. Hence, we assessed all trials at high risk of performance bias and low risk of detection bias. We also considered other issues, such as early termination of studies and subgroups of participants not predefined, to downgrade the certainty of the evidence. We found there is probably little to no difference in total mortality (risk ratio (RR) 1.05, 95% confidence interval (CI) 0.91 to 1.23; 7 studies, 9595 participants; moderate-certainty evidence) or cardiovascular mortality (RR 1.03, 95% CI 0.82 to 1.29; 6 studies, 9484 participants; moderate-certainty evidence). Similarly, we found there may be little to no differences in serious adverse events (RR 1.01, 95% CI 0.94 to 1.08; 7 studies, 9595 participants; low-certainty evidence) or total cardiovascular events (including myocardial infarction, stroke, sudden death, hospitalization, or death from congestive heart failure (CHF)) (RR 0.89, 95% CI 0.80 to 1.00; 7 studies, 9595 participants; low-certainty evidence). The evidence was very uncertain about withdrawals due to adverse effects. However, studies suggest more participants may withdraw due to adverse effects in the lower target group (RR 8.16, 95% CI 2.06 to 32.28; 3 studies, 801 participants; very low-certainty evidence). Systolic and diastolic blood pressure readings were lower in the lower target group (systolic: mean difference (MD) -8.77 mmHg, 95% CI -12.82 to -4.73; 7 studies, 8657 participants; diastolic: MD -4.50 mmHg, 95% CI -6.35 to -2.65; 6 studies, 8546 participants). More drugs were needed in the lower target group (MD 0.56, 95% CI 0.16 to 0.96; 5 studies, 7910 participants), but blood pressure targets at one year were achieved more frequently in the standard target group (RR 1.20, 95% CI 1.17 to 1.23; 7 studies, 8699 participants). AUTHORS' CONCLUSIONS: We found there is probably little to no difference in total mortality and cardiovascular mortality between people with hypertension and cardiovascular disease treated to a lower compared to a standard blood pressure target. There may also be little to no difference in serious adverse events or total cardiovascular events. This suggests that no net health benefit is derived from a lower systolic blood pressure target. We found very limited evidence on withdrawals due to adverse effects, which led to high uncertainty. At present, evidence is insufficient to justify lower blood pressure targets (135/85 mmHg or less) in people with hypertension and established cardiovascular disease. Several trials are still ongoing, which may provide an important input to this topic in the near future.

COVID-19 infection and complications according to ABO blood group in the elderly: A population-based subcohort and meta-analysis.

BACKGROUND AND OBJECTIVES: It is reported that ABO antibodies have a role in COVID-19 infection and severity; however, ABO antibody titres vary with advanced age. The aim was to analyse the association between ABO blood group and risk of COVID-19 infection and complications in elderly patients, and to contrast this data with findings in the overall adult population. MATERIALS AND METHODS: A prospective cohort study of the Navarre (Spain) population aged ≥60 years and a meta-analysis of published studies including participants of ≥60 years were carried out. RESULTS: In the Navarre elderly population, a higher risk of COVID-19 infection was identified in the A versus non-A and O group and lower risk in O versus non-O, with no significant association between hospitalization, intensive care unit admission or mortality and any of the blood groups, results that coincide with those of the overall Navarre adult population. The meta-analyses using studies that included participants of ≥60 years demonstrated a higher risk of hospitalization and mortality in A versus non-A and a lower mortality risk with B versus non-B. Similar mortality results were found in the meta-analyses of the overall adult population. CONCLUSION: There are no relevant differences between the overall adult population and population aged ≥60 years in the risk of COVID-19 infection and severity according to ABO blood groups, suggesting that age-related changes in ABO would be of limited clinical significance.

Role of the AB0 blood group in COVID-19 infection and complications: A population-based study.

Since the beginning of the COVID-19 pandemic, the ABO blood group has been described as a possible biological marker of susceptibility for the disease. This study evaluates the role of ABO group on the risk of SARS-CoV-2 infection and related complications in a population-based cohort including 87,090 subjects from the Navarre population (Northern Spain) with no history of SARS-CoV-2 infection and with known ABO blood group, after one year of the pandemic (May 2020 - May 2021). The risk of infection, hospitalization, Intensive Care Unit (ICU) admission and death was analyzed using multivariate logistic regression, adjusting for possible confounding variables. A lower risk of infection was observed in group 0 vs non-0 groups [OR 0.94 (95 %CI 0.90-0.99)], a higher risk of infection in group A vs non-A groups [OR 1.09 (95 %CI 1.04-1.15)] and a higher risk of infection in group A vs group 0 [OR 1.08 (95CI 1.03-1.14)] (when the 4 groups are analyzed separately). No association was observed between blood groups and hospitalization, ICU admission, or death in SARS-CoV-2 infected subjects. Regarding the risk of SARS-CoV-2 infection, we observed a protective role of group O and a greater risk in the A group.

Use of health services among long-term breast cancer survivors in Spain: longitudinal study based on real-world data.

PURPOSE: This study aimed to evaluate health service utilization in Spain among long-term breast cancer survivors and to compare it with that among women with no history of breast cancer. METHODS: Study based on the SURBCAN cohort includes a sample of long-term breast cancer survivors and a sample of women without breast cancer from 5 Spanish regions. Healthcare utilization was assessed through primary care, hospital visits, and tests during the follow-up period (2012 to 2016) by using electronic health records. Annual contact rates to healthcare services were calculated, and crude and multivariate count models were fitted to estimate the adjusted relative risk of healthcare services use. RESULTS: Data were obtained from 19,328 women, including 6512 long-term breast cancer survivors. Healthcare use was higher among breast cancer survivors (20.9 vs 16.6; p < 0.0001) and decreased from >10 years of survival. Breast cancer survivors who underwent a mastectomy were more likely to have a primary care visit (RR = 3.10 95% CI 3.08-3.11). Five to ten years survivors were more likely to have hospital inpatient visits and imaging test compared to women without breast cancer (RRa = 1.35 95% CI 1.30-1.39 and RRa = 1.27 95% CI 1.25-1.29 respectively). CONCLUSION: This study shows higher use of health services in long-term breast cancer survivors than in women without breast cancer regardless of survival time. IMPLICATIONS FOR CANCER SURVIVORS: These results help to estimate the health resources needed for the growing group of breast cancer survivors and to identify risk factors that drive higher use of health services.

Multisystem chronic illness prognostication in non-oncologic integrated care.

OBJECTIVES: To develop a mortality-predictive model for correct identification of patients with non-cancer multiple chronic conditions who would benefit from palliative care, recognise predictive indicators of death and provide with tools for individual risk score calculation. DESIGN: Retrospective observational study with multivariate logistic regression models. PARTICIPANTS: All patients with high-risk multiple chronic conditions incorporated into an integrated care strategy that fulfil two conditions: (1) they belong to the top 5% of the programme's risk pyramid according to the adjusted morbidity groups stratification tool and (2) they suffer simultaneously at least three selected chronic non-cancer pathologies (n=591). MAIN OUTCOME MEASURE: 1 year mortality since patient inclusion in the programme. RESULTS: Among study participants, 201 (34%) died within the 1 year follow-up. Variables found to be independently associated to 1 year mortality were the Barthel Scale (p<0.001), creatinine value (p=0.032), existence of pressure ulcers (p=0.029) and patient global status (p<0.001). The area under the curve (AUC) for our model was 0.751, which was validated using bootstrapping (AUC=0.751) and k-fold cross-validation (10 folds; AUC=0.744). The Hosmer-Lemeshow test (p=0.761) showed good calibration. CONCLUSIONS: This study develops and validates a mortality prediction model that will guide transitions of care to non-cancer palliative care services. The model determines prognostic indicators of death and provides tools for the estimation of individual death risk scores for each patient. We present a nomogram, a graphical risk calculation instrument, that favours a practical and easy use of the model within clinical practices.

Effects of a Tailored Exercise Intervention in Acutely Hospitalized Oldest Old Diabetic Adults: An Ancillary Analysis.

OBJECTIVE: To analyze the effects of a tailored exercise intervention in acutely hospitalized elderly diabetic patients. RESEARCH DESIGN AND METHODS: This is an ancillary analysis of a randomized controlled trial (RCT). A total of 103 acutely hospitalized elderly adults (mean age ~87 years) with type II diabetes were randomized to an intervention (exercise, n = 54) or control group (usual care, n = 49). The primary endpoint was change in functional status from baseline to hospital discharge as assessed with the Barthel Index and the Short Physical Performance Battery (SPPB). Secondary endpoints comprised cognitive function and mood status, quality of life (QoL), incidence of delirium, and handgrip strength. Exercise-related side effects, length of hospital stay, and incidence of falls during hospitalization were also assessed, as well as transfer to nursing homes, hospital readmission, and mortality during a 3-month follow-up. RESULTS: The median length of stay was 8 days (interquartile range, 4) for both groups. The intervention was safe and provided significant benefits over usual care on SPPB (2.7 [95% confidence interval (CI) 1.8, 3.5]) and Barthel Index (8.5 [95% CI: 3.9, 13.1]), as well as on other secondary endpoints such as cognitive status, depression, QoL, and handgrip strength (all P < 0.05). No significant between-group differences were found for the remainder of secondary endpoints. CONCLUSIONS: An in-hospital individualized multicomponent exercise intervention was safe and effective for the prevention of functional and cognitive decline in acutely hospitalized elderly diabetic patients, although it had no influence on other endpoints assessed during hospitalization or at the 3-month follow-up after discharge.

Blood pressure targets for the treatment of people with hypertension and cardiovascular disease.

BACKGROUND: This is the second update of the review first published in 2017. Hypertension is a prominent preventable cause of premature morbidity and mortality. People with hypertension and established cardiovascular disease are at particularly high risk, so reducing blood pressure to below standard targets may be beneficial. This strategy could reduce cardiovascular mortality and morbidity but could also increase adverse events. The optimal blood pressure target in people with hypertension and established cardiovascular disease remains unknown. OBJECTIVES: To determine if lower blood pressure targets (135/85 mmHg or less) are associated with reduction in mortality and morbidity as compared with standard blood pressure targets (140 to 160/90 to 100 mmHg or less) in the treatment of people with hypertension and a history of cardiovascular disease (myocardial infarction, angina, stroke, peripheral vascular occlusive disease). SEARCH METHODS: For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials (RCTs) up to November 2019: Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE (from 1946), Embase (from 1974), and Latin American Caribbean Health Sciences Literature (LILACS) (from 1982), along with the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. We applied no language restrictions. SELECTION CRITERIA: We included RCTs with more than 50 participants per group that provided at least six months' follow-up. Trial reports had to present data for at least one primary outcome (total mortality, serious adverse events, total cardiovascular events, cardiovascular mortality). Eligible interventions involved lower targets for systolic/diastolic blood pressure (135/85 mmHg or less) compared with standard targets for blood pressure (140 to 160/90 to 100 mmHg or less). Participants were adults with documented hypertension and adults receiving treatment for hypertension with a cardiovascular history for myocardial infarction, stroke, chronic peripheral vascular occlusive disease, or angina pectoris. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed search results and extracted data using standard methodological procedures expected by Cochrane. We used GRADE to assess the quality of the evidence. MAIN RESULTS: We included six RCTs that involved 9484 participants. Mean follow-up was 3.7 years (range 1.0 to 4.7 years). All RCTs provided individual participant data. None of the included studies was blinded to participants or clinicians because of the need to titrate antihypertensives to reach a specific blood pressure goal. However, an independent committee blinded to group allocation assessed clinical events in all trials. Hence, we assessed all trials at high risk of performance bias and low risk of detection bias. Other issues such as early termination of studies and subgroups of participants not predefined were also considered to downgrade the quality evidence. We found there is probably little to no difference in total mortality (risk ratio (RR) 1.06, 95% confidence interval (CI) 0.91 to 1.23; 6 studies, 9484 participants; moderate-quality evidence) or cardiovascular mortality (RR 1.03, 95% CI 0.82 to 1.29; 6 studies, 9484 participants; moderate-quality evidence). Similarly, we found there may be little to no differences in serious adverse events (RR 1.01, 95% CI 0.94 to 1.08; 6 studies, 9484 participants; low-quality evidence) or total cardiovascular events (including myocardial infarction, stroke, sudden death, hospitalization, or death from congestive heart failure) (RR 0.89, 95% CI 0.80 to 1.00; 6 studies, 9484 participants; low-quality evidence). The evidence was very uncertain about withdrawals due to adverse effects. However, studies suggest more participants may withdraw due to adverse effects in the lower target group (RR 8.16, 95% CI 2.06 to 32.28; 2 studies, 690 participants; very low-quality evidence). Systolic and diastolic blood pressure readings were lower in the lower target group (systolic: mean difference (MD) -8.90 mmHg, 95% CI -13.24 to -4.56; 6 studies, 8546 participants; diastolic: MD -4.50 mmHg, 95% CI -6.35 to -2.65; 6 studies, 8546 participants). More drugs were needed in the lower target group (MD 0.56, 95% CI 0.16 to 0.96; 5 studies, 7910 participants), but blood pressure targets were achieved more frequently in the standard target group (RR 1.21, 95% CI 1.17 to 1.24; 6 studies, 8588 participants). AUTHORS' CONCLUSIONS: We found there is probably little to no difference in total mortality and cardiovascular mortality between people with hypertension and cardiovascular disease treated to a lower compared to a standard blood pressure target. There may also be little to no difference in serious adverse events or total cardiovascular events. This suggests that no net health benefit is derived from a lower systolic blood pressure target. We found very limited evidence on withdrawals due to adverse effects, which led to high uncertainty. At present, evidence is insufficient to justify lower blood pressure targets (135/85 mmHg or less) in people with hypertension and established cardiovascular disease. Several trials are still ongoing, which may provide an important input to this topic in the near future.

Inverse-probability weighting and multiple imputation for evaluating selection bias in the estimation of childhood obesity prevalence using data from electronic health records.

BACKGROUND AND OBJECTIVES: Height and weight data from electronic health records are increasingly being used to estimate the prevalence of childhood obesity. Here, we aim to assess the selection bias due to missing weight and height data from electronic health records in children older than five. METHODS: Cohort study of 10,811 children born in Navarra (Spain) between 2002 and 2003, who were still living in this region by December 2016. We examined the differences between measured and non-measured children older than 5 years considering weight-associated variables (sex, rural or urban residence, family income and weight status at 2-5 yrs). These variables were used to calculate stabilized weights for inverse-probability weighting and to conduct multiple imputation for the missing data. We calculated complete data prevalence and adjusted prevalence considering the missing data using inverse-probability weighting and multiple imputation for ages 6 to 14 and group ages 6 to 9 and 10 to 14. RESULTS: For 6-9 years, complete data, inverse-probability weighting and multiple imputation obesity age-adjusted prevalence were 13.18% (95% CI: 12.54-13.85), 13.22% (95% CI: 12.57-13.89) and 13.02% (95% CI: 12.38-13.66) and for 10-14 years 8.61% (95% CI: 8.06-9.18), 8.62% (95% CI: 8.06-9.20) and 8.24% (95% CI: 7.70-8.78), respectively. CONCLUSIONS: Ages at which well-child visits are scheduled and for the 6 to 9 and 10 to 14 age groups, weight status estimations are similar using complete data, multiple imputation and inverse-probability weighting. Readily available electronic health record data may be a tool to monitor the weight status in children.

Blood pressure targets for the treatment of people with hypertension and cardiovascular disease.

BACKGROUND: This is the first update of the review published in 2017. Hypertension is a prominent preventable cause of premature morbidity and mortality. People with hypertension and established cardiovascular disease are at particularly high risk, so reducing blood pressure to below standard targets may be beneficial. This strategy could reduce cardiovascular mortality and morbidity but could also increase adverse events. The optimal blood pressure target in people with hypertension and established cardiovascular disease remains unknown. OBJECTIVES: To determine if 'lower' blood pressure targets (≤ 135/85 mmHg) are associated with reduction in mortality and morbidity as compared with 'standard' blood pressure targets (≤ 140 to 160/90 to 100 mmHg) in the treatment of people with hypertension and a history of cardiovascular disease (myocardial infarction, angina, stroke, peripheral vascular occlusive disease). SEARCH METHODS: For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to February 2018: Cochrane Hypertension Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), and Latin American Caribbean Health Sciences Literature (LILACS) (from 1982), along with the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. We applied no language restrictions. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that included more than 50 participants per group and provided at least six months' follow-up. Trial reports had to present data for at least one primary outcome (total mortality, serious adverse events, total cardiovascular events, cardiovascular mortality). Eligible interventions involved lower targets for systolic/diastolic blood pressure (≤ 135/85 mmHg) compared with standard targets for blood pressure (≤ 140 to 160/90 to 100 mmHg).Participants were adults with documented hypertension and adults receiving treatment for hypertension with a cardiovascular history for myocardial infarction, stroke, chronic peripheral vascular occlusive disease, or angina pectoris. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed search results and extracted data using standard methodological procedures expected by Cochrane. MAIN RESULTS: We included six RCTs that involved a total of 9484 participants. Mean follow-up was 3.7 years (range 1.0 to 4.7 years). All RCTs provided individual participant data.We found no change in total mortality (risk ratio (RR) 1.06, 95% confidence interval (CI) 0.91 to 1.23) or cardiovascular mortality (RR 1.03, 95% CI 0.82 to 1.29; moderate-quality evidence). Similarly, we found no differences in serious adverse events (RR 1.01, 95% CI 0.94 to 1.08; low-quality evidence) or total cardiovascular events (including myocardial infarction, stroke, sudden death, hospitalization, or death from congestive heart failure) (RR 0.89, 95% CI 0.80 to 1.00; low-quality evidence). Studies reported more participant withdrawals due to adverse effects in the lower target arm (RR 8.16, 95% CI 2.06 to 32.28; very low-quality evidence). Blood pressures were lower in the lower target group by 8.9/4.5 mmHg. More drugs were needed in the lower target group, but blood pressure targets were achieved more frequently in the standard target group. AUTHORS' CONCLUSIONS: We found no evidence of a difference in total mortality, serious adverse events, or total cardiovascular events between people with hypertension and cardiovascular disease treated to a lower or to a standard blood pressure target. This suggests that no net health benefit is derived from a lower systolic blood pressure target. We found very limited evidence on adverse events, which led to high uncertainty. At present, evidence is insufficient to justify lower blood pressure targets (≤ 135/85 mmHg) in people with hypertension and established cardiovascular disease. More trials are needed to examine this topic.

Blood pressure targets for the treatment of people with hypertension and cardiovascular disease.

BACKGROUND: Hypertension is a prominent preventable cause of premature morbidity and mortality. People with hypertension and established cardiovascular disease are at particularly high risk, so reducing blood pressure below standard targets may be beneficial. This strategy could reduce cardiovascular mortality and morbidity but could also increase adverse events. The optimal blood pressure target in people with hypertension and established cardiovascular disease remains unknown. OBJECTIVES: To determine if 'lower' blood pressure targets (≤ 135/85 mmHg) are associated with reduction in mortality and morbidity as compared with 'standard' blood pressure targets (≤ 140 to 160/ 90 to 100 mmHg) in the treatment of people with hypertension and a history of cardiovascular disease (myocardial infarction, angina, stroke, peripheral vascular occlusive disease). SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to February 2017: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also searched the Latin American and Caribbean Health Science Literature Database (from 1982) and contacted authors of relevant papers regarding further published and unpublished work. There were no language restrictions. SELECTION CRITERIA: We included randomized controlled trials (RCTs) with more than 50 participants per group and at least six months follow-up. Trial reports needed to present data for at least one primary outcome (total mortality, serious adverse events, total cardiovascular events, cardiovascular mortality). Eligible interventions were lower target for systolic/diastolic blood pressure (≤ 135/85 mmHg) compared with standard target for blood pressure (≤ 140 to 160/90 to 100 mmHg).Participants were adults with documented hypertension or who were receiving treatment for hypertension and cardiovascular history for myocardial infarction, stroke, chronic peripheral vascular occlusive disease or angina pectoris. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed search results and extracted data using standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: We included six RCTs that involved a total of 9795 participants. Mean follow-up was 3.7 years (range 1.0 to 4.7 years). Five RCTs provided individual patient data for 6775 participants.We found no change in total mortality (RR 1.05, 95% CI 0.90 to 1.22) or cardiovascular mortality (RR 0.96, 95% CI 0.77 to 1.21; moderate-quality evidence). Similarly, no differences were found in serious adverse events (RR 1.02, 95% CI 0.95 to 1.11; low-quality evidence). There was a reduction in fatal and non fatal cardiovascular events (including myocardial infarction, stroke, sudden death, hospitalization or death from congestive heart failure) with the lower target (RR 0.87, 95% CI 0.78 to 0.98; ARR 1.6% over 3.7 years; low-quality evidence). There were more participant withdrawals due to adverse effects in the lower target arm (RR 8.16, 95% CI 2.06 to 32.28; very low-quality evidence). Blood pressures were lower in the lower' target group by 9.5/4.9 mmHg. More drugs were needed in the lower target group but blood pressure targets were achieved more frequently in the standard target group. AUTHORS' CONCLUSIONS: No evidence of a difference in total mortality and serious adverse events was found between treating to a lower or to a standard blood pressure target in people with hypertension and cardiovascular disease. This suggests no net health benefit from a lower systolic blood pressure target despite the small absolute reduction in total cardiovascular serious adverse events. There was very limited evidence on adverse events, which lead to high uncertainty. At present there is insufficient evidence to justify lower blood pressure targets (≤ 135/85 mmHg) in people with hypertension and established cardiovascular disease. More trials are needed to answer this question.

Rethinking the Appraisal and Approval of Drugs for Fracture Prevention.

Background: In January 2014, the EMA's Pharmacovigilance Risk Assessment Committee recommended that strontium ranelate no longer be used for osteoporosis. However, EMA's Committee for Medicinal Products for Human Use decided to restrict its use rather than ban it. Starting from this fact, evidence of drugs for fracture prevention over the last 30 years was reviewed and lessons to be learnt from this story are highlighted. Findings: The general belief that drug therapy may become a "solution" for fragility fractures is challenged. The key points of the article are as follows: Lessons 1-5: Bone density and morphometric vertebral compression are not reliable surrogate endpoints. In fact, clinically relevant endpoints are essential to assess harms and benefits in clinical trials. There is a need for assessing overall harm-benefit with well-designed trials, taking into account that drug therapy may not be more effective in high-risk patients. Lessons 6-10: While bisphosphonates and strontium ranelate show a questionable harm-benefit ratio on hip fracture prevention, denosumab results are inconclusive and no benefit has been proved coming from calcitonines or teriparatide. After decades of widespread use, effectiveness of drugs for osteoporosis remains uncertain, yet adverse effects are more apparent. Conclusions: Well-designed and large trials over prolonged follow-up periods, measuring clinically relevant outcomes as hip and other disabling fractures, are urgently needed in order to properly understand the harm-benefit ratio of commonly prescribed drugs. Regulatory agencies should be more transparent and make individual-patient data from all clinical trials publicly available, allowing for independent assessment and pooled analysis.

Validity of type 2 diabetes diagnosis in a population-based electronic health record database.

BACKGROUND: The increasing burden of type 2 diabetes mellitus makes the continuous surveillance of its prevalence and incidence advisable. Electronic health records (EHRs) have great potential for research and surveillance purposes; however the quality of their data must first be evaluated for fitness for use. The aim of this study was to assess the validity of type 2 diabetes diagnosis in a primary care EHR database covering more than half a million inhabitants, 97% of the population in Navarra, Spain. METHODS: In the Navarra EPIC-InterAct study, the validity of the T90 code from the International Classification of Primary Care, Second Edition was studied in a primary care EHR database to identify incident cases of type 2 diabetes, using a multi-source approach as the gold standard. The sensitivity, specificity, positive predictive value, negative predictive value and the kappa index were calculated. Additionally, type 2 diabetes prevalence from the EHR database was compared with estimations from a health survey. RESULTS: The sensitivity, specificity, positive predictive value and negative predictive value of incident type 2 diabetes recorded in the EHRs were 98.2, 99.3, 92.2 and 99.8%, respectively, and the kappa index was 0.946. Overall prevalence of type 2 diabetes diagnosed in the EHRs among adults (35-84 years of age) was 7.2% (95% confidence interval [CI] 7.2-7.3) in men and 5.9% (95% CI 5.8-5.9) in women, which was similar to the prevalence estimated from the health survey: 8.5% (95% CI 7.1-9.8) and 5.5% (95% CI 4.4-6.6) in men and women, respectively. CONCLUSIONS: The high sensitivity and specificity of type 2 diabetes diagnosis found in the primary care EHRs make this database a good source for population-based surveillance of incident and prevalent type 2 diabetes, as well as for monitoring quality of care and health outcomes in diabetic patients.

Use of oral antidiabetic agents and risk of community-acquired pneumonia: a nested case-control study.

AIMS: To evaluate the association between use of different oral antidiabetic agents (OAD) and the risk of community-acquired pneumonia (CAP) in patients with type-2 diabetes (T2DM). METHODS: Case-control study nested in a cohort of patients with T2DM and use of OAD between 2002 and 2013, based in a Spanish general practice research database. Cases were people diagnosed with T2DM, aged >18 years and with a validated diagnosis of CAP between 2002 and 2013. Ten controls were matched on age, sex and calendar year. Odds ratio (OR) of CAP was estimated comparing patients treated with: (1) metformin vs. other monotherapies or no antidiabetic treatment; (2) metformin + sulfonylureas vs. other antidiabetic combinations. OR of CAP was also assessed according to antidiabetic treatment duration. RESULTS: From a cohort of 76 009 T2DM patients, we identified 1803 cases of CAP. No difference in the incidence of CAP was observed when comparing any OAD in monotherapy with metformin. Compared with current use of metformin + sulfonylurea, thiazolidinediones + metformin was associated with an increased risk of CAP (adjusted OR = 2.48, 95% CI 1.40-4.38). The use of any combination with thiazolidinediones was also associated with higher risk of CAP (adjusted OR = 2.00, 95% CI 1.22-3.28). Current use of DPP-4 inhibitors was not associated with an increased risk of CAP. CONCLUSIONS: No differences in the incidence of CAP were observed between the use of OAD in monotherapy vs. metformin. Thiazolidinedione use in combination was associated with an increase in the risk of CAP when compared to metformin + sulfonylureas. The use of DPP-4 inhibitors was not associated with an increased risk of CAP.

Oral bisphosphonates are associated with increased risk of subtrochanteric and diaphyseal fractures in elderly women: a nested case-control study.

OBJECTIVES: To evaluate the association between bisphosphonate use and the risk of atypical femoral fractures among women aged 65 or older. DESIGN: Nested case-control study. SETTING: General practice research database in Spain. EXPOSURES: Use of oral bisphosphonates before the occurrence of atypical fractures among cases or the corresponding index date among controls. Bisphosphonate use was categorised as ever versus never users. Ever users were divided according to the total time since first prescription. MAIN OUTCOME MEASURES: Cases were defined as women aged 65 years or older with a first diagnosis of subtrochanteric or diaphyseal fracture, recorded in the BIFAP database between 1 January 2005 and 31 December 2008, and with at least 1 year of follow-up before the index date. For each case, five age-matched and calendar-year-matched controls without a history of hip or atypical fracture were randomly selected from the database. STATISTICAL ANALYSIS: OR of atypical femoral fracture by bisphosphonate use was determined using conditional logistic regression. Models were adjusted for comorbidities and use of other medications. RESULTS: The analysis included 44 cases and 220 matched controls (mean age, 82 years). Ever use of bisphosphonates was more frequent in cases than controls (29.6% vs 10.5%). In multivariate analyses, OR (95% CI) of atypical femoral fracture was 4.30 (1.55 to 11.9) in ever versus never users of bisphosphonates. The risk increased with long-term use, with an OR of 9.46 (2.17 to 41.3) comparing those using bisphosphonates over 3 years versus no users (p for trend=0.01). CONCLUSIONS: Bisphosphonate use was associated with an increased risk of subtrochanteric or diaphyseal fractures in elderly women in a low fracture risk population, with a higher risk among long-term bisphosphonate users.

Oral bisphosphonates may not decrease hip fracture risk in elderly Spanish women: a nested case-control study.

OBJECTIVES: To evaluate the association between the long-term use of bisphosphonates and the risk of hip fracture compared to never use among women aged 65 years or older. DESIGN: Case-control study nested in a cohort. SETTING: General practice research database operated by the Spanish Medicines Agency. PARTICIPANTS: Cases of hip fracture were defined as women aged 65 years or older with a validated first diagnosis of hip fracture between 2005 and 2008. Five controls free of hip fracture were matched on age and calendar-year with each case. INTERVENTIONS: Information on bisphosphonate use, hip fractures, comedication and comorbidities was collected. PRIMARY OUTCOMES: Hip fracture risk comparing bisphosphonate users versus never users. SECONDARY OUTCOMES: Hip fracture risk comparing bisphosphonate users versus never users by individual drugs. RESULTS: The study included 2009 incident hip fractures and 10 045 matched controls. Hip-fracture risk did not differ between bisphosphonate users and never users, adjusted OR=1.09 (95% CI 0.94 to 1.27). No association was observed between hip fracture risk and cumulative duration of bisphosphonate treatment. However, when treatment duration is analysed as time since first prescription, hip fracture risks of the different subgroups compared to never users obtained were as follows: <1 year, OR 0.85 (95% CI 0.60 to 1.21); 1 to <3 years, OR 1.02 (95% CI 0.82 to 1.26); ≥3 years, OR 1.32 (95% CI 1.05 to 1.65) (p for trend=0.03). CONCLUSIONS: Ever use of oral bisphosphonates was not associated with a decreased risk of hip fracture in women aged 65 or older as compared to never use. No association was observed between hip fracture risk and cumulative duration of bisphosphonate treatment. However, when treatment duration is analysed as time since first prescription, a statistically significant increased risk for hip fracture was observed in patients exposed to bisphosphonates over 3 years. TRIAL REGISTRATION: Spanish Ministry of Health. TRA-071.