Antihypertensive medications and survival in patients with cancer: A population-based retrospective cohort study

Background: The association between antihypertensive medications and survival in cancer patients remains unclear. Objectives: To explore the association between classes of antihypertensive drugs and survival in cancer patients. Methods: Provincial Cancer Registry data was linked with a Provincial Drug Program Information Network (DPIN) for patients with lung (n = 4241), colorectal (n = 3967), breast (n = 4019) or prostate (n = 3355) cancer between the years of 2004 and 2008. Cox regression analyses were used to compare survival of patients using beta blockers (BBs), angiotensin-converting enzyme inhibitors/receptor blockers (ACEi/ARB), calcium channel blockers (CCBs) or thiazide diuretics (TDs) to survival of patients who did not use any of these antihypertensive drugs. Survival of patients using only one class of antihypertensive drugs were compared to each other, with BBs as the reference class. Results: Compared to the antihypertensive drug non-user cohort, BBs had no effect on survival for any of the cancers. ACEi/ARBs use was weakly associated with increased deaths for breast cancer (HR: 1.22, 95% CI: 1.04–1.44) and lung cancer (HR: 1.11, 95% CI: 1.03–1.21) patients. Deaths were also increased with CCB use in patients with breast cancer (HR: 1.22, 95% CI: 1.02–1.47) and with TD use in lung cancer patients (HR: 1.1, 95% CI: 1.01–1.19). There was strong evidence (p-value <0.0001) of an increase in deaths with TD use for colorectal (HR: 1.28, 95% CI: 1.15–1.42), and prostate (HR 1.41, 1.2–1.65) cancer patients. When including only antihypertensive drug users prescribed one drug class, lung cancer patients receiving CCBs had improved survival compared to BBs (HR 0.79, 95% CI: 0.64–0.98). Conclusions: Some classes of antihypertensive agents are associated with a decreased survival in certain cancers. The decrease could be due to more comorbidities in antihypertensive drug users. However, CCB use was associated with improved survival in lung cancer patients.     

Visual Impairment,Hearing Loss and Cognitive Function in an Older Population: Longitudinal Findings from the Blue Mountains Eye Study

The presence of visual impairment (VI) and hearing loss (HL) with may be a marker for subsequent cognitive decline over time in older people. A prospective, longitudinal population-based study of the 3654 participants of the Blue Mountains Eye Study were assessed for the associations between VI and HL and a decline in mini-mental state examination (MMSE) scores over a duration of 10 years from the 5-year (baseline of this report) to the 15-year follow-up visits. MMSE was assessed at the 5-, 10- and 15-year follow-up visits. A decline ≥3 scores from 5-year to 10- or 15-year visits indicated possible cognitive decline. VI was defined as best-corrected visual acuity <6/12 in the worse-eye, HL was defined as pure-tone average >40 decibels in the worse-ear and dual sensory impairment (DSI) was defined by the co-presence of VI and HL, detected at 5-year follow-up (baseline of this report). Participants with no VI and HL over the same 5- or 10-year corresponding period were controls. Associations of VI, HL and DSI with possible cognitive decline were assessed using logistic regression models adjusting for age and sex after excluding subjects with a stroke history. The presence of VI, HL or DSI was not associated with possible cognitive decline over 5 years (odds ratio (OR) 0.84, 95% confidence-intervals (CI) 0.40–1.79, OR 1.02, 95% CI 0.61–1.70 and 1.41, 95% CI 0.54–3.72, respectively) or 10 years (OR 1.09, 95% CI 0.52–2.30, OR 1.09, 95% CI 0.65–1.82 and 1.15, 95% CI 0.28–4.73, respectively). There were no changes to these findings after adjustment for other potential confounders. Age was significantly associated with possible cognitive decline (OR 1.07, 95% CI 1.04–1.10 for both periods). Neither visual impairment, hearing loss nor dual sensory impairment was independently associated with subsequent decline in cognition.     

Reduced risk of human lung cancer by selective cyclooxygenase 2 (COX-2) blockade: results of a case control study

We conducted a case control study of selective cyclooxygenase-2 (COX-2) blocking agents and lung cancer. A total of 492 newly diagnosed lung cancer cases were ascertained during January 1, 2002 to September 30, 2004, at The Ohio State University Medical Center, Columbus, Ohio. All cases were confirmed by examination of the pathology report. Healthy population controls without cancer were ascertained during the same time period. Controls were frequency matched at a rate of 2:1 to the cases by age, gender, and county of residence. We collected information on type, frequency, and duration of use of selective COX-2 inhibitors (primarily celecoxib or rofecoxib) and nonselective NSAIDs such as ibuprofen and aspirin. Estimates of odds ratios (OR) were obtained with adjustment for cigarette smoking, age and other potential confounders using logistic regression analysis. Odds Ratios for selective COX-2 inhibitors were adjusted for past use of other NSAIDs. Use of any selective COX-2 inhibitor for more than one year produced a significant (60%) reduction in the risk of lung cancer (OR=0.40, 95% CI=0.19-0.81). Observed risk reductions were consistent for men (OR=0.26, 95% CI=0.10-0.62) and women (OR=0.52, 95% CI=0.24-1.13) and for individual COX-2 inhibitors (OR=0.28, 95% CI=-0.12-0.67, for celecoxib and OR=0.55, 95% CI=0.19-1.56, for rofecoxib). Intake of ibuprofen or aspirin also produced significant risk reductions (OR=0.40, 95% CI=0.23-0.73 and OR=0.53, 95% CI=0.34-0.82, respectively), whereas acetaminophen, an analgesic with negligible COX-2 activity, had no effect on the risk (OR=1.36, 95% CI=0.53-3.37). This investigation demonstrates for the first time that selective COX-2 blocking agents have strong potential for the chemoprevention of human lung cancer.     

The relationship between long-term sunlight radiation and cognitive decline in the REGARDS cohort study

Sunlight may be related to cognitive function through vitamin D metabolism or circadian rhythm regulation. The analysis presented here sought to test whether ground and satellite measures of solar radiation are associated with cognitive decline. The study used a 15-year residential history merged with satellite and ground monitor data to determine sunlight (solar radiation) and air temperature exposure for a cohort of 19,896 cognitively intact black and white participants aged 45+ from the 48 contiguous United States. Exposures of 15, 10, 5, 2, and 1-year were used to predict cognitive status at the most recent assessment in logistic regression models; 1-year insolation and maximum temperatures were chosen as exposure measures. Solar radiation interacted with temperature, age, and gender in its relationships with incident cognitive impairment. After adjustment for covariates, the odds ratio (OR) of cognitive decline for solar radiation exposure below the median vs above the median in the 3rd tertile of maximum temperatures was 1.88 (95 % CI: 1.24, 2.85), that in the 2nd tertile was 1.33 (95 % CI: 1.09, 1.62), and that in the 1st tertile was 1.22 (95 % CI: 0.92, 1.60). We also found that participants under 60 years old had an OR?=?1.63 (95 % CI: 1.20, 2.22), those 60–80 years old had an OR?=?1.18 (95 % CI: 1.02, 1.36), and those over 80 years old had an OR?=?1.05 (0.80, 1.37). Lastly, we found that males had an OR?=?1.43 (95 % CI: 1.22, 1.69), and females had an OR?=?1.02 (0.87, 1.20). We found that lower levels of solar radiation were associated with increased odds of incident cognitive impairment.     

Choice of antihypertensive drug in the diabetic patient

The hypertensive patient with type 2 diabetes is especially at risk of adverse cardiovascular events. The United Kingdom Prospective Diabetes Study (UKPDS) and Hypertension Optimal Treatment (HOT) studies suggested that treatment to a lower target blood pressure resulted in better prevention of clinical disease in these patients. Most trials comparing antihypertensive drugs have shown only minimal differences between the various agents. The evidence from the trials suggests that diuretics, beta-blockers, calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and the angiotensin-receptor antagonists (ARBs) will all successfully reduce adverse clinical events. The largest of the comparative hypertensive drug trials, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), demonstrated that a diuretic has a better hypotensive effect, and was more successful in preventing many aspects of cardiovascular disease compared with CCBs and ACE inhibitors. The importance of good blood pressure control and the general equivalence of antihypertensive drugs were again shown in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial, which compared an ARB with a CCB. Choice of antihypertensive agent should be individualized and guided by the presence of concomitant clinical disease and the need to protect any specific target organ system in the diabetic hypertensive. Diuretics, being potent hypotensive drugs with clearly demonstrated clinical benefit, should form part of the antihypertensive regimen of most diabetic hypertensives. ACE inhibitors and ARBs are especially useful in preventing nephropathy. Most patients will require a combination of antihypertensive drugs to achieve tight blood pressure control of under 130/80 mm Hg in the diabetic hypertensive. The clinician should concentrate on seeking this lower target blood pressure rather than be excessively concerned about which is the best antihypertensive agent.     

Comparing six antihypertensive medication classes for preventing new‐onset diabetes mellitus among hypertensive patients: a network meta‐analysis

Hypertensive patients usually have a higher risk of new‐onset diabetes mellitus (NOD) which may trigger cardiovascular diseases. In this study, the effectiveness of six antihypertensive agents with respect to NOD prevention in hypertensive patients was assessed. A network meta‐analysis was conducted to compare the efficacy of specific drug classes. PubMed and Embase databases were searched for relevant articles. Results of the pairwised meta‐analysis were illustrated by odd ratios (OR) and a corresponding 95% confidence interval (CI). The probabilities and outcome of each treatment were ranked and summarized using the surface under the cumulative ranking curve (SUCRA).Twenty‐three trials were identified, including 224,832 patients with an average follow‐up period of 3.9 ± 1.0 years. The network meta‐analysis showed that patients treated by angiotensin II receptor blockers (ARBs) were associated with a lower risk of NOD compared to placebo (PCB), calcium channel blockers (CCBs) and β‐blockers, while diuretic appeared to be ineffective for NOD prevention. Network meta‐analysis results of specific drugs showed that enalapril exhibited distinct advantages and hydrochlorothiazide also exhibited a reliable performance. Our results suggested that both ARBs and angiotensin converse enzyme inhibitors (ACEIs), especially candesartan and enalapril, were preferable for NOD prevention in hypertensive patients. Hydrochlorothiazide also exhibited a reliable performance in comparison with other agents.     

Estimating Antihypertensive Effects of Combination Therapy in an Observational Study Using Marginal Structural Models

The evaluation of the antihypertensive effect of multiple antihypertensive drugs using data from an observational study requires adjustment for time‐dependent confounders. Marginal structural models (MSMs) have been proposed to address this type of confounding through inverse probability weighting. Generally, the probabilities are estimated using logistic regression models that assume linearity between the logistic link and the predictors, but the linearity might be inaccurate. In this article, we proposed MSMs to assess the blood pressure‐lowering effects of combination therapy with olmesartan medoxomil (OLM) plus calcium channel blockers (CCB) (OLM+CCB) in an observational study of OLM, and extended estimation methods of the probabilities for the MSMs using generalized additive models (GAMs). The estimation using GAMs was suggested to improve the balance of the distributions of confounder values between the therapy groups in the pseudo‐population. We obtained estimated changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) for OLM+CCB combination therapy after 12 wk compared with OLM monotherapy of ?4.3 mmHg (95% confidence interval (CI): ?7.7 and ?0.9 mmHg) and ?2.9 mmHg (95% CI: ?5.1 and ?0.7 mmHg), respectively. The estimated target BP (SBP<140 mmHg and DBP<90 mmHg) achievement rates for OLM+CCB combination therapy and OLM monotherapy were 62.0 and 46.7%, respectively. The results of the MSMs were closer to those in the randomized controlled trial, such as the combination of OLM and amlodipine besylate in controlling high blood pressure study, than those of conventional methods. The proposed MSMs provided useful information to evaluate the effects of combination therapy of antihypertensive drugs in the context of an observational study.     

Healthy Lifestyles Reduce the Incidence of Chronic Diseases and Dementia: Evidence from the Caerphilly Cohort Study

Background

Healthy lifestyles based on non-smoking, an acceptable BMI, a high fruit and vegetable intake, regular physical activity, and low/moderate alcohol intake, are associated with reductions in the incidence of certain chronic diseases, but to date there is limited evidence on cognitive function and dementia.

Methods

In 1979 healthy behaviours were recorded on 2,235 men aged 45–59 years in Caerphilly, UK. During the following 30 years incident diabetes, vascular disease, cancer and death were recorded, and in 2004 cognitive state was determined.

Findings

Men who followed four or five of the behaviours had an odds ratio (OR) and confidence intervals (CI) for diabetes, corrected for age and social class, of 0.50 (95% CI: 0.19, 1.31; P for trend with increasing numbers of healthy behaviours <0.0005). For vascular disease the OR was 0.50 (95% CI: 0.30, 0.84; P for trend <0.0005), and there was a delay in vascular disease events of up to 12 years. Cancer incidence was not significantly related to lifestyle although there was a reduction associated with non-smoking (OR: 0.65; 95% CI: 0.54, 0.79). All-cause mortality was reduced in men following four or five behaviours (OR 0.40; 95% CI: 0.24, 0.67; P for trend <0.005).After further adjustment for NART, the OR for men following four or five healthy behaviours was 0.36 (95% CI: 0.12, 1.09; P for trend <0.001) for cognitive impairment, and 0.36 (95% CI: 0.07, 1.99; P for trend <0.02) for dementia.The adoption of a healthy lifestyle by men was low and appears not to have changed during the subsequent 30 years, with under 1% of men following all five of the behaviours and 5% reporting four or more in 1979 and in 2009.

Interpretation

A healthy lifestyle is associated with increased disease-free survival and reduced cognitive impairment but the uptake remains low.     

Consumption of Green Tea,but Not Black Tea or Coffee,Is Associated with Reduced Risk of Cognitive Decline

Our objective was to determine whether the consumption of green tea, coffee, or black tea influences the incidence of dementia and mild cognitive impairment (MCI) in older people. We conducted a population-based prospective study with Japanese residents aged >60 years from Nakajima, Japan (the Nakajima Project). Participants received an evaluation of cognitive function and blood tests. The consumption of green tea, coffee, and black tea was also evaluated at baseline. Of 723 participants with normal cognitive function at a baseline survey (2007–2008), 490 completed the follow up survey in 2011–2013. The incidence of dementia during the follow-up period (mean ± SD: 4.9±0.9 years) was 5.3%, and that of MCI was 13.1%. The multiple-adjusted odds ratio for the incidence of overall cognitive decline (dementia or MCI) was 0.32 (95% CI: 0.16–0.64) among individuals who consumed green tea every day and 0.47 (95% CI: 0.25–0.86) among those who consumed green tea 1–6 days per week compared with individuals who did not consume green tea at all. The multiple-adjusted odds ratio for the incidence of dementia was 0.26 (95% CI: 0.06–1.06) among individuals who consumed green tea every day compared with those who did not consume green tea at all. No association was found between coffee or black tea consumption and the incidence of dementia or MCI. Our results indicate that green tea consumption is significantly associated with reduced risk of cognitive decline, even after adjustment for possible confounding factors.     

Prevalence of Dementia and Subtypes in Valladolid,Northwestern Spain: The DEMINVALL Study

Objective

To describe the prevalence of dementia and subtypes in a general elderly population in northwestern Spain and to analyze the influence of socio-demographic factors.

Methods

Cross-sectional, two-phase, door-to-door, population-based study. A total of 870 individuals from a rural region and 2,119 individuals from an urban region of Valladolid, Spain, were involved. The seven-minute screen neurocognitive battery was used in the screening phase. A control group was included.

Results

A total of 2,170 individuals aged 65 to 104 years (57% women) were assessed. There were 184 subjects diagnosed with dementia. The crude prevalence was 8.5% (95% CI: 7.3-9.7). Age- and sex-adjusted prevalence was 5.5 (95% CI: 4.5-6.5). Main subtypes of dementia were: Alzheimer’s disease (AD) 77.7%, Lewy Body disease, 7.6% and vascular dementia (VD) 5.9%. Crude prevalences were 6.6% (AD), 0.6% (Lewy Body disease), and 0.5% (VD). Dementia was associated with age (OR 1.14 for 1-year increase in age), female sex (OR 1.79) and the absence of formal education (OR 2.53 compared to subjects with primary education or more).

Conclusion

The prevalence of dementia in the study population was lower than the most recent estimates for Western Europe. There was a high proportion of AD among all dementia cases and very low prevalence of VD. Old age, female sex, and low education level were independent risk factors for dementia and AD.     

Adherence to Antihypertensive Therapy and Elevated Blood Pressure: Should We Consider the Use of Multiple Medications?

Background

Although a majority of patients with hypertension require a multidrug therapy, this is rarely considered when measuring adherence from refill data. Moreover, investigating the association between refill non-adherence to antihypertensive therapy (AHT) and elevated blood pressure (BP) has been advocated.

Objective

Identify factors associated with non-adherence to AHT, considering the multidrug therapy, and investigate the association between non-adherence to AHT and elevated BP.

Methods

A retrospective cohort study including patients with hypertension, identified from a random sample of 5025 Swedish adults. Two measures of adherence were estimated by the proportion of days covered method (PDC≥80%): (1) Adherence to any antihypertensive medication and, (2) adherence to the full AHT regimen. Multiple logistic regressions were performed to investigate the association between sociodemographic factors (age, sex, education, income), clinical factors (user profile, number of antihypertensive medications, healthcare use, cardiovascular comorbidities) and non-adherence. Moreover, the association between non-adherence (long-term and a month prior to BP measurement) and elevated BP was investigated.

Results

Non-adherence to any antihypertensive medication was higher among persons < 65 years (Odds Ratio, OR 2.75 [95% CI, 1.18–6.43]) and with the lowest income (OR 2.05 [95% CI, 1.01–4.16]). Non-adherence to the full AHT regimen was higher among new users (OR 2.04 [95% CI, 1.32–3.15]), persons using specialized healthcare (OR 1.63, [95% CI, 1.14–2.32]), and having multiple antihypertensive medications (OR 1.85 [95% CI, 1.25–2.75] and OR 5.22 [95% CI, 3.48–7.83], for 2 and ≥3 antihypertensive medications, respectively). Non-adherence to any antihypertensive medication a month prior to healthcare visit was associated with elevated BP.

Conclusion

Sociodemographic factors were associated with non-adherence to any antihypertensive medication while clinical factors with non-adherence to the full AHT regimen. These differing findings support considering the use of multiple antihypertensive medications when measuring refill adherence. Monitoring patients'' refill adherence prior to healthcare visit may facilitate interpreting elevated BP.     

Interactions between <Emphasis Type="Italic">CYP1A1</Emphasis> polymorphisms and cigarette smoking are associated with the risk of hepatocellular carcinoma: evidence from epidemiological studies

The Cytochrome P-450 1A1 (CYP1A1) gene has been implicated in the etiology of hepatocellular carcinoma (HCC). However, the results have been inconsistent. In this study, a meta-analysis was performed to clarify the associations of polymorphisms in CYP1A1 gene with HCC risk. Published literature from PubMed, Embase, CNKI and Wanfang Data were retrieved. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated using fixed- or random-effects model. Eight studies (1,752 cases and 2,279 controls) for Ile-Val polymorphism and eight studies (933 cases and 1,449 controls) for MspI polymorphism were identified. The results showed that there was no statistically significant association between the Ile-Val polymorphism and HCC risk under all genetic models (co-dominant model: Val/Val vs. Ile/Ile: OR = 1.62, 95% CI 0.96-2.72 and Ile/Val vs. Ile/Ile: OR = 1.15, 95% CI 0.87-1.52; dominant model: OR = 1.25, 95% CI 0.92-1.70; recessive model: OR = 1.48, 95% CI 0.99-2.21). The MspI polymorphism was also not associated with HCC risk (co-dominant model: m2m2 vs. m1m1: OR = 1.09, 95% CI 0.83-1.42 and m1m2 vs. m1m1: OR = 1.30, 95% CI 1.05-1.61; dominant model: OR = 1.20, 95% CI 0.99–1.45; recessive model: OR = 0.94, 95% CI 0.74-1.18). However, the significant associations were found between both the Ile–Val and MspI polymorphisms and HCC risk among the cigarette smoking subjects (Ile-Val: OR = 1.40, 95% CI 1.06-1.85; MspI: OR = 2.65, 95% CI 1.47-4.77). The present meta-analysis indicated that the MspI and Ile-Val polymorphisms of CYP1A1 may play important roles in increasing susceptibility to smoking-related HCC.     

Single Agent Antihypertensive Therapy and Orthostatic Blood Pressure Behaviour in Older Adults Using Beat-to-Beat Measurements: The Irish Longitudinal Study on Ageing

Background

Impaired blood pressure (BP) stabilisation after standing, defined using beat-to-beat measurements, has been shown to predict important health outcomes. We aimed to define the relationship between individual classes of antihypertensive agent and BP stabilisation among hypertensive older adults.

Methods

Cross-sectional analysis from The Irish Longitudinal Study on Ageing, a cohort study of Irish adults aged 50 years and over. Beat-to-beat BP was recorded in participants undergoing an active stand test. We defined grade 1 hypertension according to European Society of Cardiology criteria (systolic BP [SBP] 140-159mmHg ± diastolic BP [DBP] 90-99mmHg). Outcomes were: (i) initial orthostatic hypotension (IOH) (SBP drop ≥40mmHg ± DBP drop ≥20mmHg within 15 seconds [s] of standing accompanied by symptoms); (ii) sustained OH (SBP drop ≥20mmHg ± DBP drop ≥10mmHg from 60 to 110s inclusive); (iii) impaired BP stabilisation (SBP drop ≥20mmHg ± DBP drop ≥10mmHg at any 10s interval during the test). Outcomes were assessed using multivariable-adjusted logistic regression.

Results

A total of 536 hypertensive participants were receiving monotherapy with a renin-angiotensin-aldosterone-system inhibitor (n = 317, 59.1%), beta-blocker (n = 89, 16.6%), calcium channel blocker (n = 89, 16.6%) or diuretic (n = 41, 7.6%). A further 783 untreated participants met criteria for grade 1 hypertension. Beta-blockers were associated with increased odds of initial OH (OR 2.05, 95% CI 1.31–3.21) and sustained OH (OR 3.36, 95% CI 1.87–6.03) versus untreated grade 1 hypertension. Multivariable adjustment did not attenuate the results. Impaired BP stabilisation was evident at 20s (OR 2.59, 95% CI 1.58–4.25) and persisted at 110s (OR 2.90, 95% CI 1.64–5.11). No association was found between the other agents and any study outcome.

Conclusion

Beta-blocker monotherapy was associated with a >2-fold increased odds of initial OH and a >3-fold increased odds of sustained OH and impaired BP stabilisation, compared to untreated grade 1 hypertension. These findings support existing literature questioning the role of beta-blockers as first line agents for essential hypertension.     

Uso de sujeciones físicas en relación con el riesgo de caídas en una residencia de ancianos

Backgrounds and objectivesThe use of physical restraints (PR) is common in the care of the elderly. However, their efficacy and safety are not supported by scientific evidence. The aim of this study was to determine the role of PR in preventing falls.Materials and methodsA retrospective cohort study design was used, in which each fall incident (n = 575) was examined in the residents over 65 years of age who resided at the one nursing homes from February 2009 to September 2013. An analysis was made of the association between the use of PR and risk of falls using a multivariate logistic regression, adjusting for the characteristics of residents that were associated with the use of PR according to a bivariate analysis.ResultsRisk factors for falls after accounting for PR use, include: risk of falling (Tinetti test) (OR 4.57; 95% CI 1.76-11.75); ability to walk (OR 6.40; 95% CI 2.78-14.74); hearing impairment (OR 2.12; 95% CI 1.05-4.29); and history of a previous fall (OR 17.81; 95% CI 8.83-35.93). The risk of falls was greater in restrained, ambulatory residents with cognitive impairment (OR 18.95; 95% CI 7.06-50.85). No differences were found in injuries between falls that occurred with and without PR.ConclusionsRestraint use was not significantly associated with fewer falls and injuries. The risk of falls could increase in ambulatory residents with cognitive impairment. The study results suggest the need to consider whether restraints provide adequate protection against the risk of falls.     

Inappropriate Drugs in Elderly Patients with Severe Cognitive Impairment: Results from the Shelter Study

Background

It has been estimated that Nursing Home (NH) residents with impaired cognitive status receive an average of seven to eight drugs daily. The aim of this study was to determine prevalence and factors associated with use of inappropriate drugs in elderly patients with severe cognitive impairment living in NH in Europe.

Methods

Cross-sectional data from a sample of 1449 NH residents with severe cognitive impairment, participating in the Services and Health for Elderly in Long TERm care (SHELTER) study were analysed. Inappropriate drug use was defined as the use of drugs classified as rarely or never appropriate in patients with severe cognitive impairment based on the Holmes criteria published in 2008.

Results

Mean age of participating residents was 84.2±8.9 years, 1087 (75.0%) were women. Inappropriate drug use was observed in 643 (44.9%) residents. Most commonly used inappropriate drugs were lipid-lowering agents (9.9%), antiplatelet agents (excluding Acetylsalicylic Acid – ASA –) (9.9%), acetylcholinesterase, inhibitors (7.2%) and antispasmodics (6.9%). Inappropriate drug use was directly associated with specific diseases including diabetes (OR 1.64; 95% CI 1.21–2.24), heart failure (OR 1.48; 95% CI 1.04–2.09), stroke (OR 1.43; 95% CI 1.06–1.93), and recent hospitalization (OR 1.69; 95% CI 1.20–2.39). An inverse relation was shown between inappropriate drug use and presence of a geriatrician in the facility (OR 0.55; 95% CI 0.39–0.77).

Conclusion

Use of inappropriate drugs is common among older EU NH residents. Determinants of inappropriate drug use include comorbidities and recent hospitalization. Presence of a geriatrician in the facility staff is associated with a reduced rate of use of these medications.     

Marital Status,Lifestyle and Dementia: A Nationwide Survey in Taiwan

Background

Evidence of an association between lifestyle and marital status and risk of dementia is limited in Asia.

Methods

In this nationwide population-based cross-sectional survey, participants were selected by computerized random sampling from all 19 counties in Taiwan. A total of 10432 residents were assessed by a door-to-door in-person survey, among whom 7035 were normal and 929 were diagnosed with dementia using the criteria recommended by National Institute on Aging-Alzheimer’s Association. Premorbid lifestyle habits and demographic data including marital status were compared between normal subjects and participants with dementia.

Results

After adjustment for age, gender, education, body mass index, smoking, drinking, marital status, sleep habits, exercise, social engagement and co-morbidities including hypertension, diabetes and cerebrovascular diseases, an increased risk for dementia was found in people with widow or widower status (OR 1.42, 95% CI 1.15–1.77) and people who used to take a nap in the afternoon (OR 1.33, 95% CI 1.02–1.72). Decreased risk was found in people with the habit of regular exercise (OR 0.12, 95% CI 0.09–0.16), adequate night sleep (OR 0.55, 95% CI 0.39–0.76) and regular social engagement (OR 0.53, 95% CI 0.36–0.77).

Conclusions

Our results provide preliminary evidence of possible risk-reduction effects for dementia, including regular exercise even in modest amounts, social engagement and adequate night sleep, whereas people with the widow/widower status or who used to take an afternoon nap might have increased risk of dementia.     

Perioperative Use of Clevidipine: A Systematic Review and Meta-Analysis

Background

Clevidipine is an ultrashort-acting drug for rapid reduction of blood pressure by selectively acting on the L-type Ca2+ channels on arteriolar smooth muscle. The drug’s ultrashort action in reducing the blood pressure is due to its rapid hydrolysis by blood and extravascular tissue esterases, which does not depend on hepato-renal metabolism and excretion. An analysis of the perioperative management of blood pressure should be considered to compare with other intravenous antihypertensive agents.

Methods

Analyses of the available evidence in randomized clinical trials following the PRISMA methodology as well as clinical significance according to the GRADE system were conducted. Placebo versus other antihypertensive drugs studies were included. Statistical assessments were done using the X2 and I2 tests.

Results

Clevidipine was more effective in maintaining the blood pressure within pre-specified ranges compared with other antihypertensive drugs (MD, -17.87 CI 95%: -29.02 to -6.72; p = 0.02). The use of Clevidipine versus placebo and rescue antihypertensive intravenous drug showed a clear reduction in rates of treatment failure (RR 0.10; IC 95%; 0.05–0.18; p <0.0001). There was no difference in the incidence of adverse events compared with placebo (RR 1.47; 95% CI 0.89 to 2.43, p = 0.14) and with other antihypertensive drugs (RR 0.78, 95% CI 0.45 to 1.35; p = 0.37). In addition, there was no difference in the incidence of atrial fibrillation (AF) between clevidipine and control groups (RR 1.09, IC del 95%: 0.65 a 1.83; p = 0.73).

Conclusions

Clevidipine is an ultrafast-acting drug that is highly effective for management of perioperative arterial hypertension. It is devoid of adverse effects associated with the use of other IV antihypertensives. Its favorable pharmacodynamic and pharmacokinetic properties make clevidipine the drug of choice for the management of acute perioperative hypertension. It is important to emphasize the need for further studies with a larger number of patients to confirm these findings and increase the degree of evidence.     

Increased risk of cognitive and functional decline in patients with atrial fibrillation: results of the ONTARGET and TRANSCEND studies

Background:

The role of atrial fibrillation in cognitive impairment and dementia, independent of stroke, is uncertain. We sought to determine the association of atrial fibrillation with cognitive and physical impairment in a large group of patients at high cardiovascular risk.

Methods:

We conducted a post-hoc analysis of two randomized controlled trials involving 31 546 patients, the aims of which were to evaluate the efficacy of treatment with ramipril plus telmisartan (ONTARGET) or telmisartan alone (TRANSCEND) in reducing cardiovascular disease. We evaluated the cognitive function of participants at baseline and after two and five years using the Mini–Mental State Examination (MMSE). In addition, we recorded incident dementia, loss of independence in activities of daily living and admission to long-term care facilities. We used a Cox regression model adjusting for main confounders to determine the association between atrial fibrillation and our primary outcomes: a decrease of three or more points in MMSE score, incident dementia, loss of independence in performing activities of daily living and admission to long-term care.

Results:

We enrolled 31 506 participants for whom complete information on atrial fibrillation was available, 70.4% of whom were men. The mean age of participants was 66.5 years, and the mean baseline MMSE score was 27.7 (standard deviation 2.9) points. At baseline, 1016 participants (3.3%) had atrial fibrillation, with the condition developing in an additional 2052 participants (6.5%) during a median follow-up of 56 months. Atrial fibrillation was associated with an increased risk of cognitive decline (hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.03–1.26), new dementia (HR 1.30, 95% CI 1.14–1.49), loss of independence in performing activities of daily living (HR 1.35, 95% CI 1.19–1.54) and admission to long-term care facilities (HR 1.53, 95% CI 1.31–1.79). Results were consistent among participants with and without stroke or receiving antihypertensive drugs.

Interpretation:

Cognitive and functional decline are important consequences of atrial fibrillation, even in the absence of overt stroke.A trial fibrillation is an important and modifiable cause of ischemic stroke, which may result in considerable physical and cognitive disability.¹ In addition, atrial fibrillation is associated with an increased risk of covert cerebral infarction, which is reported in about one-quarter of patients with atrial fibrillation who undergo magnetic resonance imaging of the brain.² Thus, atrial fibrillation may be an important determinant of cognitive and functional decline, even in the absence of clinical ischemic stroke. However, previous epidemiologic studies evaluating atrial fibrillation’s association with cognitive function have been inconsistent,^3–13 and very few have evaluated its association with functional outcomes.¹⁴A recent systematic review showed convincing evidence of an association between atrial fibrillation and dementia in patients with a history of stroke, but it concluded that there was considerable uncertainty of a link between atrial fibrillation and dementia in patients with no history of stroke.¹⁵ Large prospective cohort studies are required to determine a true association between atrial fibrillation and cognitive outcomes.In this study, we sought to determine the prospective association between atrial fibrillation and cognitive decline, loss of independence in activities of daily living and admission to long-term care facilities, using data from a large group of patients included in the ONTARGET and TRANSCEND trials.^16,17     

Common polymorphisms (rs2241766 and rs1501299) in the ADIPOQ gene are not associated with hypertension susceptibility among the Chinese

The ADIPOQ gene has been implicated in the etiology of hypertension. However, the results have been inconsistent. In this study, a meta-analysis was performed to assess the associations of ADIPOQ polymorphisms with hypertension risk among the Chinese. Published literature from PubMed, CNKI and Wanfang Data were retrieved. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed- or random-effects model. Six studies (1,812 cases and 2,631 controls) for rs2241766 polymorphism and four studies (1,449 cases and 2,175 controls) for rs1501299 polymorphism were identified. A marginally significant association was observed for rs2241766 polymorphism under recessive genetic model (GG vs. GT+TT: OR = 1.22, 95 % CI 1.01-1.48) and for rs1501299 polymorphism under heterogeneous co-dominant model (TG vs. GG: OR = 0.86, 95 % CI 0.75-0.99) and dominant model (TT+TG vs. GG: OR = 0.85, 95 % CI 0.74-0.98). In addition, under other genetic models, there was no significant association for rs2241766 polymorphism (GG vs. TT: OR = 1.20, 95 % CI 0.98-1.48; GT vs. TT: OR = 0.97, 95 % CI 0.85-1.10; GG+GT vs. TT: OR = 1.01, 95 % CI 0.90-1.15) and for rs1501299 polymorphism (TT vs. GG: OR = 0.82, 95 % CI 0.62-1.08; TT vs. TG+GG: OR = 0.87, 95 % CI 0.66-1.14). However, the associations above were not robust by sensitivity analysis. The present meta-analysis indicated the limited evidence of the significant associations between ADIPOQ gene polymorphisms and hypertension susceptibility among the Chinese.