Studies on persistence of benzodiazepine agonist (BZDA) withdrawal in older outpatients are few, and few studies on long-term persistence over years have yet been published. To describe the persistence of temazepam, zolpidem, and zopiclone (BZDA) withdrawal among older outpatients at 3 years from the beginning of withdrawal, as well as any changes in use of other medications.

Background: Peripheral, arterial disease (PAD) is an underdiagnosed and undertreated disease because it remains asymptomatic for so long. The ankle brachial index (ABI) is a valid method for detecting PAD: in lower extremities. ABI <= 0.90 indicates incident PAD. Recent studies have found that subjects with borderline ABI values (0.91-1.00) have increased mortality rates. The objective of our 7-year follow-up study was to investigate the progression of PAD in borderline ABI subjects, who underwent, a multifactorial cardiovascular intervention.Methods: A total of 193 subjects with borderline ABI were examined in 2005-2006. None of them had previously diagnosed diabetes, cardiovascular or renal disease or intermittent claudication. They were given conventional treatment for multiple risk factors of cardiovascular diseases (hypertension, hypercholesterolemia, elevated blood glucose, smoking, and overweight). Sixty-four percent of these subjects (n = 1.23) attended a follow-up visit in 2012.Results: Of the 123 subjects with borderline ABI (mean age 59.0 years, 62% female) at baseline, 18 (15%, 95% confidence intervals {Cl] 9%-22%) developed incident PAD during the follow-up. The mean ABI was 0.97 +/- 0.03 at baseline and 1.01 +/- 0.12 at 7-year follow-up visit. The change in mean ABI was 70:04 (95% CI: 0.03-0.07), P < 0.001. ABI improved significantly in 25 (20%) subjects. In multivariate ordered logistic regression analyses high and even moderate leisure-time physical activity :(LTPA; odds ratio 6.15; 95% CI: 1.99-19.1) predicted a rise in ABI in comparison to low LTPA.Conclusions: Physical activity seems to improve significantly ABI values among men and women with borderline ABI (0.91-1.00).

Objective: The aim was to describe vitamin D status and its association with changes in PF during 12 months in Finnish community-dwelling elderly (>65 years).Methods and results: Baseline serum 25-hydroxyvitamin D (25OHD) concentration was measured by enzymeimmunoassay, and participants (n = 518) were divided according to 25OHD to three groups (I <50 nmol/l, II 50-74.9 nmol/l, and III >= 75 nmol/l). PF (maximal isometric extension strength of right and left knee, and time in five-repetition sit-to-stand test (5STS) and 10-m walking test) was measured at baseline and after 12 months. 25OHD deficiency (<50 nmol/l) was found in 20.5% of the participants. During a 12-month follow-up, differences in changes in knee extensor strength of right (p = 0.044) and left (p = 0.010) lower extremity and in 10-m walking test (p = .040) between the groups were significant. According to further pairwise comparisons these differences were between groups I and III (right knee, p = 0.036; left knee, p = 0.009; 10-m walk, p = 0.044), with the exception of left knee extensor strength in which there were also significant difference between groups I and II (p = 0.039). All significant differences in changes were in favour of group II or III. Significant differences in changes in knee extensor strengths maintained after adjustments for group (intervention/control), parathyroid hormone, and baseline level of knee extensor strength.Conclusions: Prospective analyses showed low 25OHD concentrations (<50 nmol/l) to be associated with deterioration in PF during 12 months compared with high 25OHD concentrations (>75 nmol/l). (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Negative-pressure wound therapy (NPWT) is widely used to improve skin wound healing. Although NPWT has been studied as a treatment for wound closure and healing, the molecular mechanisms explaining its therapeutic effects remain unclear. To investigate the effect of NPWT on gene expression, and to discover the genes most dominantly responding to this treatment during skin wound healing, we applied negative pressure on split-thickness skin graft donor sites from the first postoperative day (POD) to the seventh POD. Biopsies were collected from 4 NPWT-treated and 2 control patients. Two biopsy samples were taken from each patient: one from intact skin before graft harvesting, and one on the seventh POD from the donor site wound. Genome-wide microarrays were performed on all samples. Gene expression changes on the seventh POD were compared between NPWT and control patients, and were analyzed for statistical significance. In addition, we analyzed wound exudates for volume, and for concentrations of leukocytes, erythrocytes, and haemoglobin. NPWT induced major changes in gene expression during healing. These changes ranged from 10-fold induction to 27-fold suppression. The genes most induced were associated with cell proliferation and inflammation, and the most down-regulated genes were linked to epidermal differentiation. Our results provide the first insight into the molecular mechanisms behind NPWT, and suggest that NPWT enhances specific inflammatory gene expression at the acute phase associated with epithelial migration and wound healing. However, its continued use may inhibit epithelial differentiation.

Ankle–brachial index (ABI) measurement offers an easily available method to diagnose peripheral artery disease (PAD) and systemic atherosclerosis in early stage and thus to identify high-risk individuals for preventive interventions. The objective of this study was to assess the most practical criteria for the measurement of ABI in subjects with high cardiovascular risk. We examined 972 asymptomatic, middle-aged high-risk subjects without manifested cardiovascular disease or previously diagnosed diabetes. The prevalence of PAD (defined as ABI⩽0.90) and borderline PAD (0.91–1.00) were 5% (95% confidence interval (CI) 4–7%) (49/972) and 20% (95% CI 18–23%) (192/972), respectively. In multivariate analysis, female gender (odds ratio (OR) 0.71 (95% CI 0.53–0.97)), current smoking (OR 2.14 (95% CI 1.47–3.11)) and pulse pressure (OR 1.03 for each increase of 1 mm Hg (95% CI 1.01–1.04)) were associated with low ABI. Measuring ABI in subjects who smoke or have pulse pressure >65 mm Hg seems to be worthwhile.

Healing of the epidermis is a crucial process for maintaining the skin's defense integrity and its resistance to environmental threats. Compromised wound healing renders the individual readily vulnerable to infections and loss of body homeostasis. To clarify the human response of reepithelialization, we biopsied split-thickness skin graft donor site wounds immediately before and after harvesting, as well as during the healing process 3 and 7 days thereafter. In all, 25 biopsies from eight patients qualified for the study. All samples were analyzed by genome-wide microarrays. Here, we identified the genes associated with normal skin reepithelialization over time and organized them by similarities according to their induction or suppression patterns during wound healing. Our results provide the first elaborate insight into the transcriptome during normal human epidermal wound healing. The data not only reveal novel genes associated with epidermal wound healing but also provide a fundamental basis for the translational interpretation of data acquired from experimental models.

OBJECTIVE:This study aimed at investigating whether cardiovascular risk factors and their impact on total risk estimation differ between men and women. DESIGN:Cross-sectional cohort study. SUBJECTS:Finnish cardiovascular risk subjects (n = 904) without established cardiovascular disease, renal disease, or known diabetes. MAIN OUTCOME MEASURES:Ankle-brachial index (ABI), estimated glomerular filtration rate (eGFR), oral glucose tolerance test, and total cardiovascular risk using SCORE risk charts. RESULTS:According to the SCORE risk charts, 27.0% (95% CI 23.1-31.2) of the women and 63.1% (95% CI 58.3-67.7) of the men (p < 0.001) were classified as high-risk subjects. Of the women classified as low-risk subjects according to SCORE, 25% had either subclinical peripheral arterial disease or renal insufficiency. CONCLUSIONS:The SCORE system does not take into account cardiovascular risk factors typical in women, and thus underestimates their total cardiovascular risk. Measurement of ABI and eGFR in primary care might improve cardiovascular risk assessment. especially in women.

This non-randomized, controlled trial assessed the effects of ceasing fall-risk-increasing drugs (FRIDs) (psychotropics or opiates or potent anticholinergics) on the risk of falls requiring medical treatment as a sub-analysis of a randomized, controlled multifactorial fall prevention. The population in this 12-month study consisted of 528 community-dwelling subjects aged 65years or older with a history of at least one fall. The subjects were divided retrospectively into three groups according to the use of any FRID, any psychotropic drug, and benzodiazepine or related drug (BZD/BZDRD). The subjects in the intervention group (IG) ceasing the drug use were compared with the subjects in IG and the control group (CG) not ceasing the use of the corresponding type of drugs during the intervention period. Falls were recorded from medical records. For the year after the 12-month intervention the relative risk ratio (with 95% confidence intervals=CI) for controls in CG compared with the withdrawal group in IG was 8.26 (1.07–63.73) among the users of psychotropics and 8.11 (1.03–63.60) among the users of BZDs/BZDRDs. Withdrawal of psychotropics, especially BZDs/BZDRDs may have played an important role by lowering the risk of falls requiring medical treatment during the year after the 12-month multifactorial intervention.

Peripheral artery tonometry (PAT) is a novel method for assessing arterial stiffness of small digital arteries. Pulse pressure can be regarded as a surrogate of large artery stiffness. When ankle-brachial index (ABI) is calculated using the higher of the two ankle systolic pressures as denominator (ABI-higher), leg perfusion can be reliably estimated. However, using the lower of the ankle pressures to calculate ABI (ABI-lower) identifies more patients with isolated peripheral arterial disease (PAD) in ankle arteries. We aimed to compare the ability of PAT, pulse pressure, and different calculations of ABI to detect atherosclerotic disease in lower extremities. We examined PAT, pulse pressure, and ABI in 66 cardiovascular risk subjects in whom borderline PAD (ABI 0.91 to 1.00) was diagnosed 4 years earlier. Using ABI-lower to diagnose PAD yielded 2-fold higher prevalence of PAD than using ABI-higher. Endothelial dysfunction was diagnosed in 15/66 subjects (23%). In a bivariate correlation analysis, pulse pressure was negatively correlated with ABI-higher (r = -0.347, p = 0.004) and with ABI-lower (r = -0.424, p < 0.001). PAT hyperemic response was not significantly correlated with either ABI-higher (r = -0.148, p = 0.24) or with ABI-lower (r = -0.208, p = 0.095). Measurement of ABI using the lower of the two ankle pressures is an efficient method to identify patients with clinical or subclinical atherosclerosis and worth performing on subjects with pulse pressure above 65 mm Hg. The usefulness of PAT measurement in detecting PAD is vague.

High-sensitivity C-reactive protein (hsCRP) has been previously linked to different forms of vascular disease. However, some studies have not found any relationship between hsCRP and atherosclerosis. Also, studies investigating correlation between hsCRP and ankle brachial index (ABI) are scarce. We studied hsCRP in a cardiovascular risk population with a special interest in correlation between hsCRP and ABI. All men and women aged 45 to 70 years from a rural town Harjavalta, Finland were invited to participate in a population survey. Diabetics and people with known vascular disease were excluded. Seventy-three percent (n = 2085) of the invited persons participated and 70% of the respondents (n = 1496) had at least one risk factor to cardiovascular diseases. These subjects were invited to further examinations. From them we measured ABI, hsCRP, leukocyte count, glucose tolerance, systemic coronary risk evaluation (SCORE), body mass index (BMI), and waist circumference. Mean hsCRP was 1.9 mg/L. Smokers had higher hsCRP (mean 2.2 mg/L) than nonsmokers (mean 1.8 mL/L). hsCRP in women was higher than in men (mean 2.0 mg/L versus 1.8 mg/L). Mean ABI was 1.10, and the prevalence of peripheral arterial disease was 3.1%. ABI correlated weakly with hsCRP (r = -0.077, p = 0.014), leukocyte count (r = -0.107, p = 0.001), and SCORE (r = -0.116, p = 0.001). It did not have correlation between age, weight, BMI, or waist circumference. hsCRP correlated with BMI (r = 0.208, p < 0.0001) and waist circumference (r = 0.325, p < 0.0001). When we excluded subjects with hsCRP >10 mg/L, ABI no longer correlated with hsCRP. In a cardiovascular risk population, hsCRP has only a weak correlation with ABI, and this correlation disappeared when we excluded subject with hsCRP >10 mg/L. Instead, hsCRP was correlated to the measures of obesity (waist circumference and BMI), indicating its role as a marker of adipose tissue-driven inflammation. hsCRP does not seem to be a suitable screening method for peripheral arterial disease.

Introduction: The diagnosis of peripheral arterial disease (PAD) can be made by measuring the ankle-brachial index (ABI). Traditionally ABI values > 1.00-1.40 have been considered normal and ABI < 0.90 defines PAD. Recent studies, however, have shown that individuals with ABI values between 0.90-1.00 are also at risk of cardiovascular events. We studied this cardiovascular risk population subgroup in order to determine their endothelial function using peripheral arterial tonometry (PAT).Methods: We selected 66 individuals with cardiovascular risk and borderline ABI. They all had hypertension, newly diagnosed glucose disorder, metabolic syndrome, obesity, or a ten year risk of cardiovascular disease death of 5% or more according to the Systematic Coronary Risk Evaluation System (SCORE). Subjects with previously diagnosed diabetes or cardiovascular disease were excluded. Endothelial function was assessed by measuring the reactive hyperemia index (RHI) from fingertips using an Endo-PAT device.Results: The mean ABI was 0.95 and mean RHI 2.11. Endothelial dysfunction, defined as RHI < 1.67, was detected in 15/66 (23%) of the subjects. There were no statistically significant differences in RHI values between subjects with different cardiovascular risk factors. The only exception was that subjects with impaired fasting glucose (IFG) had slightly lower RHI values (mean RHI 1.91) than subjects without IFG (mean RHI 2.24) (P = 0.02).Conclusions: In a cardiovascular risk population with borderline ABI nearly every fourth subject had endothelial dysfunction, indicating an elevated risk of cardiovascular events. This might point out a subgroup of individuals in need of more aggressive treatment for their risk factors.

Background The high mortality of hip fracture patients is well documented, but sex- and cause-specific mortality after hip fracture has not been extensively studied. The purpose of the present study was to evaluate mortality and cause of death in patients after hip fracture surgery and to compare their mortality and cause of death to those in the general population. Methods Records of 428 consecutive hip fracture patients were collected on a population-basis and data on the general population comprising all Finns 65 years of age or older were collected on a cohort-basis. Cause of death was classified as follows: malignant neoplasms, dementia, circulatory disease, respiratory disease, digestive system disease, and other. Results Mean follow-up was 3.7 years (range 0-9 years). Overall 1-year postoperative mortality was 27.3% and mortality after hip fracture at the end of the follow-up was 79.0%. During the follow-up, age-adjusted mortality after hip fracture surgery was higher in men than in women with hazard ratio (HR) 1.55 and 95% confidence interval (95% CI) 1.21-2.00. Among hip surgery patients, the most common causes of death were circulatory diseases, followed by dementia and Alzheimer's disease. After hip fracture, men were more likely than women to die from respiratory disease, malignant neoplasm, and circulatory disease. During the follow-up, all-cause age- and sex-standardized mortality after hip fracture was 3-fold higher than that of the general population and included every cause-of-death category. Conclusion During the study period, the risk of mortality in hip fracture patients was 3-fold higher than that in the general population and included every major cause of death.

BACKGROUNDevidence about possibilities to help older persons to withdraw the long-term use of benzodiazepines (BZD) is scarce. Effective and practicable methods are needed.OBJECTIVEthe study aimed to assess the persistence of one-time counselling by a geriatrician to reduce psychotropic drugs, especially BZD and related drugs (RD).DESIGNa prospective randomised controlled trial with a 12-month follow-up was conducted.SUBJECTSfive hundred ninety-one community-dwelling people aged 65 or older participated in the study.METHODSinstructions to withdraw, reduce or change psychotropic drugs were given to the intervention group. A 1-h lecture about these drugs and their adverse effects was given later on. No changes in the drug therapy were suggested for the controls.RESULTSthe number of regular users of BZD and RD decreased by 35% (12/34) (odds ratios (OR) = 0.61, 95% confidence interval (95% CI) 0.44-0.86) in the intervention group while it increased by 4% (2/46) (OR = 1.05, 95% CI 0.81-1.36) in the controls (P = 0.012). No significant changes in the users of other types of psychotropics were found.CONCLUSIONone-time counselling of psychotropics and other fall-risk-increasing drugs by a geriatrician followed with a 1-h lecture about adverse effects of these drugs had positive effects in decreasing the number of regular users of BZD and RD, and these effects persisted for the total 12-month intervention period.

Thank you very much for the opportunity to revise our manuscript (manuscript titled ” Mortality and cause of death in hip fracture patients aged 65 or older a population-based study”). We have revised the manuscript according to the reviewer’s suggestions. Our point-by-point responses are below. We have removed several statements from the text and other changes are highlighted using red font in the manuscript. Please find the removed text at the end of this letter. We hope that the revisions are acceptable.

The purpose of the study was to assess the effects of 12-month risk-based multifactorial fall prevention program on postural control of the aged. Five hundred and ninety-one (97%) eligible subjects were randomized into an intervention group (IG) (n = 293) and a control group (CG) (n = 298). The effects of the program were measured on standing, dynamic, and functional balance.In standing balance, the velocity moment of semi-tandem standing decreased in IG (median change -0.54 mm(2)/s) but increased in CG (+3.84 mm(2)/s) among all women (p = 0.011) and among the women aged 65-74 years (-1.65 mm(2)/s and +2.80 mm(2)/s, correspondingly) (p=0.008). In a dynamic test, performance distance tended to decrease in IG (-26.54 mm) and increase in CG (+34.10 mm) among all women (p = 0.060). The women aged 75 years or over, showed marginally significant differences between the groups as regards changes in performance time (-2.66 s and -0.90 s) (p = 0.068) and distance (-92.32 mm and +76.46 mm) (p = 0.062) of the dynamic balance test in favor of IG. Men showed no significant differences in the changes between the groups in any balance measures. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

OBJECTIVES: To evaluate the effects of a multifactorial fall prevention program on falls and to identify the subgroups that benefit the most.DESIGN: Randomized controlled trial.SETTING: Community‐dwelling subjects who had fallen at least once during the previous 12 months.PARTICIPANTS: Five hundred ninety‐one subjects randomized into intervention (IG) (n=293) and control (CG) (n=298) groups.INTERVENTION: A multifactorial 12‐month fall prevention program.MEASUREMENTS: Incidence of falls.RESULTS: The intervention did not reduce the incidence of falls overall (incidence rate ratio (IRR) for IG vs CG=0.92, 95% confidence interval (CI)=0.72–1.19). In subgroup analyses, significant interactions between subgroups and groups (IG and CG) were found for depressive symptoms (P=.006), number of falls during the previous 12 months (P=.003), and self‐perceived risk of falling (P=.045). The incidence of falls decreased in subjects with a higher number of depressive symptoms (IRR=0.50, 95% CI=0.28–0.88), whereas it increased in those with a lower number of depressive symptoms (IRR=1.20, 95% CI=0.92–1.57). The incidence of falls decreased also in those with at least three previous falls (IRR=0.59, 95% CI=0.38–0.91) compared to those with one or two previous falls (IRR=1.28, 95% CI=0.95–1.72). The intervention was also more effective in subjects with high self‐perceived risk of falling (IRR=0.77, 95% CI=0.55–1.06) than in those with low self‐perceived risk (IRR=1.28, 95% CI=0.88–1.86).CONCLUSION: The program was not effective in reducing falls in the total sample of community‐dwelling subjects with a history of falling, but the incidence of falls decreased in participants with a higher number of depressive symptoms and in those with at least three falls.

Background and Aims: Our aim was to describe the incidence of cervical hip fractures and to describe the relationships between selected background variables and mortality at 30 days, 6 months, and 3 years postoperatively. Material and Methods: The basic material consisted of population-based data set of patients aged 65 years or older who had sustained a hip fracture and were treated operatively between 1999 and 2000. Out of these, we identified 266 consecutive patients with cervical hip fracture. Results: The age-adjusted incidence of cervical hip fractures in women was 1.3-fold compared to men. In age-adjusted analysis, occurrence of chronic lung disease, cardiovascular disease or 2–5 comorbidities, male gender, the need for 2-person mobility assistance, and poor ambulation postoperatively were associated with excess mortality at least at one evaluation point. Conclusions: Only chronic lung disease and male gender were independent predictors of increased mortality at each follow-up assessment in multivariate analysis.