Association Between Orthostatic Hypotension and Handgrip Strength With Successful Rehabilitation in Elderly Hip Fracture Patients.

OBJECTIVE: To investigate the relationship between orthostatic hypotension (OH) and muscle strength versus time to successful rehabilitation within elderly patients with hip fracture. DESIGN: A prospective, observational cohort study. Handgrip strength was measured at the day of admission and OH as soon as possible after surgery. Cox proportional hazard modeling was used to investigate the relationship between OH or handgrip strength (kg) and time to successful rehabilitation, expressed as hazard ratios (HRs). OH was defined as a decrease in systolic blood pressure of ≥20mmHg or diastolic blood pressure of ≥10mmHg after postural change (dichotomous). Handgrip strength was measured with a hand dynamometer (continuous). SETTING: General hospital. PARTICIPANTS: Patients (N=116) aged ≥70 years with a hip fracture were recruited on the day of hospital admission. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Primary outcome was time to successful rehabilitation, which was defined as discharge to patients' own homes. RESULTS: During a median follow-up period of 36 days (interquartile range, 9-57d), 103 patients (89%) were successfully rehabilitated. No statistically significant relationships were found between OH and time to successful rehabilitation (HR=1.05; 95% confidence interval [CI], .67-1.66). Also, handgrip strength and successful rehabilitation were not statistically significantly related (HR=1.03; 95% CI, .99-1.06). CONCLUSIONS: OH measured during the first days of hospitalization is not related to time to successful rehabilitation in patients with hip fracture who have undergone surgery. Although no significant relationship was seen in the present study, the width of the CIs does not exclude a relevant relationship between handgrip strength and time to successful rehabilitation.

Orthostatic hypotension does not predict recurrent falling in a nursing home population.

OBJECTIVE: Most studies regard orthostatic hypotension (OH) as a causal factor for falls. However, the evidence is lacking for this assumption. We aimed to investigate the relationship between orthostatic hypotension and fall incidents in nursing home residents. METHODS: A total of 249 patients was included in a prospective observational cohort study of nursing home residents. Falls were prospectively registered. Cox proportional hazard modelling and the conditional frailty model were used to analyse the relationship between OH and (recurrent) falling. RESULTS: Among the 249 patients, 450 falls were recorded during follow-up and OH was present in 93 out of 249 patients. No significant associations were found between OH and the first fall incident (Hazard Ratio (HR) 1.01 (95% Confidence Interval (CI) 0.60-1.69) and recurrent falling (HR 1.21 (95%CI 0.65-2.24)). CONCLUSIONS: Although falling and OH were both highly prevalent in nursing home residents, no relationship between OH and falling was found.

Health-related quality of life, rehabilitation and mortality in a nursing home population.

BACKGROUND: Health-related quality of life (HRQOL) in nursing home residents is generally low. The purpose of this study was to investigate the associations between HRQOL and two clinically relevant outcome measures, all-cause mortality and successful rehabilitation, in a nursing home population. METHODS: In an observational prospective cohort study in a nursing home population, HRQOL was assessed with the RAND-36. A total of 184 patients were included, 159 (86%) completed the RAND-36 and were included in the study. A Cox proportional hazard model was used to investigate the independent association between HRQOL, rehabilitation and mortality with adjustment for confounders. Risk prediction capabilities were assessed with Harrell's C statistics and the proportion of explained variance (R2). RESULTS: The median age (interquartile range) was 79 (75-85) years. The health dimensions vitality (HR 0.88 (95% CI 0.77-0.99)) and mental health (HR 0.86 (95% CI 0.75-0.98)) were inversely associated and role functioningphysical (HR 1.08 (95%CI 1.02-1.15)) was positively associated with mortality. The Harrell's C value and the R2 were ≤ 0.02 and ≤ 0.03 higher in the adjusted models with the dimensions role functioning- physical, mental health or vitality compared with the models without these dimensions. None of the health dimensions or summary scales were related to successful rehabilitation. CONCLUSION: HRQOL was significantly associated with mortality for three dimensions, but partly in opposite directions. Additional value of HRQOL in mortality prediction is very limited. There were no independent associations between HRQOL and successful rehabilitation. Although HRQOL is an important outcome, this study did not provide evidence for an association between HRQOL and successful rehabilitation.

The association between orthostatic hypotension, falling and successful rehabilitation in a nursing home population.

PURPOSE OF THE STUDY: Our objectives were to identify the prevalence of orthostatic hypotension (OH) in frail, elderly nursing home residents, and assess its possible association with falling and chances of successful rehabilitation. MATERIALS AND METHODS: A prospective observational cohort study. A total of 290 patients participated in this study, of which 128 were admitted to the rehabilitation department. OH was defined as a drop in systolic blood pressure of >20mmHg and diastolic blood pressure of >10mmHg after postural change within 3min. The analyses regarding falling and successful rehabilitation were only performed in the rehabilitation group. Multivariate binary logistic regression analyses were used to describe risk factors related with falling. Cox proportional hazard modeling was used to investigate the relation between OH and the time to successful rehabilitation. RESULTS: The prevalence of OH in the studied nursing home population was 36.6% (95% CI (confidence interval): 31.1-42.1%). The prevalence varied from 28.6% (95% CI: 16.8-40.4%) in somatic patients, 36.7% (95% CI: 28.4-45.1%) in rehabilitation patients, to 40.6% (95% CI: 31.3-50.0%) in psychogeriatric patients. The association between orthostatic hypotension and previous falling was not significant; Odds ratio 0.66 (95% CI: 0.30-1.48). The Hazard ratio of the relationship between OH and successful rehabilitation was 2.88 (95% CI:1.77-4.69). CONCLUSIONS: OH is highly prevalent in nursing home residents. Surprisingly, patients with OH were found to have a higher chance of successful rehabilitation compared to patients without OH. If confirmed in other studies, these results may change our view of the implications of OH.

Sex specific association between carnosinase gene CNDP1 and cardiovascular mortality in patients with type 2 diabetes (ZODIAC-22).

INTRODUCTION: Homozygosity for a 5-leucine repeat (5L-5L) in the carnosinase gene (CNDP1) has been associated with a reduced prevalence of diabetic nephropathy in cross-sectional studies in patients with type 2 diabetes, particularly in women. Prospective studies on mortality are not available. This study investigated whether 5L-5L was associated with mortality and progression of renal function loss and to what extent this effect is modified by sex. METHODS: In a prospective cohort of patients with type 2 diabetes, a Cox proportional hazard model was used to compare 5L-5L with other genotypes regarding (cardiovascular) mortality. Renal function slopes were obtained by within-individual linear regression of the estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation, and were compared between 5L-5L and other genotypes. RESULTS: 871 patients were included (38% with 5L-5L). After 9.5 years of follow-up, hazards ratios (HR) for all-cause and cardiovascular mortality in 5L-5L versus other genotypes were 1.09 [95% confidence interval (CI) 0.88-1.36] and 1.12 (95% CI 0.79-1.58), respectively. There was a significant interaction between CNDP1 and sex for the association with cardiovascular mortality (p = 0.01), not for all-cause mortality (p = 0.32). Adjusted HR in 5L-5L for cardiovascular mortality was 0.69 (95% CI 0.39-1.23) in men and 1.77 (95% CI 1.12-2.81) in women. The slopes of eGFR-MDRD did not significantly differ between 5L-5L and other genotypes. CONCLUSIONS: The association between CNDP1 and cardiovascular mortality was sex-specific, with a higher risk in women with 5L-5L genotype. CNDP1 was not associated with all-cause mortality or change in eGFR.

[SGLT-2 inhibitors: diabetes treatment by glycosuria; literature review on the effect of dapagliflozin]. / SGLT-2-remmers: glucosurie als diabetesbehandeling; literatuurstudie naar het effect van dapagliflozine.

OBJECTIVE: To describe the efficacy and safety of dapagliflozin, the first sodium-glucose co-transporter-2 (SGLT-2) inhibitor for the treatment of diabetes mellitus type 2 (DM2) to be registered in the Netherlands. DESIGN: Literature review. METHOD: We searched the Medline database for articles on the use of dapagliflozin in patients with DM2. We included randomised studies with a minimum duration of 12 weeks and systematic reviews published up to 19 October 2012. Two assessors selected the articles on the basis of title, abstract and if necessary, the complete text. RESULTS: Eleven articles were suitable for analysis. On comparison with placebo, the use of dapagliflozin gave a drop in HbA1c-value of approximately 0.5-0.8 percentage points (6-9 mmol/mol). The body weight of patients who used dapagliflozin dropped between 1.0-2.4 kg on comparison with the placebo and metformin control groups. Urinary tract infections occurred twice as often and genital infections three to four times more often. There were no data on the effect on micro- and macrovascular complications or on mortality. CONCLUSION: Dapagliflozin regulates the blood glucose levels less effectively than currently used medications, although the small number of studies that compare dapagliflozin with metformin or glipizide show no differences in the drop in HbA1c between the study groups. Dapagliflozin use leads to minor, clinically non-relevant weight loss. There are as yet no data on its long term efficacy and safety.

Educational disparities in mortality among patients with type 2 diabetes in The Netherlands (ZODIAC-23).

BACKGROUND: Relative mortality differences between educational level in mortality have been reported among diabetic as well as among non-diabetic subjects in Europe, but data on absolute differences are lacking. We studied the effect of educational disparities on mortality in a Dutch prospective cohort of type 2 diabetes mellitus (T2DM) patients. METHODS: This study was part of the ZODIAC study, a prospective observational study of patients with T2DM. Data on educational level were first collected on 19 May 1998, and from this date on, 858 patients were included in 1998; educational level was known for 656 patients. Vital status was assessed in 2009. The relationship between mortality and educational level was studied using a Cox proportional hazard model, the relative index of inequality (RII), slope index of inequality (SII) and the population attributable risk (PAR). Educational level was divided into four categories; the highest educational level was used as reference. RESULTS: After a median follow-up time of 9.7 years, 365 out of 858 patients had died. The hazard ratio of primary education for total mortality was 3.02 (95% CI 1.44-6.34). The RII was 2.85 (95% CI 1.21-6.67), the absolute difference in the risk for mortality (SII) was 384 deaths (95% CI 49-719) per 10,000 follow-up years. PAR for patients with the lowest level of education was 51.4%. CONCLUSIONS: A low educational level had a higher impact on mortality than having a macrovascular complication. Given the substantial differences in mortality between educational levels in T2DM, more understanding of underlying (modifiable) mechanisms is necessary.

Time for considering other blood pressure target values in elderly patients with type 2 diabetes?

Although blood pressure control has undoubtedly proven its benefits in reducing the high cardiovascular risk in patients with type 2 diabetes mellitus (T2DM), it still remains unclear whether intensive antihypertensive treatment in old age (> 75 years) is beneficial. Many of the current guidelines recommend a systolic blood pressure (SBP) < 140 mmHg or lower, unless patients are at high risk for possible adverse events such as postural hypotension (1,2). This perspective aims to get a discussion started on the appropriate target SBP value for patients with T2DM aged older than 75 years.We would like to propose the less stringent value of< 160 mmHg in this specific population.

[Metformin in adolescents and adults with type 1 diabetes mellitus: not evidence-based]. / Metformine bij adolescenten en volwassenen met diabetes mellitus type 1: niet evidence-based.

OBJECTIVE: Adolescents with type 1 diabetes mellitus (DM1) often have problems in achieving optimal glycaemic control. We investigated whether there is evidence of the beneficial effect of the addition of metformin to insulin therapy in adolescents with DM1. DESIGN: Systematic literature study. METHOD: Medline and Embase were searched for randomised double-blind trials in adolescents with DM1 up to May 2011 inclusive. Two reviewers selected relevant articles based on title, summary and, if necessary, the full text. The quality of the methodology was also assessed. RESULTS: We found 2 studies in adolescents, of limited scope and duration. On this basis, it was decided that the search of the literature should be extended to adults with DM1, whereby 4 studies were found. All six trials were of good methodological quality, and included 196 patients in total. Clinical and statistical heterogeneity precluded pooling the results in a meta analysis. In one study in adolescents metformin treatment showed a reduction of HbA1c by 0.6% (95% CI: -1.16-0.04) and a slight decrease in daily total insulin dose. However, the treatment groups were not comparable at baseline. In the other studies, no significant changes in HbA1c were found. All studies showed decreased daily insulin dose; in four studies this was significant. Two studies showed a beneficial effect on weight or BMI. No serious side effects were recorded. One study showed an increase in hypoglycaemic episodes during metformin treatment. CONCLUSION: The possible benefit of adding metformin to insulin in adolescents and adults with type 1 diabetes remains unclear. A well-designed double-blind randomised trial carried out over a longer time period is required to assess whether metformin is of added value.

Glycaemic control and the risk of mortality in elderly type 2 diabetic patients (ZODIAC-20).

AIMS: Studies on macrovascular consequences of glucose control in elderly patients (>75 years) with type 2 diabetes mellitus (T2DM) are lacking. The present study aimed to investigate the relationship between HbA(1c) and mortality in this specific population. METHODS: Between 1998 and 1999, 374 primary care patients with T2DM aged older than 75 years participated in the Zwolle Outpatient Diabetes project Integrating Available Care study, a prospective observational study. Early 2009, data on mortality were collected. Updated means for annually measured HbA(1c) values were calculated after a follow-up time of 10 years. Updated mean HbA(1c) was used as a time-dependent covariate in a Cox proportional hazard model. Main outcome measures were all-cause and cardiovascular disease (CVD) mortality. Analyses were performed in strata according to diabetes duration (<5, 5-11 and ≥11 years). RESULTS: In the group with a diabetes duration <5 years, an increase of 1% in the updated mean HbA(1c) level was associated with an increase in all-cause and CVD mortality risk of 51% (95% CI 17-95%) and 72% (95% CI 19-148%), respectively. Glycaemic control was not related to mortality for patients with a diabetes duration ≥5 years. CONCLUSION: Poor glycaemic control is related to increased all-cause and CVD mortality in patients >75 years with T2DM of short duration (<5 years). DISCUSSION: Because of the observational study design, our results should be interpreted with caution. Nevertheless, they are suggestive that improving glycaemic control may be beneficial in elderly patients with T2DM, especially in those with recently diagnosed T2DM. Randomised-controlled trials are necessary to investigate whether this holds true.

[New blood glucose-lowering drugs in type 2 diabetes: a review of the literature]. / Nieuwe bloedglucoseverlagende middelen bij type 2 diabetes: een literatuuroverzicht.

OBJECTIVE: To describe the efficacy and safety of the glucagon-like peptide 1 (GLP-1) analogues exenatide and liraglutide, and the dipeptidyl peptidase-4 (DPP-4) inhibitors vildagliptin and sitagliptin, registered in the Netherlands for treatment of type 2 diabetes mellitus (DM2). DESIGN: Literature study. METHOD: The Medline database was searched up to and including August 2009 for systematic reviews and randomised trials with a minimum duration of 12 weeks in patients with DM2. Two authors independently selected the studies based on the title, abstract and, if necessary, the full text. RESULTS: In addition to 1 systematic review on GLP-1 analogues and 1 review on DPP-4 inhibitors, 10 studies on DPP-4 inhibitors and 16 studies on GLP-1 analogues were included. According to these studies, the DPP-4 inhibitors sitagliptin and vildagliptin gave a mean HbA1c reduction of 0.7% and 0.6% respectively. GLP-1 analogues led to a mean HbA1c reduction of 1%, which is comparable to insulin therapy. Sitagliptin was associated with a slight increase in the number of upper respiratory tract infections. In a large number of patients, GLP-1 analogues were associated with gastrointestinal complaints. DPP-4 inhibitors were associated with a small weight gain, compared with weight loss in patients treated with GLP-1 analogues. Data on microvascular and macrovascular complications, as well as data on mortality, are not yet available in either group. CONCLUSION: GLP-1 analogues regulate blood glucose levels as effectively as the current glucose-lowering agents; DPP-4 inhibitors are less effective. GLP-1 analogues lead to a clear weight reduction while DPP-4 inhibitors cause slight weight gain. Data on efficacy and safety in the longer term are not yet available.

The relationship between obesity and cancer mortality in type 2 diabetes: a ten-year follow-up study (ZODIAC-21).

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) as well as patients with obesity have increased cancer mortality. In a previous paper we suggested that there was a trend for decreased mortality in obese individuals with T2DM. The aim of the new analyses was to investigate the same relationship after increasing our sample size and extending our follow-up period. PATIENTS AND METHODS: 1353 patients were followed prospectively as part of the ZODIAC study. The cancer mortality rate was evaluated using standardized mortality ratio (SMR) and its association with BMI (kg/m(2)) and obesity (>30 kg/m(2)) with Cox proportional hazard analysis. RESULTS: After a median follow-up time of 9.8 years, 570 patients had died, of whom 122 died from malignancy. The SMR for cancer mortality was 1.47 (95%CI 1.22-1.76). BMI and obesity were not associated with cancer death. CONCLUSION: The trend towards an inverse relationship between obesity and cancer mortality as reported previously disappeared after increasing sample size and follow-up to 9.6 years.

Diabetes specialist nurse as main care provider for patients with type 2 diabetes.

BACKGROUND: The objective of this study was to determine whether the management of type 2 diabetes (DM2) can be transferred from an internist to a nurse specialised in diabetes (NSD). METHODS: Ninety-three patients with DM2 referred by their general practitioner were randomised; 84 patients completed the study. The intervention group received care from an NSD who treated glycaemia, blood pressure and lipid profile by protocol. The control group received care from an internist. The primary endpoint was the main decrease in HbA1c. Secondary endpoints included blood pressure, lipid profile, healthcare costs, QOL , and patient satisfaction. RESULTS: HbA1c, total cholesterol, LDL cholesterol and cholesterol/HDL ratio decreased significantly in both study populations after a follow-up time of 12 months. Cholesterol/HDL ratio decreased by 0.4 and 0.9 in the NSD and control group respectively (p=0.034 for the difference between groups). The decreases (95% confidence interval) in systolic blood pressure were 8.6 mmHg (2.6, 14.7) in the NSD group and 4.0 mmHg (-0.9, 8.9) in the control group, without a significant difference between groups. After one year, 33.3% of the patients in the NSD group achieved an HbA1c level. <7% compared with 2.2%at baseline (p=0.002). Healthcare costs were less and patient satisfaction with the NSD s was significantly better(p<0.001), while maintaining the same QOL . CONCLUSION: NSD s using treatment protocols are able to provide effective care for patients with DM 2, comparable with the care provided by an internist, with respect to clinical parameters, and superior with respect to healthcare costs and patient satisfaction.