Laser therapy for onychomycosis in patients with diabetes at risk for foot ulcers: a randomized, quadruple-blind, sham-controlled trial (LASER-1).

BACKGROUND: Patients with diabetes mellitus are at high risk for onychomycosis, which is related to the development of foot ulcers. OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of the treatment of onychomycosis with local laser therapy. METHODS: In a single-centre, randomized (1:1), quadruple-blind, sham-controlled trial, patients and microbiological confirmation with diabetes mellitus, at risk for developing diabetic foot ulcers (Sims classification score 1, 2) and a clinical suspicion on onychomycosis, were randomized to either four sessions neodymium-doped yttrium aluminium garnet (Nd-YAG) 1064 nm laser or sham treatment. The primary outcome was clinical and microbiological cure of onychomycosis after 1-year follow-up. RESULTS: From March 2015 to July 2016, 64 patients were randomized; 63 could be analysed. Trichophyton rubrum was the most detected pathogen. There was no difference in the primary outcome between laser and sham treatment. With the exception of a subungual haematoma in the fifth toenail occurring 2 weeks after laser treatment, the results suggested that treatment with Nd-YAG 1064 nm laser is safe. CONCLUSION: At this moment, there is no evidence of any effect of laser treatment for onychomycosis in patients with diabetes at increased risk for foot ulcers, at least not within 1 year after treatment.

Healthcare reimbursement costs of children with type 1 diabetes in the Netherlands, a observational nationwide study (Young Dudes-4).

BACKGROUND: Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases in children. Studies on costs related to T1DM are scarce and focused primarily on the costs directly related to diabetes. We aimed to investigate both the overall healthcare costs and the more specific costs related to the management of diabetes. METHODS: This is a retrospective and observational, nationwide cohort study of all Dutch children (aged 0-18 years) with T1DM. Data were collected from the national registry for healthcare reimbursement, in which all Dutch insurance companies combine their reimbursement data. In the Netherlands for all Dutch citizens health care is covered by law and all children are treated by hospital-based paediatricians. RESULTS: We analysed 6710 children distributed over 81 hospitals: 475 children in 6 university hospitals and 6235 children in 75 general hospitals. Total reimbursement for all children with T1DM over the period 2009 to 2011 was € 167,494,732 corresponding to an annual mean of € 55,831,577 of total costs and € 8326 euros per child. When comparing small (between 26 and 54 patients), medium (57-84 patients) and large (88-248 patients) general hospitals, costs per patient were highest in the hospitals with the highest number of T1DM patients. The costs for devices, secondary care and pharmaceutics had most impact on total expenditures. Over the study period, there was a slight decrease in per person costs. CONCLUSION: The overall health expenditure of a child with T1DM is more than € 8000 per patient per annum. Given the move towards more device-intensive multidisciplinary care for these patients, the costs of treating T1DM in children are likely to increase further in the coming years.

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.

Effects of intraperitoneal insulin versus subcutaneous insulin administration on sex hormone-binding globulin concentrations in patients with type 1 diabetes mellitus.

AIMS: Elevated sex hormone-binding globulin (SHBG) concentrations have been described in patients with type 1 diabetes mellitus (T1DM), probably due to low portal insulin concentrations. We aimed to investigate whether the route of insulin administration, continuous intraperitoneal insulin infusion (CIPII), or subcutaneous (SC), influences SHBG concentrations among T1DM patients. METHODS: Post hoc analysis of SHBG in samples derived from a randomized, open-labeled crossover trial was carried out in 20 T1DM patients: 50% males, mean age 43 (±13) years, diabetes duration 23 (±11) years, and hemoglobin A1c (HbA1c) 8.7 (±1.1) (72 (±12) mmol/mol). As secondary outcomes, testosterone, 17-ß-estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were analyzed. RESULTS: Estimated mean change in SHBG was -10.3nmol/L (95% CI: -17.4, -3.2) during CIPII and 3.7nmol/L (95% CI: -12.0, 4.6) during SC insulin treatment. Taking the effect of treatment order into account, the difference in SHBG between therapies was -6.6nmol/L (95% CI: -17.5, 4.3); -12.7nmol/L (95% CI: -25.1, -0.4) for males and -1.7nmol/L (95% CI: -24.6, 21.1) for females, respectively. Among males, SHBG and testosterone concentrations changed significantly during CIPII; -15.8nmol/L (95% CI: -24.2, -7.5) and -8.3nmol/L (95% CI: -14.4, -2.2), respectively. The difference between CIPII and SC insulin treatment was also significant for change in FSH 1.2U/L (95% CI: 0.1, 2.2) among males. CONCLUSIONS: SHBG concentrations decreased significantly during CIPII treatment. Moreover, the difference in change between CIPII and SC insulin therapy was significant for SHBG and FSH among males. These findings support the hypothesis that portal insulin administration influences circulating SHBG and sex steroids.

Intraperitoneal versus subcutaneous insulin therapy in the treatment of type 1 diabetes mellitus.

BACKGROUND: Continuous intraperitoneal insulin infusion (CIPII), a last-resort type 1 diabetes mellitus (T1DM) treatment, has only been investigated in small or controlled studies. We aimed to investigate glycaemia and quality of life (QoL) with CIPII versus subcutaneous (SC) insulin therapy during usual T1DM care. METHODS: A prospective, observational case-control study. CIPII-treated cases were matched to SC controls. The primary endpoint was a non-inferiority assessment (pre-defined margin of -5.5 mmol÷mol) of the baseline adjusted difference in HbA1c between groups during a 26-week follow-up. Secondary outcomes included QoL, clinical and biochemical measurements. RESULTS: In total, 183 patients were analysed (CIPII n = 39 and SC n = 144). The HbA1c difference between treatment groups was -3.0 mmol÷mol (95% CI -5.0, -1.0), being lower in the SC group. Patients using SC insulin therapy spent less percentage of time in hyperglycaemia (-9.3% (95% CI -15.8, -2.8)) and more in euglycaemia (6.9% (95% CI 1.2, 12.5) as compared with CIPII-treated patients. Besides a 3.6 U÷l (95% CI 1.2, 6.0) lower concentration of alanine aminotransferase with CIPII, no biochemical and clinical differences were present. Most QoL scores were lower at baseline among CIPII-treated patients. However, besides lower health status, there were no differences in the baseline-adjusted general and diabetes-specific QoL and treatment satisfaction. CONCLUSION: Although patients using CIPII had a higher glycaemic profile compared with patients using SC insulin therapy, the HbA1c difference was non-inferior. Overall, health status was lower among CIPII-treated patients, although diabetes-specific QoL and treatment satisfaction was similar to subcutaneously treated patients.

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.

Differences in interpretation of haemoglobin A1c values among diabetes care professionals.

BACKGROUND: To assess the expected precision of HbA1c measurements and the magnitude of HbA1c changes eliciting the advice to change treatment among diabetes care professionals. METHODS: A seven-item questionnaire was sent to participants through a website. The survey focused on physicians and nurses involved in diabetes care. RESULTS: In total, 104 physicians, 177 diabetes specialist nurses, and 248 primary care nurses responded to the survey. A large number of the nurses (44%) and only a small number of the physicians (4%) were not aware of the inherent uncertainty of HbA1c results. Nurses considered adjusting therapy based on very small changes in HbA1c whereas physicians in general adhere to 0.5% (5.5 mmol÷mol) as a clinically meaningful cut-off point. After therapy adjustment, a very small (0.1%) or no increase in HbA1c was considered to be significant enough to conclude that glucose regulation has worsened by 49% of the nurses and only 13% of the physicians. CONCLUSION: Significant differences exist in the interpretation of changes in HbA1c results between physicians and nurses. Nurses consider therapy changes based on very small changes in HbA1c, whereas physicians preferably agree to the clinically relevant change of 0.5% (5.5 mmol÷mol). Changing therapy based on relatively small changes in HbA1c might lead to undue adjustments in the treatment of patients with diabetes. There is a clear need for more training for all diabetes care professionals about both the clinical significance and accuracy of HbA1c measurements.

Report of a 7 year case-control study of continuous intraperitoneal insulin infusion and subcutaneous insulin therapy among patients with poorly controlled type 1 diabetes mellitus: favourable effects on hypoglycaemic episodes.

AIMS: Continuous intraperitoneal insulin infusion (CIPII) is a last-resort treatment option for patients with type 1 diabetes mellitus (T1DM) who fail to reach adequate glycaemic control with subcutaneous (SC) insulin therapy. Aim was to compare the long-term effects of CIPII and SC insulin therapy among patients with T1DM in poor glycaemic control. METHODS: Patients in which CIPII was initiated in 2006 were compared with a control group of T1DM patients who continued SC therapy. Linear mixed models were used to calculate differences between the baseline (2006) and final (2013) measurements within and between groups. RESULTS: A total of 95 patients of which 21 were using CIPII and 74 using SC insulin were included. Within the CIPII group, the number of hypoglycaemic episodes decreased with -5 (95% CI -8 to -3) per 2 weeks while it remained stable among SC patients. Over time, only the number of hypoglycaemic episodes decreased more with CIPII as compared to SC insulin treatment (difference: -6 (95% CI -9 to -4)). There were no differences between treatment groups regarding clinical parameters and quality of life scores over time. Pump or catheter dysfunction led to ketoacidosis in 6 patients: 2 using CIPII and 4 SC insulin. CONCLUSIONS: After 7 years of follow-up, there is a persistent decline of hypoglycaemic events among CIPII treated T1DM patients. Besides less hypoglycaemic episodes with CIPII therapy, there are no differences between long-term CIPII and SC insulin therapy.

Effect of i.p. insulin administration on IGF1 and IGFBP1 in type 1 diabetes.

In type 1 diabetes mellitus (T1DM), low concentrations of IGF1 and high concentrations of IGF-binding protein 1 (IGFBP1) have been reported. It has been suggested that these abnormalities in the GH-IGF1 axis are due to low insulin concentrations in the portal vein. We hypothesized that the i.p. route of insulin administration increases IGF1 concentrations when compared with the s.c. route of insulin administration. IGF1 and IGFBP1 concentrations in samples derived from an open-label, randomized cross-over trial comparing the effects of s.c. and i.p. insulin delivery on glycaemia were determined. T1DM patients were randomized to receive either 6 months of continuous i.p. insulin infusion (CIPII) through an implantable pump (MIP 2007C, Medtronic) followed by 6 months of s.c. insulin infusion or vice versa with a washout phase in between. Data from 16 patients who had complete measurements during both treatment phases were analysed. The change in IGF1 concentrations during CIPII treatment was 10.4 µg/l (95% CI -0.94, 21.7 µg/l; P=0.06) and during s.c. insulin treatment was -2.2 µg/l (95% CI -13.5, 9.2 µg/l; P=0.69). When taking the effect of treatment order into account, the estimated change in IGF1 concentrations was found to be 12.6 µg/l (95% CI -3.1, 28.5 µg/l; P=0.11) with CIPII treatment compared with that with s.c. insulin treatment. IGFBP1 concentrations decreased to -100.7 µg/l (95% CI -143.0, -58.3 µg/l; P<0.01) with CIPII treatment. During CIPII treatment, parts of the GH-IGF1 axis changed compared with that observed during s.c. insulin treatment. This supports the hypothesis that the i.p. route of insulin administration is of importance in the IGF1 system.

Vitamin B12 deficiency and the lack of its consequences in type 2 diabetes patients using metformin.

OBJECTIVES: To study vitamin B12 concentrations in patients with type 2 diabetes with and without metformin use and to identify risk factors and consequences of low vitamin B12 concentrations. RESEARCH DESIGN AND METHODS: This study had a cross-sectional design. During eight weeks all patients with type 2 diabetes visiting the diabetic outpatient clinic of the Isala Clinics in Zwolle were approached for participation. Participation included measurement of haemoglobin, mean corpuscular volume and vitamin B12 levels. Data on neuropathy were retrospectively searched for in the patient records. Vitamin B12 deficiency was defined as serum B12 concentrations <150 pmol/l. RESULTS: In the total cohort (n=298), the overall prevalence of vitamin B12 concentrations <150 pml/l was 9.7% (95% CI 6.6-13.7%). In type 2 diabetes patients not taking metformin (n=134), the prevalence was 4.4% (95% CI 1.6-9.4%) compared with 14.1% in metformin users (n=164) (95% CI 9.2-20.4%; p=0.006). Each 100 mg step in metformin dose increased (OR=1.081, p=0.014), whereas PPI use lowered (OR=0.322, p=0.037) the odds of having a vitamin B12 deficiency in logistic regression. Nevertheless, metformin use did not predict the chance on having anaemia or neuropathy. CONCLUSION: Among patients with type 2 diabetes using metformin, the prevalence of vitamin B12 deficiency is higher than compared with patients not using metformin. However, metformin use did not predict the chance of having anaemia or neuropathy.

Copeptin, a surrogate marker for arginine vasopressin, is associated with declining glomerular filtration in patients with diabetes mellitus (ZODIAC-33).

AIM/HYPOTHESIS: Arginine vasopressin (AVP), the hormone important for maintaining fluid balance, has been shown to cause kidney damage in rodent models of diabetes. We investigated the potential role of AVP in the natural course of kidney function decline in diabetes in an epidemiological study. METHODS: Plasma copeptin, a surrogate for AVP, was measured in baseline samples from patients with type 2 diabetes treated in primary care and included in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) cohort. RESULTS: Samples from 1,328 patients were available; 349 were analysed separately because they used renin-angiotensin-aldosterone system inhibition (RAASi), which influences albumin/creatinine ratio (ACR) and estimated (e)GFR. In the other 979 patients (46% men, age 68 years [58-75], ACR 1.8 mg/mmol [0.9-5.7], eGFR 67 ± 14 ml min(-1) 1.73 m(-2)) baseline copeptin (5.3 pmol/l [3.2-9.5]) was significantly associated with log e [ACR] and eGFR, even after adjustment for sex, age and risk factors for kidney function decline (standardised [std] ß 0.13, p < 0.001, std ß -0.20, p < 0.001 respectively). Follow-up data were available for 756 patients (6.5 years [4.1-9.6]). Baseline copeptin was associated with increase in ACR (std ß 0.09, p = 0.02), but lost significance after adjustment (std ß 0.07, p = 0.08). Copeptin was associated with a decrease in eGFR after adjustment (std ß -0.09, p = 0.03). The strength of the association of copeptin with change in eGFR was stronger than that of established risk factors for kidney function decline (e.g. BMI, HbA1c). In patients who used RAASi there was a significant association between baseline copeptin and ACR and eGFR, but not with change in ACR and eGFR. CONCLUSIONS/INTERPRETATION: In patients with diabetes not using RAASi a higher baseline copeptin concentration is significantly associated with higher baseline ACR and lower eGFR values and with a decline in eGFR during follow-up. This last association is independent of, and stronger than, most traditional risk factors for kidney function decline.

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.

Health care in patients 1 year post-stroke in general practice: research on the utilisation of the Dutch Transmural Protocol transient ischaemic attack/cerebrovascular accident.

This study evaluates the kind of aftercare that ischaemic stroke patients receive and the extent that aftercare fulfils the criteria of the 'Dutch Transmural Protocol transient ischaemic attack/cerebrovascular accident'. Fifty-seven patients were interviewed 1 year post-stroke about secondary prevention and aftercare. Forty general practitioners (GPs) completed a questionnaire about guidance and secondary prevention (concerning medication and lifestyle advice). Most patients would like to see their GP more regularly. More aftercare was required than was planned. The use of aspirin remained the same, fewer patients used statins and more used antihypertensives. Of the 40 GPs who participated, 12% did not apply prevention. Blood pressure, glucose and cholesterol were measured in 84%, 28% and 40% of patients. All of these measures were often elevated, but treatment was not given. Lifestyle advice was offered to one-quarter of patients. Considering all of the advice given in the Dutch Protocol, several aspects can be improved in relation to secondary prevention. Too little attention is paid to giving lifestyle advice, stricter medical checkups by GPs are necessary and there is a decrease in use of preventive medication, partly because GPs monitors use of medication inadequately. The use of the Dutch Protocol in aftercare can be improved by a more detailed description of advice.

Family doctor-driven follow-up for adult childhood cancer survivors supported by a web-based survivor care plan.

PURPOSE: To facilitate family doctor-driven follow-up for adult childhood cancer survivors, we developed a survivor care plan (SCP) for adult survivors and their family doctors. METHODS: The SCP was accessible for survivors and their family doctors on a secure website and as a printed booklet. It included data on diagnosis, treatment and potential risks as well as recommendations for follow-up. Childhood cancer survivors who were off-treatment ≥5 years, aged ≥18 years and not involved in a long-term follow-up program were eligible. They were advised to visit their family doctor. The endpoints were numbers of participants, adherence of family doctors to the guidelines and satisfaction ratings. RESULTS: The eligibility criteria were fulfilled by 108 survivors. Three family doctors and 15 survivors refused, 10 survivors were non-responders. Of the remaining 80 survivors, 73 survivors visited 72 family doctors. Sixty-nine (96%) family doctors returned data of whom 60 (83%) fully adhered to the recommended tests. The majority of survivors and family doctors were satisfied about the SCP. CONCLUSIONS: A (web-based) SCP for survivors and family doctors can serve as an effective communication vehicle to provide adequate shared care by the long-term follow-up clinic and family doctors.

Coping with adverse drug events in patients with heart failure: Exploring the role of medication beliefs and perceptions.

This study describes coping strategies that patients with heart failure (HF) use to manage adverse drug events (ADEs). The included coping strategies were social support seeking, information seeking, non-adherence and taking alleviating medication. The role of beliefs about medication and ADE perceptions in explaining these coping strategies was assessed using the Self-Regulation Model. We performed a cross-sectional study including 250 HF patients who experienced an ADE. Patients completed validated questionnaires assessing their coping strategies, ADE perceptions and medication beliefs. Social support (60%) and information seeking (32%) were the most commonly used strategies to cope with ADEs. Non-adherence was reported by 7% of the patients. Multivariate linear regression analysis showed that demographics, clinical factors and medication beliefs explained only a small amount of the variance in coping strategies, whereas ADE perceptions explained a substantial amount of variance. Path analysis showed that patients' perceptions about the timeline, consequences and controllability of ADEs by the health care provider were directly related to their coping behaviour. The effect of patients' medication beliefs on their coping strategies was consistent with mediation through their ADE perceptions. Our results support the value of the Self-Regulation Model in understanding patients' coping behaviour with regard to ADEs.

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.

Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts.

Screening for chronic kidney disease is recommended in people at high risk, but data on the independent and combined associations of estimated glomerular filtration rate (eGFR) and albuminuria with all-cause and cardiovascular mortality are limited. To clarify this, we performed a collaborative meta-analysis of 10 cohorts with 266,975 patients selected because of increased risk for chronic kidney disease, defined as a history of hypertension, diabetes, or cardiovascular disease. Risk for all-cause mortality was not associated with eGFR between 60-105 ml/min per 1.73 m², but increased at lower levels. Hazard ratios at eGFRs of 60, 45, and 15 ml/min per 1.73 m² were 1.03, 1.38 and 3.11, respectively, compared to an eGFR of 95, after adjustment for albuminuria and cardiovascular risk factors. Log albuminuria was linearly associated with log risk for all-cause mortality without thresholds. Adjusted hazard ratios at albumin-to-creatinine ratios of 10, 30 and 300 mg/g were 1.08, 1.38, and 2.16, respectively compared to a ratio of five. Albuminuria and eGFR were multiplicatively associated with all-cause mortality, without evidence for interaction. Similar associations were observed for cardiovascular mortality. Findings in cohorts with dipstick data were generally comparable to those in cohorts measuring albumin-to-creatinine ratios. Thus, lower eGFR and higher albuminuria are risk factors for all-cause and cardiovascular mortality in high-risk populations, independent of each other and of cardiovascular risk factors.