No Difference in Clinical Effects When Comparing Alfredson Eccentric and Silbernagel Combined Concentric-Eccentric Loading in Achilles Tendinopathy: A Randomized Controlled Trial.

BACKGROUND: Alfredson isolated eccentric loading and Silbernagel concentric-eccentric loading have both shown beneficial effects on clinical symptoms in midportion Achilles tendinopathy (AT), but they have never been compared directly. PURPOSE: To test for differences in clinical effects at 1-year follow-up between Alfredson and Silbernagel loading in midportion AT. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: A total of 40 recreational athletes were allocated to the Alfredson group (AG) or the Silbernagel group (SG). The primary outcome was the difference in the Victorian Institute of Sports Assessment-Achilles (VISA-A) at 1-year follow-up. Secondary outcomes were the visual analog scale for pain during activities of daily living (VAS-ADL) and sports activities (VAS-sports), the EuroQol 5 Dimensions instrument (EQ-5D), and global perceived effect score. Measurements were performed at baseline and 12-week, 26-week, and 1-year follow-up. Analysis was performed using a linear mixed-regression model with intervention (AG vs SG), time (12 weeks, 26 weeks, and 1 year postoperatively), and intervention-by-time interaction. RESULTS: The VISA-A score improved for both AG and SG, from 60.7 ± 17.1 at baseline to 89.4 ± 13.0 at 1-year follow-up and from 59.8 ± 22.2 to 83.2 ± 22.4, respectively (P < .001 for both). Because the interaction term did not significantly improve the model, we reported a treatment effect without interaction term, indicating a constant difference at each follow-up. The linear mixed model with correction for baseline VISA-A and confounders revealed a nonsignificant treatment effect (2.4 [95% CI, -8.5 to 13.3]; P = .656). In addition, after adjustment for the respective baseline values and confounders, nonsignificant treatment effects were found for the VAS-ADL (-2.0 [95% CI, -11.3 to 7.3]; P = .665) and VAS-sports (1.3 [95% CI, -12.8 to 15.3], P = .858). The EQ-5D subscales improved in both groups. After 1 year, significantly more SG participants considered themselves improved (77.3% [SG] vs 50.0% [AG]; P = .04). CONCLUSION: No differences in clinical effects were found between Alfredson and Silbernagel loading at up to 1-year follow-up. Both programs significantly improved clinical symptoms, and given their high adherence rates, offering either of them as a home-based program with limited supervision appears to be an effective treatment strategy for midportion AT. REGISTRATION: NTR5638 (Netherlands Trial Register number).

Lipid levels, insulin resistance and cardiovascular risk over 96 weeks of antiretroviral therapy: a randomised controlled trial comparing low-dose stavudine and tenofovir.

BACKGROUND: HIV infection and antiretroviral treatment are associated with changes in lipid levels, insulin resistance and risk of cardiovascular disease (CVD). We investigated these changes in the first 96 weeks of treatment with low-dose stavudine or tenofovir regimens. METHODS: This is a secondary analysis of a double blind, randomised controlled trial performed in South-Africa, Uganda and India comparing low-dose stavudine (20 mg twice daily) with tenofovir in combination with efavirenz and lamivudine in antiretroviral-naïve adults (n = 1067) (Clinicaltrials.gov, NCT02670772). Over 96 weeks, data were collected on fasting lipids, glucose and insulin. Insulin resistance was assessed with the HOMA-IR index and 10-year CVD risk with the Framingham risk score (FRS). A generalized linear mixed model was used to estimate trends over time. RESULTS: Participants were on average 35.3 years old, 57.6% female and 91.8% Black African. All lipid levels increased following treatment initiation, with the sharpest increase in the first 24 weeks of treatment. The increase in all lipid subcomponents over 96 weeks was higher among those in the stavudine than the tenofovir group. Insulin resistance increased steadily with no difference detected between study groups. FRS rose from 1.90% (1.84-1.98%) at baseline to 2.06 (1.98-2.15%) at week 96 for the total group, with no difference between treatment arms (p = 0.144). Lipid changes were more marked in Indian than African participants. CONCLUSION: Lipid levels increased in both groups, with low-dose stavudine resulting in a worse lipid profile compared to tenofovir. Insulin resistance increased, with no difference between regimens. CVD risk increased over time and tended to increase more in the group on stavudine. The low CVD risk across both arms argues against routine lipid and glucose monitoring in the absence of other CVD risk factors. In high risk patients, monitoring may only be appropriate at least a year after treatment initiation.

Assessing Self-reported Medication Adherence in Inflammatory Bowel Disease: A Comparison of Tools.

BACKGROUND: Capturing (non)-adherence to medical prescriptions in patients with inflammatory bowel disease (IBD) is challenging. We aimed to compare 3 different tools to measure self-assessed medication adherence of patients with IBD. METHODS: Adult patients with Crohn's disease and ulcerative colitis were prospectively followed. IBD-specific medication use was collected by 3-monthly questionnaires. At 2.5 years of follow-up, medication adherence was assessed using 3 tools: (1) the 8-item Morisky Medication Adherence Scale (MMAS-8), (2) the single question how well patients take their daily medication using a Visual Analogue Scale (VAS), and (3) the Forget Medicine scale (FM), assessing how often patients forget their medication. Cross-sectional agreement among measures was visualized with scatterplots and quantified with Spearman's rank correlations. RESULTS: In total, 913 patients with IBD were analyzed, 697 of whom received IBD-specific medication. High adherence on the MMAS-8 was consistent with high scores on the VAS and low scores on the FM. Disagreement between tools increased when patients were less adherent. A correlation of 0.44 was found between the MMAS-8 and VAS; -0.59 between the MMAS-8 and FM, and -0.55 between the VAS and FM (all P < 0.01). The VAS most optimally represented the quantitative variability of adherence, whereas the MMAS-8 and the FM might have resulted in overestimation or underestimation of adherence due to unequal differences in outcome possibilities. CONCLUSIONS: In patients with IBD, a VAS seems the most appropriate tool for quantifying medication adherence in clinical practice. The MMAS-8 may be used additionally to provide insight in specific reasons for non-adherence.

Does pre-pregnancy BMI determine blood pressure during pregnancy? A prospective cohort study.

OBJECTIVES: To evaluate if pre-pregnancy body mass index (BMI) determines blood pressure throughout pregnancy and to explore the role of gestational weight gain in this association. In addition, the effects of pre-pregnancy BMI and gestational weight gain on the occurrence of gestational hypertension and pre-eclampsia were investigated. DESIGN: Prospective cohort study. SETTING: Maternal and child health primary care referral centre, Jakarta, Indonesia. POPULATION AND MEASUREMENTS: 2252 pregnant women visiting Budi Kemuliaan Hospital and its branch for regular antenatal care visits from July 2012 to April 2015. Pre-pregnancy BMI (kg/m(2)) was based on self-reported pre-pregnancy weight and measured height at first visit. Gestational weight gain was calculated as weight at the day of delivery minus the pre-pregnancy weight. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured during pregnancy at every visit. Linear mixed models were used to analyse this relation with repeated blood pressure measures as the outcome and pre-pregnancy BMI as the predictor. When looking at gestational hypertension and pre-eclampsia as outcomes, (multiple) logistic regression was used in the analysis. RESULTS: Independent of pre-pregnancy BMI, SBP and DBP increased by 0.99 mm Hg/month and 0.46 mm Hg/month, respectively. Higher pre-pregnancy BMI was associated with higher pregnancy SBP (0.25 mm Hg/kg/m(2); 95% CI 0.17 to 0.34; p<0.01) and DBP (0.18 mm Hg/kg/m(2); 0.13 to 0.24; p<0.01) in adjusted analysis. Every 1 kg/m(2) higher pre-pregnancy BMI was associated with 6% and 9% higher odds for gestational hypertension (adjusted OR (aOR) 1.06; 95% CI 1.03 to 1.09; p<0.01) and pre-eclampsia (aOR 1.09; 1.04 to 1.14; p<0.01). Accounting for gestational weight gain did not attenuate these associations. CONCLUSIONS: Pre-pregnancy BMI determines the level, but not the change, of blood pressure in pregnancy and is linked to higher odds for gestational hypertension and pre-eclampsia, independent of gestational weight gain.

Effect of training general practitioners in drug treatment of newly detected heart failure patients with reduced or preserved ejection fraction: A cluster randomized trial.

OBJECTIVE: To assess the effect of training general practitioners (GPs) in the optimization of drug treatment for newly detected heart failure (HF). DESIGN: Cluster randomized trial comparing the training programme to care as usual. PARTICIPANTS: Community-dwelling older persons with a new HF diagnosis after diagnostic work-up. METHODS: Thirty GPs were randomized to care as usual or the training. Sixteen GPs of the latter group received a half-day training on optimizing HF medication in HF patients with a reduced (HFrEF), or with a preserved ejection fraction (HFpEF). At baseline and after six months of follow-up, the 46 HF patients in the intervention group and the 46 cases in the care as usual group were assessed on medication use, functionality, health status, and health care visits. RESULTS: After 6months, uptake of HF medication and health status were similar in the two groups. Interestingly, patients in the intervention group had a longer walking distance with the six-minute walk test than those in the care as usual group (mean difference in all-type HF 28.0 (95% CI 2.9 to 53.1) meters; HFpEF patients 28.2 (95% CI 8.8 to 47.5) meters and HFrEF patients 55.9 (95% CI -16.3 to 128.1) meters). They also had more HF-related GP visits (RR 1.8, 95% CI 1.3 to 2.5) and fewer visits to the cardiologist (RR 0.6, 95% CI 0.3 to 1.1). CONCLUSIONS: Training GPs in optimization of drug treatment of newly detected HFrEF and HFpEF did not clearly increase HF medication, but resulted in improvement in walking distance.

Search filters for finding prognostic and diagnostic prediction studies in Medline to enhance systematic reviews.

BACKGROUND: The interest in prognostic reviews is increasing, but to properly review existing evidence an accurate search filer for finding prediction research is needed. The aim of this paper was to validate and update two previously introduced search filters for finding prediction research in Medline: the Ingui filter and the Haynes Broad filter. METHODOLOGY/PRINCIPAL FINDINGS: Based on a hand search of 6 general journals in 2008 we constructed two sets of papers. Set 1 consisted of prediction research papers (n = 71), and set 2 consisted of the remaining papers (n = 1133). Both search filters were validated in two ways, using diagnostic accuracy measures as performance measures. First, we compared studies in set 1 (reference) with studies retrieved by the search strategies as applied in Medline. Second, we compared studies from 4 published systematic reviews (reference) with studies retrieved by the search filter as applied in Medline. Next--using word frequency methods--we constructed an additional search string for finding prediction research. Both search filters were good in identifying clinical prediction models: sensitivity ranged from 0.94 to 1.0 using our hand search as reference, and 0.78 to 0.89 using the systematic reviews as reference. This latter performance measure even increased to around 0.95 (range 0.90 to 0.97) when either search filter was combined with the additional string that we developed. Retrieval rate of explorative prediction research was poor, both using our hand search or our systematic review as reference, and even combined with our additional search string: sensitivity ranged from 0.44 to 0.85. CONCLUSIONS/SIGNIFICANCE: Explorative prediction research is difficult to find in Medline, using any of the currently available search filters. Yet, application of either the Ingui filter or the Haynes broad filter results in a very low number missed clinical prediction model studies.

Refill adherence and polypharmacy among patients with type 2 diabetes in general practice.

BACKGROUND AND AIMS: Non-adherence is considered a major barrier to better outcomes of diabetes care. A relationship has been established between polypharmacy and patients' adherence. This study aims to investigate the occurrence of polypharmacy and non-adherence in general practice, their mutual relationship and the association between adherence and the intermediate outcomes of diabetes care. MATERIALS AND METHODS: We used the baseline and follow-up data of a randomised controlled trial (RCT) that compared usual care with care in accordance with a locally adapted national guideline. This study took place in the Netherlands and involved 30 general practices and 1283 patients. We obtained a complete medication profile of all participants and calculated the number of prescribed drugs and the adherence indices (AI) for oral blood glucose, blood pressure and cholesterol lowering drugs. Patients with an adherence index < 0.8 were considered non-adherent. Clustering at practice level and case-mix were taken into account. RESULTS: Approximately 80% of the participating patients demonstrated an adherence index >or= 0.8 for oral blood glucose, blood pressure and cholesterol lowering drugs. In the intervention group, increase of drug prescriptions exceeded that of controls (1.1 +/- 2.0 vs. 0.6 +/- 1.5, p < 0.001, adjusted p < 0.05). There was evidence of an inverse relationship between the number of drugs that had been prescribed during the last 6 months of the study and patients' adherence to blood pressure lowering medications (adjusted OR 0.84, 95%CI 0.78-0.91). After one year, HbA1c and total cholesterol levels were significantly lower in adherent patients. CONCLUSION: During the intervention the mean number of drug prescriptions increased in both the study groups. This did not result in a lower adherence to blood glucose and cholesterol lowering medications. Given the relationship between the number of medications and patients' adherence to blood pressure lowering drugs, it may be wise to discuss adherence before prescribing multiple drug regimens.

Overall quality of diabetes care in a defined geographic region: different sides of the same story.

BACKGROUND: In diabetes care, knowledge about what is achievable in primary and secondary care is important. There is a need for an objective method to assess the quality of care in different settings. A quality-of-care summary score has been developed based on process and outcome measures. An adapted version of this score was used to evaluate diabetes management in different settings. AIM: To evaluate the quality of diabetes management in primary and secondary care in a defined geographic region in the Netherlands, using a quality score. DESIGN OF STUDY: Cross-sectional study. SETTING: Thirty general practices in the Netherlands. METHOD: A study of 2042 patients with type 2 diabetes (1640 primary care and 402 secondary care) was conducted. Quality of diabetes management was assessed by a score of process and outcome indicators (range 0-40). Clustering at practice level and differences in patient characteristics (case mix) were taken into account. RESULTS: At the outpatient clinic, patients were younger (mean age 64.1 years, standard deviation (SD)=12.5 years, versus mean age 67.1 years, SD=11.7, P<0.001), had more diabetes-related complications (macrovascular: 39.7% versus 24.3%, P<0.001; and microvascular: 25.9% versus 7.3%, P<0.001), and lower quality-of-life scores (EuroQol-5D: mean=0.60, SD=0.29, versus mean=0.80, SD=0.21, P<0.001). After adjusting for case mix and clustering, there was a weak association between the setting of treatment and haemoglobin A1c (primary care: mean 7.1%, SD=1.1, versus secondary care: mean 7.6%, SD=1.2, P<0.016), and between setting and systolic blood pressure (primary: mean 145.7 mmHg, SD=19.2, versus secondary care: 147.77 mmHg, SD 21.0, P<0.035). Quality-of-care summary scores in primary and secondary care differed significantly, with a higher score in primary care (mean 19.6, SD=8.5 versus, mean 18.1, SD=8.7, P<0.01). However, after adjusting for case mix and clustering, this difference lost significance. CONCLUSION: GPs and internists are treating different categories of patients with type 2 diabetes. However, overall quality of diabetes management in primary and secondary care is equal. There is much room for improvement. Future guidelines may differentiate between different categories of patients.

Enhanced severity of virus associated lower respiratory tract disease in asthma patients may not be associated with delayed viral clearance and increased viral load in the upper respiratory tract.

BACKGROUND: Viral respiratory infections, particularly human rhinovirus (HRV) infections, are the most common cause of asthma exacerbation. HRV infections usually lead to more severe and longer duration of lower respiratory tract (LRT) symptoms in asthmatics than in otherwise healthy individuals. However, the exact mechanism by which viruses contribute to exacerbation of asthma is unknown. OBJECTIVES: The main objective of our study was to investigate the relationship of the enhanced severity of LRT symptoms to viral dynamics or cytokine responses in the upper respiratory tract (URT). STUDY DESIGN: Therefore, we conducted a longitudinal study in which asthmatics and healthy controls were followed during natural viral respiratory tract infections. RESULTS: Our study confirmed that viral respiratory tract infections caused more severe problems of the LRT in asthma patients as compared to healthy controls. However, for all subjects, the severity of LRT symptoms were not related to viral load or prolonged viral shedding in the URT. In addition, we did not detect differences in proinflammatory cytokines in the URT between asthmatics and controls. CONCLUSION: Persistence of the virus, as well as viral load in the URT, may not be associated with the induction and/or persistence of asthmatic symptoms.

Patient characteristics do not predict poor glycaemic control in type 2 diabetes patients treated in primary care.

Many diabetic patients in general practice do not achieve good glycaemic control. The aim of this study was to assess which characteristics of type 2 diabetes patients treated in primary care predict poor glycaemic control (HbA1c > or = 7%). Data were collected from the medical records. 1641 patients were included who had mean HbA1c 7.1(SD 1.7)% , and 42% had HbA1c > or = 7%. On univariate analysis younger age; longer duration of diabetes; higher levels of blood glucose at diagnosis; most recent fasting blood glucose (FBG), total cholesterol, and triglyceride; higher body mass index (BMI); treatment with oral hypoglycaemic agents (OHA); treatment with insulin; more GP-visits for diabetes in the last year; and lower educational level were associated with poor control. Both in multiple linear regression and in multiple logistic regression higher levels of FBG (odds ratio (OR): = 1.6, 95% confidence interval (CI): 1.49, 1.70), treatment with OHA (OR: 2.1, 95% CI: 1.41, 3.04), treatment with insulin (OR: 7.2, 95% CI: 4.18, 12.52), lower educational level (OR: 1.26, 95% CI: 1.01, 1.56) were independently associated with poor levels of HbA1c. When FBG levels were excluded from the model, higher blood glucose at diagnosis, higher values for triglyceride and total cholesterol, and younger age predicted poor glycaemic control, but these variables explained only 15% of the variation in HbA1c. In conclusion prediction of poor glycaemic control from patient characteristics in diabetic patients in general practice is hardly possible. FBG appeared to be a strong predictor of HbA1c, which underlines the usefulness of this simple test in daily diabetes care. The worse metabolic control in those treated with either OHA or insulin suggests that current treatment regimes might be not sufficiently applied to reach the targets of care. Providers of diabetes care should be attentive to patients with lower educational level.

Starting insulin in type 2 diabetes: continue oral hypoglycemic agents? A randomized trial in primary care.

OBJECTIVE: To evaluate the effects of insulin 30/70 twice daily or bedtime isophane (NPH) insulin plus continued sulfonylurea and metformin in patients with type 2 diabetes in primary care. STUDY DESIGN: Open-label, randomized trial. POPULATION: Persons younger than 76 years with type 2 diabetes whose disease had not been controlled with oral hypoglycemic agents alone. A total of 64 insulin-naive patients treated with maximal feasible dosages of sulfonylurea and metformin (baseline glycosylated hemoglobin [HbA1c]=8.5%) were randomly assigned to insulin monotherapy (IM group; n=31) or insulin in addition to unchanged oral hypoglycemic medication (IC group; n=33) for 12 months. Insulin doses were adjusted to obtain fasting glucose <7.0 mmol/L and postprandial glucose <10.0 mmol/L. OUTCOMES MEASURED: Outcome measures included HbA1c, treatment failure, weight, hypoglycemic events and symptoms, satisfaction with treatment, general well-being, and fear of injecting insulin and testing. RESULTS: HbA1c improved from 8.3% to 7.6% in the IC group, and from 8.8% to 7.6% in the IM group (P=NS). The IC group had 24% treatment failures, compared with 2% in the IM group (P=.09). Patients in the IC group had less weight gain than those in the IM group (1.3 vs 4.2 kg; P=.01), and they reported fewer hypoglycemic events (2.7 vs 4.3; P=.02). Increased satisfaction with treatment was equal in the 2 groups, and general well-being improved by 3.0 points more in the IC group (P=.05). Fear of self-injecting and self-testing did not differ. CONCLUSIONS: Bedtime NPH insulin added to maximal therapy with sulfonylurea and metformin is an effective, simple, well-tolerated approach for patients with uncontrolled type 2 diabetes.

The foot function index with verbal rating scales (FFI-5pt): A clinimetric evaluation and comparison with the original FFI.

OBJECTIVE: To assess the clinimetric value of the Dutch version of the Foot Function Index (FFI) in comparison with the original FFI using verbal rating scales (FFI-5pt) rather than visual analog scales (VAS). METHODS: A prospective study was performed on 206 patients with nontraumatic forefoot complaints. Scoring, internal consistency, and construct validity of the FFI-5pt were compared with those of the original FFI, which rates all items on VAS. We also studied agreement between the scores at baseline and after one and 8 weeks and the scale scores with regard to sex, age, presence of osteoarthritis, limitation of mobility, bodily pain, and poor physical functioning (using SF-36). RESULTS: Some items were not applicable; removal of these items left 2 scales (Pain and Disability) with high internal consistency (alpha = 0.88 to 0.94) and good agreement between both versions (intraclass correlation coefficient 0.64 to 0.79). Principal component analysis with varimax rotation using a forced 2 factor model fitted well (65% explained variance). Test-retest reliability was high (ICC 0.70 to 0.83), while the stability over 8 weeks was lower, but still good (ICC 0.63 to 0.71). Responsiveness to change was low to moderate. However, a small number of patients reported an overall change (19%). Scores of patients with limited mobility and poor physical health (SF-36) were higher than those of patients with fewer physical problems, indicating good concurrent validity. CONCLUSION: The FFI-5pt is a suitable generic measure. Its clinimetric properties are comparable with those of the original FFI. Its administration and data entry are less time consuming. However, responsiveness has to be more exactly assessed in an intervention study.