Searching for published protocols of randomized controlled trials in primary health care: an empirical systematic approach.

INTRODUCTION: Electronic search filters on family medicine or general practice studies have been developed and validated in previous work. However, there has been no systematic effort to specifically identify and record protocols of randomized controlled trials (RCT) protocols in primary health care (PHC). The aim of the present study was to systematically identify published RCT protocols in PHC and capture information about specific protocol characteristics that may describe this field. METHODS: PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Scopus from inception to December 2014 were systematically searched. Protocols of RCTs that were published in English and were relevant to PHC were considered as eligible. Protocols referred either to a mixed population, or to an intervention including a specialized part as well as pilot or feasibility trial protocols, were excluded. Specific protocol characteristics including publication year, country, prospective registration, funding, and publication sources were extracted. RESULTS: The final database included 628 published RCT protocols (median publication year 2011; interquartile range 2009-2013). The majority of protocols were designed in the UK (n=141, 22.5%), the Netherlands (n=105, 16.7%), and USA (n=93, 14.8%). Research was mainly funded by the government (n=408, 65.0%) while 45 protocols (7.2%) included industry as the funding source. Two registries - International Standard Randomised Controlled Trials Number Registry (245 (42.9%)) and ClinicalTrials.gov (209 (36.6%)) - indexed most of the protocols. Journals from several scientific fields published the articles; the field of 'Primary Health Care Medicine, General and Internal' included 69 (11.0%) articles. CONCLUSION: A compilation of published RCT protocols on PHC was feasible. The majority of protocols on PHC were published over the past 10 years, funded by the government and designed in three main countries.

Prevalence and control of hypertension by 48-h ambulatory blood pressure monitoring in haemodialysis patients: a study by the European Cardiovascular and Renal Medicine (EURECA-m) working group of the ERA-EDTA.

BACKGROUND: Population-specific consensus documents recommend that the diagnosis of hypertension in haemodialysis patients be based on 48-h ambulatory blood pressure (ABP) monitoring. However, until now there is just one study in the USA on the prevalence of hypertension in haemodialysis patients by 44-h recordings. Since there is a knowledge gap on the problem in European countries, we reassessed the problem in the European Cardiovascular and Renal Medicine working group Registry of the European Renal Association-European Dialysis and Transplant Association. METHODS: A total of 396 haemodialysis patients underwent 48-h ABP monitoring during a regular haemodialysis session and the subsequent interdialytic interval. Hypertension was defined as (i) pre-haemodialysis blood pressure (BP) ≥140/90 mmHg or use of antihypertensive agents and (ii) ABP ≥130/80 mmHg or use of antihypertensive agents. RESULTS: The prevalence of hypertension by 48-h ABP monitoring was very high (84.3%) and close to that by pre-haemodialysis BP (89.4%) but the agreement of the two techniques was not of the same magnitude (κ statistics = 0.648; P <0.001). In all, 290 participants were receiving antihypertensive treatment. In all, 9.1% of haemodialysis patients were categorized as normotensives, 12.6% had controlled hypertension confirmed by the two BP techniques, while 46.0% had uncontrolled hypertension with both techniques. The prevalence of white coat hypertension was 18.2% and that of masked hypertension 14.1%. Of note, hypertension was confined only to night-time in 22.2% of patients while just 1% of patients had only daytime hypertension. Pre-dialysis BP ≥140/90 mmHg had 76% sensitivity and 54% specificity for the diagnosis of BP ≥130/80 mmHg by 48-h ABP monitoring. CONCLUSIONS: The prevalence of hypertension in haemodialysis patients assessed by 48-h ABP monitoring is very high. Pre-haemodialysis BP poorly reflects the 48 h-ABP burden. About a third of the haemodialysis population has white coat or masked hypertension. These findings add weight to consensus documents supporting the use of ABP monitoring for proper hypertension diagnosis and treatment in this population.

Generalizability of randomized controlled trials in primary health care: Applying the PRECIS-2 tool on published protocols.

RATIONALE: Pragmatic design may facilitate the generalizability of effectiveness of randomized controlled trials (RCTs) in primary health care (PHC). AIMS AND OBJECTIVES: The aim of this study was to investigate whether published protocols in PHC were designed pragmatically and to explore whether specific trial characteristics may be related to a pragmatic design. METHODS: Using the Pragmatic Explanatory Continuum Indicator Summary-2 (PRECIS-2), we assessed pragmatism for 123 published RCT protocols. For each domain, we calculated the mean score with the 95% confidence interval (95% CI). Interrater reliability was assessed by weighted κ-coefficient with 95% CI. We examined potential associations of published protocol characteristics with overall pragmatism by performing univariate and multivariate analyses. RESULTS: We observed the highest score for primary analysis (4.66, 95% CI: 4.51, 4.82). The eligibility score was intermediate (3.16, 95% CI: 3.01, 3.32). Domains with scores towards the explanatory side included organization (2.50, 95% CI: 2.36, 2.63), flexibility of delivery (2.74, 95% CI: 2.60, 2.88) and flexibility of adherence (3.00, 95% CI: 2.83, 3.17). Interrater agreement was good (κ = 0.61; 95% CI: 0.34, 0.80; p < 0.001). Higher sample sizes were correlated to a pragmatic design (odds ratio: 6.86, 95% CI: 1.64, 28.75; p = 0.04). CONCLUSION: Most RCT protocols were rated as intermediate in the pragmatic-explanatory continuum. Future research may guide all stakeholders on how best to incorporate the level of pragmatism in the interpretation of the results so that the trials are more likely to be applicable in real-world settings.

A new simplified one port laparoscopic technique of peritoneal dialysis catheter placement with intra-abdominal fixation.

BACKGROUND: Various laparoscopic techniques have been described for the insertion of peritoneal dialysis catheters. However, most use 3 to 4 ports, thus multiplying the potential risk for abdominal wall complications (hemorrhage, hernia, leaking). METHODS: A Tenckhoff catheter was placed laparoscopically, using just 1 port, in 13 consecutive patients with end-stage renal failure. All catheters were fixed in the abdominal cavity with no additional ports for this purpose. RESULTS: After a follow-up of 76 patient-months, all catheters are working properly. There were no postoperative wall hemorrhages, early leaking, or hernias. There was 1 case of catheter migration and 2 cases of late leaking in 2 patients in total, due to severe constipation. There were no exit site or tunnel infections. One episode of peritonitis was successfully treated with antibiotics. CONCLUSION: The simplicity and the rapidity of the method justifies serious consideration for its use as the standard Tenckhoff catheter placement.

Estimation of Residual Peritoneal Volume Using Technetium-99m Sulfur Colloid Scintigraphy.

Residual peritoneal volume (RPV) may contribute in the development of ultrafiltration failure in patients with normal transcapillary ultrafiltration. The aim of this study was to estimate the RPV using intraperitoneal technetium-99m Sulfur Colloid (Tc). Twenty patients on peritoneal dialysis were studied. RPV was estimated by: 1) intraperitoneal instillation of Tc (RPV-Tc) and 2) classic Twardowski calculations using endogenous solutes, such as urea (RPV-u), creatinine (RPV-cr), and albumin (RPV-alb). Each method's reproducibility was assessed in a subgroup of patients in two consecutive measurements 48 h apart. Both methods displayed reproducibility (r = 0.93, p = 0.001 for RPVTc and r = 0.90, p = 0.001 for RPV-alb) between days 1 and 2, respectively. We found a statistically significant difference between RPV-Tc and RPV-cr measurements (347.3 ± 116.7 vs. 450.0 ± 67.8 ml; p =0.001) and RPV-u (515.5 ± 49.4 ml; p < 0.001), but not with RPV-alb (400.1 ± 88.2 ml; p = 0.308). A good correlation was observed only between RPV-Tc and RPV-alb (p < 0.001). The Tc method can estimate the RPV as efficiently as the high molecular weight endogenous solute measurement method. It can also provide an imaging estimate of the intraperitoneal distribution of RPV.

Compositional lipoprotein changes and low-density lipoprotein susceptibility to oxidation in chronic renal failure patients with heavy proteinuria.

BACKGROUND: There are limited data regarding qualitative lipoprotein abnormalities in undialysed uremic patients without proteinuria. In this report, we focused on lipoprotein changes observed in uremic patients with proteinuria as well as on the susceptibility of low-density lipoprotein (LDL) of these patients to oxidative modification in vitro. METHODS: 20 patients with chronic renal failure [serum creatinine >1.6 mg/dl (141.4 micromol/l)], but not yet on renal replacement therapy, and with heavy proteinuria (>2 g/24 h), and 18 age- and sex-matched healthy individuals participated in the study. In both patients and controls, venous blood was collected for determination of serum lipid and lipoprotein levels, lipoprotein subfraction profile and chemical composition, as well as the susceptibility of LDL subfractions to oxidation. RESULTS: Patients exhibited a more atherogenic lipid profile compared with the control population. Furthermore, the total very LDL + intermediate-density lipoprotein mass was increased in patients compared with controls, while this subfraction was triglyceride enriched in uremic patients. The total LDL concentration was significantly higher in patients compared with controls due mainly to an increase in the mass of all lipoprotein subfractions. It is noteworthy that the mass of small dense LDL was significantly elevated in patients compared with controls (135 +/- 12 vs. 115 +/- 11 mg/dl, p = 0.01), an increase which was more pronounced in hypertriglyceridemic patients. Furthermore, the subfraction high-density lipoprotein-2 mass was significantly lower in uremic patients compared with controls. Finally, no significant differences in the lag time, the rate of oxidation and the relative electrophoretic mobility values in each LDL subfraction between the two groups were observed. CONCLUSION: We conclude that uremic patients with heavy proteinuria exhibit compositional lipoprotein changes that are less marked than those observed in nonuremic patients with nephrotic syndrome. However, there is no evidence that circulating LDL isolated from these patients is more susceptible to oxidation in vitro than lipoprotein isolated from age- and gender-matched controls.

Interaction between the polymorphisms of the renin-angiotensin system in preeclampsia.

Preeclampsia is considered to be a multifactorial and multisystemic disorder with a genetic predisposition. Alterations in the renin-angiotensin system are considered to play a significant role in the pathogenesis of the disease. In order to investigate the possible association of the three most common polymorphisms of the renin-angiotensin system genes with preeclampsia we have examined 41 women with preeclampsia and 102 normotensive pregnant women. DNA samples were genotyped for the M235T polymorphism of the angiotensinogen gene (AGT), the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme gene (ACE) and the A1166C polymorphism of the angiotensin II type 1 receptor gene (AT1R) by PCR. Allele and genotype frequencies of the AGT gene polymorphism differed between the two study groups. The TT genotype of the M235T polymorphism was significantly increased in women who developed preeclampsia (P<0.02). In addition, women with preeclampsia and TT genotype had more frequently the DD genotype or the 1166C allele than the control group showing a significant interaction between the genes. In conclusion, we found an association between the angiotensinogen variant 235T and preeclampsia as well as an interaction between the variant 235T and the two other genes studied.

Serum levels of prostate-specific antigen and vitamin D in peritoneal dialysis patients.

Measuring the free:total ratio of prostate-specific antigen (f/t-PSA) can improve the specificity of single-serum PSA values, distinguishing between benign prostatic hyperplasia (BPH) and prostatic carcinoma (PCa) in men over the age of 50. Additionally, clinical trials have shown that dihydroxyvitamin D3 can slow the rate of PSA rise in PCa patients. However, little is known regarding the applicability of those findings in men undergoing chronic peritoneal dialysis (CPD). In the present study, we investigated the prevalence of increased serum PSA levels among CPD patients and correlated those values with serum levels of vitamin D [25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3]. We undertook a cross-sectional study of 71 male CPD patients without a known history of prostate cancer from 24 centers in Canada, Greece, and Turkey. All of the patients were more than 50 years of age. In these patients, we measured serum concentrations of PSA, free PSA (f-PSA), total PSA (t-PSA), prostate alkaline phosphatase (PAP), 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3, and intact parathyroid hormone (iPTH). We recorded serum PSA levels < 4 ng/mL in 62 patients (87.3%, group A) and levels > 4 ng/mL in 9 patients (12.7%, group B). The f/t-PSA ratio was < 0.25 in 16 patients (22.5%). Group B patients were older than those in group A (median: 73 years vs. 65 years, p < 0.01) and had a lower body weight (median: 66.5 kg vs. 76.7 kg, p < 0.05). We observed no statistically significant difference between the two groups for serum 1,25-dihydroxyvitamin D3 (median: 9.8 ng/mL vs. 10.1 ng/mL) or 25-hydroxyvitamin D3 (8 ng/mL vs. 8.2 ng/mL) levels. Also, we observed no correlation between vitamin D levels and f/t-PSA, but iPTH levels were significantly higher in group A (200.5 pg/mL vs. 61.2 pg/mL, p < 0.04). Also, serum PAP levels correlated significantly with PSA (r = 0.49, p = 0.01) and with f-PSA (r = 0.56, p = 0.000). Our results showed no clear relationship between vitamin D and serum levels of PSA or-of f/t-PSA in PD patients. However, further studies are needed to better define the uses of these PSA markers in PD patients because, in such patients, other relevant factors might be implicated in their predictive value.

Preclinical cardiorenal interrelationships in essential hypertension.

A diseased heart causes numerous adverse effects on kidney function, and vice versa renal disease can significantly impair cardiac function. Beyond these heart-kidney interrelationships at the clinical level, a reciprocal association has been suggested to exist even in the early stages of those organs' dysfunction. The aim of the present review is to provide evidence of the presence of a preclinical cardiorenal syndrome in the particular setting of essential hypertension, focusing on the subsequent hypertensive sequelae on heart and kidneys. In particular, a plethora of studies have demonstrated not only the predictive role of kidney damage, as expressed by either decreased glomerular filtration or increased urine albumin excretion, for adverse left ventricular functional and structural adaptations but also preclinical heart disease, i.e. left ventricular hypertrophy that is associated with deterioration of renal function. Notably, these reciprocal interactions seem to exist even at the level of microcirculation, since both coronary flow reserve and renal hemodynamics are strongly related with clinical and preclinical renal and cardiac damage, respectively. In this preclinical setting, common pathophysiological denominators, including the increased hemodynamic load, sympathetic and renin-angiotensin system overactivity, increased subclinical inflammatory reaction, and endothelial dysfunction, account not only for the reported associations between overt cardiac and renal damage but also for the parallel changes that occur in coronary and renal microcirculation.

Evidence for association of SLC7A9 gene haplotypes with cystinuria manifestation in SLC7A9 mutation carriers.

Cystinuria is a complex genetic disorder. In the present study, we report on the strict linkage disequilibrium of SLC7A9 mutations with the wild type SLC7A9 haplotype of 15 single nucleotide polymorphisms (SNPs) and their effect on cystinuria manifestation and classification. Specifically, screening for mutations and polymorphisms was performed in the family members of ten cystinuric patients with SLC7A9 gene mutations. The molecular genetic and clinical data of cystinuric patients and their relatives were combined to construct the SLC7A9 SNP haplotypes and evaluate the manifestation of the disorder in carriers for a SLC7A9 gene mutation. It was found that all carriers of a SLC7A9 mutation manifested cystinuria if their normal allele had non-wild type nucleotides in two or more of the identified polymorphic sites. Subsequently, the polymorphic background of the SLC7A9 gene probably affects the expression of the disorder in SLC7A9 mutation carriers and points to a revised genetic classification of cystinuric patients.

Sleep-disordered breathing in nondialyzed patients with chronic renal failure.

The prevalence and significance of sleep-disordered breathing (SDB) in dialysis-independent chronic renal failure (CRF) remains unknown. We studied the presence of SDB in nondialyzed CRF patients. Diagnostic polysomnography was performed in consecutive stable nondialyzed CRF patients. Inclusion criteria were age 70% pr, absence of neurologic disease or hypothyroidism, and calculated creatinine clearance <40 ml/min. Thirty-five patients (19 male, 16 female) were studied. An apnea-hypopnea index (AHI) >or=5/h was present in 54.3% (almost exclusively obstructive events). AHI correlated with urea (r = 0.35, p = 0.037), age (r = 0.379, p = 0.025), and body mass index (BMI) (r = 0.351, p = 0.038), but not with creatinine clearance. AHI or SDB were unrelated to gender. In nondiabetics (n = 25), AHI correlated with urea (r = 0.608, p = 0.001) and creatinine clearance (r = -0.50, p = 0.012). Nondiabetics with severe CRF (calculated GFR < 15 ml/min/1.73 m(2)) had a significantly higher AHI compared with less severe CRF. Restless legs syndrome (RLS) was present in 37.1% and periodic limb movements in 28.6%. Daytime sleepiness was not associated with respiratory events, but was more common in patients with RLS. The prevalence of SDB and RLS is high in dialysis-independent CRF. SDB weakly correlates with indices of kidney function and this association becomes stronger in nondiabetics.