Rapid communication: L-folinic acid versus folic acid for the treatment of hyperhomocysteinemia in hemodialysis patients

BACKGROUND: The hyperhomocysteinemia found in most hemodialysis patients is refractory to combined oral B-vitamin supplementation featuring supraphysiological doses of folic acid (FA). We evaluated whether a high-dose L-folinic acid-based regimen provided improved total homocysteine (tHcy)-lowering efficacy in chronic hemodialysis patients, as suggested by a recent uncontrolled report. METHODS: We block-randomized 48 chronic, stable hemodialysis patients based on their screening predialysis tHcy levels, sex, and dialysis center into two groups of 24 subjects treated for 12 weeks with oral FA at 15 mg/day or an equimolar amount (20 mg/day) of oral L-folinic acid (FNA) [L-5-formyltetrahydrofolate]. All 48 subjects also received 50 mg/day of oral vitamin B6 and 1.0 mg/day of oral vitamin B12. RESULTS: The mean percentage (%) reductions (with 95% CIs) in predialysis tHcy were not significantly different [FNA = 22.1% (11.8 to 31.4%), FA = 20.7% (11.7 to 30.5%), P = 0.950 by paired t test]. Final on-treatment values (mean with 95% CI) were as follows: FNA, 15.9 micromol/L (14.0 to 18.0); FA, 16.9 micromol/L (14.8 to 18.8). Moreover, in those subjects with baseline tHcy levels >/=14 micromol/L, neither treatment resulted in "normalization" of tHcy levels (that is, final on-treatment values <12 micromol/L) among a significantly different or clinically meaningful number of patients [FNA = 2 out of 22 (9.1%); FA = 2 out of 24 (8.3%); Fisher's exact test of between groups difference, P = 1.000]. CONCLUSIONS: Relative to high-dose FA, high-dose oral L-folinic acid-based supplementation does not afford improved tHcy-lowering efficacy in hemodialysis patients. The preponderance of hemodialysis patients (that is,> 90%) exhibits mild hyperhomocysteinemia refractory to treatment with either regimen.     

Evaluating 90Y-glass microsphere treatment response of unresectable colorectal liver metastases by [18F]FDG PET: a comparison with CT or MRI

The purpose of this prospective study was to evaluate yttrium-90 glass microsphere treatment of unresectable liver metastases by fluorine-18 fluorodeoxyglucose positron emission tomography ([18F]FDG PET), and to compare the effectiveness of [18F]FDG PET for this purpose with that of computed tomography (CT) or magnetic resonance imaging (MRI) and determination of the serum carcinoembryonic antigen (CEA) level. Thirteen hepatic lobes from eight consecutive patients with colorectal cancer referred for 90Y-glass microsphere treatment of unresectable liver metastases who underwent both baseline (pretreatment) and 3-month posttreatment PET were studied. All patients also had correlative pre- and posttreatment CT or MRI for evaluation of the anatomic response and serum CEA determination for assessment of the total tumor load, as well as pretreatment hepatic intra-arterial technetium-99m macroaggregated albumin scan for lung shunting evaluation and hepatic arteriography for assessment of vascular anatomy and treatment. 90Y-glass microspheres were infused via an intra-arterial catheter under low pressure. Dedicated whole-body PET scans were analyzed visually and compared by lesion and by lobe with CT or MRI. A metabolic response after 90Y treatment to single or both hepatic lobes, assessed by PET, was present in a significantly higher proportion of the lobes than was an anatomic response, evaluated by CT or MRI (12 vs 2 lobes respectively, P<0.0002). Posttreatment PET showed no, stable, progressive, and new extrahepatic metastases in two, three, one, and two patients respectively. Following treatment, serum CEA decreased significantly, correlating with PET but not with CT or MRI. Thus, the study demonstrated a significant difference between the metabolic and the anatomic response after 90Y-glass microsphere treatment for unresectable liver metastases in colorectal cancer. PET appears to be an accurate indicator of treatment response.     

Comparative study of prophylactic oral ganciclovir and valacyclovir in high-risk kidney transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) is a major pathogen in renal transplant patients causing significant post-transplant morbidity and mortality. Prophylactic antiviral therapy, currently implemented in most kidney transplant centres, has significantly reduced the incidence of CMV infection after transplantation. Oral ganciclovir has been shown to be an effective prophylactic agent in preventing CMV disease and infection with a demonstrated superior efficacy over oral acyclovir. Valacyclovir, a prodrug of acyclovir with a higher level of bioavailability than acyclovir, has also been shown to be effective in preventing CMV disease when given as prophylactic treatment. METHODS: In a retrospective analysis of 150 renal transplant recipients in our centre, we compared the efficacy of oral ganciclovir with valacyclovir in preventing CMV infection. Seventy-seven consecutive renal transplant recipients prophylactically treated with oral ganciclovir for 12 weeks after transplant were compared with 73 consecutive recipients treated with oral valacylovir for an equal length of time. RESULTS: No difference was noted in the incidence of CMV infection between the two treatment groups (5.1 vs 5.4%) after a 6 month follow-up. Likewise, the incidence of acute rejection was similar in both groups (11.6 vs 6.8%). All cases of CMV infection occurred in high-risk patients (donor positive/recipient negative). CONCLUSION: The prophylactic use of oral valacylovir is as effective as oral ganciclovir in reducing CMV infection and disease after kidney transplantation.     

A Comparison of the Assay Sensitivity of Average and Worst Pain Intensity in Pharmacologic Trials: An ACTTION Systematic Review and Meta-Analysis

Identifying methods to improve assay sensitivity in randomized clinical trials (RCTs) may facilitate the discovery of efficacious pain treatments. RCTs evaluating pain treatments typically use average pain intensity (API) or worst pain intensity (WPI) as the primary efficacy outcome. However, little evidence is available comparing the assay sensitivity of these 2 measures. In this systematic review and meta-analysis, we comprehensively reviewed all low back pain, osteoarthritis pain, fibromyalgia, diabetic peripheral neuropathy pain, and postherpetic neuralgia RCTs that used a parallel group design. Eligibility required: 1) primary RCT report published between 1980 and 2016, 2) comparing 1 or more active, efficacious pharmacologic pain treatment(s) with placebo, and 3) providing data on the standardized effect size (SES) for API as well as WPI for all treatment arms. Twenty-seven active versus placebo comparisons were identified in 23 eligible articles. Using a random-effects meta-analysis, API SES and WPI SES did not differ significantly (difference?=??.021, 95% confidence interval = ?.047 to .004, P?=?.12). The findings indicate that, depending on the objectives of the study, either API or WPI could be used as a primary outcome measure in clinical trials for the chronic pain conditions included in this analysis.

The promises and limitations of gender-transformative health programming with men: critical reflections from the field

Since the 1994 International Conference on Population and Development, researchers and practitioners have engaged in a series of efforts to shift health programming with men from being gender-neutral to being more gender-sensitive and gender-transformative. Efforts in this latter category have been increasingly utilised, particularly in the last decade, and attempt to transform gender relations to be more equitable in the name of improved health outcomes for both women and men. We begin by assessing the conceptual progression of social science contributions to gender-transformative health programming with men. Next, we briefly assess the empirical evidence from gender-transformative health interventions with men. Finally, we examine some of the challenges and limitations of gender-transformative health programmes and make recommendations for future work in this thriving interdisciplinary area of study.     

Parkinson’s disease: considerations for dental hygienists

Abstract: The prevalence of Parkinson’s disease (PD) is expected to double over the next 20 years owing to the increase in life expectancy. This progressive disease has several implications relating to oral health, and many are manageable with proper awareness and knowledge about the disease. This article reviews the epidemiology, pathophysiology, and characteristics of PD, as well as the treatments and oral health considerations to enable dental hygienists to undertake an informed approach to patient management strategies and provide optimal care.     

Reduction in length of stay for patients undergoing oesophageal and gastric resections with implementation of enhanced recovery packages

Introduction

The high mortality and morbidity associated with resection for oesophagogastric malignancy has resulted in a conservative approach to the postoperative management of this patient group. In August 2009 we introduced an enhanced recovery after surgery (ERAS) pathway tailored to patients undergoing resection for oesophagogastric malignancy. We aimed to assess the impact of this change in practice on standard clinical outcomes.

Methods

Two cohorts were studied of patients undergoing resection for oesophagogastric malignancy before (August 2008 – July 2009) and after (August 2009 – July 2010) the implementation of the ERAS pathway. Data were collected on demographics, interventions, length of stay, morbidity and in-hospital mortality.

Results

There were 53 and 55 oesophagogastric resections undertaken respectively for malignant disease in each of the study periods. The median length of stay for both gastric and oesophageal resection decreased from 15 to 11 days (Mann– Whitney U, p<0.001) following implementation of the ERAS pathway. There was no significant increase in morbidity (gastric resection 23.1% vs 5.3% and oesophageal resection 25.9% vs 16.7%) or mortality (gastric resection no deaths and oesophageal resection 1.8% vs 3.6%) associated with the changes. There was a significant decrease in the number of oral contrast studies used following oesophageal resection, with a reduction from 21 (77.8%) in 2008–2009 to 6 (16.7%) in 2009–2010 (chi-squared test, p<0.0001).

Conclusions

The introduction of an enhanced recovery programme following oesophagogastric surgery resulted in a significant decrease in length of median patient stay in hospital without a significant increase in associated morbidity and mortality.