A systematic review of high-fibre dietary therapy in diverticular disease

The exact pathogenesis of diverticular disease of the sigmoid colon is not well established. However, the hypothesis that a low-fibre diet may result in diverticulosis and a high-fibre diet will prevent symptoms or complications of diverticular disease is widely accepted. The aim of this review is to assess whether a high-fibre diet can improve symptoms and/or prevent complications of diverticular disease of the sigmoid colon and/or prevent recurrent diverticulitis after a primary episode. Clinical studies were eligible for inclusion if they assessed the treatment of diverticular disease or the prevention of recurrent diverticulitis with a high-fibre diet. The following exclusion criteria were used for study selection: studies without comparison of the patient group with a control group. No studies concerning prevention of recurrent diverticulitis with a high-fibre diet met our inclusion criteria. Three randomised controlled trials (RCT) and one case-control study were included in this systematic review. One RCT of moderate quality showed no difference in the primary endpoints. A second RCT of moderate quality and the case-control study found a significant difference in favour of a high-fibre diet in the treatment of symptomatic diverticular disease. The third RCT of moderate quality found a significant difference in favour of methylcellulose (fibre supplement). This study also showed a placebo effect. High-quality evidence for a high-fibre diet in the treatment of diverticular disease is lacking, and most recommendations are based on inconsistent level 2 and mostly level 3 evidence. Nevertheless, high-fibre diet is still recommended in several guideline

“Early Rupture of Membranes” during Induced Labor as a Risk Factor for Cesarean Delivery in Term Nulliparas

OBJECTIVE: To determine if "early rupture of membranes" (early ROM) during induction of labor is associated with an increased risk of cesarean section in term nulliparas. STUDY DESIGN: The rate of cesarean section and the timing of ROM during the course of labor were examined in term singleton nulliparas whose labor was induced. Cases were divided into 2 groups according the timing of ROM: 1)"early ROM", defined as ROM at a cervical dilatation<4 cm during labor; and 2) "late ROM", ROM at a cervical dilatation≥4 cm during labor. Nonparametric techniques were used for statistical analysis. RESULTS: 1) In a total of 500 cases of study population, "early ROM" occurred in 43% and the overall cesarean section rate was 15.8%; 2) patients with "early ROM" had a higher rate of cesarean section and cesarean section due to failure to progress than did those with "late ROM" (overall cesarean section rate: 24%[51/215] vs. 10%[28/285], p<0.01; cesarean section rate due to failure to progress: 18%[38/215] vs. 8%[22/285], p<0.01 for each) and this difference remained significant after adjusting for confounding variables. CONCLUSION: "Early ROM" during the course of induced labor is a risk factor for cesarean section in term singleton nulliparas

Prediction of drug-drug Interactions Between Various Antidepressants and Efavirenz or Boosted Protease Inhibitors Using a Physiologically Based Pharmacokinetic Modelling Approach

The rate of depression in patients with HIV is higher than in the general population. The use of antidepressants can have a beneficial effect, improving antiretroviral therapy adherence and consequently their efficacy and safety. Efavirenz and protease inhibitor boosted with ritonavir are major components of the antiretroviral therapy and are inducers and/or inhibitors of several cytochrome P450 (CYP) isoforms. Although antidepressants are prescribed to a significant proportion of patients treated with antiretrovirals, there are limited clinical data on drug-drug interactions. The aim of this study was to predict the magnitude of drug-drug interactions among efavirenz, boosted protease inhibitors and the most commonly prescribed antidepressants using an in vitro-in vivo extrapolation (IVIVE) model simulating virtual clinical trials.; In vitro data describing the chemical characteristics, and absorption, distribution, metabolism and elimination (ADME) properties of efavirenz, boosted protease inhibitors and the most commonly prescribed antidepressants were obtained from published literature or generated by standard methods. Pharmacokinetics and drug-drug interaction were simulated using the full physiologically based pharmacokinetic model implemented in the Simcyptm ADME simulator. The robustness of our modeling approach was assessed by comparing the magnitude of simulated drug-drug interactions using probe drugs to that observed in clinical studies.; Simulated pharmacokinetics and drug-drug interactions were in concordance with available clinical data. Although the simulated drug-drug interactions with antidepressants were overall weak to moderate according to the classification of the US FDA, fluoxetine and venlafaxine represent better candidates from a pharmacokinetic standpoint for patients on efavirenz and venlafaxine or citalopram for patients on boosted protease inhibitors.; The modest magnitude of interaction could be explained by the fact that antidepressants are substrates of multiple isoforms and thus metabolism can still occur through CYPs that are weakly impacted by efavirenz or boosted protease inhibitors. These findings indicate that IVIVE is a useful tool for predicting drug-drug interactions and designing prospective clinical trials, giving insight into the variability of exposure, sample size and time-dependent induction or inhibition

Effects of Switching from Stavudine to Raltegravir on Subcutaneous Adipose Tissue in HIV-Infected Patients with HIV/HAART-Associated Lipodystrophy Syndrome (HALS). A Clinical and Molecular Study

HIV-1/HAART-associated lipodystrophy syndrome (HALS) has been associated with exposure to stavudine (d4T) through mitochondrial dysfunction. We performed a 48-week study to assess the effects of switching from d4T to raltegravir (RAL) on metabolic and fat molecular parameters of patients with HALS. Forty-two patients with HALS and a median exposure to d4T > 7 years were switched to RAL and followed for 48 weeks. Fasting metabolic tests, HIV RNA, CD4 cell count, and fat measured by DEXA were obtained at baseline and week 48. mtDNA and gene transcripts for PPAR gamma, adiponectin, cytochrome b, Cox IV, TNF alpha, MCP-1 and CD68 were assessed in paired subcutaneous fat tissue biopsies. Lipid parameters, fasting glucose, insulin, and HOMA-IR did not change significantly. Whole body fat (P = 0.0027) and limb fat mass (P<0.0001) increased from baseline. Trunk/limb fat ratio (P = 0.0022), fat mass ratio (P = 0.0020), fat mass index (P = 0.0011) and percent leg fat normalized to BMI (P<0.0001) improved after 48 weeks. Relative abundance of mtDNA, expression of PPAR gamma, adiponectin, Cyt b, and MCP-1 genes increased, whereas Cox IV, TNF alpha, and CD68 did not change significantly from baseline. Switching from d4T to RAL in patients with HALS is associated with an increase in limb fat mass and an improvement in markers of adipocyte differentiation and mitochondrial function in SAT

SIMPLE:implementation of recommendations from international evidence-based guidelines on caesarean sections in the Netherlands. Protocol for a controlled before and after study

<p>Background: Caesarean section (CS) rates are rising worldwide. In the Netherlands, the most significant rise is observed in healthy women with a singleton in vertex position between 37 and 42 weeks gestation, whereas it is doubtful whether an improved outcome for the mother or her child was obtained. It can be hypothesized that evidence-based guidelines on CS are not implemented sufficiently. Therefore, the present study has the following objectives: to develop quality indicators on the decision to perform a CS based on key recommendations from national and international guidelines; to use the quality indicators in order to gain insight into actual adherence of Dutch gynaecologists to guideline recommendations on the performance of a CS; to explore barriers and facilitators that have a direct effect on guideline application regarding CS; and to develop, execute, and evaluate a strategy in order to reduce the CS incidence for a similar neonatal outcome (based on the information gathered in the second and third objectives).</p><p>Methods: An independent expert panel of Dutch gynaecologists and midwives will develop a set of quality indicators on the decision to perform a CS. These indicators will be used to measure current care in 20 hospitals with a population of 1,000 women who delivered by CS, and a random selection of 1,000 women who delivered vaginally in the same period. Furthermore, by interviewing healthcare professionals and patients, the barriers and facilitators that may influence the decision to perform a CS will be measured. Based on the results, a tailor-made implementation strategy will be developed and tested in a controlled before-and-after study in 12 hospitals (six intervention, six control hospitals) with regard to effectiveness, experiences, and costs.</p><p>Discussion: This study will offer insight into the current CS care and into the hindering and facilitating factors influencing obstetrical policy on CS. Furthermore, it will allow definition of patient categories or situations in which a tailor-made implementation strategy will most likely be meaningful and cost effective, without negatively affecting the outcome for mother and child.</p>