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The American Journal of Clinical... Jun 2020Many patients with rheumatoid arthritis (RA) report symptom relief from certain foods. Earlier research indicates positive effects of food and food components on... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Many patients with rheumatoid arthritis (RA) report symptom relief from certain foods. Earlier research indicates positive effects of food and food components on clinical outcomes in RA, but insufficient evidence exists to provide specific dietary advice. Food components may interact but studies evaluating combined effects are lacking.
OBJECTIVES
We aimed to investigate if an anti-inflammatory diet reduces disease activity in patients with RA.
METHODS
In this single-blinded crossover trial, 50 patients with RA were randomly assigned to an intervention diet containing a portfolio of suggested anti-inflammatory foods, or a control diet similar to the general dietary intake in Sweden, for 10 wk. After a 4-mo washout period the participants switched diet. Food equivalent to ∼50% of energy requirements was delivered weekly to their homes. For the remaining meals, they were encouraged to consume the same type of foods as the ones provided during each diet. Primary outcome was change in Disease Activity Score in 28 joints-Erythrocyte Sedimentation Rate (DAS28-ESR). Secondary outcomes were changes in the components of DAS28-ESR (tender and swollen joints, ESR, and visual analog scale for general health) and DAS28-C-reactive protein.
RESULTS
In the main analysis, a linear mixed ANCOVA model including the 47 participants completing ≥1 diet period, there was no significant difference in DAS28-ESR between the intervention and control periods (P = 0.116). However, in unadjusted analyses, DAS28-ESR significantly decreased during the intervention period and was significantly lower after the intervention than after the control period in the participants who completed both periods (n = 44; median: 3.05; IQR: 2.41, 3.79 compared with median: 3.27; IQR: 2.69, 4.28; P = 0.04, Wilcoxon's Signed Rank test). No significant differences in the components were observed.
CONCLUSIONS
This trial indicates positive effects of a proposed anti-inflammatory diet on disease activity in patients with RA. Additional studies are required to determine if this diet can cause clinically relevant improvements.This trial was registered at clinicaltrials.gov as NCT02941055.
Topics: Aged; Arthritis, Rheumatoid; C-Reactive Protein; Female; Humans; Male; Middle Aged; Severity of Illness Index; Sweden
PubMed: 32055820
DOI: 10.1093/ajcn/nqaa019 -
Kidney360 Oct 2021Treating hyperphosphatemia is a tenet of dialysis care. This trial assessed the safety and efficacy of tenapanor for the management of hyperphosphatemia. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Treating hyperphosphatemia is a tenet of dialysis care. This trial assessed the safety and efficacy of tenapanor for the management of hyperphosphatemia.
METHODS
In this 52-week phase 3 study (NCT03427125), participants receiving maintenance dialysis with both hyperphosphatemia (serum phosphate 6.0-10.0 mg/dl) and a 1.5 mg/dl increase after phosphate binder washout were randomized (3:1) to tenapanor 30 mg twice daily for 26 weeks (randomized treatment period) or sevelamer carbonate (52-week safety control). Participants completing 26 weeks of treatment with tenapanor were rerandomized (1:1) to tenapanor or placebo for 12 weeks (randomized withdrawal period), and were eligible to enter the 14-week safety extension period. With input from the US Food and Drug Administration, the primary efficacy end point was the difference in the change in serum phosphate from the end of the randomized treatment period to the end of the randomized withdrawal period, among participants who achieved ≥1.2 mg/dl decrease in serum phosphate during the randomized treatment period (efficacy analysis set). Efficacy was also evaluated in the intention-to-treat (ITT) analysis set.
RESULTS
Of 564 eligible participants randomized to receive tenapanor (=423) or sevelamer carbonate (=141) during the randomized treatment period, 255 (60%) in the tenapanor group subsequently were rerandomized to tenapanor (=128) or placebo (=127) during the randomized withdrawal period. In the efficacy analysis set (=131), the difference in estimated mean change in serum phosphate level between tenapanor and placebo from the beginning to the end of the randomized withdrawal period was -1.4 mg/dl (<0.0001); in the ITT analysis set (=243), the estimated mean difference was -0.7 mg/dl (=0.002). Loosened stools were the most frequently reported adverse event (53% during the randomized treatment period). Serious adverse events were reported more frequently for participants treated with sevelamer carbonate (16%-23% across the three study periods) compared with tenapanor (11%-17%).
CONCLUSIONS
Tenapanor reduced serum phosphate concentrations and maintained control of serum phosphate in participants receiving maintenance dialysis, with an acceptable safety and tolerability profile.
Topics: Humans; Isoquinolines; Phosphates; Renal Dialysis; Sulfonamides; United States
PubMed: 35372979
DOI: 10.34067/KID.0002002021 -
Clinical Nutrition (Edinburgh, Scotland) Dec 2022Fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) can provoke symptoms in patients with irritable bowel syndrome (IBS). We aimed to compare the effects of... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
Fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) can provoke symptoms in patients with irritable bowel syndrome (IBS). We aimed to compare the effects of diets with low vs. moderate FODMAP content on gastrointestinal (GI) symptoms and bowel habits, and to identify possible predictors of clinical response to a low FODMAP diet and FODMAP sensitivity in IBS.
METHODS
Adult participants with IBS (Rome IV criteria, n = 29) were included and adhered to two 7-day diet periods, with either low (4 g/day) or moderate (23 g/day) amounts of FODMAPs, in this randomized, double-blind, crossover study. The periods were separated by a wash-out period (≥14 days). IBS-Severity Scoring System (IBS-SSS) and a stool diary (Bristol Stool Form) were completed before and after the diet periods. At baseline, severity of GI symptoms and gut microbial fermentation were assessed (every 15 min, 4 h) during the Lactulose Nutrient Challenge Test (LNCT). Clinical response and FODMAP sensitivity were defined by reduction after low FODMAP period, and increase after moderate FODMAP period in IBS-SSS (≥50 points), respectively.
RESULTS
Severity of GI symptoms (P = 0.04), stool consistency (P = 0.01), and stool frequency (P = 0.01) differed between the interventions, with reduced overall GI symptom severity, abdominal pain intensity and frequency, bowel habits dissatisfaction, and daily life interference (P < 0.05 for all), as well as more firm (P = 0.03) and less frequent (P < 0.01) stools after low FODMAP intervention, but not after moderate FODMAP intervention. A third (34%) responded clinically to the low FODMAP diet, and the response could be predicted by higher IBS-SSS at baseline (P = 0.02). Although modest associations between FODMAP sensitivity (22%) and GI symptoms during LNCT were observed, no independent predictors could be identified.
CONCLUSIONS
A diet low in FODMAPs reduces GI symptoms and affects bowel habits in IBS, compared with a moderate FODMAP diet. Assessment of IBS severity before the intervention may be used to predict clinical response to a low FODMAP diet. Trial registry (http://www.
CLINICALTRIALS
gov): Registered under Clinical Trial number NCT05182593.
Topics: Adult; Humans; Irritable Bowel Syndrome; Cross-Over Studies; Diet, Carbohydrate-Restricted; Defecation; Lactulose
PubMed: 36384081
DOI: 10.1016/j.clnu.2022.11.001 -
Current Biology : CB Feb 2021A delayed eating schedule is associated with increased risk of obesity and metabolic dysfunction in humans. However, there are no prolonged, highly controlled... (Randomized Controlled Trial)
Randomized Controlled Trial
A delayed eating schedule is associated with increased risk of obesity and metabolic dysfunction in humans. However, there are no prolonged, highly controlled experimental studies testing the effects of meal timing on weight and metabolism in adults with a body mass index (BMI) of 19-27 kg/m. Twelve healthy adults (age: 26.3 ± 3.4 years; BMI: 21.9 ± 1.7 kg/m; 5 females) participated in a randomized crossover study in free-living conditions. Three meals and two snacks with comparable energy and macronutrient contents were provided during two, 8-week, counterbalanced conditions separated by a 2-week washout period: (1) daytime (intake limited to 0800 h-1900 h) and (2) delayed (intake limited to 1200 h-2300 h). Sleep-wake cycles and exercise levels were held constant. Weight, adiposity, energy expenditure, and circadian profiles of hormones and metabolites were assessed during four inpatient visits occurring before and after each condition. Body weight, insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR]), trunk-to-leg fat ratio, resting energy expenditure, respiratory quotient, and fasting glucose, insulin, total and high-density lipoprotein (dHDL) cholesterol, and adiponectin decreased on the daytime compared to the delayed schedule. These measures, as well as triglycerides, increased on the delayed compared to the daytime schedule (effect size range: d = 0.397-1.019). Circadian phase and amplitude of melatonin, cortisol, ghrelin, leptin, and glucose were not differentially altered by the eating schedules. Overall, an 8-week daytime eating schedule, compared to a delayed eating schedule, promotes weight loss and improvements in energy metabolism and insulin in adults with BMI 19-27 kg/m, underscoring the efficacy and feasibility of daytime eating as a behavioral modification for real-world conditions.
Topics: Adult; Circadian Rhythm; Cross-Over Studies; Eating; Energy Metabolism; Female; Glucose; Humans; Insulin; Insulin Resistance; Male; Obesity; Young Adult
PubMed: 33259790
DOI: 10.1016/j.cub.2020.10.092 -
Australian Prescriber Jun 2016Switching from one antidepressant to another is frequently indicated due to an inadequate treatment response or unacceptable adverse effects. All antidepressant switches... (Review)
Review
Switching from one antidepressant to another is frequently indicated due to an inadequate treatment response or unacceptable adverse effects. All antidepressant switches must be carried out cautiously and under close observation. Conservative switching strategies involve gradually tapering the first antidepressant followed by an adequate washout period before the new antidepressant is started. This can take a long time and include periods of no treatment with the risk of potentially life-threatening exacerbations of illness. Clinical expertise is needed for more rapid or cross-taper switching as drug toxicity, including serotonin syndrome, may result from inappropriate co-administration of antidepressants. Some antidepressants must not be combined. Antidepressants can cause withdrawal syndromes if discontinued abruptly after prolonged use. Relapse and exacerbation of depression can also occur. Gradual dose reduction over days to weeks reduces the risk and severity of complications.
PubMed: 27346915
DOI: 10.18773/austprescr.2016.039 -
Nutrition Journal Apr 2016Cows' milk generally contains two types of β-casein, A1 and A2 types. Digestion of A1 type can yield the peptide β-casomorphin-7, which is implicated in adverse... (Comparative Study)
Comparative Study Randomized Controlled Trial
Effects of milk containing only A2 beta casein versus milk containing both A1 and A2 beta casein proteins on gastrointestinal physiology, symptoms of discomfort, and cognitive behavior of people with self-reported intolerance to traditional cows' milk.
BACKGROUND
Cows' milk generally contains two types of β-casein, A1 and A2 types. Digestion of A1 type can yield the peptide β-casomorphin-7, which is implicated in adverse gastrointestinal effects of milk consumption, some of which resemble those in lactose intolerance. This study aimed to compare the effects of milk containing A1 β-casein with those of milk containing only A2 β-casein on inflammation, symptoms of post-dairy digestive discomfort (PD3), and cognitive processing in subjects with self-reported lactose intolerance.
METHODS
Forty-five Han Chinese subjects participated in this double-blind, randomized, 2 × 2 crossover trial and consumed milk containing both β-casein types or milk containing only A2 β-casein. Each treatment period was 14 days with a 14-day washout period at baseline and between treatment periods. Outcomes included PD3, gastrointestinal function (measured by smart pill), Subtle Cognitive Impairment Test (SCIT), serum/fecal laboratory biomarkers, and adverse events.
RESULTS
Compared with milk containing only A2 β-casein, the consumption of milk containing both β-casein types was associated with significantly greater PD3 symptoms; higher concentrations of inflammation-related biomarkers and β-casomorphin-7; longer gastrointestinal transit times and lower levels of short-chain fatty acids; and increased response time and error rate on the SCIT. Consumption of milk containing both β-casein types was associated with worsening of PD3 symptoms relative to baseline in lactose tolerant and lactose intolerant subjects. Consumption of milk containing only A2 β-casein did not aggravate PD3 symptoms relative to baseline (i.e., after washout of dairy products) in lactose tolerant and intolerant subjects.
CONCLUSIONS
Consumption of milk containing A1 β-casein was associated with increased gastrointestinal inflammation, worsening of PD3 symptoms, delayed transit, and decreased cognitive processing speed and accuracy. Because elimination of A1 β-casein attenuated these effects, some symptoms of lactose intolerance may stem from inflammation it triggers, and can be avoided by consuming milk containing only the A2 type of beta casein.
TRIAL REGISTRATION
ClinicalTrials.gov/NCT02406469.
Topics: Adult; Aged; Animals; Asian People; Biomarkers; Caseins; Cattle; Cognition; Cross-Over Studies; Digestion; Double-Blind Method; Endorphins; Feces; Female; Gastrointestinal Tract; Humans; Inflammation; Lactose Intolerance; Male; Middle Aged; Milk; Peptide Fragments; Self Report
PubMed: 27039383
DOI: 10.1186/s12937-016-0147-z -
Journal of Ophthalmology 2018Prostaglandin analogues (PGAs) are first-line medical therapy for primary open angle glaucoma (POAG) and ocular hypertension (OHT). Intraocular pressure (IOP) lowering... (Review)
Review
TOPIC
Prostaglandin analogues (PGAs) are first-line medical therapy for primary open angle glaucoma (POAG) and ocular hypertension (OHT). Intraocular pressure (IOP) lowering effects in full responders are known to be 25-33% for this class; however, partial responders and nonresponders do exist. In clinical trials or prospective series, discontinuation and washout of PGAs is necessary to evaluate true change in IOP from novel surgeries and medical therapies.
CLINICAL RELEVANCE
To identify all relevant papers with pertinent data on washout of PGAs and quantify the duration and long-term effect of reported PGA washout periods in glaucoma and OHT patients.
METHODS
A systematic review and meta-analysis was conducted to investigate the long-term effects on IOP after discontinuation of topical PGAs POAG and OHT patients. The main search was conducted in MEDLINE/PubMed, EMBASE, Cochrane Library, CINAHL, Web of Science, and BIOSIS Previews and conference proceedings.
RESULTS
1055 papers were identified, 548 were independently screened by two physicians., and 56 papers were analyzed for washout durations. The mean washout was found to be 4.56 weeks (±1.25), with the mode and median being 5 weeks. Five studies were analyzed as randomized control trials in which latanoprost was discontinued for 4 weeks prior to restarting another intraocular pressure-lowering drug. Meta-analysis revealed a 4-week discontinuation of latanoprost, on average, subjects returned to their baseline IOP.
CONCLUSION
A significant IOP-lowering effect of latanoprost was not observed beyond 4 weeks, suggesting this may be an appropriate washout period for latanoprost. We could not identify appropriate washout periods for either travoprost or bimatoprost, although a majority of articles had 4-week washout durations for the two drugs. Despite the widespread use of this class of medication, there is a paucity of literature on the effects of PGA washout in patients that are treatment naïve to other topical medications.
PubMed: 30363694
DOI: 10.1155/2018/3190684 -
The Cochrane Database of Systematic... Aug 2021Cystic fibrosis (CF) is an autosomal recessive, life-limiting, multisystem disease affecting over 70,000 individuals worldwide. Between 80% and 90% of people with CF... (Review)
Review
BACKGROUND
Cystic fibrosis (CF) is an autosomal recessive, life-limiting, multisystem disease affecting over 70,000 individuals worldwide. Between 80% and 90% of people with CF suffer with pancreatic exocrine insufficiency, which if left untreated, leads to a poor nutritional status. Pancreatic enzyme replacement therapy (PERT) has been shown to be effective in improving nutritional status and subsequently associated with improved lung function. However, the timings of PERT administration in relation to a meal are subjective and not standardised, meaning that variations in the timing of PERT dosing persist.
OBJECTIVES
The primary objective of the review is to compare the efficacy (fat absorption) and effectiveness (nutritional status, lung function and quality of life) of different PERT dosing strategies in terms of timing of administration for treating dietary malabsorption in all individuals with CF.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Date of last search: 24 June 2021. We also searched ongoing trials registers on 09 July 2021.
SELECTION CRITERIA
Randomised controlled trials (RCTs), including cross-over RCTs with a minimum washout period of two weeks, and quasi-RCTs of PERT dosing regimens in people (of any age) with CF.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed and screened the studies identified from the searches. We planned to use GRADE to assess the certainty of evidence for our pre-specified critical outcomes, but we did not identify any eligible studies.
MAIN RESULTS
No studies met the eligibility criteria and therefore we did not include any in this review. The excluded studies were either cross-over in design (but lacking a sufficient washout period between treatments) or did not assess the timing of PERT. One study which was terminated early is awaiting assessment pending further information.
AUTHORS' CONCLUSIONS
We were unable to determine whether one dosing schedule for PERT is better than another since we identified no eligible RCTs. While the introduction of PERT to people with CF can improve their nutritional status, there are a limited number of studies which address this review question, and none met our eligibility criteria. Since malnutrition and adverse gastrointestinal symptoms remain a common feature in CF, the assessment of the relative performance of dosing schedules may provide evidence to improve outcomes in people with CF who are pancreatic insufficient. Further research is needed to fully evaluate the role of dosing schedules for PERT in fat absorption. Research should also establish reliable outcome measures and minimal clinically important differences. While RCTs with a cross-over design may have advantages over a parallel group design, an adequate washout period between intervention periods is essential.
Topics: Cystic Fibrosis; Enzyme Replacement Therapy; Humans; Nutritional Status; Pancreas
PubMed: 34339047
DOI: 10.1002/14651858.CD013488.pub2 -
Respiratory Research Mar 2023Severe asthma is burdened by relevant socio-economic and clinical impact. Randomized controlled trials on Dupilumab showed efficacy and a good safety profile, but...
RATIONALE
Severe asthma is burdened by relevant socio-economic and clinical impact. Randomized controlled trials on Dupilumab showed efficacy and a good safety profile, but post-market studies are needed.
OBJECTIVES
To evaluate the impact of Dupilumab on (i) the use of anti-asthmatic drugs, including oral corticosteroids (OCS), (ii) the rates of asthma exacerbation-related hospital admissions, and (iii) the healthcare costs in patients with asthma.
METHODS
Data were retrieved from Healthcare Utilization database of Lombardy region (Italy). We compared healthcare resources use between the 6 months after Dupilumab initiation ("post-intervention period") and (i) the 6 months before Dupilumab initiation ("wash-out period") and (ii) the corresponding 6 months of the prior year ("pre-intervention period").
MAIN RESULTS
In a cohort of 176 patients, Dupilumab significantly reduced anti-asthmatic drugs use (including OCS and short-acting β2-agonists, inhaled corticosteroids (ICS)/long-acting β2-agonists and ICS alone) when comparing the "pre-intervention" to the "post-intervention" period. When considering hospital admissions, we observed a not statistically or marginally significant reduction between both periods before Dupilumab and the post-intervention period. Six-months discontinuation rate was 8%. Overall healthcare costs had a tenfold increase between the "pre-intervention" and "post-intervention" period, which was mainly led by the biologic drug cost. Conversely, expenditures connected to hospital admissions did not change.
CONCLUSIONS
Our real-world investigation suggests that Dupilumab reduced anti-asthmatic drugs use, including OCS, in comparison to a corresponding period in the prior year. However, long-term healthcare sustainability remains an open issue.
Topics: Humans; Anti-Asthmatic Agents; Antibodies, Monoclonal, Humanized; Asthma; Cohort Studies
PubMed: 36882834
DOI: 10.1186/s12931-023-02372-y -
Indian Dermatology Online Journal 2020Isotretinoin is an oral medication used for the treatment of severe acne unresponsive to other medications. This drug is teratogenic and should be prescribed with...
INTRODUCTION AND BACKGROUND
Isotretinoin is an oral medication used for the treatment of severe acne unresponsive to other medications. This drug is teratogenic and should be prescribed with appropriate caution in selected group of patients. The washout period for pregnancy post isotrenoin therapy has always been a topic of controversy. Several guidelines have recommended a wash out period of one month if pregnancy is planned in a patient being administered with the drug.
OBJECTIVE
This article discusses the available evidence for different recommended wash out periods and addresses important clinical questions that arise.
METHODS
Pubmed research was carried out to collect relevant data using the keywords isotretinoin, pregnancy, contraception, pharmacokinetics and guidelines.
CONCLUSION
Our research based on the published data concludes that a wash out period of 35 days post isotretinoin therapy is adequate in routine clinical practice.
PubMed: 32477989
DOI: 10.4103/idoj.IDOJ_101_19