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Endocrine-related Cancer Feb 2016Men receiving androgen deprivation therapy (ADT) for prostate cancer (PCa) are likely to develop metabolic conditions such as diabetes, cardiovascular disease, abdominal... (Review)
Review
Men receiving androgen deprivation therapy (ADT) for prostate cancer (PCa) are likely to develop metabolic conditions such as diabetes, cardiovascular disease, abdominal obesity and osteoporosis. Other treatment-related side effects adversely influence quality of life (QoL) including vasomotor distress, depression, anxiety, mood swings, poor sleep quality and compromised sexual function. The objective of this study was to systematically review the nature and effects of dietary and exercise interventions on QoL, androgen deprivation symptoms and metabolic risk factors in men with PCa undergoing ADT. An electronic search of CINAHL, CENTRAL, Medline, PsychINFO and reference lists was performed to identify peer-reviewed articles published between January 2004 and December 2014 in English. Eligible study designs included randomised controlled trials (RCTs) with pre- and post-intervention data. Data extraction and assessment of methodological quality with the Cochrane approach was conducted by two independent reviewers. Seven exercise studies were identified. Exercise significantly improved QoL, but showed no effect on metabolic risk factors (weight, waist circumference, lean or fat mass, blood pressure and lipid profile). Two dietary studies were identified, both of which tested soy supplements. Soy supplementation did not improve any outcomes. No dietary counselling studies were identified. No studies evaluated androgen-deficiency symptoms (libido, erectile function, sleep quality, mood swings, depression, anxiety and bone mineral density). Evidence from RCTs indicates that exercise enhances health- and disease-specific QoL in men with PCa undergoing ADT. Further studies are required to evaluate the effect of exercise and dietary interventions on QoL, androgen deprivation symptoms and metabolic risk factors in this cohort.
Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Exercise; Humans; Male; Prostatic Neoplasms; Quality of Life
PubMed: 26584972
DOI: 10.1530/ERC-15-0456 -
The Cochrane Database of Systematic... Sep 2020In the absence of treatment, endometrial hyperplasia (EH) can progress to endometrial cancer, particularly in the presence of histologic nuclear atypia. The development... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In the absence of treatment, endometrial hyperplasia (EH) can progress to endometrial cancer, particularly in the presence of histologic nuclear atypia. The development of EH results from exposure of the endometrium to oestrogen unopposed by progesterone. Oral progestogens have been used as treatment for EH without atypia, and in some cases of EH with atypia in women who wish to preserve fertility or who cannot tolerate surgery. EH without atypia is associated with a low risk of progression to atypia and cancer; EH with atypia is where the cells are structurally abnormal, and has a higher risk of developing cancer. Oral progestogen is not always effective at reversing the hyperplasia, can be associated with side effects, and depends on patient adherence. The levonorgestrel-intrauterine system (LNG-IUS) is an alternative method of administration of progestogen and may have some advantages over non-intrauterine progestogens.
OBJECTIVES
To evaluate the effectiveness and safety of the levonorgestrel intrauterine system (LNG-IUS) in women with endometrial hyperplasia (EH) with or without atypia compared to medical treatment with non-intrauterine progestogens, placebo, surgery or no treatment.
SEARCH METHODS
We searched the following databases: the Cochrane Gynaecology and Fertility Group (CGF) Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and PsycINFO, and conference proceedings of 10 relevant organisations. We handsearched references in relevant published studies. We also searched ongoing trials in ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry, and other trial registries. We performed the final search in May 2020.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and cross-over trials of women with a histological diagnosis of endometrial hyperplasia with or without atypia comparing LNG-IUS with non-intrauterine progestogens, placebo, surgery or no treatment.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed study selection, risk of bias assessment and data extraction. Our primary outcome measures were regression of EH and adverse effects associated with the LNG-IUS device (such as pelvic inflammatory disease, device expulsion, uterine perforation) when compared to treatment with non-intrauterine progestogens, placebo, surgery or no treatment. Secondary outcomes included hysterectomy, hormone-related adverse effects (such as bleeding/spotting, pelvic pain, breast tenderness, ovarian cysts, weight gain, acne), withdrawal from treatment due to adverse effects, satisfaction with treatment, and cost or resource use. We rated the overall quality of evidence using GRADE methods.
MAIN RESULTS
Thirteen RCTs (1657 women aged 22 to 75 years) met the inclusion criteria. Two studies had insufficient data for meta-analysis, thus the quantitative analysis included 11 RCTs. All trials evaluated treatment duration of six months or less. The evidence ranged from very low to moderate quality: the main limitations were risk of bias (associated with lack of blinding and poor reporting of study methods), inconsistency and imprecision. LNG-IUS versus non-intrauterine progestogens Primary outcomes Regression of endometrial hyperplasia The LNG-IUS probably improves regression of EH compared with non-intrauterine progestogens at short-term follow-up (up to six months) (OR 2.94, 95% CI 2.10 to 4.13; I² = 0%; 10 RCTs, 1108 participants; moderate-quality evidence). This suggests that if regression of EH following treatment with a non-intrauterine progestogen is assumed to be 72%, regression of EH following treatment with LNG-IUS would be between 85% and 92%. Regression of EH may be improved by LNG-IUS compared with non-intrauterine progestogens at long-term follow-up (12 months) (OR 3.80, 95% CI 1.75 to 8.23; 1 RCT, 138 participants; low-quality evidence), Adverse effects associated with LNG-IUS There was insufficient evidence to determine device-related adverse effects; only one study reported on expulsion with insufficient data for analysis. Secondary outcomes The LNG-IUS may be associated with fewer hysterectomies (OR 0.26, 95% CI 0.15 to 0.46; I² = 19%; 4 RCTs, 452 participants; low-quality evidence), fewer withdrawals from treatment due to hormone-related adverse effects (OR 0.41, 95% CI 0.12 to 1.35; I² = 0%; 4 RCTs, 360 participants; low-quality evidence) and improved patient satisfaction with treatment (OR 5.28, 95% CI 2.51 to 11.10; I² = 0%; 2 RCTs, 202 participants; very low-quality evidence) compared to non-intrauterine progestogens. The LNG-IUS may be associated with more bleeding/spotting (OR 2.13, 95% CI 1.33 to 3.43; I² = 78%; 3 RCTs, 428 participants) and less nausea (OR 0.52, 95% CI 0.28 to 0.95; I² = 0%; 3 RCTs, 428 participants) compared to non-intrauterine progestogens. Data from single trials for mood swings and fatigue had a similar direction of effect as for bleeding/spotting, nausea and weight gain. There was insufficient evidence to determine cost or resource use. LNG-IUS versus no treatment Regression of endometrial hyperplasia One study demonstrated that the LNG-IUS is associated with regression of EH without atypia (OR 78.41, 95% CI 22.86 to 268.97; I² = 0%; 1 RCT, 190 participants; moderate-quality evidence) compared with no treatment. This study did not report on any other review outcome.
AUTHORS' CONCLUSIONS
There is moderate-quality evidence that treatment with LNG-IUS used for three to six months is probably more effective than non-intrauterine progestogens at reversing EH in the short term (up to six months) and long term (up to two years). Adverse effects (device-related and hormone-related) were poorly and incompletely reported across studies. Very low quality to low-quality evidence suggests the LNG-IUS may reduce the risk of hysterectomy, and may be associated with more bleeding/spotting, less nausea, less withdrawal from treatment due to adverse effects, and increased satisfaction with treatment, compared to non-intrauterine progestogens. There was insufficient evidence to reach conclusions regarding device-related adverse effects, or cost or resource use.
Topics: Adult; Aged; Bias; Contraceptive Agents, Female; Endometrial Hyperplasia; Female; Humans; Hysterectomy; Intrauterine Device Expulsion; Intrauterine Devices, Medicated; Levonorgestrel; Middle Aged; Nausea; Patient Dropouts; Patient Satisfaction; Progestins; Randomized Controlled Trials as Topic; Remission Induction; Time Factors; Uterine Hemorrhage; Weight Gain; Young Adult
PubMed: 32909630
DOI: 10.1002/14651858.CD012658.pub2 -
International Journal of Surgery... Jan 2015Previous studies have shown that parathyroidectomy for primary hyperparathyroidism (PHPT) improve the function and quality of life of patients. The aim of this... (Meta-Analysis)
Meta-Analysis Review
The extent of improvement of health-related quality of life as assessed by the SF36 and Paseika scales after parathyroidectomy in patients with primary hyperparathyroidism--a systematic review and meta-analysis.
BACKGROUND
Previous studies have shown that parathyroidectomy for primary hyperparathyroidism (PHPT) improve the function and quality of life of patients. The aim of this systematic review and meta-analysis is to determine the health-related quality of life outcomes among those having surgical management for PHPT.
METHODS
Several databases were searched (MEDLINE, EMBASE, PubMed, Current Contents) for studies in which health-related quality of life was measured by reliable and validated instruments (SF-36 and Paseika Questionnaire) before and after parathyroidectomy for patients with primary hyperparathyroidism (PHPT). For the SF-36, score differences greater than 5 points indicate clinically relevant changes.
RESULTS
There were six studies with quality of life data. The SF-36 data was derived from 238 patients, with a mean age of 59 years and 71% were females. The range of follow up after surgery was 6 months to one year. The pre- and post-parathyroidectomy SF-36 quality of life scale scores were vitality (44 vs. 60, p<0.001), physical functioning (51 vs. 69, p<0.001), bodily pain (50 vs. 65, p<0.001), general health (54 vs. 64, p<0.001), role physical (34 vs. 52, p<0.001), role emotional (43 vs. 59, p<0.001), role social (60 vs. 74, p<0.001), and mental health (55 vs. 71, p<0.001). The Paseika data was derived from 203 patients, with a mean age of 54 years and 67% were females. The pre- and post-parathyroidectomy Paseika scores were feeling tired (51 vs. 19, p<0.001), feeling thirsty (29 vs. 12, p<0.001), mood swings (33 vs. 12, p<0.001), joint pains (32 vs. 14, p<0.001), irritability (31 vs. 10, p<0.001), feeling blue (31 vs. 14, p<0.001), feeling weak (37 vs. 15, p<0.001), itchy (17 vs. 7, p<0.001), forgetful (27 vs. 16, p<0.001), headache (18 vs. 5, p<0.001), abdominal pain (19 vs. 8, p<0.001), bone pain (38 vs. 17, p<0.001), ability to move off chair (27 vs. 11, p<0.001).
CONCLUSION
Parathyroidectomy significantly improves the short to medium-term health-related quality of life of patients suffering from primary hyperparathyroidism.
Topics: Female; Humans; Hyperparathyroidism, Primary; Middle Aged; Parathyroidectomy; Prospective Studies; Psychometrics; Quality of Life; Surveys and Questionnaires
PubMed: 25542340
DOI: 10.1016/j.ijsu.2014.12.004 -
PLOS Global Public Health 2023It is unclear whether the literature on adolescent gender dysphoria (GD) provides evidence to inform clinical decision making adequately. In the final of a series of...
It is unclear whether the literature on adolescent gender dysphoria (GD) provides evidence to inform clinical decision making adequately. In the final of a series of three papers, we sought to review published evidence systematically regarding the types of treatment being implemented among adolescents with GD, the age when different treatment types are instigated, and any outcomes measured within adolescence. Having searched PROSPERO and the Cochrane library for existing systematic reviews (and finding none at that time), we searched Ovid Medline 1946 -October week 4 2020, Embase 1947-present (updated daily), CINAHL 1983-2020, and PsycInfo 1914-2020. The final search was carried out on 2nd November 2020 using a core strategy including search terms for 'adolescence' and 'gender dysphoria' which was adapted according to the structure of each database. Papers were excluded if they did not clearly report on clinically-likely gender dysphoria, if they were focused on adult populations, if they did not include original data (epidemiological, clinical, or survey) on adolescents (aged at least 12 and under 18 years), or if they were not peer-reviewed journal publications. From 6202 potentially relevant articles (post deduplication), 19 papers from 6 countries representing between 835 and 1354 participants were included in our final sample. All studies were observational cohort studies, usually using retrospective record review (14); all were published in the previous 11 years (median 2018). There was significant overlap of study samples (accounted for in our quantitative synthesis). All papers were rated by two reviewers using the Crowe Critical Appraisal Tool v1·4 (CCAT). The CCAT quality ratings ranged from 71% to 95%, with a mean of 82%. Puberty suppression (PS) was generally induced with Gonadotropin Releasing Hormone analogues (GnRHa), and at a pooled mean age of 14.5 (±1.0) years. Cross Sex Hormone (CSH) therapy was initiated at a pooled mean of 16.2 (±1.0) years. Twenty-five participants from 2 samples were reported to have received surgical intervention (24 mastectomy, one vaginoplasty). Most changes to health parameters were inconclusive, except an observed decrease in bone density z-scores with puberty suppression, which then increased with hormone treatment. There may also be a risk for increased obesity. Some improvements were observed in global functioning and depressive symptoms once treatment was started. The most common side effects observed were acne, fatigue, changes in appetite, headaches, and mood swings. Adolescents presenting for GD intervention were usually offered puberty suppression or cross-sex hormones, but rarely surgical intervention. Reporting centres broadly followed established international guidance regarding age of treatment and treatments used. The evidence base for the outcomes of gender dysphoria treatment in adolescents is lacking. It is impossible from the included data to draw definitive conclusions regarding the safety of treatment. There remain areas of concern, particularly changes to bone density caused by puberty suppression, which may not be fully resolved with hormone treatment.
PubMed: 37552651
DOI: 10.1371/journal.pgph.0001478 -
Journal of Tropical Pediatrics Jan 2021During the current ongoing COVID-19 pandemic, psychological problems like anxiety, depression, irritability, mood swings, inattention and sleep disturbance are fairly... (Meta-Analysis)
Meta-Analysis
Psychological and Behavioral Impact of Lockdown and Quarantine Measures for COVID-19 Pandemic on Children, Adolescents and Caregivers: A Systematic Review and Meta-Analysis.
BACKGROUND
During the current ongoing COVID-19 pandemic, psychological problems like anxiety, depression, irritability, mood swings, inattention and sleep disturbance are fairly common among quarantined children in several studies. A systematic review of these publications to provide an accurate burden of these psychiatric/behavioral problems is needed for planning mitigating measures by the health authorities.
METHODS
Different electronic databases (MEDLINE, EMBASE, Web of Science, CENTRAL, medRxiv and bioRxiv) were searched for articles describing psychological/behavioral complications in children/adolescents with/without pre-existing behavioral abnormalities and their caregivers related to the COVID-19 pandemic. Only original articles with/without comparator arms and a minimum sample size of 50 were included in the analysis. The pooled estimate of various psychological/behavioral problems was calculated using a random-effect meta-analysis.
RESULTS
Fifteen studies describing 22 996 children/adolescents fulfilled the eligibility criteria from a total of 219 records. Overall, 34.5%, 41.7%, 42.3% and 30.8% of children were found to be suffering from anxiety, depression, irritability and inattention. Although the behavior/psychological state of a total of 79.4% of children was affected negatively by the pandemic and quarantine, at least 22.5% of children had a significant fear of COVID-19, and 35.2% and 21.3% of children had boredom and sleep disturbance. Similarly, 52.3% and 27.4% of caregivers developed anxiety and depression, respectively, while being in isolation with children.
CONCLUSION
Anxiety, depression, irritability, boredom, inattention and fear of COVID-19 are predominant new-onset psychological problems in children during the COVID-19 pandemic. Children with pre-existing behavioral problems like autism and attention deficit hyperactivity disorder have a high probability of worsening of their behavioral symptoms.
Topics: Adolescent; Anxiety; COVID-19; Caregivers; Child; Cross-Sectional Studies; Depression; Humans; Mental Health; Pandemics; Problem Behavior; Quarantine
PubMed: 33367907
DOI: 10.1093/tropej/fmaa122 -
Journal of Affective Disorders Apr 2022Bipolar disorder (BD) is a severe mental disorder characterized by mood swings and functional impairment. Although alterations in emotional regulation (ER) are a key... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bipolar disorder (BD) is a severe mental disorder characterized by mood swings and functional impairment. Although alterations in emotional regulation (ER) are a key feature, a comprehensive meta-analysis on abnormalities in emotion regulation in BD is still lacking.
METHODS
We performed a random-effects meta-analysis on studies comparing the ER measured with the Difficulties in Emotion Regulation Scale (DERS) in BD and healthy controls (HC) or borderline personality disorder (BPD) and calculated the standardized mean difference (SMD) of the total DERS score between those with BD and HC (primary outcome). Secondary outcomes were the SMD of the DERS subscales between BD and HC, as well as the SMD of the total score of DERS and the subscales between BD and BPD.
RESULTS
Twelve studies (858 BD, 540 BPD, 285 HC) were included. Compared to HC, BD showed significantly higher total DERS score (k=8, SMD 0.962, p<0.001) and subscale scores, including non-acceptance (k=6, SMD=0.85, p<0.001), goal-directed behavior (k=6, SMD=0.894, p<0.001), impulse control (k=6, SMD=1.08, p<0.001), strategies (k=6, SMD=1.25, p<0.001) and emotional clarity (k=6, SMD=0.694, p=0.001). Relative to BPD, BD presented significantly lower scores in all the DERS subscales. Sensitivity analyses confirmed the main analyses. The age of the participants and sample size moderated the primary outcome.
LIMITATIONS
The small number of studies and the cross-sectional design limit the generalizability of the results.
CONCLUSIONS
Our findings suggest that alterations of specific ER abilities are present in BD and their magnitude is smaller relative to BPD. Future therapeutic interventions should target ER strategies.
Topics: Bipolar Disorder; Borderline Personality Disorder; Cross-Sectional Studies; Emotional Regulation; Emotions; Humans
PubMed: 35093412
DOI: 10.1016/j.jad.2022.01.102 -
Sports Medicine (Auckland, N.Z.) Jul 2021Inertial measurement units (IMUs) are used for running gait analysis in a variety of sports. These sensors have been attached at various locations to capture stride... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Inertial measurement units (IMUs) are used for running gait analysis in a variety of sports. These sensors have been attached at various locations to capture stride data. However, it is unclear if different placement sites affect the derived outcome measures.
OBJECTIVE
The aim of this systematic review and meta-analysis was to investigate the impact of placement on the validity and reliability of IMU-derived measures of running gait.
METHODS
Online databases SPORTDiscus with Full Text, CINAHL Complete, MEDLINE (EBSCOhost), EMBASE (Ovid) and Scopus were searched from the earliest record to 6 August 2020. Articles were included if they (1) used an IMU during running (2) reported spatiotemporal variables, peak ground reaction force (GRF) or vertical stiffness and (3) assessed validity or reliability. Meta-analyses were performed for a pooled validity estimate when (1) studies reported means and standard deviation for variables derived from the IMU and criterion (2) used the same IMU placement and (3) determined validity at a comparable running velocity (≤ 1 m·s difference).
RESULTS
Thirty-nine articles were included, where placement varied between the foot, tibia, hip, sacrum, lumbar spine (LS), torso and thoracic spine (TS). Initial contact, toe-off, contact time (CT), flight time (FT), step time, stride time, swing time, step frequency (SF), step length (SL), stride length, peak vertical and resultant GRF and vertical stiffness were analysed. Four variables (CT, FT, SF and SL) were meta-analysed, where CT was compared between the foot, tibia and LS placements and SF was compared between foot and LS. Foot placement data were meta-analysed for FT and SL. All data are the mean difference (MD [95%CI]). No significant difference was observed for any site compared to the criterion for CT (foot: - 11.47 ms [- 45.68, 22.74], p = 0.43; tibia: 22.34 ms [- 18.59, 63.27], p = 0.18; LS: - 48.74 ms [- 120.33, 22.85], p = 0.12), FT (foot: 11.93 ms [- 8.88, 32.74], p = 0.13), SF (foot: 0.45 step·min [- 1.75, 2.66], p = 0.47; LS: - 3.45 step·min [- 16.28, 9.39], p = 0.37) and SL (foot: 0.21 cm [- 1.76, 2.18], p = 0.69). Reliable derivations of CT (coefficient of variation [CV] < 9.9%), FT (CV < 11.6%) and SF (CV < 4.4%) were shown using foot- and LS-worn IMUs, while the CV was < 7.8% for foot-determined stride time, SL and stride length. Vertical GRF was reliable from the LS (CV = 4.2%) and TS (CV = 3.3%) using a spring-mass model, while vertical stiffness was moderately (r = 0.66) and nearly perfectly (r = 0.98) correlated with criterion measures from the TS.
CONCLUSION
Placement of IMUs on the foot, tibia and LS is suitable to derive valid and reliable stride data, suggesting measurement site may not be a critical factor. However, evidence regarding the ability to accurately detect stride events from the TS is unclear and this warrants further investigation.
Topics: Biomechanical Phenomena; Foot; Gait; Humans; Reproducibility of Results; Running; Torso
PubMed: 33761128
DOI: 10.1007/s40279-021-01443-8 -
Frontiers in Medicine 2022Coronavirus disease-2019 (COVID-19), a worldwide disaster, has already affected lots of people. Effective care and therapy are currently being evaluated in full swing.
BACKGROUND
Coronavirus disease-2019 (COVID-19), a worldwide disaster, has already affected lots of people. Effective care and therapy are currently being evaluated in full swing.
PURPOSE
Our purpose was to investigate the effects of tocilizumab, an interleukin-6 receptor inhibitor, on treatment of adult patients with COVID-19 pneumonia.
DATA SOURCES STUDY SELECTION AND DATA EXTRACTION
We conducted a meta-analysis and searched for relevant studies on Pubmed, Embase, and the Cochrane Library without restrictions on language from inception until February 1, 2021. Fifteen studies were included for this meta-analysis. Two authors independently selected and screened these studies, assessed the quality of included studies, and extracted related information.
RESULTS
Fifteen studies were included in this meta-analysis. The main studies showed that tocilizumab was associated with lower mortality (risk ratio = 0.62, 95% confidence interval = 0.46-0.83; and hazard ratio = 0.61, 95% confidence interval = 0.51-0.72). Using tocilizumab might also affect biochemistry indicators (lowered C-reactive protein and ferritin, increased lymphocyte count).
CONCLUSION
These current bodies of evidence could indicate that early use of tocilizumab was associated with lower mortality in adult patients with COVID-19. Early use of tocilizumab could reduce the mortality rate of adult patients with COVID-19 without obvious fatal side effects, which may be a treatment option in patients with COVID-19 pneumonia.
SYSTEMATIC REVIEW REGISTRATION
The study protocol was registered on PROSPERO (ID:242811).
PubMed: 35433719
DOI: 10.3389/fmed.2022.838904 -
Frontiers in Psychiatry 2022Personal recovery from psychiatric disorders is a journey toward a satisfying and hopeful life despite the possible persistence of symptoms. This concept has gained...
Personal recovery from psychiatric disorders is a journey toward a satisfying and hopeful life despite the possible persistence of symptoms. This concept has gained interest and become an increasingly important goal in mental health care programmes. Personal Recovery is well described in the context of severe mental illnesses in general, but little is known about this journey in bipolar disorders and the factors underlying it. A systematic review was conducted according to the PRISMA recommendations, focusing on studies exploring personal recovery in bipolar disorder specifically. The latter have integrated a comprehensive approach to the concept, the existing means of measurement or have explored the levers of recovery in care. Twenty-four articles were selected, including seven qualitative, 12 observational, and five interventional studies. The Bipolar Recovery Questionnaire was the only scale developed from qualitative work with bipolar people. Personal recovery did not correlate very closely with symptomatology. Some elements of personal recovery in bipolar disorder were similar to those in other severe mental illnesses: meaning in life, self-determination, hope, and low self-stigma. Specific levers differed: mental relationships with mood swings, including acceptance and decrease in hypervigilance, and openness to others, including trust and closeness. The studies highlighted the role of caregiver posture and the quality of communication within care, as well as the knowledge gained from peers. The choice to exclude articles not focused on bipolar disorder resulted in the provision of very specific information, and the small number of articles to date may limit the scope of the evidence. New components of personal recovery in bipolar disorder emerged from this review; these components could be taken into account in the construction of care tools, as well as in the caregiving posture. Strengthening skills of openness to others could also be a central target of recovery-focused care.
PubMed: 35815013
DOI: 10.3389/fpsyt.2022.876761 -
The Cochrane Database of Systematic... Aug 2014Corticosteroids are effective for induction, but not maintenance of remission in Crohn's disease. Significant concerns exist regarding the risk for adverse events,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Corticosteroids are effective for induction, but not maintenance of remission in Crohn's disease. Significant concerns exist regarding the risk for adverse events, particularly when corticosteroids are used for long treatment courses. Budesonide is a glucocorticoid with limited systemic bioavailability due to extensive first-pass hepatic metabolism and is effective for induction of remission in Crohn's disease.
OBJECTIVES
To evaluate the efficacy and safety of oral budesonide for maintenance of remission in Crohn's disease.
SEARCH METHODS
The following databases were searched from inception to 12 June 2014: PubMed, MEDLINE, EMBASE, CENTRAL, the Cochrane IBD/FBD Group Specialised Trial Register, and ClinicalTrials.gov. Reference lists of articles, as well as conference proceedings were manually searched.
SELECTION CRITERIA
Randomized controlled trials comparing budesonide to a control treatment, or comparing two doses of budesonide, were included. The study population included patients of any age with quiescent Crohn's disease.
DATA COLLECTION AND ANALYSIS
Two independent investigators reviewed studies for eligibility, extracted data and assessed study quality using the Cochrane risk of bias tool. The primary outcome was maintenance of remission at various reported follow-up times during the study. Secondary outcomes included: time to relapse, mean change in CDAI, clinical, histological, improvement in quality of life, adverse events and study withdrawal. We calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI) for dichotomous outcomes and the mean difference (MD) and 95% CI for continuous outcomes. Data were analysed on an intention-to-treat basis. The Chi(2) and I(2) statistics were used to assess heterogeneity. Random-effects models were used to allow for expected clinical and statistical heterogeneity. The overall quality of the evidence supporting the primary outcome was assessed using the GRADE criteria.
MAIN RESULTS
Twelve studies (n = 1273 patients) were included in the review: eight studies compared budesonide to placebo, one compared budesonide to 5-aminosalicylates, one compared budesonide to traditional systemic corticosteroids, one compared budesonide to azathioprine, and one compared two doses of budesonide. Nine studies used a controlled ileal release form of budesonide, while three used a pH-modified release formulation. Nine studies were judged to be at low risk of bias. Three studies were judged to be at high risk of bias due to blinding and one of these studies also had inadequate allocation concealment. Budesonide 6 mg daily was no more effective than placebo for maintenance of remission at 3 months, 6 months or 12 months. At three months 64% of budesonide 6 mg patients remained in remission compared to 52% of placebo patients (RR 1.25, 95% CI 1.00 to 1.58; 6 studies, 540 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was low due to moderate heterogeneity (I(2) = 56%) and sparse data (315 events). At six months 61% of budesonide 6 mg patients remained in remission compared to 52% of placebo patients (RR 1.15, 95% CI 0.95 to 1.39; 5 studies, 420 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was moderate due to sparse data (238 events). At 12 months 55% of budesonide 6 mg patients remained in remission compared to 48% of placebo patients (RR 1.13; 95% CI 0.94 to 1.35; 5 studies, 420 patients). A GRADE analysis indicated that the overall quality of the evidence for this outcome was moderate due to sparse data (215 events). Similarly, there was no significant benefit for budesonide 3 mg compared to placebo at 6 and 12 months. There was no statistically significant difference in continued remission at 12 months between budesonide and weaning doses of prednisolone (RR 0.79; 95% CI 0.55 to 1.13; 1 study, 90 patients). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was low due to sparse data (51 events) and high risk of bias (no blinding). Budesonide 6 mg was better than mesalamine 3 g/day at 12 months (RR 2.51, 95% CI 1.03 to 6.12; 1 study, 57 patients). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was very low due to very sparse data (18 events) and high risk of bias (no blinding). There was no statistically significant difference in continued remission at 12 months between budesonide and azathioprine (RR 0.81; 95% CI 0.61 to 1.08; 1 study 77 patients). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was very low due to sparse data (55 events) and high risk of bias (single-blind and no allocation concealment). The use of budesonide 6 mg resulted in slight improvements in CDAI scores when assessed at 6 months (MD -24.30, 95% CI -46.31 to -2.29) and 12 months (MD -23.49, 95% CI -46.65 to -0.32) and mean time to relapse of disease (MD 59.93 days, 95% CI 19.02 to 100.84). Mean time to relapse was significantly shorter for patients receiving budesonide than for those receiving azathioprine (MD -58.00, 95% CI -96.68 to -19.32). Adverse events were not more common in patients treated with budesonide compared to placebo (6 mg: RR 1.51, 95% CI 0.90 to 2.52; 3 mg: RR 1.19, 95% CI 0.63 to 2.24). These events were relatively minor and did not result in increased rates of study withdrawal. Commonly reported treatment-related adverse effects included acne, moon facies, hirsutism, mood swings, insomnia, weight gain, striae, and hair loss. Abnormal adrenocorticoid stimulation tests were seen more frequently in patients receiving both 6 mg (RR 2.88, 95% CI 1.72 to 4.82) and 3 mg daily (RR 2.73, 95% CI 1.34 to 5.57) compared to placebo.
AUTHORS' CONCLUSIONS
These data suggest budesonide is not effective for maintenance of remission in CD, particularly when used beyond three months following induction of remission. Budesonide does have minor benefits in terms of lower CDAI scores and longer time to relapse of disease. However, these benefits are offset by higher treatment-related adverse event rates and more frequent adrenocorticoid suppression in patients receiving budesonide.
Topics: Administration, Oral; Anti-Inflammatory Agents; Budesonide; Crohn Disease; Humans; Induction Chemotherapy; Maintenance Chemotherapy; Randomized Controlled Trials as Topic; Risk; Secondary Prevention
PubMed: 25141071
DOI: 10.1002/14651858.CD002913.pub3