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Gut Dec 2019Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which... (Review)
Review
Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.
Topics: Adult; Consensus; Conservative Treatment; Disease Management; Gastroenterology; Humans; Inflammatory Bowel Diseases; Practice Guidelines as Topic; Societies, Medical; United Kingdom
PubMed: 31562236
DOI: 10.1136/gutjnl-2019-318484 -
Deutsches Arzteblatt International Feb 2023Pelvic floor disorders are common, especially in pregnancy and after delivery, in the postmenopausal period, and old age, and they can significantly impact on the... (Review)
Review
BACKGROUND
Pelvic floor disorders are common, especially in pregnancy and after delivery, in the postmenopausal period, and old age, and they can significantly impact on the patient's quality of life.
METHODS
This narrative review is based on publications retrieved by a selective search of the literature, with special consideration to original articles and AWMF guidelines.
RESULTS
Pelvic floor physiotherapy (evidence level [EL] 1), the use of pessaries (EL2), and local estrogen therapy can help alleviate stress/urge urinary incontinence and other symptoms of urogenital prolapse. Physiotherapy can reduce urinary incontinence by 62% during pregnancy and by 29% 3-6 months post partum. Anticholinergic and β-sympathomimetic drugs are indicated for the treatment of an overactive bladder with or without urinary urge incontinence (EL1). For patients with stress urinary incontinence, selective serotonin-noradrenaline reuptake inhibitors can be prescribed (EL1). The tension-free tape is the current standard of surgical treatment (EL1); in an observational follow-up study, 87.2% of patients were satisfied with the outcome 17 years after surgery. Fascial reconstruction techniques are indicated for the treatment of primary pelvic organ prolapse, and mesh-based surgical procedures for recurrences and severe prolapse (EL1).
CONCLUSION
Urogynecological symptoms should be specifically asked about by physicians of all relevant specialties; if present, they should be treated conservatively at first. Structured surgical techniques with and without mesh are available for the treatment of urinary incontinence and pelvic organ prolapse. Preventive measures against pelvic floor dysfunction should be offered during pregnancy and post partum.
Topics: Humans; Female; Follow-Up Studies; Quality of Life; Urinary Incontinence; Pelvic Organ Prolapse; Urinary Incontinence, Stress
PubMed: 36647585
DOI: 10.3238/arztebl.m2022.0406 -
Endocrine Reviews May 2023Although levothyroxine is one of the most prescribed medications in the world, its bioavailability has been reported to be impaired by many factors, including... (Review)
Review
Although levothyroxine is one of the most prescribed medications in the world, its bioavailability has been reported to be impaired by many factors, including interfering drugs or foods and concomitant diseases, and persistent hypothyroidism with a high dose of levothyroxine is thus elicited. Persistent hypothyroidism can also be induced by noninterchangeability between formulations and poor compliance. To address these issues some strategies have been developed. Novel formulations (liquid solutions and soft gel capsules) have been designed to eliminate malabsorption. Some other delivery routes (injections, suppositories, sprays, and sublingual and transdermal administrations) are aimed at circumventing different difficulties in dosing, such as thyroid emergencies and dysphagia. Moreover, nanomaterials have been used to develop delivery systems for the sustained release of levothyroxine to improve patient compliance and reduce costs. Some delivery systems encapsulating nanoparticles show promising release profiles. In this review, we first summarize the medical conditions that interfere with the bioavailability of oral levothyroxine and discuss the underlying mechanisms and treatments. The efficacy of liquid solutions and soft gel capsules are systematically evaluated. We further summarize the novel delivery routes for levothyroxine and their possible applications. Nanomaterials in the levothyroxine field are then discussed and compared based on their load and release profile. We hope the article provides novel insights into the drug delivery of levothyroxine.
Topics: Humans; Thyroxine; Capsules; Hypothyroidism
PubMed: 36412275
DOI: 10.1210/endrev/bnac030 -
Revista Brasileira de Ginecologia E... Oct 2022To evaluate the efficacy of the hormonal and nonhormonal approaches to symptoms of sexual dysfunction and vaginal atrophy in postmenopausal women. (Review)
Review
OBJECTIVE
To evaluate the efficacy of the hormonal and nonhormonal approaches to symptoms of sexual dysfunction and vaginal atrophy in postmenopausal women.
DATA SOURCES
We conducted a search on the PubMed, Embase, Scopus, Web of Science, SciELO, the Cochrane Central Register of Controlled Trials (CENTRAL), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases, as well as on clinical trial databases. We analyzed studies published between 1996 and May 30, 2020. No language restrictions were applied.
SELECTION OF STUDIES
We selected randomized clinical trials that evaluated the treatment of sexual dysfunction in postmenopausal women.
DATA COLLECTION
Three authors (ACAS, APFC, and JL) reviewed each article based on its title and abstract. Relevant data were subsequently taken from the full-text article. Any discrepancies during the review were resolved by consensus between all the listed authors.
DATA SYNTHESIS
A total of 55 studies were included in the systematic review. The approaches tested to treat sexual dysfunction were as follows: lubricants and moisturizers (18 studies); phytoestrogens (14 studies); dehydroepiandrosterone (DHEA; 8 studies); ospemifene (5 studies); vaginal testosterone (4 studies); pelvic floor muscle exercises (2 studies); oxytocin (2 studies); vaginal CO laser (2 studies); lidocaine (1 study); and vitamin E vaginal suppository (1 study).
CONCLUSION
We identified literature that lacks coherence in terms of the proposed treatments and selected outcome measures. Despite the great diversity in treatment modalities and outcome measures, the present systematic review can shed light on potential targets for the treatment, which is deemed necessary for sexual dysfunction, assuming that most randomized trials were evaluated with a low risk of bias according to the Cochrane Collaboration risk of bias tool. The present review is registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42018100488).
Topics: Female; Humans; Postmenopause; Vagina; Exercise Therapy; Atrophy
PubMed: 36446564
DOI: 10.1055/s-0042-1756148 -
JAMA Dec 2022Pelvic organ prolapse is a prevalent condition among women that negatively affects their quality of life. With increasing life expectancy, the global need for... (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
Pelvic organ prolapse is a prevalent condition among women that negatively affects their quality of life. With increasing life expectancy, the global need for cost-effective care for women with pelvic organ prolapse will continue to increase.
OBJECTIVE
To investigate whether treatment with a pessary is noninferior to surgery among patients with symptomatic pelvic organ prolapse.
DESIGN, SETTING, AND PARTICIPANTS
The PEOPLE project was a noninferiority randomized clinical trial conducted in 21 participating hospitals in the Netherlands. A total of 1605 women with symptomatic stage 2 or greater pelvic organ prolapse were requested to participate between March 2015 through November 2019; 440 gave informed consent. Final 24-month follow-up ended at June 30, 2022.
INTERVENTIONS
Two hundred eighteen participants were randomized to receive pessary treatment and 222 to surgery.
MAIN OUTCOMES AND MEASURES
The primary outcome was subjective patient-reported improvement at 24 months, measured with the Patient Global Impression of Improvement scale, a 7-point Likert scale ranging from very much better to very much worse. This scale was dichotomized as successful, defined as much better or very much better, vs nonsuccessful treatment. The noninferiority margin was set at 10 percentage points risk difference. Data of crossover between therapies and adverse events were captured.
RESULTS
Among 440 patients who were randomized (mean [SD] age, 64.7 [9.29] years), 173 (79.3%) in the pessary group and 162 (73.3%) in the surgery group completed the trial at 24 months. In the population, analyzed as randomized, subjective improvement was reported by 132 of 173 (76.3%) in the pessary group vs 132 of 162 (81.5%) in the surgery group (risk difference, -6.1% [1-sided 95% CI, -12.7 to ∞]; P value for noninferiority, .16). The per-protocol analysis showed a similar result for subjective improvement with 52 of 74 (70.3%) in the pessary group vs 125 of 150 (83.3%) in the surgery group (risk difference, -13.1% [1-sided 95% CI, -23.0 to ∞]; P value for noninferiority, .69). Crossover from pessary to surgery occurred among 118 of 218 (54.1%) participants. The most common adverse event among pessary users was discomfort (42.7%) vs urinary tract infection (9%) following surgery.
CONCLUSIONS AND RELEVANCE
Among patients with symptomatic pelvic organ prolapse, an initial strategy of pessary therapy, compared with surgery, did not meet criteria for noninferiority with regard to patient-reported improvement at 24 months. Interpretation is limited by loss to follow-up and the large amount of participant crossover from pessary therapy to surgery.
TRIAL REGISTRATION
Netherlands Trial Register Identifier: NTR4883.
Topics: Female; Humans; Middle Aged; Netherlands; Patient Reported Outcome Measures; Pelvic Organ Prolapse; Pessaries; Quality of Life; Treatment Outcome; Aged; Gynecologic Surgical Procedures
PubMed: 36538310
DOI: 10.1001/jama.2022.22385 -
JAMA Jul 2023A short cervix as assessed by transvaginal ultrasound is an established risk factor for preterm birth. Study findings for a cervical pessary to prevent preterm delivery... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
A short cervix as assessed by transvaginal ultrasound is an established risk factor for preterm birth. Study findings for a cervical pessary to prevent preterm delivery in singleton pregnancies with transvaginal ultrasound evidence of a short cervix have been conflicting.
OBJECTIVE
To determine if cervical pessary placement decreases the risk of preterm birth or fetal death prior to 37 weeks among individuals with a short cervix.
DESIGN, SETTING, AND PARTICIPANTS
We performed a multicenter, randomized, unmasked trial comparing a cervical pessary vs usual care from February 2017 through November 5, 2021, at 12 centers in the US. Study participants were nonlaboring individuals with a singleton pregnancy and a transvaginal ultrasound cervical length of 20 mm or less at gestations of 16 weeks 0 days through 23 weeks 6 days. Individuals with a prior spontaneous preterm birth were excluded.
INTERVENTIONS
Participants were randomized 1:1 to receive either a cervical pessary placed by a trained clinician (n = 280) or usual care (n = 264). Use of vaginal progesterone was at the discretion of treating clinicians.
MAIN OUTCOME AND MEASURES
The primary outcome was delivery or fetal death prior to 37 weeks.
RESULTS
A total of 544 participants (64%) of a planned sample size of 850 were enrolled in the study (mean age, 29.5 years [SD, 6 years]). Following the third interim analysis, study recruitment was stopped due to concern for fetal or neonatal/infant death as well as for futility. Baseline characteristics were balanced between participants randomized to pessary and those randomized to usual care; 98.9% received vaginal progesterone. In an as-randomized analysis, the primary outcome occurred in 127 participants (45.5%) randomized to pessary and 127 (45.6%) randomized to usual care (relative risk, 1.00; 95% CI, 0.83-1.20). Fetal or neonatal/infant death occurred in 13.3% of those randomized to receive a pessary and in 6.8% of those randomized to receive usual care (relative risk, 1.94; 95% CI, 1.13-3.32).
CONCLUSIONS AND RELEVANCE
Cervical pessary in nonlaboring individuals with a singleton gestation and with a cervical length of 20 mm or less did not decrease the risk of preterm birth and was associated with a higher rate of fetal or neonatal/infant mortality.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02901626.
Topics: Adult; Female; Humans; Infant; Infant, Newborn; Pregnancy; Cervix Uteri; Fetal Death; Infant Death; Perinatal Death; Pessaries; Premature Birth; Progesterone; Ultrasonography; Young Adult; Uterine Cervical Diseases
PubMed: 37490086
DOI: 10.1001/jama.2023.10812 -
Human Reproduction (Oxford, England) Apr 2023In women with threatened miscarriage, does progesterone supplementation until the completion of the first trimester of pregnancy increase the probability of live birth? (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY QUESTION
In women with threatened miscarriage, does progesterone supplementation until the completion of the first trimester of pregnancy increase the probability of live birth?
SUMMARY ANSWER
In women with threatened miscarriage, 400 mg vaginal progesterone nightly, from onset of bleeding until 12 weeks, did not increase live birth rates.
WHAT IS KNOWN ALREADY
Limited evidence has indicated that vaginal micronized progesterone may make little or no difference to the live birth rate when compared with placebo in women with threatened miscarriage. Subgroup analysis of one recent randomized trial reported that in women with bleeding and at least one previous miscarriage, progesterone might be of benefit.
STUDY DESIGN, SIZE, DURATION
We performed a randomized, double-blinded, placebo-controlled trial between February 2012 and April 2019. Eligible pregnant women under 10 weeks gestation, experiencing a threatened miscarriage as apparent from vaginal bleeding were randomized into two groups in a 1:1 ratio: the intervention group received 400 mg progesterone as vaginal pessaries, the control group received placebo vaginal pessaries, both until 12 weeks gestation. The primary endpoint was live birth. We planned to randomize 386 women (193 per group). The study was stopped at a planned interim analysis for futility after randomization of 278 women.
PARTICIPANTS/MATERIALS, SETTING, METHODS
This trial was conducted at the Mater Mothers' Hospital, a tertiary centre for maternity care in South Brisbane, Queensland, Australia. We randomized 139 women to the intervention group and 139 women to the placebo group. Primary outcome data were available for 136 women in the intervention group and 133 women in the placebo group.
MAIN RESULTS AND THE ROLE OF CHANCE
The live birth rates were 82.4% (112/136) and 84.2% (112/133) in the intervention group and placebo group, respectively (risk ratio (RR) 0.98, 95% CI 0.88 to 1.09; risk difference -0.02, 95% CI -0.11 to 0.07; P = 0.683). Among women with at least one previous miscarriage, live birth rates were 80.6% (54/67) and 84.4% (65/77) (RR 0.95, 95% CI 0.82-1.11; P = 0.550). No significant effect was seen from progesterone in women with two (RR 1.28, 95% CI 0.96-1.72; P = 0.096) or more (RR 0.79, 95% CI 0.53-1.19; P = 0.267) previous miscarriages. Preterm birth rates were 12.9% and 9.3%, respectively (RR 1.38; 95% CI 0.69 to 2.78; P = 0.361). Median birth weight was 3310 vs 3300 g (P = 0.992). There were also no other significant differences in obstetric and perinatal outcomes.
LIMITATIONS, REASONS FOR CAUTION
Our study was single centre and did not reach the planned sample size because it was stopped prematurely at an interim analysis.
WIDER IMPLICATIONS OF THE FINDINGS
We did not find evidence supporting the treatment effect of vaginal progesterone in women with threatened miscarriage. Progesterone in this setting should not be routinely used for threatened miscarriage. The treatment effect in women with threatened miscarriage after previous miscarriages warrants further research.
STUDY FUNDING/COMPETING INTEREST(S)
Mothers' and babies Golden Casket Clinical Fellowship (L.A.M.). Progesterone and placebo pessaries were provided by Perrigo Australia.B.W.J.M. reports grants from NHMRC, personal fees from ObsEva, personal fees from Merck KGaA, personal fees from Guerbet, personal fees from iGenomix, outside the submitted work.
TRIAL REGISTRATION NUMBER
ACTRN12611000405910.
TRIAL REGISTRATION DATE
19 April 2011.
DATE OF FIRST PATIENT’S ENROLMENT
06 February 2012.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Progesterone; Abortion, Spontaneous; Abortion, Threatened; Premature Birth; Maternal Health Services; Pregnancy Rate
PubMed: 36806843
DOI: 10.1093/humrep/dead029