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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 -
International Journal of Molecular... Oct 2020Bipolar disorder (BD) is a complex neurobiological disorder characterized by a pathologic mood swing. Digital phenotyping, defined as the 'moment-by-moment... (Meta-Analysis)
Meta-Analysis
Bipolar disorder (BD) is a complex neurobiological disorder characterized by a pathologic mood swing. Digital phenotyping, defined as the 'moment-by-moment quantification of the individual-level human phenotype in its own environment', represents a new approach aimed at measuring the human behavior and may theoretically enhance clinicians' capability in early identification, diagnosis, and management of any mental health conditions, including BD. Moreover, a digital phenotyping approach may easily introduce and allow clinicians to perform a more personalized and patient-tailored diagnostic and therapeutic approach, in line with the framework of precision psychiatry. The aim of the present paper is to investigate the role of digital phenotyping in BD. Despite scarce literature published so far, extremely heterogeneous methodological strategies, and limitations, digital phenotyping may represent a grounding research and clinical field in BD, by owning the potentialities to quickly identify, diagnose, longitudinally monitor, and evaluating clinical response and remission to psychotropic drugs. Finally, digital phenotyping might potentially constitute a possible predictive marker for mood disorders.
Topics: Biomarkers; Bipolar Disorder; Endophenotypes; Humans; Mobile Applications; Precision Medicine; Telemedicine
PubMed: 33081393
DOI: 10.3390/ijms21207684 -
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 -
CNS Drugs Dec 2019Melatonin is widely available either on prescription for the treatment of sleep disorders or as an over-the-counter dietary supplement. Melatonin has also recently been...
BACKGROUND
Melatonin is widely available either on prescription for the treatment of sleep disorders or as an over-the-counter dietary supplement. Melatonin has also recently been licensed in the UK for the short-term treatment of jetlag. Little is known about the potential for adverse events (AEs), in particular AEs resulting from long-term use. Concern has been raised over the possible risks of exposure in certain populations including pre-adolescent children and patients with epilepsy or asthma.
OBJECTIVES
The aim of this systematic review was to assess the evidence for AEs associated with short-term and longer-term melatonin treatment for sleep disorders.
METHODS
A literature search of the PubMed/Medline database and Google Scholar was conducted to identify randomised, placebo-controlled trials (RCTs) of exogenous melatonin administered for primary or secondary sleep disorders. Studies were included if they reported on both the types and frequencies of AEs. Studies of pre-term infants, studies of < 1 week in duration or involving single doses of melatonin and studies in languages other than English were excluded. Findings from open-label studies that raised concerns relating to AE reports in patients were also examined. Studies were assessed for quality of reporting against the Consolidated Standards of Reporting Trials (CONSORT) checklist and for risk of bias against the Cochrane Collaboration risk-of-bias criteria.
RESULTS
37 RCTs met criteria for inclusion. Daily melatonin doses ranged from 0.15 mg to 12 mg. Subjects were monitored for up to 29 weeks, but most studies were of much shorter duration (4 weeks or less). The most frequently reported AEs were daytime sleepiness (1.66%), headache (0.74%), other sleep-related AEs (0.74%), dizziness (0.74%) and hypothermia (0.62%). Very few AEs considered to be serious or of clinical significance were reported. These included agitation, fatigue, mood swings, nightmares, skin irritation and palpitations. Most AEs either resolved spontaneously within a few days with no adjustment in melatonin, or immediately upon withdrawal of treatment. Melatonin was generally regarded as safe and well tolerated. Many studies predated publication of the CONSORT checklist and consequently did not conform closely to the guidelines. Similarly, only eight studies were judged 'good' overall with respect to the Cochrane risk-of-bias criteria. Of the remaining papers, 16 were considered 'fair' and 13 'poor' but publication of almost half of the papers preceded that of the earliest version of the guidelines.
CONCLUSION
Few, generally mild to moderate, AEs were associated with exogenous melatonin. No AEs that were life threatening or of major clinical significance were identified. The scarcity of evidence from long-term RCTs, however, limits the conclusions regarding the safety of continuous melatonin therapy over extended periods. There are insufficient robust data to allow a meaningful appraisal of concerns that melatonin may result in more clinically significant adverse effects in potentially at-risk populations. Future studies should be designed to comply with appropriate quality standards for RCTs, which most past studies have not.
Topics: Humans; Melatonin; Randomized Controlled Trials as Topic; Sleep; Sleep Wake Disorders
PubMed: 31722088
DOI: 10.1007/s40263-019-00680-w -
La Tunisie Medicale Oct 2019During the month of Ramadan, Muslim believers of adult-aged and healthy, restrain themselves from food consumption and liquid intake from dawn to sunset (fasting...
During the month of Ramadan, Muslim believers of adult-aged and healthy, restrain themselves from food consumption and liquid intake from dawn to sunset (fasting duration varying according to the geographical location and time of the year). Differently from other fasting regimens such as caloric restriction, Ramadan fasting is a unique kind of fasting, being total (i.e., absolute abstain from food as well as fluid), time-restricted, intermittent, and circadian (following the circadian rhythm and the human biological clock). As such, the fasting athletes could potentially suffer from hypohydration, altered sleep pattern and architecture, sleep disturbances, mood swings, immunological alterations, impaired psychomotor performance and overall perceived physical and perhaps, mental fatigue, among others. Hence, Muslim athletes who continue to train and compete during Ramadan faced many challenges. Research has shown that depending on the level of effort, Ramadan fasting could have diverse effects on physical performance; from no effect to marked effects. The present review aims to provide practical recommendations based on an updated, evidence-based synthesis of the existing scholarly literature and/or experts opinions on the topic and subsequently, some useful tips for athletes, coaches, medical and scientific support, and sports managers, in order to guide them on how to promote appropriate behavioral, social and psychological strategies to cope with the changes and potential constraints induced by the observance of Ramadan fasting. These recommendations should be adjusted and coped with, utilizing a holistic approach, rather than focusing on the single alterations/perturbations. Moreover, the implemented strategies should not be "one size fits it all" approach, but should rather take into account the variability among athletes and their specific needs (biological, psychological, cognitive-behavioral), and their social and living environment; as it is clearly more challenging when the individual is performing the Ramadan fasting in a predominantly non-Muslim majority country.
Topics: Athletes; Athletic Performance; Circadian Rhythm; Competitive Behavior; Exercise; Fasting; Humans; Islam; Sports
PubMed: 31691937
DOI: No ID Found -
Molecular Psychiatry Jan 2020Bipolar disorder (BD) is a chronic affective disorder with extreme mood swings that include mania or hypomania and depression. Though the exact mechanism of BD is...
Bipolar disorder (BD) is a chronic affective disorder with extreme mood swings that include mania or hypomania and depression. Though the exact mechanism of BD is unknown, neuroinflammation is one of the numerous investigated etiopathophysiological causes of BD. This article presents a systematic review of the data regarding brain inflammation evaluating microglia, astrocytes, cytokines, chemokines, adhesion molecules, and other inflammatory markers in postmortem BD brain samples. This systematic review was performed according to PRISMA recommendations, and relevant studies were identified by searching the PubMed/MEDLINE, PsycINFO, EMBASE, LILACS, IBECS, and Web of Science databases for peer-reviewed journal articles published by March 2019. Quality of included studies appraised using the QUADAS-2 tool. Among the 1814 articles included in the primary screening, 51 articles measured inflammatory markers in postmortem BD brain samples. A number of studies have shown evidence of inflammation in BD postmortem brain samples. However, an absolute statement cannot be concluded whether neuroinflammation is present in BD due to the large number of studies did not evaluate the presence of infiltrating peripheral immune cells in the central nervous system (CNS) parenchyma, cytokines levels, and microglia activation in the same postmortem brain sample. For example, out of 15 studies that evaluated microglia cells markers, 8 studies found no effect of BD on these cells. Similarly, 17 out of 51 studies evaluating astrocytes markers, 9 studies did not find any effect of BD on astrocyte cells, whereas 8 studies found a decrease and 2 studies presented both increase and decrease in different brain regions. In addition, multiple factors account for the variability across the studies, including postmortem interval, brain area studied, age at diagnosis, undergoing treatment, and others. Future analyses should rectify these potential sources of heterogeneity and reach a consensus regarding the inflammatory markers in postmortem BD brain samples.
Topics: Astrocytes; Autopsy; Biomarkers; Bipolar Disorder; Brain; Cytokines; Humans; Inflammation; Microglia; Mood Disorders; Neuroimmunomodulation
PubMed: 31249382
DOI: 10.1038/s41380-019-0448-7 -
Neuroscience and Biobehavioral Reviews Aug 2019Several studies have shown cerebellar abnormalities during depressive and manic states, although the specific cerebellar role in mood fluctuations remains poorly...
BACKGROUND
Several studies have shown cerebellar abnormalities during depressive and manic states, although the specific cerebellar role in mood fluctuations remains poorly defined. Therefore, the study of pathologies characterized by frequent mood swings, such as bipolar disorder, is of great interest to investigate the relationship between the cerebellum and mood alterations.
METHODS
A systematic literature search on the occurrence of mood disorders in patients with cerebellar pathologies (1 research strategy) and on the presence of cerebellar alterations in mood disorders (2 research strategy) was conducted using the PubMed electronic Internet database. For this systematic review all information was written based on the PRISMA-P statement.
RESULTS
The results of the 1 research strategy generated 9 articles, and in one of these, a direct correlation between cerebellar damage and the onset of mood disorder was reported. The 2 research strategy generated 14 articles that were grouped according to the patient's mood phase (manic or depressive) or diagnosis (bipolar I or bipolar II).
CONCLUSIONS
The present review suggests that the cerebellum should be considered a key structure involved in the regulation of mood.
Topics: Bipolar Disorder; Cerebellar Diseases; Humans
PubMed: 31195001
DOI: 10.1016/j.neubiorev.2019.06.008 -
Gait & Posture Mar 2019Heel lifts, placed inside footwear are recommended for the management of numerous musculoskeletal conditions. Despite the potential therapeutic benefit of heel lifts,...
BACKGROUND
Heel lifts, placed inside footwear are recommended for the management of numerous musculoskeletal conditions. Despite the potential therapeutic benefit of heel lifts, the mechanism(s) by which they exert their effects is unclear. The aim of this systematic review was to synthesise reported findings and summarise the effects of heel lifts on lower limb biomechanics and muscle function.
RESEARCH QUESTION
Do heel lifts affect lower limb biomechanics and muscle function during walking and running?
METHODS
Electronic databases (MEDLINE, EMBASE, CINAHL, SPORTDiscus, AMED) were searched from inception to April 2018. Studies were included if they (i) included participants without a limb length discrepancy or neurological condition, (ii) evaluated the effect of bilateral heel lifts that were removable (attached to the participants' foot (barefoot) or inserted inside footwear) or an existing feature of a shoe, and (iii) assessed lower limb biomechanics or muscle function during walking or running in asymptomatic or symptomatic participants.
RESULTS
A total of 23 studies (377 participants) were included. Study quality, assessed using a Modified Quality Index, ranged from 5 to 13 out of 15. A large number of biomechanical parameters were assessed, but few effects were statistically significant. The differences that were significant and had a large effect size are described below. In asymptomatic participants, heel lifts of 10 mm decreased duration of swing phase (standardised mean difference [SMD] = -1.3) and heel lifts of at least 5 cm decreased velocity (SMD = -0.93) during walking. In asymptomatic participants, heel lifts of 15 mm decreased maximum ankle dorsiflexion angle (SMD = -1.5) and heel lifts of 12 and 18 mm decreased gastrocnemius muscle tendon unit length (SMD = -0.96) during running. In participants with restricted ankle joint dorsiflexion, heel lifts of 6 and 9 mm increased medial gastrocnemius electromyography amplitude (SMD between 0.68 and 0.98) during walking. In participants with haemophilia, heel lifts of 9 mm increased ankle joint maximum range of motion (SMD = 1.6) during walking.
SIGNIFICANCE
Heel lifts affect specific lower limb biomechanical and muscle function parameters during walking and running. The clinical relevance and potential therapeutic benefits of these effects needs further investigation.
Topics: Biomechanical Phenomena; Foot Orthoses; Heel; Humans; Lower Extremity; Muscle, Skeletal; Range of Motion, Articular; Running; Walking
PubMed: 30870745
DOI: 10.1016/j.gaitpost.2019.01.023 -
The Cochrane Database of Systematic... Mar 2019This is an update of the original review published in the Cochrane Database of Systematic Reviews 2011, Issue 11, and updated in 2015, Issue 4.Chemotherapy has... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This is an update of the original review published in the Cochrane Database of Systematic Reviews 2011, Issue 11, and updated in 2015, Issue 4.Chemotherapy has significantly improved prognosis for women with malignant and some non-malignant conditions. This treatment, however, is associated with ovarian toxicity. The use of gonadotropin-releasing hormone (GnRH) analogues, both agonists and antagonists, may have a protective effect on the ovaries. The primary mechanism of action of GnRH analogues is to suppress the gonadotropin levels to simulate pre-pubertal hormonal milieu and subsequently prevent primordial follicles from maturation and therefore decrease the number of follicles that are more vulnerable to chemotherapy.
OBJECTIVES
To assess the efficacy and safety of GnRH analogues given before or in parallel to chemotherapy to prevent chemotherapy-related ovarian damage in premenopausal women with malignant or non-malignant conditions.
SEARCH METHODS
The search was run for the original review in July 2011, and for the first update in July 2014. For this update we searched the following databases in November 2018: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and the Chinese Biomedicine Database (CBM).
SELECTION CRITERIA
Randomised controlled trials (RCTs), in all languages, which examined the effect of GnRH analogues for chemotherapy-induced ovarian failure in premenopausal women, were eligible for inclusion in the review.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed trial quality using the Cochrane 'Risk of bias' tool. We analysed binary data using risk ratios (RRs) with 95% confidence intervals (CI) and for continuous data, we used the standardized mean difference (SMD) to combine trials. We applied the random-effects model in our analyses. We used the GRADE approach to produce a 'Summary of findings' table for our main outcomes of interest.
MAIN RESULTS
We included 12 RCTs involving 1369 women between the ages of 12 and 51.1 years. Participants were diagnosed with breast malignancy, ovarian malignancy, or Hodgkin's lymphoma, and most of them received alkylating, or platinum complexes, based chemotherapy. The included studies were funded by a university (n = 1), research centres (n = 4), and pharmaceutical companies (n = 1). Trials were at high or unclear risk of bias.Comparison 1: GnRH agonist plus chemotherapy versus chemotherapy aloneThe incidence of menstruation recovery or maintenance was 178 of 239 (74.5%) in the GnRH agonist group and 110 of 221 (50.0%) in the control group during a follow-up period no longer than 12 months (RR 1.60, 95% CI 1.14 to 2.24; 5 studies, 460 participants; I = 79%; low-certainty evidence), with an overall effect favouring treatment with GnRH agonist (P = 0.006). However, we observed no difference during a follow-up period longer than 12 months between these two groups (P = 0.24). In the GnRH agonist group, 326 of 447 participants had menstruation recovery or maintenance (72.9%) in comparison to the control group, in which 276 of 422 participants had menstruation recovery or maintenance (65.4%) during a follow-up period longer than 12 months (RR 1.08, 95% CI 0.95 to 1.22; 8 studies, 869 participants; I = 56%; low-certainty evidence).The incidence of premature ovarian failure was 43 of 401 (10.7%) in the GnRH agonist group and 96 of 379 (25.3%) in the control group (RR 0.44, 95% CI 0.31 to 0.61; 4 studies, 780 participants; I = 0%; moderate-certainty evidence), with an overall effect favouring treatment with GnRH agonist (P < 0.00001).The incidence of pregnancy was 32 of 356 (9.0%) in the GnRH agonist group and 22 of 347 (6.3%) in the control group (RR 1.59, 95% CI 0.93 to 2.70; 7 studies, 703 participants; I = 0%; low-certainty evidence), with no difference between groups (P = 0.09). However, we are cautious about this conclusion because there were insufficient data about whether the participants intended to become pregnant.The incidence of ovulation was 29 of 47 (61.7%) in the GnRH agonist group and 12 of 48 (25.0%) in the control group (RR 2.47, 95% CI 1.43 to 4.26; 2 studies, 95 participants; I = 0%; low-certainty evidence) with an overall effect favouring treatment with GnRH (P = 0.001).The most common adverse effects of GnRH analogues included hot flushes, vaginal dryness, urogenital symptoms, and mood swings. The pooled analysis of safety data showed no difference in adverse effects between GnRH agonist group and control group.Comparison 2: GnRH agonist-antagonist cotreatment plus chemotherapy versus chemotherapy aloneOnly one RCT discussed GnRH agonist-antagonist cotreatment. The limited evidence showed the incidence of menstruation recovery or maintenance was 20 of 25 (80%) in both cotreatment group and control group during a 12-month follow-up period (RR 1.00, 95% CI 0.76 to 1.32; 50 participants; very low-certainty evidence), with no difference between groups (P = 1.00). In the cotreatment group, 13 of 25 participants had menstruation recovery or maintenance (52.0%) in comparison to the control group, in which 14 of 25 participants had menstruation recovery or maintenance (56.0%) during a follow-up period longer than 12 months (RR 0.93, 95% CI 0.56 to 1.55; 50 participants; very low-certainty evidence), with no difference between groups (P = 0.78). The incidence of pregnancy was 1 of 25 (4.0%) in the cotreatment group and 0 of 25 (0%) in the control group (RR 3.00, 95% CI 0.13 to 70.30; 50 participants; very low-certainty evidence), with no difference between groups (P = 0.49).
AUTHORS' CONCLUSIONS
GnRH agonist appears to be effective in protecting the ovaries during chemotherapy, in terms of maintenance and resumption of menstruation, treatment-related premature ovarian failure and ovulation. Evidence for protection of fertility was insufficient and needs further investigation. Evidence was also insufficient to assess the effect of GnRH agonist and GnRH antagonist cotreatment on ovarian protection against chemotherapy. The included studies differed in some important aspects of design, and most of these studies had no age-determined subgroup analysis. Large and well-designed RCTs with longer follow-up duration should be conducted to clarify the effects of GnRH analogues in preventing chemotherapy-induced ovarian failure, especially on different age groups or different chemotherapy regimens. Furthermore, studies should address the effects on pregnancy rates and anti-tumour therapy.
Topics: Administration, Intranasal; Adolescent; Adult; Antineoplastic Agents; Child; Female; Gonadotropin-Releasing Hormone; Humans; Injections, Intramuscular; Injections, Subcutaneous; Menstruation; Middle Aged; Ovulation; Pregnancy; Pregnancy Rate; Premenopause; Primary Ovarian Insufficiency; Randomized Controlled Trials as Topic; Recovery of Function; Young Adult
PubMed: 30827035
DOI: 10.1002/14651858.CD008018.pub3 -
Nephrology, Dialysis, Transplantation :... Sep 2017Decision-making regarding immunosuppression after transplantation relies on robust evidence on the benefits and harms of available drugs. We aimed to evaluate the... (Review)
Review
BACKGROUND
Decision-making regarding immunosuppression after transplantation relies on robust evidence on the benefits and harms of available drugs. We aimed to evaluate the reporting of adverse events (AEs) in trials of maintenance immunosuppression in kidney transplantation.
METHODS
We conducted a systematic review of published randomized controlled trials of maintenance immunosuppression following kidney transplantation in the Cochrane Kidney and Transplant Register (January 2003-December 2015). Appraisal against the 23-item harms extension of the Consolidated Standards of Reporting Trials statement was conducted.
RESULTS
Of 233 trials, 163 (69%) reported at least one AE. Only 17 (10%) provided definitions or justified the AEs, 13 (8%) described methods and 27 (17%) measured severity. Forty AE types were reported, with gastrointestinal being the most common [116 (71%)]. The frequency of reporting did not reflect known drug side-effect profiles. For example, of 90 calcineurin inhibitor trials, only 22% reported tremors, 3% paresthesia and none anxiety, aggression or mood swings. Trials that reported at least one adverse effect were more likely to be industry funded {adjusted odds ratio [OR] 7.6 [95% confidence interval (CI) 3.4-17.1]}, multicenter [OR 5.9 (95% CI 1.7-18.7)] and with follow-up time <24 months [OR 3.7 (95% CI 1.4-10.2)].
CONCLUSIONS
AEs in kidney transplant immunosuppression trials appear to be selectively reported and may be unreliable for clinical decisions. Adherence to the Consolidated Standards of Reporting Trials harms extension should be mandatory to ensure transparent reporting of AEs that are important to patients and clinicians.
Topics: Drug-Related Side Effects and Adverse Reactions; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Maintenance Chemotherapy; Patient Outcome Assessment
PubMed: 29059401
DOI: 10.1093/ndt/gfx216