-
Dental and Medical Problems 2023Laser protocols for the treatment of dentin hypersensitivity (DH) have not yet been studied systematically. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Laser protocols for the treatment of dentin hypersensitivity (DH) have not yet been studied systematically.
OBJECTIVES
The present study aimed to review clinical trials on the treatment of DH with laser therapy through a systematic review and meta-analysis.
MATERIAL AND METHODS
The search of electronic databases resulted in 562 publications up to April 2020. The inclusion criteria were studies carried out on humans and reporting on the treatment of DH with laser therapy. Case reports, literature reviews and systematic reviews were excluded. Selected by abstract, potentially eligible papers were read in full (n = 160). Independent examiners performed data extraction and the assessment of the risk of bias.
RESULTS
A total of 34 studies were included in the analysis, and 11 in the quantitative analysis. It was observed that most studies followed up patients for a maximum of 6 months (55%). Through the meta-analysis, we observed statistically significant differences between the average pain before and after 3 months of treatment with highand low-power lasers. However, through indirect comparisons, it was observed that the high-power laser showed a greater tendency to reduce the pain levels after 3 months of treatment as compared to the low-power laser, but without a statistically significant difference.
CONCLUSIONS
It was possible to conclude that regardless of the type of laser used in the treatment of DH, this treatment is an effective option for the control of pain symptoms. However, it was not possible to establish a defined treatment protocol, since the evaluation methods are very different from each other. Text for Rewiew and clinical cases.
Topics: Humans; Dentin Sensitivity; Laser Therapy; Low-Level Light Therapy; Treatment Outcome; Lasers
PubMed: 37023343
DOI: 10.17219/dmp/151482 -
Environment International Aug 2021Mental health is an important public health issue globally. A potential link between heat exposure and mental health outcomes has been recognised in the scientific... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mental health is an important public health issue globally. A potential link between heat exposure and mental health outcomes has been recognised in the scientific literature; however, the associations between heat exposure (both high ambient temperatures and heatwaves) and mental health-related mortality and morbidity vary between studies and locations.
OBJECTIVE
To fill gaps in knowledge, this systematic review aims to summarize the epidemiological evidence and investigate the quantitative effects of high ambient temperatures and heatwaves on mental health-related mortality and morbidity outcomes, while exploring sources of heterogeneity.
METHODS
A systematic search of peer-reviewed epidemiological studies on heat exposure and mental health outcomes published between January 1990 and November 2020 was conducted using five databases (PubMed, Embase, Scopus, Web of Science and PsycINFO). We included studies that examined the association between high ambient temperatures and/or heatwaves and mental health-related mortality and morbidity (e.g. hospital admissions and emergency department visits) in the general population. A range of mental health conditions were defined using ICD-10 classifications. We performed random effects meta-analysis to summarize the relative risks (RRs) in mental health outcomes per 1 °C increase in temperature, and under different heatwaves definitions. We further evaluated whether variables such as age, sex, socioeconomic status, and climate zone may explain the observed heterogeneity.
RESULTS
The keyword search yielded 4560 citations from which we identified 53 high temperatures/heatwaves studies that comprised over 1.7 million mental health-related mortality and 1.9 million morbidity cases in total. Our findings suggest associations between heat exposures and a range of mental health-related outcomes. Regarding high temperatures, our meta-analysis of study findings showed that for each 1 °C increase in temperature, the mental health-related mortality and morbidity increased with a RR of 1.022 (95%CI: 1.015-1.029) and 1.009 (95%CI: 1.007-1.015), respectively. The greatest mortality risk was attributed to substance-related mental disorders (RR, 1.046; 95%CI: 0.991-1.101), followed by organic mental disorders (RR, 1.033; 95%CI: 1.020-1.046). A 1 °C temperature rise was also associated with a significant increase in morbidity such as mood disorders, organic mental disorders, schizophrenia, neurotic and anxiety disorders. Findings suggest evidence of vulnerability for populations living in tropical and subtropical climate zones, and for people aged more than 65 years. There were significant moderate and high heterogeneities between effect estimates in overall mortality and morbidity categories, respectively. Lower heterogeneity was noted in some subgroups. The magnitude of the effect estimates for heatwaves varied depending on definitions used. The highest effect estimates for mental health-related morbidity was observed when heatwaves were defined as "mean temperature ≥90th percentile for ≥3 days" (RR, 1.753; 95%CI: 0.567-5.421), and a significant effect was also observed when the definition was "mean temperature ≥95th percentile for ≥3 days", with a RR of 1.064 (95%CI: 1.006-1.123).
CONCLUSIONS
Our findings support the hypothesis of a positive association between elevated ambient temperatures and/or heatwaves and adverse mental health outcomes. This problem will likely increase with a warming climate, especially in the context of climate change. Further high-quality studies are needed to identify modifying factors of heat impacts.
Topics: Climate Change; Hot Temperature; Humans; Morbidity; Outcome Assessment, Health Care; Temperature
PubMed: 33799230
DOI: 10.1016/j.envint.2021.106533 -
International Journal of Sports... 2022Quadriceps strength and mass deficits are common after anterior cruciate ligament (ACL) reconstruction. Postoperatively, heavy load resistance training can have...
BACKGROUND
Quadriceps strength and mass deficits are common after anterior cruciate ligament (ACL) reconstruction. Postoperatively, heavy load resistance training can have detrimental effects on knee joint pain and ACL graft laxity. Therefore, low-load blood flow restriction (LL-BFR) training has been suggested as an alternative to traditional strength rehabilitation.
PURPOSE
The present systematic review aimed to investigate the effect of LL-BFR training on quadriceps strength, quadriceps mass, knee joint pain, and ACL graft laxity after ACL reconstruction compared to non-BFR training.
STUDY DESIGN
Systematic review.
METHODS
A systematic literature search of PubMed, EMBASE.com, Cochrane Library/Wiley, CINAHL/Ebsco and Web of Science/Clarivate Analytics was performed on 19 February 2021. Studies were included if they compared LL-BFR and non-BFR training after ACL reconstruction with pre- and post-intervention quadriceps strength, quadriceps mass, knee joint pain or ACL graft laxity measurement. Systematic reviews, editorials, case reports and studies not published in a scientific peer reviewed journal were excluded. The risk of bias of randomized studies was assessed with the use of the Cochrane Risk of Bias Tool.
RESULTS
A total of six randomized controlled trials were included. Random sequence generation and allocation concealment was defined as high risk in two of the six studies. In all studies blinding of participants and personnel was unclear or could not be performed. The included studies used different LL-BFR and non-BFR protocols with heterogeneous outcome measurements. Therefore, a qualitative analysis was performed. Two of the six studies assessed quadriceps strength and demonstrated significant greater quadriceps strength after LL-BFR compared to non-BFR training. Quadriceps mass was evaluated in four studies. Two studies observed significant greater quadriceps mass after LL-BFR compared to non-BFR training, while two studies observed no significant difference in quadriceps mass. Knee joint pain was assessed in three studies with significantly less knee joint pain after LL-BFR compared to non-BFR training. Two studies evaluated ACL graft laxity and observed no significant difference in ACL graft laxity between LL-BFR and non-BFR training.
CONCLUSION
The results of this systematic review indicate that LL-BFR training after ACL reconstruction may be beneficial on quadriceps strength, quadriceps mass, and knee joint pain compared to non-BFR training with non-detrimental effects on ACL graft laxity. However, more randomized controlled trials with standardized intervention protocols and outcome measurements are needed to add evidence on the clinical value of LL-BFR training.
LEVEL OF EVIDENCE
2a.
PubMed: 35391871
DOI: 10.26603/001c.33151 -
Journal of Cachexia, Sarcopenia and... Apr 2023Anorexia/appetite loss in older subjects is frequently underrecognized in clinical practice, which may reflect deficient understanding of clinical sequelae. Therefore,... (Review)
Review
Anorexia/appetite loss in older subjects is frequently underrecognized in clinical practice, which may reflect deficient understanding of clinical sequelae. Therefore, we performed a systematic literature review to assess the morbidity and mortality burden of anorexia/appetite loss in older populations. Following PRISMA guidelines, searches were run (1 January 2011 to 31 July 2021) in PubMed, Embase® and Cochrane databases to identify English language studies of adults aged ≥ 65 years with anorexia/appetite loss. Two independent reviewers screened titles, abstracts and full text of identified records against pre-defined inclusion/exclusion criteria. Population demographics were extracted alongside risk of malnutrition, mortality and other outcomes of interest. Of 146 studies that underwent full-text review, 58 met eligibility criteria. Most studies were from Europe (n = 34; 58.6%) or Asia (n = 16; 27.6%), with few (n = 3; 5.2%) from the United States. Most were conducted in a community setting (n = 35; 60.3%), 12 (20.7%) were inpatient based (hospital/rehabilitation ward), 5 (8.6%) were in institutional care (nursing/care homes) and 7 (12.1%) were in other (mixed or outpatient) settings. One study reported results separately for community and institutional settings and is counted in both settings. Simplified Nutritional Appetite Questionnaire (SNAQ Simplified, n = 14) and subject-reported appetite questions (n = 11) were the most common methods used to assess anorexia/appetite loss, but substantial variability in assessment tools was observed across studies. The most commonly reported outcomes were malnutrition and mortality. Malnutrition was assessed in 15 studies, with all reporting a significantly higher risk of malnutrition in older individuals with anorexia/appetite loss (vs. without) regardless of country or healthcare setting (community n = 9, inpatient n = 2, institutional n = 3, other n = 2). Of 18 longitudinal studies that assessed mortality risk, 17 (94%) reported a significant association between anorexia/appetite loss and mortality regardless of either healthcare setting (community n = 9, inpatient n = 6, institutional n = 2) or method used to assess anorexia/appetite loss. This association between anorexia/appetite loss and mortality was observed in cohorts with cancer (as expected) but was also observed in older populations with a range of comorbid conditions other than cancer. Overall, our findings demonstrate that, among individuals aged ≥ 65 years, anorexia/appetite loss is associated with increased risk of malnutrition, mortality and other negative outcomes across community, care home and hospital settings. Such associations warrant efforts to improve and standardize screening, detection, assessment and management of anorexia/appetite loss in older adults.
Topics: Humans; Aged; Anorexia; Appetite; Malnutrition; Hospitals; Europe
PubMed: 36807868
DOI: 10.1002/jcsm.13186 -
Nutrients Sep 2022Obesity is one of the most dangerous epidemics of the 21st century. In 2019, the COVID-19 pandemic began and caused many deaths among patients with obesity with and... (Review)
Review
Obesity is one of the most dangerous epidemics of the 21st century. In 2019, the COVID-19 pandemic began and caused many deaths among patients with obesity with and without complications. Simultaneously, the lockdown related to the COVID-19 pandemic caused a host of emotional problems including anxiety, depression, and sleep disturbances. Many people began to cope with their emotions by increasing food (emotional eating) and alcohol consumption and in combination with decreased physical activity, promoted the development of overweight and obesity. Emotional eating, also known as stress eating, is defined as the propensity to eat in response to positive and negative emotions and not physical need. It should be noted that emotional eating may be the first step in the development of binge eating disorder and its extreme subtypes such as food addiction. Interestingly in some post-bariatric surgery patients, an increased frequency of addictive disorders has been observed, for example food addiction replaced by alcohol addiction called: "cross addiction" or "addiction transfer". This data indicates that obesity should be treated as a psychosomatic disease, in the development of which external factors causing the formation of negative emotions may play a significant role. Currently, one of these factors is the COVID-19 pandemic. This manuscript discusses the relationships between the COVID-19 pandemic and development of emotional eating as well as potential implications of the viral pandemic on the obesity pandemic, and the need to change the approach to the treatment of obesity in the future.
Topics: COVID-19; Communicable Disease Control; Emotions; Feeding Behavior; Feeding and Eating Disorders; Humans; Mental Health; Obesity; Pandemics
PubMed: 36235642
DOI: 10.3390/nu14193989 -
JBRA Assisted Reproduction Jan 2022This study aimed to assess the effect of endometrioma surgery on ovarian reserve by measuring anti-Müllerian hormone (AMH) levels. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to assess the effect of endometrioma surgery on ovarian reserve by measuring anti-Müllerian hormone (AMH) levels.
METHODS
This systematic review and meta-analysis included observational studies and randomized clinical trials published in English referenced in MEDLINE, SCOPUS and Cochrane (1982-2019). We included studies that reported AMH levels in the pre and post-operative period of patients undergoing laparoscopic surgery for endometrioma. Preoperative AMH was defined as the baseline AMH; short term AMH was measured no later than a month after surgery; medium term AMH was measured between one and six months after surgery; and long-term AMH was measured six or more months after surgery.
RESULTS
Thirty-six studies met the inclusion criteria. A significant decrease was observed in short, medium and long-term post-operative AMH levels when compared with baseline AMH. However, there were no differences between short and long-term post-operative AMH levels, suggesting a non-significant recovery after one year of follow-up. A significant decrease in post-operative AMH was observed in bilateral endometriomas compared with unilateral cases. In addition, patients with endometriomas presented a significant decline in post-operative AMH compared with patients with other benign ovarian conditions. The decrease in post-operative AMH was significantly greater in bilateral cystectomy when compared with vaporization with bipolar energy or laser. We also observed a greater decrease in post-operative AMH with bipolar energy hemostasis compared with suture and hemostatic agents. These results should be taken with caution due to the high heterogeneity of the studies analyzed.
CONCLUSIONS
Endometrioma surgery has a deleterious effect on short, medium, and long-term post-operative AMH levels. Bilateral endometriomas and endometriomas greater than 7 cm have been associated with greater decreases in AMH. The mechanical resection of healthy tissue and the inflammatory damage on the ovarian cortex might explain the diminishing of ovarian reserve.
Topics: Anti-Mullerian Hormone; Endometriosis; Female; Humans; Laparoscopy; Observational Studies as Topic; Ovarian Diseases; Ovarian Reserve
PubMed: 34755503
DOI: 10.5935/1518-0557.20210060 -
Diabetologia Feb 2022The term prediabetes is used for individuals who have impaired glucose metabolism whose glucose or HbA levels are not yet high enough to be diagnosed as diabetes.... (Meta-Analysis)
Meta-Analysis
AIMS/HYPOTHESIS
The term prediabetes is used for individuals who have impaired glucose metabolism whose glucose or HbA levels are not yet high enough to be diagnosed as diabetes. Prediabetes may already be associated with an increased risk of chronic 'diabetes-related' complications. This umbrella review aimed to provide a systematic overview of the available evidence from meta-analyses of prospective observational studies on the associations between prediabetes and incident diabetes-related complications in adults and to evaluate their strength and certainty.
METHODS
For this umbrella review, systematic reviews with meta-analyses reporting summary risk estimates for the associations between prediabetes (based on fasting or 2 h postload glucose or on HbA) and incidence of diabetes-related complications, comorbidities and mortality risk were included. PubMed, Web of Science, the Cochrane Library and Epistemonikos were searched up to 17 June 2021. Summary risk estimates were recalculated using a random effects model. The certainty of evidence was evaluated by applying the GRADE tool. This study is registered with PROSPERO, CRD42020153227.
RESULTS
Ninety-five meta-analyses from 16 publications were identified. In the general population, prediabetes was associated with a 6-101% increased risk for all-cause mortality and the incidence of cardiovascular outcomes, CHD, stroke, heart failure, atrial fibrillation and chronic kidney disease, as well as total cancer, total liver cancer, hepatocellular carcinoma, breast cancer and all-cause dementia with moderate certainty of evidence. No associations between prediabetes and incident depressive symptoms and cognitive impairment were observed (with low or very low certainty of evidence). The association with all-cause mortality was stronger for prediabetes defined by impaired glucose tolerance than for prediabetes defined by HbA.
CONCLUSIONS/INTERPRETATION
Prediabetes was positively associated with risk of all-cause mortality and the incidence of cardiovascular outcomes, CHD, stroke, chronic kidney disease, cancer and dementia. Further high-quality studies, particularly on HbA-defined prediabetes and other relevant health outcomes (e. g. neuropathy) are required to support the evidence.
Topics: Cardiovascular Diseases; Cause of Death; Dementia; Diabetes Complications; Glucose Intolerance; Humans; Kidney Diseases; Neoplasms; Prediabetic State; Risk Factors
PubMed: 34718834
DOI: 10.1007/s00125-021-05592-3 -
The Cochrane Database of Systematic... Jul 2022Accurate rapid diagnostic tests for SARS-CoV-2 infection would be a useful tool to help manage the COVID-19 pandemic. Testing strategies that use rapid antigen tests to... (Review)
Review
BACKGROUND
Accurate rapid diagnostic tests for SARS-CoV-2 infection would be a useful tool to help manage the COVID-19 pandemic. Testing strategies that use rapid antigen tests to detect current infection have the potential to increase access to testing, speed detection of infection, and inform clinical and public health management decisions to reduce transmission. This is the second update of this review, which was first published in 2020.
OBJECTIVES
To assess the diagnostic accuracy of rapid, point-of-care antigen tests for diagnosis of SARS-CoV-2 infection. We consider accuracy separately in symptomatic and asymptomatic population groups. Sources of heterogeneity investigated included setting and indication for testing, assay format, sample site, viral load, age, timing of test, and study design.
SEARCH METHODS
We searched the COVID-19 Open Access Project living evidence database from the University of Bern (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) on 08 March 2021. We included independent evaluations from national reference laboratories, FIND and the Diagnostics Global Health website. We did not apply language restrictions.
SELECTION CRITERIA
We included studies of people with either suspected SARS-CoV-2 infection, known SARS-CoV-2 infection or known absence of infection, or those who were being screened for infection. We included test accuracy studies of any design that evaluated commercially produced, rapid antigen tests. We included evaluations of single applications of a test (one test result reported per person) and evaluations of serial testing (repeated antigen testing over time). Reference standards for presence or absence of infection were any laboratory-based molecular test (primarily reverse transcription polymerase chain reaction (RT-PCR)) or pre-pandemic respiratory sample.
DATA COLLECTION AND ANALYSIS
We used standard screening procedures with three people. Two people independently carried out quality assessment (using the QUADAS-2 tool) and extracted study results. Other study characteristics were extracted by one review author and checked by a second. We present sensitivity and specificity with 95% confidence intervals (CIs) for each test, and pooled data using the bivariate model. We investigated heterogeneity by including indicator variables in the random-effects logistic regression models. We tabulated results by test manufacturer and compliance with manufacturer instructions for use and according to symptom status.
MAIN RESULTS
We included 155 study cohorts (described in 166 study reports, with 24 as preprints). The main results relate to 152 evaluations of single test applications including 100,462 unique samples (16,822 with confirmed SARS-CoV-2). Studies were mainly conducted in Europe (101/152, 66%), and evaluated 49 different commercial antigen assays. Only 23 studies compared two or more brands of test. Risk of bias was high because of participant selection (40, 26%); interpretation of the index test (6, 4%); weaknesses in the reference standard for absence of infection (119, 78%); and participant flow and timing 41 (27%). Characteristics of participants (45, 30%) and index test delivery (47, 31%) differed from the way in which and in whom the test was intended to be used. Nearly all studies (91%) used a single RT-PCR result to define presence or absence of infection. The 152 studies of single test applications reported 228 evaluations of antigen tests. Estimates of sensitivity varied considerably between studies, with consistently high specificities. Average sensitivity was higher in symptomatic (73.0%, 95% CI 69.3% to 76.4%; 109 evaluations; 50,574 samples, 11,662 cases) compared to asymptomatic participants (54.7%, 95% CI 47.7% to 61.6%; 50 evaluations; 40,956 samples, 2641 cases). Average sensitivity was higher in the first week after symptom onset (80.9%, 95% CI 76.9% to 84.4%; 30 evaluations, 2408 cases) than in the second week of symptoms (53.8%, 95% CI 48.0% to 59.6%; 40 evaluations, 1119 cases). For those who were asymptomatic at the time of testing, sensitivity was higher when an epidemiological exposure to SARS-CoV-2 was suspected (64.3%, 95% CI 54.6% to 73.0%; 16 evaluations; 7677 samples, 703 cases) compared to where COVID-19 testing was reported to be widely available to anyone on presentation for testing (49.6%, 95% CI 42.1% to 57.1%; 26 evaluations; 31,904 samples, 1758 cases). Average specificity was similarly high for symptomatic (99.1%) or asymptomatic (99.7%) participants. We observed a steady decline in summary sensitivities as measures of sample viral load decreased. Sensitivity varied between brands. When tests were used according to manufacturer instructions, average sensitivities by brand ranged from 34.3% to 91.3% in symptomatic participants (20 assays with eligible data) and from 28.6% to 77.8% for asymptomatic participants (12 assays). For symptomatic participants, summary sensitivities for seven assays were 80% or more (meeting acceptable criteria set by the World Health Organization (WHO)). The WHO acceptable performance criterion of 97% specificity was met by 17 of 20 assays when tests were used according to manufacturer instructions, 12 of which demonstrated specificities above 99%. For asymptomatic participants the sensitivities of only two assays approached but did not meet WHO acceptable performance standards in one study each; specificities for asymptomatic participants were in a similar range to those observed for symptomatic people. At 5% prevalence using summary data in symptomatic people during the first week after symptom onset, the positive predictive value (PPV) of 89% means that 1 in 10 positive results will be a false positive, and around 1 in 5 cases will be missed. At 0.5% prevalence using summary data for asymptomatic people, where testing was widely available and where epidemiological exposure to COVID-19 was suspected, resulting PPVs would be 38% to 52%, meaning that between 2 in 5 and 1 in 2 positive results will be false positives, and between 1 in 2 and 1 in 3 cases will be missed.
AUTHORS' CONCLUSIONS
Antigen tests vary in sensitivity. In people with signs and symptoms of COVID-19, sensitivities are highest in the first week of illness when viral loads are higher. Assays that meet appropriate performance standards, such as those set by WHO, could replace laboratory-based RT-PCR when immediate decisions about patient care must be made, or where RT-PCR cannot be delivered in a timely manner. However, they are more suitable for use as triage to RT-PCR testing. The variable sensitivity of antigen tests means that people who test negative may still be infected. Many commercially available rapid antigen tests have not been evaluated in independent validation studies. Evidence for testing in asymptomatic cohorts has increased, however sensitivity is lower and there is a paucity of evidence for testing in different settings. Questions remain about the use of antigen test-based repeat testing strategies. Further research is needed to evaluate the effectiveness of screening programmes at reducing transmission of infection, whether mass screening or targeted approaches including schools, healthcare setting and traveller screening.
Topics: COVID-19; COVID-19 Testing; Humans; Pandemics; Point-of-Care Systems; SARS-CoV-2; Sensitivity and Specificity
PubMed: 35866452
DOI: 10.1002/14651858.CD013705.pub3 -
The Cochrane Database of Systematic... Mar 2020Approximately 80% of breast cancers amongst premenopausal women are hormone receptor-positive. Adjuvant endocrine therapy is an integral component of care for hormone... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Approximately 80% of breast cancers amongst premenopausal women are hormone receptor-positive. Adjuvant endocrine therapy is an integral component of care for hormone receptor-positive breast cancer and in premenopausal women includes oestrogen receptor blockade with tamoxifen, temporary suppression of ovarian oestrogen synthesis by luteinising hormone releasing hormone (LHRH) agonists, and permanent interruption of ovarian oestrogen synthesis with oophorectomy or radiotherapy. Recent international consensus statements recommend single-agent tamoxifen or aromatase inhibitors with ovarian function suppression (OFS) as the current standard adjuvant endocrine therapy for premenopausal women (often preceded by chemotherapy). This review examined the role of adding OFS to another treatment (i.e. chemotherapy, endocrine therapy, or both) or comparing OFS to no further adjuvant treatment.
OBJECTIVES
To assess effects of OFS for treatment of premenopausal women with hormone receptor-positive early breast cancer.
SEARCH METHODS
For this review update, we searched the Specialised Register of the Cochrane Breast Cancer Group, MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 8), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov on 26 September 2019. We screened the reference lists of related articles, contacted trial authors, and applied no language restrictions.
SELECTION CRITERIA
We included all randomised trials assessing any method of OFS, that is, oophorectomy, radiation-induced ovarian ablation, or LHRH agonists, as adjuvant treatment for premenopausal women with early-stage breast cancer. We included studies that compared (1) OFS versus observation, (2) OFS + chemotherapy versus chemotherapy, (3) OFS + tamoxifen versus tamoxifen, and (4) OFS + chemotherapy + tamoxifen versus chemotherapy + tamoxifen.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data and assessed risk of bias and certainty of evidence using the GRADE approach. Hazard ratios (HRs) were derived for time-to-event outcomes, and meta-analysis was performed using a fixed-effect model. The primary outcome measures were overall survival (OS) and disease-free survival (DFS). Toxicity, contralateral breast cancer, and second malignancy were represented as risk ratios (RRs), and quality of life data were extracted when provided.
MAIN RESULTS
This review update included 15 studies involving 11,538 premenopausal women with hormone receptor-positive early breast cancer; these studies were conducted from 1978 to 2014. Some of these treatments are not current standard of care, and early studies did not assess HER2 receptor status. Studies tested OFS versus observation (one study), OFS plus chemotherapy versus chemotherapy (six studies), OFS plus tamoxifen versus tamoxifen (six studies), and OFS plus chemotherapy and tamoxifen versus chemotherapy and tamoxifen (two studies). Of those studies that reported the chemotherapy regimen, an estimated 72% of women received an anthracycline. The results described below relate to the overall comparison of OFS versus no OFS. High-certainty evidence shows that adding OFS to treatment resulted in a reduction in mortality (hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.78 to 0.94; 11 studies; 10,374 women; 1933 reported events). This treatment effect was seen when OFS was added to observation, to tamoxifen, or to chemotherapy and tamoxifen. The effect on mortality was not observed when OFS was added to chemotherapy without tamoxifen therapy (HR 0.95, 95% CI 0.82 to 1.09; 5 studies; 3087 women; median follow-up: range 7.7 to 12.1 years). The addition of OFS resulted in improved DFS (HR 0.83, 95% CI 0.77 to 0.90; 10 studies; 8899 women; 2757 reported events; high-certainty evidence). The DFS treatment effect persisted when OFS was added to observation, to tamoxifen, and to chemotherapy and tamoxifen. The effect on DFS was reduced when OFS was added to chemotherapy without tamoxifen therapy (HR 0.90, 95% CI 0.79 to 1.01; 5 studies; 2450 women). Heterogeneity was low to moderate across studies for DFS and OS (respectively). Evidence suggests that adding OFS slightly increases the incidence of hot flushes (grade 3/4 or any grade; risk ratio (RR) 1.60, 95% CI 1.41 to 1.82; 6 studies; 5581 women; low-certainty evidence, as this may have been under-reported in these studies). Two other studies that could not be included in the meta-analysis reported a higher number of hot flushes in the OFS group than in the no-OFS group. Seven studies involving 5354 women collected information related to mood; however this information was reported as grade 3 or 4 depression, anxiety, or neuropsychiatric symptoms, or symptoms were reported without the grade. Two studies reported an increase in depression, anxiety, and neuropsychiatric symptoms in the OFS group compared to the no-OFS group, and five studies indicated an increase in anxiety in both treatment groups (but no difference between groups) or no difference overall in symptoms over time or between treatment groups. A single study reported bone health as osteoporosis (defined as T score < -2.5); this limited evidence suggests that OFS increases the risk of osteoporosis compared to no-OFS at median follow-up of 5.6 years (RR 1.16, 95% CI 1.10 to 28.82; 2011 women; low-certainty evidence). Adding OFS to treatment likely reduces the risk of contralateral breast cancer (HR 0.75, 95% CI 0.57 to 0.97; 9 studies; 9138 women; moderate-certainty evidence). Quality of life was assessed in five studies; four studies used validated tools, and the fifth study provided no information on how data were collected. Two studies reported worse quality of life indicators (i.e. vaginal dryness, day and night sweats) for women receiving OFS compared to those in the no-OFS group. The other two studies indicated worsening of symptoms (e.g. vasomotor, gynaecological, vaginal dryness, decline in sexual interest, bone and joint pain, weight gain); however these side effects were reported in both OFS and no-OFS groups. The study that did not use a validated quality of life tool described no considerable differences between groups.
AUTHORS' CONCLUSIONS
This review found evidence that supports adding OFS for premenopausal women with early, hormone receptor-positive breast cancers. The benefit of OFS persisted when compared to observation, and when added to endocrine therapy (tamoxifen) or chemotherapy and endocrine therapy (tamoxifen). The decision to use OFS may depend on the overall risk assessment based on tumour and patient characteristics, and may follow consideration of all side effects that occur with the addition of OFS.
Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemotherapy, Adjuvant; Female; Gonadotropin-Releasing Hormone; Humans; Premenopause; Randomized Controlled Trials as Topic; Survival Analysis; Tamoxifen; Treatment Outcome
PubMed: 32141074
DOI: 10.1002/14651858.CD013538 -
The Cochrane Database of Systematic... Jun 2021Miscarriage, defined as the spontaneous loss of a pregnancy before 24 weeks' gestation, is common with approximately 25% of women experiencing a miscarriage in their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Miscarriage, defined as the spontaneous loss of a pregnancy before 24 weeks' gestation, is common with approximately 25% of women experiencing a miscarriage in their lifetime. An estimated 15% of pregnancies end in miscarriage. Miscarriage can lead to serious morbidity, including haemorrhage, infection, and even death, particularly in settings without adequate healthcare provision. Early miscarriages occur during the first 14 weeks of pregnancy, and can be managed expectantly, medically or surgically. However, there is uncertainty about the relative effectiveness and risks of each option.
OBJECTIVES
To estimate the relative effectiveness and safety profiles for the different management methods for early miscarriage, and to provide rankings of the available methods according to their effectiveness, safety, and side-effect profile using a network meta-analysis.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth's Trials Register (9 February 2021), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (12 February 2021), and reference lists of retrieved studies.
SELECTION CRITERIA
We included all randomised controlled trials assessing the effectiveness or safety of methods for miscarriage management. Early miscarriage was defined as less than or equal to 14 weeks of gestation, and included missed and incomplete miscarriage. Management of late miscarriages after 14 weeks of gestation (often referred to as intrauterine fetal deaths) was not eligible for inclusion in the review. Cluster- and quasi-randomised trials were eligible for inclusion. Randomised trials published only as abstracts were eligible if sufficient information could be retrieved. We excluded non-randomised trials.
DATA COLLECTION AND ANALYSIS
At least three review authors independently assessed the trials for inclusion and risk of bias, extracted data and checked them for accuracy. We estimated the relative effects and rankings for the primary outcomes of complete miscarriage and composite outcome of death or serious complications. The certainty of evidence was assessed using GRADE. Relative effects for the primary outcomes are reported subgrouped by the type of miscarriage (incomplete and missed miscarriage). We also performed pairwise meta-analyses and network meta-analysis to determine the relative effects and rankings of all available methods.
MAIN RESULTS
Our network meta-analysis included 78 randomised trials involving 17,795 women from 37 countries. Most trials (71/78) were conducted in hospital settings and included women with missed or incomplete miscarriage. Across 158 trial arms, the following methods were used: 51 trial arms (33%) used misoprostol; 50 (32%) used suction aspiration; 26 (16%) used expectant management or placebo; 17 (11%) used dilatation and curettage; 11 (6%) used mifepristone plus misoprostol; and three (2%) used suction aspiration plus cervical preparation. Of these 78 studies, 71 (90%) contributed data in a usable form for meta-analysis. Complete miscarriage Based on the relative effects from the network meta-analysis of 59 trials (12,591 women), we found that five methods may be more effective than expectant management or placebo for achieving a complete miscarriage: · suction aspiration after cervical preparation (risk ratio (RR) 2.12, 95% confidence interval (CI) 1.41 to 3.20, low-certainty evidence), · dilatation and curettage (RR 1.49, 95% CI 1.26 to 1.75, low-certainty evidence), · suction aspiration (RR 1.44, 95% CI 1.29 to 1.62, low-certainty evidence), · mifepristone plus misoprostol (RR 1.42, 95% CI 1.22 to 1.66, moderate-certainty evidence), · misoprostol (RR 1.30, 95% CI 1.16 to 1.46, low-certainty evidence). The highest ranked surgical method was suction aspiration after cervical preparation. The highest ranked non-surgical treatment was mifepristone plus misoprostol. All surgical methods were ranked higher than medical methods, which in turn ranked above expectant management or placebo. Composite outcome of death and serious complications Based on the relative effects from the network meta-analysis of 35 trials (8161 women), we found that four methods with available data were compatible with a wide range of treatment effects compared with expectant management or placebo: · dilatation and curettage (RR 0.43, 95% CI 0.17 to 1.06, low-certainty evidence), · suction aspiration (RR 0.55, 95% CI 0.23 to 1.32, low-certainty evidence), · misoprostol (RR 0.50, 95% CI 0.22 to 1.15, low-certainty evidence), · mifepristone plus misoprostol (RR 0.76, 95% CI 0.31 to 1.84, low-certainty evidence). Importantly, no deaths were reported in these studies, thus this composite outcome was entirely composed of serious complications, including blood transfusions, uterine perforations, hysterectomies, and intensive care unit admissions. Expectant management and placebo ranked the lowest when compared with alternative treatment interventions. Subgroup analyses by type of miscarriage (missed or incomplete) agreed with the overall analysis in that surgical methods were the most effective treatment, followed by medical methods and then expectant management or placebo, but there are possible subgroup differences in the effectiveness of the available methods. AUTHORS' CONCLUSIONS: Based on relative effects from the network meta-analysis, all surgical and medical methods for managing a miscarriage may be more effective than expectant management or placebo. Surgical methods were ranked highest for managing a miscarriage, followed by medical methods, which in turn ranked above expectant management or placebo. Expectant management or placebo had the highest chance of serious complications, including the need for unplanned or emergency surgery. A subgroup analysis showed that surgical and medical methods may be more beneficial in women with missed miscarriage compared to women with incomplete miscarriage. Since type of miscarriage (missed and incomplete) appears to be a source of inconsistency and heterogeneity within these data, we acknowledge that the main network meta-analysis may be unreliable. However, we plan to explore this further in future updates and consider the primary analysis as separate networks for missed and incomplete miscarriage.
Topics: Abortion, Incomplete; Abortion, Missed; Abortion, Spontaneous; Drug Therapy, Combination; Female; Humans; Mifepristone; Misoprostol; Network Meta-Analysis; Oxytocics; Placebos; Pregnancy; Pregnancy Trimester, First; Randomized Controlled Trials as Topic; Suction; Vacuum Curettage; Watchful Waiting
PubMed: 34061352
DOI: 10.1002/14651858.CD012602.pub2