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Oncology (Williston Park, N.Y.) Dec 2023Purpose To study the potential utility of danazol for treating patients with myelodysplastic syndromes, with a focus on efficacy and adverse effects (AEs). Methods... (Review)
Review
Purpose To study the potential utility of danazol for treating patients with myelodysplastic syndromes, with a focus on efficacy and adverse effects (AEs). Methods MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus were searched for relevant publications from inception June 1, 1950, until June 28, 2022. The studies were screened by title and abstract, followed by full-text screening. The quality of the included studies was assessed via a prespecified set of questionnaires. Data on the efficacy measures and adverse outcomes were extracted and included in a descriptive summary. Results Nine studies consisting of 246 participants were included in our review. The overall quality of the included studies was fair. The age of the participants ranged from 61 to 78 years. In all 9 studies, more male patients had been enrolled than female patients. Overall, a proportion of patients in all the studies reported a desired major response to a danazol dose of 400 to 800 mg/day. Few studies did not observe any improvement in the platelet count. Elevated liver enzyme levels, weight gain, headache, dermatitis, and weakness were the most common AEs observed. One study reported a fatal intracerebral hemorrhage in 1 participant. Conclusions Danazol has been effective in increasing platelet count and hemoglobin level. Despite a few AEs, danazol is a safe drug for the treatment of patients with myelodysplastic syndromes.
Topics: Aged; Female; Humans; Male; Middle Aged; Danazol; Myelodysplastic Syndromes
PubMed: 38133562
DOI: 10.46883/2023.25921009 -
Medicine Aug 2023Endometriosis (EMT) is a benign and common estrogen-dependent disease. Hormonal therapy improves pain symptoms in most women with EMT. However, in many cases,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Endometriosis (EMT) is a benign and common estrogen-dependent disease. Hormonal therapy improves pain symptoms in most women with EMT. However, in many cases, laparoscopic fertility preservation surgery is considered a common treatment for EMT. The present study aimed to evaluate the efficacy and safety of dienogest, leuprolide, danazol, gestrinone, mifepristone and levonorgestrel intrauterine system (LNG-IUS) in relieving symptoms and delaying the recurrence of EMT cysts after fertility protection surgery.
METHODS
We searched PubMed, the Cochrane Library, Web of Science, EMBase, China National Knowledge Infrastructure, VIP Database, China Biology Medicine disc, WanFang Data databases to collect randomized controlled trials (RCT) related to dienogest, leuprolide, danazol, gestrinone, mifepristone and LNG-IUS as a follow-up treatment after fertility preserving surgery for EMT. After literature screening, data extraction and quality evaluation, effective rate, recurrence rate, pregnancy rate and adverse reaction rate were used as outcome indicators to evaluate the efficacy and safety of drugs. Evidence networks included in the study were drawn and publication bias was assessed. The drugs most likely to be the best postoperative treatment were explored through mixed comparison of different drugs and efficacy ranking.
RESULT
Effective rate: dienogest, leprerelin, gestrinone and LNG-IUS were better than placebo after EMT fertility preservation surgery; dienogest was superior to mifepristone and danazol. LNG-IUS is superior to danazol. LNG-IUS has the highest potential for improving the effectiveness of EMT symptoms. Recurrence rate: the application of dienogest, leuprolide, gestrinone, mifepristone and LNG-IUS after EMT fertility preservation surgery was lower than that of placebo; dienogest and LNG-IUS were lower than danazol. The recurrence rate of dinorgestrel was the last place with the highest performance. Pregnancy rate: in the cases with fertility requirements, dienogest and,leuprolide were better than placebo after EMT fertility preservation surgery; dienogest was superior to danazol, gestrinone and mifepristone. Leuprolide is superior to danazol and gestrinone. The first rank of dienogest pregnancy rate was the highest. Adverse reaction rate: the application of dienogest, leuprolide, danazol, gestrinone, mifepristone and LNG-IUS after EMT fertility preservation surgery was higher than that of placebo. After placebo, LNG-IUS had the highest adverse reaction rate.
CONCLUSION
For patients after fertility preserving surgery for EMT, the recurrence rate of dienogest was the last place with highest preference. The first rank of dienogest pregnancy was the highest.
Topics: Female; Humans; Endometriosis; Danazol; Gestrinone; Leuprolide; Mifepristone; Network Meta-Analysis; Levonorgestrel
PubMed: 37543781
DOI: 10.1097/MD.0000000000034496 -
The Cochrane Database of Systematic... Jun 2023Endometriosis is a common gynaecological condition affecting 6 to 11% of reproductive-age women and may cause dyspareunia, dysmenorrhoea, and infertility. One treatment... (Review)
Review
BACKGROUND
Endometriosis is a common gynaecological condition affecting 6 to 11% of reproductive-age women and may cause dyspareunia, dysmenorrhoea, and infertility. One treatment strategy is medical therapy with gonadotrophin-releasing hormone analogues (GnRHas) to reduce pain due to endometriosis. One of the adverse effects of GnRHas is a decreased bone mineral density. In addition to assessing the effect on pain, quality of life, most troublesome symptom and patients' satisfaction, the current review also evaluated the effect on bone mineral density and risk of adverse effects in women with endometriosis who use GnRHas versus other treatment options.
OBJECTIVES
To assess the effectiveness and safety of GnRH analogues (GnRHas) in the treatment of painful symptoms associated with endometriosis and to determine the effects of GnRHas on bone mineral density of women with endometriosis.
SEARCH METHODS
We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO and the trial registries in May 2022 together with reference checking and contact with study authors and experts in the field to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) which compared GnRHas with other hormonal treatment options, including analgesics, danazol, intra-uterine progestogens, oral or injectable progestogens, gestrinone and also GnRHas compared with no treatment or placebo. Trials comparing GnRHas versus GnRHas in conjunction with add-back therapy (hormonal or non-hormonal) or calcium-regulation agents were also included in this review. DATA COLLECTION AND ANALYSIS: We used standard methodology as recommended by Cochrane. Primary outcomes are relief of overall pain and the objective measurement of bone mineral density. Secondary outcomes include adverse effects, quality of life, improvement in the most troublesome symptoms and patient satisfaction. Due to high risk of bias associated with some of the studies, primary analyses of all review outcomes were restricted to studies at low risk of selection bias. Sensitivity analysis including all studies was then performed.
MAIN RESULTS
Seventy-two studies involving 7355 patients were included. The evidence was very low to low quality: the main limitations of all studies were serious risk of bias due to poor reporting of study methods, and serious imprecision. Trials comparing GnRHas versus no treatment We did not identify any studies. Trials comparing GnRHas versus placebo There may be a decrease in overall pain, reported as pelvic pain scores (RR 2.14; 95% CI 1.41 to 3.24, 1 RCT, n = 87, low-certainty evidence), dysmenorrhoea scores (RR 2.25; 95% CI 1.59 to 3.16, 1 RCT, n = 85, low-certainty evidence), dyspareunia scores (RR 2.21; 95% CI 1.39 to 3.54, 1 RCT, n = 59, low-certainty evidence), and pelvic tenderness scores (RR 2.28; 95% CI 1.48 to 3.50, 1 RCT, n = 85, low-certainty evidence) after three months of treatment. We are uncertain of the effect for pelvic induration, based on the results found after three months of treatment (RR 1.07; 95% CI 0.64 to 1.79, 1 RCT, n = 81, low-certainty evidence). Besides, treatment with GnRHas may be associated with a greater incidence of hot flushes at three months of treatment (RR 3.08; 95% CI 1.89 to 5.01, 1 RCT, n = 100, low-certainty evidence). Trials comparing GnRHas versus danazol For overall pain, for women treated with either GnRHas or danazol, a subdivision was made between pelvic tenderness, partly resolved and completely resolved. We are uncertain about the effect on relief of overall pain, when a subdivision was made for overall pain (MD -0.30; 95% CI -1.66 to 1.06, 1 RCT, n = 41, very low-certainty evidence), pelvic pain (MD 0.20; 95% CI -0.26 to 0.66, 1 RCT, n = 41, very low-certainty evidence), dysmenorrhoea (MD 0.10; 95% CI -0.49 to 0.69, 1 RCT, n = 41, very low-certainty evidence), dyspareunia (MD -0.20; 95% CI -0.77 to 0.37, 1 RCT, n = 41, very low-certainty evidence), pelvic induration (MD -0.10; 95% CI -0.59 to 0.39, 1 RCT, n = 41, very low-certainty evidence), and pelvic tenderness (MD -0.20; 95% CI -0.78 to 0.38, 1 RCT, n = 41, very low-certainty evidence) after three months of treatment. For pelvic pain (MD 0.50; 95% CI 0.10 to 0.90, 1 RCT, n = 41, very low-certainty evidence) and pelvic induration (MD 0.70; 95% CI 0.21 to 1.19, 1 RCT, n = 41, very low-certainty evidence), the complaints may decrease slightly after treatment with GnRHas, compared to danazol, for six months of treatment. Trials comparing GnRHas versus analgesics We did not identify any studies. Trials comparing GnRHas versus intra-uterine progestogens We did not identify any low risk of bias studies. Trials comparing GnRHas versus GnRHas in conjunction with calcium-regulating agents There may be a slight decrease in bone mineral density (BMD) after 12 months treatment with GnRHas, compared to GnRHas in conjunction with calcium-regulating agents for anterior-posterior spine (MD -7.00; 95% CI -7.53 to -6.47, 1 RCT, n = 41, very low-certainty evidence) and lateral spine (MD -12.40; 95% CI -13.31 to -11.49, 1 RCT, n = 41, very low-certainty evidence). AUTHORS' CONCLUSIONS: For relief of overall pain, there may be a slight decrease in favour of treatment with GnRHas compared to placebo or oral or injectable progestogens. We are uncertain about the effect when comparing GnRHas with danazol, intra-uterine progestogens or gestrinone. For BMD, there may be a slight decrease when women are treated with GnRHas, compared to gestrinone. There was a bigger decrease of BMD in favour of GnRHas, compared to GnRHas in conjunction with calcium-regulating agents. However, there may be a slight increase in adverse effects when women are treated with GnRHas, compared to placebo or gestrinone. Due to a very low to low certainty of the evidence, a wide range of outcome measures and a wide range of outcome measurement instruments, the results should be interpreted with caution.
Topics: Female; Humans; Endometriosis; Danazol; Progestins; Gestrinone; Dysmenorrhea; Calcium; Dyspareunia; Pelvic Pain; Calcium, Dietary; Drug-Related Side Effects and Adverse Reactions; Gonadotropin-Releasing Hormone
PubMed: 37341141
DOI: 10.1002/14651858.CD014788.pub2 -
Revista Brasileira de Ginecologia E... Oct 2022Different drugs are used to treat mastalgia, such as danazol and bromocriptine, and both are associated with side effects, due to which most of women and healthcare... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Different drugs are used to treat mastalgia, such as danazol and bromocriptine, and both are associated with side effects, due to which most of women and healthcare providers are interested in herbal medicines. Therefore we aim to study the effectiveness of phytoestrogens on the severity of cyclic mastalgia.
METHODS
To carry out the present study, English electronic resources such as the Cochrane Library, ISI Web of Science, Scopus, and PubMed were used systematically and with no time limitation up to February 10, 2020.
RESULTS
In total, 20 studies were included in the present meta-analysis. The results of the meta-analysis showed that herbal medicines versus the control group (standard mean difference [SMD] = - 0.585; 95% confidence interval [CI]: - 0.728-- 0.44; heterogeneity; = 0.02; I2 = 42%), herbal medicines versus the B group (SMD = - 0.59; 95%CI: - 0.75-- 0.44; heterogeneity; = 0.03; I2 = 42%), and its subgroups, such as phytoestrogen (SMD = - 0.691; 95%CI: - 0.82-- 0.55; heterogeneity; = 0.669; I2 = 0%), Vitex-agnus-castus (SMD = - 0.642; 95%CI: - 0.84-- 0.44; < 0.001; = 203; I2 = 32%), flaxseed (SMD = - 0.63; 95%CI: - 0.901-- 0.367; = 0.871; I2 = 0%), and evening primrose (SMD= - 0.485; 95%CI:- 0.84-- 0.12; = 0.008; heterogeneity; = 0.06; I2 = 56%] may have effective and helpful effects on improving cyclic breast mastalgia. Also, chamomile, isoflavone, cinnamon, and nigella sativa significantly reduced mastalgia symptoms.
CONCLUSION
Herbal medicines and their subgroups may have effective and helpful effects on improving cyclic breast mastalgia. The findings of our meta-analysis must be done cautiously because low methodological quality in some evaluated studies of this systematic review.
Topics: Female; Humans; Mastodynia; Plants, Medicinal; Breast; Plant Extracts
PubMed: 36446563
DOI: 10.1055/s-0042-1755456 -
The Cochrane Database of Systematic... Nov 2022Hereditary angioedema (HAE) is a serious and potentially life-threatening condition that causes acute attacks of swelling, pain and reduced quality of life. People with... (Review)
Review
BACKGROUND
Hereditary angioedema (HAE) is a serious and potentially life-threatening condition that causes acute attacks of swelling, pain and reduced quality of life. People with Type I HAE (approximately 80% of all HAE cases) have insufficient amounts of C1 esterase inhibitor (C1-INH) protein; people with Type II HAE (approximately 20% of all cases) may have normal C1-INH concentrations, but, due to genetic mutations, these do not function properly. A few people, predominantly females, experience HAE despite having normal C1-INH levels and C1-INH function (rare Type III HAE). Several new drugs have been developed to treat acute attacks and prevent recurrence of attacks. There is currently no systematic review and meta-analysis that included all preventive medications for HAE.
OBJECTIVES
To assess the benefits and harms of interventions for the long-term prevention of HAE attacks in people with Type I, Type II or Type III HAE.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 3 August 2021.
SELECTION CRITERIA
We included randomised controlled trials in children or adults with HAE that used medications to prevent HAE attacks. The comparators could be placebo or active comparator, or both; approved and experimental drug trials were eligible for inclusion. There were no restrictions on dose, frequency or intensity of treatment. The minimum length of four weeks of treatment was required for inclusion; this criterion excluded the acute treatment of HAE attacks.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. HAE attacks (number of attacks per person, per population) and change in number of HAE attacks; 2. mortality and 3. serious adverse events (e.g. hepatic dysfunction, hepatic toxicity and deleterious changes in blood tests). Our secondary outcomes were 4. quality of life; 5. severity of breakthrough attacks; 6. disability and 7. adverse events (e.g. weight gain, mild psychological changes and body hair). We used GRADE to assess certainty of evidence for each outcome.
MAIN RESULTS
We identified 15 studies (912 participants) that met the inclusion criteria. The studies included people with Type I and II HAE. The studies investigated avoralstat, berotralstat, subcutaneous C1-INH, plasma-derived C1-INH, nanofiltered C1-INH, recombinant human C1-INH, danazol, and lanadelumab for the prevention of HAE attacks. We did not find any studies on the use of tranexamic acid for prevention of HAE attacks. All drugs except avoralstat reduced the number of HAE attacks compared with placebo. For breakthrough attacks that occurred despite prophylactic treatment, intravenous and subcutaneous forms of C1-INH and lanadelumab reduced attack severity. It is not known whether other drugs have a similar effect, as the severity of breakthrough attacks in people taking drugs other than C1-INH and lanadelumab was not reported. For quality of life, avoralstat, berotralstat, C1-INH (all forms) and lanadelumab increased quality of life compared with placebo; there were no data for danazol. Four studies reported on changes in disability during treatment with C1-INH, berotralstat and lanadelumab; all three drugs decreased disability compared with placebo. Adverse events, including serious adverse events, did not occur at a rate higher than placebo. However, serious adverse event data and other adverse event data were not available for danazol, which prevented us from drawing conclusions about the absolute or relative safety of this drug. No deaths were reported in the included studies. The analysis was limited by the small number of studies, the small number of participants in each study and the lack of data on older drugs, therefore the certainty of the evidence is low. Given the rarity of HAE, it is not surprising that drugs were rarely directly compared, which does not allow conclusions on the comparative efficacy of the various drugs for people with HAE. Finally, we did not identify any studies that included people with Type III HAE. Therefore, we cannot draw any conclusions about the efficacy or safety of any drug in people with this form of HAE.
AUTHORS' CONCLUSIONS
The available data suggest that berotralstat, C1-INH (subcutaneous, plasma-derived, nanofiltered and recombinant), danazol and lanadelumab are effective in lowering the risk or incidence (or both) of HAE attacks. In addition, C1-INH and lanadelumab decrease the severity of breakthrough attacks (data for other drugs were not available). Avoralstat, berotralstat, C1-INH (all forms) and lanadelumab increase quality of life and do not increase the risk of adverse events, including serious adverse events. It is possible that danazol, subcutaneous C1-INH and recombinant human C1-INH are more effective than berotralstat and lanadelumab in reducing the risk of breakthrough attacks, but the small number of studies and the small size of the studies means that the certainty of the evidence is low. This and the lack of head-to-head trials prevented us from drawing firm conclusions on the relative efficacy of the drugs.
Topics: Adult; Child; Female; Humans; Male; Angioedemas, Hereditary; Quality of Life; Danazol; Complement C1 Inhibitor Protein; Administration, Intravenous; Treatment Outcome
PubMed: 36326435
DOI: 10.1002/14651858.CD013403.pub2 -
The Cochrane Database of Systematic... May 2022Heavy menstrual bleeding (HMB) is excessive menstrual blood loss that interferes with women's quality of life, regardless of the absolute amount of bleeding. It is a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Heavy menstrual bleeding (HMB) is excessive menstrual blood loss that interferes with women's quality of life, regardless of the absolute amount of bleeding. It is a very common condition in women of reproductive age, affecting 2 to 5 of every 10 women. Diverse treatments, either medical (hormonal or non-hormonal) or surgical, are currently available for HMB, with different effectiveness, acceptability, costs and side effects. The best treatment will depend on the woman's age, her intention to become pregnant, the presence of other symptoms, and her personal views and preferences.
OBJECTIVES
To identify, systematically assess and summarise all evidence from studies included in Cochrane Reviews on treatment for heavy menstrual bleeding (HMB), using reviews with comparable participants and outcomes; and to present a ranking of the first- and second-line treatments for HMB.
METHODS
We searched for published Cochrane Reviews of HMB interventions in the Cochrane Database of Systematic Reviews. The primary outcomes were menstrual bleeding and satisfaction. Secondary outcomes included quality of life, adverse events and the requirement of further treatment. Two review authors independently selected the systematic reviews, extracted data and assessed quality, resolving disagreements by discussion. We assessed review quality using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) 2 tool and evaluated the certainty of the evidence for each outcome using GRADE methods. We grouped the interventions into first- and second-line treatments, considering participant characteristics (desire for future pregnancy, failure of previous treatment, candidacy for surgery). First-line treatments included medical interventions, and second-line treatments included both the levonorgestrel-releasing intrauterine system (LNG-IUS) and surgical treatments; thus the LNG-IUS is included in both groups. We developed different networks for first- and second-line treatments. We performed network meta-analyses of all outcomes, except for quality of life, where we performed pairwise meta-analyses. We reported the mean rank, the network estimates for mean difference (MD) or odds ratio (OR), with 95% confidence intervals (CIs), and the certainty of evidence (moderate, low or very low certainty). We also analysed different endometrial ablation and resection techniques separately from the main network: transcervical endometrial resection (TCRE) with or without rollerball, other resectoscopic endometrial ablation (REA), microwave non-resectoscopic endometrial ablation (NREA), hydrothermal ablation NREA, bipolar NREA, balloon NREA and other NREA.
MAIN RESULTS
We included nine systematic reviews published in the Cochrane Library up to July 2021. We updated the reviews that were over two years old. In July 2020, we started the overview with no new reviews about the topic. The included medical interventions were: non-steroidal anti-inflammatory drugs (NSAIDs), antifibrinolytics (tranexamic acid), combined oral contraceptives (COC), combined vaginal ring (CVR), long-cycle and luteal oral progestogens, LNG-IUS, ethamsylate and danazol (included to provide indirect evidence), which were compared to placebo. Surgical interventions were: open (abdominal), minimally invasive (vaginal or laparoscopic) and unspecified (or surgeon's choice of route of) hysterectomy, REA, NREA, unspecified endometrial ablation (EA) and LNG-IUS. We grouped the interventions as follows. First-line treatments Evidence from 26 studies with 1770 participants suggests that LNG-IUS results in a large reduction of menstrual blood loss (MBL; mean rank 2.4, MD -105.71 mL/cycle, 95% CI -201.10 to -10.33; low certainty evidence); antifibrinolytics probably reduce MBL (mean rank 3.7, MD -80.32 mL/cycle, 95% CI -127.67 to -32.98; moderate certainty evidence); long-cycle progestogen reduces MBL (mean rank 4.1, MD -76.93 mL/cycle, 95% CI -153.82 to -0.05; low certainty evidence), and NSAIDs slightly reduce MBL (mean rank 6.4, MD -40.67 mL/cycle, -84.61 to 3.27; low certainty evidence; reference comparator mean rank 8.9). We are uncertain of the true effect of the remaining interventions and the sensitivity analysis for reduction of MBL, as the evidence was rated as very low certainty. We are uncertain of the true effect of any intervention (very low certainty evidence) on the perception of improvement and satisfaction. Second-line treatments Bleeding reduction is related to the type of hysterectomy (total or supracervical/subtotal), not the route, so we combined all routes of hysterectomy for bleeding outcomes. We assessed the reduction of MBL without imputed data (11 trials, 1790 participants) and with imputed data (15 trials, 2241 participants). Evidence without imputed data suggests that hysterectomy (mean rank 1.2, OR 25.71, 95% CI 1.50 to 439.96; low certainty evidence) and REA (mean rank 2.8, OR 2.70, 95% CI 1.29 to 5.66; low certainty evidence) result in a large reduction of MBL, and NREA probably results in a large reduction of MBL (mean rank 2.0, OR 3.32, 95% CI 1.53 to 7.23; moderate certainty evidence). Evidence with imputed data suggests hysterectomy results in a large reduction of MBL (mean rank 1.0, OR 14.31, 95% CI 2.99 to 68.56; low certainty evidence), and NREA probably results in a large reduction of MBL (mean rank 2.2, OR 2.87, 95% CI 1.29 to 6.05; moderate certainty evidence). We are uncertain of the true effect for REA (very low certainty evidence). We are uncertain of the effect on amenorrhoea (very low certainty evidence). Evidence from 27 trials with 4284 participants suggests that minimally invasive hysterectomy results in a large increase in satisfaction (mean rank 1.3, OR 7.96, 95% CI 3.33 to 19.03; low certainty evidence), and NREA also increases satisfaction (mean rank 3.6, OR 1.59, 95% CI 1.09 to 2.33; low certainty evidence), but we are uncertain of the true effect of the remaining interventions (very low certainty evidence).
AUTHORS' CONCLUSIONS
Evidence suggests LNG-IUS is the best first-line treatment for reducing menstrual blood loss (MBL); antifibrinolytics are probably the second best, and long-cycle progestogens are likely the third best. We cannot make conclusions about the effect of first-line treatments on perception of improvement and satisfaction, as evidence was rated as very low certainty. For second-line treatments, evidence suggests hysterectomy is the best treatment for reducing bleeding, followed by REA and NREA. We are uncertain of the effect on amenorrhoea, as evidence was rated as very low certainty. Minimally invasive hysterectomy may result in a large increase in satisfaction, and NREA also increases satisfaction, but we are uncertain of the true effect of the remaining second-line interventions, as evidence was rated as very low certainty.
Topics: Amenorrhea; Antifibrinolytic Agents; Child, Preschool; Female; Humans; Menorrhagia; Network Meta-Analysis; Progestins; Quality of Life; Systematic Reviews as Topic
PubMed: 35638592
DOI: 10.1002/14651858.CD013180.pub2 -
BMC Pulmonary Medicine Sep 2021Dyskeratosis congenita (DC) is a rare genetic disorder of poor telomere maintenance. Pulmonary fibrosis (PF) related to DC is rarely reported.
BACKGROUND
Dyskeratosis congenita (DC) is a rare genetic disorder of poor telomere maintenance. Pulmonary fibrosis (PF) related to DC is rarely reported.
CASE PRESENTATION
A 23-year-old student presented with a four-year history of progressive cough and exertional dyspnea. Physical examination was remarkable for typical mucocutaneous abnormalities. Chest computerized tomography scan revealed interstitial fibrosis. Testing of peripheral blood leukocytes confirmed that his telomeres were 30th percentile of age-matched controls. A heterozygous missense mutation located in exon 22 of PARN gene was identified in the patient by whole exome sequencing. The patient refused danazol therapy and lung transplantation, and died of respiratory failure 2 years later. In addition, this case and 26 reported cases of DC-related PF identified through the comprehensive search of PubMed, Web of Science, WANFANG and CNKI were reviewed. Later-onset PF was observed in 11 patients (40.7%). Radiological usual interstitial pneumonia (UIP) pattern or possible UIP pattern was noted only in half of patients. However, histopathological UIP or probable UIP patterns were found in 63.6% of patients. Age at bone marrow failure (BMF) and the frequency of normal to mild thrombocytopenia in later-onset patients was significantly higher than in early-onset patients (p = 0.017 and p = 0.021, respectively). Age at PF and age at BMF in DC patients with TERC/TERT variants was significantly higher than in those with TINF2 variants or DKC1/NHP2 variants (p = 0.004 and p = 0.003, respectively). The patients with TERT/TERC/RTEL1/PARN variants had a significantly better transplant-free survival than those with TINF2 variants or DKC1/NHP2 variants (p < 0.05). Patients who underwent surgical lung biopsy had significantly worse transplant-free survival than those without lung biopsy (p = 0.042). Worse survival was found in patients with immunosuppression therapy than in those without (p = 0.012).
CONCLUSIONS
It is common for DC-associated PF to occur later in life without significant hematological manifestations. Mutations in the genes encoding different components of the telomere maintenance pathway were associated with clinical phenotypes and prognosis. PF caused by DC should be kept in mind by clinicians in the differential diagnosis of patients with unexplained PF and should be excluded before diagnostic surgical lung biopsy is undertaken or empirical immunosuppression therapy is prescribed.
Topics: Cell Cycle Proteins; DNA Helicases; Dyskeratosis Congenita; Fatal Outcome; Humans; Idiopathic Pulmonary Fibrosis; Male; Nuclear Proteins; Telomere-Binding Proteins; Young Adult
PubMed: 34479523
DOI: 10.1186/s12890-021-01645-w -
International Journal of Environmental... Jun 2021Mastalgia, or breast pain, is common among women which can lead to significant impairment in daily living. Hence, finding an effective treatment that can alleviate the... (Meta-Analysis)
Meta-Analysis Review
Mastalgia, or breast pain, is common among women which can lead to significant impairment in daily living. Hence, finding an effective treatment that can alleviate the symptom is very important. Thus, we carry out this study to determine the efficacy of evening primrose oil (EPO) for mastalgia treatment in women. The review included published randomised clinical trials that evaluated EPO used for treating mastalgia against a placebo or other treatments, irrespective of the blinding procedure, publication status, or sample size. Two independent authors screened the titles and abstracts of the identified trials; full texts of relevant trials were evaluated for eligibility. Two reviewers independently extracted data on the methods, interventions, outcomes, and risk of bias. The random-effects model was used for estimating the risk ratios and mean differences with 95% confidence intervals. Thirteen trials with 1752 randomised patients were included. The results showed that EPO has no difference to reduce breast pain compared to topical NSAIDS, danazol, or vitamin E. The number of patients who achieved pain relief was no different compared to the placebo or other treatments. The EPO does not increase adverse events, such as nausea, abdominal bloating, headache or giddiness, increase weight gain, and altered taste compared to a placebo or other treatments. EPO is a safe medication with similar efficacy for pain control in women with mastalgia compared to a placebo, topical NSAIDS, danazol, or vitamin E.
Topics: Female; Humans; Linoleic Acids; Mastodynia; Oenothera biennis; Plant Oils; Randomized Controlled Trials as Topic; gamma-Linolenic Acid
PubMed: 34200727
DOI: 10.3390/ijerph18126295 -
Fertility and Sterility Oct 2021To quantify the efficacy of medical management of uterine arteriovenous malformation (AVM) and compare efficacy between different classes of medication. In addition, we... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
To quantify the efficacy of medical management of uterine arteriovenous malformation (AVM) and compare efficacy between different classes of medication. In addition, we evaluated for factors associated with treatment success and pregnancy outcomes after medical management.
DESIGN
Systematic review and meta-analysis.
SETTING
Not applicable.
PATIENT(S)
Thirty-two studies representing 121 premenopausal women with medically-treated uterine AVM were identified via database searches of MEDLINE, Embase, Web of Science, and cited references.
INTERVENTION(S)
Medical treatment with progestins, gonadotropin-releasing hormone agonists (GnRH-a), methotrexate, combined hormonal contraception , uterotonics, danazol, or combination of the above.
MAIN OUTCOME MEASURE(S)
Primary outcome of treatment success was defined as AVM resolution without subsequent procedural interventions. Secondary outcome was treatment complication (readmission or transfusion).
RESULT(S)
The overall success rate of medical management was 88% (106/121). After adjusting for clustering effects, success rates for progestin (82.5%; 95% confidence interval [CI], 70.1%-90.4%), GnRH-a (89.3%; 99% CI, 71.4%-96.5%) and methotrexate (90.0%; 99% CI, 55.8%-98.8%) were significantly different from the null hypothesis of 50% success. The agents with the lowest adjusted proportion of complications were progestins (10.0%; 99% CI, 3.3%-26.8%) and GnRH-a (10.7%; 99% CI, 3.5%-28.4%). No clinical factors were found to predict treatment success. Twenty-six subsequent pregnancies are described, with no reported recurrences of AVM.
CONCLUSION(S)
Medical management for uterine AVM is a reasonable approach in a well selected patient. These data should be interpreted in the context of significant publication bias.
Topics: Arteriovenous Fistula; Blood Transfusion; Clinical Decision-Making; Female; Humans; Patient Readmission; Patient Selection; Pregnancy; Pregnancy Rate; Risk Assessment; Risk Factors; Treatment Outcome; Uterine Artery; Uterus
PubMed: 34130801
DOI: 10.1016/j.fertnstert.2021.05.095 -
The Cochrane Database of Systematic... Sep 2019Heavy menstrual bleeding (HMB) is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies...
BACKGROUND
Heavy menstrual bleeding (HMB) is an important cause of ill health in premenopausal women. Although surgery is often used as a treatment, a range of medical therapies are also available. Non-steroidal anti-inflammatory drugs (NSAIDs) reduce prostaglandin levels, which are elevated in women with excessive menstrual bleeding and also may have a beneficial effect on dysmenorrhoea.
OBJECTIVES
To determine the effectiveness, safety and tolerability of NSAIDs in achieving a reduction in menstrual blood loss (MBL) in women of reproductive years with HMB.
SEARCH METHODS
We searched, in April 2019, the Cochrane Gynaecology and Fertility specialised register, Cochrane Central Register of Studies Online (CENTRAL CRSO), MEDLINE, Embase, PsycINFO, the clinical trial registries and reference lists of articles.
SELECTION CRITERIA
The inclusion criteria were randomised comparisons of individual NSAIDs or combined with other medical therapy with each other, placebo or other medical treatments in women with regular heavy periods measured either objectively or subjectively and with no pathological or iatrogenic (treatment-induced) causes for their HMB.
DATA COLLECTION AND ANALYSIS
We identified 19 randomised controlled trials (RCTs) (759 women) that fulfilled the inclusion criteria for this review and two review authors independently extracted data. We estimated odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes from the data of nine trials. We described in data tables the results of the remaining seven cross-over trials with data unsuitable for pooling, one trial with skewed data, and one trial with missing variances. One trial had no data available for analysis.
MAIN RESULTS
As a group, NSAIDs were more effective than placebo at reducing HMB but less effective than tranexamic acid, danazol or the levonorgestrel-releasing intrauterine system (LNG IUS). Treatment with danazol caused a shorter duration of menstruation and more adverse events than NSAIDs, but this did not appear to affect the acceptability of treatment, based on trials from 1980 to 1990. However, currently danazol is not a usual or recommended treatment for HMB. There was no clear evidence of difference between NSAIDs and the other treatments (oral luteal progestogen, ethamsylate, an older progesterone-releasing intrauterine system and the oral contraceptive pill (OCP), but most studies were underpowered. There was no evidence of a difference between the individual NSAIDs (naproxen and mefenamic acid) in reducing HMB. The evidence quality ranged from low to moderate, the main limitations being risk of bias and imprecision.
AUTHORS' CONCLUSIONS
NSAIDs reduce HMB when compared with placebo, but are less effective than tranexamic acid, danazol or LNG IUS. However, adverse events are more severe with danazol therapy. In the limited number of small studies suitable for evaluation, there was no clear evidence of a difference in efficacy between NSAIDs and other medical treatments such as oral luteal progestogen, ethamsylate, OCP or the older progesterone-releasing intrauterine system.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Contraceptives, Oral, Combined; Dysmenorrhea; Female; Humans; Menorrhagia; Naproxen; Progesterone; Randomized Controlled Trials as Topic
PubMed: 31535715
DOI: 10.1002/14651858.CD000400.pub4