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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 -
Blood Research Apr 2023Myelofibrosis (MF) includes primary MF, post-essential thrombocythemia MF, and post-polycythemia vera MF. MF is a progressive myeloid neoplasm characterized by... (Review)
Review
Myelofibrosis (MF) includes primary MF, post-essential thrombocythemia MF, and post-polycythemia vera MF. MF is a progressive myeloid neoplasm characterized by ineffective clonal hematopoiesis, extramedullary hematopoiesis, a reactive bone marrow environment resulting in reticulin deposition and fibrosis, and a propensity for leukemia transformation. The identification of driver mutations in , , and has contributed to a better understanding of disease pathogenesis and has led to the development of MF-specific therapies, such as JAK2 inhibitors. Despite the fact that ruxolitinib and fedratinib have been clinically developed and approved, their use is limited due to adverse effects such as anemia and thrombocytopenia. Recently, pacritinib has been approved for a group of thrombocytopenic patients with significant unmet clinical needs. In symptomatic and anemic patients with prior JAK inhibitor exposure, momelotinib was superior to danazol in preventing exacerbation of anemia and in controlling MF-associated signs and symptoms, such as spleen size. Although the development of JAK inhibitors is remarkable, modifying the natural course of the disease remains a priority. Therefore, many novel treatments are currently under clinical development. Agents targeting bromodomain and extra-terminal protein, anti-apoptotic protein Bcl-xL, and phosphatidylinositol-3-kinase delta have been studied in combination with JAK inhibitors. These combinations have been employed in both the frontline and "add-on" approaches. In addition, several agents are being studied as monotherapies for ruxolitinib-resistant or -ineligible patients. We reviewed several new MF treatments in the advanced stages of clinical development and treatment options for cytopenic patients.
PubMed: 36891574
DOI: 10.5045/br.2023.2023012 -
BMJ Clinical Evidence Jan 2012Menorrhagia limits normal activities, and causes anaemia in two-thirds of women with objective menorrhagia (loss of 80 mL blood per cycle). Prostaglandin disorders may... (Review)
Review
INTRODUCTION
Menorrhagia limits normal activities, and causes anaemia in two-thirds of women with objective menorrhagia (loss of 80 mL blood per cycle). Prostaglandin disorders may be associated with idiopathic menorrhagia, and with heavy bleeding due to fibroids, adenomyosis, or use of intrauterine devices (IUDs). Fibroids have been found in 10% of women with menorrhagia overall, and in 40% of women with severe menorrhagia; but half of women having a hysterectomy for menorrhagia are found to have a normal uterus.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of medical treatments for menorrhagia? What are the effects of surgical treatments for menorrhagia? What are the effects of endometrial thinning before endometrial destruction in treating menorrhagia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations, such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 39 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following medical interventions: combined pill, danazol, etamsylate, gonadorelin analogues, intrauterine progesterone, non-steroidal anti-inflammatory drugs (NSAIDs), progestogens, and the following surgical interventions: dilatation and curettage, endometrial destruction, and hysterectomy.
Topics: Administration, Oral; Danazol; Dilatation and Curettage; Endometrial Ablation Techniques; Female; Humans; Intrauterine Devices, Medicated; Menorrhagia; Progestins
PubMed: 22305976
DOI: No ID Found -
International Journal of Women's... Dec 2019Cutaneous endometriosis is a disorder that primarily affects women of reproductive age. The disorder is most commonly associated with cyclical pain during menses, but it...
Cutaneous endometriosis is a disorder that primarily affects women of reproductive age. The disorder is most commonly associated with cyclical pain during menses, but it can be difficult to diagnose in the absence of these symptoms and requires biopsy testing for a definitive diagnosis. We report on a case of a 41-year-old patient undergoing hormonal therapy for infertility who presented with a painful firm subcutaneous nodule in the umbilicus. She was ultimately diagnosed with cutaneous endometriosis and underwent surgical excision. In this report, we discuss the differential diagnosis and comment on treatment options, including surgical excision with wide margins or treatment with hormonal agents, such as danazol or leuprolide. Finally, we discuss whether patients with cutaneous endometriosis should receive an additional evaluation for pelvic endometriosis.
PubMed: 31909163
DOI: 10.1016/j.ijwd.2019.06.025 -
British Journal of Haematology Jun 2016With prolonged life expectancy, immune thrombocytopenia (ITP) is frequent in elderly people. In this setting, ITP diagnosis is challenging because of the concern about... (Review)
Review
With prolonged life expectancy, immune thrombocytopenia (ITP) is frequent in elderly people. In this setting, ITP diagnosis is challenging because of the concern about an underlying myelodysplastic syndrome. Studies of older adults are lacking, and recommendations for treatment are based mainly on expert opinion. The therapeutic strategy differs from that for younger patients and must take into account the greater risk of bleeding and thrombosis, presence of comorbidities, possible impaired cognitive performance or poor life expectancy and concomitant medications, such as anticoagulant and antiplatelet therapy. Steroids and intravenous immunoglobulin (IVIg) therapy remain the first-line treatments in elderly patients, but prolonged treatment with steroids should be avoided and IVIg treatment may lead to renal failure. Splenectomy is less effective than in young patients and risk of thrombosis is increased. Severe co-morbidities can also contraindicate surgery. Therefore, other second-line treatments are frequently preferred. Danazol and dapsone can be an option for the less severe ITP form. Rituximab is a good option except in patients with a history of infection or with hypogammaglobulinaemia. Thrombopoietin agonists are attractive, especially for patients with severe comorbidities or with limited life expectancy but the risk of thrombosis is a concern.
Topics: Aged; Aged, 80 and over; Danazol; Dapsone; Disease Management; Female; Humans; Immunoglobulins, Intravenous; Male; Middle Aged; Purpura, Thrombocytopenic, Idiopathic; Rituximab; Steroids; Thrombopoietin
PubMed: 27062054
DOI: 10.1111/bjh.14067 -
BMJ Clinical Evidence Aug 2010Ectopic endometrial tissue is found in 1.5% to 6.2% of women of reproductive age, in up to 60% of those with dysmenorrhoea, and in up to 30% of women with subfertility,... (Review)
Review
INTRODUCTION
Ectopic endometrial tissue is found in 1.5% to 6.2% of women of reproductive age, in up to 60% of those with dysmenorrhoea, and in up to 30% of women with subfertility, with a peak incidence at around 40 years of age. However, symptoms may not correlate with laparoscopic findings.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of hormonal treatments given at diagnosis of endometriosis? What are the effects of hormonal treatments before surgery for endometriosis? What are the effects of non-hormonal medical treatments for endometriosis? What are the effects of surgical treatments for endometriosis? What are the effects of hormonal treatment after conservative surgery for endometriosis? What are the effects of hormonal treatment after oophorectomy (with or without hysterectomy) for endometriosis? What are the effects of treatments for ovarian endometrioma? We searched: Medline, Embase, The Cochrane Library, and other important databases up to December 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 40 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: combined oral contraceptives, danazol, dydrogesterone, gestrinone, gonadorelin analogues, aromatase inhibitors, hormonal treatment before surgery, hormonal treatment, laparoscopic cystectomy, laparoscopic removal of endometriotic deposits (alone or with uterine nerve ablation), laparoscopic removal plus presacral neurectomy, laparoscopic uterine nerve ablation, non-steroidal anti-inflammatory drugs, presacral neurectomy alone, and progestogens other than dydrogesterone.
Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Aromatase Inhibitors; Contraceptives, Oral, Combined; Danazol; Drug Administration Schedule; Dysmenorrhea; Endometriosis; Female; Humans; Pelvic Pain
PubMed: 21418683
DOI: No ID Found -
BMJ Clinical Evidence Sep 2008Menorrhagia limits normal activities, and causes anaemia in two thirds of women with objective menorrhagia (loss of 80 mL blood per cycle). Prostaglandin disorders may... (Review)
Review
INTRODUCTION
Menorrhagia limits normal activities, and causes anaemia in two thirds of women with objective menorrhagia (loss of 80 mL blood per cycle). Prostaglandin disorders may be associated with idiopathic menorrhagia, and with heavy bleeding due to fibroids, adenomyosis, or use of intrauterine devices (IUDs). Fibroids have been found in 10% of women with menorrhagia overall, and in 40% of women with severe menorrhagia; but half of women having a hysterectomy for menorrhagia are found to have a normal uterus.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of medical treatments for menorrhagia? What are the effects of surgical treatments for menorrhagia? What are the effects of endometrial thinning before endometrial destruction in treating menorrhagia? We searched: Medline, Embase, The Cochrane Library, and other important databases up to October 2007 (BMJ Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 39 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following medical interventions: combined pill, danazol, etamsylate, gonadorelin analogues, intrauterine progesterone, non-steroidal inflammatory drugs (NSAIDs), progestogens, and the following surgical interventions: dilatation and curretage, endometrial destruction, and hysterectomy.
Topics: Administration, Oral; Danazol; Endometrium; Female; Humans; Incidence; Menorrhagia; Progestins; Treatment Outcome
PubMed: 19445802
DOI: No ID Found -
Przeglad Menopauzalny = Menopause Review Mar 2016Endometriosis is a chronic inflammatory condition in which foci of endometrial tissue grow outside of the uterine cavity. Endometriosis was estimated to affect 176... (Review)
Review
Endometriosis is a chronic inflammatory condition in which foci of endometrial tissue grow outside of the uterine cavity. Endometriosis was estimated to affect 176 million women of childbearing potential all over the world in 2010. The presence of extrauterine endometrial tissue is associated with pain and infertility. Typical symptoms of endometriosis include dysmenorrhoea, dyspareunia, heavy menstrual periods (menorrhagia), pelvic pain that is not related to menstrual cycles, dysuria, and chronic fatigue. Medical treatments for endometriosis include combined oral contraceptive pills, danazol, gestrinone, medroxyprogesterone acetate, and gonadotropin-releasing hormone agonists (aGnRHs). A new class of medications called aromatase inhibitors has been identified in recent years as potential therapeutic agents for endometriosis. This article provides general information about aromatase inhibitors, their use in gynaecology, and their adverse effects. In particular, the paper discusses the use of aromatase inhibitors in the treatment of endometriosis in postmenopausal women. Unlike oral contraceptives, gestagens, aGnRHs, and danazol, which suppress ovarian oestrogen synthesis, aromatase inhibitors inhibit mainly extra-ovarian synthesis of oestrogens. Therefore, the use of aromatase inhibitors seems to be particularly relevant in older patients, as most of the body's oestrogen is produced outside the ovaries after menopause. The paper discusses also the use of aromatase inhibitors in the treatment of pain associated with endometriosis and infertility caused by endometriosis.
PubMed: 27095958
DOI: 10.5114/pm.2016.58773 -
BMJ Clinical Evidence Mar 2007Ectopic endometrial tissue is found in up to 20% of asymptomatic women, up to 60% of those with dysmenorrhoea, and up to 30% of women with subfertility, with a peak... (Review)
Review
INTRODUCTION
Ectopic endometrial tissue is found in up to 20% of asymptomatic women, up to 60% of those with dysmenorrhoea, and up to 30% of women with subfertility, with a peak incidence at around 40 years of age. However, symptoms may not correlate with laparoscopic findings.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of hormonal treatments given at diagnosis of endometriosis? What are the effects of hormonal treatments before surgery for endometriosis? What are the effects of non-hormonal medical treatments for endometriosis? What are the effects of surgical treatments for endometriosis? What are the effects of hormonal treatment after conservative surgery for endometriosis? What are the effects of hormonal treatment after oophorectomy (with or without hysterectomy) for endometriosis? What are the effects of treatments for ovarian endometrioma? We searched: Medline, Embase, The Cochrane Library and other important databases up to April 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 32 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: combined oral contraceptives; danazol; dydrogesterone; gestrinone; gonadorelin analogues; hormonal treatment before surgery; hormonal treatment; laparoscopic cystectomy; laparoscopic removal of endometriotic deposits (alone or with uterine nerve ablation); laparoscopic removal plus presacral neurectomy; laparoscopic uterine nerve ablation; non-steroidal anti-inflammatory drugs; presacral neurectomy alone; and progestogens other than dydrogesterone.
Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Contraceptives, Oral; Danazol; Dysmenorrhea; Endometriosis; Female; Humans; Laparoscopy; Progestins
PubMed: 19454060
DOI: No ID Found