Critical review of current clinical practice guidelines for antifungal therapy in paediatric haematology and oncology

PURPOSE: The incidence of invasive fungal disease (IFD) is rising, but its treatment in paediatric haematology and oncology patients is not yet standardised. This review aimed to critically appraise and analyse the clinical practice guidelines (CPGs) that are available for paediatric IFD. METHODS: Electronic searches of MEDLINE, MEDLINE in-Process & Other non-Indexed Citations, the Guidelines International Network (GIN), guideline.gov and Google were performed and combined fungal disease (Fung* OR antifung*OR Candida* OR Aspergill*) with prophylaxis or treatment (prophyl* OR therap* OR treatment). All guidelines were assessed using the AGREE II tool and recommendations relating to prophylaxis, empirical treatment and specific therapy were extracted. RESULTS: Nineteen guidelines met the inclusion criteria. The AGREE II scores for the rigour of development domain ranged from 11 to 92 % with a median of 53 % (interquartile range 32-69 %). Fluconazole was recommended as antifungal prophylaxis in all nine of the included guidelines which recommended a specific drug. Liposomal amphotericin B was recommended in all five guidelines giving empirical therapy recommendations. Specific therapy recommendations were given for oral or genital candidiasis, invasive candida infection, invasive aspergillosis and other mould infections. CONCLUSIONS: In many areas, recommendations were clear about appropriate practice but further clarity was required, particularly relating to the decision to discontinue empirical antifungal treatment, the relative benefits of empiric and pre-emptive strategies and risk stratification. Future CPGs could consider working to published guideline production methodologies and sharing summaries of evidence appraisal to reduce duplication of effort, improving the quality and efficiency of CPGs in this area

Treating symptomatic uterine fibroids with myomectomy: current practice and views of UK consultants

Background: The demand for uterus-sparing treatments is increasing as more women postpone childbirth to their 30–40s, when fibroids are more symptomatic. With an increasing choice of treatment options and changing care-provider profiles, now is an opportune time to survey current practices and opinions. Using a 25-stem questionnaire, a web-based survey was used to capture the practices and opinions of UK consultant gynecologists on the treatment of symptomatic fibroids, including the types of procedure most frequently used, methods used to reduce blood loss, and awareness and acceptability of treatment options, and to assess the impact of gender and experience of the treating gynecologist. Results: The response rate was 22%. Laparascopic myomectomy is used least frequently, with 80% of the respondents using GnRHa preoperatively to minimize blood loss and correct anemia, while vasopressin is most frequently used to reduce intraoperative blood loss. Female consultants operate significantly less frequently than males. Those with more than 10 years consultant experience are more likely to perform an open myomectomy compared to those with less than 10 years experience. Conclusions: Compared to a similar survey performed 10 years ago, surgical methods remain to be the most common treatments, but use of less invasive treatments such as UAE has increased. Consultants’ attitudes appear to be responding to the patient demand for less radical treatments. However, it is yet to be seen if the changing consultant demographics will keep up with this demand. The low response rate warrants cautious interpretation of the results, but they provide an interesting snapshot of current views and practices

A randomised controlled trial of the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia: the ECLIPSE trial

Background: Heavy menstrual bleeding (HMB) is a common problem, yet evidence to inform decisions about initial medical treatment is limited. Objectives: To assess the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) (Mirena®, Bayer) compared with usual medical treatment, with exploration of women’s perspectives on treatment. Design: A pragmatic, multicentre randomised trial with an economic evaluation and a longitudinal qualitative study. Setting: Women who presented in primary care. Participants: A total of 571 women with HMB. A purposeful sample of 27 women who were randomised or ineligible owing to treatment preference participated in semistructured face-to-face interviews around 2 and 12 months after commencing treatment. Interventions: LNG-IUS or usual medical treatment (tranexamic acid, mefenamic acid, combined oestrogen–progestogen or progesterone alone). Women could subsequently swap or cease their allocated treatment. Outcome measures: The primary outcome was the patient-reported score on the Menorrhagia Multi-Attribute Scale (MMAS) assessed over a 2-year period and then again at 5 years. Secondary outcomes included general quality of life (QoL), sexual activity, surgical intervention and safety. Data were analysed using iterative constant comparison. A state transition model-based cost–utility analysis was undertaken alongside the randomised trial. Quality-adjusted life-years (QALYs) were derived from the European Quality of Life-5 Dimensions (EQ-5D) and the Short Form questionnaire-6 Dimensions (SF-6D). The intention-to-treat analyses were reported as cost per QALY gained. Uncertainty was explored by conducting both deterministic and probabilistic sensitivity analyses. Results: The MMAS total scores improved significantly in both groups at all time points, but were significantly greater for the LNG-IUS than for usual treatment [mean difference over 2 years was 13.4 points, 95% confidence interval (CI) 9.9 to 16.9 points; p < 0.001]. However, this difference between groups was reduced and no longer significant by 5 years (mean difference in scores 3.9 points, 95% CI –0.6 to 8.3 points; p = 0.09). By 5 years, only 47% of women had a LNG-IUS in place and 15% were still taking usual medical treatment. Five-year surgery rates were low, at 20%, and were similar, irrespective of initial treatments. There were no significant differences in serious adverse events between groups. Using the EQ-5D, at 2 years, the relative cost-effectiveness of the LNG-IUS compared with usual medical treatment was £1600 per QALY, which by 5 years was reduced to £114 per QALY. Using the SF-6D, usual medical treatment dominates the LNG-IUS. The qualitative findings show that women’s experiences and expectations of medical treatments for HMB vary considerably and change over time. Women had high expectations of a prompt effect from medical treatments. Conclusions: The LNG-IUS, compared with usual medical therapies, resulted in greater improvement over 2 years in women’s assessments of the effect of HMB on their daily routine, including work, social and family life, and psychological and physical well-being. At 5 years, the differences were no longer significant. A similar low proportion of women required surgical intervention in both groups. The LNG-IUS is cost-effective in both the short and medium term, using the method generally recommended by the National Institute for Health and Care Excellence. Using the alternative measures to value QoL will have a considerable impact on cost-effectiveness decisions. It will be important to explore the clinical and health-care trajectories of the ECLIPSE (clinical effectiveness and cost-effectiveness of levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia) trial participants to 10 years, by which time half of the cohort will have reached menopause. Trial registration: Current Controlled Trials ISRCTN86566246

Usual medical treatments or levonorgestrel-IUS for women with heavy menstrual bleeding:long-term randomised pragmatic trial in primary care

Background: Heavy menstrual bleeding (HMB) is a common, chronic problem affecting women and health services. However, long-term evidence on treatment in primary care is lacking. Aim: To assess the effectiveness of commencing the levonorgestrel-releasing intrauterine system (LNG-IUS) or usual medical treatments for women presenting with HMB in general practice. Design and setting: A pragmatic, multicentre, parallel, open-label, long term, randomised controlled trial in 63 primary care practices across the English Midlands. Method: In total, 571 women aged 25–50 years, with HMB were randomised to LNG-IUS or usual medical treatment (tranexamic/mefenamic acid, combined oestrogen–progestogen, or progesterone alone). The primary outcome was the patient reported Menorrhagia Multi-Attribute Scale (MMAS, measuring effect of HMB on practical difficulties, social life, psychological and physical health, and work and family life; scores from 0 to 100). Secondary outcomes included surgical intervention (endometrial ablation/hysterectomy), general quality of life, sexual activity, and safety. Results: At 5 years post-randomisation, 424 (74%) women provided data. While the difference between LNG-IUS and usual treatment groups was not significant (3.9 points; 95% confidence interval = −0.6 to 8.3; P = 0.09), MMAS scores improved significantly in both groups from baseline (mean increase, 44.9 and 43.4 points, respectively; P<0.001 for both comparisons). Rates of surgical intervention were low in both groups (surgery-free survival was 80% and 77%; hazard ratio 0.90; 95% CI = 0.62 to 1.31; P = 0.6). There was no difference in generic quality of life, sexual activity scores, or serious adverse events. Conclusion: Large improvements in symptom relief across both groups show treatment for HMB can be successfully initiated with long-term benefit and with only modest need for surgery

Epidemiology and management of uterine fibroids

Uterine leiomyomas are one of the most common and yet understudied diseases in women. These tumors, commonly known as fibroids, affect women mainly during their reproductive years and are diagnosed in up to 70% of white women and more than 80% of women of African ancestry during their lifetime. This disease has a profound impact on health care delivery and costs worldwide. Though most women with fibroids are asymptomatic, approximately 30% of them will present with severe symptoms which can include abnormal uterine bleeding, anemia, pelvic pain and pressure, back pain, urinary frequency, constipation, or infertility, and will require intervention. Furthermore, fibroids have been associated with poor obstetrical outcomes. The current options for symptomatic fibroid treatment include expectant, medical, and surgical management, and interventional radiology procedures. This article reviews the recent progress and available management strategies for uterine fibroids and highlights areas where further research is needed to find new therapeutic targets and better personalize treatments.We provide a review of the management options for uterine fibroids.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154526/1/ijgo13102.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154526/2/ijgo13102_am.pd

Laparoscopic Hernia Repair: a Two-Port Technique

Results of this study suggest that laparoscopic herniorrhaphy with a 2-port technique may allow a safe, efficient repair of ventral and incisional hernias

Economic inequality, within the context of the 2030 Agenda

Estudio de Caso para optar al grado académico de Magíster en Desarrollo y Cooperación Internacional.En Chile, el tema de la desigualdad es de larga data y se ve reflejado en la vida cotidiana de sus habitantes en diversas áreas, como en educación, salud, sistema previsional, territorialmente, entre otros. Es más, esto ha traído consigo un aumento del descontento social, lo que se ha visto reflejado en una variedad de movilizaciones sociales, las cuales llegaron a una cúspide el año 2019 con el llamado “Estallido Social”, lo que demostró, entre otras cosas, la urgencia que requiere enfrentar este problema en el país. No obstante, es importante primero definir cómo se entiende la desigualdad económica, la cual es multidimensional, por cuanto contempla dimensiones ex-ante y ex-post, es decir, de oportunidades y de ingresos y recompensas, respectivamente. En este sentido, la reducción de las disparidades económicas debe responder a ambas dimensiones si estas se quieren disminuir efectivamente. Además, el año 2015, Chile firmó una resolución de la Asamblea General de las Naciones Unidas, la cual dio vida a una hoja de ruta internacional, llamada Agenda 2030, con el fin de guiar a los países en la implementación del desarrollo sostenible. Dentro de esta agenda, se encuentra el Objetivo de Desarrollo Sostenible 10 sobre “Reducir la desigualdad en y entre los países”, el cual contempla diez metas para este propósito. Así, en este Estudio de Caso se analizarán las 28 acciones públicas, presentadas por el Consejo Nacional para la implementación de la Agenda 2030 para el Desarrollo Sostenible, con el fin de determinar si la estrategia chilena, llevada a cabo entre el 2015 y 2018, considera un concepto multidimensional de las disparidades económicas o no.In Chile, inequality has been a long-time problem, which can be seen in its inhabitants’ everyday life in diverse areas, such as in education, health, pension system, territorially, among others. Moreover, this has resulted in an increasing of social discontent, which can be reflected in the great number of social movements that triggered the so-called “Social Outbreak” in 2019. This demonstrated, among other things, the urgency of addressing the problem of inequalities in Chile. Nonetheless, it is important first to define how economic inequality is understood, which is multidimensional, since it comprises ex-ante and ex-post dimensions, that is to say, of opportunities and of incomes or rewards, respectively. In this sense, the reduction of economic inequalities has to answer to these both dimensions, if these are to be effectively diminished. Furthermore, in 2015, Chile signed a resolution of the United Nations General Assembly, which gave birth to an international road map, called 2030 Agenda, in order to guide the diverse countries on the implementation of sustainable development. Within this agenda, there is the Sustainable Development Goal 10 about “Reducing inequalities within and among countries”, which is comprised of ten targets for this. Thus, this Study Case will analyse the 28 public actions, presented by the National Council for the implementation of the 2030 Agenda for Sustainable Development, in order to determine if the Chilean strategy, pursued between 2015 and 2018, considers the multidimensional concept of economic inequalities, or not

Hormone replacement therapy in postmenopausal women: endometrial hyperplasia and irregular bleeding

Background: The decline in circulating oestrogen around the time of the menopause often induces unacceptable symptoms that affect the health and well being of women. Hormone replacement therapy (both unopposed oestrogen and oestrogen and progestogen combinations) is an effective treatment for these symptoms. In women with an intact uterus, unopposed oestrogen may induce endometrial stimulation and increase the risk of endometrial hyperplasia and carcinoma. The addition of progestogen reduces this risk but may cause unacceptable symptoms, bleeding and spotting which can affect adherence to therapy. Objectives: The objective of this review is to assess which hormone replacement therapy regimens provide effective protection against the development of endometrial hyperplasia and/or carcinoma with a low rate of abnormal vaginal bleeding. Search strategy: Electronic searches for relevant randomised controlled trials of the Cochrane Menstrual Disorders and Subfertility Group Register of Trials, MEDLINE, EMBASE, PsycLIT, Current Contents, Biological Abstracts, Social Sciences Index and CINAHL were performed. Attempts were also made to identify trials from citation lists of review articles and drug companies were contacted for unpublished data. In most cases, the corresponding author of each included trial was contacted for additional information. Selection criteria: The inclusion criteria were randomised comparisons of unopposed oestrogen therapy, combined continuous oestrogen-progestogen therapy and sequential oestrogen-progestogen therapy with each other and placebo administered over a minimum treatment period of six months. Trials had to assess which regimen was the most protective against the development of endometrial hyperplasia/carcinoma and/or caused the lowest rate of irregular bleeding. Data collection and analysis: Twenty three RCTs were identified and five were excluded. The reviewers assessed the eighteen included studies for quality, extracted the data independently and odds ratios for dichotomous outcomes were estimated. Outcomes analysed included frequency of endometrial hyperplasia or carcinoma, frequency of irregular bleeding and unscheduled biopsies or dilation and curettage, and adherence to therapy. Main results: Unopposed moderate or high dose oestrogen therapy was associated with a significant increase in rates of endometrial hyperplasia with increasing rates at longer duration of treatment and follow up. Odds ratios ranged from 5.4 (1.4-20.9) for 6 months of treatment to 16.0 (9.3-27.5) for 36 months of treatment with moderate dose oestrogen (in the PEPI trial, 62% of those who took moderate dose oestrogen had some form of hyperplasia at 36 months compared to 2% of those who took placebo). Irregular bleeding and non adherence to treatment were also significantly more likely under these unopposed oestrogen regimens with greater effects with higher dose therapy. There was no evidence of increased hyperplasia rates, however, with low dose oestrogen. The addition of progestogens, either in continuous combined or sequential regimens, helped to prevent the development of endometrial hyperplasia and improved adherence to therapy (odds ratios of 3.7 for sequential therapy and 6.0 for continuous therapy). Irregular bleeding, however, was more likely under a continuous than a sequential oestrogen-progestogen regimen (OR = 2.3, 95% CI 2.1-2.5) but at longer duration of treatment, continuous therapy was more protective than sequential therapy in preventing endometrial hyperplasia (OR = 0.3, 95% CI 0.1-0.97). There was evidence of a higher incidence of hyperplasia under long cycle sequential therapy (progestogen given every three months) compared to monthly sequential therapy (progestogen given every month). No increase in endometrial cancer was seen in any of the treatment groups during the limited duration (maximum of three years) of these trials. Reviewers' conclusions: There is strong and consistent evidence in this review that unopposed oestrogen therapy, at moderate and high doses, is associated with increased rates of endometrial hyperplasia, irregular bleeding and consequent non adherence to therapy. The addition of oral progestogens administered either cyclically or continuously is associated with reduced rates of hyperplasia and improved adherence to therapy. Irregular bleeding is less likely under sequential than continuous therapy but there is a suggestion that continuous therapy over long duration is more protective than sequential therapy in the prevention of endometrial hyperplasia. Hyperplasia is more likely when progestogen is given every three months in a sequential regimen compared to a monthly progestogen sequential regimen.Output Type: Revie

Medical Therapies for Uterine Fibroids - A Systematic Review and Network Meta-Analysis of Randomised Controlled Trials

BACKGROUND: Uterine fibroids are common, often symptomatic and a third of women need repeated time off work. Consequently 25% to 50% of women with fibroids receive surgical treatment, namely myomectomy or hysterectomy. Hysterectomy is the definitive treatment as fibroids are hormone dependent and frequently recurrent. Medical treatment aims to control symptoms in order to replace or delay surgery. This may improve the outcome of surgery and prevent recurrence. PURPOSE: To determine whether any medical treatment can be recommended in the treatment of women with fibroids about to undergo surgery and in those for whom surgery is not planned based on currently available evidence. STUDY SELECTION: Two authors independently identified randomised controlled trials (RCT) of all pharmacological treatments aimed at the treatment of fibroids from a list of references obtained by formal search of MEDLINE, EMBASE, Cochrane library, Science Citation Index, and ClinicalTrials.gov until December 2013. DATA EXTRACTION: Two authors independently extracted data from identified studies. DATA SYNTHESIS: A Bayesian network meta-analysis was performed following the National Institute for Health and Care Excellence-Decision Support Unit guidelines. Odds ratios, rate ratios, or mean differences with 95% credible intervals (CrI) were calculated. RESULTS AND LIMITATIONS: A total of 75 RCT met the inclusion criteria, 47 of which were included in the network meta-analysis. The overall quality of evidence was very low. The network meta-analysis showed differing results for different outcomes. CONCLUSIONS: There is currently insufficient evidence to recommend any medical treatment in the management of fibroids. Certain treatments have future promise however further, well designed RCTs are needed

Ancient Egypt 1920 Part 4

Part 4 of the 1920 Ancient Egypt books. Contents include Coptic twists and plaits, the sphinxes of Tanis, Alexandrian world maps, passages of Aleppo Citadel, and Kheker friezes.https://knowledge.e.southern.edu/kweeks_coll/1013/thumbnail.jp