An integrated care pathway for menorrhagia across the primary–secondary interface : patients' experience, clinical outcomes, and service utilisation

Background: ‘‘Referral’’ characterises a significant area of interaction between primary and secondary care. Despite advantages, it can be inflexible, and may lead to duplication. Objective: To examine the outcomes of an integrated model that lends weight to general practitioner (GP)-led evidence based care. Design: A prospective, non-random comparison of two services: women attending the new (Bridges) pathway compared with those attending a consultant-led one-stop menstrual clinic (OSMC). Patients’ views were examined using patient career diaries, health and clinical outcomes, and resource utilisation. Follow-up was for 8 months. Setting: A large teaching hospital and general practices within one primary care trust (PCT). Results: Between March 2002 and June 2004, 99 women in the Bridges pathway were compared with 94 women referred to the OSMC by GPs from non-participating PCTs. The patient career diary demonstrated a significant improvement in the Bridges group for patient information, fitting in at the point of arrangements made for the patient to attend hospital (ease of access) (p,0.001), choice of doctor (p = 0.020), waiting time for an appointment (p,0.001), and less ‘‘limbo’’ (patient experience of non-coordination between primary and secondary care) (p,0.001). At 8 months there were no significant differences between the two groups in surgical and medical treatment rates or in the use of GP clinic appointments. Significantly fewer (traditional) hospital outpatient appointments were made in the Bridges group than in the OSMC group (p,0.001). Conclusion: A general practice-led model of integrated care can significantly reduce outpatient attendance while improving patient experience, and maintaining the quality of care

Cesarean delivery on maternal request: Can the ethical problem be solved by the principlist approach?

In this article, we use the principlist approach to identify, analyse and attempt to solve the ethical problem raised by a pregnant woman's request for cesarean delivery in absence of medical indications

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Endometrial responses to hormone replacement therapy

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Classifying Adenomyosis: Progress and Challenges

Classically, the diagnosis of adenomyosis relied on histological examination of uteri following hysterectomy and classifications focused on the depth of endometrial invasion within the myometrium. There remain uncertainties around the cut-off point for the histological diagnosis. Imaging-based diagnosis enables recognition of the condition in women not undergoing surgery and facilitates the assessment of the extent of adenomyosis within the whole uterus, as well as of affections of the uterovesical pouch and of the pouch of Douglas. In this article, we explore the diagnostic uncertainties, the need to produce a classification of the condition and the challenges towards that goal. A distinction should be drawn between disease mapping and a classification that may link histological or image-based features with clinical characteristics, or with pathophysiology. An agreed system for reporting adenomyotic lesions may enable comparisons of research studies and thus contribute towards an informed classification. To this aim, we outline the features of the condition and explore the characteristics that are considered when producing a taxonomy. These include the latest proposal for subdivision of adenomyosis into an internal and an external variant. We also explore the uncertainties linked to classifying involvement of the uterovesical pouch, the pouch of Douglas and lesions in the outer myometrium. The limitations of currently available evidence suggest that agreement on a hypothesis to underpin a classification is unlikely at present. Therefore, current efforts will probably remain focused on disease mapping

The inter-role confidentiality conflict in recruitment for clinical research

Recruiting patients into clinical research is essential for the advancement of medical knowledge. However, when the physician undertaking the care of the patient is also responsible for recruitment into clinical research, a situation arises of an inter-role breach of confidentiality which is distinguishable from other conflicts of interest. Such discord arises as the physician utilizes confidential information obtained within the therapeutic relationship beyond its primary objective, and safeguards ought to be observed in order to avert this important, and generally overlooked, problem. The moral worth of the pledge of confidentiality is based not on its innate value but on its being a promise on which subsequent interactions and disclosures are founded. Within the patient-doctor interaction, confidentiality is an important facet of the promised fidelity and, as such, a loose interpretation of the notion threatens the essence of the relationship, and any violation thereof requires compelling moral justification. To avoid conflict, patients' confidential information ought not be used for the purpose of recruitment, which needs to be undertaken through general education and non-directed appeals, and a preliminary consent to be approached for research should be obtained from the patient prior to her being identified as a suitable research subject. Securing this prior consent would avoid one source of potential, albeit unintended, coercion

The History of the Discovery of Ectopic Epithelial Cells in Lower Peritoneal Organs: The So-Called Mucosal Invasion

Through microscopy, early researchers identified the epithelium on the inner surfaces of the uterus, cervix and Fallopian tubes. The identification of ectopic epithelium was gradual, starting from the gross pathology study of unusual cystic lesions. Towards the end of the nineteenth century, attention focused on the epithelium as a critical component. The term ‘adenomyoma’ was coined around eighteen eighty to designate the majority of mucosa-containing lesions. Several theories were advanced to explain its aetiology. In the main, lesions were considered to arise from invasion from uterine epithelium; implantation of endometrium through retrograde menstruation; hematogenous or lymphatic spread; or from embryonic remnants. Although initially widely rejected, around 1920, an almost unanimous consensus formed on the endometrial nature of epithelial invasions. During the following years, adenomyosis and endometriosis came to be used to distinguished lesions within or outside the uterus. Adenomyosis was attributed to direct infiltration of uterine mucosa into the myometrium, and endometriosis to the implantation of endometrial cells and stroma into the peritoneal cavity through retrograde menstruation. Around the same time, ovarian lesions, initially described as ovarian hematomas or chocolate cysts, were regarded as a form of endometriosis. Three variants of endometriosis were thus described: superficial peritoneal, deep nodular and ovarian endometriomas. Ectopic epithelium has long been recognised as having similarities to tubal, or cervical epithelium. Lesions containing mixed epithelium are often termed Müllerianosis. This article demonstrates the stepwise evolution of knowledge, the role of the pioneers and the difficulties that needed to be overcome. It also demonstrates the value of collaboration and the inter-connected nature of the scientific endeavour

The pathogenesis of uterine adenomyosis

The exact aetiology and pathogenesis of uterine adenomyosis are not clear. Increased endometrial invasiveness has been proposed in the literature, but without conclusive evidence. This thesis was undertaken to examine the pathogenesis of adenomyosis and the differences between affected and unaffected uteri, testing two possibilities with adenomyosis: (i) that the myometrium is permissive to invasion by a normal basal endometrium, or (ii) that the basal endometrium has a higher invasive potential and penetrates a normal myometrium. To examine the early phases of development of adenomyosis, a mouse model was used, where adenomyosis was induced by dosing female pups with tamoxifen. The same experiment was used on C57/BL6J strain to examine strain differences in response to tamoxifen and predisposition to adenomyosis. Adenomyosis in the human uterus was characterised, examining the immunohistochemical, light and electron microscopy structure, and RNA microarrays of affected and unaffected uteri. The invasive properties of the stroma and its interaction with the underlying myometrium were further studied in a co-culture model. Adenomyosis was successfully induced in the CD1 mice, with abnormal development and disruption of the inner circular myometrium. However, the C57/BL6J did not develop adenomyosis inspite of the presence of inner myometrial abnormalities comparable to the CD1 mice. Affected human uteri showed distinct myometrial features such as reduced myometrial cellular density and enlarged nuclei with hypertrophy and hyperplasia seen on light microscopy. Electron microscopy revealed ultrastructural features (e.g. reduced caveolae and increased myelin bodies, intermediate filaments and dense bands) in adenomyotic uteri. A large number of dysregulated genes were detected between affected and unaffected uteri, with Wnt5a being a key downregulated gene. Steroid reception expression was equally altered in cases of adenomyosis (e.g. reduced progesterone receptors and increased estrogen receptor beta). Increased vimentin immunostaining was equally observed in the inner myometrium of diseased uteri. An increased adenomyotic stromal invasiveness and increased myometrial permissiveness was observed in the co-culture model. The thesis demonstrates that the endometrial – myometrial interface behaves differently in uteri with adenomyosis, concluding that adenomyosis is a uterine disease characterized by both increased endometrial invasiveness and myometrial defects that play a facilitative role for this invasion. Both the myometrium and endometrial stroma of diseased uteri show a unique phenotype, gene expression and protein expression profiles.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

From Retrograde Menstruation to Endometrial Determinism and a Brave New World of “Root Treatment” of Endometriosis: Destiny or a Fanciful Utopia?

Practically unknown outside of China, the “endometrial determinism” theory was proposed to account for the apparent gap between the relatively low prevalence of endometriosis and nearly universal retrograde menstruation. Attracting uncritical advocacy, the theory culminates in a recent consensus by elite Chinese gynecologists in favor of “root treatment”, intended to nip endometriosis in the bud. Correcting endometrial “defects” can gain further momentum by the presence of cancer-driver mutations such as KRAS mutations in the endometrium of women with endometriosis and the recent introduction of therapeutics aiming to rectify the effect of these mutations for cancer treatment. We provide a critical appraisal of evidence for endometrial aberrations in endometriosis and relevant experimental evidence. All available evidence of endometrial “defect” is invariably post hoc and may well be secondary to induced endometriosis. We propose that the theory of “endometrial determinism” needs to demonstrate a clear causal and a phylogenetic relationship between endometrial aberrations and endometriosis. We argue that while it is highly likely that endometriosis is a consequence of retrograde menstruation, the case that molecular aberrations as a sole or a necessary determinant remains to be proven. “Root treatment” is a worthy ambition but as of now it is close to a fanciful Utopia