Optimising health after early menopause.

The typical age at menopause is 50-51 years in high-income countries. However, early menopause is common, with around 8% of women in high-income countries and 12% of women globally experiencing menopause between the ages of 40 years and 44 years. Menopause before age 40 years (premature ovarian insufficiency) affects an additional 2-4% of women. Both early menopause and premature ovarian insufficiency can herald an increased risk of chronic disease, including osteoporosis and cardiovascular disease. People who enter menopause at younger ages might also experience distress and feel less supported than those who reach menopause at the average age. Clinical practice guidelines are available for the diagnosis and management of premature ovarian insufficiency, but there is a gap in clinical guidance for early menopause. We argue that instead of distinct age thresholds being applied, early menopause should be seen on a spectrum between premature ovarian insufficiency and menopause at the average age. This Series paper presents evidence for the short-term and long-term consequences of early menopause. We offer a practical framework for clinicians to guide diagnosis and management of early menopause, which considers the nature and severity of symptoms, age and medical history, and the individual's wishes and priorities to optimise their quality of life and short-term and long-term health. We conclude with recommendations for future research to address key gaps in the current evidence.

Associations between socioeconomic deprivation and pharmaceutical prescribing in primary care in England.

BACKGROUND: Socioeconomic deprivation is associated with health inequality. Previous studies have described associations between primary care prescribing rates and deprivation for individual drugs or drug classes. We explore the correlation between socioeconomic deprivation and the rate of prescribing of individual pharmaceutical drugs, and drug classes, in primary care in England, to identify prescribing inequalities that would require further investigation. METHODS: In this cross-sectional study, national primary care prescribing data, by primary care practice, were retrieved for the calendar year 2019 in England. Socioeconomic deprivation was quantified using the Index of Multiple Deprivation (IMD) score. Correlations were calculated using Spearman's rank correlation coefficient (ρ), adjusting for practice list size and demographics, with a Bonferroni-corrected p value threshold of 5×10-5. RESULTS: We included 1.05 billion prescription items dispensed from 6896 England practices. 142/206 (69%) drug classes and 505/774 (65%) drugs were significantly correlated with IMD score (p<5×10-5). Of the 774 included drugs, 31 (4%) were moderately positively associated with IMD score (ρ>0.4). Only one was moderately negatively correlated with IMD score (ρ<-0.4), suggesting higher prescribing rates in more affluent areas. The drug classes most strongly associated with IMD score included opioid and non-opioid analgesics, antipsychotics and reflux medications. Drug classes most strongly associated with affluence included epinephrine, combined oral contraceptives and hormone replacement therapy. CONCLUSION: We identify novel associations of prescribing with deprivation. Further work is required to identify the underlying reasons for these associations so that appropriate interventions can be formulated to address drivers of inequality.

The impact of disasters on contraception in OECD member countries: a scoping review.

OBJECTIVES: Review evidence is lacking about how contraception is affected by severe social disruption, such as that caused by the COVID-19 pandemic. The purpose of this scoping review was to explore the impact of natural and man-made disasters on contraception in OECD member countries. METHODS: Manual searches and systematic searches in six electronic databases were conducted with no language restrictions. All articles were screened by at least two researchers. The data were analysed thematically. RESULTS: 108 articles were included. Most focussed on the Zika virus outbreak (n = 50) and the COVID-19 pandemic (n = 28). Four key themes were identified: importance of contraception during disasters, impact of disasters on contraceptive behaviour, barriers to contraception during disasters and ways of improving use of contraception during disasters. Despite efforts to increase access to contraception including by transforming ways of delivery, barriers to use meant that unmet need persisted. CONCLUSIONS: To prevent adverse health outcomes and reduce health costs as a result of failure to have access to contraception during disasters, there is a need to intensify efforts to remove barriers to use. This should include increasing access and information on methods of contraception and their side effects (e.g., menstrual suppression) and making contraception freely available.

Parental experiences of prenatal whole exome sequencing (WES) in cases of ultrasound diagnosed fetal structural anomaly.

OBJECTIVE: To explore parental experiences of whole exome sequencing (WES) for prenatal diagnosis and ascertain what influenced their decision-making to undergo testing. METHOD: Twelve women comprised a purposeful sample in a series of semistructured interviews. All had received a fetal anomaly diagnosis on ultrasound. A topic guide was used, and transcripts were thematically analyzed to elicit key themes. RESULTS: Five main themes (parental experiences of prenatal WES, need for information, consent/reasons for prenatal WES, sources of support for prenatal WES, and return of WES findings to families) emerged, some with multiple subthemes. CONCLUSIONS: Parents desired as much information as possible and appreciated information being repeated and provided in various formats. Many struggled with clinical uncertainty relating to the cause and prognosis following a fetal anomaly diagnosis and found it difficult to balance the risks of invasive testing against their need for more definitive information. Parents trusted their clinicians and valued their support with decisions in pregnancy. Testing was sometimes pursued to reassure parents that their baby was "normal" rather than to confirm an underlying genetic problem. Parents were motivated to undergo WES for personal and altruistic reasons but disliked waiting times for results and were uncertain about what findings might be returned.

Exome sequencing improves genetic diagnosis of structural fetal abnormalities revealed by ultrasound.

The genetic etiology of non-aneuploid fetal structural abnormalities is typically investigated by karyotyping and array-based detection of microscopically detectable rearrangements, and submicroscopic copy-number variants (CNVs), which collectively yield a pathogenic finding in up to 10% of cases. We propose that exome sequencing may substantially increase the identification of underlying etiologies. We performed exome sequencing on a cohort of 30 non-aneuploid fetuses and neonates (along with their parents) with diverse structural abnormalities first identified by prenatal ultrasound. We identified candidate pathogenic variants with a range of inheritance models, and evaluated these in the context of detailed phenotypic information. We identified 35 de novo single-nucleotide variants (SNVs), small indels, deletions or duplications, of which three (accounting for 10% of the cohort) are highly likely to be causative. These are de novo missense variants in FGFR3 and COL2A1, and a de novo 16.8 kb deletion that includes most of OFD1. In five further cases (17%) we identified de novo or inherited recessive or X-linked variants in plausible candidate genes, which require additional validation to determine pathogenicity. Our diagnostic yield of 10% is comparable to, and supplementary to, the diagnostic yield of existing microarray testing for large chromosomal rearrangements and targeted CNV detection. The de novo nature of these events could enable couples to be counseled as to their low recurrence risk. This study outlines the way for a substantial improvement in the diagnostic yield of prenatal genetic abnormalities through the application of next-generation sequencing.

Prenatal whole exome sequencing: the views of clinicians, scientists, genetic counsellors and patient representatives.

OBJECTIVE: Focus groups were conducted with individuals involved in prenatal diagnosis to determine their opinions relating to whole exome sequencing in fetuses with structural anomalies. METHOD: Five representatives of patient groups/charities (PRGs) and eight clinical professionals (CPs) participated. Three focus groups occurred (the two groups separately and then combined). Framework analysis was performed to elicit themes. A thematic coding frame was identified based on emerging themes. RESULTS: Seven main themes (consent, analysis, interpretation/reinterpretation of results, prenatal issues, uncertainty, incidental findings and information access) with subthemes emerged. The main themes were raised by both groups, apart from 'analysis', which was raised by CPs only. Some subthemes were raised by PRGs and CPs (with different perspectives). Others were raised either by PRGs or CPs, showing differences in patient/clinician agendas. CONCLUSIONS: Prenatal consent for whole exome sequencing is not a 'perfect' process, but consent takers should be fully educated regarding the test. PRGs highlighted issues involving access to results, feeling that women want to know all information. PRGs also felt that patients want reinterpretation of results over time, whilst CPs felt that interpretation should be performed at the point of testing only. © 2016 John Wiley & Sons, Ltd.

BAC chromosomal microarray for prenatal detection of chromosome anomalies in fetal ultrasound anomalies: an economic evaluation.

INTRODUCTION: To determine the cost-effectiveness of prenatal chromosomal microarray (CMA) when performed for structural anomalies on fetal ultrasound scan over conventional techniques. METHOD: A decision tree was populated using data from a prospective cohort of women undergoing testing when a fetal ultrasound scan showed a structural abnormality. Nine strategies of testing were modeled including combinations of the tests: QFPCR, G-band karyotyping, CMA and FISH for DiGeorge (22q) microdeletion. RESULTS: When CMA costs GBP 405 and using a 1-Mb BAC array it would cost GBP 24,600 for every additional case detected by CMA over a combination of QFPCR, followed by G-band karyotype, followed lastly by FISH (for DiGeorge syndrome). If CMA is performed instead of conventional karyotyping alone it costs GBP 33,000 for every additional case detected. However, if the cost of CMA is reduced to GBP 360 than when CMA is performed instead of conventional karyotyping alone it would cost GBP 9,768 for every additional case detected. DISCUSSION: The use of a prenatal BAC CMA is not currently cost-effective when compared to other testing strategies. However, as CMA costs decrease and resolution (and detection rates) increase it is likely to become the cost-effective option of the future.

GP's role in supporting women with anal incontinence after childbirth injury: a qualitative study.

BACKGROUND: Obstetric anal sphincter injury is the most common cause of anal incontinence for women, which often has profound impacts on women's lives. GPs offer a first line of contact for many women, but we know that very few women experiencing anal incontinence postnatally report discussing it with their GPs. AIM: To identify key ways in which GPs can support women with anal incontinence caused by childbirth injuries. DESIGN AND SETTING: A qualitative study investigating women's experiences with their GP, and GPs' perspectives about providing such care. METHOD: This qualitative study combined two phases: first, a series of in-depth semi-structured interviews with women experiencing anal incontinence caused by childbirth injuries (n = 41); and second, focus groups with GPs (n = 13) stratified by experience. Thematic analysis was conducted and relevant themes from across the two datasets were examined. RESULTS: Mediating factors in GP care for women with anal incontinence caused by childbirth injuries centred around three key themes: the role of the GP, access and pathways, and communication. CONCLUSION: The findings demonstrate multifactorial challenges in identifying the problem and supporting women experiencing anal incontinence after childbirth injury in primary care settings. Many GPs lacked confidence in their role in supporting women, and women were often reluctant to seek help. Those women who did seek help often experienced frustrations consulting with their GPs. In a context where women are often reluctant to ask for help, their concerns are not always taken seriously, and where GPs do not routinely ask about anal incontinence, potential anal incontinence after childbirth injury appears to be often missed in a primary care setting.

"If it helps..." the use of microarray technology in prenatal testing: patient and partners reflections.

The objective was to gain insight into the experiences of women and their partners diagnosed with a fetal abnormality on prenatal ultrasound examination and receiving genetic testing including microarray. Twenty-five semi-structured interviews were performed with women +/- their partners after receiving the results of prenatal genetic testing. Framework analysis was performed to elicit themes and subthemes. Five main themes were recognized; diagnosis, genetic testing, family and support, reflections of the treatment received and emotions. Our results showed that women recall being told about QFPCR for trisomy 13, 18, and 21 but often no further testing. Women expected the conventional karyotype and microarray result would be normal following a normal QFPCR result. There were frequent misconceptions by couples regarding aspects of counseling/testing. Communication of variants of unknown (clinical) significance (VOUS) presents a particularly difficult challenge. Good clear communication by health care professionals is paramount. When counseling women and their partners for fetal chromosomal testing it should be reinforced that although the most common, trisomy 13, 18, and 21 only account for some of the chromosomal changes resulting in abnormal scan findings. Couples should have literature to take home summarizing scan anomalies and reinforcing information about genetic testing.

Qualitative systematic review of general practitioners' (GPs') views and experiences of providing postnatal care.

OBJECTIVES: Develop an understanding of the views and experiences of general practitioners (GPs) about their role in postnatal care, including barriers and facilitators to good care, and timing and content of planned postnatal checks. DESIGN: Qualitative systematic review. DATA SOURCES: Electronic database searches of MEDLINE, EMBASE, CINAHL, PubMed, Web of Science, PsychINFO from January 1990 to September 2021. Grey literature and guideline references from National Institute of Health and Care Excellence, WHO, International Federation of Gynecology and Obstetrics, Royal College of General Practitioners, Royal College of Obstetrics and Gynaecology. INCLUSION CRITERIA: Papers reporting qualitative data on views and experiences of GPs about postnatal care, including discrete clinical conditions in the postnatal period. Papers were screened independently by two reviewers and disputes resolved by a third reviewer. QUALITY APPRAISAL: The Critical Appraisal Skills Programme checklist was used to appraise studies. DATA EXTRACTION AND SYNTHESIS: Thematic synthesis involving line-by-line coding, generation of descriptive then analytical themes was conducted by the review team. The Capability, Opportunity, Motivation-Behaviour (COM-B) model was used to develop analytical themes. RESULTS: 20 reports from 18 studies met inclusion criteria. Studies were published from 2008 to 2021, reporting on 469 GPs. 13 were from UK or Australia. Some also reported views of non-GP participants. The clinical focus of studies varied, for example: perinatal mental health, postnatal contraception. Five themes were generated, four mapped to COM-B: psychological capability, physical opportunity, social opportunity and motivation. One theme was separate from the COM-B model: content and timing of postnatal checks. Strong influences were in physical and social opportunity, with time and organisation of services being heavily represented. These factors sometimes influenced findings in the motivation theme. CONCLUSIONS: GPs perceived their role in postnatal care as a positive opportunity for relationship building and health promotion. Addressing organisational barriers could impact positively on GPs' motivation to provide the best care. PROSPERO REGISTRATION NUMBER: 268982.

Women's experiences of anal incontinence following vaginal birth: A qualitative study of missed opportunities in routine care contacts.

OBJECTIVES: This study aimed to explore experiences of women with anal incontinence following a childbirth injury, and to identify areas of missed opportunities within care they received. DESIGN: This is a qualitative study involving semi-structured interviews. SETTING: Participants were recruited via five hospitals in the UK, and via social media adverts and communication from charity organisations. PARTICIPANTS: Women who have experienced anal incontinence following a childbirth injury, either within 7 years of sustaining the injury, or if they identified new, or worsening symptoms of AI at the time of menopause. MAIN OUTCOME MEASURES: Main outcomes are experiences of women with anal incontinence following childbirth injury, and missed opportunities within the care they received. RESULTS: The following main themes were identified: opportunities for diagnosis missed, missed opportunities for information sharing and continuity and timeliness of care. CONCLUSIONS: Anal Incontinence following a childbirth injury has a profound impact on women. Lack of information and awareness both amongst women and healthcare professionals contributes to delays in accurate diagnosis and appropriate treatment.

Guidance impact on primary care prescribing rates of simple analgesia: an interrupted time series analysis in England.

BACKGROUND: In March 2018, NHS England published guidance for clinical commissioning groups (CCGs) to encourage implementation of policy to reduce primary care prescriptions of over-the-counter medications, including simple analgesia. AIM: To investigate the impact of guidance publication on prescribing rates of simple analgesia (oral paracetamol, oral ibuprofen, and topical non-steroidal anti-inflammatory drugs) in primary care; CCG guidance implementation intentions; and whether the guidance has created health inequality based on socioeconomic status. DESIGN AND SETTING: Interrupted time series analysis of primary care prescribing data in England. METHOD: Practice-level prescribing data from January 2015 to March 2019 were obtained from NHS Digital. Interrupted time series analyses were used to assess the association of guidance publication with prescribing rates. The association between practice-level prescribing rates and Index of Multiple Deprivation scores before and after publication was quantified using multivariable Poisson regression. Freedom of information requests were submitted to all CCGs. RESULTS: There was a statistically significant 4.4% reduction in prescribing of simple analgesia following guidance publication (adjusted incidence rate ratio 0.96, 95% CI = 0.92 to 0.99, P = 0.027), adjusting for underlying time trend and seasonality. There was considerable diversity across CCGs in whether or how they chose to implement the guidance. Practice-level prescribing rates were greater in more deprived areas. CONCLUSION: Guidance publication was associated with a small reduction in the prescribing rates of simple analgesia across England, without evidence of creating additional health inequality. Careful implementation by CCGs would be required to optimise cost saving to the NHS.

Women's experiences of diagnosis and management of polycystic ovary syndrome: a mixed-methods study in general practice.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common lifelong metabolic condition with serious associated comorbidities. Evidence points to a delay in diagnosis and inconsistency in the information provided to women with PCOS. AIM: To capture women's experiences of how PCOS is diagnosed and managed in UK general practice. DESIGN AND SETTING: This was a mixed-methods study with an online questionnaire survey and semi-structured telephone interviews with a subset of responders. METHOD: An online survey to elicit women's experiences of general practice PCOS care was promoted by charities and BBC Radio Leicester. The survey was accessible online between January 2018 and November 2018. A subset of responders undertook a semi-structured telephone interview to provide more in-depth data. RESULTS: A total of 323 women completed the survey (average age 35.4 years) and semi-structured interviews were conducted with 11 women. There were five key themes identified through the survey responses. Participants described a variable lag time from presentation to PCOS diagnosis, with a median of 6-12 months. Many had experienced mental health problems associated with their PCOS symptoms, but had not discussed these with the GP. Many were unable to recall any discussion about associated comorbidities with the GP. Some differences were identified between the experiences of women from white British backgrounds and those from other ethnic backgrounds. CONCLUSION: From the experiences of the women in this study, it appears that PCOS in general practice is not viewed as a long-term condition with an increased risk of comorbidities including mental health problems. Further research should explore GPs' awareness of comorbidities and the differences in PCOS care experienced by women from different ethnic backgrounds.

Socioeconomic status and HRT prescribing: a study of practice-level data in England.

BACKGROUND: Concerns have been raised that women from deprived backgrounds are less likely to be receiving hormone replacement therapy (HRT) treatment and its benefits, although evidence in support of this is lacking. AIM: To investigate general practice HRT prescription trends and their association with markers of socioeconomic deprivation. DESIGN AND SETTING: Cross-sectional study of primary care prescribing data in England in 2018. METHOD: Practice-level prescribing rate was defined as the number of items of HRT prescribed per 1000 registered female patients aged ≥40 years. The association between Index of Multiple Deprivation (IMD) score and HRT prescribing rate was tested using multivariate Poisson regression, adjusting for practice proportions of obesity, smoking, hypertension, diabetes, coronary heart disease and cerebrovascular disease, and practice list size. RESULTS: The overall prescribing rate of HRT was 29% lower in practices from the most deprived quintile compared with the most affluent (incidence rate ratio [IRR] = 0.71; 95% confidence interval [CI] = 0.68 to 0.73). After adjusting for all cardiovascular disease outcomes and risk factors, the prescribing rate in the most deprived quintile was still 18% lower than in the least deprived quintile (adjusted IRR = 0.82; 95% CI = 0.77 to 0.86). In more deprived practices, there was a significantly higher tendency to prescribe oral HRT than transdermal preparations (P<0.001). CONCLUSION: This study highlights inequalities associated with HRT prescription. This may reflect a large unmet need in terms of menopause care in areas of deprivation. Further research is needed to identify the factors from patient and GP perspectives that may explain this.

Using the International Classification of Functioning, Disability, and Health Model to Gain Perspective of the Benefits of Yoga in Stroke, Multiple Sclerosis, and Children to Inform Practice for Children with Cerebral Palsy: A Meta-Analysis.

OBJECTIVE: Research pertaining to yoga and children with cerebral palsy (CP) is negligible. The primary purpose of this study was to determine the domains of the International Classification of Functioning, Disability, and Health (ICF) model and levels of evidence for yoga and adults with stroke and multiple sclerosis (MS), and children. A secondary purpose was to decide whether any inferences could be made for children with CP. DESIGN: This study included a meta-analysis. INTERVENTIONS: A systematic review was performed of yoga and said populations. Outcome measures were categorized according to the ICF model domains of body structures and function, activity, and quality of life. Effect sizes (ESs) were calculated by using Cohen's d. Since there were few commonalities among outcome measures and reporting of outcomes within and among diagnostic groups, direct comparisons of ESs were difficult. Hence, we chose to evaluate the impact of yoga as compared with the control group or other physical exercise by using a General Linear Mixed Model. RESULTS: There were 5 yoga studies with stroke, 15 with MS, and 12 with children. Studies with children used outcomes related to body structure and function, whereas those with stroke and MS used outcomes across all three domains of the ICF. ESs varied from negligible to medium for stroke, from negligible to large for MS and children. CONCLUSIONS: The findings of this meta-analysis indicate that yoga is no better or worse than other exercise modalities as a treatment intervention for adults with stroke and MS, and children. Group yoga classes are typically social environments that can contribute to increased physical progress and feelings that contribute to quality of life, which may benefit individuals with CP. More research on yoga and particularly in children and adults with CP would yield valuable information for creating effective and safe yoga programs with a rich array of benefits.