Maternal cardiac adaptation and fetal growth.

BACKGROUND: Pregnancies with small-for-gestational-age fetuses are at increased risk of adverse maternal-fetal outcomes. Previous studies examining the relationship between maternal hemodynamics and fetal growth were mainly focused on high-risk pregnancies and those with fetuses with extreme birthweights, such as less than the 3rd or 10th percentile and assumed a similar growth pattern in fetuses above the 10th percentile throughout gestation. OBJECTIVE: This study aimed to evaluate the trends in maternal cardiac function, fetal growth, and oxygenation with advancing gestational age in a routine obstetrical population and all ranges of birthweight percentiles. STUDY DESIGN: This was a prospective, longitudinal study assessing maternal cardiac output and peripheral vascular resistance by bioreactance at 11+0 to 13+6, 19+0 to 24+0, 30+0 to 34+0, and 35+0 to 37+0 weeks' gestation, sonographic estimated fetal weight in the last 3 visits and the ratio of the middle cerebral artery by umbilical artery pulsatility indices or cerebroplacental ratio in the last 2 visits. Women were divided into the following 5 groups according to birthweight percentile: group 1, <10th percentile (n=261); group 2, 10 to 19.9 percentile (n=180); group 3, 20 to 29.9 percentile (n=189); group 4, 30 to 69.9 percentile (n=651); and group 5, ≥70th percentile (n=508). The multilevel linear mixed-effects model was performed to compare the repeated measures of hemodynamic variables and z scores of the estimated fetal weight and cerebroplacental ratio. RESULTS: In visit 2, compared with visit 1, in all groups, cardiac output increased, and peripheral vascular resistance decreased. At visit 3, groups 1, 2, and 3, compared with 4 and 5, demonstrated an abrupt decrease in cardiac output and increase in peripheral vascular resistance. From visit 2, group 1 had a constant decline in estimated fetal weight, coinciding with the steepest decline in maternal cardiac output and rise in peripheral vascular resistance. In contrast, in groups 4 and 5, the estimated fetal weight had a stable or accelerative pattern, coinciding with the greatest increase in cardiac output and lowest peripheral vascular resistance. Groups 2 and 3 showed a stable growth pattern with intermediate cardiac output and peripheral vascular resistance. Increasing birthweight was associated with higher cerebroplacental ratio. Groups 3, 4, and 5 had stable cerebroplacental ratio across visits 3 and 4, whereas groups 1 and 2 demonstrated a significant decline (P<.001). CONCLUSION: In a general obstetrical population, maternal cardiac adaptation at 32 weeks' gestation parallels the pattern of fetal growth and oxygenation; babies with birthweight<20th percentile have progressive decline in fetal cerebroplacental ratio, decline in maternal cardiac output, and increase in peripheral vascular resistance.

Long-Term Trends in Stroke Survivors Discharged to Care Homes: The South London Stroke Register.

Background and Purpose- Care homes provide care to many stroke survivors, yet little is known about changes in care home use over time. We aim to determine trends in discharge to care homes, to explore the characteristics of stroke survivors over time (1995-2018), and to identify the associations between these characteristics and discharge to care homes poststroke. Methods- Using data from the South London Stroke Register between 1995 and 2018, we estimated the proportions discharged to care homes and their characteristics over time, assessed by tests for trends. Multivariable logistic regression models were built to assess the associations between their characteristics and discharge destination. Results- Of 4172 stroke survivors, 484 (12%) were discharged to care homes. This proportion has decreased from 24% in 1995 to 2000 to 5% in 2013 to 2018. The mean age of those discharged to care homes has increased over time, from 73 to 75 (P<0.001). Among stroke survivors discharged to a care home, the proportion with a prestroke Barthel Index <15 has also increased over time from 7% to 21% (P=0.027), while the proportion with a 7-day poststroke Barthel Index <15 remains largely unchanged over time (93% in 1995-2000, 90% in 2013-2018). The characteristics most strongly associated with discharge to care homes were (odds ratio [95% CI]) age (1.05 [1.04-1.07] per year), stroke subtype (hemorrhagic; 0.64 [0.43-0.95]), stroke severity (Glasgow Coma Scale score, <13; 1.67 [1.19-2.35]), failed swallow test at admission (1.65 [1.20-2.25]), 7-day poststroke Barthel Index <15 (3.58 [2.20-6.03]), and a longer hospital stay (1.02 [1.02-1.03] per day). Conclusions- Over >20 years, there has been an 80% reduction in the proportion of stroke survivors discharged to care homes, influenced by changes in the demographics, disability, and stroke care in the underlying stroke population. In those moving to care homes, the level of poststroke disability remains high, requiring continued attention and investment.

The effect of parity on longitudinal maternal hemodynamics.

BACKGROUND: Parous women have a lower risk for pregnancy complications, such as preeclampsia or delivery of small-for-gestational-age neonates. However, parous women are a heterogeneous group of patients because they contain a low-risk cohort with previously uncomplicated pregnancies and a high-risk cohort with previous pregnancies complicated by preeclampsia and/or small for gestational age. Previous studies examining the effect of parity on maternal hemodynamics, including cardiac output and peripheral vascular resistance, did not distinguish between parous women with and without a history of preeclampsia or small for gestational age and reported contradictory results. OBJECTIVE: The objective of the study was to compare maternal hemodynamics in nulliparous women and in parous women with and without previous preeclampsia and/or small for gestational age. STUDY DESIGN: This was a prospective, longitudinal study of maternal hemodynamics, assessed by a bioreactance method, measured at 11+0 to 13+6, 19+0 to 24+0, 30+0 to 34+0, and 35+0 to 37+0 weeks' gestation in 3 groups of women. Group 1 was composed of parous women without a history of preeclampsia and/or small for gestational age (n = 632), group 2 was composed of nulliparous women (n = 829), and group 3 was composed of parous women with a history of preeclampsia and/or small for gestational age (n = 113). A multilevel linear mixed-effects model was performed to compare the repeated measures of hemodynamic variables controlling for maternal characteristics, medical history, and development of preeclampsia or small for gestational age in the current pregnancy. RESULTS: In groups 1 and 2, cardiac output increased with gestational age to a peak at 32 weeks and peripheral vascular resistance showed a reversed pattern with its nadir at 32 weeks; in group 1, compared with group 2, there was better cardiac adaptation, reflected in higher cardiac output and lower peripheral vascular resistance. In group 3 there was a hyperdynamic profile of higher cardiac output and lower peripheral vascular resistance at the first trimester followed by an earlier sharp decline of cardiac output and increase of peripheral vascular resistance from midgestation. The incidence of preeclampsia and small for gestational age was highest in group 3 and lowest in group 1. CONCLUSION: There are parity-specific differences in maternal cardiac adaptation in pregnancy.

Women Administered Standard Dose Imatinib for Chronic Myeloid Leukemia Have Higher Dose-Adjusted Plasma Imatinib and Norimatinib Concentrations Than Men.

BACKGROUND: The standard dose of imatinib for the treatment of chronic-phase chronic myeloid leukemia (CML) is 400 mg·d. A predose plasma imatinib concentration of >1 mg·L is associated with improved clinical response. This study aimed to assess the plasma imatinib and norimatinib concentrations attained in patients with chronic myeloid leukemia administered standard doses of imatinib adjusted for dose, age, sex, body weight, and response. METHODS: We evaluated data from a cohort of patients treated between 2008 and 2014 with respect to dose, age, sex, body weight, and response. RESULTS: The study comprised 438 samples from 93 patients (54 male, 39 female). The median imatinib dose was 400 mg·d in men and in women. The plasma imatinib concentration ranged 0.1-5.0 mg·L and was below 1 mg·L in 20% and 16% of samples from men and women, respectively. The mean dose normalized plasma imatinib and norimatinib concentrations were significantly higher in women in comparison with men. This was partially related to body weight. Mixed effects ordinal logistic regression showed no evidence of an association between sex and plasma imatinib (P = 0.13). However, there was evidence of an association between sex and plasma norimatinib, with higher norimatinib concentrations more likely in women than in men (P = 0.02). CONCLUSIONS: Imatinib therapeutic drug monitoring only provides information on dosage adequacy and on short-term adherence; longer-term adherence cannot be assessed. However, this analysis revealed that approximately 1 in 5 samples had a plasma imatinib concentration <1 mg·L, which was suggestive of inadequate dosage and/or poor adherence and posed a risk of treatment failure. Higher imatinib exposure in women may be a factor in the increased rate of long-term, stable, deep molecular response (undetectable breakpoint cluster-Abelson (BCR-ABL) transcript levels with a PCR sensitivity of 4.5 log, MR4.5) reported in women.

Testing for type 2 diabetes in Indigenous Australians: guideline recommendations and current practice.

OBJECTIVES: To determine the proportion of Aboriginal Controlled Community Health Service (ACCHS) patients tested according to three national diabetes testing guidelines; to investigate whether specific patient characteristics were associated with being tested. DESIGN, SETTING AND PARTICIPANTS: Cross-sectional study of 20 978 adult Indigenous Australians not diagnosed with diabetes attending 18 ACCHSs across Australia. De-identified electronic whole service data for July 2010 - June 2013 were analysed. MAIN OUTCOMES MEASURES: Proportions of patients appropriately screened for diabetes according to three national guidelines for Indigenous Australians: National Health and Medical Research Council (at least once every 3 years for those aged 35 years or more); Royal Australian College of General Practitioners and Diabetes Australia (at least once every 3 years for those aged 18 years or more); National Aboriginal Community Controlled Health Organisation (annual testing of those aged 18 years or more at high risk of diabetes). RESULTS: 74% (95% CI, 74-75%) of Indigenous adults and 77% (95% CI, 76-78%) of 10 760 patients aged 35 or more had been tested for diabetes at least once in the past 3 years. The proportions of patients tested varied between services (range: all adults, 16-90%; people aged 35 years or more, 23-92%). 18% (95% CI, 18-19%) of patients aged 18 or more were tested for diabetes annually (range, 0.1-43%). Patients were less likely to be tested if they were under 50 years of age, were transient rather than current patients of the ACCHS, or attended the service less frequently. CONCLUSIONS: Some services achieved high rates of 3-yearly testing of Indigenous Australians for diabetes, but recommended rates of annual testing were rarely attained. ACCHSs may need assistance to achieve desirable levels of testing.

Weighing as a stand-alone intervention does not reduce excessive gestational weight gain compared to routine antenatal care: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: Excessive gestational weight gain is associated with short and long-term adverse maternal and infant health outcomes, independent of pre-pregnancy body mass index. Weighing pregnant women as a stand-alone intervention during antenatal visits is suggested to reduce pregnancy weight gain. In the absence of effective interventions to reduce excessive gestational gain within the real world setting, this study aims to test if routine weighing as a stand-alone intervention can reduce total pregnancy weight gain and, in particular, excessive gestational weight gain. METHODS: A systematic review and meta-analysis of randomised controlled trials (RCTs) was conducted between November 2014 and January 2016, and reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Seven databases were searched. A priori eligibility criteria were applied to published literature by at least two independent reviewers. Studies considered methodologically rigorous, as per the Academy of Nutrition and Dietetics Quality Criteria Checklist for Primary Research, were included. Meta-analysis was conducted using fixed-effects models. RESULTS: A total of 5223 (non-duplicated) records were screened, resulting in two RCTs that were pooled for meta-analysis (n = 1068 randomised participants; n = 538 intervention, n = 534 control). No difference in total weight gain per week was observed between intervention and control groups (weighted mean difference (WMD) -0.00 kg/week, 95% confidence interval (CI) -0.03 to 0.02). There was also no reduction in excessive gestational weight gain between intervention and control, according to pre-pregnancy body mass index (BMI). However, total weight gain was lower in underweight women (n = 23, BMI <18.5 kg/m2) in the intervention compared to control group (-0.12 kg/week, 95% CI -0.23 to -0.01). No significant differences were observed for other pregnancy, birth and infant outcomes. CONCLUSION: Weighing as a stand-alone intervention is not worse nor better at reducing excessive gestational weight gain than routine antenatal care.

Just how high-risk are ongoing smokers? Exploring clusters of health risk behaviours among current and ex-smokers.

There is limited research about the patterns of multiple health risks among smokers, despite the associated increased risk of poor health. This study aimed to identify which risk behaviours were evident in a sample of smokers and ex-smokers who had previously been offered cessation support. A cross-sectional telephone interview in 2013 involved participants from New South Wales, Australia, from the control condition (self-help materials only) of a randomised smoking cessation trial conducted approximately five years earlier. The interview assessed smoking, weight, height, fruit and vegetable intake, physical activity, alcohol intake and depression. Of the 626 eligible participants, 321 were interviewed (consent rate=85.6%, response rate=51.3%); 62% were current smokers. Most participants (57%) reported four or five health risk behaviours. Three risk clusters were identified using latent class analysis: i) 'high risk' (42% of sample): smokers, overweight, inadequate intake of fruit and vegetables and low levels of physical activity; ii) 'lower risk non-depressed' (22% of sample): adequate physical activity and an absence of depression; and iii) 'lower risk, low alcohol' (36% of sample): low alcohol consumption, overweight and depressed. Males and current smokers were more likely to be 'high risk', while women and ex-smokers were more likely to be members of the 'lower risk, low alcohol' cluster. Those who continue to smoke have multiple additional health risks; as do ex-smokers in the 'lower risk, low alcohol' cluster. Achieving good health outcomes for these sizeable groups will require tailored, intensive or case-management approaches which can address multiple health risk behaviours.

The impact of cancer diagnosis and treatment on employment, income, treatment decisions and financial assistance and their relationship to socioeconomic and disease factors.

PURPOSE: The financial impact of cancer diagnosis and treatment can be considerable to individuals and their households, leading to changes in treatment decision making. This study aimed to quantify effects on income and employment; describe how cost-related factors influence treatment decision making and need for financial assistance; and to identify patient sociodemographic factors associated with treatment decision making, use of financial assistance and financial effects. METHODS: A cross-sectional self-report questionnaire was administered to oncology outpatients from two hospitals in Australia: one regional and one metropolitan. RESULTS: Of 255 participants, 67 % indicated a change in employment and 63 % of those reported reduced household income since their diagnosis. Travel (15 %), loss of income (14 %) and cost of treatments (11 %) were commonly cited factors influencing treatment decision making. Seventy-four percent of participants reported that they did not access financial assistance, with more than a third (37 %) of those being unaware that financial assistance was available. Being currently not employed and more recent diagnosis were associated with a reduced income since diagnosis. After adjusting for employment status and age, patients with private health insurance had higher odds of reporting that financial factors had influenced treatment decision making (OR = 2.5). CONCLUSION: Unemployment is a major driver of the financial impact of cancer. The costs of treatment may be particularly challenging for those with private health insurance who are more likely to be treated in the private health system where out-of-pocket costs are greater. Improved access to financial assistance is required to better avoid potential inequities.

Patterns of type 2 diabetes monitoring in rural towns: How does frequency of HbA1c and lipid testing compare with existing guidelines?

OBJECTIVE: To indicate levels of monitoring of type 2 diabetes in rural and regional Australia by examining patterns of glycated haemoglobin (HbA1c) and blood lipid testing. DESIGN AND SETTING: Retrospective analysis of pathology services data from twenty regional and rural towns in eastern Australia over 24 months. PARTICIPANTS: Of 13 105 individuals who had either a single HbA1c result ≥7.0% (53 mmol mol-1 ); or two or more HbA1c tests within the study period. MAIN OUTCOME MEASURES: Frequency of testing of HbA1c and blood lipids (cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides) were compared with guideline recommendations. RESULTS: About 58.3% of patients did not have the recommended 6-monthly HbA1c tests and 30.6% did not have annual lipid testing. For those who did not receive tests at the recommended interval, the mean between-test interval was 10.5 months (95% CI = 7.5-13.5) rather than 6 months for HbA1c testing; and 15.7 (95% CI = 13.3-18.1) months rather than annually for blood lipids. For those with at least one out-of-range test result, 77% of patients failed to receive a follow-up HbA1c test and 86.5% failed to receive a follow-up blood lipid test within the recommended 3 months. Patients less than 50 years of age, living in a more remote area and with poor diabetes control were less likely to have testing at the recommended intervals (P < 0.0001). CONCLUSIONS: Although poor diabetes testing is not limited to rural areas, more intensive diabetes monitoring is likely to be needed for patients living in non-metropolitan areas, particularly for some subgroups.

Effects of dietary interventions on pregnancy outcomes: a systematic review and meta-analysis.

Dietary intake during pregnancy influences maternal health. Poor dietary practices during pregnancy have been linked to maternal complications. The objective was to determine the effect of dietary intervention before or during pregnancy on pregnancy outcomes. A systematic review was conducted without date restrictions. Randomised controlled trials (RCTs) evaluating whole diet or dietary components and pregnancy outcomes were included. Two authors independently identified papers for inclusion and assessed methodological quality. Meta-analysis was conducted separately for each outcome using random effects models. Results were reported by type of dietary intervention: (1) counselling; (2) food and fortified food products; or (3) combination (counseling + food); and collectively for all dietary interventions. Results were further grouped by trimester when the intervention commenced, nutrient of interest, country income and body mass index. Of 2326 screened abstracts, a total of 28 RCTs were included in this review. Dietary counselling during pregnancy was effective in reducing systolic [standardised mean difference (SMD) -0.26, 95% confidence interval (CI) -0.45 to -0.07; P < 0.001] and diastolic blood pressure (SMD -0.57, 95% CI -0.75 to -0.38; P < 0.001). Macronutrient dietary interventions were effective in reducing the incidence of preterm delivery (SMD -0.19, 95% CI -0.34 to -0.04; P = 0.01). No effects were seen for other outcomes. Dietary interventions showed some small, but significant differences in pregnancy outcomes including a reduction in the incidence of preterm birth. Further high-quality RCTs, investigating micronutrient provision from food, and combination dietary intervention, are required to identify maternal diet intakes that optimise pregnancy outcomes.

Characteristics of the home food environment that mediate immediate and sustained increases in child fruit and vegetable consumption: mediation analysis from the Healthy Habits cluster randomised controlled trial.

BACKGROUND: The home food environment can influence the development of dietary behaviours in children, and interventions that modify characteristics of the home food environment have been shown to increase children's fruit and vegetable consumption. However to date, interventions to increase children's fruit and vegetable consumption have generally produced only modest effects. Mediation analysis can help in the design of more efficient and effective interventions by identifying the mechanisms through which interventions have an effect. This study aimed to identify characteristics of the home food environment that mediated immediate and sustained increases in children's fruit and vegetable consumption following the 4-week Healthy Habits telephone-based parent intervention. METHOD: Analysis was conducted using 2-month (immediate) and 12-month (sustained) follow-up data from a cluster randomised control trial of a home food environment intervention to increase the fruit and vegetable consumption of preschool children. Using recursive path analysis, a series of mediation models were created to investigate the direct and indirect effects of immediate and sustained changes to characteristics of the home food environment (fruit and vegetable availability, accessibility, parent intake, parent providing behaviour, role-modelling, mealtime eating practices, child feeding strategies, and pressure to eat), on the change in children's fruit and vegetable consumption. RESULTS: Of the 394 participants in the randomised trial, 357 and 329 completed the 2- and 12-month follow-up respectively. The final mediation model suggests that the effect of the intervention on the children's fruit and vegetable consumption was mediated by parent fruit and vegetable intake and parent provision of these foods at both 2- and 12-month follow-up. CONCLUSION: Analysis of data from the Healthy Habits trial suggests that two environmental variables (parental intake and parent providing) mediate the immediate and sustained effect of the intervention, and it is recommended these variables be targeted in subsequent home food environment interventions to bring about immediate and sustained changes in child fruit and vegetable intake. TRIAL REGISTRATION: ACTRN12609000820202 .

Is identification of smoking, risky alcohol consumption and overweight and obesity by General Practitioners improving? A comparison over time.

BACKGROUND: Detection of lifestyle risk factors by GPs is the first step required for intervention. Despite significant investment in preventive health care in general practice, little is known about whether GP detection of lifestyle risk factors have improved over time. OBJECTIVES: To examine whether sensitivity and specificity of GP detection of smoking, risky alcohol consumption and overweight and obesity has increased in patients presenting to see their GP, by comparing results from four Australian studies conducted between 1982 and 2011. METHODS: Demographic characteristics of patient and GP samples and the prevalence, sensitivity and specificity of detection of each risk factor were extracted from published studies. Differences between GP and patient sample characteristics were examined. To identify trends over time in prevalence of risk factors, sensitivity and specificity of detection across studies and the Cochran-Armitage test for trend were calculated for each risk factor for the overall sample and by male and female subgroups. RESULTS: There were no statistically significant changes in the sensitivity of GP detection of smoking or overweight or obesity over time. Specificity of detection of smoking increased from 64.7% to 98% (P < 0.0001) and decreased for overweight or obesity from 92% to 89% (P = 0.01). There was a small decrease in the sensitivity of detection of alcohol consumption (P = 0.02) and an increase in specificity (P = 0.01). CONCLUSIONS: Despite significant investment to increase GP detection and intervention for lifestyle risk factors, accurate detection of smoking, risky alcohol consumption and overweight and obesity occurs for less than two-thirds of all patients.

Missed opportunities: general practitioner identification of their patients' smoking status.

BACKGROUND: In order to provide smoking cessation support to their patients in line with clinical practice guidelines, general practitioners must first ascertain whether their patients' use tobacco. This study examined (i) the sensitivity, specificity, positive predictive value and negative predictive value of general practitioner detection of smoking, and (ii) the general practitioner and patient characteristics associated with detection of tobacco use. METHODS: Eligible patients completed a touchscreen computer survey while waiting for an appointment with their general practitioner. Patients self-reported demographic characteristics, medical history, and current smoking status. Following the patient's consultation, their general practitioner was asked to indicate whether the patient was a current smoker (yes/no/unsure/not applicable). Smoking prevalence, sensitivity, specificity, positive predictive value and negative predictive values (with 95% confidence intervals) were calculated using patient self-report of smoking status as the gold standard. Generalised estimating equations were used to examine the general practitioner and patient characteristics associated with detection of tobacco use. RESULTS: Fifty-one general practitioners and 1,573 patients in twelve general practices participated. Patient self-report of smoking was 11.3% compared to general practitioner estimated prevalence of 9.5%. Sensitivity of general practitioner assessment was 66% [95% CI 59-73] while specificity was 98% [95% CI 97-98]. Positive predictive value was 78% [95% CI 71-85] and negative predictive value was 96% [95% CI 95-97]. No general practitioner factors were associated with detection of smoking. Patients with a higher level of education or who responded 'Other' were less likely to be detected as smokers than patients who had completed a high school or below level of education. CONCLUSION: Despite the important role general practitioners play in providing smoking cessation advice and support, a substantial proportion of general practitioners do not know their patient's smoking status. This represents a significant missed opportunity in the provision of preventive healthcare. Electronic waiting room assessments may assist general practitioners in improving the identification of smokers.

Costs of UK community care for individuals with recessive dystrophic epidermolysis bullosa: Findings of the Prospective Epidermolysis Bullosa Longitudinal Evaluation Study.

Background: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited skin fragility disorder requiring multidisciplinary management. Information regarding costs of current standard treatment is scant. Objectives: As part of a longitudinal natural history study, we explored the community care costs of UK patients with different forms of RDEB. Methods: Fifty-nine individuals with RDEB provided detailed information on multiple facets of RDEB including disease severity scores (iscorEB, BEBS) and patient reported outcomes (quality of life evaluation in epidermolysis bullosa, iscorEB patient questionnaire). Costs data included time spent doing dressings, frequency of dressing changes, details of materials used, and paid and unpaid care. Results: Overall costs of dressing materials and associated care were high in RDEB. Median annual costs across all subtypes for those using dressings (n = 51) were over £26 000. For severe RDEB (RDEB-S), median costs were almost £90 000 per annum, with a median of 18 h per week spent on dressing changes. Half of working-age adults with RDEB were unemployed and 39% of carers were unable to take on full-time or part-time paid employment, adding to indirect costs and the financial burden from RDEB on families and society. Conclusions: The findings demonstrate the high costs of care of RDEB, particularly for RDEB-S. The current expense supports the drive to develop new therapies which accelerate wound healing and diminish total wound burden, thereby reducing costs of dressings and care. While costly to bring to market, these might ultimately reduce the overall cost of treatment and also the impact on individuals living with this rare disease. The data also highlight the need for adequate reimbursement for EB care which can place significant financial strain on families.

Itch in recessive dystrophic epidermolysis bullosa: findings of PEBLES, a prospective register study.

BACKGROUND: Itch is common and distressing in epidermolysis bullosa (EB) but has not previously been studied in depth in different recessive dystrophic EB (RDEB) subtypes. OBJECTIVES: As part of a prospective register study of the natural history of RDEB we explored features of itch, medications used, and correlation with disease severity and quality of life. METHODS: Fifty individuals with RDEB aged 8 years and above completed the Leuven Itch Scale (LIS) (total 243 reviews over a 7-year period). Data included itch frequency, severity, duration, distress, circumstances, consequences, itch surface area and medications for itch. The iscorEB disease severity score and the validated EB quality of life tool, QOLEB, were compared to LIS domains and analysed by RDEB subtype. RESULTS: Itch was frequent, present in the preceding month in 93% of reviews. Itch severity and distress were significantly greater in severe (RDEB-S) and pruriginosa (RDEB-Pru) subtypes compared to intermediate RDEB (RDEB-I). Itch medications were reported in just over half of reviews including emollients, topical corticosteroids and antihistamines; the proportion of participants not using medication despite frequent pruritus suggests limited efficacy. In inversa RDEB (RDEB-Inv) and RDEB-I, LIS domains correlated with iscorEB and QOLEB. In contrast to previous studies, correlations were lacking in RDEB-S suggesting that global disease burden relatively reduces the contribution of itch. CONCLUSIONS: This comprehensive study of RDEB-associated itch highlights differences between RDEB subtypes, suggests an unmet need for effective treatments and could serve as control data for future clinical trials incorporating itch as an endpoint.

Factors affecting dementia care practitioners' decision-making on moves to a care home for persons living with dementia: A factorial survey.

Deciding if and when might be the 'optimal' time for a person living with dementia to move to a care home is often difficult for the individual, family and practitioners. In this study, we describe the outcome of a factorial survey conducted with 100 dementia care practitioners (a frontline health or social care worker who works with people living with dementia) in England, which investigated factors used in deciding when a person living with dementia moves to a care home. Using findings from qualitative interviews with older people living with dementia, family carers, care home managers and social workers, we identified four factors that appeared to influence the decision to move to a care home: (1) Family carers' ability to support the person with daily activities, (2) amount of support provided by home care workers, (3) level of risk of harm and (4) the person living with dementia's wishes. These factors were then randomised within skeleton vignettes that told the story of a fictitious woman (Jane) living with dementia at home with her husband. Fifty-four variations of the vignettes were produced and randomly assigned to 100 surveys. A total of 100 volunteer dementia care practitioners (78% female, 54% over 50 years of age) received their own personalised online survey link via email and were asked to read each vignette and decide whether to suggest Jane (a) move to a care home or (b) continue living at home. Results indicated that Jane's wishes principally drove most dementia care practitioners' decision on whether to suggest a move to a care home or stay living at home (odds ratio = 6.5-19.5). Findings will inform a better understanding of the factors that contribute toward a decision to move to a care home and be of relevance to policy, practice, training and support.

Identifying multimorbidity clusters with the highest primary care use: 15 years of evidence from a multi-ethnic metropolitan population.

BACKGROUND: People with multimorbidity have complex healthcare needs. Some co-occurring diseases interact with each other to a larger extent than others and may have a different impact on primary care use. AIM: To assess the association between multimorbidity clusters and primary care consultations over time. DESIGN AND SETTING: A retrospective longitudinal (panel) study design was used. Data comprised electronic primary care health records of 826 166 patients registered at GP practices in an ethnically diverse, urban setting in London between 2005 and 2020. METHOD: Primary care consultation rates were modelled using generalised estimating equations. Key controls included the total number of long-term conditions, five multimorbidity clusters, and their interaction effects, ethnic group, and polypharmacy (proxy for disease severity). Models were also calibrated by consultation type and ethnic group. RESULTS: Individuals with multimorbidity used two to three times more primary care services than those without multimorbidity (incidence rate ratio 2.30, 95% confidence interval = 2.29 to 2.32). Patients in the alcohol dependence, substance dependence, and HIV cluster (Dependence+) had the highest rate of increase in primary care consultations as additional long-term conditions accumulated, followed by the mental health cluster (anxiety and depression). Differences by ethnic group were observed, with the largest impact in the chronic liver disease and viral hepatitis cluster for individuals of Black or Asian ethnicity. CONCLUSION: This study identified multimorbidity clusters with the highest primary care demand over time as additional long-term conditions developed, differentiating by consultation type and ethnicity. Targeting clinical practice to prevent multimorbidity progression for these groups may lessen future pressures on primary care demand by improving health outcomes.

Longitudinal changes in lung function in very prematurely born young people receiving high-frequency oscillation or conventional ventilation from birth.

OBJECTIVE: To examine changes in lung function over time in extremely prematurely born adolescents. WORKING HYPOTHESIS: Changes in lung function during adolescence would vary by ventilation mode immediately after birth. STUDY DESIGN: Longitudinal follow-up study. PATIENT SUBJECT SELECTION: Participants from the United Kingdom Oscillation Study who were randomized at birth to high-frequency oscillation (HFO) or conventional ventilation (CV) were assessed at 11-14 years (n = 319) and at 16-19 years (n = 159). METHODOLOGY: Forced expiratory flow (FEF), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and lung volumes including functional residual capacity (FRC) were reported as z-scores. The diffusion capacity of the lungs for carbon monoxide (DLCO) was measured. Lung function trajectories were compared by mode of ventilation using mixed models. Changes in z-scores were scaled to 5-year average follow-up. RESULTS: There were significant changes in the mean FEF75, FEF50, FEF25, FEV1, FVC, and DLCO z-scores within the CV and HFO cohorts, but no significant differences in the changes between the two groups. The mean FRC z-score increased in both groups, with an average change of greater than one z-score. The mean FEV1/FVC z-score increased significantly in the CV group, but not in the HFO group (difference in slopes: p = 0.02). Across the population, deterioration in lung function was associated with male sex, white ethnicity, lower gestational age at birth, postnatal corticosteroids, oxygen dependency at 36 weeks postmenstrual age, and lower birth weight, but not ventilation mode. CONCLUSIONS: There was little evidence that the mode of ventilation affected changes in lung function over time.

Inequalities in developing multimorbidity over time: A population-based cohort study from an urban, multi-ethnic borough in the United Kingdom.

BACKGROUND: Social and material deprivation accelerate the development of multimorbidity, yet the mechanisms which drive multimorbidity pathways and trajectories remain unclear. We aimed to examine the association between health inequality, risk factors and accumulation or resolution of LTCs, taking disease sequences into consideration. METHODS: We conducted a retrospective cohort of adults aged 18 years and over, registered between April 2005 and May 2020 in general practices in one inner London borough (n = 826,936). Thirty-two long term conditions (LTCs) were selected using a consensus process, based on a definition adapted to the demographic characteristics of the local population. sThe development and resolution of these LTCs were examined according to sociodemographic and clinical risk factors (hypertension; moderate obesity (BMI 30·0-39·9 kg/m2), high cholesterol (total cholesterol > 5 mmol/L), smoking, high alcohol consumption (>14 units per week), and psychoactive substance use), through the application of multistate Markov chain models. FINDINGS: Participants were followed up for a median of 4.2 years (IQR = 1·8 - 8·4); 631,760 (76%) entered the study with no LTCs, 121,424 (15%) with 1 LTC, 41,720 (5%) with 2 LTCs, and 31,966 (4%) with three or more LTCs. At the end of follow-up, 194,777 (24%) gained one or more LTCs, while 45,017 (5%) had resolved LTCs and 27,021 (3%) died. In multistate models, deprivation (hazard ratio [HR] between 1·30 to 1·64), female sex (HR 1·13 to 1·20), and Black ethnicity (HR 1·20 to 1·30; vs White) were independently associated with increased risk of transition from one to two LTCs, and shorter time spent in a healthy state. Substance use was the strongest risk factor for multimorbidity with an 85% probability of gaining LTCs over the next year. First order Markov chains identified consistent disease sequences including: chronic pain or osteoarthritis followed by anxiety and depression; alcohol and substance dependency followed by HIV, viral hepatitis, and liver disease; and morbid obesity followed by diabetes, hypertension, and chronic pain. INTERPRETATION: We examined the relations among 32 LTCs, taking the order of disease occurrence into consideration. Distinctive patterns for the development and accumulation of multimorbidity have emerged, with increased risk of transitioning from no conditions to multimorbidity and mortality related to ethnicity, deprivation and gender. Musculoskeletal disorders, morbid obesity and substance abuse represent common entry points to multimorbidity trajectories.