The role of area level social deprivation on childhood and adolescent consultation rate in primary care:a population based, cohort study

BACKGROUND: Studies show that children and adolescents in the most socially deprived areas (SDA) consult their general practitioner (GP) more often than those in the least socially deprived areas (Non-SDA). Given that GPs see a wide range of diseases, it is important to know which clinical diagnoses are shaped by socioeconomic factors. The primary objective was to determine the association between area level social deprivation and consultation rates in a pediatric population. The secondary objective was to explore this association across a wide range of clinical diagnoses. METHODS: A cohort study using the Rijnmond Primary Care Database (RPCD) was conducted. Between 2013 and 2020, a total of 69,861 patients aged 0 to 17 years registered with a GP were analysed. A consultation was defined as patient contact and entry of a diagnosis using the International Classification of Primary Care (ICPC-1) code. Associations between consultation rates, ICPC-1 codes and area level social deprivation were explored using a Poisson regression model. The incidence risk ratio (IRR) and 95% confidence interval (CI) were reported. RESULTS: Over the 7-year study period the consultation rate of the study population was 3.8 per person-years. The top 5 reasons for children and adolescents to consult their GP was related to skin, respiratory, general unspecified, musculoskeletal and digestive symptoms or diagnoses. Consultation rate was higher in SDA group compared to Non-SDA group (IRR 1.20, 95% CI 1.19–1.20). Consultation rate for ICPC-1 code related to pregnancy and family planning was significantly lower in SDA group compared to Non-SDA group. Upon further exploration of this code, SDA group were less likely to consult for oral contraception and more likely to contact a GP for induced termination of pregnancy compared to Non-SDA group (IRR 0.36; 95% CI 0.33–0.44 and IRR 2.94; 95% CI 1.58–5.46 respectively). CONCLUSIONS: Overall, SDA group had higher GP consultation rates for the majority of clinical diagnoses except for pregnancy and family planning. In this latter category, adolescent females in SDA consulted less frequently for oral contraception. This study illustrates the need to understand the underlying health seeking behaviors of children and adolescents at different development phases of their lives. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12875-022-01873-x

Gut microbiota-derived propionate reduces cancer cell proliferation in the liver

Peer reviewedPublisher PD

Patterns of knee osteoarthritis management in general practice:a retrospective cohort study using electronic health records

Objective: This study determined patterns of knee osteoarthritis (OA) management by general practitioners (GPs) using routine healthcare data from Dutch general practices from 2011 to 2019. Design: A retrospective cohort study was conducted using the Integrated Primary Care Information database between 2011 and 2019. Electronic health records (EHRs) of n = 750 randomly selected knee OA patients (with either codified or narrative diagnosis) were reviewed against eligibility criteria and n = 503 patients were included. Recorded information was extracted on GPs’ management from six months before to three years after diagnosis and patterns of management were analysed.Results: An X-ray referral was the most widely recorded management modality (63.2%). The next most widely recorded management modalities were a referral to secondary care (56.1%) and medication prescription or advice (48.3%). Records of recommendation of/referral to other primary care practitioners (e.g. physiotherapists) were found in only one third of the patients. Advice to lose weight was least common (1.2%). Records of medication prescriptions or recommendation of/referral to other primary care practitioners were found more frequently in patients with an X-ray referral compared to patients without, while records of secondary care referrals were found less frequently. Records of an X-ray referral were often found in narratively diagnosed knee OA patients before GPs recorded a code for knee OA in their EHR. Conclusion: These findings emphasize the importance of better implementing non-surgical management of knee OA in general practice and on initiatives for reducing the overuse of X-rays for diagnosing knee OA in general practice.</p

Asthma beliefs among mothers and children from different ethnic origins living in Amsterdam, the Netherlands

<p>Abstract</p> <p>Background</p> <p>Doctors and patients hold varying beliefs concerning illness and treatment. Patients' and families' explanatory models (EMs) vary according to personality and sociocultural factors. In a multi-ethnic society, it is becoming increasingly significant that doctors understand the different beliefs of their patients in order to improve patient/doctor communication as well as patient adherence to treatment.</p> <p>Methods</p> <p>Twelve focus groups were formed, consisting of 40 children diagnosed with asthma, as well as 28 mothers of these children. These groups included mothers and children of different ethnicities who were living in Amsterdam, the Netherlands. In order to understand the beliefs that both mothers and children hold regarding asthma and its treatment, the explanatory models were analysed and compared.</p> <p>Results</p> <p>Study findings show that mothers and children, regardless of ethnicity and age, have their own EMs. Overall, there is a great deal of uncertainty related to the causes, consequences, problems, and symptoms of asthma and its treatment. It also seems that many concerns and feelings of discomfort are the result of lack of knowledge. For instance, the fact that asthma is not seen as a chronic disease requiring daily intake of an inhaled corticosteroid, but rather as an acute phenomenon triggered by various factors, may be very relevant for clinical practice. This particular belief might suggest an explanation for non-adherent behaviour.</p> <p>Conclusion</p> <p>A thorough understanding of the mothers' and children's beliefs regarding the illness and its treatment is an important aspect in the management of asthma. Gaining an understanding of these beliefs will provide a foundation for a solid clinician-patient/family partnership in asthma care. Although ethnic differences were observed, the similarities between the mothers' and children's beliefs in this multi-ethnic population were striking. In particular, a common belief is that asthma is considered an acute rather than a chronic condition. In addition, there is a lack of knowledge about the course and the self-management of asthma. Health care providers should be aware of these commonly held beliefs, and this information could be shared in educational programs.</p

Functional tests to guide management in an adult with loss of function of type-1 angiotensin II receptor

BACKGROUND: Genetic loss of function of AGT (angiotensinogen), REN (renin), ACE (angiotensin-converting enzyme), or AGTR1 (type-1 angiotensin II receptor) leads to renal tubular dysgenesis (RTD). This syndrome is almost invariably lethal. Most surviving patients reach stage 5 chronic kidney disease at a young age. METHODS: Here, we report a 28-year-old male with a homozygous truncating mutation in AGTR1 (p.Arg216*), who survived the perinatal period with a mildly impaired kidney function. In contrast to classic RTD, kidney biopsy showed proximal tubules that were mostly normal. During the subsequent three decades, we observed evidence of both tubular dysfunction (hyperkalemia, metabolic acidosis, salt-wasting and a urinary concentrating defect) and glomerular dysfunction (reduced glomerular filtration rate, currently ~30 mL/min/1.73 m(2), accompanied by proteinuria). To investigate the recurrent and severe hyperkalemia, we performed a patient-tailored functional test and showed that high doses of fludrocortisone induced renal potassium excretion by 155%. Furthermore, fludrocortisone lowered renal sodium excretion by 39%, which would have a mitigating effect on salt-wasting. In addition, urinary pH decreased in response to fludrocortisone. Opposite effects on urinary potassium and pH occurred with administration of amiloride, further supporting the notion that a collecting duct is present and able to react to fludrocortisone. CONCLUSIONS: This report provides living proof that even truncating loss-of-function mutations in AGTR1 are compatible with life and relatively good GFR and provides evidence for the prescription of fludrocortisone to treat hyperkalemia and salt-wasting in such patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00467-021-05018-7

Synbiotic approach restores intestinal homeostasis and prolongs survival in leukaemia mice with cachexia

Cancer cachexia is a multifactorial syndrome that includes muscle wasting and inflammation. As gut microbes influence host immunity and metabolism, we investigated the role of the gut microbiota in the therapeutic management of cancer and associated cachexia. A community-wide analysis of the caecal microbiome in two mouse models of cancer cachexia (acute leukaemia or subcutaneous transplantation of colon cancer cells) identified common microbial signatures, including decreased Lactobacillus spp. and increased Enterobacteriaceae and Parabacteroides goldsteinii/ASF 519. Building on this information, we administered a synbiotic containing inulin-type fructans and live Lactobacillus reuteri 100-23 to leukaemic mice. This treatment restored the Lactobacillus population and reduced the Enterobacteriaceae levels. It also reduced hepatic cancer cell proliferation, muscle wasting and morbidity, and prolonged survival. Administration of the synbiotic was associated with restoration of the expression of antimicrobial proteins controlling intestinal barrier function and gut immunity markers, but did not impact the portal metabolomics imprinting of energy demand. In summary, this study provided evidence that the development of cancer outside the gut can impact intestinal homeostasis and the gut microbial ecosystem and that a synbiotic intervention, by targeting some alterations of the gut microbiota, confers benefits to the host, prolonging survival and reducing cancer proliferation and cachexia

Examining teacher responses to a professional learning program addressing learning disabilities

Mutations in PCBD1 are causative for transient neonatal hyperphenylalaninemia and primapterinuria (HPABH4D). Until now, HPABH4D has been regarded as a transient and benign neonatal syndrome without complications in adulthood. In our study of three adult patients with homozygous mutations in the PCBD1 gene, two patients were diagnosed with hypomagnesemia and renal Mg(2+) loss, and two patients developed diabetes with characteristics of maturity onset diabetes of the young (MODY), regardless of serum Mg(2+) levels. Our results suggest that these clinical findings are related to the function of PCBD1 as a dimerization cofactor for the transcription factor HNF1B. Mutations in the HNF1B gene have been shown to cause renal malformations, hypomagnesemia, and MODY. Gene expression studies combined with immunohistochemical analysis in the kidney showed that Pcbd1 is expressed in the distal convoluted tubule (DCT), where Pcbd1 transcript levels are upregulated by a low Mg(2+)-containing diet. Overexpression in a human kidney cell line showed that wild-type PCBD1 binds HNF1B to costimulate the FXYD2 promoter, the activity of which is instrumental in Mg(2+) reabsorption in the DCT. Of seven PCBD1 mutations previously reported in HPABH4D patients, five mutations caused proteolytic instability, leading to reduced FXYD2 promoter activity. Furthermore, cytosolic localization of PCBD1 increased when coexpressed with HNF1B mutants. Overall, our findings establish PCBD1 as a coactivator of the HNF1B-mediated transcription necessary for fine tuning FXYD2 transcription in the DCT and suggest that patients with HPABH4D should be monitored for previously unrecognized late complications, such as hypomagnesemia and MODY diabetes

Reducing progression of knee OA features assessed by MRI in overweight and obese women: Secondary outcomes of a preventive RCT

Objective: To evaluate the preventive effects of a randomized controlled trial on progression of Magnetic Resonance Imaging (MRI) features of knee osteoarthritis (OA) in overweight and obese women. Design: In a 2 × 2 factorial design, 2.5 years effects of a diet and exercise program and of glucosamine sulphate (double-blind, placebo-controlled) were evaluated in 407 middle-aged women with body mass index (BMI) ≥ 27 kg/m2 without clinical signs of knee OA at baseline (ISRCTN 42823086). MRIs were scored with the MRI Osteoarthritis Knee Score (MOAKS). Progression was defined for bone marrow lesions (BMLs), cartilage defects, osteophytes, meniscal abnormalities and meniscal extrusion. Analyses on knee level were performed over the four intervention groups using adjusted Generalized Estimating Equations (GEE). Results: 687 knees of 347 women with mean age 55.7 years (±3.2 SD) and mean BMI 32.3 kg/m2 (±4.2 SD) were analyzed. Baseline prevalence was 64% for BMLs, 70% for cartilage defects, 24% for osteophytes, 66% for meniscal abnormalities and 52% for meniscal extrusions. The diet and exercise program + placebo intervention showed significantly less progression of meniscal extrusion compared to placebo only (12% vs 22%, OR 0.50, 95% CI [0.27-0.92]). The interventions did not result in significant differences on other OA MRI features. Conclusions: In subjects at high risk for future knee OA development, a diet and exercise program, glucosamine sulphate and their combination showed small and mainly non-significant effects on the progression of OA MRI features. Only progression of meniscal extrusion was significantly diminished by the diet and exercise program