Primary Registry Research Articles

Cortisol-producing adenoma-related somatic mutations in unilateral primary aldosteronism with concurrent autonomous cortisol secretion: their prevalence and clinical characteristics.

Concurrent autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA) is being reported more frequently. Several somatic mutations including PRKACA, GNAS, and CTNNB1 were identified in cortisol-producing adenomas (CPAs). The presence of these mutations in unilateral PA (uPA) patients concurrent with ACS (uPA/ACS) is not well known. This study aimed to investigate the prevalence of these mutations and their clinical vs pathological characteristics in uPA/ACS. This is a retrospective cohort study. Totally 98 uPA patients from the Taiwan Primary Aldosteronism Investigation registry having overnight 1-mg dexamethasone suppression test (DST) and adrenalectomy from 2016 to 2018 were enrolled. Their adrenal tumors were tested for PRKACA, GNAS, and CTNNB1 mutations. 11 patients had CPA-related mutations (7 PRKACA and 4 GNAS). The patients carrying these mutations had higher post-DST cortisol (5.6 vs 2.6 μg/dL, P = 0.003) and larger adenoma (2.2 ± 0.3 vs 1.9 ± 0.7 cm, P = 0.025). Adenomas with these mutations had a higher prevalence of non-classical uPA (72.7% vs 26.3%, P = 0.014). Numerically, slightly more complete clinical success of uPA patients with these mutations was noticed after adrenalectomy, although it was statistically non-significant. Post-DST cortisol levels, adenoma size >1.9 cm, and the interaction of adenoma size >1.9 cm with potassium level were found to be associated with the presence of these mutations. Our study showed that CPA-related mutations were detected in 36.7% of uPA/ACS adenomas. The presence of these mutations was associated with higher post-DST cortisol levels, larger adenoma sizes, and a high percentage of non-classical uPA. However, these mutations did not significantly affect the clinical and biochemical outcomes after adrenalectomy of uPA/ACS patients but they showed a better trend.

Brentuximab vedotin in the treatment of cutaneous T-cell lymphomas: Data from the Spanish Primary Cutaneous Lymphoma Registry.

Brentuximab vedotin (BV) has been approved for CD30-expressing cutaneous T-cell lymphoma (CTCL) after at least one previous systemic treatment. However, real clinical practice is still limited. To evaluate the response and tolerance of BV in a cohort of patients with CTCL. We analysed CTCL patients treated with BV from the Spanish Primary Cutaneous Lymphoma Registry (RELCP). Sixty-seven patients were included. There were 26 females and the mean age at diagnosis was 59 years. Forty-eight were mycosis fungoides (MF), 7 Sézary syndrome (SS) and 12 CD30+ lymphoproliferative disorders (CD30 LPD). Mean follow-up was 18 months. Thirty patients (45%) showed at least 10% of CD30+ cells among the total lymphocytic infiltrate. The median number of BV infusions received was 7. The overall response rate (ORR) was 67% (63% in MF, 71% in SS and 84% in CD30 LPD). Ten of 14 patients with folliculotropic MF (FMF) achieved complete or partial response (ORR 71%). The median time to response was 2.8months. During follow-up, 36 cases (54%) experienced cutaneous relapse or progression. The median progression free survival (PFS) was 10.3months. The most frequent adverse event was peripheral neuropathy (PN) (57%), in most patients (85%), grades 1 or 2. These results confirm the efficacy and safety of BV in patients with advanced-stage MF, and CD30 LPD. In addition, patients with FMF and SS also showed a favourable response. Our data suggest that BV retreatment is effective in a proportion of cases.

Ther-PO-02 - Brentuximab vedotin in the treatment of cutaneous T-cell lymphomas: data from the Spanish Primary Cutaneous Lymphoma Registry

Ther-PO-02 - Brentuximab vedotin in the treatment of cutaneous T-cell lymphomas: data from the Spanish Primary Cutaneous Lymphoma Registry

Changes in primary care management of atrial fibrillation patients following the shift from warfarin to non-vitamin K antagonist oral anticoagulants: a Norwegian population based study

BackgroundTo assess baseline characteristics, drug utilisation and healthcare use for oral anticoagulants (OACs) following the introduction of non-vitamin K antagonist oral anticoagulants among patients with atrial fibrillation in primary care in Norway.MethodsIn this retrospective longitudinal cohort study, 92,936 patients with atrial fibrillation were identified from the Norwegian Primary Care Registry between 2010 and 2018. Linking to the Norwegian Prescription Database, we identified 64,112 patients (69.0%) treated with OACs and 28,824 (31%) who were untreated. Participants were followed until 15 May 2019, death, or loss to follow-up, whichever came first. For each OAC, predictors of initiation were assessed by modelling the probability of initiating the OAC using logistic regression, and predictors of the first switch after index date were assessed using multivariable Cox proportional hazards models. The numbers of primary care visits per quarter by index OAC were plotted and analysed with negative binomial regression analyses offset for the log of days at risk.ResultsPatients treated with OACs were older, had more comorbidities, and higher CHA2DS2-VASc scores than untreated patients. However, the mean CHA2DS2-VASc in the non-OAC group was 1.58 for men and 3.13 for women, suggesting an indication for OAC therapy. The percentage of patients with atrial fibrillation initiating OACs increased from 59% in 2010 to 79% in 2018. Non-vitamin K antagonist oral anticoagulant use increased throughout the study period to 95% of new OAC-treated patients in 2018, and switches from warfarin to non-vitamin K antagonist oral anticoagulants were common. The persistence of OAC treatment was > 60% after four years, with greatest persistence for apixaban. Patients treated with non-vitamin K antagonist oral anticoagulants had fewer primary care visits compared with those treated with warfarin (incidence rate ratio: 0.73, 95% confidence interval 0.71 to 0.75).ConclusionIn this Norwegian primary care study, we found that the shift from warfarin to non-vitamin K antagonist oral anticoagulants was successful with 95% use in patients initiating OACs in 2018, and associated with fewer general practitioner visits. Persistence with OACs was high, particularly for apixaban. However, many patients eligible for treatment with OACs remained untreated.

Cardiac magnetic resonance for prophylactic implantable-cardioverter defibrillator therapy international study: prognostic value of cardiac magnetic resonance-derived right ventricular parameters substudy.

Right ventricular systolic dysfunction (RVSD) is an important determinant of outcomes in heart failure (HF) cohorts. While the quantitative assessment of RV function is challenging using 2D-echocardiography, cardiac magnetic resonance (CMR) is the gold standard with its high spatial resolution and precise anatomical definition. We sought to investigate the prognostic value of CMR-derived RV systolic function in a large cohort of HF with reduced ejection fraction (HFrEF). Study cohort comprised of patients enrolled in the CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DefibrillAtor ThErapy registry who had HFrEF and had simultaneous baseline CMR and echocardiography (n = 2449). RVSD was defined as RV ejection fraction (RVEF) <45%. Kaplan-Meier curves and cox regression were used to investigate the association between RVSD and all-cause mortality (ACM). Mean age was 59.8 ± 14.0 years, 42.0% were female, and mean left ventricular ejection fraction (LVEF) was 34.0 ± 10.8. Median follow-up was 959 days (interquartile range: 560-1590). RVSD was present in 936 (38.2%) and was an independent predictor of ACM (adjusted hazard ratio = 1.44; 95% CI [1.09-1.91]; P = 0.01). On subgroup analyses, the prognostic value of RVSD was more pronounced in NYHA I/II than in NYHA III/IV, in LVEF <35% than in LVEF ≥35%, and in patients with renal dysfunction when compared to those with normal renal function. RV systolic dysfunction is an independent predictor of ACM in HFrEF, with a more pronounced prognostic value in select subgroups, likely reflecting the importance of RVSD in the early stages of HF progression.

Cardiac Complications in Patients with Common Variable Immune Deficiency: A Longitudinal Study

Background: The common variable immune deficiency (CVID) is known as the most prevalent symptomatic primary immune deficiency (PID) diseases, which is characterized by hypogammaglobulinemia with variable infectious and noninfectious manifestations. In this study, the researchers aimed to evaluate the frequency of cardiac disorders and investigate its association with other manifestations in CVID patients.&#x0D; Method: A total of 337 CVID patients registered in the Iranian Primary Immunodeficiency Registry were evaluated in this study. The questionnaire was completed for all patients to collect the participants’ demographic data, clinical manifestations and laboratory finding. The analysis was performed between the two groups of the study including CVID patients with cardiac manifestation and those without it.&#x0D; Results: The prevalence rate of cardiac manifestation was calculated to be 9.1%. pericardial and myocardial diseases and pulmonary hypertension were the most prevalent complications. CVID patients with a history of cardiac problem had significantly higher prevalence rates of otitis media, lymphoproliferative disorders, splenomegaly, hepatomegaly, failure to thrive and lower numbers of CD8+ T cells and CD19+ B cells compared to the patients without cardiac disorders. Notably, no significant differences were observed in immunoglobulins serum levels, CD3+ and CD4+ T cells between the patients with and without cardiac manifestation.&#x0D; Conclusion: Regular echocardiographic evaluation and of CVID patients for cardiac complications especially for inflammatory cardiac disease, heart failure and pulmonary hypertension, is critical to reduce the risk of heart disease.

Peripheral-blood cytopenia, an early indicator of inborn errors of immunity.

SummaryInborn errors of immunity (IEI) are inherited monogenic disorders resulting in defective immune response. Non‐infectious presentations are increasingly more apparent. Widely available, cost‐effective early indicators are needed. Peripheral‐blood cytopenia may be a presenting laboratory feature or an observed secondary phenomenon. This retrospective review of the South African Primary Immunodeficiency Registry (SAPIDR) aimed to assess the haematological indices at presentation and their association with the International Union of Immunological Societies (IUIS) 2019 IEI classification and mortality. Of 396 patients on the SAPIDR, 66% (n = 257) had available haematological results. Sixty percent were males and 85% under 18 years. A majority (53%) had predominantly antibody deficiency. At presentation, infection was prominent (86%) followed by cytopenia (62%). Neutropenia was associated with IUIS III [odds ratio (OR) 3.65, confidence interval (CI) 1.44–9.25], thrombocytopenia with IUIS II (OR 14.39, CI 2.89–71.57), lymphopenia with IUIS I (OR 12.16, CI 2.75–53.73) and pancytopenia with IUSI I (OR 12.24, CI 3.82–39.05) and IUIS II (OR 5.99, CI 2.80–12.76). Cytopenia showed shorter overall survival (OR 2.81, CI 1.288–4.16). Cytopenias that are severe, persistent, unusual and/or recurrent should prompt further investigation for IEI. The full blood count and leucocyte differential may facilitate earlier identification and serve as an adjunct to definitive molecular classification.

Clinical and pathologic features of primary membranous nephropathy in Turkey: a multicenter study by the Turkish Society of Nephrology Glomerular Diseases Working Group

Background We aimed to evaluate the features of primary membranous nephropathy (MNP) in Turkish people. Methods This is a retrospective analysis of patients with biopsy-proven primary MNP. We obtained the data collected between 2009 and 2019 in the primary glomerulonephritis registry of the Turkish Society of Nephrology Glomerular Diseases Study Group (TSN-GOLD). Patients with a secondary cause for MNP were excluded. Clinical, demographic, laboratory, and histopathological findings were analyzed. Results A total of 995 patients with primary MNP were included in the analyses. Males constituted the majority (58.8%). The mean age was 48.4 ± 13.9 years. The most common presentation was the presence of nephrotic syndrome (81.7%) and sub nephrotic proteinuria (10.3%). Microscopic hematuria was detected in one-third of patients. The median estimated glomerular filtration rate (eGFR) was 100.6 mL/min/1.73 m2 (IQR, 75.4–116.3), and median proteinuria was 6000 mg/d (IQR, 3656–9457). Serum C3 and C4 complement levels were decreased in 3.7 and 1.7% of patients, respectively. Twenty-four (2.4%) patients had glomerular crescents in their kidney biopsy samples. Basal membrane thickening was detected in 93.8% of cases under light microscopy. Mesangial proliferation and interstitial inflammation were evident in 32.8 and 55.9% of the patients, respectively. The most commonly detected depositions were IgG (93%), C3 complement (68.8%), and kappa and lambda immunoglobulin light chains (70%). Although renal functions were normal at presentation, vascular, interstitial, and glomerular findings were more prominent on biopsy in hypertensive patients. No significant effect of BMI on biopsy findings was observed. Conclusions Despite some atypical findings, the main features of primary MNP in Turkey were similar to the published literature. This is the largest MNP study to date conducted in Turkish people.

The clinical effectiveness and cost-effectiveness of a ‘stepping into day treatment’ approach versus inpatient treatment as usual for anorexia nervosa in adult specialist eating disorder services (DAISIES trial): a study protocol of a randomised controlled multi-centre open-label parallel group non-inferiority trial

BackgroundAnorexia nervosa (AN) is a serious and disabling mental disorder with a high disease burden. In a proportion of cases, intensive hospital-based treatments, i.e. inpatient or day patient treatment, are required, with day patient treatment often being used as a ‘step-down’ treatment after a period of inpatient treatment. Demand for such treatment approaches has seen a sharp rise. Despite this, the relative merits of these approaches for patients, their families, and the NHS and wider society are relatively unknown. This paper describes the rationale for, and protocol of, a two-arm multi-centre open-label parallel group non-inferiority randomised controlled trial, evaluating the effectiveness and cost-effectiveness of these two intensive treatments for adults with severe AN: inpatient treatment as usual and a stepped care day patient approach (the combination of day patient treatment with the option of initial inpatient treatment for medical stabilisation). The main aim of this trial is to establish whether, in adults with severe AN, a stepped care day patient approach is non-inferior to inpatient treatment as usual in relation to improving body mass index (BMI) at 12 months post-randomisation.Methods386 patients with a Diagnostic and Statistical Manual 5th edition diagnosis of severe AN or related disorder, with a BMI of ≤16 kg/m2 and in need of intensive treatment will be randomly allocated to either inpatient treatment as usual or a stepped care day patient approach. Patients in both groups will receive treatment until they reach a healthy weight or get as close to this point as possible. Assessments will be conducted at baseline (prior to randomisation), and at 6 and 12 months post-randomisation, with additional monthly symptom monitoring. The primary outcome will be BMI at the 12-month post-randomisation assessment. Other outcomes will include psychosocial adjustment; treatment motivation, expectations and experiences; cost-effectiveness; and carer burden.DiscussionThe results of this study will provide a rigorous evaluation of two intensive treatment approaches which will inform future national and international treatment guidelines and service provision.Trial registrationISRCTN ISRCTN10166784. Registered 28 February 2020. ISRCTN is a primary registry of the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) network and includes all items from the WHO Trial Registration Data Set.

A pragmatic multi-setting lifestyle intervention to improve leisure-time physical activity from adolescence to young adulthood: the vital role of sex and intervention onset time.

BackgroundThe long-term effectiveness of healthy lifestyle interventions on improving leisure-time physical activity (LTPA) in adolescents and its factors in low- and middle-income communities is unclear. This study is the first to investigate LTPA trends in a population of Iranian adolescents who underwent a multi-setting lifestyle intervention, considering sex and the time of intervention onset.MethodsParticipants were 2374 adolescents (57.2% girls), aged 12–18 years, who participated in the Tehran Lipid and Glucose Study (TLGS) during 1999–2001 and followed for a median follow-up of 15.9 over five data points every 3 years. Adolescent participants were assigned to the intervention or control groups based on their residential areas. Boys and girls were categorized into 12–15 or 16–18 years old to minimize participants’ bio-psychological differences, facilitate environmental interventions by more compliance with the Iranian educational system and identify the best time to start the intervention. All adolescents in the intervention area received healthy lifestyle interventions via the school-, family-, and community-based programs. LTPA was assessed using the reliable and validated Iranian Modifiable Activity Questionnaire (MAQ) version over the five data points. The Generalized Estimating Equations method was used to evaluate educational intervention’s effect on LTPA in adolescents during the follow-up.ResultsIn boys who experienced the early onset of intervention (12–15 years), the interaction effect of follow-up examinations and the intervention was significant where the impact of the intervention differed over time. In this group, LTPA was higher in the control group than in the intervention group at the first follow-up examination (β = − 1088.54). However, an increasing trend of LTPA was observed in the intervention group until the third follow-up examination (β = 1278.21, p = 0.08, and β = 1962.81, p = 0.02, respectively), with borderline significance levels at the 2nd (P = 0.08) and the 4th (P = 0.08) measurements. The interaction terms and main effects of intervention and follow-up examinations were not significant in boys with late intervention onset. Although older boys in the intervention group had higher LTPA than the control group, there were no significant differences among study groups in all follow-up examinations. Regarding girls, LTPA did not differ significantly between intervention and control groups in all follow-up examinations (P > 0.05).ConclusionOur results showed that a multi-setting practical lifestyle intervention could improve long-term energy expenditure in LTPA in adolescent boys who have experienced an early onset intervention. Findings emphasized the vital role of gender and the onset of these interventions. The current results would be valuable to plan tailored interventions to improve LTPA and community health.Trial registrationThis study is registered at Iran Registry for Clinical Trials (IRCT), a WHO primary registry (http://irct.ir). The TLGS clinical trial was the very first registration in the IRCT (Iran Registry of Clinical Trials). it was registered on 2008-10-29 by the registration number IRCT138705301058N1. Based on the international committee of medical journal Editors (ICMJE), “retrospective registration” is acceptable for trials that began before July 1, 2005.

Opportunities and obstacles in linking large health care registries: the primary secondary cancer care registry - breast cancer

BackgroundThe growing volume of health data provides new opportunities for medical research. By using existing registries, large populations can be studied over a long period of time. Patient-level linkage of registries leads to even more detailed and extended information per patient, but brings challenges regarding responsibilities, privacy and security, and quality of data linkage. In this paper we describe how we dealt with these challenges when creating the Primary Secondary Cancer Care Registry (PSCCR)- Breast Cancer.MethodsThe PSCCR – Breast Cancer was created by linking two existing registries containing data on 1) diagnosis, tumour and treatment characteristics of all Dutch breast cancer patients (NCR), and 2) consultations and diagnoses from primary care electronic health records of about 10% of Dutch GP practices (Nivel-PCD). The existing registry governance structures and privacy regulations were incorporated in those of the new registry. Privacy and security risks were reassessed. Data were restricted to females and linked using postal code and date of birth. The breast cancer diagnosis was verified in both registries and for a subsample of 44 patients with the GP as well.ResultsA collaboration agreement was signed in which the organisations retained data responsibility and accountability for ‘their’ registry. A Trusted Third Party performed the record linkage. Ten percent of the patients with breast cancer could be linked to the primary care registry, as was expected based on the coverage of Nivel-PCD, and finally 7 % could be included. The breast cancer diagnosis was verified by the GP in 42 of the 44 patients.ConclusionsWe developed and validated a procedure for patient-level linkage of health data registries without a unique identifier, while preserving the integrity and privacy of the original registries. The method described may help researchers wishing to link existing health data registries.

Assessing gait, balance, and muscle strength among breast cancer survivors with chemotherapy-induced peripheral neuropathy (CIPN): study protocol for a randomized controlled clinical trial

BackgroundChemotherapy-induced peripheral neuropathy (CIPN) is a common and understudied consequence of taxane chemotherapy for breast cancer treatment. CIPN symptoms include numbness combined with tingling sensations, persistent shooting, stabbing, or burning pain even in the absence of painful stimuli, lower extremity muscle weakness, and impaired balance. CIPN symptoms often persist for a long time after completion of chemotherapy, causing significant loss of functional abilities and increased risk of falls. Persistent CIPN caused by taxanes represents a therapeutic challenge due to the limited treatment options. Resistance exercise has shown promising results; however, the effect of exercise on CIPN remains understudied. This study aims to assess the effects of exercise on gait, balance, and lower extremity muscle strength after a 16-week home-based exercise program compared to an educational attention control condition.MethodsA sample of 312 women who completed taxane-based chemotherapy for breast cancer and have symptomatic neuropathy is recruited from a community-dwelling sample. Participants are randomized to either a 16-week Home-Based Physical Activity Intervention or an Educational Attention control group. The home-based intervention protocol consists of targeted lower extremity stretches, followed by 10 min each of gait/balance and 10 min of resistive training accessed by hyperlink or DVD. An Exercise Diary records quantitative exercise data. The gait assessment includes temporospatial parameters and lower extremity joint angles using APDM motion sensors. Participants’ balance is assessed using the Sensory Organization Test (SOT) performed using a NeuroCom Balance Master. Isometric strength of hip, knee, and ankle flexor and extensor muscles is assessed using an isokinetic dynamometer, Biodex BX Advantage. In addition, we assess neuropathy symptoms using the FACT-Taxane Additional Concerns Subscale and nerve conduction velocity of the sural and peroneal nerve action potentials. Outcomes are assessed at baseline (prior to randomization) and 16 weeks.DiscussionThere are currently no evidence-based interventions that address the functional declines associated with CIPN. If successful, this program is simple and easy to implement in the standard of care for individuals with CIPN. Gait and balance training have the potential to reduce physical dysfunction associated with CIPN and reduce the burden of disease in cancer survivors.Trial registrationClinicalTrials.gov NCT04621721. Registered on August 3, 2020. ClincialTrials.gov is a primary registry of the World Health Organization International Clinical Trials Registry Platform (WHO ICTEP) network and includes all items from the WHO Trial Registration data set in Trial registration.

The risk of unexpected hospital admissions and primary care visits after an elective day-case gastroscopy: a cohort study within England.

SummaryAimTo determine the excess of acute medical contacts following a day‐case diagnostic gastroscopy.MethodsCohort study using English linked primary, secondary care and death registry electronic health data. We included 277,535 diagnostic day‐case gastroscopies in 225,304 people between 1998 and 2016 and followed up for 30 days. 1,383,535 30‐day periods without a gastroscopy within 991,249 people frequency matched on year, gender and decade of birth. Non‐cancer deaths, emergency non‐cancer admissions and cardio, vascular or respiratory (CVR) primary care consultations were identified and adjusted for each other as competing risks. Outcomes related to possible indications for gastroscopy were censored.Results5.1% of day‐case diagnostic gastroscopies were followed by emergency hospital admission, 0.4% for a CVR diagnosis. Adjusted for age, sex, morbidity, time trends, indications and competing risks, there was a 0.1% excess of CVR‐related hospital admissions compared to controls. This reduced to 0.05% (95% confidence interval 0.04–0.06%) in people under 40 years without morbidity and increased to 1.1% (0.6%–1.6%) in people over 90 years with high comorbidity. Similarly, by 30 days, 3.8% had a primary care consultation for a CVR problem, with an excess after adjustment ranging from 0.13% (0.11%–0.16%) to 0.31% (0.14%–0.50%). Overall numbers needed to harm ranged from 1 in 294 gastroscopies to 1 in 67 gastroscopies.ConclusionsThere was an excess of vascular and respiratory events associated with a diagnostic gastroscopy. In younger patients, this risk manifested as an increase in primary care consultations while in older patients there was an increase in emergency hospital admissions.

INFLATE: a protocol for a randomised controlled trial comparing nasal balloon autoinflation to no nasal balloon autoinflation for otitis media with effusion in Aboriginal and Torres Strait Islander children

BackgroundOtitis media with effusion (OME) is common and occurs at disproportionately higher rates among Indigenous children. Left untreated, OME can negatively affect language, development, learning, and health and wellbeing throughout the life-course. Currently, OME care includes observation for 3 months followed by consideration of surgical ventilation tube insertion. The use of a non-invasive, low-cost nasal balloon autoinflation device has been found beneficial in other populations but has not been investigated among Aboriginal and Torres Strait Islander children.Methods/designThis multi-centre, open-label, randomised controlled trial will determine the effectiveness of nasal balloon autoinflation compared to no nasal balloon autoinflation, for the treatment of OME among Aboriginal and Torres Strait Islander children in Australia. Children aged 3–16 years with unilateral or bilateral OME are being recruited from Aboriginal Health Services and the community. The primary outcome is the proportion of children showing tympanometric improvement of OME at 1 month. Improvement is defined as a change from bilateral type B tympanograms to at least one type A or C1 tympanogram, or from unilateral type B tympanogram to type A or C1 tympanogram in the index ear, without deterioration (type A or C1 to type C2, C3, or B tympanogram) in the contralateral ear. A sample size of 340 children (170 in each group) at 1 month will detect an absolute difference of 15% between groups with 80% power at 5% significance. Anticipating a 15% loss to follow-up, 400 children will be randomised. The primary analysis will be by intention to treat. Secondary outcomes include tympanometric changes at 3 and 6 months, hearing at 3 months, ear health-related quality of life (OMQ-14), and cost-effectiveness. A process evaluation including perspectives of parents or carers, health care providers, and researchers on trial implementation will also be undertaken.DiscussionINFLATE will answer the important clinical question of whether nasal balloon autoinflation is an effective and acceptable treatment for Aboriginal and Torres Strait Islander children with OME. INFLATE will help fill the evidence gap for safe, low-cost, accessible OME therapies.Trial registrationAustralia New Zealand Clinical Trials Registry ACTRN12617001652369. Registered on 22 December 2017. The Australia New Zealand Clinical Trials Registry is a primary registry of the WHO ICTRP network and includes all items from the WHO Trial Registration data set. Retrospective registration.

The sexual and reproductive health of women with mental illness: a primary care registry study

The purpose of this study is to characterise the sexual and reproductive health risks associated with mental illness among women. This was a retrospective cohort study of 2,680,149 women aged 14 to 45 years in the Clinical Practice Research Datalink, a UK primary care register, linked to 1,702,211 pregnancies that ended between the 1st January 1990 and 31st December 2017. Mental illness was identified in primary care and categorised into the following: common mental illness (depression/anxiety); addiction (alcohol/drug misuse); serious mental illness (affective/non-affective psychosis); other mental illness (eating/personality disorders). Logistic regression estimated the association between mental illness and subsequent risk of recurrent miscarriage and termination. Cox proportional hazards estimated the association between mental illness and time to gynaecological diseases, sexually transmitted infections, reproductive cancers, cervical screen, contraception and emergency contraception. Models were adjusted for calendar year, year of birth, smoking status and ethnicity, region and index of socioeconomic status. Compared to women without mental illness, exposed women were more likely to experience recurrent miscarriage (adjOR = 1.50, 95%CI 1.41 to 1.60), termination (adjOR = 1.48, 95%CI 1.45 to 1.50), gynaecological diseases (adjHR = 1.39, 95%CI 1.37 to 1.40), sexually transmitted infections (adjHR = 1.47, 95%CI 1.43 to 1.51), reproductive cancers (adjHR = 1.10, 95%CI 1.02 to 1.19), contraception (adjHR = 1.28 95%CI 1.26 to 1.29) and emergency contraception (adjHR = 2.30, 95%CI 2.26 to 2.34), and less likely to attend for cervical screening (adjHR = 0.91, 95%CI 0.90 to 0.92). Currently, the sexual and reproductive health needs of women with mental illness are unmet representing significant health inequalities. Clinicians must create opportunities to engage with women in primary care and mental health services to address this gap.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00737-022-01214-y.

Pre-diagnostic clinical features and blood tests in patients with colorectal cancer: a retrospective linked-data study.

BackgroundThe majority of colorectal cancer is diagnosed in patients following symptomatic presentation in the UK.AimTo identify windows of opportunity for timely investigations or referrals in patients presenting with colon and rectal cancer-relevant symptoms or abnormal blood tests.Design and settingA retrospective cohort study was undertaken using linked primary care and cancer registry data for patients with colorectal cancer diagnosed in England between 2012 and 2015.MethodMonthly consultation rates for relevant clinical features (change in bowel habit, rectal bleeding, abdominal pain, abdominal mass, constitutional symptoms, and other bowel symptoms) and abnormal blood test results (low haemoglobin, high platelets, and high inflammatory markers) up to 24 months pre-diagnosis were calculated. Poisson regression adjusted for age, sex, and relevant comorbidities was used to estimate the most likely month when consultation rates increased above baseline.ResultsIn total, 5033 patients with colon cancer and 2516 with rectal cancer were included. Consultations for all examined clinical features and abnormal blood tests increased in the year pre-diagnosis. Rectal bleeding was the earliest clinical feature to increase from the baseline rate: at 10 months (95% confidence interval [CI] = 8.3 to 11.7) pre-diagnosis for colon cancer and at 8 months (95% CI = 6.1 to 9.9) pre-diagnosis for rectal cancer. Low haemoglobin, high platelets, and high inflammatory markers increased from as early as 9 months pre-diagnosis.ConclusionThis study found evidence for an early increase in rates of consultation for relevant clinical features and abnormal blood tests in patients with colorectal cancer, suggesting that earlier instigation of cancer-specific investigations or referrals may be warranted in some patients who were symptomatic.

Primary Care Severe Asthma Registry and Education Project (PCSAR-EDU): Phase 1 – an e-Delphi for registry definitions and indices of clinician behaviour

IntroductionAlthough most asthma is mild to moderate, severe asthma accounts for disproportionate personal and societal costs. Poor co-ordination of care between primary care and specialist settings is recognised as a...

Patient Research Interest Differences by Gender and Race/Ethnicity: A North Texas Primary Care Practice-Based Research Network (NorTex) Study.

Recruiting and increasing participation of women and racial/ethnic groups remains an ongoing struggle despite the National Institutes of Health Revitalization Act mandating the inclusion of these populations. This study examined gender and racial/ethnic differences in research interest in participating in Practice-Based Research Network studies focused on cardiovascular disease (CVD), diabetes, cancer, and mental health research. A total of 1348 participants and 18 NorTex clinics from the North Texas Primary Care Registry Project (NRP) database were included in this cross-sectional study. Participants who signed up through the registry to participate in future research projects and self-reported as non-Hispanic White, Hispanic, or non-Hispanic Black were included. Research interest in heart disease, high cholesterol, high blood pressure and heart failure were categorized as CVD; depression and anxiety were categorized as mental health; diabetes and cancer research were coded as single item dependent variables. Of registry participants, 72% were female, 34.5% were Black, and 24.4% were Hispanic. Of participants, 70% (n = 942) were interested in CVD research, the leading area of interest. Mental health research (56.3%, n = 755) was the second highest area of interest, while cancer had the least interest (38.4%, n = 515). After controlling for age, smoking, and having a diagnosis of the medical condition, gender did not predict interest in CVD, diabetes, cancer, or mental health research. However, race/ethnicity significantly predicted interest in diabetes and cancer research. Results indicate there are racial/ethnic differences in interest in specific research topics among our registry participants. This information may be helpful to develop successful recruitment strategies.

Inflawell® improves neutrophil-to-lymphocyte ratio and shortens hospitalization in patients with moderate COVID-19, in a randomized double-blind placebo-controlled clinical trial.

AimsCOVID-19 is a significant global threat to public health. Despite the availability of vaccines and anti-viral drugs, there is an urgent need for alternative treatments to help prevent and/or manage COVID-19 symptoms and the underlying dysregulated immune response. We hypothesized that administration of Inflawell® syrup, a Boswellia extract formulation enriched for boswellic acids (BAs), can reduce the excessive or persistent inflammation and thereby prevent disease progression. BAs are medicinally activated triterpenoids found in the resins of Boswellia spp., and possess an immense therapeutic potential due to their anti-inflammatory and immunoregulatory activities. We investigated the effect of Inflawell® syrup, on moderate COVID-19 patients along with the current standard of care treatment.MethodsA randomized placebo-controlled double-blind clinical trial was conducted, following definitive confirmation of COVID-19. Forty-seven hospitalized patients with moderate COVID-19 were enrolled and received either the Inflawell® syrup or placebo. Clinical symptoms and markers of inflammation were evaluated at baseline and completion of the trial.ResultsOur clinical trial revealed an increase in the percentage of oxygen saturation level in patients that received the BAs compared to placebo (P < 0.0001). In addition, the average duration of hospitalization was significantly shorter in the BAs group compared with the placebo group (P < 0.04). Concomitantly, some improvement in the clinical symptoms including cough, dyspnea, myalgia, headache, and olfactory and gustatory dysfunction were detected in the BAs group. Hematologic findings showed a significant decrease in the percentage of neutrophils (P < 0.006) and neutrophil-to-lymphocyte ratio (NLR) levels (P < 0.003), associated with a significant increase in the percentage of lymphocytes in the BAs group compared with the placebo (P < 0.002). Additionally, a significant decrease in CRP, LDH, IL − 6 and TNF − α levels was detected in the BAs group. Following the intervention, fewer patients in the BAs group were PCR-positive for COVID-19 compared to placebo, though not statistically significant.ConclusionOverall, the treatment with Inflawell® resulted in shorter hospital stay, alleviation of COVID-19 clinical symptoms and decline in the level of pro-inflammatory cytokines.Trial registrationThe trial has been registered in https://www.irct.ir with unique identifier: IRCT20170315033086N10 (https://en.irct.ir/trial/51631). IRCT is a primary registry in the WHO registry network (https://www.who.int/clinical-trials-registry-platform/network/primary-registries).

Endoscopic retrograde appendicitis therapy versus laparoscopic appendectomy versus open appendectomy for acute appendicitis: a pilot study

BackgroundAn increasing number of studies have shown the merits of endoscopic retrograde appendicitis therapy (ERAT) in diagnosing and treating acute uncomplicated appendicitis. However, no related prospective controlled studies have been reported yet. Our aim is to assess the feasibility and safety of ERAT in the treatment of acute uncomplicated appendicitis.MethodsIn this open-label, randomized trial, participants were randomly allocated to the ERAT group, laparoscopic appendectomy (LA) group and open appendectomy (OA) group. The primary outcome was the clinical success rate of the treatment. Intention-to-treat analysis was used in the study.ResultsThe study comprised of 99 patients, with 33 participants in each group. The clinical success rate was 87.88% (29/33), 96.97% (32/33) and 100% (33/33) in the ERAT, LA and OA group, respectively. In the ERAT group, 4 patients failed ERAT due to difficult cannulation. In LA group, 1 patient failed because of abdominal adhesion. There were no significant differences among the three treatment groups regarding the clinical success rate (P = 0.123). The median duration of follow-up was 22 months. There were no significant differences (P = 0.693) among the three groups in terms of adverse events and the final crossover rate of ERAT to surgery was 21.21% (7/33).ConclusionERAT can serve as an alternative and efficient method to treat acute uncomplicated appendicitis.Trial registration The study is registered with the WHO Primary Registry-Chinese Clinical Trial Registry (ChiCTR1900025812).