Adaptation and validation of a German version of the Multimorbidity Treatment Burden Questionnaire

BACKGROUND: Patients with multiple long-term conditions often face a variety of challenges arising from the requirements of their health care. Knowledge of perceived treatment burden is crucial for optimizing treatment. In this study, we aimed to create a German version of the Multimorbidity Treatment Burden Questionnaire (MTBQ) and to evaluate its validity. METHODS: The steps to translate the MTBQ included forward/back translation, cognitive interviews (n = 6) and a pilot test (n = 7). Psychometric properties of the scale were assessed in a cross-sectional survey with primary care patients aged 65 and older with at least 3 long-term conditions (n = 344). We examined the distribution of responses, dimensionality, internal reliability and construct validity. RESULTS: Cognitive interviewing and piloting led to minor modifications and showed overall good face validity and acceptability. As expected, we observed a positively skewed response distribution for all items. Reliability was acceptable with McDonald’s omega = 0.71. Factor analysis suggested one common factor while model fit indices were inconclusive. Predefined hypotheses regarding the construct validity were supported by negative associations between treatment burden and health-related quality of life, self-rated health, social support, patient activation and medication adherence, and positive associations between treatment burden and number of comorbidities. Treatment burden was found to be higher in female participants (Mdn(1) = 6.82, Mdn(2) = 4.55; U = 11,729, p = 0.001) and participants with mental health diagnoses (Mdn(1) = 9.10, Mdn(2) = 4.55; U = 3172, p = 0.024). CONCLUSIONS: The German MTBQ exhibited good psychometric properties and can be used to assess the perceived treatment burden of patients with multimorbidity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12955-022-01993-z

Development of a model of medication review for use in clinical practice:Bristol Medication Review Model

Abstract Background Medication review is a core aspect of medicine optimisation, yet existing models of review vary substantially in structure and content and are not necessarily easy to implement in clinical practice. This study aimed to use evidence from the existing literature to identify key medication review components and use this to inform the design of an improved review model. Methods A systematic review was conducted (PROSPERO: CRD42018109788) to identify randomised control trials of stand-alone medication review in adults (18+ years). The review updated that by Huiskes et al. (BMC Fam Pract. 18:5, 2017), using the same search strategy implemented in MEDLINE and Embase. Studies were assessed using the Cochrane risk of bias tool. Key review components were identified, alongside relevant clinical and health service outcomes. A working group (patients, doctors and pharmacists) developed the model through an iterative consensus process (appraisal of documents plus group discussions), working from the systematic review findings, brief evidence summaries for core review components and examples of previous models, to agree on the main purpose of the review model, overarching model structure, review components and supporting material. Results We identified 28 unique studies, with moderate bias overall. Consistent medication review components included reconciliation (26 studies), safety assessment (22), suboptimal treatment (19), patient knowledge/preferences (18), adherence (14), over-the-counter therapy (13) and drug monitoring (10). There was limited evidence from studies for improvement in key clinical outcomes. The review structure was underpinned by patient values and preferences, with parallel information gathering and evaluation stages, feeding into the final decision-making and implementation. Most key components identified in the literature were included. The final model was considered to benefit from a patient-centred, holistic approach, which captured both patient-orientated and medication-focused problems, and aligned with traditional consultation methods thus facilitating implementation in practice. Conclusions The Bristol Medication Review Model provides a framework for standardised delivery of structured reviews. The model has the potential for use by all healthcare professionals with relevant clinical experience and is designed to offer flexibility of implementation not limited to a particular healthcare setting

Why test study protocol: a UK-wide audit using the primary care academic collaborative to explore the reasons for primary care testing

This is the author accepted manuscript. The final version is available on open access from the Royal College of General Practitioners via the DOI in this recordBackground The number of blood tests done in primary care has been increasing over the last 20 years. Some estimates suggest that up to a quarter of these tests may not have been needed. This could lead to a cascade effect of further investigations, appointments, or referrals, as well as anxiety for patients, increased workload and costs to the health service. To better understand the impact and sequelae of blood tests on patients, we need to know why blood tests are requested and what is done with the results. Aims To explore who orders blood tests and why, and how test results are actioned in primary care. Design & Setting Retrospective audit of electronic health records in general practices across the UK. Method The Primary care Academic CollaboraTive (PACT), a UK-wide network of primary care health professionals, will be utilised to collect data from individual practices. PACT members will be asked to review the electronic health records of 50 patients who had recent blood tests in their practice, and manually extract anonymised data on who requested the test, the indication, the result, and subsequent actions. Data will also be collected from PACT members to assess the feasibility of the collaborative model. Conclusion PACT offers a unique opportunity to extract clinical data which cannot otherwise be obtained. Understanding the indications for tests will help identify priority areas for research to optimise testing and patient safety in primary care.Bristol, North Somerset and South Gloucestershire Clinical Commissioning Grou

Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22

A substantial proportion of familial colorectal cancer (CRC) is not a consequence of known susceptibility loci, such as mismatch repair (MMR) genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no loss of tumor expression of MMR proteins, no microsatellite instability (MSI)-high tumors, or no evidence of linkage to MMR genes). Families were ascertained via the Colon Cancer Family Registry multi-site NCI-supported consortium (Colon CFR), the City of Hope Comprehensive Cancer Center, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family including 2.2 affected) were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori-defined family groups. Five lod scores greater than 3.0 were observed assuming heterogeneity. The greatest were among families with mean age of diagnosis less than 50 years at 4q21.1 (dominant HLOD = 4.51, α = 0.84, 145.40 cM, rs10518142) and among all families at 12q24.32 (dominant HLOD = 3.60, α = 0.48, 285.15 cM, rs952093). Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLOD = 3.07, α = 0.29; dominant HLOD = 3.03, α = 0.32, respectively). Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLOD = 3.02, α = 0.51, 132.52 cM, rs1319036). These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated. © 2012 Cicek et al

A patient-centred intervention to improve the management of multimorbidity in general practice:the 3D RCT

Background: People with multimorbidity experience impaired quality of life, poor health and a burden from treatment. Their care is often disease-focused rather than patient-centred and tailored to their individual needs. Objective: To implement and evaluate a patient-centred intervention to improve the management of patients with multimorbidity in general practice. Design: Pragmatic, cluster randomised controlled trial with parallel process and economic evaluations. Practices were centrally randomised by a statistician blind to practice identifiers, using a computer-generated algorithm. Setting: Thirty-three general practices in three areas of England and Scotland. Participants: Practices had at least 4500 patients and two general practitioners (GPs) and used the EMIS (Egton Medical Information Systems) computer system. Patients were aged ≥ 18 years with three or more long-term conditions. Interventions: The 3D (Dimensions of health, Depression and Drugs) intervention was designed to offer patients continuity of care with a named GP, replacing separate reviews of each long-term condition with comprehensive reviews every 6 months. These focused on individualising care to address patients’ main problems, attention to quality of life, depression and polypharmacy and on disease control and agreeing treatment plans. Control practices provided usual care. Outcome measures: Primary outcome – health-related quality of life (assessed using the EuroQol-5 Dimensions, five-level version) after 15 months. Secondary outcomes – measures of illness burden, treatment burden and patient-centred care. We assessed cost-effectiveness from a NHS and a social care perspective. Results: Thirty-three practices (1546 patients) were randomised from May to December 2015 [16 practices (797 patients) to the 3D intervention, 17 practices (749 patients) to usual care]. All participants were included in the primary outcome analysis by imputing missing data. There was no evidence of difference between trial arms in health-related quality of life {adjusted difference in means 0.00 [95% confidence interval (CI) –0.02 to 0.02]; p = 0.93}, illness burden or treatment burden. However, patients reported significant benefits from the 3D intervention in all measures of patient-centred care. Qualitative data suggested that both patients and staff welcomed having more time, continuity of care and the patient-centred approach. The economic analysis found no meaningful differences between the intervention and usual care in either quality-adjusted life-years [(QALYs) adjusted mean QALY difference 0.007, 95% CI –0.009 to 0.023] or costs (adjusted mean difference £126, 95% CI –£739 to £991), with wide uncertainty around point estimates. The cost-effectiveness acceptability curve suggested that the intervention was unlikely to be either more or less cost-effective than usual care. Seventy-eight patients died (46 in the intervention arm and 32 in the usual-care arm), with no evidence of difference between trial arms; no deaths appeared to be associated with the intervention. Limitations: In this pragmatic trial, the implementation of the intervention was incomplete: 49% of patients received two 3D reviews over 15 months, whereas 75% received at least one review. Conclusions: The 3D approach reflected international consensus about how to improve care for multimorbidity. Although it achieved the aim of providing more patient-centred care, this was not associated with benefits in quality of life, illness burden or treatment burden. The intervention was no more or less cost-effective than usual care. Modifications to the 3D approach might improve its effectiveness. Evaluation is needed based on whole-system change over a longer period of time. Trial registration: Current Controlled Trials ISRCTN06180958. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 7, No. 5. See the NIHR Journals Library website for further project information

A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk

Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Geneenvironment interactions (G x E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G x E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G x E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G x E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant GxBMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer

Discovery of common and rare genetic risk variants for colorectal cancer.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.Goncalo R Abecasis has received compensation from 23andMe and Helix. He is currently an employee of Regeneron Pharmaceuticals. Heather Hampel performs collaborative research with Ambry Genetics, InVitae Genetics, and Myriad Genetic Laboratories, Inc., is on the scientific advisory board for InVitae Genetics and Genome Medical, and has stock in Genome Medical. Rachel Pearlman has participated in collaborative funded research with Myriad Genetics Laboratories and Invitae Genetics but has no financial competitive interest