Improving mental health in chronic care in general practice: study protocol for a cluster-randomised controlled trial of the Healthy Mind intervention.

BACKGROUND: Mental health issues are common among patients with chronic physical conditions, affecting approximately one in five patients. Poor mental health is associated with worse disease outcomes and increased mortality. Problem-solving therapy (PST) may be a suitable treatment for targeting poor mental health in these patients. This study protocol describes a randomised controlled trial of the Healthy Mind intervention, a general practice-based intervention offering PST to patients with type 2 diabetes and/or ischaemic heart disease and poor mental well-being. METHODS: A stepped-wedge cluster-randomised controlled trial with 1-year follow-up will be conducted in Danish general practice. At the annual chronic care consultation, patients with type 2 diabetes and/or chronic ischaemic heart disease will be screened for poor mental well-being. Patients in the control group will be offered usual care while patients in the intervention group will be offered treatment with PST provided by general practitioners (GPs) or general practice staff, such as nurses, who will undergo a 2-day PST course before transitioning from the control to the intervention group. The primary outcome is change in depressive symptoms after 6 and 12 months. Secondary outcomes include change in mental well-being, anxiety, and diabetes distress (patients with type 2 diabetes) after 6 and 12 months as well as change in total cholesterol levels, low-density lipoprotein (LDL) levels, and blood glucose levels (patients with diabetes) after 12 months. Process outcomes include measures of implementation and mechanisms of impact. We aim to include a total of 188 patients, corresponding to approximately 14 average-sized general practices. DISCUSSION: The Healthy Mind trial investigates the impact of PST treatment for patients with chronic disease and poor mental well-being in general practice. This will be the first randomised controlled trial determining the effect of PST treatment for patients with chronic diseases in general practice. The results of this study will provide relevant insights to aid GPs, and general practice staff manage patients with poor mental well-being. TRIAL REGISTRATION: ClinicalTrials.gov NCT05611112. Registered on October 28, 2022.

A comparison of the original major depression inventory with a modified version: A Danish validation study.

BACKGROUND: The Major Depression Inventory (MDI) is a patient-reported outcome measure used by general practitioners to assist with diagnosing and evaluation of the severity of a patient's depression. However, recent studies have questioned the structural validity of the MDI. OBJECTIVES: We proposed a modified version (mMDI) of the MDI with fewer response categories and four rephrased items and aimed to compare the psychometric properties of the changes in a joint cohort of patients from general practice and mental health associations. METHODS: We used Rasch analysis, confirmatory factor analysis, and the area under the receiver operating curve (AUROC) to assess the validity and reliability of the two versions. Equipercentile linking was used to compute cut-off points for the mMDI. RESULTS: For both versions, local dependence was found between the three item pairs (loss of interest, lack of energy), (lack of self-confidence, feelings of guilt), and (concentration problems, feeling restless/slowed down). The mMDI displayed lower measurement error in the upper end of the scale and better item level fit for three of the four reformulated items compared to the MDI. For the MDI, 5.3% of the respondents gave improbable responses; the corresponding number was 3.4% for the mMDI. The mMDI displayed better fit to a one-factor model compared to the MDI. When comparing the correlation of the scales with the WHO-5 instrument, the corresponding AUROC estimates for the mMDI and MDI were found to be 0.93 (0.92; 0.96) and 0.91 (0.87; 0.94), respectively. The cut-off points for mild, moderate, and severe depression in the mMDI were found to be 17, 20, and 23, respectively. CONCLUSION: The proposed changes of the MDI are psychometrically sound upgrades of the original.

Mental healthcare utilisation among Danish formerly deployed military personnel and their civilian counterparts: a cohort study.

Background: Prior studies comparing the mental healthcare utilisation (MHU) of Danish formerly deployed military personnel (FDP) with the general population have not included data on psychotherapy through the Defence or talking therapy with the general practitioner. This study included these and several other data sources in a comprehensive comparison of MHU between Danish FDP and civilians.Methods: First-time deployed military personnel (N = 10,971) who had returned from a mission to Kosovo, Afghanistan, Iraq or Lebanon between January 2005 and July 2017 were included. A sex and birth-year-matched civilian reference group was randomly drawn from the entire Danish non-deployed population (N = 253,714). Furthermore, a sub-cohort, including male FDP and civilians deemed eligible for military service, was defined. These cohorts were followed up in military medical records and registers covering the primary and secondary civilian health sectors from 2005 to 2018, and the rates of MHU were compared.Results: Approximately half of the initial help-seeking for FDP took place through the Defence (49.4%), and the remainder through the civilian healthcare system. When help-seeking through the Defence was not included, MHU was significantly lower among FDP in the main cohort during the first two years (IRR = 0.84, 95% CI: [0.77, 0.92]) compared to civilians. When help-seeking through the Defence was included, MHU was significantly higher among FDP compared to civilians both in the first two years of follow-up (IRR = 2.01, 95% CI: [1.89, 2.13]) and thereafter (IRR = 1.18, 95% CI: [1.13, 1.23]). In the sub-cohort, these differences were even more pronounced both in the first two years of follow-up and thereafter.Conclusions: MHU was higher among Danish FDP compared to civilians only when data from the Defence was included. The inclusion of data on both civilian and military healthcare services is necessary to evaluate the full impact of deployment on MHU among Danish FDP.

This study compared mental healthcare utilisation among Danish deployed military personnel and civilians.Most personnel sought help first through the Defence.When all data sources were included, mental healthcare utilisation was significantly higher among military personnel.

Patient Health Questionnaire-9: A clinimetric analysis.

OBJECTIVE: The Patient Health Questionnaire-9 (PHQ-9) is a widely used self-reported measure of depression, which was found to display only acceptable psychometric properties. Insufficient attention has been devoted to its clinimetric validity and its clinical utility is still debated, particularly when used for assessing depression severity. This is the first study testing PHQ-9 construct validity and clinical utility based on clinimetric principles. METHODS: An online survey involving a sample of 3,398 participants was conducted. Item Response Theory models (Rasch and Mokken analyses) were used to assess PHQ-9 validity and determine its clinical utility. RESULTS: Fit to the Rasch model was achieved after adjusting the sample size. Items 2, 4, 6, 9 displayed over-discrimination, items 1, 5, 7 showed under-discrimination. Indication of local dependency between items 2 and 6 was found. PHQ-9 was not unidimensional. A Loevinger's coefficient of 0.49 was found, indicating an acceptable level of scalability. CONCLUSIONS: PHQ-9 is a measure of potential clinical utility to be used as an overall index of depression, mainly for screening purposes. Substantial revisions, particularly in the wording of over- and under-discriminating items, are needed.

Real-World Evidence on Clinical Outcomes of Commonly Used Antidepressants in Older Adults Initiating Antidepressants for Depression: A Nationwide Cohort Study in Denmark.

OBJECTIVE: The authors investigated the clinical outcomes of commonly used antidepressants among older adults who initiated first-time antidepressants for depression by analyzing the 1-year risk of selected clinically relevant outcomes. METHODS: This cohort study used nationwide Danish registry data and included all older adults who redeemed a first-time (since 1995) antidepressant prescription with an indication of depression between 2006 and 2017. Only the 10 most frequently redeemed antidepressants were included in the analyses. Outcomes included discontinuation, switching, augmentation, psychiatric hospital contacts, suicide attempt or self-harm, fall-related injuries, cardiovascular events, and all-cause mortality. Incidence rate ratios (IRRs) and 95% confidence intervals were estimated using Poisson regression models, controlling for potential confounders. RESULTS: The study sample included 93,883 older adults (mean age, 78.0 years, SD=7.5 years; 56% female). The most frequently prescribed antidepressants were selective serotonin reuptake inhibitors (citalopram, 47.04%; escitalopram, 11.81%; fluoxetine, 0.55%; paroxetine, 0.52%; sertraline, 11.17%), serotonin-norepinephrine reuptake inhibitors (duloxetine, 0.71%; venlafaxine, 1.54%), a tricyclic antidepressant (amitriptyline, 1.86%), and two atypical antidepressants (mianserin, 1.93%; mirtazapine, 22.87%). Compared with users of sertraline (the reference drug in this analysis, as Danish guidelines recommend it as the first-choice treatment for depression), users of most of the other nine antidepressants had a significantly higher risk of discontinuation (e.g., mirtazapine: IRR=1.55, 95% CI=1.50-1.61; venlafaxine: IRR=1.22, 95% CI=1.12-1.32), switching (amitriptyline: IRR=1.45, 95% CI=1.15-1.81; venlafaxine: IRR=1.47, 95% CI=1.20-1.80), augmentation, cardiovascular events, and mortality. Overall, mirtazapine and venlafaxine users had the most adverse outcomes compared with sertraline users. These results remained consistent in analyses stratified by sex and age (≤75 years vs. >75 years). CONCLUSIONS: This real-world evidence suggests that clinical outcomes may vary among initiators of commonly used antidepressants in older adults, which may inform benefit-risk evaluation at treatment initiation, and highlights the importance of careful selection of antidepressant treatment.

Managing mental health in chronic care in general practice: a feasibility study of the Healthy Mind intervention.

BACKGROUND AND OBJECTIVE: Mental health issues are common among patients with chronic physical conditions. This study aims to evaluate the feasibility of the Healthy Mind intervention, a general practice-based programme that provides problem-solving therapy (PST) to patients with poor mental well-being and type 2 diabetes (T2D) and/or ischaemic heart disease (IHD). DESIGN AND SETTING: A one-arm feasibility study was conducted in three general practices in the Central Denmark Region. INTERVENTION: Eight healthcare providers from the included general practices underwent a two-day course to acquire PST skills. Screening for poor mental health was carried out at the annual chronic care consultation for T2D or IHD, and PST sessions were offered to patients on indication of poor mental health. Nine patients received PST. METHODS: Semi-structured interviews with eight healthcare providers and six patients were conducted. Data were analysed deductively focusing on appropriateness, acceptability and fidelity of the intervention. RESULTS: The intervention was considered appropriate for the patient group and the general practice setting. The providers acknowledged PST as a valuable tool for managing psychological issues in general practice, and the patients perceived PST as an effective and tangible treatment. Since practice nurses' schedules were generally better suited for longer consultations, they were often the preferred intervention providers. The intervention was largely delivered as intended. However, the GPs generally expected patients to prefer a more directive approach, which sometimes challenged their role as facilitator and guide. CONCLUSION: The Healthy Mind intervention was found to be feasible, and the results support proceeding to a full-scale evaluation trial.

Patients with type 2 diabetes and/or ischaemic heart disease often experience poor mental well-being, revealing a shortage of general practice-based interventions targeting this issue.This study evaluates the feasibility of a problem-solving therapy intervention in general practice for patients with poor mental health and type 2 diabetes and/or chronic ischemic heart disease.Both patients and healthcare providers regarded problem-solving therapy as an acceptable intervention for managing psychological issues in general practice.Healthcare providers preferred practice nurses as the providers of problem-solving therapy since their schedules were often more suitable for longer consultations.In problem-solving therapy, the provider is expected to take a facilitating and guiding role, but GPs sometimes struggled remaining in this role due to a preconceived anticipation that patients expected them to take a more directive approach.

The Brief Health Literacy Scale for Adults: Adaptation and Validation of the Health Literacy for School-Aged Children Questionnaire.

The Health Literacy for School-Aged Children (HLSAC) is a brief, generic instrument measuring health literacy among school-aged children. Given its brevity and broad conceptualization of health literacy, the HLSAC is a potentially valuable measuring instrument among adults as well. This validation study aimed to adapt the HLSAC questionnaire to an adult population through assessment of content validity and subsequently determine the structural validity of the adapted instrument, the Brief Health Literacy scale for Adults (B-HLA). The content validity of the HLSAC was assessed through interviews with respondents and experts, and the structural validity of the adapted instrument (B-HLA) was evaluated using Rasch analysis. The content validity assessment (n = 25) gave rise to adjustments in the wording of five items. The B-HLA demonstrated an overall misfit to the Rasch model (n = 290). Items 6 and 8 had the poorest individual fits. We found no signs of local dependency or differential item functioning concerning sex, age, education, and native language. The B-HLA demonstrated unidimensionality and ability to discriminate across health literacy levels (PSI = 0.80). Discarding items 6 or 8 resulted in an overall model fit and individual fit of all items. In conclusion, the B-HLA appears to be a valid and reliable instrument for assessing health literacy among adults.

Do sociodemographic and clinical factors affect the selection of initial antidepressant treatment for depression in older adults? Results from a nationwide descriptive study in Denmark.

BACKGROUND: The choice of antidepressants for initial pharmacological treatment of depression in older adults and associated patients' characteristics are understudied. We aimed to describe the first selected antidepressant (first-choice) for depression in older adults (≥65 years) and whether patients' sociodemographic and clinical characteristics influence selecting an alternative first-choice (any other antidepressant than the nationally recommended first-choice sertraline) in Denmark. METHODS: Register-based cross-sectional study including all older adults who redeemed their first antidepressant prescription for depression at community pharmacies in Denmark in 2015-2019. We analyzed the effect of patients' characteristics on the first-choice antidepressant selection using multinomial logistic regression. RESULTS: Among 34,337 older adults with a first antidepressant-prescription, over two-thirds filled alternative first-choice antidepressants than sertraline (28.9 %): escitalopram or citalopram (30.3 %) or mirtazapine (34.4 %). Socially disadvantaged older adults (e.g., with short educational attainment, being single, or of non-western ethnicity) and clinically vulnerable older adults (e.g., having somatic diagnoses and hospital contacts) were more likely to use alternative first-choice antidepressants. LIMITATIONS: Information on prescribers and in-hospital medications was not included in this study. CONCLUSIONS: Further investigation of the first antidepressant selection and its impact on depression treatment outcomes in older adults is necessary. Moreover, for older patients, national guidelines on depression treatment should be more specific. ARTICLE SUMMARY: Antidepressant selection for initial pharmacological treatment of depression in older adults can be difficult due to comorbidity, polypharmacy, and age-related changes in pharmacokinetics and pharmacodynamics. Real-world evidence/knowledge on first-choice antidepressant selection and associated user characteristics are rare. This Danish register-based cross-sectional study found over two-thirds of older adults filled alternative antidepressants (primarily escitalopram/citalopram or mirtazapine) than nationally recommended first-choice sertraline for depression treatment and identified wide-ranging sociodemographic and clinical factors influencing the first antidepressant selection.

Comparing the construct validity of the Patient Health Questionnaire (PHQ-9) and the Major Depression Inventory (MDI) using Rasch analysis.

OBJECTIVE: The Patient Health Questionnaire (PHQ-9) and the Major Depression Inventory (MDI) are psychometric instruments frequently used for depression diagnosis and monitoring in primary care settings. The goal of this study was to assess and compare the construct validity of the PHQ-9 and the MDI using Rasch analysis. METHODS: The PHQ-9 and the MDI were distributed in random ordering (first or last) to a waiting room sample of Danish primary care patients. Analysis of fit to the Rasch model, ordering of response categories, dimensionality-testing, test for differential item functioning, test for local dependency, and calculation of reliability indices were used to evaluate the psychometric characteristics of the instruments. RESULTS: A sample of 281 persons (18-87 years, 72 % females) responded to both instruments. Reliability was acceptable for PHQ-9 (PSI 0.80) and excellent for MDI (PSI 0.88). Both instruments demonstrated fit to the Rasch model after rescoring of all items. Dimensionality testing supports that both instruments are unidimensional. Indication of local dependency was observed for PHQ-9 item 2&6 and MDI item 1&4. No indication of differential item functioning regarding age, gender or ordering of instruments was found. CONCLUSION: The PHQ-9 and the MDI both demonstrate measurement problems. Modifying individual items and reducing the number of response categories in both instruments could potentially improve their measurement capabilities. Study findings do not provide a conclusive indication of which instrument has superior operating characteristics.

Treatment indications and potential off-label use of antidepressants among older adults: A population-based descriptive study in Denmark.

OBJECTIVES: Off-label prescriptions of antidepressants may be of special concern in older-adults. We aimed to study the potential off-label use of antidepressants among adults ≥65 years by describing the patterns, trends, and factors associated with missing and unspecified treatment indications. METHODS: We used registry data to describe indications of all antidepressant prescriptions (N = 13.8 million) redeemed by older-adults in 2006-2019. We investigated factors associated with off-label use by considering prescriptions with missing and unspecified indications of the first antidepressant prescription using a multinomial logistic regression with the 'depression' indication as a reference category and reported odds ratios (ORs) with 95% confidence intervals (CI). RESULTS: Overall, 18.1% of all antidepressant prescriptions had missing indications, and 9.9% had unspecified indications. The proportion of potential off-label use based on missing and unspecified prescriptions remained mostly consistent during 2006-2019. We identified similar associations in user characteristics whether considering missing or unspecified first prescription. ORs with 95% CI were raised in non-western ethnicity (vs. Danish, 1.12 (0.99-1.26) for missing indication and 1.28 (1.11-1.48) for unspecified indication) and female sex (vs. male, 1.05 (1.02-1.07) and 1.05 (1.02-1.07) respectively). ORs were reduced for shorter educational attainment (vs. long, 0.90 (0.87-0.94) and 0.92 (0.88-0.96)), older age (≥81 vs. 67-70 years, 0.66 (0.65-0.71) and 0.73 (0.70-0.76)) and hospital psychiatric diagnosis (per diagnosis 0.76 (0.73-0.78) and 0.88 (0.86-0.91)). CONCLUSIONS: Nearly one-third of all antidepressant prescriptions redeemed by older-adults in Denmark had either missing or unspecified treatment indications. Whether these prescriptions were actual off-label use needs to be validated. Clinicians should pay special attention to patients' characteristics linking missing and unspecified indications and maintain adequate documentation while prescribing medication.

Cancer risk in persons with new-onset anaemia: a population-based cohort study in Denmark.

BACKGROUND: The time interval from first symptom and sign until a cancer diagnosis significantly affects the prognosis. Therefore, recognising and acting on signs of cancer, such as anaemia, is essential. Evidence is sparse on the overall risk of cancer and the risk of specific cancer types in persons with new-onset anaemia detected in an unselected general practice population. We aimed to assess the risk of cancer in persons with new-onset anaemia detected in general practice, both overall and for selected cancer types. METHODS: This observational population-based cohort study used individually linked electronic data from laboratory information systems and nationwide healthcare registries in Denmark. We included persons aged 40-90 years without a prior history of cancer and with new-onset anaemia (no anaemia during the previous 15 months) detected in general practice in 2014-2018. We measured the incidence proportion and standardised incidence ratios of a new cancer diagnosis (all cancers except for non-melanoma skin cancers) during 12 months follow-up. RESULTS: A total of 48,925 persons (median [interquartile interval] age, 69 [55-78] years; 55.5% men) were included in the study. In total, 7.9% (95% confidence interval (CI): 7.6 to 8.2) of men and 5.2% (CI: 4.9 to 5.5) of women were diagnosed with cancer during 12 months. Across selected anaemia types, the highest cancer incidence proportion was seen in women with 'anaemia of inflammation' (15.3%, CI: 13.1 to 17.5) (ferritin > 100 ng/mL and increased C-reactive protein (CRP)) and in men with 'combined inflammatory iron deficiency anaemia' (19.3%, CI: 14.5 to 24.1) (ferritin < 100 ng/mL and increased CRP). For these two anaemia types, the cancer incidence across cancer types was 10- to 30-fold higher compared to the general population. CONCLUSIONS: Persons with new-onset anaemia detected in general practice have a high cancer risk; and markedly high for 'combined inflammatory iron deficiency anaemia' and 'anaemia of inflammation'. Anaemia is a sign of cancer that calls for increased awareness and action. There is a need for research on how to improve the initial pathway for new-onset anaemia in general practice.

Cross-cultural validity of the WHO-5 Well-Being Index and Euthymia Scale: A clinimetric analysis.

BACKGROUND: The assessment of psychological well-being and euthymia represents an emerging issue in clinical psychology and psychiatry. Rating scales and indices such as the 5-item version of the World Health Organization Well-Being Index (WHO-5) and the Euthymia Scale (ES) were developed but insufficient attention has been devoted to the evaluation of their cross-cultural validity. This is the first study using Clinimetric Patient-Reported Outcome Measures (CLIPROM) criteria to assess cross-cultural validity and sensitivity of five different versions of the WHO-5 and ES. METHODS: A multicenter cross-sectional study involving a total of 3762 adult participants from different European (i.e., Italy, Poland, Denmark) and non-European (i.e., China, Japan) countries was conducted. Item Response Theory models (Mokken and Rasch analyses) were applied. RESULTS: Mokken coefficients of scalability were found to range from 0.42 to 0.84. The majority of the versions of the WHO-5 fitted the Rasch model expectations. Paired t-tests revealed that the Italian and Danish WHO-5 versions were unidimensional. Person Separation Reliability indices showed that the Polish, Danish, and Japanese ES versions could reliably discriminate between subjects with different levels of euthymia. LIMITATIONS: A convenience sampling was used, thus limiting the generalizability of study findings. In addition, no measures of negative mental health were administered. CONCLUSIONS: WHO-5 can be used in international studies for cross-cultural comparisons since it covers transcultural components of subjective well-being. Findings also suggest that the ES can be used as a cross-cultural screening tool since it entailed the clinimetric property of sensitivity.

Rasch analysis of the structural validity of the anxiety symptom scale in the lolland-falster health study.

BACKGROUND: We aimed to assess the psychometric properties of the ten-item Anxiety Symptom Scale (ASS) using Rasch analysis. Data from the Lolland-Falster Health Study (LOFUS) were used including ASS data for 16,137 persons aged 18-90 years. METHODS: Fit to the Rasch model, ordering of response categories, dimensionality testing, test for differential item functioning, test for local dependency of items, and calculation of reliability were used to evaluate the psychometric characteristics of the ASS. RESULTS: Ordered response categories were achieved for nine of ten items after modifying the original six-point scoring system into a five-point system. After adjustment of the sample size to 500 persons, the ASS fitted the Rasch Model (p = 0.051). Dimensionality testing supported combining the ten items into a total score. No significant differential item functioning was observed for sex, age group, and educational level. Items 1 and 9 and items 4 and 5 demonstrated indication of local dependency. Combining these two item pairs improved the fit of the ASS to the Rasch model. LIMITATIONS: The total ASS was poorly targeted for the LOFUS population as the majority of persons were located at the lower end of the construct. This poor alignment could explain the low reliability (PSI 0.49). Analyzing a balanced random sample of responders with high and low ASS scores demonstrated a sufficient PSI (0.81). CONCLUSIONS: Despite problems with the measurement structure, the ASS seems to be a promising instrument for measuring anxiety. However, it may prove more reliable for use in clinical samples of respondents.

The Hopkins Symptom Checklist (SCL-90-R): A Patient-Reported Outcome Measure in Parkinson's Disease.

Objective: This is the first study applying Clinimetric Patient-Reported Outcome Measures (CLIPROM) criteria to evaluate the construct validity, sensitivity, and clinical utility of the SCL-90-R in patients with Parkinson's disease (PD). Methods: A Rasch analysis was conducted using a sample of 488 PD outpatients. Results: Testing for dimensionality revealed that less than 5% of t-tests were significant, indicating that the SCL-90-R subscales entailed the property of construct validity. As to the total score, a Person Separation Reliability Index of .96 was found. Conclusions: The SCL-90-R total score is a sensitive screening measure that can be used not only to differentiate healthy stress reactions from symptoms of psychological distress but also to detect PD patients with an increased risk for psychiatric complications. As to the subscales, the brief versions that did not include misfitting items should be used to assess the severity of specific symptoms of psychological distress affecting PD patients.

Comparing treatments for post-traumatic stress disorder - a systematic review.

INTRODUCTION: The recommended treatments for post-traumatic stress disorder (PTSD) are psychological therapies and medication, but the best approach is still discussed. Exposure to traumatic events in psychotherapy tends to cause high drop-out rates. Likewise, little effect or adverse events of medications may lead to attrition. The aim of this study was to compare the outcomes of treatment by psychotherapy and medications. An additional aim was to explore the combinations of treatment modalities in adults with PTSD and to investigate differences in drop-out rates. METHODS: A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. PubMed and Embase were searched for relevant randomised clinical trials. The Cochrane risk-of-bias tool was used to assess the quality of the retrieved trials. RESULTS: Seven eligible studies were identified. Three studies showed that psychotherapy was superior to selective serotonin reuptake inhibitors. Two studies showed an augmenting effect with prolonged exposure. Two studies showed no differences across the treatment groups. In four of the included studies, patients treated with psychotherapy were more likely to drop out. CONCLUSIONS: Extant evidence is insufficient to assess whether combined therapy is superior to monotherapy. Both medication and psychotherapy have an effect on PTSD, but psychotherapy tends to provide greater and more long-lasting outcome improvements. Trauma type, PTSD severity and other variables affect drop-out rates and treatment outcomes.

Diagnostic workup of cancer in patients with new-onset anaemia: a Danish cohort study in general practice.

BACKGROUND: Anaemia is associated with adverse outcomes, including increased morbidity and all-cause mortality. Diagnostic workup of patients with anaemia is essential to detect underlying disease, especially undiagnosed malignancy. OBJECTIVE: To describe the cancer-relevant diagnostic workup in patients with new-onset anaemia detected in general practice. An additional aim was to analyse associations between patient characteristics and the diagnostic workup. DESIGN: Observational population-based cohort study using electronic laboratory and register data. SETTING: Danish general practice. SUBJECTS: Patients aged 40-90 years with new-onset anaemia (no anaemia in the preceding 15 months) detected in general practice. Patients were identified in Danish laboratory information systems and nationwide registries in 2014-2018. MAIN OUTCOME MEASURES: We measured the proportion of patients receiving predefined diagnostic investigations, that is, cancer patient pathway, colonoscopy, gastroscopy, computerised tomography (CT) scan, faecal test for haemoglobin, and bone marrow examination within three months of the anaemia index date. RESULTS: We included 59,993 patients, and around half of the patients with 'iron deficiency anaemia', 'anaemia of inflammation', or 'combined inflammatory iron deficiency anaemia' had no cancer-relevant diagnostic investigations performed. Patients aged 60-79 years and patients with severe anaemia were more likely to have investigations performed, while patients with comorbidity were less likely to have investigations performed. CONCLUSION: Around half of the patients with anaemia subtypes that may indicate underlying cancer had no cancer-relevant diagnostic investigations performed. This may represent missed diagnostic opportunities. Future interventions are needed to improve the diagnostic workup of cancer in patients with anaemia, for example, laboratory alert systems and clinical decision support.KEY POINTSThe general practitioners are often the first to detect anaemia and its underlying disease (e.g. undiagnosed malignancy).Large-scale studies are needed on the diagnostic workup of patients with anaemia in general practice in relation to an underlying malignancy.This study shows that the majority of patients with anaemia had no cancer-relevant diagnostic investigations performed, which may cause diagnostic delay.Interventions seems needed to improve the diagnostic workup of cancer in these patients to ensure timely diagnosis.

Insufficient classification of anaemia in general practice: a Danish register-based observational study.

BACKGROUND: Anaemia can be a pointer of underlying severe disease, including undiagnosed malignancy. Subsequent blood tests are essential to classify the anaemia into subtypes and to facilitate targeted diagnostic investigation to ensure timely diagnosis of underlying disease. OBJECTIVE: We aimed to describe and classify anaemia based on laboratory tests from patients with new-onset anaemia detected in general practice. An additional aim was to analyse associations between patient characteristics and unclassified anaemia (not classifiable according to an algorithm). DESIGN: Population-based cross-sectional study. SETTING: Danish general practice. SUBJECTS: A total of 62,731 patients (age: 40-90 years) with new-onset anaemia were identified in Danish laboratory information systems and nationwide registries, and data were obtained for 2014-2018. MAIN OUTCOME MEASURES: We measured the proportion of patients classified into subtypes of anaemia based on blood tests requested by general practitioners within 31 days of the anaemia index date. RESULTS: Of the 62,731 patients with new-onset anaemia, we identified unclassified anaemia in 78.9% (95% confidence interval (CI): 77.3-80.5) of men and 65.1% (CI: 63.4-66.9) of women. The likelihood of unclassified anaemia increased with age, increasing comorbidity and decreasing severity of anaemia. CONCLUSION: The majority of patients with new-onset anaemia could not be classified through a simple algorithm due to missing blood tests, which highlights a potential missed opportunity for diagnosis. Standardised laboratory testing of patients with anaemia is warranted to ensure adequate follow-up and early detection of underlying severe disease.KEY POINTSAnaemia can be a sign of malignancy, and anaemia classification is an important step in the diagnosis of underlying disorders.The majority of patients with anaemia could not be classified according to a simple algorithm due to missing blood tests.Some patient characteristics were associated with a high risk of unclassified anaemia: high age, high comorbidity, and severe anaemia.Standardised laboratory testing in patients with anaemia is needed to inform targeted diagnostic investigation to ensure timely diagnosis.

Improving the precision of depression diagnosis in general practice: a cluster-randomized trial.

BACKGROUND: Methods to enhance the accuracy of the depression diagnosis continues to be of relevance to clinicians. The primary aim of this study was to compare the diagnostic precision of two different diagnostic strategies using the Mini International Neuropsychiatric Interview (MINI) as a reference standard. A secondary aim was to evaluate accordance between depression severity found via MINI and mean Major Depression Inventory (MDI) sum-scores presented at referral. METHODS: This study was a two-armed, cluster-randomized superiority trial embedded in the Collabri trials investigating collaborative care in Danish general practices. GPs performing case-finding were instructed always to use MDI when suspecting depression. GPs performing usual clinical assessment were instructed to detect depression as they would normally do. According to guidelines, GPs would use MDI if they had a clinical suspicion, and patients responded positively to two or three core symptoms of depression. We compared the positive predictive value (PPV) in the two groups. RESULTS: Fifty-one GP clusters were randomized. In total, 244 participants were recruited in the case-finding group from a total of 19 GP clusters, and 256 participants were recruited in the usual clinical assessment group from a total of 19 GP clusters. The PPV of the GP diagnosis, when based on case-finding, was 0.83 (95% CI 0.78-0.88) and 0.93 (95% CI 0.89-0.96) when based on usual clinical assessment. The mean MDI sum-scores for each depression severity group indicated higher scores than suggested cut-offs. CONCLUSIONS: In this trial, systematic use of MDI on clinical suspicion of depression did not improve the diagnostic precision compared with the usual clinical assessment of depression. TRIAL REGISTRATION: The trial was retrospectively registered on 07/02/2016 at ClinicalTrials.gov. No. NCT02678845 .

Clinimetric Criteria for Patient-Reported Outcome Measures.

Patient-reported outcome measures (PROMs) are self-rated scales and indices developed to improve the detection of the patients' subjective experience. Given that a considerable number of PROMs are available, it is important to evaluate their validity and usefulness in a specific research or clinical setting. Published guidelines, based on psychometric criteria, do not fit in with the complexity of clinical challenges, because of their quest for homogeneity of components and inadequate attention to sensitivity. Psychometric theory has stifled the field and led to the routine use of scales widely accepted yet with a history of poor performance. Clinimetrics, the science of clinical measurements, may provide a more suitable conceptual and methodological framework. The aims of this paper are to outline the major limitations of the psychometric model and to provide criteria for clinimetric patient-reported outcome measures (CLIPROMs). The characteristics related to reliability, sensitivity, validity, and clinical utility of instruments are critically reviewed, with particular reference to the differences between clinimetric and psychometric approaches. Of note is the fact that PROMs, rating scales, and indices developed according to psychometric criteria may display relevant clinimetric properties. The present paper underpins the importance of the clini-metric methodology in choosing the appropriate PROMs. CLIPROM criteria may also guide the development of new indices and the validation of existing PROMs to be employed in clinical settings.