Multiple myeloma: unplanned diagnostic pathways and association with risk factors and survival - a nationwide register-based cohort study in Denmark.

BACKGROUND: Multiple myeloma often presents with vague and non-specific symptoms. Many patients are diagnosed in unplanned rather than elective (planned) diagnostic pathways. This study investigates the diagnosis of multiple myeloma in unplanned pathways and the association with patient characteristics, disease profile, and survival. METHODS: We conducted a nationwide register-based study, including all patients diagnosed with multiple myeloma in Denmark in 2014-2018. Patients were categorised as diagnosed in an unplanned pathway if registered with an acute admission within 30 days prior to the multiple myeloma diagnosis and no other previously registered pathway to this diagnosis. Unplanned pathways were compared to all other pathways combined. RESULTS: We included 2,213 patients diagnosed with multiple myeloma, hereof 32% diagnosed in an unplanned pathway. Comorbidity, no prior cancer diagnosis, a history of few visits to the general practitioner (GP), multiple myeloma complications at diagnosis, high-risk cytogenetics, and advanced cancer stage were associated with a higher probability of being diagnosed in an unplanned pathway. For example, 24.4% (95% confidence interval (CI): 21.8-27.0) of patients with low comorbidity (Charlson Comorbidity Index (CCI) score 0) were diagnosed in an unplanned pathway as were 50.9% (95% CI: 45.6-56.1) of patients with high comorbidity (CCI score 3+). For patients with dialysis need at the time of diagnosis the probability was 66.0% (95% CI 54.2-77.8) and 30.9% (95% CI: 28.9-32.9) for patients with no dialysis need. Patients diagnosed in an unplanned pathway had inferior survival (hazard ratio 1.44 (95% CI: 1.26-1.64)). However, this association was not seen in analyses restricted to patients surviving for more than three years. CONCLUSIONS: High comorbidity level, few usual GP visits, advanced disease status at diagnosis, and complications were associated with diagnosis in an unplanned pathway. Further, patients diagnosed in an unplanned pathway had inferior survival. Promoting earlier diagnosis and preventing unplanned pathways may help improve survival in multiple myeloma.

Healthcare fragmentation, multimorbidity, potentially inappropriate medication, and mortality: a Danish nationwide cohort study.

BACKGROUND: Patients with multimorbidity are frequent users of healthcare, but fragmented care may lead to suboptimal treatment. Yet, this has never been examined across healthcare sectors on a national scale. We aimed to quantify care fragmentation using various measures and to analyze the associations with patient outcomes. METHODS: We conducted a register-based nationwide cohort study with 4.7 million Danish adult citizens. All healthcare contacts to primary care and hospitals during 2018 were recorded. Clinical fragmentation indicators included number of healthcare contacts, involved providers, provider transitions, and hospital trajectories. Formal fragmentation indices assessed care concentration, dispersion, and contact sequence. The patient outcomes were potentially inappropriate medication and all-cause mortality adjusted for demographics, socioeconomic factors, and morbidity level. RESULTS: The number of involved healthcare providers, provider transitions, and hospital trajectories rose with increasing morbidity levels. Patients with 3 versus 6 conditions had a mean of 4.0 versus 6.9 involved providers and 6.6 versus 13.7 provider transitions. The proportion of contacts to the patient's own general practice remained stable across morbidity levels. High levels of care fragmentation were associated with higher rates of potentially inappropriate medication and increased mortality on all fragmentation measures after adjusting for demographic characteristics, socioeconomic factors, and morbidity. The strongest associations with potentially inappropriate medication and mortality were found for ≥ 20 contacts versus none (incidence rate ratio 2.83, 95% CI 2.77-2.90) and ≥ 20 hospital trajectories versus none (hazard ratio 10.8, 95% CI 9.48-12.4), respectively. Having less than 25% of contacts with your usual provider was associated with an incidence rate ratio of potentially inappropriate medication of 1.49 (95% CI 1.40-1.58) and a mortality hazard ratio of 2.59 (95% CI 2.36-2.84) compared with full continuity. For the associations between fragmentation measures and patient outcomes, there were no clear interactions with number of conditions. CONCLUSIONS: Several clinical indicators of care fragmentation were associated with morbidity level. Care fragmentation was associated with higher rates of potentially inappropriate medication and increased mortality even when adjusting for the most important confounders. Frequent contact to the usual provider, fewer transitions, and better coordination were associated with better patient outcomes regardless of morbidity level.

Fear of cancer recurrence at 2.5 years after a cancer diagnosis: a cross-sectional study in Denmark.

PURPOSE: The aim was to investigate the characteristics of cancer survivors with high levels of fear of cancer recurrence, and how such fear is associated with their needs for care. METHODS: This cross-sectional study was based on survey data from Danish cancer survivors at 2.5 years after a cancer diagnosis. These data were linked to nationwide register data. We used the 7-item Fear of Cancer Recurrence Inventory (FCR7) to measure fear of cancer recurrence, focussing on emotional, cognitive and behavioural reactions to such fear. The FCR7 score was dichotomised at the 75th percentile. A logistic regression model was used to analyse the associations between a high level of fear of cancer recurrence and (1) characteristics of patient and primary cancer and (2) cancer survivors' statements concerning follow-up for cancer. RESULTS: We included 1538 cancer survivors in the study. The median FCR7 score was 18 (interquartile interval: 13-21), and 366 (23.8%) respondents had an FCR7 score of > 21, defined as a high level of fear. In the adjusted analyses, a high level of fear was associated with female sex, younger age, comorbidity, advanced tumour stage and negative statements concerning follow-up, including feeling less safe in the follow-up programme. Fear was not related to the professional background of care providers involved in cancer follow-up. CONCLUSION: Fear of cancer recurrence was associated with female sex, younger age, comorbidity, advanced tumour stage and discontent with cancer follow-up.

A nationwide register-study of healthcare utilisation in the year preceding a colorectal cancer recurrence diagnosis.

OBJECTIVE: To analyse healthcare utilisation in colorectal cancer (CRC) survivors in the 12 months preceding a diagnosis of CRC recurrence. METHODS: This register-based cohort study included curatively treated survivors of CRC diagnosed in 2008-2018. Survivors with CRC recurrence were matched 1:5 with recurrence-free survivors. We estimated the monthly frequency of healthcare utilisation before the recurrence diagnosis and a corresponding index date assigned to the matched population. A regression model was used to compare healthcare utilisation between groups. RESULTS: We included 3045 survivors with recurrence and 15,225 recurrence-free survivors. At study entry, both groups had on average one contact per month to general practice. Compared with recurrence-free survivors, survivors with recurrence had more contacts to general practice from 10 months before the diagnosis and more haemoglobin measurements from 4 months before the diagnosis. They had more contacts to hospitals and follow-up clinics from 7 months before the diagnosis and more diagnostic investigations from 2 months before the diagnosis. CONCLUSION: General practitioners have regular contact with CRC survivors and are involved in detecting recurrence. The increased number of contacts in the months before the rise in diagnostic investigations indicates an opportunity to expedite referral to diagnostics and the diagnosis of CRC recurrence.

Time from incident primary cancer until recurrence or second primary cancer: Risk factors and impact in general practice.

OBJECTIVE: Specialised follow-up care after cancer treatment is changing towards increased involvement of general practice. To ensure timely detection of new cancer events, knowledge is warranted on the timing of cancer recurrence (CR) and second primary cancer (SPC), including risk factors for CR. METHODS: This population-based register study included 67,092 patients diagnosed with malignant melanoma, bladder, lung, ovarian, endometrial, colorectal and breast cancer in Denmark in 2008-2016. The time from primary cancer to CR or SPC and risk factors for prolonged time to CR were analysed and stratified on sex and primary cancer type. RESULTS: Cancer recurrence proportions ranged from 6% to 35%. The risk of CR increased profoundly within the first 3 years and then levelled off, except for breast cancer. A total of 3%-6% of patients had SPC, with monotonously increasing cumulative incidence proportions. Besides primary tumour characteristics, lower educational level, living alone and comorbidity were associated with earlier CR. For example, in female malignant melanoma, HRs and 95% confidence intervals were 0.47 (0.37-0.61) for high educational level, 1.40 (1.16-1.68) for living alone and 2.38 (1.53-3.70) for high comorbidity. CONCLUSION: The results may inform stratified risk assessment in decision of frequency, location and duration of post-cancer follow-up care.

Healthcare utilisation in general practice and hospitals in the year preceding a diagnosis of cancer recurrence or second primary cancer: a population-based register study.

BACKGROUND: The organisation of cancer follow-up is under scrutiny in many countries, and general practice is suggested to become more involved. A central focus is timely detection of recurring previous cancer and new second primary cancer. More knowledge on the patient pathway before cancer recurrence and second primary cancer is warranted to ensure the best possible organisation of follow-up. We aimed to describe the healthcare utilisation in the year preceding a diagnosis of cancer recurrence or second primary cancer. METHODS: This nationwide register study comprises patients diagnosed with bladder, breast, colorectal, endometrial, lung, malignant melanoma and ovarian cancer in Denmark in 2008-2016. The frequency of healthcare contacts during the 12 months preceding a cancer recurrence or second primary cancer was estimated and compared to the frequency of cancer survivors in cancer remission. The main analyses were stratified on sex and healthcare setting. Furthermore, two sub-analyses were stratified on 1) sex, healthcare setting and age group and on 2) sex, healthcare setting and comorbidity status. RESULTS: The study population consisted of 7832 patients with recurrence and 2703 patients with second primary cancer. On average, the patients were in contact with general practice one time per month in the 12th month preceding a new cancer diagnosis (recurrence or second primary cancer). Increasing contact rates were seen from 7 months before diagnosis in general practice and from 12 months before diagnosis in hospitals. This pattern was more pronounced in patients with cancer recurrence, younger patients and patients with no comorbidity. For instance, the contact rate ratios for hospital contacts in non-comorbid women with recurrence demonstrated 30% more contacts in the 12th month before recurrence and 127% more contacts in the 2nd month before recurrence. CONCLUSIONS: The results show that cancer survivors are already seen in general practice on a regular basis. The increasing contact rates before a diagnosis of cancer recurrence or second primary cancer indicate that a window of opportunity exists for more timely diagnosis; this is seen in both general practice and in hospitals. Thus, cancer survivors may benefit from improvements in the organisation of cancer follow-up.

The path to cancer diagnosis for the elderly.

Older cancer patients are more often than younger diagnosed via an unplanned hospital admission which may negatively influence the prognosis. An increasing number of cancers is expected due to ageing of populations, and these phenomena are likely to result in an increase in older cancer patients with multiple complications, extended hospital stays, and reduced quality of life and survival. In this review, we present recent data about routes to cancer diagnosis for older vs younger patients to emphasize that diagnostic pathways need improvements to avoid an increase in unplanned hospital admissions due to cancer.

Positive end-expiratory pressure influences echocardiographic measures of diastolic function: a randomized, crossover study in cardiac surgery patients.

BACKGROUND: Ultrasonography of the cardiovascular system is pivotal for hemodynamic assessment. Diastolic function is evaluated with a combination of tissue Doppler (e' and a') and pulsed Doppler (E and A) measures of transmitral- and mitral valve annuli velocities. However, accurate echocardiographic evaluation in the intensive care unit or perioperative setting is contingent on relative resistance to positive pressure ventilation and changes in preload. This study aimed to evaluate the effects of positive end-expiratory pressure (PEEP) and positioning on echocardiographic measures of diastolic function. METHODS: The study was a prospective, randomized, crossover study. Cardiac surgery patients with ejection fraction greater than 45% and averaged e' of 9 or more were included. Postoperatively, anesthetized patients were randomized into six combinations of PEEP (0, 6, 12 cm H2O) and positions (horizontal, Trendelenburg). At each combination, e' (primary endpoint), a', E, and A were obtained with transesophageal echocardiography along with left ventricular area. Image analysis was performed blinded to the protocol. RESULTS: Thirty patients completed the study. PEEP decreased lateral e' from 6.6±3.6 to 5.3±3.0 cm/s (P<0.001) in the horizontal position and from 7.4±4.2 to 6.5±3.3 cm/s (P<0.001) in Trendelenburg. Similar results were found for septal e', a' bilaterally and transmitral pulsed Doppler measures, and PEEP decreased left ventricular area. E/A, E/e', and e'/a' remained unaffected by PEEP and positioning. CONCLUSIONS: When evaluating diastolic function by echocardiography, the levels of PEEP and its effect on ventricular area have to be taken into account. In addition, this study dissuades the use of E/e' for tracking changes in left ventricular filling pressures in cardiac surgery patients.

Healthcare use and fear of recurrence in adult cancer survivors at 2.5 years after a cancer diagnosis: a nationwide register study in Denmark.

PURPOSE: To investigate the association between fear of cancer recurrence (FCR) and healthcare use in general practice among cancer survivors. METHODS: We linked nationwide register data to survey data on FCR in cancer survivors at 2.5 years after a cancer diagnosis. Multiple regression models were used to analyse the association between high FCR level and quartiles of healthcare use at 18-30 months before the cancer diagnosis (habitual healthcare use) and between high FCR level and healthcare use at 18-30 months after the cancer diagnosis (survivorship healthcare use). RESULTS: We included 1538 cancer survivors in the study. High habitual healthcare use was associated with a high level of FCR (odds ratio = 2.07 (95% confidence interval (CI): 1.36-3.15)) for the 4th quartile of healthcare use compared to the 1st quartile. A high FCR score was also associated with higher healthcare use during cancer survivorship (incidence rate ratio (IRR) = 1.26 (95% CI: 1.14-1.40)). This association remained statistically significant when adjusting for habitual healthcare use (IRR = 1.20 (95% CI: 1.09-1.33)). CONCLUSION: High healthcare use before the cancer diagnosis was associated with high FCR during survivorship. This indicates that FCR is partly explained by a general (pre-diagnostic) health concern. High FCR predicted high healthcare use during cancer survivorship, even when adjusting for habitual healthcare use. IMPLICATIONS FOR CANCER SURVIVORS: Our results suggest that FCR in cancer survivors is triggered by a general high level of health concern, and the cancer diagnosis may further exacerbate this concern.

A Validated Register-Based Algorithm to Identify Patients Diagnosed with Recurrence of Surgically Treated Stage I Lung Cancer in Denmark.

Introduction: Recurrence of cancer is not routinely registered in Danish national health registers. This study aimed to develop and validate a register-based algorithm to identify patients diagnosed with recurrent lung cancer and to estimate the accuracy of the identified diagnosis date. Material and Methods: Patients with early-stage lung cancer treated with surgery were included in the study. Recurrence indicators were diagnosis and procedure codes recorded in the Danish National Patient Register and pathology results recorded in the Danish National Pathology Register. Information from CT scans and medical records served as the gold standard to assess the accuracy of the algorithm. Results: The final population consisted of 217 patients; 72 (33%) had recurrence according to the gold standard. The median follow-up time since primary lung cancer diagnosis was 29 months (interquartile interval: 18-46). The algorithm for identifying a recurrence reached a sensitivity of 83.3% (95% CI: 72.7-91.1), a specificity of 93.8% (95% CI: 88.5-97.1), and a positive predictive value of 87.0% (95% CI: 76.7-93.9). The algorithm identified 70% of the recurrences within 60 days of the recurrence date registered by the gold standard method. The positive predictive value of the algorithm decreased to 70% when the algorithm was simulated in a population with a recurrence rate of 15%. Conclusion: The proposed algorithm demonstrated good performance in a population with 33% recurrences over a median of 29 months. It can be used to identify patients diagnosed with recurrent lung cancer, and it may be a valuable tool for future research in this field. However, a lower positive predictive value is seen when applying the algorithm in populations with low recurrence rates.

A Validated Algorithm for Register-Based Identification of Patients with Relapse of Clinical Stage I Testicular Cancer.

Purpose: The Danish Testicular Cancer (DaTeCa) database aims to monitor and improve quality of care for testicular cancer patients. Relapse data registered in the DaTeCa database rely on manual registration. Currently, some safeguarding against missing registrations is attempted by a non-validated register-based algorithm. However, this algorithm is inaccurate and entails time-consuming medical record reviews. We aimed (1) to validate relapse data as registered in the DaTeCa database, and (2) to develop and validate an improved register-based algorithm identifying patients diagnosed with relapse of clinical stage I testicular cancer. Patients and Methods: Patients registered in the DaTeCa database with clinical stage I testicular cancer from 2013 to 2018 were included. Medical record information on relapse data served as a gold standard. A pre-specified algorithm to identify relapse was tested and optimized on a random sample of 250 patients. Indicators of relapse were obtained from pathology codes in the Danish National Pathology Register and from diagnosis and procedure codes in the Danish National Patient Register. We applied the final algorithm to the remaining study population to validate its performance. Results: Of the 1377 included patients, 284 patients relapsed according to the gold standard during a median follow-up time of 5.9 years. The completeness of relapse data registered in the DaTeCa database was 97.2% (95% confidence interval (CI): 95.2-99.1). The algorithm achieved a sensitivity of 99.6% (95% CI: 98.7-100), a specificity of 98.9% (95% CI: 98.2-99.6), and a positive predictive value of 95.9% (95% CI: 93.4-98.4) in the validation cohort (n = 1127, 233 relapses). Conclusion: The registration of relapse data in the DaTeCa database is accurate, confirming the database as a reliable source for ongoing clinical quality assessments. Applying the provided algorithm to the DaTeCa database will optimize the accuracy of relapse data further, decrease time-consuming medical record review and contribute to important future clinical research.

A Validated Register-Based Algorithm to Identify Patients Diagnosed with Recurrence of Malignant Melanoma in Denmark.

PURPOSE: Information on cancer recurrence is rarely available outside clinical trials. Wide exclusion criteria used in clinical trials tend to limit the generalizability of findings to the entire population of people living beyond a cancer disease. Therefore, population-level evidence is needed. The aim of this study was to develop and validate a register-based algorithm to identify patients diagnosed with recurrence after curative treatment of malignant melanoma. PATIENTS AND METHODS: Indicators of recurrence were diagnosis and procedure codes recorded in the Danish National Patient Register and pathology results recorded in the Danish National Pathology Register. Medical records on recurrence status and recurrence date in the Danish Melanoma Database served as the gold standard to assess the accuracy of the algorithm. RESULTS: The study included 1747 patients diagnosed with malignant melanoma; 95 (5.4%) were diagnosed with recurrence of malignant melanoma according to the gold standard. The algorithm reached a sensitivity of 93.7% (95% confidence interval (CI) 86.8-97.6), a specificity of 99.2% (95% CI: 98.6-99.5), a positive predictive value of 86.4% (95% CI: 78.2-92.4), and negative predictive value of 99.6% (95% CI: 99.2-99.9). Lin's concordance correlation coefficient was 0.992 (95% CI: 0.989-0.996) for the agreement between the recurrence dates generated by the algorithm and by the gold standard. CONCLUSION: The algorithm can be used to identify patients diagnosed with recurrence of malignant melanoma and to establish the timing of recurrence. This can generate population-level evidence on disease-free survival and diagnostic pathways for recurrence of malignant melanoma.

A validated algorithm to identify recurrence of bladder cancer: a register-based study in Denmark.

PURPOSE: Recurrence of cancer is not routinely registered in the national registers in Denmark. The aim of this study was to develop and validate a register-based algorithm to identify patients diagnosed with recurrence of invasive bladder cancer (BC). MATERIALS AND METHODS: We performed a cohort study based on data from Danish national health registers. Diagnosis codes and procedural codes in the Danish National Patient Register and Systematized Nomenclature of Medicine codes in the Danish National Pathology Register were used as indicators of cancer recurrence. Status and date of recurrence as registered in the Danish Bladder Cancer Database (DaBlaCa-data) were used as the gold standard of BC recurrence to ascertain the accuracy of the algorithm. RESULTS: The algorithm reached a sensitivity of 85% (95% CI: 78-91), a specificity of 90% (95% CI: 79-96), and a positive predictive value of 95% (95% CI: 89-98). The algorithm demonstrated superior performance in patients undergoing cystectomy compared to patients undergoing radiotherapy as primary BC treatment. The concordance correlation coefficient for the agreement between the recurrence dates generated by the algorithm and the gold standard was 0.96 (95% CI: 0.95-0.98), and the estimated date was set within 90 days of the gold standard date for 90% of patients. CONCLUSION: The proposed algorithm to identify patients diagnosed with BC recurrence from Danish national registries showed excellent performance in terms of ascertaining occurrence and the timing of BC recurrence.

Quality assurance of the Western Denmark Heart Registry, a population-based healthcare register.

INTRODUCTION: During the past decade, the mandatory population-based healthcare database, the Western Denmark Heart Registry (WDHR), has provided the data for several research projects. As in most clinical registries, the data quality has not been validated thoroughly. This study was undertaken to evaluate the quality of registrations in the WDHR. METHODS: The audit supervised procedures from involved departments that were performed in 2013. An experienced research nurse completed data collection, and an experienced consultant evaluated the agreement between the WDHR and patient records. Indistinct data from patient records were determined after consulting a specialist from the department in question. Patient files were double-checked in case of disagreements between the involved systems. RESULTS: The total proportion of errors in the referral date was 16.4% in surgery, 9.8% in percutaneous invasive procedures (PCI), 16.1% in coronary angiography (CAG) and 19.5% in computed tomography (CT)-CAG, while the errors in inhospital dates were slightly lower. In the cardiac surgery registries, the proportion of errors was 3.3% in the history and EuroSCORE module, 1.0% in the procedure module and 2.8% in the discharge module. For PCI procedures, the errors were 3.8% in the history module, 2.2% in the procedure module and 1.6% in the discharge module. CAG and CT-CAG had slightly more errors. CONCLUSIONS: The quality control of the WDHR revealed that overall data errors were lower than 3% and for procedure-specific registrations including indications and complications, the error rate was below 1.5%. The WDHR is valid and may be used in contemporary epidemiological studies. FUNDING: none. TRIAL REGISTRATION: not relevant.