Structured alcohol cessation support program versus current practice in acute alcoholic pancreatitis (PANDA): Study protocol for a multicentre cluster randomised controlled trial.

BACKGROUND/OBJECTIVES: The most important risk factor for recurrent pancreatitis after an episode of acute alcoholic pancreatitis is continuation of alcohol use. Current guidelines do not recommend any specific treatment strategy regarding alcohol cessation. The PANDA trial investigates whether implementation of a structured alcohol cessation support program prevents pancreatitis recurrence after a first episode of acute alcoholic pancreatitis. METHODS: PANDA is a nationwide cluster randomised superiority trial. Participating hospitals are randomised for the investigational management, consisting of a structured alcohol cessation support program, or current practice. Patients with a first episode of acute pancreatitis caused by harmful drinking (AUDIT score >7 and < 16 for men and >6 and < 14 for women) will be included. The primary endpoint is recurrence of acute pancreatitis. Secondary endpoints include cessation or reduction of alcohol use, other alcohol-related diseases, mortality, quality of life, quality-adjusted life years (QALYs) and costs. The follow-up period comprises one year after inclusion. DISCUSSION: This is the first multicentre trial with a cluster randomised trial design to investigate whether a structured alcohol cessation support program reduces recurrent acute pancreatitis in patients after a first episode of acute alcoholic pancreatitis, as compared with current practice. TRIAL REGISTRATION: Netherlands Trial Registry (NL8852). Prospectively registered.

TARGET-HF: developing a model for detecting incident heart failure among symptomatic patients in general practice using routine health care data.

BACKGROUND: Timely diagnosis of heart failure (HF) is essential to optimize treatment opportunities that improve symptoms, quality of life, and survival. While most patients consult their general practitioner (GP) prior to HF, the early stages of HF may be difficult to identify. An integrated clinical support tool may aid in identifying patients at high risk of HF. We therefore constructed a prediction model using routine health care data. METHODS: Our study involved a dynamic cohort of patients (≥35 years) who consulted their GP with either dyspnoea and/or peripheral oedema within the Amsterdam metropolitan area from 2011 to 2020. The outcome of interest was incident HF, verified by an expert panel. We developed a regularized, cause-specific multivariable proportional hazards model (TARGET-HF). The model was evaluated with bootstrapping on an isolated validation set and compared to an existing model developed with hospital insurance data as well as patient age as a sole predictor. RESULTS: Data from 31,905 patients were included (40% male, median age 60 years) of whom 1,301 (4.1%) were diagnosed with HF over 124,676 person-years of follow-up. Data were allocated to a development (n = 25,524) and validation (n = 6,381) set. TARGET-HF attained a C-statistic of 0.853 (95% CI, 0.834 to 0.872) on the validation set, which proved to provide a better discrimination than C = 0.822 for age alone (95% CI, 0.801 to 0.842, P < 0.001) and C = 0.824 for the hospital-based model (95% CI, 0.802 to 0.843, P < 0.001). CONCLUSION: The TARGET-HF model illustrates that routine consultation codes can be used to build a performant model to identify patients at risk for HF at the time of GP consultation.

Use of the Smoking Cessation App Ex-Smokers iCoach and Associations With Smoking-Related Outcomes Over Time in a Large Sample of European Smokers: Retrospective Observational Study.

BACKGROUND: Digital interventions are increasingly used to support smoking cessation. Ex-smokers iCoach was a widely available app for smoking cessation used by 404,551 European smokers between June 15, 2011, and June 21, 2013. This provides a unique opportunity to investigate the uptake of a freely available digital smoking cessation intervention and its effects on smoking-related outcomes. OBJECTIVE: We aimed to investigate whether there were distinct trajectories of iCoach use, examine which baseline characteristics were associated with user groups (based on the intensity of use), and assess if and how these groups were associated with smoking-related outcomes. METHODS: Analyses were performed using data from iCoach users registered between June 15, 2011, and June 21, 2013. Smoking-related data were collected at baseline and every 3 months thereafter, with a maximum of 8 follow-ups. First, group-based modeling was applied to detect distinct trajectories of app use. This was performed in a subset of steady users who had completed at least 1 follow-up measurement. Second, ordinal logistic regression was used to assess the baseline characteristics that were associated with user group membership. Finally, generalized estimating equations were used to examine the association between the user groups and smoking status, quitting stage, and self-efficacy over time. RESULTS: Of the 311,567 iCoach users, a subset of 26,785 (8.6%) steady iCoach users were identified and categorized into 4 distinct user groups: low (n=17,422, 65.04%), mild (n=4088, 15.26%), moderate (n=4415, 16.48%), and intensive (n=860, 3.21%) users. Older users and users who found it important to quit smoking had higher odds of more intensive app use, whereas men, employed users, heavy smokers, and users with higher self-efficacy scores had lower odds of more intensive app use. User groups were significantly associated with subsequent smoking status, quitting stage, and self-efficacy over time. For all groups, over time, the probability of being a smoker decreased, whereas the probability of being in an improved quitting stage increased, as did the self-efficacy to quit smoking. For all outcomes, the greatest change was observed between baseline and the first follow-up at 3 months. In the intensive user group, the greatest change was seen between baseline and the 9-month follow-up, with the observed change declining gradually in moderate, mild, and low users. CONCLUSIONS: In the subset of steady iCoach users, more intensive app use was associated with higher smoking cessation rates, increased quitting stage, and higher self-efficacy to quit smoking over time. These users seemed to benefit most from the app in the first 3 months of use. Women and older users were more likely to use the app more intensively. Additionally, users who found quitting difficult used the iCoach app more intensively and grew more confident in their ability to quit over time.

Reasons for No Colonoscopy After an Unfavorable Screening Result in Dutch Colorectal Cancer Screening: A Nationwide Questionnaire.

PURPOSE: We aimed to assess participant-reported factors associated with non-follow-up with colonoscopy in colorectal cancer (CRC) screening. METHODS: In May 2019, we distributed a nationwide cross-sectional questionnaire (n = 4,009) to participants in the Dutch CRC screening program who received a positive fecal immunochemical test (FIT). Among respondents who reported no colonoscopy, we assessed the presence of a contraindication, and those without were compared with those who reported colonoscopy by logistic regression analysis. RESULTS: Of 2,225 respondents (56% response rate), 730 (33%) reported no colonoscopy. A contraindication was reported by 55% (n = 404). Decisional difficulties (odds ratio [OR] = 0.29; 95% CI, 0.18-0.47), lacking the opportunity to discuss the FIT outcome (OR = 0.45; 95% CI, 0.28-0.72), and a low estimated risk of CRC (OR = 0.45; 95% CI, 0.26-0.76) were negatively associated with follow-up. Knowledge items negatively associated with follow-up included having an alternative explanation for the positive FIT (OR = 0.3; 95% CI, 0.21-0.43), having trust in the ability to self-detect CRC (OR = 0.42; 95% CI, 0.27-0.65), and thinking that polyp removal is ineffective (OR = 0.59; 95% CI, 0.43-0.82). The belief that the family physician would support colonoscopy showed the strongest positive association with follow-up (OR = 2.84; 95% CI, 2.01-4.02) CONCLUSIONS: Because decisional difficulties and certain convictions regarding CRC and screening are associated with non-follow-up, personalized screening counseling might be an intervention worth exploring as a means of improving follow-up in the Dutch CRC screening program. Involving family physicians might also prove beneficial.

Addressing colon cancer patients' needs during follow-up consultations at the outpatient clinic: a multicenter qualitative observational study.

PURPOSE: To describe colon cancer patients' needs and how healthcare providers respond to these needs during routine follow-up consultations in hospital. METHODS: A multicenter qualitative observational study, consisting of follow-up consultations by surgeons and specialized oncology nurses. Consultations were analyzed according to Verona Coding Definitions of Emotional Sequences. Patients' questions, cues, and concerns were derived from the data and categorized into supportive care domains. Responses of healthcare providers were defined as providing or reducing space for disclosure. Patient satisfaction with care was measured with a short questionnaire. RESULTS: Consultations with 30 patients were observed. Questions typically centered around the health system and information domain (i.e., follow-up schedule and test results; 92%). Cues and concerns were mostly associated with the physical and daily living domain (i.e., experiencing symptoms and difficulties resuming daily routine; 43%), followed by health system and information (i.e., miscommunication or lack of clarity about follow-up; 28%), and psychological domain (i.e., fear of recurrence and complications; 28%). Problems in the sexuality domain hardly ever arose (0%). Healthcare providers provided space to talk about half of the cues and concerns (54%). Responses to cancer-related versus unrelated problems were similar. Overall, the patients were satisfied with the information and communication received. CONCLUSIONS: Colon cancer patients express various needs during consultations. Healthcare providers respond to different types of needs in a similar fashion. We encourage clinicians to discuss all supportive care domains, including sexuality, and provide space for further disclosure. General practitioners are trained to provide holistic care and could play a greater role.

Symptoms and seeking supportive care and associations with quality of life after treatment for colon cancer: Results from the I CARE cohort study.

OBJECTIVE: Patients treated for colon cancer report many symptoms that affect quality of life (QoL). Survivorship care aims at QoL improvement. In this study, we assess associations between symptoms and seeking supportive care and lower QoL and QoL changes overtime during survivorship care. METHODS: A prospective cohort of colon cancer survivors. Questionnaires are administered at inclusion and 6 months later to evaluate symptoms, functioning and seeking supportive care including associations with QoL, using the EORTC QLQ-C30. RESULTS: The mean QoL score at the first questionnaire was 82 (scale 1-100), which improved over time. Pain, bowel symptoms and problems in physical, role, cognitive or social functioning are associated with lower QoL at inclusion but are not associated with QoL changes over time. Seeking support for lower bowel symptoms, physical functioning or fatigue is associated with lower QoL. After 6 months, seeking support for upper bowel symptoms or physical functioning is associated with a tendency towards less QoL improvement. CONCLUSION: QoL of colon cancer survivors improves over 6 months, but seeking support for specific symptoms barely contribute to this improvement. IMPLICATIONS: This study confirms the importance of addressing symptoms, problems related to functioning and seeking supportive care during survivorship care.

Effect of general practitioner-led versus surgeon-led colon cancer survivorship care, with or without eHealth support, on quality of life (I CARE): an interim analysis of 1-year results of a randomised, controlled trial.

BACKGROUND: Colon cancer is associated with an increased risk of physical and psychosocial morbidity, even after treatment. General practitioner (GP) care could be beneficial to help to reduce this morbidity. We aimed to assess quality of life (QOL) in patients who received GP-led survivorship care after treatment for colon cancer compared with those who received surgeon-led care. Furthermore, the effect of an eHealth app (Oncokompas) on QOL was assessed in both patient groups. METHODS: We did a pragmatic two-by-two factorial, open-label, randomised, controlled trial at eight hospitals in the Netherlands. Eligible patients were receiving primary surgical treatment for stage I-III colon cancer or rectosigmoid carcinoma and qualified for routine follow-up according to Dutch national guidelines. Patients were randomly assigned (1:1:1:1)-via computer-generated variable block randomisation stratified by age and tumour stage-to survivorship care overseen by a surgeon, survivorship care overseen by a surgeon with access to Oncokompas, survivorship care overseen by a GP, or survivorship care overseen by a GP with access to Oncokompas. Blinding of the trial was not possible. The primary endpoint of the trial was QOL at 5 years, as measured by the change from baseline in the European Organistion for Research and Treatment of Cancer QLQ-C30 summary score. Here, we report an unplanned interim analysis of QOL at the 12-month follow-up. Grouped comparisons were done (ie, both GP-led care groups were compared with both surgeon-led groups, and both Oncokompas groups were compared with both no Oncokompas groups). Differences in change of QOL between trial groups were estimated with linear mixed-effects models. A change of ten units was considered clinically meaningful. Analysis was by intention to treat. This trial is registered with the Netherlands Trial Register, NTR4860. FINDINGS: Between March 26, 2015, and Nov 21, 2018, 353 patients were enrolled and randomly assigned. There were 50 early withdrawals (27 patient decisions and 23 GP withdrawals). Of the remaining 303 participants, 79 were assigned to surgeon-led care, 83 to surgeon-led care with Oncokompas, 73 to GP-led care, and 68 to GP-led care with Oncokompas. Median follow-up was 12·2 months (IQR 12·0-13·0) in all groups. At baseline, QOL was high in all trial groups. At 12 months, there was no clinically meaningful difference in change from baseline in QOL between the GP-led care groups and the surgeon-led care groups (difference in summary score -2·3 [95% CI -5·0 to 0·4]) or between the Oncokompas and no Oncokompas groups (-0·1 [-2·8 to 2·6]). INTERPRETATION: In terms of QOL, GP-led survivorship care can be considered as an alternative to surgeon-led care within the first year after colon cancer treatment. Other outcomes, including patient and physician preferences, will be important for decisions about the type of survivorship care. FUNDING: Dutch Cancer Society (KWF).

Evaluation of general practitioners' single-lead electrocardiogram interpretation skills: a case-vignette study.

BACKGROUND: Handheld single-lead electrocardiograms (1L-ECG) present a welcome addition to the diagnostic arsenal of general practitioners (GPs). However, little is known about GPs' 1L-ECG interpretation skills, and thus its reliability in real-world practice. OBJECTIVE: To determine the diagnostic accuracy of GPs in diagnosing atrial fibrillation or flutter (AF/Afl) based on 1L-ECGs, with and without the aid of automatic algorithm interpretation, as well as other relevant ECG abnormalities. METHODS: We invited 2239 Dutch GPs for an online case-vignette study. GPs were asked to interpret four 1L-ECGs, randomly drawn from a pool of 80 case-vignettes. These vignettes were obtained from a primary care study that used smartphone-operated 1L-ECG recordings using the AliveCor KardiaMobile. Interpretation of all 1L-ECGs by a panel of cardiologists was used as reference standard. RESULTS: A total of 457 (20.4%) GPs responded and interpreted a total of 1613 1L-ECGs. Sensitivity and specificity for AF/Afl (prevalence 13%) were 92.5% (95% CI: 82.5-97.0%) and 89.8% (95% CI: 85.5-92.9%), respectively. PPV and NPV for AF/Afl were 45.7% (95% CI: 22.4-70.9%) and 98.8% (95% CI: 97.1-99.5%), respectively. GP interpretation skills did not improve in case-vignettes where the outcome of automatic AF-detection algorithm was provided. In detecting any relevant ECG abnormality (prevalence 22%), sensitivity, specificity, PPV and NPV were 96.3% (95% CI: 92.8-98.2%), 68.8% (95% CI: 62.4-74.6%), 43.9% (95% CI: 27.7-61.5%) and 97.9% (95% CI: 94.9-99.1%), respectively. CONCLUSIONS: GPs can safely rule out cardiac arrhythmias with 1L-ECGs. However, whenever an abnormality is suspected, confirmation by an expert-reader is warranted.

Design of the PROstate cancer follow-up care in Secondary and Primary hEalth Care study (PROSPEC): a randomized controlled trial to evaluate the effectiveness of primary care-based follow-up of localized prostate cancer survivors.

BACKGROUND: In its 2006 report, From cancer patient to cancer survivor: lost in transition, the U.S. Institute of Medicine raised the need for a more coordinated and comprehensive care model for cancer survivors. Given the ever increasing number of cancer survivors, in general, and prostate cancer survivors, in particular, there is a need for a more sustainable model of follow-up care. Currently, patients who have completed primary treatment for localized prostate cancer are often included in a specialist-based follow-up care program. General practitioners already play a key role in providing continuous and comprehensive health care. Studies in breast and colorectal cancer suggest that general practitioners could also consider to provide survivorship care in prostate cancer. However, empirical data are needed to determine whether follow-up care of localized prostate cancer survivors by the general practitioner is a feasible alternative. METHODS: This multicenter, randomized, non-inferiority study will compare specialist-based (usual care) versus general practitioner-based (intervention) follow-up care of prostate cancer survivors who have completed primary treatment (prostatectomy or radiotherapy) for localized prostate cancer. Patients are being recruited from hospitals in the Netherlands, and randomly (1:1) allocated to specialist-based (N = 195) or general practitioner-based (N = 195) follow-up care. This trial will evaluate the effectiveness of primary care-based follow-up, in comparison to usual care, in terms of adherence to the prostate cancer surveillance guideline for the timing and frequency of prostate-specific antigen assessments, the time from a biochemical recurrence to retreatment decision-making, the management of treatment-related side effects, health-related quality of life, prostate cancer-related anxiety, continuity of care, and cost-effectiveness. The outcome measures will be assessed at randomization (≤6 months after treatment), and 12, 18, and 24 months after treatment. DISCUSSION: This multicenter, prospective, randomized study will provide empirical evidence regarding the (cost-) effectiveness of specialist-based follow-up care compared to general practitioner-based follow-up care for localized prostate cancer survivors. TRIAL REGISTRATION: Netherlands Trial Registry, Trial NL7068 (NTR7266). Prospectively registered on 11 June 2018.

Prognosis and Survival of Older Patients With Dizziness in Primary Care: A 10-Year Prospective Cohort Study.

PURPOSE: The prognosis of older patients with dizziness in primary care is unknown. Our objective was to determine the prognosis and survival of patients with different subtypes and causes of dizziness. METHODS: In a primary care prospective cohort study, 417 older adults with dizziness (mean age 79 years) received a full diagnostic workup in 2006-2008. A panel of physicians classified the subtype and primary cause of dizziness. Main outcome measures were mortality and dizziness-related impairment assessed at 10-year follow-up. RESULTS: At 10-year follow-up 169 patients (40.5%) had died. Presyncope was the most common dizziness subtype (69.1%), followed by vertigo (41.0%), disequilibrium (39.8%), and other dizziness (1.7%). The most common primary causes of dizziness were cardiovascular disease (56.8%) and peripheral vestibular disease (14.4%). Multivariable adjusted Cox models showed a lower mortality rate for patients with the subtype vertigo compared with other subtypes (hazard ratio [HR] = 0.62; 95% CI, 0.40-0.96), and for peripheral vestibular disease vs cardiovascular disease as primary cause of dizziness (HR = 0.46; 95% CI, 0.25-0.84). After 10 years, 47.7% of patients who filled out the follow-up measurement experienced substantial dizziness-related impairment. No significant difference in substantial impairment was seen between different subtypes and primary causes of dizziness. CONCLUSIONS: The 10-year mortality rate was lower for the dizziness subtype vertigo compared with other subtypes. Patients with dizziness primarily caused by peripheral vestibular disease had a lower mortality rate than patients with cardiovascular disease. Substantial dizziness-related impairment in older patients with dizziness 10 years later is high, and indicates that current treatment strategies by family physicians may be suboptimal.

Prediction models for atrial fibrillation applicable in the community: a systematic review and meta-analysis.

AIMS: Atrial fibrillation (AF) is a common arrhythmia associated with an increased stroke risk. The use of multivariable prediction models could result in more efficient primary AF screening by selecting at-risk individuals. We aimed to determine which model may be best suitable for increasing efficiency of future primary AF screening efforts. METHODS AND RESULTS: We performed a systematic review on multivariable models derived, validated, and/or augmented for AF prediction in community cohorts using Pubmed, Embase, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) through 1 August 2019. We performed meta-analysis of model discrimination with the summary C-statistic as the primary expression of associations using a random effects model. In case of high heterogeneity, we calculated a 95% prediction interval. We used the CHARMS (Critical Appraisal and Data Extraction for Systematic Reviews of Prediction Modelling Studies) checklist for risk of bias assessment. We included 27 studies with a total of 2 978 659 unique participants among 20 cohorts with mean age ranging from 42 to 76 years. We identified 21 risk models used for incident AF risk in community cohorts. Three models showed significant summary discrimination despite high heterogeneity: CHARGE-AF (Cohorts for Heart and Aging Research in Genomic Epidemiology) [summary C-statistic 0.71; 95% confidence interval (95% CI) 0.66-0.76], FHS-AF (Framingham Heart Study risk score for AF) (summary C-statistic 0.70; 95% CI 0.64-0.76), and CHA2DS2-VASc (summary C-statistic 0.69; 95% CI 0.64-0.74). Of these, CHARGE-AF and FHS-AF had originally been derived for AF incidence prediction. Only CHARGE-AF, which comprises easily obtainable measurements and medical history elements, showed significant summary discrimination among cohorts that had applied a uniform (5-year) risk prediction window. CONCLUSION: CHARGE-AF appeared most suitable for primary screening purposes in terms of performance and applicability in older community cohorts of predominantly European descent.

Diagnostic Accuracy of a Smartphone-Operated, Single-Lead Electrocardiography Device for Detection of Rhythm and Conduction Abnormalities in Primary Care.

PURPOSE: To validate a smartphone-operated, single-lead electrocardiography (1L-ECG) device (AliveCor KardiaMobile) with an integrated algorithm for atrial fibrillation (AF) against 12-lead ECG (12L-ECG) in a primary care population. METHODS: We recruited consecutive patients who underwent 12L-ECG for any nonacute indication. Patients held a smartphone with connected 1L-ECG while local personnel simultaneously performed 12L-ECG. All 1L-ECG recordings were assessed by blinded cardiologists as well as by the smartphone-integrated algorithm. The study cardiologists also assessed all 12L-recordings in random order as the reference standard. We determined the diagnostic accuracy of the 1L-ECG in detecting AF or atrial flutter (AFL) as well as any rhythm abnormality and any conduction abnormality with the simultaneously performed 12L-ECG as the reference standard. RESULTS: We included 214 patients from 10 Dutch general practices. Mean ± SD age was 64.1 ± 14.7 years, and 53.7% of the patients were male. The 12L-ECG diagnosed AF/AFL, any rhythm abnormality, and any conduction abnormality in 23, 44, and 28 patients, respectively. The 1L-ECG as assessed by cardiologists had a sensitivity and specificity for AF/AFL of 100% (95% CI, 85.2%-100%) and 100% (95% CI, 98.1%-100%). The AF detection algorithm had a sensitivity and specificity of 87.0% (95% CI, 66.4%-97.2%) and 97.9% (95% CI, 94.7%-99.4%). The 1L-ECG as assessed by cardiologists had a sensitivity and specificity for any rhythm abnormality of 90.9% (95% CI, 78.3%-97.5%) and 93.5% (95% CI, 88.7%-96.7%) and for any conduction abnormality of 46.4% (95% CI, 27.5%-66.1%) and 100% (95% CI, 98.0%-100%). CONCLUSIONS: In a primary care population, a smartphone-operated, 1L-ECG device showed excellent diagnostic accuracy for AF/AFL and good diagnostic accuracy for other rhythm abnormalities. The 1L-ECG device was less sensitive for conduction abnormalities.

Frequent premature atrial contractions are associated with atrial fibrillation, brain ischaemia, and mortality: a systematic review and meta-analysis.

AIMS: Premature atrial contractions (PACs) are a common cardiac phenomenon, traditionally considered to be of little clinical significance. Recent studies, however, suggest that PACs are associated with atrial fibrillation (AF), as well as ischaemic stroke, transient ischaemic attack, and mortality. This systematic review aims to investigate the association between PACs on standard electrocardiogram (ECG) as well as PAC-count on Holter monitor and future detection of AF, brain ischaemia, and all-cause mortality in patients without a history of AF. METHODS AND RESULTS: We searched PubMed, Embase (OVID), and Cochrane Database of Systematic Reviews from inception through 11 April 2018 and performed a systematic review and meta-analysis. We assessed risk of bias using a modified Quality In Prognosis Studies tool. The primary expression of associations in meta-analysis was the unadjusted hazard ratio (HR) using a random effects model. We identified 33 eligible studies including 198 876 patients from Western and East Asian populations with mean age ranging 52-76 years. Frequent PACs on 24-48 h Holter was associated with AF [HR 2.96, 95% confidence interval (CI) 2.33-3.76; 15 cohorts, n = 16 613], first stroke (HR 2.54, 95% CI 1.68-3.83; 3 cohorts, n = 1468), and all-cause mortality (HR 2.14, 95% CI 1.94-2.37; 6 cohorts, n = 7571). There was insufficient evidence to conclude that presence of ≥1 PAC on standard 12-lead ECG is associated with future AF detection. CONCLUSION: In older patients without a history of AF, frequent PACs on 24-48 h Holter are significantly associated with AF, first stroke, and mortality.

Impact of Polypharmacy and P-Glycoprotein- and CYP3A4-Modulating Drugs on Safety and Efficacy of Oral Anticoagulation Therapy in Patients with Atrial Fibrillation.

PURPOSE: To study whether polypharmacy or drug-drug interactions have differential effect on safety and efficacy in patients treated with direct oral anticoagulants (DOACs) versus warfarin. METHODS: We performed a systematic review and meta-analysis of studies that randomized patients with atrial fibrillation to DOACs or warfarin stratified by the number of concomitant drugs. Outcomes included stroke or systemic embolism (SE), all-cause mortality, major bleeding, and intracranial hemorrhage. Risk ratios (RR) were calculated and Mantel-Haenszel random effects were applied. RESULTS: Two high-quality studies were eligible, including 32,465 participants who received apixaban, rivaroxaban, or warfarin, with a median follow-up of 1.9 years. Of participants, 29% used < 5 drugs, 55% used 5-9 drugs, and 16% used ≥ 10 drugs. Drugs interacting with DOACs (P-glycoprotein/CYP3A4) were used by 6460 (20%) of patients. Patients with higher number of drugs (0-4 vs 5-9 vs ≥ 10) had higher rates of mortality (5.8%, 7.9%, 10.0%) and major bleeding (3.4%, 4.8%, 7.7%). Comparative efficacy or safety of DOACs versus warfarin was not affected by polypharmacy status or P-glycoprotein/CYP3A4 inhibitor use. However, the presence of polypharmacy (p = 0.001) or glycoprotein/CYP3A4-modulating drugs (p = 0.03) was correlated with increased risk of major bleeding when compared with warfarin. Overall, DOAC use was associated with a lower risk of stroke/SE (RR, 0.84; 95%CI, 0.74-0.94), all-cause mortality (RR, 0.91; 95%CI, 0.84-0.98), and intracranial hemorrhage (RR, 0.51; 95%CI, 0.38-0.70) compared with warfarin. CONCLUSIONS: DOACs were more effective than warfarin, and at least as safe. Polypharmacy was associated with adverse outcomes and attenuated the advantage in risk of major bleeding among rivaroxaban users, particularly in the presence of P-glycoprotein/CYP3A4-modulating drugs.

General practitioners' involvement during survivorship care of colon cancer in the Netherlands: primary health care utilization during survivorship care of colon cancer, a prospective multicentre cohort study.

BACKGROUND: Primary health care use increases when cancer is diagnosed. This increase continues after cancer treatment. More generalist care is suggested to improve survivorship care. It is unknown to what extent cancer-related symptoms are currently presented in primary care in this survivorship phase. OBJECTIVE: To analyse primary health care utilization of colon cancer patients during and after treatment with curative intent. METHODS: In a prospective multicentre cohort study among patients with curatively treated colon cancer, we describe the primary health care utilization during the first 5 years of follow-up. Data were collected at general practitioner (GP) practices during 6 months. RESULTS: Of 183 included participants, 153 (84%) consulted their GP resulting in 606 contacts (mean 3.3, standard deviation 3.01) with on average 0.9 contact for colon-cancer-related (CCR) problems in the 6-month study period. Median time after surgery at inclusion was 7.6 months (range 0-58). Abdominal pain and chemotherapy-related problems were the most frequently reported CCR reasons. Of the CCR contacts, 83% was managed in primary care. As time after surgery passed, the number of CCR contacts declined in patients without chemotherapy and remained constant in patients who received chemotherapy. CONCLUSION: Colon cancer survivors contact their GP frequently also for reasons related to cancer. Currently, a formal role for GPs in survivorship care is lacking, but nevertheless GPs provide a substantial amount of care. Working agreements between primary and secondary care are necessary to formalize the GP's role in order to improve the quality of survivorship care.

Predicting an Unfavorable Course of Dizziness in Older Patients.

PURPOSE: Because dizziness in older people is often chronic and can substantially affect daily functioning, it is important to identify those at risk for an unfavorable course of dizziness to optimize their care. We aimed to develop and externally validate a prediction model for an unfavorable course of dizziness in older patients in primary care, and to construct an easy-to-use risk prediction tool. METHODS: We used data from 2 prospective cohorts: a development cohort with 203 patients aged 65 years or older who consulted their primary care physician for dizziness and had substantial dizziness-related impairment (Dizziness Handicap Inventory [DHI] ≥30), and a validation cohort with 415 patients aged 65 years or older who consulted their primary care physician for dizziness of any severity. An unfavorable course was defined as presence of substantial dizziness-related impairment (DHI ≥30) after 6 months. RESULTS: Prevalence of an unfavorable course of dizziness was 73.9% in the development cohort and 43.6% in the validation cohort. Predictors in the final model were the score on the screening version of the DHI, age, history of arrhythmia, and looking up as a provoking factor. The model showed good calibration and fair discrimination (area under the curve = 0.77). On external validation, discriminative ability remained stable (area under the curve = 0.78). The constructed risk score was strongly correlated with the prediction model. Performance measures for risk score cut-off values are presented to determine the optimal cut-off point for clinical practice. CONCLUSIONS: We developed an easy-to-use risk score for dizziness-related impairment in primary care. The risk score, consisting of only 4 predictors, will help primary care physicians identify patients at high risk for an unfavorable course of dizziness.

Burden of atrial high-rate episodes and risk of stroke: a systematic review.

Aims: Atrial fibrillation (AF) patients have increased risk of stroke. In paroxysmal AF, the combination of duration and frequency of episodes defines AF burden. In patients with cardiac implantable electronic devices (CIEDs), atrial high-rate episodes (AHREs) can be monitored continuously and are considered as a proxy for AF. This systematic review aims to determine the relationship between AF burden and risk of thrombo-embolic events (TBEs). Methods and results: We searched Medline, Embase, PubMed, and Cochrane Library databases and performed a review and meta-analysis. Eligible studies reported rhythm registration with specified AF burden and 3 months of follow-up for TBEs. Of the 8849 identified publications, 7 met the inclusion criteria. Of the 18 943 included patients, 215 (1.1%) patients developed a TBE. We detected only studies registering AHRE with a duration over 5 min detected by CIED. In a meta-analysis, patients with an AHRE burden over 6 min had an increased risk of TBE when compared with patients without AHRE, but this risk did not increase for an AHRE burden over 6 h [hazard ratio (HR) 1.82 vs. 1.78]. In a second meta-analysis, only patients with AHRE burden over 24 h had an increased risk for stroke (HR 3.2, 95% confidence interval 1.75-5.86), while patients with an AHRE burden shorter than 24 h did not. Conclusion: Patients with an AHRE burden over 6 min have an increased risk for stroke. A trend in which a higher AHRE burden leads to a higher risk for TBEs was observed but not substantiated due to heterogeneity and low numbers.

Clinical Pattern of Recurrent Disease during the Follow-Up of Rectal Carcinoma.

BACKGROUND/AIMS: Several initiatives have started to transfer colorectal cancer follow-up (FU) from secondary to primary care. For this purpose, it is important to assess when and how recurrences of rectal carcinoma are detected after treatment with curative intent. METHODS: Retrospective multicentre cohort study. Patients participating in an FU programme after curative intended treatment for rectal cancer stages I-III between 2007 and 2014. RESULTS: Of the 378 patients, 64 (17%) developed recurrent disease (RD). Most were detected during scheduled FU consultations (n = 55) by (a combination of) radiological examinations and carcinoembryonic antigen levels, and were asymptomatic (n = 53); outside scheduled FU consultations, RD was detected during the treatment of postoperative complications or ostomy reversal (n = 5), or due to symptoms (n = 4). Most frequent sites of recurrence were liver (50%), lung (44%), multiple (22%) or locoregional (16%). Treatment of RD with curative intent was performed more frequently when detected during scheduled FU (60 vs. 22%). The only predictive factor for developing RD was stage III disease on initial presentation. CONCLUSIONS: The majority of rectal cancer patients are diagnosed with RD at an asymptomatic stage during scheduled FU consultations. Only a few patients presented with RD outside the FU programme. Arguably, general practitioners could order these same diagnostic tests during FU.

Who should provide care for patients receiving palliative chemotherapy? A qualitative study among Dutch general practitioners and oncologists.

INTRODUCTION: While close collaboration between general practitioners (GPs) and hospital specialists is considered important, the sharing of care responsibilities between GPs and oncologists during palliative chemotherapy has not been clearly defined. OBJECTIVE: Evaluate the opinions of GPs and oncologists about who should provide different aspects of care for patients receiving palliative chemotherapy. DESIGN: We conducted semi-structured interviews using six hypothetical scenarios with purposively sampled GPs (n = 12) and oncologists (n = 10) in the Netherlands. Each represented an example of a clinical problem requiring different aspects of care: problems likely, or not, related to cancer or chemotherapy, need for decision support, and end-of-life care. RESULTS: GPs and oncologists agreed that GPs should provide end-of-life care and that they should be involved in decisions about palliative chemotherapy; however, for the other scenarios most participants considered themselves the most appropriate provider of care. Themes that emerged regarding who would provide the best care for the patients in the different scenarios were expertise, continuity of care, accessibility of care, doctor-patient relationship, and communication. Most participants mentioned improved communication between the GP and oncologist as being essential for a better coordination and quality of care. CONCLUSION: GPs and oncologists have different opinions about who should ideally provide different aspects of care during palliative chemotherapy. Findings raise awareness of the differences in reasoning and approaches and in current communication deficits between the two groups of health professionals. These findings could be used to improve coordination and collaboration and, ultimately, better patient care as results demonstrated that both disciplines can add value to the care for patients with advanced cancer. Key points This study identified contrasting opinions of GPs and oncologists about who should provide different aspects of care for patients receiving palliative chemotherapy. Important themes that emerged were expertise, continuity of care, doctor-patient relations, accessibility of care, and communication. Although frequently using the same arguments, GPs and oncologists often considered themselves to be the most appropriate providers of palliative care.

Selective Cutoff Reporting in Studies of Diagnostic Test Accuracy: A Comparison of Conventional and Individual-Patient-Data Meta-Analyses of the Patient Health Questionnaire-9 Depression Screening Tool.

In studies of diagnostic test accuracy, authors sometimes report results only for a range of cutoff points around data-driven "optimal" cutoffs. We assessed selective cutoff reporting in studies of the diagnostic accuracy of the Patient Health Questionnaire-9 (PHQ-9) depression screening tool. We compared conventional meta-analysis of published results only with individual-patient-data meta-analysis of results derived from all cutoff points, using data from 13 of 16 studies published during 2004-2009 that were included in a published conventional meta-analysis. For the "standard" PHQ-9 cutoff of 10, accuracy results had been published by 11 of the studies. For all other relevant cutoffs, 3-6 studies published accuracy results. For all cutoffs examined, specificity estimates in conventional and individual-patient-data meta-analyses were within 1% of each other. Sensitivity estimates were similar for the cutoff of 10 but differed by 5%-15% for other cutoffs. In samples where the PHQ-9 was poorly sensitive at the standard cutoff, authors tended to report results for lower cutoffs that yielded optimal results. When the PHQ-9 was highly sensitive, authors more often reported results for higher cutoffs. Consequently, in the conventional meta-analysis, sensitivity increased as cutoff severity increased across part of the cutoff range-an impossibility if all data are analyzed. In sum, selective reporting by primary study authors of only results from cutoffs that perform well in their study can bias accuracy estimates in meta-analyses of published results.