Determinants of Physical Activity among Patients with Colorectal Cancer: From Diagnosis to 5 Years after Diagnosis.

INTRODUCTION: Physical activity (PA) is associated with higher quality of life and probably better prognosis among colorectal cancer (CRC) patients. This study focuses on determinants of PA among CRC patients from diagnosis until 5 yr postdiagnosis. METHODS: Sociodemographic and disease-related factors of participants of two large CRC cohort studies were combined. Moderate-to-vigorous PA during sport and leisure time (MVPA-SL) was measured at diagnosis (T0) and 6, 12, 24, and 60 months (T6 to T60) postdiagnosis, using the SQUASH questionnaire. Mixed-effects models were performed to identify sociodemographic and disease-related determinants of MVPA-SL, separately for stage I-III colon (CC), stage I-III rectal cancer (RC), and stage IV CRC (T0 and T6 only). Associations were defined as consistently present when significant at ≥4 timepoints for the stage I-III subsets. MVPA-SL levels were compared with an age- and sex-matched sample of the general Dutch population. RESULTS: In total, 2905 CC, 1459 RC and 436 stage IV CRC patients were included. Patients with higher fatigue scores, and women compared with men had consistently lower MVPA-SL levels over time, regardless of tumor type and stage. At T6, having a stoma was significantly associated with lower MVPA-SL among stage I-III RC patients. Systemic therapy and radiotherapy were not significantly associated with MVPA-SL changes at T6. Compared with the general population, MVPA-SL levels of CRC patients were lower at all timepoints, most notably at T6. CONCLUSIONS: Female sex and higher fatigue scores were consistent determinants of lower MVPA-SL levels among all CRC patients, and MVPA-SL levels were lowest at 6 months postdiagnosis. Our results can inform the design of intervention studies aimed at improving PA, and guide healthcare professionals in optimizing individualized support.

Potential utility of B-type natriuretic peptides in secondary prevention following percutaneous coronary intervention in remote communities of Western Australia.

INTRODUCTION: A third of all acute coronary events that present in the Australian population occur in patients with established coronary heart disease. This study assessed the prognostic value of combined B-type natriuretic peptides (BNP) measurement and quantitative myocardial perfusion scan (MPS) data for cardiac events (CE). MATERIAL AND METHODS: This retrospective cohort study involved 133 patients from rural Western Australia. The cut-off for normality was 6.0 for qualitative summed difference scores (SDS) of MPS and 400 pg/mL for BNP. RESULTS: Patients with no CE had a mean SDS and BNP (1.52 with a 95% CI of 0.34 to 2.69), (175.9 with a 95% CI of 112.7-239.1) that was lower than patients with CE (6.54 with 95% CI 4.18-9.89) (P = 0.0003), (669.1 with 95% CI 543.9-794.3) (P < 0.0001). The sensitivity and specificity of combined testing for predicting CE respectively were 79.6% and 86.3% for SDS, 84.6% and 94.1% for BNP, and 100% and 92.7% for SDS and BNP combined. DISCUSSION AND CONCLUSION: Elevated BNP is marginally superior to MPS in predicting CEs in patients who have previously undergone percutaneous coronary intervention (PCI); however, MPS can identify the region of myocardium most at risk. Routine BNP monitoring in this subgroup may serve as secondary prevention by identifying subclinical disease.

Rural communities are disproportionately affected by preventable coronary heart disease-related deaths and access to cardiac imaging techniques can be infrequent or unavailable.Secondary prevention strategies can reduce hospital readmissions and contribute to improving the management of chronic conditions.This study demonstrated that elevated B-type natriuretic peptides levels were marginally superior to myocardial perfusion scans in predicting cardiac events in patients with prior percutaneous coronary intervention.Monitoring BNP levels in rural patients with prior percutaneous coronary interventions is a relatively non-invasive and inexpensive, and may lead to improved risk estimation, identify the subclinical disease and provoke further investigation as clinically appropriate.

Real-world palbociclib effectiveness in patients with metastatic breast cancer: Focus on neutropenia-related treatment modification strategies and clinical outcomes.

INTRODUCTION: In addition to clinical trials, real-world data is needed to verify the effectiveness of the CDK 4/6 inhibitor palbociclib. The primary aim was to examine real-world variation in treatment modification strategies for neutropenia and its relation to progression-free survival (PFS). The secondary aim was to assess if there is a gap between real-world and clinical trial outcomes. MATERIALS AND METHODS: In this multicenter, retrospective observational cohort study 229 patients were analyzed who started palbociclib and fulvestrant as second- or later-line therapy for HR-positive, HER2-negative metastatic breast cancer in the Santeon hospital group in the Netherlands between September 2016 and December 2019. Data were manually retrieved from patients' electronic medical records. PFS was examined using the Kaplan-Meier method to compare neutropenia-related treatment modification strategies within the first three months after neutropenia grade 3 - 4 occurred, as well as patients' eligibility to have participated in the PALOMA-3 clinical trial or not. RESULTS: Even though treatment modification strategies differed from those in PALOMA-3 (dose interruptions: 26 vs 54%, cycle delays: 54 vs 36%, and dose reductions: 39 vs 34%), these did not influence PFS. Patients who were PALOMA-3 ineligible experienced a shorter median PFS than those who were eligible (10.2 vs. 14.1 months; HR 1.52; 95% CI 1.12 - 2.07). An overall longer median PFS was found compared to PALOMA-3 (11.6 vs. 9.5 months; HR 0.70; 95% CI 0.54 - 0.90). CONCLUSION: This study suggests no impact of neutropenia-related treatment modifications on PFS and confirms inferior outcomes outside clinical trial eligibility.

A new prediction model for giant cell arteritis in patients with new onset headache and/or visual loss.

OBJECTIVE: The gold standard for diagnosis of giant cell arteritis (GCA) is a temporal artery biopsy (TAB). We sought for a clinical useful model to predict when an invasive TAB is not necessary to confirm GCA. METHODS: A prospective cohort study was conducted with patients > 50 years with possible GCA, presenting with newly onset headache and/or visual loss. Demographical, clinical, laboratory findings and histological data were collected. RESULTS: Fifty-six (70%) of the 94 patients showed 1 or more halos of the superficial temporal artery branches. Ultrasound-guided biopsy was positive in 28 patients (30%). Four independent variables predicted a positive TAB: weight loss, bilateral headache, positive halo sign and thrombocytosis. The ROC of the model had an area under the curve of 0.932 with a PPV of 83% and a NPV of 94%. CONCLUSIONS: Weight loss, bilateral headache, a positive halo sign with duplex and thrombocytosis are the most important clinical and laboratory predictors for GCA in a selected group of patients. SIGNIFICANCE: In patients > 50 years presenting with new onset headache or visual loss with 3 or more of the above mentioned risk factors, a biopsy of the temporal artery is not needed to confirm the diagnosis GCA.KEY MESSAGESIn our study biopsy of the temporal artery was positive in 30% of the patients with possible GCAWeight loss, bilateral headache, a positive halo sign on duplex and thrombocytosis are predictors for GCAThe halo sign had a high sensitivity but a low specificity for a biopsy proven GCA.

Physical Activity Is Associated with Improved Overall Survival among Patients with Metastatic Colorectal Cancer.

Regular physical activity (PA) is associated with improved overall survival (OS) in stage I-III colorectal cancer (CRC) patients. This association is less defined in patients with metastatic CRC (mCRC). We therefore conducted a study in mCRC patients participating in the Prospective Dutch Colorectal Cancer cohort. PA was assessed with the validated SQUASH questionnaire, filled-in within a maximum of 60 days after diagnosis of mCRC. PA was quantified by calculating Metabolic Equivalent Task (MET) hours per week. American College of Sports and Medicine (ACSM) PA guideline adherence, tertiles of moderate to vigorous PA (MVPA), and sport and leisure time MVPA (MVPA-SL) were assessed as well. Vital status was obtained from the municipal population registry. Cox proportional-hazards models were used to study the association between PA determinants and all-cause mortality adjusted for prognostic patient and treatment-related factors. In total, 293 mCRC patients (mean age 62.9 ± 10.6 years, 67% male) were included in the analysis. Compared to low levels, moderate and high levels of MET-hours were significantly associated with longer OS (fully adjusted hazard ratios: 0.491, (95% CI 0.299-0.807, p value = 0.005) and 0.485 (95% CI 0.303-0.778, p value = 0.003), respectively), as were high levels of MVPA (0.476 (95% CI 0.278-0.816, p value = 0.007)) and MVPA-SL (0.389 (95% CI 0.224-0.677, p value < 0.001)), and adherence to ACSM PA guidelines compared to non-adherence (0.629 (95% CI 0.412-0.961, p value = 0.032)). The present study provides evidence that higher PA levels at diagnosis of mCRC are associated with longer OS.

Cardiovascular malformations caused by NOTCH1 mutations do not keep left: data on 428 probands with left-sided CHD and their families.

PURPOSE: We aimed to determine the prevalence and phenotypic spectrum of NOTCH1 mutations in left-sided congenital heart disease (LS-CHD). LS-CHD includes aortic valve stenosis, a bicuspid aortic valve, coarctation of the aorta, and hypoplastic left heart syndrome. METHODS: NOTCH1 was screened for mutations in 428 nonsyndromic probands with LS-CHD, and family histories were obtained for all. When a mutation was detected, relatives were also tested. RESULTS: In 148/428 patients (35%), LS-CHD was familial. Fourteen mutations (3%; 5 RNA splicing mutations, 8 truncating mutations, 1 whole-gene deletion) were detected, 11 in familial disease (11/148 (7%)) and 3 in sporadic disease (3/280 (1%)). Forty-nine additional mutation carriers were identified among the 14 families, of whom 12 (25%) were asymptomatic. Most of these mutation carriers had LS-CHD, but 9 (18%) had right-sided congenital heart disease (RS-CHD) or conotruncal heart disease (CTD). Thoracic aortic aneurysms (TAAs) occurred in 6 mutation carriers (probands included 6/63 (10%)). CONCLUSION: Pathogenic mutations in NOTCH1 were identified in 7% of familial LS-CHD and in 1% of sporadic LS-CHD. The penetrance is high; a cardiovascular malformation was found in 75% of NOTCH1 mutation carriers. The phenotypic spectrum includes LS-CHD, RS-CHD, CTD, and TAA. Testing NOTCH1 for an early diagnosis in LS-CHD/RS-CHD/CTD/TAA is warranted.Genet Med 18 9, 914-923.

18-FDG PET/ CT Scan in the Diagnosis and Follow-up of Chronic Q fever Aortic Valve Endocarditis.

Chronic Q fever endocarditis is a rare but important infection associated with risk of morbidity and mortality. Echocardiography rarely visualises the vegetative lesion. We describe the first Australian report of chronic Q fever aortic valve endocarditis confirmed with the use of 18 -FDG PET/ CT scan. Following valvular replacement, the patient had ongoing high serological titres despite active treatment and he was managed with yearly serial PET/ CT scan to confirm the absence of active infection. The utility of serial PET /CT scan imaging as a follow-up management strategy has not been described in the literature previously and should be investigated further.

[Diarrhoea and malabsorption due to olmesartan use]. / Diarree en malabsorptie door gebruik van olmesartan.

BACKGROUND: The differential diagnosis of diarrhoea in combination with villous atrophy is broad. Coeliac disease heads the list but medication-induced villous atrophy should also be taken into consideration. CASE DESCRIPTION: We report the case of a 63-year-old man presenting with recurrent secretory diarrhoea, acute renal failure and metabolic acidosis. Initial work-up revealed total villous atrophy (Marsh stage IIIC) with intraepithelial lymphocytosis. A gluten-free diet did not have any effect on the diarrhoea. During several periods of hospitalization antihypertensive medications were temporarily stopped due to dehydration; this resulted in reduction of his symptoms. Eventually an association between the enteropathy and the antihypertensive olmesartan was suspected. Indeed, permanent withdrawal of olmesartan resulted in permanent clinical improvement. CONCLUSION: Olmesartan is frequently prescribed in the Netherlands and it should be included in the differential diagnosis of diarrhoea accompanying villous atrophy.

Referral patterns of patients presenting with chest pain at two rural emergency departments in Western Australia.

INTRODUCTION: Coronary heart disease is the largest single cause of death in Australia. In Western Australia invasive diagnostics and therapies for acute coronary syndromes are only provided in the metropolitan hospitals of Perth. Patients in rural hospitals who need invasive cardiac care have to be transferred to Perth. The aim of our research was to determine which patient factors are associated with referral to advanced cardiac care at metropolitan level and how this compares to Australian guidelines for the management of acute coronary syndromes. METHOD: Data was collected from patients presenting with chest pain to the rural emergency department, who were at least 18 years old and had given their consent. Exclusion criteria were chest pain accompanied or precipitated by significant co morbidity and prior enrolment in this study protocol. Socioeconomic and medical information of patients was collected from their medical records. Data was analysed using chi(2) tests, independent sample t-tests and multivariable logistic-regression models (stepwise backwards procedure). RESULTS: The study included 115 rural patients with chest pain with a mean age of 58 years: 66 (57%) men, 12 (10%) indigenous Australians and 38 (33%) transferred patients. Of all transferred patients 19 (50%) had a positive peak troponin-T, 13 (36%) a high peak creatine kinase (CK) and 12 (32%) persistent ST-elevation on their electrocardiogram, compared with 10 (14%), 12 (17%) and 11 (14%) respectively for non-transferred patients. Chi-square-tests showed significant differences between transfer groups in all three essential initial cardiac investigations and known dyslipidaemia. In multivariate analyses the positive peak troponin-T increased odds of transfer (OR6.40; 95% CI 2.55-16.08). This effect increased after adjustment for gender, serum creatinine and known dyslipidaemia (OR27.61; 95% CI 6.41-119.04). When adjusted for the peak troponin-T, neither ECG with persistent ST-elevation nor high peak CK remained significant. Known dyslipidaemia remained significant and serum creatinine became significant. Gender became significant when adjusted for troponin-T, known dyslipidaemia and serum creatinine. CONCLUSIONS: Peak troponin-T is an independent determinant associated with the transfer to advanced care at metropolitan level, but ECG with persistent ST-elevation and peak CK (other essential initial cardiac investigations) are not. Further investigation of the available and provided cardiac care in rural Western Australia is required.

A preliminary assessment of Internet-based nuclear telecardiology to support the clinical management of cardiac disease in a remote community.

A portable nuclear medicine (NM) processing system was established in Kalgoorlie and an acute myocardial perfusion scintigraphy (MPS) service was provided for the local regional hospital. After scanning the patient, the data were processed on a laptop computer and JPEG images were transmitted to a secure Web server. A secure email message, with the URL link enclosed and a provisional indication of normal or abnormal findings, was sent to the referring clinician from the NM facility. Use of the Internet allowed for a group consultation between the NM technician, the referrer and the cardiologist in Perth. During a three-month study period, 42 patients were referred for exclusion of acute coronary syndrome. Of these, 21 (50%) demonstrated abnormal perfusion studies, two of which were classified as requiring urgent medical intervention. Seventeen studies were normal (41%) and four (10%) were designated equivocal. There was an alteration in the treatment plan for 32 patients (76%), including four for whom admission or further investigation was deemed unwarranted. The results suggest that MPS findings, distributed via the Internet, allow for earlier risk stratification and have a direct affect on clinical decision making.