Single and combined impacts of irradiation and surgery on lymphatic vasculature and fibrosis associated to secondary lymphedema.

Lymphedema (LD) refers to a condition of lymphatic dysfunction associated with excessive fluid accumulation, fibroadipose tissue deposition and swelling. In industrialized countries, LD development mainly results from a local disruption of the lymphatic network by an infection or cancer-related surgery (secondary LD). In the absence of efficient therapy, animal models are needed to decipher the cellular and molecular mechanisms underlying LD and test putative drugs. In this study, we optimized and characterized a murine model of LD that combines an irradiation of the mice hind limb and a radical surgery (lymph node resection associated to lymphatic vessel ligation). We investigated the respective roles of irradiation and surgery in LD formation by comparing their impacts, alone or in combination (with different intervention sequences), on eight different features of the pathology: swelling (paw thickness), indocyanine green (ICG) clearance, lymphatic vasculature remodeling, epidermal and dermal thickening, adipocyte accumulation, inflammatory cell infiltration and collagen deposition. This study supports the importance of radiation prior to surgery to experimentally induce a rapid, severe and sustained tissue remodeling harboring the different hallmarks of LD. We provide the first experimental evidence for an excessive deposition of periostin (POSTN) and tenascin-C (TNC) in LD. Through a computerized method of digital image quantification, we established the spatial map of lymphatic expansion, as well as collagen, POSTN and TNC deposition in papillary and reticular dermis of lymphedematous skins. This mouse model is available to study the patho-physiology of LD and test potential therapeutic targets.

Geographical variation of COVID-19 vaccination coverage, ethnic diversity and population composition in Flanders.

The vaccination coverage in Flanders is high, but some regions show lower vaccination willingness as compared to the overall vaccination coverage. Beginning November of 2021, the vaccination rate in Flanders was above 93% in age groups above 45 years, and around 85% in the age groups 12 to 44 years. Apart from Flanders as a whole, focus here is on the health sector Maasland, which has a slightly lower vaccination rate, especially in the age groups 12 to 44 years. In the Maasland region, located on the eastern border of Flanders, there are between 1% and 10% less vaccinated individuals than expected according to the vaccination rate in the whole of Flanders, with lowest vaccination rates in the south of the Maasland region. We study the impact of ethnic diversity in the population, population composition with respect to the ethnicity of individuals (in the sense of how the local population composition differs from the Flemish average), and socio-economic status on the vaccination rate at the level of the statistical sector, apart from the effect of age. We explain the statistical methods to investigate geographical differences and illustrate how one can deal with incomplete information in vaccination registries. Ethnic diversity in a region is associated with lower vaccination rates, as is a lower regional socio-economic status. The composition of the population in Maasland is associated with a 35% reduction in the odds to get vaccinated as compared to the overall Flemish population.

Uptake of hepatitis C virus screening and treatment in persons under opioid substitution therapy between 2008 and 2013 in Belgium.

BACKGROUND: Hepatitis C is a viral infection caused by the hepatitis C virus (HCV) with people who inject drugs as the main group at risk worldwide. AIM: This study investigated the differences in uptake for HCV screening and treatment between persons in opioid substitution therapy (OST) and the other members of the Christian Health Insurance Fund in Belgium. METHODS: Invoice data were retrospectively collected from the Christian Health Insurance Fund, representing 42% of the healthcare users. Information on demographics, screening, diagnostic tests, treatment and disease progression was obtained from 2008 till 2013. All people in this study were aged 20-65 year. Persons in the OST group were identified as having at least one prescription reimbursed for methadone. This group was compared to the other members of the Insurance Fund not on OST (NOST). RESULTS: The Insurance Fund registered 8,409 unique OST and 3,525,190 members in the general group. HCV RNA screening rate was higher in the OST group after correction for age and gender (4.3% vs. 0.2%). Ribavirin reimbursement, did not differ between the OST and NOST group screened for HCV RNA (16.9% vs. 14.4%), though the probability of having ribavirin reimbursed was smaller for females than for males. Procedures concerning disease progression were reimbursed less frequently in the HCV RNA screened OST group compared to the NOST group (0.3% vs. 1.2%). CONCLUSION: People on OST were screened more often for HCV RNA. However, the general uptake for HCV screening and treatment in both populations remained suboptimal.

Occurrence of Malnutrition and Associated Factors in Community-Dwelling Older Adults: Those with a Recent Diagnosis of Cancer Are at Higher Risk.

OBJECTIVES: In older adults, nutritional health is essential for good quality of life and living independently at home. Especially in cancer patients, malnutrition is common and known to complicate treatment. This study aims to evaluate the nutritional status and its associated factors in community-dwelling older adults with and without cancer. DESIGN: This is an observational study. SETTING: This study focuses on older community-dwelling people. PARTICIPANTS: This study included older people with and without cancer (≥70 years). Cancer patients included patients with a new diagnosis of breast, lung, prostate, or colorectal cancer. MEASUREMENTS: Data collection included measures of nutritional status, quality of life, depression, fatigue, distress and functional status. We used multivariate logistic regression analysis to assess the association between personal characteristics and malnutrition. RESULTS: Data were available for 657 people; 383 people without cancer and 274 with a cancer diagnosis. Overall, malnutrition was detected in 245 (37.5%) people; in cancer patients this was 66.1%. Multivariate analysis showed that having cancer (OR 14.4, 95% CI: 8.01 - 23.3), being male (OR 2.38, 95% CI: 1.49 - 3.70), having depression (OR 13.5, 95% CI: 6.02-30.0), distress (OR 2.60, 95% CI: 1.55 - 4.37) and impaired instrumental activities of daily living (IADL) (OR 2.63, 95% CI: 1.63 - 4.24) were associated with a higher risk of malnutrition. CONCLUSION: The prevalence of malnutrition in community-dwelling older people is high, particularly in patients with cancer. Benchmarking and routine screening of older patients may be helpful strategies to increase awareness of (risk of) malnutrition among professionals.

Association between self-perception of aging, view of cancer and health of older patients in oncology: a one-year longitudinal study.

BACKGROUND: Identifying older people affected by cancer who are more at risk of negative health outcomes is a major issue in health initiatives focusing on medical effectiveness. In this regard, psychological risk factors such as patients' perception of their own aging and cancer could be used as indicators to improve customization of cancer care. We hypothesize that more negative self-perception of aging (SPA) and view of cancer could be linked to worse physical and mental health outcomes in cancer patients. METHODS: One hundred one patients diagnosed with cancer (breast, gynecological, lung or hematological) were followed for 1 year. They were evaluated on four occasions (baseline, 3, 6 and 12 months after the baseline). Their SPA, view of cancer and health (physical and mental) were assessed at each time of evaluation. RESULTS: Negative SPA and/or view of cancer at baseline are associated with negative evolution of patients' physical and mental health. Moreover, when the evolution of SPA and cancer view were taken into account, these two stigmas are still linked with the evolution of mental health. In comparison, only a negative evolution of SPA was linked to worse physical health outcomes. CONCLUSIONS: Such results indicate that SPA and view of cancer could be used as markers of vulnerability in older people with cancer.

Belgian experience with triple therapy with boceprevir and telaprevir in genotype 1 infected patients who inject drugs.

No data have been reported yet on treatment outcome in persons who inject drugs (PWID) infected with hepatitis C virus treated with boceprevir or telaprevir in combination with peginterferon (Peg IFN) and ribavirin (RBV). Additionally, there are concerns about the safety of boceprevir and telaprevir in some subgroups of patients with hepatitis C (HCV). In a cohort of HCV patients infected with genotype 1 in Belgium, treatment outcome of patients infected due to IV drug use was analyzed and compared with patients who have no history of substance use. The study population consisted of 179 patients: 78 PWID and 101 controls treated with boceprevir (n = 79) or telaprevir (n = 100) additional to Peg IFN and RBV; 53 (30%) had advanced disease (F3, F4) and 79 (44%) had an antiviral therapy previously. There were no significant differences in the baseline characteristics between both groups, except that PWID patients were more frequently infected with genotype 1a (67% vs 21%), were younger and were predominantly male. Psychiatric complaints during follow-up occurred more frequently in the PWID patients: 24% versus 11% (P = .02). Treatment failure for other reasons than absence of viral response was 70% and 64% in PWID and non-PWID respectively. The sustained viral response (SVR) rates were similar in both groups (71% in PWID vs 72% in non-PWID); with a non-inferiority test with -5% margin there is a difference of -1% (95% CI [-15%, 13%]) and P = 0.30. There are no reasons to exclude PWID from treatment with boceprevir, telaprevir and novel antiviral therapies.

Association between recent herpes zoster but not herpes simplex infection and subsequent risk of malignancy in women: a retrospective cohort study.

The association between herpes zoster and subsequent cancer risk is still unclear. Consequently, doubts remain regarding the need for investigation of herpes patients for co-existing or subsequent malignancy. This is a retrospective cohort study comparing cancer risk in patients after herpes zoster and age-/sex-matched non-herpes zoster patients, in a primary care-based continuous morbidity database. We tested for interaction by gender, age, diabetes, HRT use or antiviral therapy. Analyses were repeated for patients with and without herpes simplex. The hazard ratio (HR) comparing cancer risk in herpes zoster vs. control patients was significant in all women, women aged > 65 years and subgroups of breast and colorectal cancer (HRs 1·60, 1·82, 2·14, 2·19, respectively). For men, a significant association was found for haematological cancers (HR 2·92). No associations were found with herpes simplex. No interaction was identified with antiviral therapy, diabetes or HRT treatment. We concluded that there was a moderate significant association between herpes zoster and subsequent cancer risk in women aged > 65 years, without any influence of antiviral therapy. No association was found with herpes simplex. There is insufficient reason for extensively testing older patients with herpes zoster or herpes simplex for the presence of occult cancer.

Systematic review and validation of prediction rules for identifying children with serious infections in emergency departments and urgent-access primary care.

BACKGROUND: Although the vast majority of children with acute infections are managed at home, this is one of the most common problems encountered in children attending emergency departments (EDs) and primary care. Distinguishing children with serious infection from those with minor or self-limiting infection is difficult. This can result in misdiagnosis of children with serious infections, which results in a poorer health outcome, or a tendency to refer or admit children as a precaution; thus, inappropriately utilising secondary-care resources. OBJECTIVES: We systematically identified clinical features and laboratory tests which identify serious infection in children attending the ED and primary care. We also identified clinical prediction rules and validated those using existing data sets. DATA SOURCES: We searched MEDLINE, Medion, EMBASE, Cumulative Index to Nursing and Allied Health Literature and Database of Abstracts of Reviews of Effects in October 2008, with an update in June 2009, using search terms that included terms related to five components: serious infections, children, clinical history and examination, laboratory tests and ambulatory care settings. We also searched references of included studies, clinical content experts, and relevant National Institute for Health and Clinical Excellence guidelines to identify relevant studies. There were no language restrictions. Studies were eligible for inclusion if they were based in ambulatory settings in economically developed countries. REVIEW METHODS: Literature searching, selection and data extraction were carried out by two reviewers. We assessed quality using the quality assessment of diagnostic accuracy studies (QUADAS) instrument, and used spectrum bias and validity of the reference standard as exclusion criteria. We calculated the positive likelihood ratio (LR+) and negative likelihood ratio (LR-) of each feature along with the pre- and post-test probabilities of the outcome. Meta-analysis was performed using the bivariate method when appropriate. We externally validated clinical prediction rules identified from the systematic review using existing data from children attending ED or primary care. RESULTS: We identified 1939 articles, of which 35 were selected for inclusion in the review. There was only a single study from primary care; all others were performed in the ED. The quality of the included studies was modest. We also identified seven data sets (11,045 children) to use for external validation. The most useful clinical features for ruling in serious infection was parental or clinician overall concern that the illness was different from previous illnesses or that something was wrong. In low- or intermediate-prevalence settings, the presence of fever had some diagnostic value. Additional red flag features included cyanosis, poor peripheral circulation, rapid breathing, crackles on auscultation, diminished breath sounds, meningeal irritation, petechial rash, decreased consciousness and seizures. Procalcitonin (LR+ 1.75-2.96, LR- 0.08-0.35) and C-reactive protein (LR+ 2.53-3.79, LR- 0.25-0.61) were superior to white cell counts. The best performing clinical prediction rule was a five-stage decision tree rule, consisting of the physician's gut feeling, dyspnoea, temperature ≥ 40 °C, diarrhoea and age. It was able to decrease the likelihood of serious infections substantially, but on validation it provided good ruling out value only in low-to-intermediate-prevalence settings (LR- 0.11-0.28). We also identified and validated the Yale Observation Scale and prediction rules for pneumonia, meningitis and gastroenteritis. LIMITATIONS: Only a single study was identified from primary-care settings, therefore results may lack generalisability. CONCLUSIONS: Several clinical features are useful to increase or decrease the probability that a child has a serious infection. None is sufficient on its own to substantially raise or lower the risk of serious infection. Some are highly specific ('red flags'), so when present should prompt a more thorough or repeated assessment. C-reactive protein and procalcitonin demonstrate similar diagnostic characteristics and are both superior to white cell counts. However, even in children with a serious infection, red flags will occur infrequently, and their absence does not lower the risk. The diagnostic gap is currently filled by using clinical 'gut feeling' and diagnostic safety-netting, which are still not well defined. Although two prediction rules for serious infection and one for meningitis provided some diagnostic value, we do not recommend widespread implementation at this time. Future research is needed to identify predictors of serious infection in children in primary-care settings, to validate prediction rules more widely, and determine the added value of blood tests in primary-care settings. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Validation of the IMMIDIET food frequency questionnaire in an adult Belgian population: a report from the Belgian case-control study on bladder cancer risk.

We evaluated the performance of the IMMIDIET food frequency questionnaire (FFQ) used to collect dietary data for the Belgian case-control study on bladder cancer. Thirty-seven men and women aged 50 years and older were recruited from the University Hospital in Leuven, Belgium. Participants completed the IMMIDIET FFQ, a 7-day diet diary and a 24-hour diet recall. Median intakes and inter-quartile ranges were calculated for 27 foods and nutrients from each dietary assessment method. All dietary factors were log-transformed and adjusted for energy using the nutrient density method. Pearson correlation coefficients were used to compare the different dietary assessment methods. Bland-Altman plots were also used to assess levels of agreement between the dietary methods. Energy, fruit and vegetable intake estimates were higher from the IMMIDIET FFQ compared with the two reference methods.The highest deattenuated correlations between the FFQ and 7-day diary were meat (0.58), bread (0.44), fruit (0.38) and fish (0.38). The highest deattenuated correlations between the FFQ and 24-hour recall were for fruit (0.72), fat (0.48), alcohol (0.44), cholesterol (0.42), monounsaturated fatty acid (0.42) and polyunsaturated fatty acid (0.41). Generally, correlation was lower for the micro-nutrients except for phosphorus (0.42), vitamin C (0.41) and calcium (0.40). The IMMIDIET FFQ is an appropriate instrument to measure usual dietary intake for the Belgian case-control study on bladder cancer risk. Further investigation of nutritional assessment methods is necessary.

Mortality of young patients with diabetes in Kinshasa, DR Congo.

AIMS: As data on mortality of young patients with diabetes is not available in the Democratic Republic of Congo (DRC), we studied mortality rates, the influence of some determinants and causes of death. METHODS: A retrospective review of standardized medical records of all patients with diabetes aged

Previous intravenous substance use and outcome of liver transplantation in patients with chronic hepatitis C infection.

BACKGROUND: End-stage liver disease due to hepatitis C viral (HCV) infection is the most common reason for liver transplantation. One of the major risk factors for infection with HCV is intravenous drug use (IVDU). The pretransplantation characteristics and outcome of liver transplantation in patients with chronic hepatitis C (CHC) infected after IVDU are poorly known. METHODS: We performed a retrospective cohort study in patients with CHC who underwent liver transplantation between 1998 and 2002 in Belgium. Seven patients with and 60 patients without a history of IVDU were compared. RESULTS: Patients with CHC infected after IVDU were primarily men, significantly younger, and affected more by genotype 2 or 3. There was no relapse in substance use. No patients required a second transplantation or developed surgical complications. Progression to fibrosis in the posttransplantation period seemed to be slower. Graft and patient survival, and compliance were similar in both groups. CONCLUSIONS: Compared with patients in the non-IVDU group, patients with CHC infected after IVDU in complete remission have the same compliance, and patient and graft survival after liver transplantation. Therefore, patients with IVDU should not be excluded for liver transplantation because of HCV-induced cirrhosis.

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Randomised controled trials (RCT's) and meta analyses of RCT's are known as the best research designs to evaluate if interventions are doing more good than bad. Some interventions can not be evaluated by RCT's because of the heterogeneity of the problems, the cost of the evaluation study or ethical arguments against the study. This is often the case with population based interventions. A typical example is suicide prevention. The shortcomings of the "classic" research designs for the evaluation of suicide prevention are discussed and feasible solutions are suggested for future research.

Interval cancers in the beginning years of the breast cancer screening programme in the Belgian province of Limburg.

OBJECTIVE: To assess the occurrence of interval breast cancers among those women who attended the mammography screening programme in the Belgian province of Limburg. Interval cancers are tumours that are being diagnosed before the next scheduled screening round and are related to the sensitivity and the screening interval. METHODS: Biennial screening is provided to all women aged 50-69. The records of the screening programme were linked to those of the cancer registry. The interval cancer rate, expressed as a proportion of the underlying (expected) breast cancer incidence rate was calculated. The observed interval cancer incidence is the number of interval cancers per 10,000 'negative' screening tests. RESULTS: The interval cancer rate in the first year was 25.37% for all cancers (ductal carcinoma in situ included) and 21.7% when the analysis was restricted to invasive tumours. Proportional incidence of interval cancer in the second year after screening was 12.02% for all cancers. CONCLUSION: In conclusion, the interval cancer rates in the Belgian province of Limburg were compatible with the European guidelines. However, increasing the recall rate in our programme and systematically reviewing the interval cancers may improve the quality of the programme even further.

Relationship between quality of life and cognitive decline in dementia.

AIMS: We aimed to examine the association of cognitive decline with quality of life (QoL) in dementia compared to controls and to determine variables associated with QoL. METHODS: Every subject was placed within a specific group depending on their designation by the Mini Mental State Examination and evaluated by the Alzheimer's Disease Related Quality of Life (ADRQL) and clinical assessments. RESULTS: QoL for the mild dementia group was lower (p = 0.08) than that of controls. The very severe dementia group had a significantly lower QoL than the other dementia groups, which all had similar ADRQL scores. The only predictor of ADRQL scores was found to be the behavioral and psychological symptoms of dementia. CONCLUSION: There is no direct relationship between cognitive decline and QoL.

The epidemic history of hepatitis C among injecting drug users in Flanders, Belgium.

We employed recently developed statistical methods to explore the epidemic behaviour of hepatitis C subtype 1a and subtype 3a among injecting drug users (IDUs) in Flanders, Belgium, using new gene sequence data sampled among two geographically distinct populations of IDUs. First the extent of hepatitis C transmission across regions/countries was studied through calculation of association indices. It was shown that viral exchange had occurred between both populations in Flanders as well as across international borders. Furthermore, evidence was found suggestive of subtypes 1a and 3a predominantly circulating in subpopulations of Flemish IDUs, exhibiting different degrees of travelling/migration behaviour. Secondly, through coalescent-based analysis the viral epidemic history of the hepatitis C subtype 1a and 3a epidemics was inferred. Evidence was found for different dynamic forces driving both epidemics. Moreover, results suggested that the hepatitis C subtype 3a epidemic has reached a steady state, while the hepatitis C 1a epidemic has not, which therefore might become the predominant subtype among IDUs.

The investigation of a geographical cluster of bladder cancer.

Previous analyses of the Limburg Cancer registry (LIKAR) indicated the existence of a geographical cluster of bladder cancer incidence, particularly transitional cell carcinomas, amongst males in the surrounding area of the Belgian cities Hasselt and Alken. In subsequent ecologic analyses no risk factors were identified which could explain the existence of this cluster. Therefore, an epidemiological case-control study has been performed in the province of Limburg to explore the possible determinants of the cluster. The following cluster determinants were investigated: socio-demographic characteristics, life style factors, occupational and environmental exposures, and genetic predisposition. A weight was assigned to all the study subjects. Secondly, we used unconditional logistic regression to calculate crude odd ratios (ORs) and 95% confidence intervals (CIs) for each source of exposure and bladder cancer. Thirdly, we used a multivariate logistic regression analysis which included all the parameters found to be significant at the 0.1 significance level in the univariate analysis. Although some of the specific odds ratios decreased compared with the crude results, the overall excess did not change specifically. In conclusion, we were not able to identify a clear-cut explanation for the existence of the geographical cluster. We therefore recommend an increased surveillance of bladder cancer incidence for 3 to 5 years. If the "excess" of cancer cases has occurred due to random variation, the rate will return to the "expected" range in the next years. If the rate remains elevated, further studies may need to be performed using investigative tools that are not available currently.

The evaluation of diagnostic tests: evidence on technical and diagnostic accuracy, impact on patient outcome and cost-effectiveness is needed.

OBJECTIVE: Before introducing a test in clinical practice, its characteristics and added value should be assessed. Diagnostic accuracy studies only are not sufficient; the test's impact on patient outcome ought to be assessed as well. To do this, we propose a stepwise evaluation of diagnostic tests. STUDY DESIGN AND SETTING: Theoretical-conceptual approach. RESULTS: First, the test's technical accuracy refers to the ability to produce usable information under standardized conditions. In a second step, the place of the new test in the clinical pathway is determined. Thirdly, the test's diagnostic accuracy is assessed, depending on its intended goal. The fourth step assesses the test's impact on the patient outcome. Depending on the place of the test in the clinical pathway, existing evidence can be used, or new evidence will be needed. At the final step, a cost-effectiveness analysis assesses the test's financial and societal consequences. CONCLUSION: Diagnostic tests evaluation should consider the technical accuracy, the test's place in the clinical pathway, its diagnostic accuracy, and its impact on patient outcome.