Silicone adhesive multilayer foam dressings as adjuvant prophylactic therapy to prevent hospital-acquired pressure ulcers: a pragmatic noncommercial multicentre randomized open-label parallel-group medical device trial.

BACKGROUND: Silicone adhesive multilayer foam dressings are used as adjuvant therapy to prevent hospital-acquired pressure ulcers (PUs). OBJECTIVES: To determine whether silicone foam dressings in addition to standard prevention reduce the incidence of PUs of category 2 or worse compared with standard prevention alone. METHODS: This was a multicentre, randomized controlled medical device trial conducted in eight Belgian hospitals. At-risk adult patients were centrally randomized (n = 1633) to study groups based on a 1 : 1 : 1 allocation: experimental groups 1 (n = 542) and 2 (n = 545) - pooled as the treatment group - and the control group (n = 546). The experimental groups received PU prevention according to hospital protocol, and a silicone foam dressing on the relevant body sites. The control group received standard of care. The primary endpoint was the incidence of a new PU of category 2 or worse at the studied body sites. RESULTS: In the intention-to-treat population (n = 1605), PUs of category 2 or worse occurred in 4·0% of patients in the treatment group and 6·3% in the control group [relative risk (RR) 0·64, 95% confidence interval (CI) 0·41-0·99, P = 0·04]. Sacral PUs were observed in 2·8% and 4·8% of the patients in the treatment group and the control group, respectively (RR 0·59, 95% CI 0·35-0·98, P = 0·04). Heel PUs occurred in 1·4% and 1·9% of patients in the treatment and control groups, respectively (RR 0·76, 95% CI 0·34-1·68, P = 0·49). CONCLUSIONS: Silicone foam dressings reduce the incidence of PUs of category 2 or worse in hospitalized at-risk patients when used in addition to standard of care. The results show a decrease for the sacrum, but no statistical difference for the heel and trochanter areas.

[«KCE Trials¼ : innovation based on practice oriented clinical trials]. / «KCE Trials¼ : des essais cliniques plus proches de la pratique.

Many questions in healthcare can only be answered after the conduct of clinical trials. For medicinal products and medical devices the industry finances most studies to bring their products to market. However, there is a need for further research in certain areas e.g. children, older people and comparative research of different treatment options (comparative effectiveness). In addition, interventions that are less industry-driven such as surgery, radiotherapy, psychotherapy, diet, physical medicine, needappropriately funded large scale clinical trials. Such clinical trials can be a good investment for the government and the healthcare payer. At the end of 2015 the Belgian Healthcare Knowledge Centre (KCE) received the mission and budget to run a programme of practice-oriented comparative clinical trials. Two years later the recruitment of patients in the first trials is ongoing. In addition to its yearly national calls for trial proposals, early in 2018 KCE launched its first international common call for comparative clinical trials with its Dutch counterpart ZonMw (BeNeFIT).

Les études cliniques financées par l'industrie, essentiellement effectuées dans le but d'obtenir la mise sur le marché de médicaments et de dispositifs médicaux, laissent de nombreuses questions cliniques sans réponse satisfaisante. Ainsi, par exemple, les produits y sont généralement comparés à un placebo, alors que la question réellement pertinente pour le clinicien serait une comparaison avec d'autres options thérapeutiques. De même, les domaines qui présentent un intérêt moindre pour l'industrie sont rarement explorés par des études à large échelle; c'est le cas, notamment, de la chirurgie, de la radiothérapie, des psychothérapies, de l'alimentation et de la médecine physique. Un programme d'études cliniques non commerciales, financé par les pouvoirs publics, permet de remédier à ces problèmes tout en constituant un excellent investissement pour les autorités de santé et le contribuable. Fin 2015, le Centre fédéral d'Expertise des Soins de Santé (KCE) a été chargé de mettre sur pied un tel programme d'études cliniques comparatives et axées sur la pratique. Deux ans plus tard, le recrutement des premiers essais bat son plein. Un appel annuel à sujets d'études a été mis en place et, début 2018, un premier appel international conjoint du KCE et de son homologue néerlandais le ZonMw a également été lancé (BeNeFIT).

Multidisciplinary work in oncology: Population-based analysis for seven invasive tumours.

The concept of multidisciplinary team meetings (MDTs) in cancer care is endorsed internationally, but its uptake varies considerably. In Belgium, MDT meetings were financially recognised in 2003 to encourage healthcare professionals to join their knowledge and competences to improve the quality and coordination of cancer care. This study aimed to evaluate for seven cancer types diagnosed between 2004 and 2011, the practices of MDT meetings in Belgium by means of population-based administrative databases. Results show a clear increase over time in the proportion of individual patients discussed at MDT meetings. Although this evolution may be partly explained by the legal implementation of several financial initiatives to stimulate MDT meetings, it also suggests an increase in specialists' awareness of the importance of such meetings. Nevertheless, there is still room for improvement, for specific cancer types as well as for certain subgroups such as older patients. From the specialists' point of view, reducing the administrative burden and time these meetings demand may entail a greater participation to MDT meetings. Further research is needed to identify the barriers to discuss more patients at MDT meetings and to elucidate the impact of MDT meetings on the quality of cancer care.

Patterns of care for non-small cell lung cancer patients in Belgium: A population-based study.

Guidelines recommend surgery for Stage I-II, chemoradiation for Stage III and systemic therapy for Stage IV non-small cell lung cancer (NSCLC). However, patient related factors and patient preferences influence treatment decisions. We investigated patterns of care for Belgian NSCLC patients in 2010-2011, based on population-based data from the Belgian Cancer Registry and administrative databases. The relationship between patient characteristics, institutional diagnostic volume, type of treatment and survival was investigated. Overall, 20.8% of patients received no oncological treatment. 59% and 22.1% of Stage I-II patients received primary surgery or (chemo)radiation respectively. 34% of Stage III patients received chemoradiation and 17% of Stage IIIA patients had surgery. 70% of Stage IV patients received chemotherapy or targeted therapy. Moderate variability between centres was observed. For Stage IV, systemic therapy was less frequently used in higher volume centres and 1-year survival was lower in centres that had ≥ 50 new patients yearly. Although not all NSCLC patients received treatment as ideally recommended by guidelines, these results do not necessarily represent poor quality of care as patient characteristics and preferences need to be taken into account. Treatment options targeted towards patients with co-morbidity or unfit patients is warranted to improve outcomes of all NSCLC patients.

Reference centres for adults with rare and complex cancers - Policy recommendations to improve the organisation of care in Belgium.

BACKGROUND: Rare and/or complex cancers call for a very specific expertise and adequate infrastructure. In Belgium, every hospital with a programme in oncology can deliver care for adults with rare and/or complex cancer types, without having demonstrated a specific know-how to adequately manage these patients. Therefore, the Minister of Health ordered a scenario for the organisation of care for adults with rare and/or complex cancers, taking into account the current Belgian situation and relevant foreign experience. METHODS: Combined methods were used in this study: a literature review, the consultation of stakeholders, in depth discussions in 14 multidisciplinary groups leading to concrete proposals for several rare/complex cancers and the consultation of a panel of expert pathologists. RESULTS: The core recommendation is the set-up of shared care networks around reference centres, with multidisciplinary teams of recognised expertise in specific rare/complex cancers. The definition of minimum caseloads for hospitals and medical specialists, the evaluation of the quality of care, a model of diagnostic confirmation and the set-up of a national portal website which provides information on rare and/or complex cancers and reference centres are highly recommended. CONCLUSION: It is no longer practicable, efficient or ethical that every hospital or every practitioner continues to offer care for every rare/complex cancer. Improving the quality of rare/complex cancer care requires to concentrate expertise and sophisticated infrastructure in reference centres. Furthermore, the formation of networks between reference centres and peripheral centres will allow a delivery of care combining expertise and proximity. The next step is the translation of the recommendations into policy decisions. It is very well realised that this will take some courage and that a certain degree of resistance will have to be surmounted, but eventually, the best interest of the patient should prevail.

Quality indicators for oesophageal and gastric cancer: a population-based study in Belgium, 2004-2008.

This study aimed at developing and measuring quality indicators for oesophageal cancer (OC) and gastric cancer (GC) and to support quality improvement for practitioners. Quality indicators were identified from a systematic literature search including clinical guidelines. The selection process involved experts evaluating relevance, reliability, interpretability and actionability of each indicator. Three national databases were linked: the cancer registry, the population registry and the claims database. Completeness and validity of the data were validated before being measured for 10,660 patients diagnosed between 2004 and 2008. From a final set of 29 indicators, 18 were measurable using the available data. In 2008, less than 50% of patients were discussed at a multidisciplinary team meeting and less than 90% underwent a computed tomography scan 1 month after incidence date for cancer staging. Five-year relative survival was 22% for OC and 34.3% for GC. The post-operative mortality in OC patients was 4.8% (30 days) and 9.9% (90 days), whereas it reached 5.6 and 12.0% respectively in GC patients. This study demonstrates the feasibility to develop a set of quality indicators for gastro-oesophageal cancer. A mixed picture of the quality of care was illustrated for some relevant care processes. Nevertheless, 5-year survival is higher than reported in neighbouring countries.

Hospital-acquired infections in Belgian acute-care hospitals: an estimation of their global impact on mortality, length of stay and healthcare costs.

Assessing the overall burden of disease which can be attributed to hospital-acquired infections (HAIs) remains a challenge. A matched cohort study was performed to estimate excess mortality, length of stay and costs attributable to HAIs in Belgian acute-care hospitals, using six matching factors (hospital, diagnosis-related group, age, ward, Charlson score, estimated length of stay prior to infection). Information was combined from different sources on the epidemiology and burden of HAIs to estimate the impact at national level. The total number of patients affected by a HAI each year was 125 000 (per 10·9 million inhabitants). The excess mortality was 2·8% and excess length of stay was 7·3 days, corresponding to a public healthcare cost of €290 million. A large burden was observed outside the intensive-care unit setting (87% of patients infected and extra costs, 73% of excess deaths).

Hospital-acquired, laboratory-confirmed bloodstream infections: linking national surveillance data to clinical and financial hospital data to estimate increased length of stay and healthcare costs.

This matched cohort study estimates the effect of hospital-acquired bloodstream infection (HA-BSI) on length of stay (LOS) and costs during hospitalisation of 1839 patients (age range <1 to >80 years) gathered from 19 acute hospitals in Belgium. A second objective was to evaluate the impact of the choice of matching criteria. Data from national surveillance of HA-BSI were linked to hospital administrative discharge data, with respect for the patients' right to confidentiality of their health record. Controls were identified based on a set of matching factors: hospital, All-Patient Refined Diagnosis Related Groups, age, principal diagnosis, Charlson Comorbidity Index and time to infection. The results showed that, depending on the choice of matching factors, the estimation of additional LOS decreased from 26 to 10 days, with the most critical factor being the time to infection. The additional LOS attributable to HA-BSI was 9.9 days [95% confidence interval (CI): 7.8, 11.9]. The additional cost per infection was euro4900 [95% CI: euro4035, euro5750]; 58% of those costs were due to LOS, 10% were due to antibiotics, 10% due to other pharmaceutical products and 15% were due to billed medical acts. The main conclusion is that laboratory-confirmed HA-BSIs increase the LOS by 10 days for patients surviving the infection, and that the time to infection plays a crucial role in this estimation.

The 2007 Belgian national prevalence survey for hospital-acquired infections.

Despite ongoing targeted surveillance efforts, no overall in-hospital prevalence data for hospital-acquired infections (HAIs) have been published for Belgium. Sixty-three Belgian acute hospitals participated in a point-prevalence study among either all patients admitted in their institution or 50% of the patients in each ward. HAIs were registered bed-site at a single day per ward during the period October-November 2007. The diagnosis was made according to the Centers for Disease Control and Prevention (CDC) criteria implemented in a custom-made rule-based software expert system available on a portable computer. The total number of patients surveyed nationally was 17 343, from 543 distinct hospital wards. The overall prevalence of HAIs was 7.1% (95% confidence interval: 6.7-7.4%); 6.2% (5.9-6.5%) of the patients suffered from at least one HAI. Prevalence of HAIs on adult intensive care was 31.3%. The major proportion of HAIs was observed among patients admitted on non-intensive care unit (non-ICU) wards, mainly on the wards of internal medicine, surgery, geriatrics and rehabilitation. Urinary tract infections were the most common type of HAI at geriatric and rehabilitation wards. This study demonstrates that the use of a portable computer system with a designated expert system for diagnosing HAIs according to the CDC criteria in a large point prevalence study is feasible and may reduce the within-subject variation. In Belgium, the prevalence of HAIs in acute hospitals thus identified is similar to that of neighbouring countries. As more than 80% of all HAIs occur on non-ICU wards, preventive efforts need to extend beyond the ICU.

Randomized, placebo-controlled trial of rofecoxib in the acute treatment of migraine.

OBJECTIVE: To investigate the clinical profile of rofecoxib, a long-acting (approximately 17-hour half-life) selective cyclo-oxygenase-2 inhibitor, for the acute treatment of migraine. METHODS: A randomized, double-blind, placebo-controlled, parallel-group study was conducted. Patients age > or =18 treated a moderate or severe migraine headache with placebo (n = 182), rofecoxib 25 mg (n = 183), or rofecoxib 50 mg (n = 192). The primary efficacy measure was headache relief (mild or no pain) 2 hours after dose. RESULTS: The proportions of patients with migraine headache relief at 2 hours after dose were 34.3% for placebo, 54.0% for rofecoxib 25 mg (p < 0.001 vs placebo), and 56.7% for rofecoxib 50 mg (p < 0.001 vs placebo). Rofecoxib 25 and 50 mg were superior to placebo in providing pain freedom at 2 hours, 24-hour sustained headache relief, and 24-hour sustained pain freedom; in reducing photophobia, phonophobia, nausea (50 mg only), and functional disability at 2 hours after dose; and in improving some quality-of-life scores over 24 hours. More patients on rofecoxib 50 mg reported adverse events (39.6%) than patients on rofecoxib 25 mg (26.8%) or placebo (23.6%) regardless of drug relatedness; however, the incidences of drug-related adverse events were similar between treatment groups. These adverse events were generally mild or moderate in severity. The most commonly reported adverse events were dry mouth, dizziness, somnolence, nausea, dyspepsia, paresthesia, and asthenia, with similar incidences between treatment groups. CONCLUSION: Rofecoxib 25 and 50 mg were effective and generally well tolerated for the acute treatment of migraine attacks.

Comparison of low-dose rofecoxib versus 1000 mg naproxen in patients with osteoarthritis. Results of two randomized treatment trials of six weeks duration.

OBJECTIVE: To compare the efficacy and safety of rofecoxib 12.5 mg once daily to naproxen 500 mg twice daily in patients > or = 40 years of age with knee or hip osteoarthritis (OA). METHOD: Two identical 6-week, randomized, double-blind studies were conducted (1 in Africa, Australia, Europe, Canada, Mexico, & South America; 1 in Asia). Primary endpoints were pain walking on a flat surface, patient global assessment of response to therapy, and investigator global assessment of disease status. RESULTS: Overall, 944 patients participated. For all efficacy endpoints, treatment effects for rofecoxib and naproxen were comparable and seen at the first measures of efficacy. Both compounds were generally well-tolerated, with an improved gastrointestinal safety profile for rofecoxib versus naproxen. CONCLUSIONS In these studies, rofecoxib 12.5 mg once daily (the lowest indicated dose) and naproxen 500 mg twice daily showed similar treatment effects in OA patients. Rofecoxib and naproxen were generally well tolerated.

Comparison of preference for rizatriptan 10-mg wafer versus sumatriptan 50-mg tablet in migraine.

Rizatriptan (MAXALT, a registered trademark of Merck & Co. Inc.) is a selective 5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action in the acute treatment of migraine. This randomized, open-label, crossover outpatient study assessed the preference of 481 patients for rizatriptan 10-mg rapidly disintegrating tablets versus sumatriptan (IMIGRAN, a registered trademark of GlaxoWellcome PLC) 50-mg tablets in the treatment of a single migraine attack with each therapy. Almost twice as many patients preferred rizatriptan 10-mg rapidly disintegrating tablet to sumatriptan 50-mg tablet (64.3 vs. 35.7%, p < or = 0.001). Faster relief of headache pain was the most important reason for the preference, cited by 46.9% of patients preferring rizatriptan and 43.4% of patients who preferred sumatriptan. Headache relief at 2 h was 75.9% with rizatriptan and 66.6% with sumatriptan (p < or = 0.001), with rizatriptan being superior to sumatriptan within 30 min of dosing. Fifty-five percent of patients were pain free 2 h after rizatriptan, compared with 42.1% treated with sumatriptan (p < or = 0.001), rizatriptan being superior within 1 h of treatment. Forty-one percent of patients taking rizatriptan were pain free at 2 h and had no recurrence or need for additional medication, compared to 32.3% of patients on sumatriptan. Rizatriptan was also superior to sumatriptan in terms of the proportions of patients with no nausea, phonophobia or photophobia, and patients with normal function 2 h after treatment intake (p < 0.05). More patients were (completely, very or somewhat) satisfied 2 h after treatment with rizatriptan (73.3%) than 2 h after treatment with sumatriptan (59.0%) (p < or = 0.001). Additionally, 2 h after the dose, more patients found rizatriptan to be very convenient, convenient or somewhat convenient (87.2%) than they did sumatriptan (76.3%) (p < or = 0.001). Both active treatments were well tolerated. The most common side effects with rizatriptan and sumatriptan were nausea (6.6 and 6.9% of patients, respectively), dizziness (6.1 and 5.8%) and somnolence (7.4 and 6.7%).

Oral montelukast versus inhaled beclomethasone in 6- to 11-year-old children with asthma: results of an open-label extension study evaluating long-term safety, satisfaction, and adherence with therapy.

This 6-month, open-label extension study of a previously described base study compared oral montelukast with inhaled beclomethasone in terms of safety, forced expiratory volume in one second (FEV1) measurements, parent and patient satisfaction with treatment, asthma-related medical resource utilization, school absenteeism, and parental work loss in children with asthma. A total of 124 of 266 asthmatic children, 6 to 11 years of age, who enrolled in the base study entered a 6-month open-label extension study (74 boys, 50 girls) and were re-randomized (2:1 ratio) to receive once-daily oral montelukast (n = 83) or inhaled beclomethasone 100 mcg three times daily (n = 41). Children were evaluated in the clinic prior to re-randomization (Month 0) and at regular visits at 1, 3, and 6 months. Children and their parents showed a significantly higher overall satisfaction for montelukast at 6 months than for inhaled beclomethasone (p = 0.001 and p < 0.05, respectively). According to parents, montelukast was more convenient (p < 0.001), less difficult to use (p = 0.005), and was used as instructed more of the time (p = 0.006) compared with beclomethasone. Oral corticosteroid use was similar in the montelukast (13% of patients) and beclomethasone (17%) treatment groups. The montelukast treatment group was more adherent with their regimen than the inhaled beclomethasone treatment group; almost twice as many children on montelukast compared with inhaled beclomethasone were highly compliant (82% versus 45%). The two study groups were similar with respect to overall safety, change in FEV1, asthma-related medical resource utilization, school absenteeism, and parental work loss. Montelukast represents a safe and effective asthma treatment regimen to which children with asthma are more likely to adhere.

Comparison of rizatriptan 10 mg vs. zolmitriptan 2.5 mg in the acute treatment of migraine. Rizatriptan-Zolmitriptan Study Group.

The efficacy and tolerability of rizatriptan (MAXALT) and zolmitriptan (ZOMIG) were compared in a randomized, double-blind, double-dummy, stratified (on prior use of rizatriptan and/or zolmitriptan), placebo-controlled, single attack study in 766 patients. Rizatriptan tended to provide freedom from pain sooner than zolmitriptan (hazard ratio 1.26, P = 0.075), acting within 60 min following dosing. More patients were pain free at 2 h on rizatriptan than on zolmitriptan (43.2% vs. 35.6%, P=0.041), while headache relief at 2 h was similar (70.5% vs. 66.8%). At 2 h, fewer patients on rizatriptan had symptoms of photophobia (35.6% vs. 43.5%, P = 0.029) and nausea (25.2% vs. 32.5%, P=0.046), and more patients on rizatriptan had normal function (45.4% vs. 37.0%, P=0.025) than zolmitriptan. Headache recurred in 28% of patients taking rizatriptan, 29% taking zolmitriptan and 26% taking placebo. Both active treatments were effective compared to placebo and were well tolerated. The most common side-effects with rizatriptan were asthenia/fatigue, somnolence and dizziness, while the most common side-effects with zolmitriptan were asthenia/fatigue and dizziness.

The efficacy and tolerability of losartan versus atenolol in patients with isolated systolic hypertension. Losartan ISH Investigators Group.

OBJECTIVE: To compare the efficacy and tolerability of angiotensin II (Ang II) antagonist losartan and the beta-blocker atenolol in the treatment of patients with isolated systolic hypertension (ISH) after 16 weeks of treatment. METHODS: A double-blind, randomized, multi-country study was carried out in 273 patients with ISH. Patients with a sitting systolic blood pressure (SiSBP) of 160-205 mmHg, and a sitting diastolic blood pressure (SiDBP) < 90 mmHg at screening and at placebo baseline were subjected to a 4-week placebo period and then randomly grouped to receive 50 mg losartan or 50 mg atenolol once daily for 16 weeks. At 8 and 12 weeks, patients not controlled (SiDBP > or = 160 mmHg) were given additional treatment of 12.5 mg hydrochlorothiazide (HCTZ) once daily. RESULTS: Similar significant reductions in SiSBPs (mean +/- SD) were obtained with 50 mg losartan and 50 mg atenolol, from 173.7 +/- 10.3 and 173.5 +/- 10.7 mmHg at baseline to 149.0 +/- 15.5 and 148.2 +/- 15.3 mmHg after 16 weeks of losartan or atenolol treatment respectively. Sixty-seven percent of the losartan-treated and 64% of the atenolol-treated patients remained on monotherapy throughout the study. Only 1.5% of the losartan-treated patients withdrew because of a clinical adverse event (CAE) compared with 7.2% in the atenolol-treatment group (P= 0.035). Drug-related CAEs were observed significantly more frequently with atenolol than with losartan treatment (20.3 versus 10.4%; P = 0.029). CONCLUSION: It is concluded that 50 mg losartan and 50 mg atenolol produced comparable reductions in SiSBP in patients with ISH but losartan was better tolerated. This is the first demonstration of the therapeutic value of selective Ang II receptor blockade with losartan in the treatment of ISH.