Time to reimbursement of novel anticancer drugs in Europe: a case study of seven European countries.

BACKGROUND: Time to reimbursement (TTR) of new anticancer medicines differs between countries and contributes to unequal access. We aimed to investigate TTR of new anticancer medicines and explore factors influencing the reimbursement process in seven high-income European countries. MATERIALS AND METHODS: We carried out a retrospective case study of anticancer medicines with European Union Market Access (EU-MA) and a positive Committee for Medicinal Products for Human Use opinion from 2016 until 2021 with subsequent national reimbursement approval (NRA). The National Health Technology Assessment (HTA) and reimbursement websites of Germany, France, UK, the Netherlands, Belgium, Norway and Switzerland were used to identify TTR, defined as time from EU-MA to NRA. Additionally, we investigated medication-, country-, indication- and pharma-related factors potentially influencing TTR. RESULTS: Thirty-five medicines were identified for which TTR ranged from -81 days to 2320 days (median 407 days). At data cut-off, 16 (46%) were reimbursed in all seven countries. Overall, the shortest TTR was in Germany (median 3 days, all medicines reimbursed <5 days). The time limit for reimbursement of 180 days stated by the Council of European Communities after the EU-MA (EU Transparency Directive) was met for 100% of included medicines in Germany, 51% in France, 29% in the UK and the Netherlands, 14% in Switzerland, 6% in Norway and 3% in Belgium. The TTR was significantly different between countries (P < 0.001). In multivariate analysis, factors associated with shorter TTR were higher gross domestic product (GDP), absence of a pre-assessment procedure and submission by a big pharmaceutical company. CONCLUSIONS: TTR of anticancer medicines varies significantly between seven high-income European countries and leads to inequality in access. Among explored medication-, country-, indication- and pharma-related factors we found that a high GDP, the absence of a pre-assessment procedure and submission by big pharmaceutical companies were associated with shorter TTR.

Essential diseases in prescribing: A national Delphi study towards a core curriculum in pharmacotherapy education.

AIMS: Prescribing is a core skill for junior doctors, yet 8-10% of their prescriptions contain errors. To ensure adequate training in prescribing, it is important to define the diseases for which junior doctors should be competent to prescribe. The aim of the present study was therefore to identify the essential diseases in prescribing for junior doctors. METHODS: A two-round Delphi consensus study was conducted among medical specialists, general practitioners, junior doctors, pharmacists and pharmacotherapy teachers from all eight academic hospitals in the Netherlands. Using a five-point Likert scale, the participants indicated for each item on an initial questionnaire whether it should be considered an essential disease for junior doctors. The items for which ≥80% of all respondents agreed or strongly agreed were accepted as essential diseases. RESULTS: Sixty-two participants completed the Delphi survey. In total, 63 of 220 items were considered to be essential diseases. CONCLUSION: This is the first Delphi consensus study identifying exact conditions that junior doctors must be able to prescribe for. The essential diseases can be used for training in prescribing and assessment of junior doctors' prescribing competence.

Essential competencies in prescribing: A first european cross-sectional study among 895 final-year medical students.

European medical students should have acquired adequate prescribing competencies before graduation, but it is not known whether this is the case. In this international multicenter study, we evaluated the essential knowledge, skills, and attitudes in clinical pharmacology and therapeutics (CPT) of final-year medical students across Europe. In a cross-sectional design, 26 medical schools from 17 European countries were asked to administer a standardized assessment and questionnaire to 50 final-year students. Although there were differences between schools, our results show an overall lack of essential prescribing competencies among final-year students in Europe. Students had a poor knowledge of drug interactions and contraindications, and chose inappropriate therapies for common diseases or made prescribing errors. Our results suggest that undergraduate teaching in CPT is inadequate in many European schools, leading to incompetent prescribers and potentially unsafe patient care. A European core curriculum with clear learning outcomes and assessments should be urgently developed.

Never ignore extremely elevated D-dimer levels: they are specific for serious illness.

BACKGROUND: D-dimer is routinely measured as part of the clinical diagnosis algorithms for venous thromboembolism (VTE). In these algorithms, low D- dimer cut-off values are used to generate a dichotomous test result that is sensitive, but very non-specific for VTE. A consequence of any test dichotomisation is loss of information that is hidden in the continuous spectrum of results. For D-dimer, the information conveyed by extremely elevated results may be particularly relevant. Our aim was to assess the differential diagnosis of extremely elevated D-dimer levels in a hospital setting. METHODS: Retrospective cohort study of patients > 18 years with an extremely elevated (> 5000 µg/l; > 10x cut-off to exclude VTE) D-dimer test result. Electronic medical records were reviewed for diagnoses. RESULTS: A total of 759 extremely elevated D-dimer results were identified. After exclusion of 120 duplicate cases, 53 patients undergoing cardiopulmonary resuscitation, and 5 cases without diagnostic information, 581 cases were analysed. Their D-dimer ranged between 5030 and 239,000 µg/l, with a mean of 17,598 µg/l (SD 22,972 µg/l). Altogether, 89% of these patients had a diagnosis of VTE, sepsis and/or cancer. The prevalence was highest for pulmonary embolism (183 patients; 32%), followed by cancer (168 patients; 29%), sepsis (142 patients; 24%), trauma/surgery (142 patients; 24%), and deep vein thrombosis (73 patients; 13%). CONCLUSION: Although D-dimer testing has a reputation for being very non-specific, an extremely elevated D-dimer is uniquely associated with severe disease, mainly including VTE, sepsis and/or cancer. These results suggest that, even if sharply elevated D-dimers are a seemingly solitary finding, clinical suspicion of severe underlying disease should be maintained.

'Single' v. 'panel' appointed forensic mental observations: Is the referral process ethically justifiable?

OBJECTIVE: To compare the outcome and psychiatric morbidity of the forensic mental observation referrals, in the two legally created groups of detainees awaiting trial - the 'singles', representing the minor violent and non-violent offenders evaluated by a single-state appointed psychiatrist, v. the 'panels', representing the seriously violent offenders evaluated by two or more psychiatrists. METHODS: A retrospective record review covered 200 cases, comprising all individuals admitted to the forensic unit of Sterkfontein Hospital for 30 days psychiatric observation from January to August 2010. Pearson's χ2 test for categorical data were used to determine statistical significance. RESULTS: Of 110 singles, 49 (44.55%) were found fit for trial and 40 (40.4%) were found criminally responsible. Of the 90 'panel' cases 60 (66.67%) were found ft for trial and 57 (64.77%) were found criminally responsible (p=0.002 and p=0.001, respectively). CONCLUSION: Those charged with seriously violent offences appear more likely to be found both fit and responsible, compared with those charged with less serious offences.

Varicella pneumonia complicating pregnancy: a report of seven cases.

BACKGROUND: Pneumonia is the most common complication of varicella-zoster infection in adults and has potentially devastating effects when complicating pregnancy. Due to the significant morbidity and mortality associated with this complication during pregnancy and the small number of reported cases in the literature, we present this report to help educate physicians who care for pregnant women. CASES: Seven patients are presented in this report. These patients presented at various stages in pregnancy, from 17 to 31 weeks of gestation. Three of the patients had unremarkable hospital courses. Three of the patients had hospital stays over 21 days in duration. One patient died from complications of varicella pneumonia after 31 days of hospitalization. The obstetric outcomes of the 7 patients described include 1 non-viable delivery at 20 weeks gestation, 3 term deliveries, 2 preterm deliveries, and 1 patient who has not yet delivered. All of the patients presented were treated with intravenous acyclovir therapy. Of the patients described, 3 required intubation and ventilatory support. Other complications encountered include disseminated intravascular coagulation (DIC), adult respiratory distress syndrome (ARDS), metabolic encephalopathy, pneumothorax, superimposed bacterial pneumonia, and sepsis. CONCLUSION: The course and treatment of varicella pneumonia complicating pregnancy are discussed. Current recommendations regarding the use of varicella-zoster immune globulin (VZIG) are also reviewed.

Bivariate cytokeratin/DNA flow cytometric analysis of paraffin-embedded samples from colorectal carcinomas.

Admixture of normal and neoplastic cells is a serious problem in the evaluation of tumor cell kinetic parameters by flow cytometry, in particular for DNA diploid tumors. The admixture of non-neoplastic cells, such as stromal cells and inflammatory cells, can disturb the estimation of the proliferative tumor fraction. This problem has been addressed in fresh tumor samples by applying bivariate flow cytometric analyses for DNA and cytokeratin. We have adapted this approach for formalin-fixed and paraffin-embedded tissue samples of colorectal carcinomas. After preparation of a single cell suspension from paraffin blocks by means of an enzymatic digestion step, the cells of epithelial origin were selectively stained with a panel of subtype specific cytokeratin antibodies. DNA analysis could thus be performed on the cytokeratin-positive cells. The proliferative fractions of the paraffin-embedded samples could be compared with those of the fresh tissue samples and a very good correlation was seen between DNA indices from fresh and paraffin-embedded material. As expected, after gating on the cytokeratin-positive cells an enrichment of the S-phase fraction was seen compared with the ungated cell population. However, this enrichment was more pronounced in the cell suspensions derived from the paraffin-embedded part of the tumor compared with the fresh disaggregated, ethanol-fixed part of the tumor.

[Rehabilitative treatment of cerebral apoplectic insults in advanced age and evaluating its effectiveness--results of a model project]. / Zur rehabilitativen Behandlung von zerebralen apoplektischen Insulten im höheren Lebensalter und ihrer Effizienzbeurteilung--Ergebnisse eines Modellprojekts.

This report is of a two year study of stroke rehabilitation. Given certain conditions with specialized personnel and equipment the rehabilitation of elderly stroke patients can be managed co-operatively in hospitals and old age care centres. The rehabilitation of stroke affected is based on the support of multidisciplinary diagnosis and interdisciplinary teamwork between physicians, physiotherapists, occupational therapists, speech therapists, psychologists and social workers. Each patient requires an individual treatment program. In this study were 72 patients ranging in age from 42-87 years, average age 73 years. They had been judged as progressively degenerative and helpless following their stroke and consequently regarded as patients for a nursing home. Following special rehabilitation treatment 75% (54 patients) had improved enough that it was possible for them to return to their homes. Only 12.5% (9 patients) had to remain in a nursing home. 6.6% (4 patients) transferred to an old people's home. 6.9% (9 patients) were readmitted to hospital because of additional serious complications. The average duration of rehabilitative treatment was 72.3 days. The degree of hemiplegia and the patients ability to lead their own active daily independent life was reviewed before and after rehabilitation and used as control. 76.6% showed an improvement in their motor function. 61.1% returned to their own independent daily life as measured by ADL-Indices. (a. Barthel Index, b. ADL-Index-Katz-, c. Patient Classification for Long Term Care-Jones-, d. Crichton Royal Behavioural Rating Scale-Robinson-.).(ABSTRACT TRUNCATED AT 250 WORDS)