Bosjes van Poot : onderzoek bezoekers en honden

De Bosjes van Poot is een duingebied dat sinds 1990 behoort tot Natuurmonument Westduinpark. Daarmee valt het onder de Natuurbeschermingswet en in 2008 wordt de aanwijzing tot Natura 2000 gebied verwacht. In opdracht van Dienst Stadsbeheer van Den Haag is nu een onderzoek opgezet en uitgevoerd om beter zicht te krijgen op een gewenst hondenbeleid. De vraagstelling is hoeveel honden er gebruik maken van het gebied en hoe dat over het gebied verdeeld i

Bortezomib maintenance after R-CHOP, cytarabine and autologous stem cell transplantation in newly diagnosed patients with mantle cell lymphoma, results of a randomised phase II HOVON trial

Rituximab-containing induction followed by autologous stem cell transplantation (ASCT) is the standard first-line treatment for young mantle cell lymphoma patients. However, most patients relapse after ASCT. We investigated in a randomised phase II study the outcome of a chemo-immuno regimen and ASCT with or without maintenance therapy with bortezomib. Induction consisted of three cycles R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), two cycles high-dose cytarabine, BEAM (carmustine, etoposide, cytarabine, melphalan) and ASCT. Patients responding were randomised between bortezomib maintenance (1·3 mg/m2 intravenously once every 2 weeks, for 2 years) and observation. Of 135 eligible patients, 115 (85%) proceeded to ASCT, 60 (44%) were randomised. With a median follow-up of 77·5 months for patients still alive, 5-year event-free survival (EFS) was 51% (95% CI 42–59%); 5-year overall survival (OS) was 73% (95% CI 65–80%). The median follow-up of randomised patients still alive was 71·5 months. Patients with bortezomib maintenance had a 5-year EFS of 63% (95% CI 44–78%) and 5-year OS of 90% (95% CI 72–97%). The patients randomised to observation had 5-year PFS of 60% (95% CI, 40–75%) and OS of 90% (95% CI 72–97%). In conclusion, in this phase II study we found no indication of a positive effect of bortezomib maintenance after ASCT

Sex-based differences in treatment with immune checkpoint inhibition and targeted therapy for advanced melanoma: a nationwide cohort study

Simple Summary Melanoma is a malignant form of skin cancer. The overall survival of patients with advanced stages of disease were initially low. Fortunately, in recent years systemic treatment with immunotherapy has prolonged survival. We set out to answer the question whether men and women with advanced melanoma differ in prognostic factors, tumor-response to immunotherapy, and treatment-related adverse events. All patients in the Netherlands were registered between July 2013 and July 2018. We showed that although clinical and tumor characteristics differ, the safety profile of immunotherapy is comparable. Furthermore, overall, a 10% survival advantage for women was seen. Following immunotherapy there was no survival difference. Recent meta-analyses show conflicting data on sex-dependent benefit following systemic treatment for advanced melanoma patients. We examined the nationwide Dutch Melanoma Treatment Registry (July 2013-July 2018), assessing sex-dependent differences in advanced melanoma patients (stage IIIC/IV) with respect to clinical characteristics, mutational profiles, treatments initiated, grade 3-4 adverse events (AEs), treatment responses, and mortality. We included 3985 patients, 2363 men (59%) and showed that although men and women with advanced melanoma differ in clinical and tumor characteristics, the safety profile of immune checkpoint inhibition (ICI) is comparable. The data suggest a 10% survival advantage for women, mainly seen in patients >= 60 years of age and patients with BRAF V600 mutant melanoma. Following ICI there was no survival difference.Clinical epidemiolog

Checkpoint inhibitor induced hepatitis and the relation with liver metastasis and outcome in advanced melanoma patients

Background Checkpoint inhibitor-induced hepatitis is an immune-related adverse event of programmed cell death protein 1 (PD-1) inhibition, cytotoxic T-lymphocyte associated 4 (CTLA-4) inhibition or the combination of both. Aim of this study was to assess whether checkpoint inhibitor-induced hepatitis is related to liver metastasis and outcome in a real-world nationwide cohort. Methods Data from the prospective nationwide Dutch Melanoma Treatment Registry (DMTR) was used to analyze incidence, risk factors of checkpoint inhibitor-induced grade 3-4 hepatitis and outcome. Results 2561 advanced cutaneous melanoma patients received 3111 treatments with checkpoint inhibitors between May 2012 and January 2019. Severe hepatitis occurred in 30/1620 (1.8%) patients treated with PD-1 inhibitors, in 29/1105 (2.6%) patients treated with ipilimumab and in 80/386 (20.7%) patients treated with combination therapy. Patients with hepatitis had a similar prevalence of liver metastasis compared to patients without hepatitis (32% vs. 27%; p = 0.58 for PD-1 inhibitors; 42% vs. 29%; p = 0.16 for ipilimumab; 38% vs. 43%; p = 0.50 for combination therapy). There was no difference in median progression free and overall survival between patients with and without hepatitis (6.0 months vs. 5.4 months progression-free survival; p = 0.61; 17.0 vs. 16.2 months overall survival; p = 0.44). Conclusion Incidence of hepatitis in a real-world cohort is 1.8% for PD-1 inhibitor, 2.6% for ipilimumab and 20.7% for combination therapy. Checkpoint inhibitor-induced hepatitis had no relation with liver metastasis and had no negative effect on the outcome.Experimentele farmacotherapi

The World Federation of ADHD International Consensus Statement:208 Evidence-based conclusions about the disorder

Background: Misconceptions about ADHD stigmatize affected people, reduce credibility of providers, and prevent/delay treatment. To challenge misconceptions, we curated findings with strong evidence base. Methods: We reviewed studies with more than 2000 participants or meta-analyses from five or more studies or 2000 or more participants. We excluded meta-analyses that did not assess publication bias, except for meta-analyses of prevalence. For network meta-analyses we required comparison adjusted funnel plots. We excluded treatment studies with waiting-list or treatment as usual controls. From this literature, we extracted evidence-based assertions about the disorder. Results: We generated 208 empirically supported statements about ADHD. The status of the included statements as empirically supported is approved by 80 authors from 27 countries and 6 continents. The contents of the manuscript are endorsed by 366 people who have read this document and agree with its contents. Conclusions: Many findings in ADHD are supported by meta-analysis. These allow for firm statements about the nature, course, outcome causes, and treatments for disorders that are useful for reducing misconceptions and stigma.</p

Metastatic uveal melanoma: Treatment strategies and survival—results from the dutch melanoma treatment registry

Uveal melanoma (UM) is the most common primary intraocular tumor in adults. Up to 50% of UM patients will develop metastases. We present data of 175 metastatic UM patients diagnosed in the Netherlands between July 2012 and March 2018. In our cohort, elevated lactate dehydrogenase level (LDH) is an important factor associated with poorer survival (Hazard Ratio (HR) 9.0, 95% Confidence Interval (CI) 5.63–14.35), and the presence of liver metastases is negatively associated with survival (HR 2.09, 95%CI 1.07–4.08). We used data from the nation-wide Dutch Melanoma Treatment Registry (DMTR) providing a complete overview of the location of metastases at time of stage IV disease. In 154 (88%) patients, the liver was affected, and only 3 patients were reported to have brain metastases. In 63 (36%) patients, mutation analysis was performed, showing a GNA11 mutation in 28.6% and a GNAQ mutation in 49.2% of the analyzed patients. In the absence of standard care of treatment options, metastatic UM patients are often directed to clinical trials. Patients participating in clinical trials are often subject to selection and usually do not represent the entire metastatic UM population. By using our nation-wide cohort, we are able to describe real-life treatment choices made in metastatic UM patients and 1-year surv

Supporting patients : pharmacy based interventions to improve medication adherence

For many patients it is not easy to adhere to the agreed treatment with medication. Adherence has been defined as “the extent to which a person’s behaviour - taking medication - corresponds with agreed recommendations from a health care provider”. Numerous factors influence this taking behaviour and non-adherence must not be seen as the patients’ problem only. Health care providers, including pharmacists, should support patients to adhere. The overall aim of this thesis was to evaluate interventions in community pharmacies focussing on improving medication adherence both at the start of therapy and in the implementation of the therapy. Moreover, we studied frequency, nature and the quality of counselling in pharmacies and proposed definitions and standardization for assessing adherence using dispensing data. The thesis includes two large randomized studies. The first study focussed on patients initiating treatment: the Telephone Counselling Intervention by Pharmacists (TelCIP)-trial. The intervention consisted of a telephone call 7 to 21 days after the start of therapy and focussed on patients starting with Renin-Angiotensin-System (RAS)-inhibitors, bisphosphonates, lipid-lowering drugs and antidepressants. This telephone call aimed at improving patient’s adherence. Counselling during this phone call focused on patients’ information needs and barriers to take medication such as side effects, low necessity beliefs and forgetfulness. Intervention patients were compared with patients receiving usual care. After receiving telephone counselling patients were more satisfied with counselling in general than patients who received usual care. They were also more satisfied with the information on their medication and fewer patients had concerns about the medication. Interestingly, all effects were more pronounced in men than in women. Main objective of this service was to improve medication adherence and this study demonstrated that counselling by telephone clearly improved adherence with Renin-Angiotensin-System (RAS)-inhibitors and indicated an improvement with bisphosphonates and lipid-lowering drugs. However no effect was found in patients using antidepressants. It is important not to focus exclusively on patients initiating treatment but also on patients already using the medication. Therefore, a second trial focussed on non-adherent patients who were using lipid-lowering drugs (statins) for over a year. Two interventions were compared with usual care: provision of an electronic reminder device (ERD) combined with counselling in the pharmacy or the provision of an ERD only. Results showed that patients were difficult to motivate to visit the pharmacy for counselling. In general, medication adherence did not improve by using the ERD, both with and without counselling, but the provision of an ERD improved adherence in women using a statins for secondary prevention compared to women receiving usual care. This thesis concluded that pharmacists can support patients in medication use but that the effectiveness of interventions is not the same for different groups of patients. Within the multidisciplinary team involved in medication adherence, it is time that pharmacists take up the challenge to expand their role in promoting medication adherence

Dynamic balance control in transfemoral amputees: Individual contribution of the prosthesis side

1. Summary/conclusions\ud This study explores the use of a new developed method to assess the individual contribution of both legs to postural control. The results imply that the contribution of the prosthetic leg in balance control is not a mere reflection of the weight distribution.\ud \ud 2. Introduction\ud A major goal in the rehabilitation of lower limb amputees is to regain effective postural control. Particularly in transfemoral amputees this requires complex adaptation strategies in both the prosthesis side and the non-amputated side [1] and [2]. This study explores the use of a new developed method [3] to assess the Dynamic Balance Control (DBC). Unlike previous methods using weight distribution as a measure of balance, this method determines the individual contribution of both legs to postural control during perturbations.\ud \ud 3. Statement of clinical significance\ud Assessments of the DBC may indicate the necessity for (and efficacy of) balance training and guide the prescription of prosthetic components.\ud \ud 4. Methods\ud Four unilateral transfemoral amputees were included. Subjects stood on a force platform mounted on a motion platform and were instructed to stand still. The experiment consisted of one static and three perturbation trials of 90 s each. During the static trial the platform did not move. During the (dynamic) perturbation trials, balance responses were elicited by continuous random sagital platform movements consisting of a multiple sine signal (ranging from 0.06 to 2.37 Hz). Weight distribution during the static (SW) and the dynamic perturbation trial (DW) were calculated by dividing the average vertical force below the prosthesis foot by the sum of forces below both feet. The Dynamic Balance control (DBC) represents the ratio between the stabilizing mechanism of the prosthetic leg to the stabilizing mechanism of the non-amputated leg. The stabilizing mechanism is calculated from the corrective ankle torque (assessed with inverse dynamics) in response to sway (assessed by the movement of CoM) and averaged over all the perturbation frequencies.\ud \ud 5. Results\ud All patients showed a clear asymmetric weight bearing in favor of the non-amputated leg (see Fig. 1). However the DBC ratio showed that the contribution of both legs to balance control was even more asymmetric