Design and rationale of the NetherLands registry of invasive Coronary vasomotor Function Testing (NL-CFT).

BACKGROUND: Angina without angiographic evidence of obstructive coronary artery disease (ANOCA) is a highly prevalent condition with insufficient pathophysiological knowledge and lack of evidence-based medical therapies. This affects ANOCA patients prognosis, their healthcare utilization and quality of life. In current guidelines, performing a coronary function test (CFT) is recommended to identify a specific vasomotor dysfunction endotype. The NetherLands registry of invasive Coronary vasomotor Function testing (NL-CFT) has been designed to collect data on ANOCA patients undergoing CFT in the Netherlands. METHODS: The NL-CFT is a web-based, prospective, observational registry including all consecutive ANOCA patients undergoing clinically indicated CFT in participating centers throughout the Netherlands. Data on medical history, procedural data and (patient reported) outcomes are gathered. The implementation of a common CFT protocol in all participating hospitals promotes an equal diagnostic strategy and ensures representation of the entire ANOCA population. A CFT is performed after ruling out obstructive coronary artery disease. It comprises of both acetylcholine vasoreactivity testing as well as bolus thermodilution assessment of microvascular function. Optionally, continuous thermodilution or Doppler flow measurements can be performed. Participating centers can perform research using own data, or pooled data will be made available upon specific request via a secure digital research environment, after approval of a steering committee. CONCLUSION: NL-CFT will be an important registry by enabling both observational and registry based (randomized) clinical trials in ANOCA patients undergoing CFT.

Characteristics of chest pain in COVID-19 patients in the emergency department.

INTRODUCTION: Patients with coronavirus disease 2019 (COVID-19) can present with chest pain. However, the characteristics of this chest pain are unknown. We performed a single-centre observational study to review and summarise chest pain characteristics in COVID-19 patients at first presentation to the emergency department (ED). METHODS: We collected data on characteristics of 'chest pain' reported by COVID-19 patients who attended the ED of Bernhoven Hospital, the Netherlands from 4 through 30 March 2020. RESULTS: We included 497 COVID-19 patients, of whom 83 (17%) reported chest pain upon presentation to the ED. Chest pain characteristics were: present since disease onset (88%), retrosternal location (43%), experienced as compressing/pressure pain (61%), no radiation (61%) and linked to heavy coughing (39%). Patients who reported chest pain were younger than those without chest pain (61 vs 73 years; p < 0.001). Patients with syncope were older (75 vs 72 years; p = 0.017), had a shorter duration of symptoms (5 vs 7 days; p < 0.001) and reported fewer respiratory complaints (68% vs 90%; p < 0.001) than those without syncope. Patients with new-onset atrial arrhythmias presented with a shorter duration of symptoms (5 vs 7 days; p = 0.013), experienced fewer respiratory complaints (72% vs 89%; p = 0.012) and more frequently had a history of cardiovascular disease (79% vs 50%; p = 0.003) than patients who presented without arrythmias. CONCLUSION: Chest pain and other cardiac symptoms were frequently observed in COVID-19 patients. Treating physicians should be aware that chest pain, arrhythmias and syncope can be presenting symptoms of COVID-19.

Assessing the dynamic changes in vitiligo: reliability and validity of the Vitiligo Disease Activity Score (VDAS) and Vitiligo Disease Improvement Score (VDIS).

BACKGROUND: The assessment of the individual evolution of vitiligo is important for therapeutic decision making in daily practice. A fast, simple and validated physician-reported score to assess clinical changes in depigmentation over time in separate parts (activity and improvement) is currently missing. OBJECTIVE: The main objective of the study was to develop and validate the Vitiligo Disease Activity Score (VDAS) and Vitiligo Disease Improvement Score (VDIS). METHODS: The Vitiligo Disease Activity Score (VDAS) and Vitiligo Disease Improvement Score (VDIS) were evaluated based on a photo set of 66 patients with two different time points. In the first (short) version, only the number of changing body regions was counted based on 15 predefined areas (VDAS15 and VDIS15 ), while in the second (extensive) version the degree of worsening or improvement from +4 to -4 for each body area was added for a more detailed assessment (VDAS60 and VDIS60 ). Content and construct validity were tested. In addition inter-, intrarater reliability and feasibility were evaluated by 7 (test) and 5 (retest) physicians. RESULTS: Evidence for content and construct validity was provided. Overall, VDAS15 , VDIS15 , VDAS60 and VDIS60 demonstrated good to excellent inter-rater reliability [intraclass correlation (ICC): VDAS: range = 0.797-0.900; VDIS: range = 0.726-0.798]. The intrarater reliability ICCs were 0.865 and 0.781 for the VDAS15 and VDIS15 , respectively. Similar results were obtained for the VDAS60 and VDIS60 (ICC = 0.913 and 0.800, respectively). Completion time was short (median: 122 s/patient (first round); 95 s/patient (second round)]. LIMITATIONS: Single tertiary centre mainly of skin phototype 2 to 3. CONCLUSION: The VDAS and VDIS appear to be valid, reliable and feasible instruments to score the evolution of vitiligo lesions. This accommodates the current urgent need for a simple, standardized and practical assessment of vitiligo activity and improvement over time.

Decision making in treatment of symptomatic severe aortic stenosis: a survey study in Dutch heart centres.

AIM: To provide insight into the basic characteristics of decision making in the treatment of symptomatic severe aortic stenosis (SSAS) in Dutch heart centres with specific emphasis on the evaluation of frailty, cognition, nutritional status and physical functioning/functionality in (instrumental) activities of daily living [(I)ADL]. METHODS: A questionnaire was used that is based on the European and American guidelines for SSAS treatment. The survey was administered to physicians and non-physicians in Dutch heart centres involved in the decision-making pathway for SSAS treatment. RESULTS: All 16 Dutch heart centres participated. Before a patient case is discussed by the heart team, heart centres rarely request data from the referring hospital regarding patients' functionality (n = 5), frailty scores (n = 0) and geriatric consultation (n = 1) as a standard procedure. Most heart centres 'often to always' do their own screening for frailty (n = 10), cognition/mood (n = 9), nutritional status (n = 10) and physical functioning/functionality in (I)ADL (n = 10). During heart team meetings data are 'sometimes to regularly' available regarding frailty (n = 5), cognition/mood (n = 11), nutritional status (n = 8) and physical functioning/functionality in (I)ADL (n = 10). After assessment in the outpatient clinic patient cases are re-discussed 'sometimes to regularly' in heart team meetings (n = 10). CONCLUSIONS: Dutch heart centres make an effort to evaluate frailty, cognition, nutritional status and physical functioning/functionality in (I)ADL for decision making regarding SSAS treatment. However, these patient data are not routinely requested from the referring hospital and are not always available for heart team meetings. Incorporation of these important data in a structured manner early in the decision-making process may provide additional useful information for decision making in the heart team meeting.

Measuring Activated Clotting Time during Cardiac Catheterization and PCI: The Effect of the Sampling Site.

RESULTS: In 100 patients (mean age 67.1, 65% male), no significant differences were observed in ACT values obtained from the guiding catheter and arterial sheath (mean difference (MD) -18.3 s; standard deviation (SD) 96 s; P=0.067). Contrarily, ACT values obtained from the intravenous line were significantly lower as compared to values obtained from the guiding catheter (MD 25.7 s; SD 75.5; P=0.003) and arterial sheath (MD 39 s; SD 102.8; P < 0.001). Furthermore, ACT measurements from the arterial sheath showed a statistically significant proportional bias when compared to the other sampling sites (sheath vs. catheter, r = 0.761, P=0.001; sheath vs. IVL, r = 1.013, P < 0.001). CONCLUSIONS: The present study shows statistical significance and possibly clinically relevant variations between ACT measurements from different sample sites. Bias in ACT measurements may be minimized by using uniform protocols for ACT measurement during cardiac catheterization.

2020 ESC Guidelines on acute coronary syndrome without ST-segment elevation : Recommendations and critical appraisal from the Dutch ACS and Interventional Cardiology working groups.

Recently, the European Society of Cardiology (ESC) has updated its guidelines for the management of patients with acute coronary syndrome (ACS) without ST-segment elevation. The current consensus document of the Dutch ACS working group and the Working Group of Interventional Cardiology of the Netherlands Society of Cardiology aims to put the 2020 ESC Guidelines into the Dutch perspective and to provide practical recommendations for Dutch cardiologists, focusing on antiplatelet therapy, risk assessment and criteria for invasive strategy.

Parameters of poor prognosis in preimplantation genetic testing for monogenic disorders.

STUDY QUESTION: What is the likelihood of success of a single cycle of preimplantation genetic testing for monogenic disorders (PGT-M), measured as the cumulative live birth rate (CLBR) and based on various patient demographics? SUMMARY ANSWER: For all women aged ≤40 years, the CLBR was at least 10% when the number of oocytes was ≥7 (range 10-30%) or was at least 5% when the number of oocytes was ≥3 (range 5-17%). WHAT IS KNOWN ALREADY: The number of oocytes is significantly associated with the number of embryos for genetic testing and the clinical outcome in PGT-M. Embryos diagnosed as affected or embryos that remain without diagnosis cannot be used for embryo transfer. The size of the group of embryos non-suitable for transfer varies between 25% and 81%, depending on the indication. Thus, PGT-M is more likely to be more severely impacted by suboptimal ovarian response, poor fertilization and suboptimal embryo development than conventional IVF/ICSI schemes without PGT. STUDY DESIGN, SIZE, DURATION: This was a single-centre retrospective comparative cohort study, of cycles between January 2011 and December 2015. A total number of 2265 PGT-M cycles were compared to 2833 conventional ICSI cycles. The principal aim of our study was the identification of the parameters of poor CLBR in couples undergoing PGT-M using multiplex short tandem repeat (STR) markers on blastomere biopsy DNA. The secondary aim was to compare the parameters of poor CLBR of the PGT-M population to those of couples undergoing ICSI without PGT. PARTICIPANTS/MATERIALS, SETTING, METHODS: The baseline characteristics of the PGT-M group were compared to the conventional ICSI group. A multiple regression analysis was applied to account for the following potential confounding factors: female age, number of previous ART cycles, number of oocytes/suitable embryos for transfer and dosage of gonadotrophins used for ovarian stimulation. MAIN RESULTS AND THE ROLE OF CHANCE: The PGT-M group was younger (female age 32.0 vs 34.5 years), had a higher number of previous ART cycles (1.1 vs 0.9 cycles) and used more gonadotrophins (2367 vs 1984 IU). Per cycle, the PGT-M group had more retrieved oocytes (11.8 vs 8.3 oocytes), fewer suitable embryos for transfer (1.7 vs 2.8 embryos) and a lower CLBR (29.4% vs 35.0%). Multiple regression analysis showed that the CLBR in the PGT-M group was significantly influenced by female age, the number of previous ART cycles, the number of oocytes and the dose of ovarian stimulation. In both groups, the predicted CLBR increased with increasing numbers of oocytes and suitable embryos. At least two retrieved oocytes or one embryo per single PGT-M cycle could confer an estimated CLBR above 10%. By assessing female age and the number of retrieved oocytes together, it was shown that for all women aged ≤40 years, the predicted CLBR per single PGT-M cycle was ≥10% when the number of oocytes was ≥7 or was ≥5% when the number of oocytes was ≥3. LIMITATIONS, REASONS FOR CAUTION: Despite the large sample size, the findings are confined by limited confounder adjustment and the lack of specific PGT-M comparators. WIDER IMPLICATIONS OF THE FINDINGS: This study aimed to describe the likelihood of success of PGT-M treatment, measured as CLBR, based on various patient demographics. In a PGT-M program, couples need to be informed of the prognosis more specifically when it is futile. The table of predicted CLBRs presented in this study is a useful tool in counselling PGT-M couples for making reproductive choices. STUDY FUNDING/COMPETING INTEREST(S): No funding was required and there are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

mTOR-driven glycolysis governs induction of innate immune responses by bronchial epithelial cells exposed to the bacterial component flagellin.

Human bronchial epithelial (HBE) cells play an essential role during bacterial infections of the airways by sensing pathogens and orchestrating protective immune responses. We here sought to determine which metabolic pathways are utilized by HBE cells to mount innate immune responses upon exposure to a relevant bacterial agonist. Stimulation of HBE cells by the bacterial component flagellin triggered activation of the mTOR pathway resulting in an increased glycolytic flux that sustained the secretory activity of immune mediators by HBE cells. The mTOR inhibitor rapamycin impeded glycolysis and limited flagellin-induced secretion of immune mediators. The role of the mTOR pathway was recapitulated in vivo in a mouse model of flagellin-triggered lung innate immune responses. These data demonstrate that metabolic reprogramming via the mTOR pathway modulates activation of the respiratory epithelium, identifying mTOR as a potential therapeutic target to modulate mucosal immunity in the context of bacterial infections.

Expanding the time interval between ovulation triggering and oocyte injection: does it affect the embryological and clinical outcome?

STUDY QUESTION: Is the time interval between ovulation triggering and oocyte denudation/injection associated with embryological and clinical outcome after ICSI? SUMMARY ANSWER: Expanding the time interval between ovulation triggering and oocyte denudation/injection is not associated with any clinically relevant impact on embryological or clinical outcome. WHAT IS KNOWN ALREADY: The optimal time interval between ovulation triggering and insemination/injection appears to be 38-39 h and most authors agree that an interval of >41 h has a negative influence on embryological and clinical pregnancy outcomes. However, in ART centres with a heavy workload, respecting these exact time intervals is frequently challenging. Therefore, we questioned to what extent a wider time interval between ovulation triggering and oocyte injection would affect embryological and clinical outcome in ICSI cycles. STUDY DESIGN, SIZE, DURATION: A single-centre retrospective cohort analysis was performed including 8811 ICSI cycles from 2010 until 2015. Regarding the time interval between ovulation triggering and oocyte injection, seven categories were considered: <36 h, 36 h, 37 h, 38 h, 39 h, 40 h and ≥41 h. In all cases, denudation was performed immediately prior to injection. The main outcome measures were oocyte maturation, fertilization and embryo utilization rate (embryos adequate for transfer or cryopreservation) per fertilized oocyte. Clinical pregnancy rate (CPR) and live birth rate (LBR) were considered as secondary outcomes. Utilization rate, CPR and LBR were subdivided into two groups according to the day of embryo transfer: Day 3 or Day 5. PARTICIPANTS/MATERIALS, SETTING, METHODS: During the study period, oocyte retrieval was routinely performed 36 h post-triggering except in the <36 h group. The interval of <36 h occurred only if OR was carried out before the planned 36 h trigger interval and was followed by immediate injection. Only cycles with fresh autologous gametes were included. The exclusion criteria were: injection with testicular/epididymal sperm, managed natural cycles, conventional IVF, combined conventional IVF/ICSI, preimplantation genetic testing and IVM cycles. Female age, number of oocytes, pre-preparation sperm concentration, post-preparation sperm concentration and motility, day of transfer, number of embryos transferred and quality of the best embryo transferred were identified as potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Among the seven interval groups, adjusted mean maturation rates ranged from 76.4% to 83.2% and differed significantly (P < 0.001). Similarly, there was a significant difference in adjusted mean fertilization rates (range 69.2-79.3%; P < 0.001). The adjusted maturation and fertilization rates were significantly higher when denudation/injection was performed >41 h post-triggering compared to 38 h post-triggering (reference group). Oocyte denudation/injection at <36 h post-triggering had no significant effect on maturation, fertilization or embryo utilization rates compared to injection at 38 h. No effect of the time interval was observed on CPRs and LBRs, after adjusting for potential confounders. When oocyte injection was performed before 36 h the adjusted analysis showed that compared to 38 h after ovulation triggering the chance of having a live birth tends to be lower although the difference was not statistically significant (odds ratio 0.533, 95% CI: 0.252-1.126; P = 0.099). Injection ≥41 h post-triggering did not affect LBR compared to injection at 38 h post-ovulation. LIMITATIONS, REASONS FOR CAUTION: As this is a large retrospective study, the influence of uncontrolled variables cannot be excluded. These results should not be extrapolated to other ART procedures such as IVM, conventional IVF or injection with testicular/epididymal sperm. WIDER IMPLICATIONS OF THE FINDINGS: Our results indicate that the optimal injection time window may be less stringent than previously thought as both embryological and clinical outcome parameters were not significantly affected in our analysis. This is reassuring for busy ART centres that might not always be able to follow strict time intervals. STUDY FUNDING/COMPETING INTEREST(S): No funding. The authors declare no conflict of interest related to the present study. TRIAL REGISTRATION NUMBER: N/A.

Brain areas associated with clinical and cognitive insight in psychotic disorders: A systematic review and meta-analysis.

In the past years, ample interest in brain abnormalities related to clinical and cognitive insight in psychosis has contributed several neuroimaging studies to the literature. In the current study, published findings on the neural substrates of clinical and cognitive insight in psychosis are integrated by performing a systematic review and meta-analysis. Coordinate-based meta-analyses were performed with the parametric coordinate-based meta-analysis approach, non-coordinate based meta-analyses were conducted with the metafor package in R. Papers that could not be included in the meta-analyses were systematically reviewed. Thirty-seven studies were retrieved, of which 21 studies were included in meta-analyses. Poorer clinical insight was related to smaller whole brain gray and white matter volume and gray matter volume of the frontal gyri. Cognitive insight was predominantly positively associated with structure and function of the hippocampus and ventrolateral prefrontal cortex. Impaired clinical insight is not associated with abnormalities of isolated brain regions, but with spatially diffuse global and frontal abnormalities suggesting it might rely on a range of cognitive and self-evaluative processes. Cognitive insight is associated with specific areas and appears to rely more on retrieving and integrating self-related information.

Preimplantation genetic testing with HLA matching: from counseling to birth and beyond.

Preimplantation genetic testing-human leukocyte antigen '(PGT-HLA) only' refers to the HLA typing of single or few cells biopsied from in vitro fertilized preimplantation embryos. The aim of the procedure is to establish a pregnancy, in which the fetus is HLA compatible with an affected sibling in need of a hematopoietic stem cell transplantation (HSCT). During PGT-M-HLA, the identification of a HLA-compatible embryo is combined with the detection of mutation(s) underlying immunodeficiencies and hemoglobinopathies. We report a combined retrospective and prospective cohort analysis of PGT-(M-)HLA procedures carried out from 1998 until 2017, with follow-up of transplantations to 2019. During the study period, 234 couples from 22 countries were invited for a multidisciplinary consultation. Two couples were rejected and 70 couples declined (various reasons), leaving 162 couples for which 414 clinical cycles were carried out. Cleavage stage biopsy followed by single-cell multiplex PCR for short tandem repeat-based haplotyping was applied in most cases (98.7%). The diagnostic efficiency was high (94.8%) but only 16.5% of the embryos was genetically suitable for transfer. Fresh and frozen-thawed embryo transfer resulted in 67 clinical pregnancies, 63 deliveries, and 74 live births, of which 60 children were HLA compatible. This yielded a live birth delivery rate of 30.3% per transfer. Information on neonatal characteristics of the matching PGT-(M-)HLA children showed reassuring outcomes. So far, HSCT was carried out successfully for 25 out of 26 cases. In conclusion, our data show that PGT-(M-)HLA is a valuable procedure: the high complexity and limited delivery rate are balanced by the successful HSCT outcome and the positive impact on families.

Factors influencing the clinical outcome of preimplantation genetic testing for polycystic kidney disease.

STUDY QUESTION: What are the factors influencing the success rate for couples undergoing preimplantation genetic testing (PGT) for polycystic kidney disease (PKD)? SUMMARY ANSWER: In our study cohort, the live birth delivery rate is significantly associated with female age while the male infertility accompanying autosomal dominant PKD (ADPKD) does not substantially affect the clinical outcome. WHAT IS KNOWN ALREADY: While women with ADPKD have no specific fertility problems, male ADPKD patients may present with reproductive system abnormalities and infertility. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study involves 91 PGT cycles for PKD for 43 couples (33 couples for PKD1, 2 couples for PKD2 and 8 couples for autosomal recessive PKD (ARPKD)) from January 2005 until December 2016 with follow-up of transfers until end of 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sixteen single-cell clinical tests for PKD based on multiplex PCR of short tandem repeat markers, with or without a specific mutation were developed and applied for diagnosis of 584 Day 3 cleavage stage embryos. In 18 couples, the male partner was affected with ADPKD (=Group A) and 12 of them had a documented infertility status. Group A underwent 52 cycles to oocyte retrieval. For 18 other couples, the female partner was affected with ADPKD (=Group B) and four male partners from this group had a documented history of infertility. This group underwent 31 cycles to OR. MAIN RESULTS AND THE ROLE OF CHANCE: Genetic analysis resulted in 545 embryos (93.3%) with a diagnosis, of which 215 (36.8%) were genetically transferable. Transfer of 74 embryos in 53 fresh cycles and of 34 cryopreserved embryos in 33 frozen-warmed embryo transfer cycles resulted in a live birth delivery rate of 38.4% per transfer with 31 singleton live births, two twin live births and one ongoing pregnancy. The observed cumulative delivery rate was 57.8% per couple after five treatment cycles. Thirty cryopreserved embryos still remain available for transfer. The clinical pregnancy rate per transfer (fresh + frozen; 45.9% in group A versus 60.0% in group B, P < 0.05) and the live birth delivery rate per transfer (fresh + frozen; 27.0% in group A versus 42.9% in group B, P < 0.05) was significantly lower for couples with the male partner affected with ADPKD compared with couples with the female partner affected with ADPKD. However, a multivariate logistic regression analysis showed that only female age was associated with live birth delivery rate (odds ratio = 0.87; 95% CI: 0.77-0.99; P = 0.032). LIMITATIONS, REASONS FOR CAUTION: This study is based on retrospective data from a single centre with Day 3 one-cell and two-cell biopsy. Further analysis of a larger cohort of PKD patients undergoing PGT is required to determine the impact of male infertility associated with ADPKD on the cumulative results. WIDER IMPLICATIONS OF THE FINDINGS: Knowledge about factors affecting the clinical outcome after PGT can be a valuable tool for physicians to counsel PKD patients about their reproductive options. Males affected with ADPKD who suffer from infertility should be advised to seek treatment in time to improve their chances of conceiving a child. STUDY FUNDING/COMPETING INTEREST(S): No funding was obtained. There are no competing interests to declare. TRIAL REGISTRATION NUMBER: Not applicable.

Social cognitive group treatment for impaired insight in psychosis: A multicenter randomized controlled trial.

PURPOSE: The majority of people with schizophrenia has impaired insight, which is related to a poorer outcome. In this study, we evaluate a new psychosocial intervention 'REFLEX' aimed at improving insight in people with schizophrenia. REFLEX focuses on targeting stigma-sensitivity, perspective taking and self-reflection in people with schizophrenia and low insight. Primary objective is to improve insight and subsequently to improve functional outcome and symptoms. METHOD: A total of 121 people diagnosed with schizophrenia according to DSM IV criteria with impaired insight was included in 2012-2015 from seven sites in a multicenter randomized controlled trial. REFLEX was compared to an active control condition consisting of group-wise simplified cognitive remediation training. Primary outcome of the study were the preconditions of insight: internalized stigma, self-reflection, mental flexibility and perspective taking. Clinical insight and cognitive insight were secondary outcomes. RESULTS: Although perspective taking, self-reflection, mental flexibility and stigma sensitivity remained unchanged after the intervention, results showed a significant improvement of clinical insight in both conditions directly after treatment (SAI-E Rater, p < .001, PANSS G12, p < .005) and at follow-up (SAI-E Rater, p < .01, SAI-E interview, p < .001, PANSS G12, p < .0001). Improvement of clinical insight directly after treatment was larger in the REFLEX condition (SAI-E Rater, p < .05). Other outcomes (self-esteem, quality of life and depression) remained unchanged. CONCLUSION: Though insight improved in both conditions, REFLEX was not superior to simplified drill-and-practice cognitive remediation training. Nevertheless, this study indicates that structured interventions can significantly improve insight. Further research on the underlying mechanisms of both conditions is needed, as insight is unlikely to improve spontaneously in chronic patients.

The development of hospital-based palliative care services in public hospitals in the Western Cape, South Africa.

With the recent approval of a South African (SA) National Policy Framework and Strategy for Palliative Care by the National Health Council, it is pertinent to reflect on initiatives to develop palliative care services in public hospitals. This article reviews the development of hospital-based palliative care services in the Western Cape, SA. Palliative care services in SA started in the non-governmental sector in the 1980s. The first SA hospital-based palliative care team was established in Charlotte Maxeke Johannesburg Academic Hospital in 2001. The awareness of the benefit of palliative care in the hospital setting led to the development of isolated pockets of excellence providing palliative care in the public health sector in SA. This article describes models for palliative care at tertiary, provincial and district hospital level, which could inform development of hospital-based palliative care as the national policy for palliative care is implemented in SA.

[Geriatric rehabilitation care: Doing the right things right]. / Geriatrische Revalidatiezorg: De juiste dingen goed doen.

BACKGROUND: Geriatric rehabilitation concerns short-term integrated multidisciplinary care aimed at functional recovery and social participation for relatively frail elderly. Given the geriatric clients' complex care issues, nurses should possess sufficient and appropriate competencies in order to identify and assess the relevant symptoms and intervene effectively. Yet, nurses experience a certain apprehensiveness to perform their tasks and express difficulties in multidisciplinary communication and collaboration in a constructive manner. In addition to the client's and informal care giver's perception of their input in the geriatric rehabilitation process, this study provides an in-depth understanding of the way nurses perceive their role in geriatric rehabilitation. METHODS/DESIGN: This descriptive study entails a quantitative and a qualitative component. The quantitative component concerns questionnaires for clients, informal care givers, nurses, and team leaders. The qualitative component aims to obtain in-depth information (i. e. opinions, meanings, and reflections) with regard to the decision making process and the performance of the rehabilitation care by means of open-ended questions (in the questionnaire) and semi-structured interviews. RESULTS: Clients and informal care givers rate specific themes in geriatric rehabilitation in a more negative light than nurses and team leaders do. These themes concern the provision of information in the hospital (prior to admission in the rehabilitation facility), involvement in the draw-up of the treatment plan and rehabilitation goals, geriatric rehabilitation as a 24/7 activity, and taking into account the client's other life events. The latter three findings in particular, are caused by nurses' apprehensiveness to perform their tasks adequately. DISCUSSION: Nurses working in geriatric rehabilitation, experience apprehensiveness to perform their tasks adequately. Uncertainty about the client's reaction or fear of damaging the relationship of trust, results in nurses not involving the clients and informal care givers in the draw-up of the rehabilitation goals. Apprehensiveness also submerges as the lack of experience or specific competences in considering the client's other life events. The recommendations address these aspects in particular.

Effectiveness of Africa's tropical protected areas for maintaining forest cover.

The effectiveness of parks for forest conservation is widely debated in Africa, where increasing human pressure, insufficient funding, and lack of management capacity frequently place significant demands on forests. Tropical forests house a substantial portion of the world's remaining biodiversity and are heavily affected by anthropogenic activity. We analyzed park effectiveness at the individual (224 parks) and national (23 countries) level across Africa by comparing the extent of forest loss (as a proxy for deforestation) inside parks to matched unprotected control sites. Although significant geographical variation existed among parks, the majority of African parks had significantly less forest loss within their boundaries (e.g., Mahale Park had 34 times less forest loss within its boundary) than control sites. Accessibility was a significant driver of forest loss. Relatively inaccessible areas had a higher probability (odds ratio >1, p < 0.001) of forest loss but only in ineffective parks, and relatively accessible areas had a higher probability of forest loss but only in effective parks. Smaller parks less effectively prevented forest loss inside park boundaries than larger parks (T = -2.32, p < 0.05), and older parks less effectively prevented forest loss inside park boundaries than younger parks (F2,154 = -4.11, p < 0.001). Our analyses, the first individual and national assessment of park effectiveness across Africa, demonstrated the complexity of factors (such as geographical variation, accessibility, and park size and age) influencing the ability of a park to curb forest loss within its boundaries.

General, but not myeloid or type II lung epithelial cell, myeloid differentiation factor 88 deficiency abrogates house dust mite induced allergic lung inflammation.

Asthma is a highly prevalent chronic allergic inflammatory disease of the airways affecting people worldwide. House dust mite (HDM) is the most common allergen implicated in human allergic asthma. HDM-induced allergic responses are thought to depend upon activation of pathways involving Toll-like receptors and their adaptor protein myeloid differentiation factor 88 (MyD88). We sought here to determine the role of MyD88 in myeloid and type II lung epithelial cells in the development of asthma-like allergic disease using a mouse model. Repeated exposure to HDM caused allergic responses in control mice characterized by influx of eosinophils into the bronchoalveolar space and lung tissue, lung pathology and mucus production and protein leak into bronchoalveolar lavage fluid. All these responses were abrogated in mice with a general deficiency of MyD88 but unaltered in mice with MyD88 deficiency, specifically in myeloid or type II lung epithelial cells. We conclude that cells other than myeloid or type II lung epithelial cells are responsible for MyD88-dependent HDM-induced allergic airway inflammation.

A novel approach to detect test-seeking behaviour in the blood donor population: making the invisible visible.

BACKGROUND AND OBJECTIVES: Individuals may donate blood in order to determine their infection status after exposure to an increased infection risk. Such test-seeking behaviour decreases transfusion safety. Instances of test seeking are difficult to substantiate as donors are unlikely to admit to such behaviour. However, manifestation in a population of repeat donors may be determined using statistical inference. MATERIALS AND METHODS: Test-seeking donors would be highly motivated to donate following infection risk, influencing the timing of their donation. Donation intervals within 2005-2014 of all Dutch blood donors who acquired syphilis (N = 50), HIV (N = 13), HTLV (N = 4) or HCV (N = 2) were compared to donation intervals of uninfected blood donors (N = 7 327 836) using the Anderson-Darling test. We adjusted for length bias as well as for age, gender and donation type of the infected. Additionally, the power of the proposed method was investigated by simulation. RESULTS: Among the Dutch donors who acquired infection, we found only a non-significant overrepresentation of short donation intervals (P = 0·54). However, we show by simulation that both relatively short and long donation intervals among infected donors can reveal test seeking. The power of the method is >90% if among 69 infected donors >35 (51%) are test seeking, or if among 320 infected donors >90 (30%) are test seeking. CONCLUSION: We show how statistical analysis may be used to reveal the extent of test seeking in repeat blood donor populations. In the Dutch setting, indications for test-seeking behaviour were not statistically significant. This may, however, be due to the low number of infected individuals.

[Functional remission of people with serious mental illness (SMI): psychometric properties of a new ROM-instrument]. / Functionele remissie bij mensen met een ernstige psychiatrische aandoening; psychometrische eigenschappen van een nieuw ROM-instrument.

BACKGROUND: Instruments are used for routine outcome monitoring of patients with severe mental illness in order to measure psychiatric symptoms, care needs and quality of life. By adding an instrument for measuring functional remission a more complete picture can be given of the complaints, the symptoms and general functioning, which can give direction to providing care for patients with severe mental illness. AIM: To describe the development and testing of a new instrument of functional remission (FR) among people with a psychotic disorder or another serious mental disorder (SMI) as an addition to the symptomatic remission (SR), according to international criteria. METHOD: The FR-assessment involves assessment by a mental health professional who conducts a semi-structured interview with the patient and his or her family and/or uses patient files relating to the three areas of functioning: daily living and self-care; work, study and housekeeping; and social contacts. These areas are rated on a three-point scale of 0: independent; 1: partially independent; 2: dependent. The assessment covers a period of six months, in accordance with the measurement of symptomatic remission and should be part of regular routine outcome monitoring (ROM) procedures. The FR-instrument was used in 2012 with 840 patients from eight Dutch mental care institutions and included a one-year follow-up among 523 patients (response 62%). RESULTS: The results showed that the instrument is relatively easily to complete. It was also relevant for clinical practice, although further research is needed because of the raters' low response. Intra- and inter-rater reliability, discriminating and convergent validity, and sensitivity to change were rated sufficient to good. CONCLUSION: If the FR-instrument becomes part of regular ROM-procedures and is used as a measure of societal participation, it could be a useful addition to current measures of symptomatic remission.

Deposition of the spermatozoon in the human oocyte at ICSI: impact on oocyte survival, fertilization and blastocyst formation.

PURPOSE: To evaluate whether the deposition of the spermatozoon in the human oocyte at ICSI has any effect on oocyte survival, fertilization, blastocyst development and quality. METHODS: In a prospective study, including 78 ICSI cycles, sibling oocytes were injected with "no intention" (group A, standard ICSI, n = 393) or "intention" to deposit the spermatozoon under the cortex (group B, n = 354). Outcome parameters were oocyte survival and fertilization, as well as blastocyst formation and quality. RESULTS: Depositing the sperm under the cortex of the oocyte was not always successful for its final position, therefore, group B was divided into three subgroups: B1 successful deposition (119 oocytes, 33.6 % of oocytes in group B); B2 initially successful but spermatozoon spontaneously relocated after 2 min (136 oocytes, 38.4 %); and B3 unsuccessful deposition (99 oocytes, 28.0 %). Group A and B were compared on an intention-to-treat basis. Additionally, A, B1, B2 and B3 were also compared. The oocyte survival and fertilization, blastocyst and top-quality blastocyst developmental rates were not significantly different. CONCLUSIONS: The procedure of depositing the spermatozoon intentionally under the oocyte cortex demanded high technical skills. Successful positioning was only obtained in 34 % of the attempts. We obtained no evidence of improved oocyte survival and fertilization, blastocyst formation and quality when the spermatozoon was permanently positioned under the oocyte cortex. Taken together, depositing the spermatozoon under the oocyte cortex is not recommended for routine ICSI application.