Efficacy and safety of camrelizumab combined with TACE for hepatocellular carcinoma: a systematic review and meta-analysis.

OBJECTIVE: Hepatocellular carcinoma (HCC) represents a highly lethal and recurrent neoplasm, with limited effective treatment regimens available. Camrelizumab, as a novel PD1 inhibitor combined with transcatheter arterial chemoembolization (TACE), has been widely used in the treatment of HCC. However, there remains a contentious debate regarding the clinical value of the TACE and camrelizumab combination. This study seeks to investigate the efficacy and safety of this combination treatment regimen in patients with HCC. MATERIALS AND METHODS: The related studies were retrieved from four online databases, including Pubmed, Cochrane Library, EMBASE, and Web of Science, up to June 1, 2023. The selection of studies was based on screening of titles, abstracts, and full-texts. The primary efficacy outcomes included complete response (CR), objective response rate (ORR), and disease control rate (DCR), while safety outcomes evaluated all treatment-related adverse events (AEs). Additionally, secondary outcomes such as overall (OS) and progression-free survival (PFS) were extracted for further survival analysis. The quality of the included trials was assessed using the MINORS tool. Publication bias was evaluated through funnel plot and Egger's test. RESULTS: A total of 17 publications involving 1,377 cases were included. The pooled CR rate, ORR, and DCR of the patients treated with TACE plus camrelizumab had a pooled CR rate of 8% (95% CI: 0.01-0.15, p=0.03), ORR of 47% (95% CI: 0.42-0.52, p<0.00001) and DCR of 82% (95% CI: 0.77-0.88, p<0.00001), respectively. Compared with a control group that did not receive TACE or camrelizumab, the pooled RR of CR rate, ORR, and DCR were 1.61 (95% CI: 1.27-2.04, p<0.0001), 1.56 (95% CI: 1.19-2.05, p=0.001) and 1.55 (95% CI: 1.19-2.03, p=0.001), respectively. Besides, the combination regimen can prolong the OS (HR=2.60, 95% CI: 2.25-3.02, p<0.00001) and PFS (HR=4.90, 95% CI: 1.94-12.38, p=0.0008). However, the incidence of treatment-related AEs was relatively high (77%), with 29% for grade 3 AEs. The most common AEs observed were pain (47%), fever (46%), hepatic function abnormalities (44%), hypoalbuminemia (39%), and hypertension (37%). The combination treatment did not increase the incidence of AEs compared to the control group, except for the hand-foot skin reaction (RR=0.85, 0.74-0.97, p=0.01), hepatic encephalopathy (RR=4.29, 2.51-7.35, p<0.00001) and nausea (RR=1.35, 1.13-1.61, p=0.001). CONCLUSIONS: Combination therapy of TACE plus camrelizumab has shown notable clinical benefits, improved survival, and a manageable safety profile in patients with HCC, but it is essential to monitor and manage the specific toxicities, especially for the camrelizumab-related AEs.

Efficacy and safety of PD1/PDL1 inhibitors combined with radiotherapy and antiangiogenic drugs for hepatocellular carcinoma: a systematic review and meta-analysis.

OBJECTIVE: The triplet regimen based on the programmed cell death 1 (PD1)/ programmed cell death ligand 1 (PDL1) inhibitors combined radiotherapy and antiangiogenic drugs is a novel therapeutic strategy for hepatocellular carcinoma. We conducted a meta-analysis to evaluate the efficacy and safety of the triplet therapeutic regimen in the treatment of hepatocellular carcinoma. MATERIALS AND METHODS: We searched scientific literature databases and clinical trial databases through October 31, 2022, for required studies. The pooled hazard ratio (HR) was used to analyze the overall survival (OS), progression-free survival (PFS), and the pooled relative risk (RR) was used to analyze the objective response rate (ORR), disease control rate (DCR), mortality rate (MR), and adverse events (AEs) through random or fixed effects model, 95% confidence interval (CI) was determined for all outcomes. Qualities of the included literature were assessed by MINORS Critical appraisal checklist. Funnel plot was used to assess publication bias in the included studies. RESULTS: Five studies (3 single-arm and 2 non-randomized comparative trials), including 358 cases, were enrolled. Meta-analysis showed that the pooled ORR, DCR, and MR were 51% (95% CI: 34%-68%), 86% (95% CI: 69-102%), and 38% (95% CI: 18-59%), respectively. Compared with triplet regimen, the single or dual-combination treatments had shorter OS (HR=0.53, 95%: 0.34-0.83 via univariate analysis; HR=0.49, 95%: 0.31-0.78 via multivariable analysis) and PFS (HR=0.52, 95%: 0.35-0.77 via univariate analysis; HR=0.54, 95%: 0.36-0.80 via multivariable analysis). Common AEs to triplet regimens included skin reaction (17%), nausea/vomiting (27%), fatigue (23%), while severe AEs (10%), fever (18%), diarrhea (15%), and hypertension (5%) without statistically significant differences. CONCLUSIONS: In the treatment of hepatocellular carcinoma, PD1/PDL1 inhibitors combined radiotherapy and antiangiogenic drugs achieved better survival benefits than alone or dual-combination regimens. In addition, the triple-combination therapy has tolerable safety.

Capacity of Trolox to improve the development and quality of metabolically compromised bovine oocytes and embryos invitro during different windows of development.

Trials to improve oocyte developmental competence under metabolic stress by using antioxidants may start before or after oocyte maturation. In the present conceptual study, we aimed to identify the most efficient timing of antioxidant application in relation to a metabolic insult using a bovine invitro embryo production model. Pathophysiological concentrations of palmitic acid (PA) were used to induce metabolic stress during oocyte maturation or embryo development. Trolox (TR; antioxidant) treatment prior to, during or after the PA insult was tested to evaluate the protective, neutralising and rescuing capacity of TR respectively. Changes in embryo developmental competence, mitochondrial activity, reactive oxygen species (ROS) concentrations, blastocyst cell allocation and apoptosis and cell stress-related gene expression were monitored. The improvement in developmental capacity was most obvious when oocytes were preloaded with TR before the PA insult. This protective effect could be explained by the observed combination of increased mitochondrial activity with reduced ROS production. This resulted in blastocysts with normal cell counts and apoptosis, as well as increased nuclear factor erythroid 2-related factor 2 (NRF2) expression (a marker for redox regulatory processes) and normalised the expression of the mitochondrial transcription factor A (TFAM), a marker of mitochondrial biogenesis. These results indicate that 'pretreatment' of oocytes with antioxidants produces embryos that seem to be more resilient to a metabolic stress insult.

Comparison of PR, QRS, and QT interval measurements by seven ECG interpretation programs.

BACKGROUND: Electrocardiograph-generated measurements of PR, QRS, and QT intervals are generally thought to be more precise than manual measurements on paper records. However, the performance of different programs has not been well compared. METHODS: Routinely obtained digital electrocardiograms (ECGs), including over 500 pediatric ECGs, were used to create over 2000 10 s analog ECGs that were replayed through seven commercially available electrocardiographs. The measurements for PR interval, QRS duration, and QT interval made by each program were extracted and compared against each other (using the median of the programs after correction for program bias) and the population mean values. RESULTS: Small but significant systematic biases were seen between programs. The smallest and largest variation from the population mean differed by 4.7 ms for PR intervals, 5.8 ms for QRS duration, and 12.4 ms for QT intervals. In pairwise comparison programs showed similar accuracy for most ECGs, with the average absolute errors at the 75th percentile for PR intervals being 4-6 ms from the median, QRS duration 4-8 ms, and QT interval 6-10 ms. However, substantial differences were present in the numbers and extent of large, clinically significant errors (e.g at the 98th percentile), for which programs differed by a factor of two for absolute errors, as well as differences in the mix of overestimations and underestimations. CONCLUSIONS: When reading digital ECGs, users should be aware that small systematic differences exist between programs and that there may be large clinically important errors in difficult cases.

Performance of seven ECG interpretation programs in identifying arrhythmia and acute cardiovascular syndrome.

BACKGROUND: No direct comparison of current electrocardiogram (ECG) interpretation programs exists. OBJECTIVE: Assess the accuracy of ECG interpretation programs in detecting abnormal rhythms and flagging for priority review records with alterations secondary to acute coronary syndrome (ACS). METHODS: More than 2,000 digital ECGs from hospitals and databases in Europe, USA, and Australia, were obtained from consecutive adult and pediatric patients and converted to 10 s analog samples that were replayed on seven electrocardiographs and classified by the manufacturers' interpretation programs. We assessed ability to distinguish sinus rhythm from non-sinus rhythm, identify atrial fibrillation/flutter and other abnormal rhythms, and accuracy in flagging results for priority review. If all seven programs' interpretation statements did not agree, cases were reviewed by experienced cardiologists. RESULTS: All programs could distinguish well between sinus and non-sinus rhythms and could identify atrial fibrillation/flutter or other abnormal rhythms. However, false-positive rates varied from 2.1% to 5.5% for non-sinus rhythm, from 0.7% to 4.4% for atrial fibrillation/flutter, and from 1.5% to 3.0% for other abnormal rhythms. False-negative rates varied from 12.0% to 7.5%, 9.9% to 2.7%, and 55.9% to 30.5%, respectively. Flagging of ACS varied by a factor of 2.5 between programs. Physicians flagged more ECGs for prompt review, but also showed variance of around a factor of 2. False-negative values differed between programs by a factor of 2 but was high for all (>50%). Agreement between programs and majority reviewer decisions was 46-62%. CONCLUSIONS: Automatic interpretations of rhythms and ACS differ between programs. Healthcare institutions should not rely on ECG software "critical result" flags alone to decide the ACS workflow.

DUSP facilitates RPMI8226 myeloma cell aging and inhibited TLR4 expression.

OBJECTIVE: Myeloma severely threatens public health, and molecular targeting treatment becomes the future perspective. Dual specificity phosphatases (DSUP) protein has multiple functions including modulating cell proliferation, differentiation, aging, and apoptosis. Whether DUSP can regulate myeloma cell is unclear. This study thus aimed to investigate the effect of DUSP on myeloma cell line RPMI8226 cell aging and provide evidence for the clinical treatment of myeloma. MATERIALS AND METHODS: H2O2-induced aging model of myeloma cell line RPMI8226 was generated. DUSP over-expression plasmid or specific siRNA was transfected by liposome. Western blot was used to detect the expression of DUSP in RPMI8226 cells. Cell aging condition was evaluated by ß-galactosidase assay. Aging proteins P53 and P16 expression levels, the activation of TLR4 signal pathway were tested by immunoblotting. TLR4 signal pathway was then suppressed by Verteporfin for testing RPMI8226 cell aging. RESULTS: Growing levels of DUSP, aging proteins P53 and P16, with inhibition of TLR4 signal pathway were found in the H2O2-induced aging model of myeloma cell line RPMI8226. Transfection of DUSP over-expression plasmid or siRNA potentiated or inhibited the aging of RPMI8226 cells induced by H2O2 and suppressed or enhanced TLR4 signal pathway, respectively. Verteporfin, an inhibitor of TLR4, increased the level of P53 and aging of RPMI8226 cells. CONCLUSIONS: DUSP facilitates H2O2-induced aging of myeloma cell line RPMI8226 and suppresses TLR4 expression, which provides academic basis for clinical intervention.

Differential effects of high and low glucose concentrations during lipolysis-like conditions on bovine in vitro oocyte quality, metabolism and subsequent embryo development.

Lipolytic metabolic conditions are traditionally associated with elevated non-esterified fatty acid (NEFA) concentrations, but may also be accompanied by hyperglycaemia in obesity or by hypoglycaemia during a negative energy balance status. Elevated NEFA concentrations disrupt oocyte and embryo development and quality, but little is known about whether the effects of lipolytic conditions on oocyte developmental competence are modulated by glucose availability. To answer this, bovine cumulus-oocyte complexes (COCs) were matured under different conditions: physiological NEFA (72µM) and normal glucose (5.5mM), pathophysiologically high NEFA (420µM) and normal glucose, high NEFA and high glucose (9.9mM), high NEFA and low glucose (2.8mM). Developmental potential, cumulus expansion and metabolism of COCs exposed to high NEFA and low glucose were affected to a greater extent compared with COCs matured under high NEFA and high glucose conditions. High NEFA and high glucose conditions caused a moderate increase in oocyte reactive oxygen species compared with their high NEFA and low glucose or control counterparts. Blastocyst metabolism and the transcriptome of metabolic and oxidative stress-related genes were not affected. However, both lipolytic conditions associated with hyper- or hypoglycaemia led to surviving embryos of reduced quality with regards to apoptosis and blastomere allocation.

Progesterone Alters Kynurenine Pathway Activation in IFN-γ-Activated Macrophages - Relevance for Neuroinflammatory Diseases.

We have previously demonstrated that the kynurenine pathway (KP), the major biochemical pathway for tryptophan metabolism, is dysregulated in many inflammatory disorders that are often associated with sexual dimorphisms. We aimed to identify a potential functional interaction between the KP and gonadal hormones. We have treated primary human macrophages with progesterone in the presence and absence of inflammatory cytokine interferon-gamma (interferon-γ) that is known to be a potent inducer of regulating the KP enzyme. We found that progesterone attenuates interferon-γ-induced KP activity, decreases the levels of the excitotoxin quinolinic acid, and increases the neuroprotective kynurenic acid levels. We also showed that progesterone was able to reduce the inflammatory marker neopterin. These results may shed light on the gender disparity in response to inflammation.

Kynurenines, Gender and Neuroinflammation; Showcase Schizophrenia.

Schizophrenia has a clear sexual dimorphism in age of onset and progression. The underlying mechanisms of this dimorphism are not known, but may be found in the interactions of sex hormones with the tryptophan catabolising kynurenine pathway. Schizophrenia is associated with general inflammation and disruption of glutamatergic and dopaminergic signalling. Metabolites of the kynurenine pathway have been shown to be immunomodulatory and have effects on glutamatergic and dopaminergic signalling. This review discusses the currently available literature on sex hormones and their effect on the kynurenine pathway in the context of the glutamatergic, dopaminergic and immunological features of schizophrenia.

The effect of a negative energy balance status on ß-carotene availability in serum and follicular fluid of nonlactating dairy cows.

Maternal metabolic pressure due to a cow's negative energy balance (NEB) has a negative effect on oocyte quality as a result of increased oxidative stress. In this study, we hypothesized that a NEB status may negatively affect the availability of ß-carotene (bC, an antioxidant) in the micro-environment of the oocyte or follicular fluid (FF) and that daily bC supplementation can increase bC availability. We aimed to (1) determine the effect of a nutritionally induced NEB on bC concentrations in serum and FF as well as on the presence of bC metabolites, oxidative stress levels, and follicular growth in a nonlactating dairy cow model, and (2) investigate how this effect could be altered by dietary bC supplementation. Six multiparous nonlactating Holstein Friesian cows were subjected to 4 consecutive dietary treatments, 28 d each: (1) 1.2 × maintenance (M) or positive energy balance (PEB) without bC supplement (PEB-bC), (2) 1.2 × M with daily supplement of 2,000mg of bC comparable to the level of bC intake at grazing (PEB+bC), (3) 0.6 × M with 2,000mg of bC (NEB+bC), and (4) 0.6 × M (NEB-bC). At the end of each treatment, estrous cycles were synchronized and blood and FF of the largest follicle were sampled and analyzed for bC, retinol, α-tocopherol, free fatty acids, estradiol, and progesterone. Serum cholesterol, triglycerides, urea, insulin growth factor 1, growth hormone, total antioxidant status (TAS), and red blood cell glutathione (GSH) concentrations were determined as well. All cows lost body weight during both energy restriction periods and showed increased serum free fatty acid concentrations, illustrating a NEB. A dietary induced NEB reduced FF bC, but not plasma bC or plasma and FF retinol concentrations. However, bC and retinol concentrations drastically increased in both fluid compartments after bC supplementation. Follicular diameter was increased in supplemented PEB cows. Energy restriction reduced the TAS and red blood cell GSH, whereas daily bC supplementation could restore GSH concentrations, but not the TAS, to levels present in healthy PEB cows. In conclusion, daily bC supplementation can substantially improve bC and retinol availability in the oocyte's micro-environment, irrespective of the energy balance, which may affect follicular development and oocyte quality in the presence of maternal metabolic stress. This knowledge can be of importance to optimize nutritional strategies in the dairy industry to feed for optimal oocyte quality and fertility.

Systematic analysis to identify a key role of CDK1 in mediating gene interaction networks in cervical cancer development.

OBJECTIVE: This study aims to identify corresponding differentially expressed genes in cervical cancer by comparing gene expression profiles between normal and cervical cancer samples. METHOD: To identify differentially expressed genes in cervical cancer, two groups of Affymetrix microarray data available online were analyzed. One group consisted of 43 carcinomatous cervical epithelial cell samples, and the other was composed of 17 healthy cervical epithelial cell samples, both from the Amerindian. R packages-GO.db, KEGG.db and KEGGREST were used to detect GO categories and KEGG pathways with significant overrepresentation in differentially expressed genes comparing with the whole genome. Cytoscape was utilized to construct biological networks. RESULTS: By comparing gene expression profile of normal and cervical cancer samples, 122 differentially expressed genes were identified including 46 up-regulated genes and 76 down-regulated genes. Using the identified differentially expressed genes, a large and a small biological network was constructed. In addition, 402 GO biological processes and 9 KEGG pathways were over-represented. Top significant biological processes included cell cycle and cell proliferation. Moreover, top significant KEGG pathways were oocyte meiosis, cell cycle and progesterone-mediated oocyte maturation. Most importantly, CDK1 frequently appeared in these processes and pathways, which indicated its significant role in the progression of cervical cancer. CONCLUSION: CDK1 plays a comprehensive role in mediating genetic networks implicated in the progression of cervical cancer. Novel therapeutics targeting CDK1 or its related pathways might help improve prognosis of advanced stage cervical cancer.

Effects of sugammadex on incidence of postoperative residual neuromuscular blockade: a randomized, controlled study.

BACKGROUND: This study aimed to investigate whether reversal of rocuronium-induced neuromuscular blockade with sugammadex reduced the incidence of residual blockade and facilitated operating room discharge readiness. METHODS: Adult patients undergoing abdominal surgery received rocuronium, followed by randomized allocation to sugammadex (2 or 4 mg kg(-1)) or usual care (neostigmine/glycopyrrolate, dosing per usual care practice) for reversal of neuromuscular blockade. Timing of reversal agent administration was based on the providers' clinical judgement. Primary endpoint was the presence of residual neuromuscular blockade at PACU admission, defined as a train-of-four (TOF) ratio <0.9, using TOF-Watch® SX. Key secondary endpoint was time between reversal agent administration and operating room discharge-readiness; analysed with analysis of covariance. RESULTS: Of 154 patients randomized, 150 had a TOF value measured at PACU entry. Zero out of 74 sugammadex patients and 33 out of 76 (43.4%) usual care patients had TOF-Watch SX-assessed residual neuromuscular blockade at PACU admission (odds ratio 0.0, 95% CI [0-0.06], P<0.0001). Of these 33 usual care patients, 2 also had clinical evidence of partial paralysis. Time between reversal agent administration and operating room discharge-readiness was shorter for sugammadex vs usual care (14.7 vs. 18.6 min respectively; P=0.02). CONCLUSIONS: After abdominal surgery, sugammadex reversal eliminated residual neuromuscular blockade in the PACU, and shortened the time from start of study medication administration to the time the patient was ready for discharge from the operating room. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov:NCT01479764.

Knowledge, use and attitude toward eHealth among patients with chronic lung diseases.

BACKGROUND: Despite high expectations and numerous initiatives in the area of eHealth, implementation and use of eHealth applications on a national level is no common practice yet. There is no full understanding of patients' attitude on eHealth yet. Aim of this study is to gain insight into the level of knowledge and experiences with eHealth of people with chronic lung diseases. METHOD: A telephone survey among 400 people with a medical diagnosis of asthma or COPD was conducted. All patients participated in the larger research program National Panel of people with Chronic diseases or Disabilities (NPCD) conducted by NIVEL. RESULTS: Eight percent of the asthma and COPD patients knew of the term eHealth. Knowledge of specific eHealth applications (e.g. electronic medical record, electronic consultations, monitoring from a distance) was higher and ranged from 21 to 88%. Most available applications were used by less than 20% of the patients, although figures differ by age and educational level. People who have used applications were in general rather positive about their use. Non-users did not see clear advantages of using eHealth applications. A majority thought that eHealth decreases human contact in health care and will not contribute to a higher quality of care. On the contrary, almost half of the patients considered eHealth as a possibility to take more responsibility in their own care. Asthma and COPD patients were unanimous that the use of eHealth should always be a free choice. CONCLUSION: Although most asthma and COPD patient know of one or more eHealth applications, actual use remains low. Patients who do have experience with the use of eHealth are on the whole positive. However, patients without experience have no clear ideas about the advantages. They should be convinced first, and stressing the possibilities for more personal control might be an important argument to persuade them.

Dietary fat supplementation and the consequences for oocyte and embryo quality: hype or significant benefit for dairy cow reproduction?

In many countries, fat supplementation in the diet has become common in the dairy industry. There are several ideas as to how dietary fat could influence reproductive performance. Saturated fatty acids, such as palm oil, can increase milk yield but may aggravate negative energy balance and thus may impair fertility when fed during the first week post-partum. However, priming the lipid oxidation in the liver by feeding saturated fats during the dry period has recently been shown to be a potentially promising strategy to mitigate fat mobilization and liver accumulation post-partum. Furthermore, polyunsaturated fats (omega-3 fatty acids and conjugated linoleic acids) are fed to reduce the 'de novo' fat synthesis in the udder and thus the milk fat content, which may be of modest benefit for overall energy balance. Furthermore, omega-6 and omega-3 polyunsaturated fatty acids are reported to alter follicular growth, steroid synthesis and prostaglandin metabolism in the ovary and endometrium, respectively. Omega-6 fatty acids are believed to have pro-inflammatory and thus PGF2α-stimulating properties rendering them extra value as 'nutraceutical' early post-partum, while omega-3 fatty acids can weaken this inflammatory potency, leading to a higher chance of survival of the embryo when supplemented during the periconceptual period. Unfortunately, research results rarely provide a consensus in this perspective. The consequences of these fat-feeding strategies on oocyte and embryo quality remain an intriguing issue for debate. Fat feeding may alter the microenvironment of the growing and maturing oocyte of the early and older embryo and thus may affect reproductive outcome. We recently reported that dietary-induced hyperlipidaemic conditions can be harmful for embryo development and metabolism. However, to date, research results remain somewhat conflicting most probably due to differences in fat sources used, in diet and duration of supplementation and in experimental set-up in general.

The development of quality indicators for community pharmacy care.

AIMS: To develop a national system of quality indicators for community pharmacy care, reported by community pharmacies. METHODS: After preliminary validation, an online consensus study was conducted. Pharmacy practice experts (round 1) and practising pharmacists (round 2) were approached. Face-validity scores for risk of harm and quality of care were obtained, as well as data on feasibility and clarity. To field test the data collection a random sample of 30 community pharmacies reported on the indicators, and were visited by a healthcare inspector to discuss practical and interpretation issues. RESULTS: After preliminary validation of 159 topics, 53 indicators were rated in round 1 by 14 of the 16 experts who were approached. The resulting 48 indicators were rated by 76 pharmacists of the 150 pharmacists who were approached (response 50%). Of the 48 indicators in the second round, 33 (69%) were rated face valid (median relevance score ≥ 7) for risk of harm to patients, while 43 (90%) were rated face valid for quality of care. In the field test the participating pharmacies reported on the resulting set of 44 indicators. This resulted in an adjusted set of 42 indicators. The set contains indicators on patient counselling (6), clinical risk management (10), compounding (7), dispensing (3), monitoring of medication use (11) and quality management (5). CONCLUSIONS: A set of 42 quality indicators was developed for community pharmacy care. It is expected that this will have a positive impact on quality and safety of community pharmacy care in the Netherlands.

[Frontal syndrome resulting from an intracerebral amyloidoma]. / Frontaal syndroom door een intracerebraal amyloïdoom.

A 51-year-old woman suffering an epileptic seizure came to the emergency unit. A ct scan showed a mass lesion in the right frontal lobe. The psychiatric examination indicated a frontal syndrome with severe cognitive impairment. A stereotactical biopsy was carried out. Histopathology produced an unusual diagnosis, namely an intracerebral amyloidoma. By reviewing the literature on intracerebral amyloidoma we were able to compare the psychiatric symptoms of published cases with those of this case.

Risky procedures by nurses in hospitals: problems and (contemplated) refusals of orders by physicians, and views of physicians and nurses.

Occurrence of problems with, refusals of orders and contemplated refusals of orders for risky procedures by nurses in Dutch hospitals and views on the safety of performance was studied using postal questionnaires (600 physicians and 3200 nurses, response 60-71%). Of the respondents, 11-30% experienced problems with and (contemplated) refusals of orders for risky procedures in the previous 12 months. Gynaecologists and internists most frequently mentioned problems concerning the practical performance of the procedure (44% and 30%, respectively). The reason for a problem or a contemplated refusal most frequently given by nurses was that they disagreed with the medication policy (34% and 35%, respectively). The reason for a refusal most frequently given by the gynaecologists, internists and nurses was that the nurses themselves were of the opinion that they did not have the necessary authorisation (95%, 67%, and 62%, respectively). With regard to certain procedures, the views of professionals are more strict than the current legal regulations.

Risky procedures by nurses in hospitals: problems and (contemplated) refusals of orders by physicians, and views of physicians and nurses: a questionnaire survey.

Occurrence of problems with, refusals of orders and contemplated refusals of orders for risky procedures by nurses in Dutch hospitals and views on the safety of performance was studied using postal questionnaires (600 physicians and 3200 nurses, response 60--71%). Of the respondents, 11--30% experienced problems with and (contemplated) refusals of orders for risky procedures in the previous 12 months. Gynaecologists and internists most frequently mentioned problems concerning the practical performance of the procedure (44% and 30%, respectively). The reason for a problem or a contemplated refusal most frequently given by nurses was that they disagreed with the medication policy (34% and 35%, respectively). The reason for a refusal most frequently given by the gynaecologists, internists, and nurses was that the nurses themselves were of the opinion that they did not have the necessary authorisation (95%, 67%, and 62%, respectively). With regard to certain procedures, the views of professionals are more strict than the current legal regulations.