Batch vs. continuous direct compression - a comparison of material processability and final tablet quality.

In this study, an in-depth comparison was made between batch and continuous direct compression using similar compression set-ups. The overall material processability and final tablet quality were compared and evaluated. Correlations between material properties, process parameters and final tablet properties were made via multivariate data analyses. In total, 10 low-dosed (1% w/w) and 10 high-dosed (40% w/w) formulations were processed, using a total of 10 different fillers/filler combinations. The trials indicated that the impact of filler type, drug load or process settings was similar for batch and continuous direct compression. The main differentiator between batch and continuous was the flow dynamics in the operating system, where properties related to flow, compressibility and permeability played a crucial role. The less consistent flow throughout a batch process resulted in a significantly higher variability within the tablet press (σCF) and for the tablet quality responses (σMass, σTS). However, the better controlled blending procedure prior to batch processing was reflected in a more consistent API concentration variability. Overall, the comparison showed the benefits of selecting appropriate excipients and process settings to achieve a specific outcome, keeping in mind some key differentiators between both processes.

Characterization of the long-term effects of lethal total body irradiation followed by bone marrow transplantation on the brain of C57BL/6 mice.

PURPOSE: Total body irradiation (TBI) followed by bone marrow transplantation (BMT) is used in pre-clinical research to generate mouse chimeras that allow to study the function of a protein specifically on immune cells. Adverse consequences of irradiation on the juvenile body and brain are well described and include general fatigue, neuroinflammation, neurodegeneration and cognitive impairment. Yet, the long-term consequences of TBI/BMT performed on healthy adult mice have been poorly investigated. MATERIAL AND METHODS: We developed a robust protocol to achieve near complete bone marrow replacement in mice using 2x550cGy TBI and evaluated the impact of the procedure on their general health, mood disturbances, memory, brain atrophy, neurogenesis, neuroinflammation and blood-brain barrier (BBB) permeability 2 and/or 16 months post-BMT. RESULTS: We found a persistent decrease in weight along with long-term impact on locomotion after TBI and BMT. Although the TBI/BMT procedure did not lead to anxiety- or depressive-like behavior 2- or 16-months post-BMT, long-term spatial memory of the irradiated mice was impaired. We also observed radiation-induced impaired neurogenesis and cortical microglia activation 2 months post-BMT. Moreover, higher levels of hippocampal IgG in aged BMT mice suggest an enhanced age-related increase in BBB permeability that could potentially contribute to the observed memory deficit. CONCLUSIONS: Overall health of the mice did not seem to be majorly impacted by TBI followed by BMT during adulthood. Yet, TBI-induced alterations in the brain and behavior could lead to erroneous conclusions on the function of a protein on immune cells when comparing mouse chimeras with different genetic backgrounds that might display altered susceptibility to radiation-induced damage. Ultimately, the BMT model we here present could also be used to study the related long-term consequences of TBI and BMT seen in patients.

Effect of viewing distance on object responses in macaque areas 45B, F5a and F5p.

To perform tasks like grasping, the brain has to process visual object information so that the grip aperture can be adjusted before touching the object. Previous studies have demonstrated that the posterior subsector of the Anterior Intraparietal area is connected to area 45B, and its anterior counterpart to F5a. However, the role of area 45B and F5a in visually-guided grasping is poorly understood. Here, we investigated the role of area 45B, F5a and F5p in object processing during visually-guided grasping in two monkeys. We tested whether the presentation of an object in near peripersonal space activated F5p neurons more than objects with the same retinal size presented beyond reachable distance and conversely, whether neurons in 45B and F5a-which may encode a purely visual object representation-were less affected by viewing distance when equalizing retinal size. Contrary to our expectations, we found that most neurons in area 45B were object- and viewing distance-selective, and preferred mostly Near presentations. Area F5a showed much weaker object selectivity compared to 45B, with a similar preference for objects presented at the Near position. Finally, F5p neurons were less object selective and frequently Far-preferring. In sum, area 45B-but not F5p- prefers objects presented in peripersonal space.

Mental health among the Moroccan population during SARS-CoV-2 outbreak: MAROCOVID study.

BACKGROUND: The SARS-CoV-2 pandemic's unpredictability and ambiguity, combined with the lockdown, social distancing, containment measures, and economic impact could increase the risk of mental health issues. OBJECTIVE: To assess the magnitude of mental health outcomes and risk factors among Moroccans, using an online survey, during the SARS-CoV-2 outbreak. METHODS: This cross-sectional, survey-based study collected demographic data and mental health measurements from 11,123 participants. The degree of depression, anxiety, and insomnia symptoms were assessed by the 9-item Patient Health Questionnaire, the 7-items Generalized Anxiety disorder, and the 7-items Insomnia Severity Index. RESULTS: The survey was completed by 11,123 individuals out of a total of 15,008 contacts. 7315 (65.8%) were women, and 7182 (64.6%) were aged 18 to 34. A significant proportion of respondents experienced depression (5894 [53%]), anxiety (5544 [49.8%]), and insomnia (4410 [39.6%]). Multivariable logistic regression analysis showed that being a woman, being married, and being a parent of children aged less than five years were associated with severe symptoms of depression and anxiety (e.g. severe depression among women vs. men (OR, 1.19; 95%CI, 1.06-1.33; P = .003), severe depression among married compared to unmarried respondents (OR, 1.92; 95%CI, 1.71-2.16; P < .000), e.g. severe anxiety among women vs. men (OR, 1.40; 95%CI, 1.24-1.58; <0.000), severe anxiety among married people compared to unmarried (OR, 1.14; 95%CI, 1.00-1.28; P < .003). CONCLUSION: Our findings reported a significant mental health burden on the general public during the COVID-19 lockdown. In addition to efforts deployed to prevent the spread of the disease, timely and culturally-specific mental health care needs to be developed urgently.

An interprofessional model of care for oral health during pregnancy.

The study aim was to appraise the relevance and appropriateness of an interprofessional prenatal oral care model among pregnant women and healthcare providers in British Columbia (BC), Canada. Audio-recorded semi-structured interviews with 39 purposefully selected participants (13 pregnant women and 26 healthcare professionals) were used qualitatively to appraise relevance of an existing model. The existing model emphasizes communication and collaboration among multiple health providers for the delivery of integrated prenatal oral care. All interviews were transcribed verbatim and analyzed using an inductive thematic approach and N-Vivo® software. During the first round of interviews, most participants considered the existing model as simple and well-defined but not fully relevant to the BC context. The participants suggested revisions to Steven's model to incorporate facilitators of integrated care, including interprofessional education, oral health funding, and advocacy for oral healthcare. Participants suggested a different graphical portrayal for the revised model; an implementation guide was also suggested. A revised model based on participants' feedback, was shared with 14 of the initial participants during secondary interviews. Further evaluation of the appropriateness of the revised model is warranted.

Pregnant women's perspectives on integrating preventive oral health in prenatal care.

BACKGROUND: Oral diseases are considered a silent epidemic including among pregnant women. Given the prevalence of oral conditions among pregnant women and the reported association with adverse pregnancy outcomes, there have been suggestions for the inclusion of preventive oral care in routine prenatal care. However, due to the different administrative and funding structure for oral health and prenatal care in Canada, progress towards this integration has been slow. Our study sought to qualitatively explore the views of pregnant women in British Columbia (BC) on the strategies for integrating preventive oral health care into prenatal care services. METHODS: A qualitative approach was utilized involving semi-structured interviews with fourteen (14) purposefully selected pregnant women in Vancouver and Surrey, BC. The interviews were audio-recorded and transcribed. The transcripts were analyzed using an inductive thematic approach. Study validity was ensured via memoing, field-notes, and member checking. RESULTS: Interviews ranged from 28 to 65 min producing over 140 pages of transcripts. Analysis resulted in three major themes: oral health experiences during pregnancy, perspectives on integration and integrated prenatal oral care, and strategies for addressing prenatal oral health care. A majority of participants were supportive of integrating preventive oral care in routine prenatal services, with referrals identified as a critical strategy. Oral health education was recognized as important before, during, and after pregnancy; oral health assessments should therefore be included in the prenatal care checklist. Limited funding was acknowledged as a barrier to oral health care access, which may explain why few participants visited their dentists during pregnancy. Interprofessional education surfaced as a bridge to provide prenatal oral health education. CONCLUSION: Pregnant women interviewed in this study support the inclusion of educational and preventive oral care during prenatal care, although their views differed on how such inclusion can be achieved in BC. They advocated the establishment of a referral system as an acceptable strategy for providing integrated prenatal oral health care.

The Causal Role of Three Frontal Cortical Areas in Grasping.

Efficient object grasping requires the continuous control of arm and hand movements based on visual information. Previous studies have identified a network of parietal and frontal areas that is crucial for the visual control of prehension movements. Electrical microstimulation of 3D shape-selective clusters in AIP during functional magnetic resonance imaging activates areas F5a and 45B, suggesting that these frontal areas may represent important downstream areas for object processing during grasping, but the role of area F5a and 45B in grasping is unknown. To assess their causal role in the frontal grasping network, we reversibly inactivated 45B, F5a, and F5p during visually guided grasping in macaque monkeys. First, we recorded single neuron activity in 45B, F5a, and F5p to identify sites with object responses during grasping. Then, we injected muscimol or saline to measure the grasping deficit induced by the temporary disruption of each of these three nodes in the grasping network. The inactivation of all three areas resulted in a significant increase in the grasping time in both animals, with the strongest effect observed in area F5p. These results not only confirm a clear involvement of F5p, but also indicate causal contributions of area F5a and 45B in visually guided object grasping.

A Qualitative Study of Health Care Providers' Views on Integrating Oral Health into Prenatal Care.

OBJECTIVE: Providing preventive oral health during prenatal care is a recognized strategy for improving pregnant women's access to oral health care. This study sought to qualitatively explore the views of health care providers in British Columbia (BC), Canada, on strategies for integrating preventive oral health into prenatal care. METHODS: Twenty-four purposefully selected health care providers (13 oral health and 11 prenatal care providers) in Vancouver and Surrey BC participated in audio-recorded semistructured interviews. Interviews lasted from 31 to 61 min, were transcribed verbatim, and were analyzed using an inductive thematic analysis with N-Vivo software. Study validity was ensured via memoing, fieldnotes, member checking, and external audit. RESULTS: Thematic analysis revealed 5 major themes: perception of integrated care, relevance of integrated prenatal oral health, strategies for achieving integrated prenatal oral health, drivers of the integration process, and barriers to integrating oral health during pregnancy. Interprofessional collaboration based on information sharing and communication was identified as a critical factor for integrated care. Oral health checks should be a component of prenatal assessments for achieving integrated prenatal oral health. Participants recommended that prenatal providers should offer oral health education and use screening questions to identify the pregnant woman's oral health needs. The establishment of referral systems was advocated, while dental assessments and oral prophylaxis via the medical services plan were proposed. The inclusion of dental providers in prenatal teams and educating health care providers on interprofessional collaboration were also supported. CONCLUSION: Oral health and prenatal providers in BC are positively disposed to adopting integrated preventive prenatal oral health care based on interprofessional collaborative practices. The inclusion of oral health providers in prenatal teams was suggested. KNOWLEDGE TRANSFER STATEMENT: The results of this study can be used by policymakers for advocacy and decision making when planning care delivery programs for women during pregnancy. Including the suggested strategies could lead to increased access to, and utilization of, oral health services among pregnant women.

Modelling thermodynamic feedback on the metabolism of hydrogenotrophic methanogens.

The magnitude of the Gibbs free energy change of the substrate transformation that supports the growth of a microbe is decreased when the concentrations of the substrates are decreased and when the concentrations of the products of metabolism are increased. Microbes require a supply of ATP for cell maintenance and growth, and coupling the transformation of substrates to products with the formation of ATP also decreases the magnitude of the Gibbs free energy change. Here we include these three thermodynamic controllers (substrate and product concentration, and ATP formation) in a model of substrate transformation by hydrogenotrophic methanogens that results in a number of realistic behaviours. First, a threshold for substrate use emerges, below which the methanogen cannot metabolise its substrate. Under this model, microbes that capture more of the Gibbs free energy change from substrate transformation in the form of ATP have greater thresholds for their substrate, in line with observations of actual microbes. Second, an apparent saturation constant emerges that is controlled by the thermodynamics of the reaction. This increases with increasing ATP synthesis per substrate, so that methanogens that conserve more ATP grow faster at higher substrate concentrations, but are less competitive at low substrate concentrations. As a result, simply changing the ATP yield (moles of ATP per mole of substrate) results in methanogens with differing ecological strategies through thermodynamic impacts on their metabolism. Third, end-product inhibition through thermodynamic feedback can limit the growth of microbes, and those that capture more ATP per substrate are limited by smaller product concentrations than those that capture less ATP.

Temporal fermentation and microbial community dynamics in rumens of sheep grazing a ryegrass-based pasture offered either in the morning or in the afternoon.

Eight ruminally-fistulated wethers were used to examine the temporal effects of afternoon (PM; 1600h) v. morning (AM; 0800 h) allocation of fresh spring herbage from a perennial ryegrass (Lolium perenne L.)-based pasture on fermentation and microbial community dynamics. Herbage chemical composition was minimally affected by time of allocation, but daily mean ammonia concentrations were greater for the PM group. The 24-h pattern of ruminal fermentation (i.e. time of sampling relative to time of allocation), however, varied considerably for all fermentation variables (P⩽0.001). Most notably amongst ruminal fermentation characteristics, ammonia concentrations showed a substantial temporal variation; concentrations of ammonia were 1.7-, 2.0- and 2.2-fold greater in rumens of PM wethers at 4, 6 and 8h after allocation, respectively, compared with AM wethers. The relative abundances of archaeal and ciliate protozoal taxa were similar across allocation groups. In contrast, the relative abundances of members of the rumen bacterial community, like Prevotella 1 (P=0.04), Bacteroidales RF16 group (P=0.005) and Fibrobacter spp. (P=0.008) were greater for the AM group, whereas the relative abundance of Kandleria spp. was greater (P=0.04) for the PM group. Of these taxa, only Prevotella 1 (P=0.04) and Kandleria (P<0.001) showed a significant interaction between time of allocation and time of sampling relative to feed allocation. Relative abundances of Prevotella 1 were greater at 2h (P=0.05), 4h (P=0.003) and 6h (P=0.01) after AM allocation of new herbage, whereas relative abundances of Kandleria were greater at 2h (P=0.003) and 4h (P<0.001) after PM allocation. The early post-allocation rise in ammonia concentrations in PM rumens occurred simultaneously with sharp increases in the relative abundance of Kandleria spp. and with a decline in the relative abundance of Prevotella. All measures of fermentation and most microbial community composition data showed highly dynamic changes in concentrations and genus abundances, respectively, with substantial temporal changes occurring within the first 8h of allocating a new strip of herbage. The dynamic changes in the relative abundances of certain bacterial groups, in synchrony with a substantial diurnal variation in ammonia concentrations, has potential effects on the efficiency by which N is utilised by the grazing ruminant.

Association between use of antidepressants or benzodiazepines and the risk of subsequent fracture among those aged 65+ in the Netherlands.

This is the first study to examine the association between antidepressant and benzodiazepine use following a MOF and risk of subsequent fracture in those 65+. Using national data, drug use following MOF showed that the 1-year fully adjusted risk of subsequent MOF in those on antidepressants was more than doubled. INTRODUCTION: We evaluated the association between the use of antidepressants or benzodiazepines and the risk of a subsequent major osteoporotic fracture. METHODS: A cohort study was performed using the Dutch PHARMO Database Network. Between 2002 and 2011, a total of 4854 patients sustained a first major osteoporotic fracture after the age of 65 years, of which 1766 sustained a hip fracture. Incidence rates and adjusted hazard ratios were calculated using Cox proportional hazards models. RESULTS: Within 1 year following a major osteoporotic fracture, 15% (95% CI 13.7-15.7) and 31% (95% CI 30.1-32.8) of patients were dispensed an antidepressant or benzodiazepine, respectively. Current use of antidepressants in the first year following a major osteoporotic fracture was associated with subsequent fracture (adjusted HR 2.17 (95% CI 1.37-3.43)). Recent and past use of antidepressants were also associated with an increased risk of subsequent fracture. When the complete follow-up period was included, only the current use of antidepressants was associated with subsequent fracture following a major osteoporotic fracture (adjusted HR 1.48; 95% CI 1.06-2.06). Current benzodiazepine use was not associated with an increased risk of fracture within 1 year following a major osteoporotic fracture (adjusted HR 1.18; 95% CI 0.76-1.81) or during the complete follow-up period (adjusted HR 1.18; 95% CI 0.90-1.55). CONCLUSION: This study provides evidence that antidepressants should be used with caution following a major osteoporotic fracture. It provides needed insights that can be used to inform clinicians when assessing subsequent fracture risk in patients.

Long-term outcomes of a Malone antegrade continence enema (MACE) for the treatment of fecal incontinence or constipation in adults.

PURPOSE: The aim of the study was to assess the long-term outcome of a Malone antegrade continence enema (MACE) procedure for fecal incontinence or constipation in adults. METHODS: This retrospective single-center study assessed the long-term outcome and quality of life (QoL) of patients who underwent a MACE procedure between 2005 and 2014 at the Maastricht University Medical Centre. Success rate was quantified by using Malone's continence scale. Quality of life was assessed by validated questionnaires covering general quality of life (SF-36 and Karnofsky scale), current pain level (visual analog scale), fecal incontinence (Vaizey incontinence survey), or constipation (Cleveland Clinic Constipation Score). RESULTS: Based on patients' records, 22 out of 30 patients (73%; 95% CI 54-87%) were still using their MACE. Mean follow-up was 43 months (SD 25.9) since time of surgery. According to the Malone continence scale, the overall success rate was 37% (95% CI 20.0-53.3). Nine patients developed a postoperative complication. Eighteen out of 22 patients (13 with constipation and 5 with fecal incontinence) returned the QoL questionnaires (82% response rate). Long-term quality of life of patients with a MACE did not differ from the general Dutch population. CONCLUSIONS: In our cohort of patients with fecal incontinence or constipation, MACE resulted in a disappointed overall success rate of 37%. However, it may be indicated in patients who do not prefer more invasive surgical procedures or a definite stoma. The success and morbidity rate should be thoroughly discussed with the patients preoperatively.

Behavioral outcomes of a novel, pelvic nerve damage rat model of fecal incontinence.

BACKGROUND: Fecal incontinence (FI) has a multifactorial pathophysiology with a severe social impact. The most common cause for FI is pudendal nerve damage, which mostly occurs in women during or after labor. A better understanding of the pathophysiology is required to optimize treatment of FI. In this study, we evaluate the use of a novel pelvic nerve damage rat model of FI. METHODS: This new model simulates the forces on the pelvic floor during labor by prolonged transvaginal, retro-uterine intrapelvic balloon distention in female rats. Number of fecal pellets produced per day and defecation pattern was compared between the experimental and control group for 2 weeks. The cages of the rats were divided in food, nesting and latrine areas to evaluate changes in defecation pattern. The FI Index (FII) was calculated to assess the ratio of fecal pellets between the non-latrine areas and the total number of pellets. A higher score represents more random distribution of feces outside the latrine area. RESULTS: Total number of fecal pellets was higher in the experimental group as compared with the controls. In both groups most fecal pellets were deposited in the nesting area, which is closest to the food area. The experimental group deposited more fecal pellets in the latrine area and had a lower FII indicating less random distribution of feces outside the latrine area. CONCLUSION: Transvaginal, retro-uterine intrapelvic balloon distention is a safe and feasible animal model simulating the human physiologic impact of labor by downwards pressure on the pelvic floor.

Long-term outcome of intractable constipation treated by sacral neuromodulation: a comparison between children and adults.

AIM: Sacral neuromodulation (SNM) is a minimally invasive therapy for functional constipation (FC) and is most often used to treat adults. Recent studies suggest that SNM may also beneficial in children. However, comparative data regarding preferred age of SNM for FC are lacking. Therefore, long-term results of SNM for FC were compared between children and adults. METHOD: All patients treated with SNM for FC between 2004 and 2015 were evaluated. Outcomes of children (age 10-18 years) were compared with those for adults (≥ 18 years). The primary end-point was a defaecation frequency of three or more times per week, which is consistent with the ROME-III criteria. Secondary outcomes were quality of life (QoL; SF-36) and the Cleveland Clinic Constipation Score. RESULTS: One hundred and eighty patients (45 children, 135 adults) were eligible for SNM. The mean age was 15.8 (children) and 41.4 years (adults). One hundred and twenty-six patients received permanent SNM (38 children, 88 adults). Mean follow-up was 47 months in both groups. Defaecation frequency increased in both groups after SNM compared with baseline. Defaecation frequency in adults was higher than in children. The increased defaecation frequency was maintained during the entire follow-up period in both groups. QoL of children was impaired compared with the Dutch population with regard to bodily pain, general health and vitality. Adults had worse QoL with regard to physical functioning, bodily pain, general health, vitality and social functioning compared with the Dutch population. QoL of children did not differ from adults. CONCLUSION: Sacral neuromodulation (SNM) should be considered in children (< 18 years) with FC. However, the indication of SNM for FC remains debatable considering the limited improvements and high costs.

Perioperative management of antiplatelet treatment in patients undergoing isolated coronary artery bypass grafting in Dutch cardiothoracic centres.

BACKGROUND: International guidelines do not provide uniform recommendations regarding the use of antiplatelet treatment in the perioperative period in patients undergoing coronary artery bypass grafting (CABG). METHODS: A questionnaire was sent to all 16 cardiothoracic centres in the Netherlands to determine which antiplatelet treatment is used in the perioperative setting. Furthermore, a single-centre prospective observational cohort study was performed which included all patients undergoing isolated CABG in July 2014. RESULTS: Eleven centres responded to the survey. Acetylsalicylic acid monotherapy was discontinued before surgery in 6 centres. In patients with an acute coronary syndrome receiving dual antiplatelet therapy (DAPT), most centres discontinued the P2Y12 inhibitor preoperatively. DAPT was restarted after surgery in 4 centres. However, 6 centres continued DAPT in patients who had undergone coronary stenting within one month of surgery. In patients with coronary stents, variation in the management of antiplatelet therapy increased in proportion to the interval between stenting and surgery. A total of 70 patients were included in the registry. Acetylsalicylic acid monotherapy was discontinued in 51% of patients and restarted in all patients. P2Y12 inhibitor treatment was discontinued before surgery in 70% of patients and re-initiated after CABG in 29%. CONCLUSIONS: Major differences were observed in the preoperative and postoperative management of antiplatelet treatment between different Dutch cardiothoracic centres and within a single centre. Part of this variation is probably due to lack of evidence and differences between the current guidelines; however, many of the strategies were not in accordance with any of these guidelines.

Impact of detection bias on the risk of gastrointestinal cancer and its subsites in type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) may be a risk factor for gastrointestinal (GI) cancers, but variations in study designs of observational studies may have yielded biased results due to detection bias. Furthermore, differences in risk for GI cancer subsites have not been extensively evaluated. We aimed to determine the risk of GI cancer and its subsites in patients with T2DM and how it is affected by detection bias. METHODS: A matched cohort study was performed using the NCR-PHARMO database. New-users of ≥1 non-insulin anti-diabetic drug during 1998-2011 were matched with non-diabetic controls by year of birth, sex, and time between database entry and index. Cox regression analyses were performed with and without lag-period to estimate hazard ratios (HRs) for GI cancer and its subsites. Covariables included age, sex, use of other drugs and history of hospitalisation. RESULTS: An increased risk of GI cancer was observed in T2DM patients (HR 1.5, 95% confidence interval [CI] 1.3-1.7) compared with controls, which was attenuated in the 1-year lagged analysis (HR 1.4, 95% CI 1.2-1.7). Stratified by subsite, statistically significant increased risks of pancreatic (HR 4.7, 95% CI 3.1-7.2), extrahepatic bile duct (HR 4.2, 95% CI 1.5-11.8) and distal colon cancer (HR 1.5, 95% CI 1.1-2.1) were found, which remained statistically significantly increased in the lagged analysis. CONCLUSIONS: T2DM patients had a 40% increased risk of GI cancer. Increased GI cancer risks tended to be weaker when reducing detection bias by applying a 1-year lag-period. Future observational studies should therefore include sensitivity analyses in which this bias is minimised.

Does percutaneous coronary stent implantation increase platelet reactivity?

High platelet reactivity (PR) values on treatment with clopidogrel are associated with an increased rate of thrombotic events after a percutaneous coronary intervention (PCI). However, we do not know the optimal timing of the performance of the PR measurements. Platelets might be activated during a PCI, which means that the timing of PR measurements, before or after PCI, could influence the outcome. In turn, this could lead to misinterpretation of the patient's response to antiplatelet therapy and a less accurate prediction of the patient's risk of thrombotic events during follow-up. We aimed to evaluate the effect of stent implantation on PR in patients with and without acute coronary syndromes who undergo PCI to assess the optimal timing of PR measurements. A systematic literature search was performed and the results are summarized in this review.

The effect of correcting VerifyNow P2Y12 assay results for hematocrit in patients undergoing percutaneous coronary interventions.

Essentials Platelet reactivity is correlated with thrombotic risk after percutaneous coronary intervention (PCI). Hematocrit (HCT) is associated with platelet reactivity as measured with the VerifyNow P2Y12 assay. We tested a formula proposed to correct VerifyNow measurements for HCT in 978 PCI patients. Correcting platelet reactivity for HCT did not improve the prediction of thrombotic events after PCI. SUMMARY: Background High on-treatment platelet reactivity is predictive for the occurrence of atherothrombotic events following percutaneous coronary interventions (PCIs). A low hematocrit (HCT) value is associated with higher platelet reactivity values, expressed in P2Y12 reaction units (PRU), as measured with the VerifyNow P2Y12 assay. However, it is suggested that this is only an in vitro phenomenon. Objective To determine whether adjusting PRU for HCT improves the predictive value for thrombotic events following PCI. Material and methods The VerifyNow P2Y12 assay was performed in clopidogrel-treated patients undergoing non-urgent PCI included in a prospective cohort study. PRU values were corrected for HCT with a formula proposed in recent literature. Receiver operating characteristic (ROC) curves were made to determine the optimal cut-off values to predict the occurrence of the primary endpoint, a composite of all-cause death and non-fatal myocardial infarction, stent thrombosis and ischemic stroke, during 1 year of follow-up. The chi-squared test was performed to determine whether correcting PRU for HCT improved the prediction of the primary endpoint. Results A total of 978 patients were analyzed. A negative correlation between PRU and HCT was observed (R2 = 0.104). The optimal cut-off value for the corrected PRU was 215. ROC analyses showed that prediction of the primary endpoint did not differ for the corrected PRU (area under the curve, 0.61; sensitivity, 0.57; specificity, 0.64) and the uncorrected PRU (area under the curve, 0.61; sensitivity, 0.69; specificity, 0.53). Conclusion Correcting PRU for HCT does not improve the prediction of thrombotic events following PCI.

Treatment of cefuroxime-induced neurotoxicity with continuous venovenous haemofiltration.

A 61-year-old woman with decreased consciousness, myoclonus, tremors, nystagmus and bradypnoea, due to cefuroxime-induced neurotoxicity, was admitted to the intensive care unit. Continuous venovenous haemofiltration (CVVH) rapidly reduced plasma cefuroxime concentrations and improved neurological manifestations within the next few hours. Retrospective pharmacokinetic assessment showed a total cefuroxime clearance of 166 ml/min during the CVVH.

Spontaneous haemoperitoneum in pregnancy and endometriosis: a case series.

OBJECTIVE: To report pregnancy outcomes of SHiP (spontaneous haemoperitoneum in pregnancy) and the association with endometriosis. DESIGN: Retrospective case note review. SETTING: Dutch referral hospitals for endometriosis. SAMPLE: Eleven women presenting with 15 events of SHiP. METHODS: In collaboration with the Dutch Working Group on Endometriosis, unpublished cases of SHiP that occurred in the Netherlands between 2010 and 2015 were retrieved. MAIN OUTCOME MEASURES: Maternal and perinatal mortality and morbidity. RESULTS: SHiP occurred predominantly in the second and third trimester of pregnancy. The earliest and major presenting symptom was an acute onset of abdominal pain, often combined with low haemoglobin levels or signs of fetal distress. Imaging was a diagnostic tool when free peritoneal fluid could be observed. For surgical treatment of the bleeding site, a midline laparotomy was mostly needed, the median estimated amount of blood loss was 2000 mL. No fetomaternal or perinatal mortality was reported, despite a high rate of preterm births (54.5%). In all women, endometriosis was diagnosed at a certain moment in time and therefore was probably involved in the pathogenesis of SHiP. Four women showed recurrence of SHiP. In one of these cases the second event of SHiP occurred in a subsequent pregnancy. CONCLUSION: Pregnancy outcomes of SHiP are improving when compared with previous reports, with absent fetomaternal and perinatal mortality in this recent series. Growing knowledge and adequate multidisciplinary intervention may have contributed to these favourable results. Increasing awareness of this serious complication of pregnancy is advocated, especially in women diagnosed with endometriosis. TWEETABLE ABSTRACT: Growing awareness of SHiP is advocated, especially in women diagnosed with endometriosis.