Q94 is not a selective modulator of proteinase-activated receptor 1 (PAR1) in platelets.

Thrombin is a potent platelet activator, acting through proteinase-activated receptors -1 and -4 (PAR1 and PAR4). Of these, PAR-1 is activated more rapidly and by lower thrombin concentrations. Consequently, PAR-1 has been extensively investigated as a target for anti-platelet drugs to prevent myocardial infarction. Q94 has been reported to act as an allosteric modulator of PAR1, potently and selectively inhibiting PAR1-Gαq coupling in multiple cell lines, but its effects on human platelet activation have not been previously studied. Platelet Ca2+ signaling, integrin αIIbß3 activation and α-granule secretion were monitored following stimulation by a PAR1-activating peptide (PAR1-AP). Although Q94 inhibited these responses, its potency was low compared to other PAR1 antagonists. In addition, αIIbß3 activation and α-granule secretion in response to other platelet activators were also inhibited with similar potency. Finally, in endothelial cells, Q94 did not inhibit PAR1-dependent Ca2+ signaling. Our data suggest that Q94 may have PAR1-independent off-target effects in platelets, precluding its use as a selective PAR1 allosteric modulator.

Aspiring to establish a family: Reproductive health among young unmarried women in Abidjan, Côte d'Ivoire.

In Abidjan, Côte d'Ivoire, young women navigate a complicated transition from adolescence to adult life. In an evolving context, young women are expected to succeed in education and the economy, while negotiating the social pressure to start families and prove womanhood by becoming mothers. In this project, we closely followed twenty young adult unmarried women who desire to find a life partner or have a child soon. The study sought to understand women's experiences and reproductive health needs using a variety of methods, including daily diary keeping, in-depth interviews, focus groups and interactive exercises. Research indicated that young adult women who aspire to establish a family must navigate conflicting pressures, making it challenging for them to identify and act on their own fertility needs. Women who use family planning prioritise their future fertility and navigate complex social dynamics while selecting a method. The study builds on existing literature and contributes additional insight into the nuanced family planning needs and experiences of single women who aspire to establish a family, particularly around fertility desires, the use of calendar methods, and economic and social empowerment.

Pathways to Modern Family Planning: A Longitudinal Study on Social Influence among Men and Women in Benin.

Despite improvements in family planning (FP) knowledge and services in West Africa, unmet need for FP continues to grow. Many programs apply a demographically and biologically driven definition of unmet need, overlooking the complex social environment in which fertility and FP decisions are made. This longitudinal, qualitative cohort study captures the changing nature of FP need, attitudes and behaviors, taking into account life context to inform understanding of the complex behavior change process. Purposively sampled, 25 women and 25 men participated in three rounds of in-depth interviews over 18 months. Analyses used a social network influence lens. Findings suggest alignment of six foundational building blocks operating at individual, couple, services, and social levels is essential to meet FP need. If one block is weak, a person may not achieve met need. Women and men commonly follow five pathways as they seek to fulfill their FP need. Some pathways achieve met need (determined users, quick converters), some do not (side effect avoiders), and some do not lead to consistent FP outcomes (male-priority decision makers, gender-egalitarian decision makers). Findings clarify the role of social determinants of FP and offer insight into program approaches informed by user typologies and return on program investments.

Measuring Family Planning Provider Bias: A Discrete Choice Experiment among Burkinabé, Pakistani, and Tanzanian Providers.

The unmet need for modern contraception remains high around the world, particularly for youth. While some of this unmet need is driven by limited health infrastructure and method mix availability, many adolescents who visit family planning providers still do not receive methods that fit their needs. This suggests that providers may be biased against youth and that interventions to change provider behavior could help close this gap. However, it is unclear if this bias is a result of age or other characteristics common among young women such as not being married and not having children. We use a discrete choice experiment in Burkina Faso, Pakistan, and Tanzania to disentangle the effects of age on providers' decisions to provide contraception from the effects of other potential confounding factors. We find that, although young women may experience the most bias, age is not the main driver. Rather, marital status and parity seem to influence provider decisions to offer services or counsel on modern methods. These findings suggest that interventions to reduce provider bias should focus on changing behavior towards unmarried and nulliparous women, regardless of their age.

Cytosolic and mitochondrial Ca2+ signaling in procoagulant platelets.

SummaryPlatelets are the major cellular contributor to arterial thrombosis. However, activated platelets form two distinct subpopulations during thrombosis. Pro-aggregatory platelets aggregate to form the main body of the thrombus. In contrast, procoagulant platelets expose phosphatidylserine on their outer surface and promote thrombin generation. This apparently all-or-nothing segregation into subpopulations indicates that, during activation, platelets commit to becoming procoagulant or pro-aggregatory. Although the signaling pathways that control this commitment are not understood, distinct cytosolic and mitochondrial Ca2+ signals in different subpopulations are likely to be central. In this review, we discuss how these Ca2+ signals control procoagulant platelet formation and whether this process can be targeted pharmacologically to prevent arterial thrombosis.

Metabolic basis to Sherpa altitude adaptation.

The Himalayan Sherpas, a human population of Tibetan descent, are highly adapted to life in the hypobaric hypoxia of high altitude. Mechanisms involving enhanced tissue oxygen delivery in comparison to Lowlander populations have been postulated to play a role in such adaptation. Whether differences in tissue oxygen utilization (i.e., metabolic adaptation) underpin this adaptation is not known, however. We sought to address this issue, applying parallel molecular, biochemical, physiological, and genetic approaches to the study of Sherpas and native Lowlanders, studied before and during exposure to hypobaric hypoxia on a gradual ascent to Mount Everest Base Camp (5,300 m). Compared with Lowlanders, Sherpas demonstrated a lower capacity for fatty acid oxidation in skeletal muscle biopsies, along with enhanced efficiency of oxygen utilization, improved muscle energetics, and protection against oxidative stress. This adaptation appeared to be related, in part, to a putatively advantageous allele for the peroxisome proliferator-activated receptor A (PPARA) gene, which was enriched in the Sherpas compared with the Lowlanders. Our findings suggest that metabolic adaptations underpin human evolution to life at high altitude, and could have an impact upon our understanding of human diseases in which hypoxia is a feature.

Evaluation of tranexamic acid in trauma patients: A retrospective quantitative analysis.

INTRODUCTION: Tranexamic acid (TXA) has been shown to decrease mortality in adult trauma patients with or at significant risk of hemorrhage when administered within 3 h of injury. The use and appropriateness of TXA in adult trauma patients presenting to Royal Columbian Hospital (RCH) was investigated. METHODS: This retrospective chart review utilized the British Columbia Trauma Registry to identify 100 consecutive trauma patients that presented to the emergency department at RCH between April 2012 to June 2015 and met the following indications for TXA: systolic blood pressure <90 mm Hg and/or heart rate >110 bpm and presentation within 8 h of injury. Primary outcomes included: percentage that met indications for TXA, received TXA according to the CRASH-2 protocol, received a pre-hospital dose, and received TXA ≤1, >1 to ≤3, or >3 h from injury. RESULTS: During the given time period, 117 subjects (2.7%) met indications for TXA. 67 patients (57%) received TXA in any dose, with 10 subjects (8.5%) receiving TXA according to the CRASH-2 protocol. Of the 67 patients who received any TXA, 76% did so ≤3 h. 22 patients (19%) received TXA as a pre-hospital dose. CONCLUSIONS: <10% of adult trauma patients that met the indication for TXA received it according to the CRASH-2 protocol. Of those patients that received TXA, 76% did so within 3 h. Further inquiry to identify reasons trauma patients are not receiving TXA as well as quality improvement initiatives in trauma care are required. LEVEL OF EVIDENCE: III STUDY TYPE: Therapeutic.

Processing gender: lived experiences of reproducing and transforming gender norms over the life course of young people in Northern Uganda.

The years between 10-19 represent a critical stage of human development during which boys and girls learn and embody socially constructed gender norms, with long-term implications for their sexual and reproductive health. This ethnographic cohort study sought to understand how gendered norms and practices develop during the transition from child to young adult in post-conflict northern Uganda. A total of 60 girls and boys aged 10-19 were selected using purposive sampling for in-depth interviews over a three-year period; 47 individuals completed all four interviews. Drawing on feminist theory and an ecological perspective, findings were used to create a conceptual framework displaying the experiences of young people navigating patriarchal and alternative norms, emphasising their lived processes of performing and negotiating norms within six key domains (work, puberty, family planning, intimate partner relations, child discipline and alcohol). The framework identifies: (1) personal factors (knowledge, agency and aspirations); (2) social factors (socialisation processes, capital, costs and consequences); and (3) structural factors (health/educational systems, religious institutions, government policies) which may encourage young people towards one norm or another as they age. These findings can inform policies and programmes to transform gender norms and promote equitable, healthy relationships.

Rapid kinetics of changes in oxygen consumption rate in thrombin-stimulated platelets measured by high-resolution respirometry.

Platelet activation plays a key role in normal haemostasis and pathological thrombosis. Platelet activation is rapid; within minutes of stimulation, platelets generate bioactive phospholipids, secrete their granule contents, activate integrins and aggregate together to form a haemostatic plug. These events are dependent on ATP synthesis. Mitochondrial function in platelets from healthy volunteers and patients with a range of diseases indicate an important role for oxygen consumption in oxidative phosphorylation in normal and pathological function. Platelets also consume oxygen during oxidation reactions, such as cyclooxygenase-dependent thromboxane A2 synthesis. In this study, we used high-resolution respirometry to investigate rapid changes in oxygen consumption during platelet activation. We demonstrated a rapid, transient increase in oxygen consumption rate within minutes of platelet stimulation by the physiological activator, thrombin. This was partly inhibited by aspirin and by oligomycin. This shows that high resolution respirometry can provide information regarding rapid and dynamic changes in oxygen consumption during platelet activation.

A Systematic Review of Randomized Controlled Trials Comparing Hypertonic Sodium Solutions and Mannitol for Traumatic Brain Injury: Implications for Emergency Department Management.

OBJECTIVE: To comparatively evaluate hypertonic sodium (HTS) and mannitol in patients following acute traumatic brain injury (TBI) on the outcomes of all-cause mortality, neurological disability, intracranial pressure (ICP) change from baseline, ICP treatment failure, and serious adverse events. DATA SOURCES: PubMed, EMBASE, CENTRAL, Cochrane Database of Systematic Reviews, ClinicalTrials.gov, and WHO ICTRP (World Health Organization International Clinical Trials Registry Platform) were searched (inception to November 2015) using hypertonic saline solutions, sodium chloride, mannitol, osmotic diuretic, traumatic brain injury, brain injuries, and head injury. Searches were limited to humans. Clinical practice guidelines and bibliographies were reviewed. STUDY SELECTION AND DATA EXTRACTION: Prospective, randomized trials comparing HTS and mannitol in adults (≥16 years) with severe TBI (Glasgow Coma Scale score ≤8) and elevated ICP were included. ICP elevation, ICP reduction, and treatment failure were defined using study definitions. DATA SYNTHESIS: Of 326 articles screened, 7 trials enrolling a total of 191 patients met inclusion criteria. Studies were underpowered to detect a significant difference in mortality or neurological outcomes. Due to significant heterogeneity and differences in reporting ICP change from baseline, this outcome was not meta-analyzed. No difference between HTS and mannitol was observed for mean ICP reduction; however, risk of ICP treatment failure favored HTS (risk ratio [RR] = 0.39; 95% CI = 0.18-0.81). Serious adverse events were not reported. CONCLUSIONS: Based on limited data, clinically important differences in mortality, neurological outcomes, and ICP reduction were not observed between HTS or mannitol in the management of severe TBI. HTS appears to lead to fewer ICP treatment failures.

Concordance of sustained virologic response at weeks 4, 12 and 24 post-treatment of hepatitis c in the era of new oral direct-acting antivirals: A concise review.

The goal of treatment for chronic hepatitis C viral (HCV) infection is to cure the infection rather than suppress the virus. Historically, a sustained virological response (SVR) defined as undetectable HCV RNA at 24 weeks following the completion of treatment was considered the gold standard to define successful eradication of the virus as a primary endpoint in clinical trials. SVR measured at 12 weeks post-treatment has been shown to be highly concordant with SVR24 in trials of pegylated interferon and ribavirin. The appropriateness and durability of SVR12 as the efficacy endpoint with new oral direct-acting antivirals is less established. A literatura search was performed using PubMed, EMBASE and CENTRAL databases to identify any studies that examined the concordance between SVR24 and earlier time points. Two studies and 4 abstracts were found that performed concordance analyses using positive and negative predictive values. Overall, SVR4 and SVR12 were highly concordant with SVR24 with high positive (> 97%) and negative (> 94%) predictive values; however there was a higher risk of HCV relapse occurring after post-treatment week 4. The majority of the data focused on SVR12 and demonstrated that SVR12 reliably predicted SVR24 in several populations infected with HCV (treatment-naïve, prior null responders, different genotypes) using various new oral direct-acting antiviral regimens. In conclusion, the available data suggests that SVR12 is a reliable assessment of HCV eradication and could be used instead of SVR24 for drug development clinical trials assessing efficacy of new direct-acting antivirals. Data on the long-term durability of SVR12 is still needed.

Creating the next steps to care: Maternal heath, improvisation, and Fulani women in Niamey, Niger.

On paper, Niger's maternal healthcare system is extensively outlined by policies which assure access to certain services and create hierarchical referral chains. In practice it remains intensely improvisational: actors in the system must frequently make up the next steps to giving and receiving care, often outside the existing policies and procedures. Although population health in Niger has improved since the recently enacted gratuité des soins policy (which guarantees free access to certain material and child health services), care on the ground is still dictated by difficult circumstances and scarce resources. Health workers often lack the required medications and supplies; nevertheless, they must find ways to deliver services. Patients seeking maternal health services are frequently dissatisfied with the care they receive and so move forward of their own volition, by negotiating with health workers or by looking for services elsewhere. This research builds on recent scholarly work on improvisation, and asks us to further look at the ways that improvisation can be informed by the identity of the actors. Examining case studies of women from the Fulani ethnic group illustrates how particular cultural differences can inform improvisation. Analysing improvisation can also have policy implications; identifying typical points of departure from the official maternal health care system can reveal points where Niger can bolster its commitment to a universally high quality of care.

Evaluating outcomes of alternative dosing strategies for cefepime: a qualitative systematic review.

OBJECTIVE: To perform a qualitative systematic review of the evidence comparing traditional with prolonged intermittent or continuous infusions of cefepime based on clinical and pharmacodynamic outcomes. DATA SOURCES: PubMed (1946 to October 2014), EMBASE (1980 to October 2014), CENTRAL, Cochrane Database of Systematic Reviews, Web of Science, and International Pharmaceutical Abstracts (1970 to October 2014) were searched using the terms cefepime, pharmacokinetics, pharmacodynamics, drug administration, intravenous infusions, intravenous drug administration, continuous infusion, extended infusion, and intermittent therapy. Reference lists from relevant materials were reviewed. STUDY SELECTION AND DATA EXTRACTION: Articles evaluating administration regimens of cefepime, one of which included the traditional, manufacturer-recommended 0.5-hour infusion and the other a prolonged or continuous infusion were included. Prespecified clinical outcomes of interest included all-cause mortality, length of hospital stay, clinical cure, and adverse events. The primary pharmacodynamic outcome was percentage time of unbound drug concentration remaining above the minimum inhibitory concentration. DATA SYNTHESIS: In all, 18 studies were included; 6 studies assessed clinical outcomes, and 12 assessed pharmacodynamic outcomes. Prolonged or continuous infusions of cefepime achieved the pharmacodynamic targets more often than traditional infusions. The association of improved clinical outcomes with prolonged or continuous infusions is unclear. All-cause mortality was significantly decreased with the use of a prolonged cefepime infusion in a retrospective study. Two prospective, randomized studies demonstrated no statistically significant difference in mortality between prolonged and intermittent infusions. CONCLUSIONS: The available literature on prolonged and continuous infusions of cefepime demonstrated an improved achievement of pharmacodynamic targets; however, the effect on clinical outcomes is inconclusive. Well-designed prospective studies are required to determine optimal dosing and administration strategies.

Drug Interactions With Direct-Acting Antivirals for Hepatitis C: Implications for HIV and Transplant Patients.

OBJECTIVE: Review pharmacokinetics of new direct-acting antivirals (DAAs) for hepatitis C (HCV) infection and interactions with concomitant immunosuppressant and antiretroviral therapies (ART). DATA SOURCES: MEDLINE (1948-January 2015), EMBASE (1964-January 2015), International Pharmaceutical Abstracts (1970-January 2015), Google, and Google Scholar were searched combining the terms simeprevir, sofosbuvir, ledipasvir, daclatasvir, paritaprevir, ABT-450, ombitasvir, dasabuvir, pharmacokinetics, drug interaction, drug metabolism, HIV, antiretroviral, immunosuppressant, transplant. Articles, conference proceedings, abstracts, and product monographs were reviewed. STUDY SELECTION AND DATA EXTRACTION: Literature on pharmacokinetic or pharmacodynamic interactions with DAAs and immunosuppressants or ART was considered for inclusion. Pertinent information was extracted and summarized in the review. In the absence of data, pharmacokinetic and pharmacodynamic principles were used to predict the likelihood of interactions. DATA SYNTHESIS: DAA pharmacokinetics are reviewed and drug interaction data are presented with provision of management strategies. Fixed-dose combination paritaprevir/ritonavir/ombitasvir plus dasabuvir is most susceptible to drug interactions with immunosuppressants and ART mainly due to the influence of ritonavir on multiple enzymes. Simeprevir is also prone to drug interactions because of cytochrome P450(CYP) 3A4, CYP1A2, P-glycoprotein, and OATP1 involvement and is not recommended for use in combination with several HIV antiretrovirals (ARVs). Close therapeutic drug monitoring of calcineurin inhibitors is required with concomitant simeprevir. Few clinically significant interactions are expected with sofosbuvir or ledipasvir. Limited data suggest that daclatasvir may be coadministered with immunosuppressants but requires dose adjustments with certain ARVs. CONCLUSIONS: None of the DAAs are completely free of drug interactions. Awareness and management of drug interactions is critical to optimize outcomes and minimize adverse effects in these patient populations.

Opioid and Sedative Coprescription: Prescribing Patterns after an ICU Admission.

Background: Opioid misuse constitutes a health care crisis in Canada, and coprescription of opioids with sedatives has been associated with adverse events. Opioids and sedatives are frequently administered in the intensive care unit (ICU). The rate of continuation of opioid-sedative combinations after an ICU admission at the study institution was unknown. Objectives: To determine the rates of opioid and sedative coprescriptions following an ICU admission and to identify factors associated with continuation of hospital-initiated opioid-sedative coprescriptions at ICU transfer and hospital discharge. Methods: This retrospective chart review involved patients admitted to ICUs at a tertiary care centre between April 1, 2018, and March 31, 2019. Baseline characteristics were obtained from a clinical database and medication information from medication reconciliation forms. An opioid coprescription was defined as prescription of an opioid in combination with a sedative (benzodiazepine, z-drug, gabapentinoid, tricyclic antidepressant, or antipsychotic), and hospital-initiated coprescriptions encompassed various predefined scenarios of therapy started or modified before ICU transfer. Factors associated with hospital-initiated opioid coprescription were analyzed by multivariable logistic regression. Results: A total of 735 patients met the inclusion criteria. At ICU transfer, 23.0% (169/735) of the patients had an opioid coprescription, and 87.0% (147/169) of these coprescriptions were hospital-initiated. At hospital discharge, 8.6% (44/514) of the patients had an opioid coprescription, and 56.8% (25/44) of these coprescriptions were hospital-initiated. Male sex, home opioid coprescription, surgical patient, prolonged hospital stay, and in-hospital death were significantly associated with hospital-initiated opioid coprescription at the time of ICU transfer. Home opioid coprescription was significantly associated with opioid coprescription at the time of hospital discharge. Conclusions: Hospital-initiated opioid coprescriptions accounted for the majority of opioid coprescriptions at ICU transfer and hospital discharge. Pharmacists should assess all opioid coprescriptions to determine whether discontinuation and/or dose reduction is appropriate.

Contexte: L'abus d'opioïdes est une crise sanitaire au Canada, et les opioïdes coprescrits avec des sédatifs ont été associés à des événements indésirables. Les opioïdes et les sédatifs sont fréquemment utilisés en unité de soins intensifs (USI). Sur le lieu de l'étude, on ne connaissait pas le taux de maintien de l'utilisation de la combinaison opioïdes-sédatifs après une admission en USI. Objectifs: Déterminer les taux de coprescription d'opioïdes et de sédatifs suite à une admission en USI et identifier les facteurs associés au maintien de l'utilisation des coprescriptions d'opioïdes et de sédatifs amorcées par l'hôpital au moment du transfert hors de l'USI et du congé hospitalier. Méthodes: Cet examen rétrospectif des dossiers portait sur des patients admis en USI d'un centre de soins tertiaires entre le 1er avril 2018 et le 31 mars 2019. Les caractéristiques de base ont été obtenues à partir d'une base de données clinique et des informations sur les médicaments à partir des formulaires de bilan comparatif des médicaments. Une coprescription d'opioïdes a été définie comme « La prescription d'un opioïde associée à un sédatif (benzodiazépine, médicament z, gabapentinoïde, antidépresseur tricyclique ou antipsychotique) ¼. Les « coprescriptions amorcées par l'hôpital ¼ correspondaient à des coprescriptions initiées ou modifiées avant le transfert hors de l'USI, selon des scénarios préalablement définis. Les facteurs associés à la coprescription d'opioïdes amorcée par l'hôpital ont été analysés par régression logistique multivariée. Résultats: Au total, 735 patients répondaient aux critères d'inclusion. Lors du transfert hors de l'USI, des opioïdes étaient coprescrits à 23,0 % (169/735) d'entre eux; de ces coprescriptions, 87,0 % (147/169) étaient amorcées par l'hôpital. Au moment du congé hospitalier, des opioïdes étaient coprescrits à 8,6 % (44/514) d'entre eux; de ces coprescriptions, 56,8 % (25/44) étaient amorcées par l'hôpital. Le sexe masculin, la coprescription d'opioïdes à domicile, l'admission en chirurgie, le séjour prolongé à l'hôpital et le décès à l'hôpital étaient fortement associés à la coprescription d'opioïdes amorcée par l'hôpital au moment du transfert hors de l'USI. La coprescription d'opioïdes à domicile était fortement associée à la coprescription d'opioïdes au moment du congé de l'hôpital. Conclusions: Les coprescriptions d'opioïdes amorcées par l'hôpital représentaient la majorité des coprescriptions au moment du transfert hors de l'USI et au moment du congé de l'hôpital. Les pharmaciens doivent évaluer toutes les coprescriptions d'opioïdes pour déterminer si l'arrêt et/ou la réduction de la dose est appropriée.

Environmental scan of current strategies to decrease sedative-hypnotic drug use and promote sleep in hospital patients.

BACKGROUND: Sedative-hypnotic drugs are often initiated in hospital to manage insomnia and anxiety. Guidelines discourage their use, particularly in older adults, due to risks of falls, fractures, and delirium. AIM: To identify publicly available resources to decrease the use of sedative-hypnotic drugs and promote sleep in hospital. METHOD: An advanced Google search with 6 search strategies was conducted. Key websites were also identified and searched. Hospital- or community-based resources using non-pharmacologic measures to reduce sedative-hypnotic drug use and/or to promote sleep were included if they were publicly available in English within the past 5 years. Full text screening and data extraction was performed independently by 2 reviewers; a third reviewer resolved disagreements by consensus. RESULTS: A total of 79 resources met inclusion criteria, with 65 (82.3%) providing education and 31 (39.2%) describing sleep hygiene strategies. Other resources included deprescribing (17, 21.5%), relaxation training (13, 16.5%), cognitive behavioural therapy for insomnia (9, 11.4%), and policies (7, 8.9%). The resources primarily targeted patients (59, 74.7%) followed by healthcare providers (9, 11.4%). There were 9 resources (11.4%) that applied to both community and hospital settings, and another 2 (2.5%) designed specifically for hospital. CONCLUSION: Many resources were available to patients and healthcare providers to reduce inappropriate or ineffective use of sedative-hypnotic drugs and promote better sleep. Specific resources for the hospital setting were infrequent and recommended that clinicians stop hospital-initiated sedatives when patients are discharged. Identified resources can be adapted by healthcare organizations to develop sedative-hypnotic prescribing programs and policies.

Comparison of nimodipine formulations and administration techniques via enteral feeding tubes in patients with aneurysmal subarachnoid hemorrhage: A multicenter retrospective cohort study.

BACKGROUND: Nimodipine improves outcomes following aneurysmal subarachnoid hemorrhage (aSAH) and current guidelines suggest that patients with aSAH receive nimodipine for 21 days. Patients with no difficulty swallowing will swallow the whole capsules or tablets; otherwise, nimodipine liquid must be drawn from capsules, tablets need to be crushed, or the commercially available liquid product be used to facilitate administration through an enteral feeding tube (FT). It is not clear whether these techniques are equivalent. The goal of the study was to determine if different nimodipine formulations and administration techniques were associated with the safety and effectiveness of nimodipine in aSAH. METHODS: This was a retrospective multicenter observational cohort study conducted in 21 hospitals across North America. Patients admitted with aSAH and received nimodipine by FT for ≥3 days were included. Patient demographics, disease severity, nimodipine administration, and study outcomes were collected. Safety end points included the prevalence of diarrhea and nimodipine dose reduction or discontinuation secondary to blood pressure reduction. Predictors of the study outcomes were analyzed using regression modeling. RESULTS: A total of 727 patients were included. Administration of nimodipine liquid product was independently associated with higher prevalence of diarrhea compared to other administration techniques/formulations (Odds ratio [OR] 2.28, 95% confidence interval [CI] 1.41-3.67, p-value = 0.001, OR 2.76, 95% CI 1.37-5.55, p-value = 0.005, for old and new commercially available formulations, respectively). Bedside withdrawal of liquid from nimodipine capsules prior to administration was significantly associated with higher prevalence of nimodipine dose reduction or discontinuation secondary to hypotension (OR 2.82, 95% CI 1.57-5.06, p-value = 0.001). Tablet crushing and bedside withdrawal of liquid from capsules prior to administration were associated with increased odds of delayed cerebral ischemia (OR 6.66, 95% CI 3.48-12.74, p-value <0.0001 and OR 3.92, 95% CI 2.05-7.52, p-value <0.0001, respectively). CONCLUSIONS: Our findings suggest that enteral nimodipine formulations and administration techniques might not be equivalent. This could be attributed to excipient differences, inconsistency and inaccuracy in medication administration, and altered nimodipine bioavailability. Further studies are needed.

Rhabdomyolysis: An evidence-based approach.

A 76-year-old lady was found on the floor following a fall at home. She was uninjured, but unable to get up, and had been lying on the floor for roughly 18 hours before her son arrived. She had been unwell for the past 3 days with a cough and shortness of breath. She had a past medical history of diabetes, hypertension, hypercholesterolaemia and atrial fibrillation (AF). On examination, she was alert but distressed, clinically dehydrated, febrile and tachycardic. She was treated for community acquired pneumonia with co-amoxiclav and was fluid resuscitated with Hartmann's solution. Her hyperkalaemia was treated with 50 mL of 50% glucose containing 10 units of rapid-acting insulin. Her creatinine kinase (CK) on admission was 200,000, and she had an acute kidney injury (AKI). Urine dipstick was positive for blood. However, her renal function continued to deteriorate over the succeeding 48 h, when she required renal replacement therapy (RRT) due to fluid overload and anuria.