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Working as a front-line worker during a pandemic is a unique situation that requires a supportive work environment. An informed understanding of nurses' and midwives’ workplace experiences during a pandemic, such as COVID-19, may enable better preparation and targeted support for future pandemics at an individual, organisational, and policy level.

MW01‐6‐189WH (MW189) is a novel central nervous system–penetrant small‐molecule drug candidate that selectively attenuates stressor‐induced proinflammatory cytokine overproduction and is efficacious in intracerebral hemorrhage and traumatic brain injury animal models. We report first‐in‐human, randomized, double‐blind, placebo‐controlled phase 1 studies to evaluate the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending intravenous doses of MW189 in healthy adult volunteers. MW189 was safe and well tolerated in single and multiple doses up to 0.25 mg/kg, with no clinically significant concerns. The most common drug‐related treatment‐emergent adverse event was infusion‐site reactions, likely related to drug solution acidity. No clinically concerning changes were seen in vital signs, electrocardiograms, physical or neurological examinations, or safety laboratory results. PK analysis showed dose‐proportional increases in plasma concentrations of MW189 after single or multiple doses, with approximately linear kinetics and no significant drug accumulation. Steady state was achieved by dose 3 for all dosing cohorts. A pilot pharmacodynamic study administering low‐dose endotoxin to induce a systemic inflammatory response was done to evaluate the effects of a single intravenous dose of MW189 on plasma cytokine levels. MW189 treatment resulted in lower levels of the proinflammatory cytokine TNF‐α and higher levels of the anti‐inflammatory cytokine IL‐10 compared with placebo treatment. The outcomes are consistent with the pharmacological mechanism of MW189. Overall, the safety profile, PK properties, and pharmacodynamic effect support further development of MW189 for patients with acute brain injury.

Several lines of emerging data point to an imbalance between neuronal excitation and inhibition in at least a subgroup of individuals with autism spectrum disorder (ASD), including in those with fragile X syndrome (FXS), one of the most common genetic syndromes within ASD. In animal models of FXS and of ASD, GABA-B agonists have improved both brain and behavioral phenotypes, including social behavior. A phase 2 randomized, placebo-controlled, crossover trial found that the GABA-B agonist arbaclofen improved social avoidance symptoms in FXS. A pilot open-label trial of arbaclofen suggested similar benefits in ASD. We therefore evaluated arbaclofen in a randomized, placebo-controlled, phase 2 study of 150 participants, aged 5–21 years, with ASD. No difference from placebo was detected on the primary outcome measure, the parent-rated Aberrant Behavior Checklist Social Withdrawal/Lethargy subscale. However, a specified secondary analysis found improvement on the clinician-rated Clinical Global Impression of Severity. An exploratory post hoc analysis of participants with a consistent rater across the trial revealed greater improvement in the Vineland Adaptive Behavior Scales II socialization domain in participants receiving arbaclofen. Affect lability (11%) and sedation (9%) were the most common adverse events. In this exploratory study, secondary analyses suggest that arbaclofen may have the potential to improve symptoms in some children with ASD, but further study will be needed to replicate and extend these initial findings.

The famous Antwerp printers and book publishers Jan II and Balthasar I Moretus, worked closely together with the so called ‘Galle workshop’ for the production of book illustrations and title pages. Balthasar Moretus, who was responsible for the substantive direction of the company, had a particular interest in the appearance and quality of the illustrations adorning his publications. The correspondence between him and his brothers-in-law, the engravers Cornelis I and II Galle, who were established in Brussels during the second half of the 1630s, reveals the hierarchical relationship between the employer and his employees. Cornelis I Galle had to follow the publishing schedule and standards of Balthasar. In fact, the latter expected the Galle brothers to be available at all times. Nevertheless Cornelis I got some responsibilities from Balthasar, like buying the copperplates or the permission to alter images when necessary. During the production of engravings, annotated and corrected proof impressions were sent back and forth between the two parties. Consultation and confidence in each others skills seemed very crucial in the context of quality control.

Internationally, rapid response systems have been implemented to recognise and categorise hospital patients at risk of deterioration. Whilst rapid response systems have been implemented with a varying amount of success, there remains ongoing concern about the lack of improvement in the escalation, and management of the deteriorating patient. It also remains unclear why some clinicians fail to escalate concerns for the deteriorating patient.

A controlled-release (CR) formulation of zileuton was developed to simplify administration from 600 mg 4 times daily (Zyflo) to 1,200 mg twice daily.

Opioids are the best medications for managing chronic pain in patients who are approaching the ends of their lives. There are no ethical or legal barriers to prescribing these medications in therapeutic doses with the intention of relieving pain. “Opiophobia,” including fear of hastening death or inducing addiction are not supportable with contemporary evidence and must be overcome for practitioners to prescribe adequate doses of opioids for appropriate patients. Strong pure opioid agonists are the medications of choice. These include morphine, oxycodone, hydromorphone, fentanyl, and methadone. Skill in rotating between the opioids and in performing accurate conversions is essential to good practice. Weaker opioids, particularly when compounded together with acetaminophen, should be avoided. There is no role for meperidine in managing chronic pain. Neither should the agonist-antagonist combinations be prescribed because of their higher incidence of psychomimetic effects. Finally, bothersome side effects of opioids may be controlled by prophylactically prescribing medications before the side effects become unmanageable. Central respiratory depression, which occurs rarely if at all with therapeutic opioid prescribing, and never without first the onset of sedation, should receive less attention and be less a cause for concern on the part of the prescribing physician.

Background:Results of recent growth studies suggest that inhaled glucocorticosteroids may affect growth in children. Objective:Three 52-week, open-label extension studies (studies A, B, and C) were conducted to compare the effects of budesonide inhalation suspension (BIS) with conventional asthma therapy (CAT) on long-term safety, including intermediate-term growth, in 3 different pediatric asthma populations. Methods:Pediatric asthma patients (ages 6 months to 8 years) from 3 multicenter, randomized, 12-week, double-blind, placebo-controlled studies were eligible to enroll in the 52-week, open-label extension studies. The extension studies were multicenter, randomized, open-label, active-controlled, parallel-group studies performed at 26 centers in the United States. Subjects in each extension study were randomized in a 2:1 ratio to receive either BIS or CAT. BIS was initially administered at a dose of 0.5 mg once (studies A and C) or twice daily (study B), with attempts made at each clinical visit to gradually reduce the dose to the minimum effective dose that maintains asthma control, as judged by the investigator. CAT consisted of any available therapy for asthma, including inhaled glucocorticosteroids in studies B and C only. Height SD scores, growth velocity, and skeletal age (only in studies B and C) were examined. Results:In total, 670 subjects were randomized; 223 subjects received CAT and 447 received BIS. Mean ages at entry were 63.0 months and 60.9 months in CAT and BIS groups, respectively. Median total daily doses of BIS ranged from 0.5 to 1.0 mg and the mean duration of treatment exposure was 304 ± 119 days and 342 ± 83 days in CAT and BIS groups, respectively. Changes in height SD scores differed significantly between the BIS and CAT groups in study A (–0.19, P= .003), and there was a small, statistically significant decrease in growth velocity (–0.8 cm/y, P= .002) in the BIS-treated group compared with the CAT group. No significant differences were observed between BIS and CAT groups in the changes in height SD scores or in growth velocities in studies B (+0.10 and +0.7 cm/y, respectively) and C (+0.12 and +0.8 cm/y, respectively). No differences in skeletal age were observed between BIS and CAT groups in studies B and C. Conclusion:There was a small, statistically significant decrease in growth velocity in the BIS-treated group compared with the CAT group in the study (study A) where inhaled glucocorticosteroid use was prohibited before entry and in the CAT group during the study. In the studies (B and C) where inhaled glucocorticosteroids were allowed in the CAT group, no differences were observed in height SD scores or growth velocity. The clinical relevance of these effects, including impact on final adult height, remain to be determined in prospectively planned studies that assess growth in children. (J Allergy Clin Immunol 2000;105:259-68.)

Inhaled glucocorticosteroids (GCS) are the most effective long-term controller medications for the treatment of persistent asthma. Currently, however, available delivery devices limit their use in young children. A nebulized formulation of budesonide has been developed to address the needs of infants and young children.

We conducted a double-blind, placebo-controlled, multicenter trial comparing the efficacy of famotidine 40 mg administered at bedtime (HS), 20 mg given twice daily (BID), and placebo to relieve heartburn and to heal endoscopically documented esophageal erosions or ulcerations. A total of 338 patients were randomized: 135 to receive famotidine 40 mg HS, 137 to receive famotidine 20 mg BID, and 66 to receive placebo. In the group given famotidine 20 mg BID, there was a significantly greater proportion of patients with complete relief of daytime heartburn, and both famotidine groups demonstrated statistically significant advantages over placebo in global scores or by successful outcome. Antacid consumption was significantly reduced in the group given famotidine 20 mg BID as compared with placebo. Both famotidine regimens resulted in a significantly greater proportion of patients with complete endoscopic healing than placebo, with the BID dosing being numerically superior to the 40-mg HS dose.(Arch Intern Med. 1991;151:2394-2400)

The present study determined whether the rate of relapse of duodenal ulcer was reduced after ulcer healing with omeprazole compared with ranitidine or placebo. It was made up of a double-blind, randomized, controlled multiple-center trial set within the United States. Patients were candidates if their duodenal or pyloric channel ulcer successfully healed in one of two large multicenter U.S. trials; one compared omeprazole, 20 mg once daily, before breakfast with ranitidine, 150 mg twice daily, and the other compared the same dose of omeprazole with placebo. Two hundred forty (73.8%) of the 325 patients with complete ulcer healing within 4 weeks of starting therapy who were eligible to enter the follow-up study were enrolled. There was no intervention. Endoscopic assessment of ulcer status was performed at 2, 4, and 6 months and whenever patients had symptoms thought to represent return of an ulcer. The lifetable relapse rates for duodenal ulcer according to initial ulcer therapy with omeprazole, ranitidine, or placebo were 76.7% [95% confidence interval (CI), 64%–89.3%], 59.8% (95% CI, 47.8–71.7%), and 50.4% (95% CI, 15.7%–85.2%), respectively. These rates were not statistically significantly different. Seventeen percent of recurrent ulcers occurred at a site different from that of the original ulcer. It is concluded that despite the more rapid rate of duodenal ulcer healing with omeprazole therapy, the rate of ulcer relapse appears similar and independent of whether ulcer healing was accelerated with omeprazole or ranitidine.

Glanzmann's thrombasthenia is a qualitativeplatelet disorder characterized by a deficiency in the platelet membrane glycoproteins (GP) IIb‐IIIa. It belongs to a group of hereditary platelet disorders typified by normal platelet numbers and a prolonged bleeding time. The bleeding seen in Glanzmann's thrombasthenia usually includes bruising, epistaxis, gingival hemorrhage, and menorrhagia. Spontaneous, unprovoked bleeding is unusual. The severity of bleeding is unpredictable in thrombasthenia and does not correlate with the severity of the platelet GP IIb‐IIIa abnormality. The present case report describes the dental treatment of a patient with Glanzmann's thrombasthenia. A 39‐year‐old female with a history of Glanzmann's thrombasthenia presented for periodontal therapy for spontaneous gingival hemorrhage. The patient had been sporadically seen in the past and had a record of only returning for appointments on an “emergency” basis. The periodontal findings revealed a diagnosis of moderate to advanced adult periodontitis in all quadrants. After all dental options had been discussed, the treatment of choice was determined to be extraction of the remaining dentition and fabrication of immediate dentures. The patient received a loading dose of 5 grams of aminocaproic acid (EACA) intravenously 3 hours prior to the surgery. At the beginning of the extractions 1 gram of EACA per hour continuous infusion and a 6 pack of platelets was administered. The patient tolerated the extractions well. All sites healed normally. The patient has had no difficulty in adjusting to the dentures. The case report discusses a possible treatment option in a noncompliant patient having Glanzmann's thrombasthenia and briefly discusses other hereditary bleeding disorders with similar presentations. J Periodontol 1996;67:536–540.

The objective of our course is to provide a general understanding of statistical reasoning, an appreciation of the statistician's role in drug development, and to facilitate effective communication between statisticians and clinical researchers. Brief lectures are followed immediately by interactive workshops which reinforce statistical concepts. Major subject areas include study design, data handling, data analysis, and interpretation of results. Specific topics include bias, sample size, data collection, descriptive statistics, and basic statistical methods. One continuing workshop requires students to create a protocol and then to analyze, interpret, and present data “collected” by course staff. Other workshops exhibit concepts of random sampling and making decisions with uncertainty. Student learning and course acceptability are greatly enhanced by discussions generated by the workshops, breaking the class into small study groups during the workshops, and the personalized attention that students receive from teaching assistants.

Administration of a selective GABABagonist to individuals with fragile X syndrome improves their deficits in social avoidance, a core symptom of the disease.

Narrates the author's success in losing weight. Diet plan; Workout schedule; Weight maintenance tips.