The Impact of a Post-Prescription Review and Feedback Antimicrobial Stewardship Program in Lebanon

Antimicrobial stewardship programs (ASPs) are effective means to optimize prescribing practices. They are under-utilized in the Middle East where many challenges exist for ASP implementation. We assessed the effectiveness of infectious disease physician-driven post-prescription review and feedback as an ASP in Lebanon. This prospective cohort study was conducted over an 18-month period in the medical, surgical, and intensive care units of a tertiary care hospital. It consisted of three phases: the baseline, intervention, and follow-up. There was a washout period of two months between each phase. Patients aged ≥16 years receiving 48 h of antibiotics were included. During the intervention phase, the AMS team reviewed antimicrobial use within 72 h post-prescription and gave alternate recommendations based on the guidelines for use. The acceptance of the recommendations was measured at 72 h. The primary outcome of the study was days of therapy per 1000 study patient days. A total of 328 patients were recruited in the baseline phase (August-October 2020), 467 patients in the intervention phase (January-June 2021), and 301 patients in the post-intervention phase (September-December 2021). The total days of therapy decreased from 11.46 during the baseline phase to 8.64 during the intervention phase (p \u3c 0.001). Intervention acceptance occurred 88.5% of the time. The infectious disease physician-driven implementation of an ASP was successful in reducing antibiotic utilization in an acute care setting in Lebanon

Polysomnography in insomnia disorder

Introduction: A recent meta-analysis compared polysomnograms (PSGs) of people with insomnia to healthy controls; results showed short sleep time and reduced slow-wave and REM sleep in insomnia. Among people with insomnia, studies have shown morbidity associated with insomnia is found primarily in people with PSG short sleep. Here we characterize the distribution and nature of PSG sleep among people diagnosed with DSM-V insomnia disorder. Methods: Insomnia disorder (DSM-V) subjects, aged 23-61 yrs, (n=67, 63 females), absent other sleep disorders, unstable medical or psychiatric disorders or drug dependency volunteered for a clinical trial. The final enrollment step involved collection of a standard 8-hr PSG evaluating sleep disturbance among trial participants. PSGs were scored following ASSM criteria, by reliable scorers, for sleep efficiency (SE), latency to persistent sleep (LPS), wake after sleep onset (WASO) and percent sleep stages (N1, N2 N3, and NR). Results: There was wide variation in SE ranging from 40-97% with a mean of 82% and a median of 84% (6.5 hrs sleep). The SE distribution was divided into quartiles (worst - best; Q1: ≤ 76.8%; Q2: 77\u3e84.2%; Q3: 84.3% \u3e90.7%; Q4: ≥91%). As might be expected, LPS (F=9.82, p\u3c.001) and WASO (F=38.12, p\u3c.001) similarly improved across the SE quartiles with parallel declines in LPS and WASO over the quartiles. N1% declined (F=6.96, p\u3c.001) and both N3% (F=4.78, p\u3c.001), corrected for age, and NR% increased (F=5.12, p\u3c.001) over quartiles. In post hoc pairwise comparisons between quartiles, SEs of \u3c 77% were associated with reduced N3% and NR% and increased N1% (p\u3c.05) relative to efficiencies of \u3e84%. Conclusion: People meeting DSM-V diagnostic criteria for insomnia disorder display a broad range of PSG-defined sleep disturbance with 50% having SE of less than 84%. SE of \u3c77% (6.2 hrs) is associated with reduced N3% and NR% and increased N1%

Effects of suvorexant on pain sensitivity in fibromyalgia

Introduction: The chronic widespread pain disorder, fibromyalgia, is known for its nociceptive hypersensitization and disturbed sleep. The relation of sleep and pain is bidirectional and data suggest that improving sleep in chronic pain disorders would attenuate daytime pain sensitivity. Here we report on suvorexant\u27s next-day pain effects following night-time use gathered as part of a feasibility study. Methods: Women, 21- 65 yrs old, with fibromyalgia and co-morbid insomnia (n=10) were treated for 9 nights with suvorexant 20 mg and placebo with the order of treatment nights counterbalanced. Subjects were in good psychiatric health and stable physical condition and met American College of Rheumatology criteria for fibromyalgia and DSM-V criteria for insomnia. On a baseline screening 8-hr PSG other primary sleep disorders were ruled out. On days 2 and 9 of each treatment condition pain sensitivity was assessed at 1100 and 1500 hr by measuring finger withdrawal latency (FWL) to a radiant heat stimulus at 5 randomly presented intensity levels. FWL on the two tests of days 2 and 9 were compared between treatments using repeated measures ANOVAs with days and drug condition as factors. Results: FWL on both am and pm tests varied as a function of intensity (p\u3c.001) with no time of day effects or interaction (hi intensity = short latency; low = long latency). On days 2 and 9 after suvorexant versus placebo pain sensitivity was reduced (i.e., latency increased). Average FWL (over 5 intensities and both days) was increased on both the am test (13.9 vs 13.1 sec) and pm tests (15.8 vs 14.1 sec, p\u3c.03) following suvorexant the previous night. There were no time of day effects or interaction. Conclusion: Following hypnotic use of suvorexant 20 mg versus placebo by patients with fibromyalgia, next-day pain sensitivity was reduced on both am and pm assessments of FWL to a radiant heat stimulus

Are people with severe insomnia able to discontinue hypnotics after chronic use?

Introduction: A concern among physicians prescribing hypnotics is the inability to discontinue hypnotics after chronic use. This concern has never been directly tested in a controlled prospective study. This is a report of results from an on-going “blinded” trial in which insomnia subjects are instructed to stop taking study medication after 6 months of nightly use. Methods: DSM-V diagnosed insomnia subjects, 23-61 yrs, (n=25, 21 females), with disturbed sleep (i.e. polysomnographic sleep efficiency of ≤85%), no other sleep disorder, unstable medical or psychiatric disorder or drug dependency completed the trial. Participants were randomized to zolpidem XR (12.5 mg), eszopiclone (3 mg) or placebo nightly for 6 months (groups A: n=10, B: n=6, C: n=9). After 6 months of nighty use, over a 2-week choice period, they were instructed to discontinue hypnotic use, but if necessary, to take either 1, 2, or 3 capsules of medication (zolpidem XR 6.25 mg, 6.25 mg, placebo; eszopiclone 2 mg, 1 mg, placebo 1, 2 and 3 respectively; or 3 placebos). Results: The number of capsules taken declined from week 1 to 2 (p\u3c .01). Over 2 weeks 13 participants took 0 (48%), 8 ≤ 6 (32%) and 4 ≥10 capsules (1 each took 42, 19, 13, and 10). Among those taking capsules most took one capsule per night and 9 took \u3e 1 capsule. Those 4 taking ≥ 10 were younger (p\u3c.05), but did not differ in screening sleep efficiency or blinded treatment group. Importantly 1 subject took every capsule available. Conclusion: The majority (80%) of the participants discontinued 6-month nightly hypnotic use (i.e. took \u3c 6 total capsules over 2 weeks) and among those taking capsules the rate declined from week 1 to 2. Age may help identify the few with difficulty discontinuing

Effects of suvorexant on sleep in fibromyalgia

Introduction: The chronic pain disorder, fibromyalgia, is associated with sleep disturbance, typically sleep maintenance. Pharmacological treatment studies have either focused on the pain or the sleep disturbance with equivocal results in that few studies have improved both sleep and pain. No studies have evaluated the effect of sleep medication on pain sensitivity. Suvorexant, an orexin antagonist, approved for treatment of insomnia may provide benefit for both the sleep and pain of fibromyalgia. Here we report on suvorexant\u27s sleep effects in patients with fibromyalgia and comorbid insomnia disorder gathered as part of a feasibility study. Methods: Women, 21- 65 yrs old, with fibromyalgia and co-morbid insomnia (n=10) were treated for 9 nights with suvorexant, 20 mg, and placebo with the order of the treatments counterbalanced. They were in good psychiatric and stable physical health and met American College of Rheumatology criteria for fibromyalgia and DSM-V criteria for insomnia. On a screening 8-hr PSG other primary sleep disorders were ruled out. On nights 8 and 9 of each treatment 8-hr PSGs were collected. All PSGs were scored following ASSM criteria and PSG measures were compared using repeated measures ANOVAs with night and drug condition as factors. Results: Suvorexant vs placebo increased total sleep time (7.2 vs 6.7 hrs, p\u3c .05) and reduced wake after sleep onset (37 vs 67 min, p\u3c.04) with no night effects or interaction. Suvorexant also reduced wake during the last half (20 vs 41 min, p\u3c .03) and quarter (13 vs 20 min, p\u3c .03) of the night. Latency to persistent sleep and sleep stage measures were not altered by suvorexant. Conclusion: In patients with fibromyalgia and comorbid insomnia disorder suvorexant, 20 mg, improved total sleep time and reduced wake after sleep onset with sustained effects through the last quarter of the sleep period and no alteration of normal sleep staging

Sleep and Pain in Subjects with Fibromyalgia and Comorbid Insomnia: Double-blind, Crossover, Study of Suvorexant 20 mg versus Placebo.

OBJECTIVES: The chronic pain disorder, fibromyalgia, is associated with sleep disturbance, typically sleep maintenance. No studies have evaluated the effect of sleep medication on pain sensitivity in this population. Suvorexant, an orexin antagonist, approved for treatment of insomnia was evaluated for effects on both the sleep and pain of fibromyalgia. METHODS: Women, 21- 65 yrs old, with fibromyalgia and co-morbid insomnia (n=10) were treated, double-blind, for 9 nights each with suvorexant, 20 mg, and placebo in counterbalanced order. All were in good psychiatric and stable physical health and met American College of Rheumatology 2010 criteria for fibromyalgia and DSM-V criteria for insomnia. A screening 8-hr PSG was used to rule out other sleep disorders. On nights 8 and 9 of each treatment 8-hr PSGs were collected and on days 1 and 8 pain sensitivity was assessed at 1100 and 1500 hr by measuring finger withdrawal latency (FWL) to a radiant heat stimulus at 5 randomly presented intensity levels. RESULTS: Suvorexant vs placebo increased total sleep time (7.2 vs 6.7 hrs, p\u3c .05) and reduced wake after sleep onset (37 vs 67 min, p\u3c.04) with no night effects or interaction. Latency to persistent sleep and sleep stage measures were not altered. FWL on both am and pm tests varied as a function of intensity (p\u3c.001). Average FWL (over 5 intensities and both days) was increased relative to placebo on both the am test (13.9 vs 13.1 sec) and pm tests (15.8 vs 14.1 sec, p\u3c.03) following suvorexant the previous night. CONCLUSIONS: Suvorexant 20 mg in patients with fibromyalgia, improved sleep time and reduced next-day pain sensitivity on assessments of FWL to a radiant heat stimulus

Sleep and pain in humans with fibromyalgia and comorbid insomnia: double-blind, crossover study of suvorexant 20 mg versus placebo

STUDY OBJECTIVES: The chronic pain disorder, fibromyalgia, is associated with sleep disturbance, typically sleep maintenance. No studies have evaluated the effect of sleep medication on pain sensitivity in this population. Suvorexant, an orexin antagonist approved for treatment of insomnia, was evaluated for effects on both sleep and the pain of fibromyalgia. METHODS: Women age 21 to 65 years with fibromyalgia and comorbid insomnia (n = 10) were treated, double-blind, for 9 nights each with suvorexant, 20 mg and placebo in counterbalanced order. All were in good psychiatric and stable physical health and met American College of Rheumatology 2010 criteria for fibromyalgia and Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition criteria for insomnia. Screening 8-hour polysomnography (PSG) was used to rule out other sleep disorders. On nights 8 and 9 of each treatment 8-hour PSG were collected and on days 1 and 8 pain sensitivity was assessed at 1100 and 1500 hours by measuring finger withdrawal latency (FWL) to a radiant heat stimulus at 5 randomly presented intensity levels. RESULTS: Suvorexant versus placebo increased total sleep time (7.2 versus 6.7 hours, P \u3c .05) and reduced wake after sleep onset (37 versus 67 minutes, P \u3c .04) with no night effects or interaction. Latency to persistent sleep and sleep stage measures were not altered. FWL on both am and pm tests varied as a function of intensity (P \u3c .001). Average FWL (over 5 intensities and both days) was increased relative to placebo on both the am (13.9 versus 13.1 seconds) and pm tests (15.8 versus 14.1 seconds, P \u3c .03) following suvorexant the previous night. CONCLUSIONS: Suvorexant 20 mg in patients with fibromyalgia, improved sleep time and reduced next-day pain sensitivity on assessments of FWL to a radiant heat stimulus