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Neurology Mar 2023Studies on tumefactive brain lesions in myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG)-associated disease (MOGAD) are lacking. We sought to characterize the...
BACKGROUND AND OBJECTIVES
Studies on tumefactive brain lesions in myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG)-associated disease (MOGAD) are lacking. We sought to characterize the frequency clinical, laboratory, and MRI features of these lesions in MOGAD and compare them with those in multiple sclerosis (MS) and aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD).
METHODS
We retrospectively searched 194 patients with MOGAD and 359 patients with AQP4+NMOSD with clinical/MRI details available from the Mayo Clinic databases and included those with ≥1 tumefactive brain lesion (maximum transverse diameter ≥2 cm) on MRI. Patients with tumefactive MS were identified using the Mayo Clinic medical record linkage system. Binary multivariable stepwise logistic regression identified independent predictors of MOGAD diagnosis; Cox proportional regression models were used to assess the risk of relapsing disease and gait aid in patients with tumefactive MOGAD vs those with nontumefactive MOGAD.
RESULTS
We included 108 patients with tumefactive demyelination (MOGAD = 43; AQP4+NMOSD = 16; and MS = 49). Tumefactive lesions were more frequent among those with MOGAD (43/194 [22%]) than among those with AQP4+NMOSD (16/359 [5%], < 0.001). Risk of relapse and need for gait aid were similar in tumefactive and nontumefactive MOGAD. Clinical features more frequent in MOGAD than in MS included headache (18/43 [42%] vs 10/49 [20%]; = 0.03) and somnolence (12/43 [28%] vs 2/49 [4%]; = 0.003), the latter also more frequent than in AQP4+NMOSD (0/16 [0%]; = 0.02). The presence of peripheral T2-hypointense rim, T1-hypointensity, diffusion restriction (particularly an arc pattern), ring enhancement, and Baló-like or cystic appearance favored MS over MOGAD ( ≤ 0.001). MRI features were broadly similar in MOGAD and AQP4+NMOSD, except for more frequent diffusion restriction in AQP4+NMOSD (10/15 [67%]) than in MOGAD (11/42 [26%], = 0.005). CSF analysis revealed less frequent positive oligoclonal bands in MOGAD (2/37 [5%]) than in MS (30/43 [70%], < 0.001) and higher median white cell count in MOGAD than in MS (33 vs 6 cells/μL, < 0.001). At baseline, independent predictors of MOGAD diagnosis were the presence of somnolence/headache, absence of T2-hypointense rim, lack of T1-hypointensity, and no diffusion restriction (Nagelkerke = 0.67). Tumefactive lesion resolution was more common in MOGAD than in MS or AQP4+NMOSD and improved model performance.
DISCUSSION
Tumefactive lesions are frequent in MOGAD but not associated with a worse prognosis. The clinical, MRI, and CSF attributes of tumefactive MOGAD differ from those of tumefactive MS and are more similar to those of tumefactive AQP4+NMOSD with the exception of lesion resolution, which favors MOGAD.
Topics: Humans; Neuromyelitis Optica; Multiple Sclerosis; Immunoglobulin G; Retrospective Studies; Sleepiness; Aquaporin 4; Myelin-Oligodendrocyte Glycoprotein; Recurrence; Autoantibodies
PubMed: 36690455
DOI: 10.1212/WNL.0000000000206820 -
Sleep Jun 2022To assess the efficacy and safety of FT218, a novel once-nightly formulation of sodium oxybate (ON-SXB), in patients with narcolepsy in the phase 3 REST-ON trial. (Randomized Controlled Trial)
Randomized Controlled Trial
STUDY OBJECTIVES
To assess the efficacy and safety of FT218, a novel once-nightly formulation of sodium oxybate (ON-SXB), in patients with narcolepsy in the phase 3 REST-ON trial.
METHODS
Narcolepsy patients aged ≥16 years were randomized 1:1 to uptitration of ON-SXB (4.5, 6, 7.5, and 9 g) or placebo. Three coprimary endpoints were change from baseline in mean sleep latency on the Maintenance of Wakefulness Test, Clinical Global Impression-Improvement rating, and weekly cataplexy attacks at 9, 7.5, and 6 g. Secondary endpoints included change from baseline on the Epworth Sleepiness Scale. Safety included adverse drug reactions and clinical laboratory assessments.
RESULTS
In total, 222 patients were randomized; 212 received ≥1 dose of ON-SXB (n = 107) or placebo (n = 105). For the three coprimary endpoints and Epworth Sleepiness Scale, all three doses of ON-SXB demonstrated clinically meaningful, statistically significant improvement versus placebo (all p < 0.001). For ON-SXB 9 g versus placebo, increase in mean sleep latency was 10.8 versus 4.7 min (Least squares mean difference, LSMD [95% CI], 6.13 [3.52 to 8.75]), 72.0% versus 31.6% were rated much/very much improved on Clinical Global Impression-Improvement (OR [95% CI], 5.56 [2.76 to 11.23]), change in mean weekly number of cataplexy attacks was -11.5 versus -4.9 (LSMD [95% CI], -6.65 [-9.32 to -3.98]), and change in Epworth Sleepiness Scale was -6.5 and -2.7 (LSMD [95% CI], -6.52 [-5.47 to -2.26]). Common adverse reactions included nausea, vomiting, headache, dizziness, and enuresis.
CONCLUSIONS
ON-SXB significantly improved narcolepsy symptoms; its safety profile was consistent with SXB. ON-SXB conferred efficacy with a clearly beneficial single nighttime dose.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov: NCT02720744, https://clinicaltrials.gov/ct2/show/NCT02720744.
Topics: Cataplexy; Double-Blind Method; Humans; Narcolepsy; Sleepiness; Sodium Oxybate; Treatment Outcome; Wakefulness
PubMed: 34358324
DOI: 10.1093/sleep/zsab200 -
Epilepsy Research Aug 2019Since 2014, patients with severe treatment-resistant epilepsies (TREs) have been receiving add-on cannabidiol (CBD) in an ongoing, expanded access program (EAP), which... (Clinical Trial)
Clinical Trial
BACKGROUND
Since 2014, patients with severe treatment-resistant epilepsies (TREs) have been receiving add-on cannabidiol (CBD) in an ongoing, expanded access program (EAP), which closely reflects clinical practice. We conducted an interim analysis of long-term efficacy and tolerability in patients with Lennox-Gastaut syndrome (LGS) or Dravet syndrome (DS) who received CBD treatment through December 2016.
METHODS
Children and adults with LGS/DS taking stable doses of antiepileptic drugs (AEDs) at baseline were included from 25 EAP sites across the United States. During the 4-week baseline period, parents/caregivers kept diaries of all countable seizure types. Patients received a pharmaceutical formulation of highly purified CBD (Epidiolex®; 100 mg/mL) in oral solution at 2-10 mg/kg/day, titrated until tolerability limit or a maximum dose of 25-50 mg/kg/day. Patient visits were every 2-4 weeks. The percentage change from baseline in median monthly convulsive (ie, major motor) and total seizures was evaluated at 12-week intervals through 96 weeks. The percentages of patients who had ≥50%, ≥75%, and 100% reduction in monthly seizures relative to the baseline period were also evaluated. Adverse events (AEs) were monitored and summarized for the safety analysis set (SAS) through 144 weeks.
RESULTS
Of the 607 patients in the SAS, 58 had DS and 94 had LGS (N = 152); 455 patients had other TREs. Twenty-eight percent of LGS/DS patients withdrew, primarily owing to lack of efficacy (20%). LGS/DS patients were taking a median of 3 (0-10) concomitant AEDs. Median treatment duration was 78.3 (range, 4.1-146.4) weeks. Between weeks 12 and 96, median CBD dose ranged from 21 to 25 mg/kg/day. At 12 weeks, add-on CBD reduced median monthly major motor seizures by 50% and total seizures by 44%, with consistent reductions in both seizure types through 96 weeks. At 12 weeks, the proportions of patients with ≥50%, ≥75%, and 100% reductions in major motor seizures were 53%, 23%, and 6%; the proportions with corresponding reductions in total seizures were 46%, 26%, and 5%. Responder rates for both seizure types were consistent through 96 weeks. CBD had an acceptable safety profile; the most common AEs were somnolence (30%) and diarrhea (24%).
CONCLUSIONS
Results from this interim analysis support add-on CBD as an effective long-term treatment option in LGS or DS.
Topics: Adolescent; Adult; Anticonvulsants; Cannabidiol; Child; Child, Preschool; Diarrhea; Drug Resistant Epilepsy; Duration of Therapy; Epilepsies, Myoclonic; Female; Humans; Infant; Lennox Gastaut Syndrome; Male; Middle Aged; Sleepiness; Treatment Outcome; Young Adult
PubMed: 31022635
DOI: 10.1016/j.eplepsyres.2019.03.015 -
JAMA Otolaryngology-- Head & Neck... Jun 2023Evidence is lacking from randomized clinical trials of hypoglossal nerve stimulation in obstructive sleep apnea (OSA).
IMPORTANCE
Evidence is lacking from randomized clinical trials of hypoglossal nerve stimulation in obstructive sleep apnea (OSA).
OBJECTIVE
To evaluate the safety and effectiveness of targeted hypoglossal nerve stimulation (THN) of the proximal hypoglossal nerve in patients with OSA.
DESIGN, SETTING, AND PARTICIPANTS
This randomized clinical trial (THN3) was conducted at 20 centers and included 138 patients with moderate to severe OSA with an apnea-hypopnea index (AHI) of 20 to 65 events per hour and body mass index (calculated as weight in kilograms divided by height in meters squared) of 35 or less. The trial was conducted from May 2015 through June 2018. Data were analyzed from January 2022 through January 2023.
INTERVENTION
Implant with THN system; randomized 2:1 to activation at month 1 (treatment) or month 4 (control). All received 11 months of THN with follow-up at months 12 and 15, respectively.
MAIN OUTCOMES AND MEASURES
Primary effectiveness end points comprised AHI and oxygen desaturation index (ODI) responder rates (RRs). Treatment responses at months 4 and 12/15 were defined as a 50% or greater reduction in AHI to 20 or less per hour and an ODI decrease of 25% or greater. Coprimary end points comprised (1) month 4 AHI and ODI RR in the treatment greater than the control group and (2) month 12/15 AHI and ODI RR in the entire cohort exceeding 50%. Secondary end points included sleep apnea severity (AHI and ODI) and patient-reported outcomes (Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, and EQ-5D visual analog scale).
RESULTS
Among 138 participants, the mean (SD) age was 56 (9) years, and 19 (13.8%) were women. Month 4 THN RRs were substantially greater in those in the treatment vs control group (AHI, 52.3% vs 19.6%; ODI, 62.5% vs 41.3%, respectively) with treatment-control standardized mean differences of 0.725 (95% CI, 0.360-1.163) and 0.434 (95% CI, 0.070-0.843) for AHI and ODI RRs, respectively. Months 12/15 RRs were 42.5% and 60.4% for AHI and ODI, respectively. Improvements in AHI, ODI, Epworth Sleepiness Scale, Functional Outcomes of Sleep Questionnaire, and EQ-5D visual analog scale scores were all clinically meaningful (medium to large effect size). Two serious adverse events and 100 nonserious related adverse events were observed from the implant procedure or study protocol.
CONCLUSIONS AND RELEVANCE
This randomized clinical trial found that THN demonstrated improvements in sleep apnea, sleepiness, and quality of life in patients with OSAs over an extended AHI and body mass index range without prior knowledge of pharyngeal collapse pattern. Clinically meaningful improvements in AHI and patient-reported responses compared favorably with those of distal hypoglossal nerve stimulation trials, although clinically meaningful differences were not definitive for ODI.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02263859.
Topics: Humans; Female; Middle Aged; Male; Hypoglossal Nerve; Quality of Life; Sleepiness; Sleep Apnea, Obstructive; Sleep Apnea Syndromes
PubMed: 37022679
DOI: 10.1001/jamaoto.2023.0161 -
JAMA Sep 2020Many adults with obstructive sleep apnea (OSA) use device treatments inadequately and remain untreated. (Comparative Study)
Comparative Study Randomized Controlled Trial
Effect of Multilevel Upper Airway Surgery vs Medical Management on the Apnea-Hypopnea Index and Patient-Reported Daytime Sleepiness Among Patients With Moderate or Severe Obstructive Sleep Apnea: The SAMS Randomized Clinical Trial.
IMPORTANCE
Many adults with obstructive sleep apnea (OSA) use device treatments inadequately and remain untreated.
OBJECTIVE
To determine whether combined palatal and tongue surgery to enlarge or stabilize the upper airway is an effective treatment for patients with OSA when conventional device treatment failed.
DESIGN, SETTING, AND PARTICIPANTS
Multicenter, parallel-group, open-label randomized clinical trial of upper airway surgery vs ongoing medical management. Adults with symptomatic moderate or severe OSA in whom conventional treatments had failed were enrolled between November 2014 and October 2017, with follow-up until August 2018.
INTERVENTIONS
Multilevel surgery (modified uvulopalatopharyngoplasty and minimally invasive tongue volume reduction; n = 51) or ongoing medical management (eg, advice on sleep positioning, weight loss; n = 51).
MAIN OUTCOMES AND MEASURES
Primary outcome measures were the apnea-hypopnea index (AHI; ie, the number of apnea and hypopnea events/h; 15-30 indicates moderate and >30 indicates severe OSA) and the Epworth Sleepiness Scale (ESS; range, 0-24; >10 indicates pathological sleepiness). Baseline-adjusted differences between groups at 6 months were assessed. Minimal clinically important differences are 15 events per hour for AHI and 2 units for ESS.
RESULTS
Among 102 participants who were randomized (mean [SD] age, 44.6 [12.8] years; 18 [18%] women), 91 (89%) completed the trial. The mean AHI was 47.9 at baseline and 20.8 at 6 months for the surgery group and 45.3 at baseline and 34.5 at 6 months for the medical management group (mean baseline-adjusted between-group difference at 6 mo, -17.6 events/h [95% CI, -26.8 to -8.4]; P < .001). The mean ESS was 12.4 at baseline and 5.3 at 6 months in the surgery group and 11.1 at baseline and 10.5 at 6 months in the medical management group (mean baseline-adjusted between-group difference at 6 mo, -6.7 [95% CI, -8.2 to -5.2]; P < .001). Two participants (4%) in the surgery group had serious adverse events (1 had a myocardial infarction on postoperative day 5 and 1 was hospitalized for observation following hematemesis of old blood).
CONCLUSIONS AND RELEVANCE
In this preliminary study of adults with moderate or severe OSA in whom conventional therapy had failed, combined palatal and tongue surgery, compared with medical management, reduced the number of apnea and hypopnea events and patient-reported sleepiness at 6 months. Further research is needed to confirm these findings in additional populations and to understand clinical utility, long-term efficacy, and safety of multilevel upper airway surgery for treatment of patients with OSA.
TRIAL REGISTRATION
Australian New Zealand Clinical Trials Registry: ACTRN12614000338662.
Topics: Adult; Blood Pressure; Continuous Positive Airway Pressure; Female; Humans; Male; Middle Aged; Oxygen; Palate, Soft; Polysomnography; Self Report; Severity of Illness Index; Sleep Apnea, Obstructive; Sleep Latency; Sleepiness; Tongue
PubMed: 32886102
DOI: 10.1001/jama.2020.14265 -
Drugs & Aging Oct 2022The dual orexin receptor antagonist daridorexant, studied in two phase III trials, dose-dependently improved objective and subjective sleep variables and daytime... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND OBJECTIVE
The dual orexin receptor antagonist daridorexant, studied in two phase III trials, dose-dependently improved objective and subjective sleep variables and daytime functioning in adults with insomnia. Because treatment of insomnia in older adults is challenging and has limited options, the purpose of the current analysis was to further analyse the phase III trial studying the higher doses of daridorexant, those that showed efficacy (daridorexant 50 mg, daridorexant 25 mg and placebo, nightly for 3 months), and compare the safety and efficacy of daridorexant in patients aged ≥ 65 ('older adults') to those aged < 65 years ('younger adults').
METHODS
Analyses by age (≥ 65 years, n = 364; < 65 years, n = 566) were performed on data from the randomised, double-blind, placebo-controlled Trial 1 in adult patients with insomnia (NCT03545191). Efficacy endpoints included a change from baseline at month 1 and month 3 in polysomnography-measured wake after sleep onset (WASO) and latency to persistent sleep (LPS), self-reported total sleep time (sTST) and daytime functioning assessed using the validated Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ). Safety endpoints included adverse events and the Visual Analog Scale for morning sleepiness.
RESULTS
At baseline, mean [standard deviation] WASO was numerically greater (110 [39] vs 92 [38] min) in older than younger adults, while LPS was comparable (~ 65 min). Mean baseline IDSIQ total and all domain scores were numerically lower (i.e. better) in older adults. Daridorexant caused similar reductions in WASO and LPS, and similar increases in sTST, from baseline, in both age groups; improvements were numerically greater with daridorexant 50 mg than 25 mg. At month 3, daridorexant 50 mg, compared with placebo, decreased WASO by a least-squares mean of 19.6 (95% confidence interval 9.7, 29.5) in older patients versus 17.4 min (10.7, 24.0) in younger patients and decreased LPS by a least-squares mean of 14.9 (7.5, 22.3) in older patients versus 9.7 min (3.7, 15.7) in younger patients. Daridorexant 50 mg increased sTST from baseline to month 3 by a least-squares mean of 59.9 (49.6, 70.3) in older patients versus 57.1 min (48.9, 65.3) in younger patients. Daridorexant 50 mg progressively improved IDSIQ total and domain scores from week 1 onwards similarly in both groups; daridorexant 25 mg improved IDSIQ scores, but only in younger adults. In both age groups, in comparison with placebo, the overall incidence of adverse events was comparable, and there were fewer falls on daridorexant. Daridorexant improved Visual Analog Scale morning sleepiness in both groups; daridorexant 50 mg increased the mean (standard deviation) Visual Analog Scale morning sleepiness score by 15.9 (20.7) in older adults and by 14.9 (18.7) in younger adults from baseline to month 3. In older adults, there was one case of sleep paralysis, and no cases of narcolepsy, cataplexy, or complex sleep behaviour.
CONCLUSIONS
In older patients with insomnia, as in younger patients, the efficacy of daridorexant is maximal on night-time and daytime variables at the higher dose of 50 mg. Older patients particularly require this dose to improve daytime functioning. Older patients are not at an increased risk of adverse events or residual effects the next morning after night-time administration of daridorexant, even at 50 mg. The dose of daridorexant does not need to be decreased for older patients.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov (NCT03545191) [first posted: 4 June, 4 2018], https://clinicaltrials.gov/ct2/show/NCT03545191 .
Topics: Aged; Double-Blind Method; Humans; Imidazoles; Lipopolysaccharides; Orexin Receptor Antagonists; Pyrrolidines; Sleep Initiation and Maintenance Disorders; Sleepiness; Treatment Outcome
PubMed: 36098936
DOI: 10.1007/s40266-022-00977-4 -
American Journal of Respiratory and... Sep 2022Randomized controlled trials of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) have not demonstrated protection against... (Randomized Controlled Trial)
Randomized Controlled Trial
Randomized controlled trials of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) have not demonstrated protection against adverse cardiovascular outcomes. Recently, observational studies revealed that OSA-related cardiovascular risk is concentrated in patients with an elevated pulse rate response to respiratory events (ΔHR). Here, in this analysis of a prospective clinical trial, we test the hypothesis that a greater pretreatment ΔHR is associated with greater CPAP-related protection against adverse cardiovascular outcomes. ΔHR was measured from baseline polysomnography of the RICCADSA (Randomized Intervention with CPAP in CAD and OSA) randomized controlled trial (patients with coronary artery disease [CAD] and OSA [apnea-hypopnea index ⩾ 15 events/h] with Epworth Sleepiness Scale score < 10; : = 113:113; male, 85%; age, 66 ± 8 [mean ± SD] yr). The primary outcome was a composite of repeat revascularization, myocardial infarction, stroke, and cardiovascular mortality. Multivariable Cox regression assessed whether the effect of CPAP was moderated by ΔHR (treatment-by-ΔHR interaction). The CPAP-related reduction in risk increased progressively with increasing pretreatment ΔHR (interaction hazard ratio [95% confidence interval], 0.49 [0.27 to 0.90] per SD increase in ΔHR; < 0.05). This means that in patients with a ΔHR of 1 SD above the mean (i.e., 10 beats/min), CPAP was estimated to reduce cardiovascular risk by 59% (6% to 82%) ( < 0.05), but no significant risk reduction was estimated in patients with a mean ΔHR (6 beats/min; CPAP risk reduction, 16% [-53% to 54%]; = 0.6). The protective effect of CPAP in patients with CAD and OSA without excessive sleepiness was modified by the ΔHR. Specifically, patients with higher ΔHR exhibit greater cardiovascular benefit from CPAP therapy.
Topics: Adult; Aged; Continuous Positive Airway Pressure; Coronary Artery Disease; Disorders of Excessive Somnolence; Female; Humans; Male; Middle Aged; Prospective Studies; Sleep Apnea, Obstructive; Sleepiness; Treatment Outcome
PubMed: 35579605
DOI: 10.1164/rccm.202111-2608OC -
Journal of Global Health Dec 2023Unhealthy lifestyle and diet may contribute to the development of cardiovascular disease (CVD), but limited evidence exists regarding the association between sleep...
Interplay of sleep patterns and oxidative balance score on total cardiovascular disease risk: Insights from the National Health and Nutrition Examination Survey 2005-2018.
BACKGROUND
Unhealthy lifestyle and diet may contribute to the development of cardiovascular disease (CVD), but limited evidence exists regarding the association between sleep patterns, oxidative stress-related exposures to diet and lifestyle, and CVD risk.
METHODS
We analysed data from 10 212 adults in the National Health and Nutrition Examination Survey (NHANES) database (2005-2018). Self-report questionnaires were used to collect data on sleep duration, sleepiness, and trouble sleeping, classified into three categories: healthy, intermediate, and poor sleep patterns. Healthy sleep was defined as sleeping seven to nine hours per night with no self-reported sleepiness or trouble sleeping, while intermediate and poor sleep patterns indicated one and two to three sleep problems, respectively. The oxidative balance score (OBS) was calculated based on twenty oxidative stress-related exposures to dietary and lifestyle factors, with a higher score indicating greater antioxidant exposure. Survey-based multivariable-adjusted regression analysis was conducted to examine the association of sleep patterns or OBS alone and combined with the total and specific CVD risk.
RESULTS
Participants with poor sleep patterns had a higher likelihood of developing CVD (odds ratio (OR) = 1.76; 95% confidence interval (CI) = 1.26-2.45, P < 0.05), while an inverse association was found between OBS and CVD risk (quartile (Q) 4 vs Q1: OR = 0.67; 95% CI = 0.47-0.94, P = 0.02, P for trend <0.05). There was an interaction between sleep patterns and OBS (P for interaction = 0.03). Participants with unhealthy (intermediate and poor) sleep patterns and pro-oxidant OBS (Q1 and Q2) were significantly associated with increased risk of total CVD (OR = 2.31; 95% CI = 1.42-3.74, P < 0.05), as well as angina and congestive heart failure, but not coronary heart disease (CHD). Stratified analysis showed that among individuals without hyperlipidaemia, participants with both unhealthy sleep patterns and pro-oxidant OBS exhibited a higher risk of CHD compared to those with healthy sleep patterns and antioxidative OBS.
CONCLUSIONS
Unhealthy sleep patterns and reduced oxidative balance are positively associated with an increased risk of overall and specific CVD. Interventions that target healthy sleep habits and antioxidant-rich diets and lifestyles may be important for reducing the risk of CVD.
Topics: Adult; Humans; Nutrition Surveys; Cardiovascular Diseases; Antioxidants; Reactive Oxygen Species; Risk Factors; Sleepiness; Oxidative Stress; Sleep
PubMed: 38085249
DOI: 10.7189/jogh.14.04170 -
The Cochrane Database of Systematic... Jun 2022Many people with cancer experience moderate to severe pain that requires treatment with strong opioids, such as oxycodone and morphine. Strong opioids are, however, not... (Review)
Review
BACKGROUND
Many people with cancer experience moderate to severe pain that requires treatment with strong opioids, such as oxycodone and morphine. Strong opioids are, however, not effective for pain in all people, neither are they well tolerated by all people. The aim of this review was to assess whether oxycodone is associated with better pain relief and tolerability than other analgesic options for adults with cancer pain. This is an updated Cochrane review previously published in 2017.
OBJECTIVES
To assess the effectiveness and tolerability of oxycodone by any route of administration for pain in adults with cancer.
SEARCH METHODS
For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE and MEDLINE In-Process (Ovid), Embase (Ovid), Science Citation Index, Conference Proceedings Citation Index - Science (ISI Web of Science), BIOSIS (ISI), and PsycINFO (Ovid) to November 2021. We also searched four trial registries, checked the bibliographic references of relevant studies, and contacted the authors of the included studies. We applied no language, date, or publication status restrictions.
SELECTION CRITERIA
We included randomised controlled trials (parallel-group or cross-over) comparing oxycodone (any formulation or route of administration) with placebo or an active drug (including oxycodone) for cancer background pain in adults by examining pain intensity/relief, adverse events, quality of life, and participant preference.
DATA COLLECTION AND ANALYSIS
Two review authors independently sifted the search, extracted data and assessed the included studies using standard Cochrane methodology. We meta-analysed pain intensity data using the generic inverse variance method, and pain relief and adverse events using the Mantel-Haenszel method, or summarised these data narratively along with the quality of life and participant preference data. We assessed the overall certainty of the evidence using GRADE.
MAIN RESULTS
For this update, we identified 19 new studies (1836 participants) for inclusion. In total, we included 42 studies which enrolled/randomised 4485 participants, with 3945 of these analysed for efficacy and 4176 for safety. The studies examined a number of different drug comparisons. Controlled-release (CR; typically taken every 12 hours) oxycodone versus immediate-release (IR; taken every 4-6 hours) oxycodone Pooled analysis of three of the four studies comparing CR oxycodone to IR oxycodone suggest that there is little to no difference between CR and IR oxycodone in pain intensity (standardised mean difference (SMD) 0.12, 95% confidence interval (CI) -0.1 to 0.34; n = 319; very low-certainty evidence). The evidence is very uncertain about the effect on adverse events, including constipation (RR 0.71, 95% CI 0.45 to 1.13), drowsiness/somnolence (RR 1.03, 95% CI 0.69 to 1.54), nausea (RR 0.85, 95% CI 0.56 to 1.28), and vomiting (RR 0.66, 95% CI 0.38 to 1.15) (very low-certainty evidence). There were no data available for quality of life or participant preference, however, three studies suggested that treatment acceptability may be similar between groups (low-certainty evidence). CR oxycodone versus CR morphine The majority of the 24 studies comparing CR oxycodone to CR morphine reported either pain intensity (continuous variable), pain relief (dichotomous variable), or both. Pooled analysis indicated that pain intensity may be lower (better) after treatment with CR morphine than CR oxycodone (SMD 0.14, 95% CI 0.01 to 0.27; n = 882 in 7 studies; low-certainty evidence). This SMD is equivalent to a difference of 0.27 points on the Brief Pain Inventory scale (0-10 numerical rating scale), which is not clinically significant. Pooled analyses also suggested that there may be little to no difference in the proportion of participants achieving complete or significant pain relief (RR 1.02, 95% CI 0.95 to 1.10; n = 1249 in 13 studies; low-certainty evidence). The RR for constipation (RR 0.75, 95% CI 0.66 to 0.86) may be lower after treatment with CR oxycodone than after CR morphine. Pooled analyses showed that, for most of the adverse events, the CIs were wide, including no effect as well as potential benefit and harm: drowsiness/somnolence (RR 0.88, 95% CI 0.74 to 1.05), nausea (RR 0.93, 95% CI 0.77 to 1.12), and vomiting (RR 0.81, 95% CI 0.63 to 1.04) (low or very low-certainty evidence). No data were available for quality of life. The evidence is very uncertain about the treatment effects on treatment acceptability and participant preference. Other comparisons The remaining studies either compared oxycodone in various formulations or compared oxycodone to different alternative opioids. None found any clear superiority or inferiority of oxycodone for cancer pain, neither as an analgesic agent nor in terms of adverse event rates and treatment acceptability. The certainty of this evidence base was limited by the high or unclear risk of bias of the studies and by imprecision due to low or very low event rates or participant numbers for many outcomes.
AUTHORS' CONCLUSIONS
The conclusions have not changed since the previous version of this review (in 2017). We found low-certainty evidence that there may be little to no difference in pain intensity, pain relief and adverse events between oxycodone and other strong opioids including morphine, commonly considered the gold standard strong opioid. Although we identified a benefit for pain relief in favour of CR morphine over CR oxycodone, this was not clinically significant and did not persist following sensitivity analysis and so we do not consider this important. However, we found that constipation and hallucinations occurred less often with CR oxycodone than with CR morphine; but the certainty of this evidence was either very low or the finding did not persist following sensitivity analysis, so these findings should be treated with utmost caution. Our conclusions are consistent with other reviews and suggest that, while the reliability of the evidence base is low, given the absence of important differences within this analysis, it seems unlikely that larger head-to-head studies of oxycodone versus morphine are justified, although well-designed trials comparing oxycodone to other strong analgesics may well be useful. For clinical purposes, oxycodone or morphine can be used as first-line oral opioids for relief of cancer pain in adults.
Topics: Adult; Analgesics, Opioid; Cancer Pain; Constipation; Humans; Morphine; Nausea; Neoplasms; Oxycodone; Pain; Quality of Life; Reproducibility of Results; Sleepiness; Vomiting
PubMed: 35679121
DOI: 10.1002/14651858.CD003870.pub7 -
Revista de Neurologia Jul 2023Narcolepsy type 1 is a focal degenerative disease of the hypothalamus that selectively affects orexin (hypocretin)-producing neurons. It presents multiple clinical...
INTRODUCTION
Narcolepsy type 1 is a focal degenerative disease of the hypothalamus that selectively affects orexin (hypocretin)-producing neurons. It presents multiple clinical manifestations, both in wakefulness and in sleep. The symptoms are often so disruptive that they cause enormous suffering and impair patients' quality of life. Although a non-pharmacological approach is sometimes sufficient, the vast majority of patients need medication for adequate clinical management.
CASE REPORT
A male who, at 43 years of age, began to present acutely with excessive daytime sleepiness and episodes of cataplexy. After a thorough examination, he was diagnosed with narcolepsy type 1. Throughout the course of the disease, he was prescribed antidepressants, neurostimulants and sodium oxybate, in monotherapy or in combination. The response to pharmacological treatment was insufficient and accompanied by numerous side effects. Following the introduction of pitolisant, there was a marked improvement in his symptoms and a reduction in the dose of the other drugs and their adverse effects was achieved.
CONCLUSION
A number of measures are now available to address the cardinal symptoms of the disease, although there are still cases that are resistant to anti-narcoleptic treatment. Drugs with mechanisms of action that act upon receptors in the histaminergic system can be very useful in these cases.
Topics: Humans; Male; Antidepressive Agents; Cataplexy; Central Nervous System Stimulants; Narcolepsy; Quality of Life; Sodium Oxybate; Adult; Drug Resistance, Multiple; Sleepiness
PubMed: 37477029
DOI: 10.33588/rn.77s01.2023198