Analgesic Medication Research Articles

Determinants of neural tube defect among newborns admitted to neonatal intensive care units of teaching hospitals in Gedeo Zone and Sidama Region, Southern Ethiopia: a case–control study

BackgroundNeural tube defects are a significant cause of morbidity and mortality that can occur in the early pregnancy periods. Though the burden is high, it gains only limited attention. In...

Pupillometry as a Potential Objective Measurement of Pain Assessment in Healthy Volunteers.

Pain leads to activation of the autonomic nervous system and thus, among other things, to pupillary reflex dilation (PRD). Previous studies have already confirmed a correlation between the perception of pain and the pupillary reaction, measured using pupillometry. However, the previous study populations were under the influence of medication for analgesia in perioperative setting or suffered from pain. This study examines the relationship between pupillary reaction and pain perception in healthy controls and addresses the question of whether endogenous pain inhibition, clinically tested by conditioned pain modulation (CPM), can be quantified using pupillometry. Forty-two healthy volunteers (21 females, 21 males, mean age 27.9 ± 5.8 years, range 20-39 years) were included in this study. The PRD, as a measure of the pupillary reaction (variance from the base diameter in percent), was investigated during baseline, heat application and during CPM testing and results compared to the reported pain intensity on the numerical rating scale (NRS). The volunteers showed higher variances under painful conditions compared to the measurement at rest corresponding to higher sympathetic activity during pain. Volunteers with a higher variance, ie a stronger pupillary reaction, gave higher pain ratings than subjects with a lower pupil variance. However, there was no correlation between the NRS and PRD. PRD and pain ratings during CPM were significantly lower compared to heat pain application alone. However, there was no correlation between the calculated CPM effect and the PRD. Pupillometry is capable of objectively reflecting the pain response, eg pain relief through CPM testing. However, the CPM effect calculated from the subjective pain ratings and the objective PRD measurements is not associated suggesting that both measure different aspects of pain perception. It must be discussed whether the CPM effect can be the correct measure for the functionality of the pain system.

A Brief Insight into Nanotherapeutic Approaches in the Management of Analgesia

Background: Growing public awareness of chronic pain resulting from illness and injury has prompted pharmaceutical researchers and drug corporations to create better, more targeted painkillers. For effective pain management, prolonged analgesic medication delivery at the intended areas continues to be a major problem such as addiction, tolerance and other serious side effects, which can prolong suffering and decrease painkiller effectiveness. Objective: The present paper focuses on review of current advances in the field of pain treatment by different nanoparticles formulations of various drugs, by enhancing their pharmacokinetic factors and diminishing associated adverse effects. Results: According to literature survey, usage of nano-carriers enables the delivery of these drugs to target locations with less systemic toxicity. Nanotechnology for varied therapeutic purposes, different analgesics have been loaded onto different nano carriers, including those that are natural, synthetic, and polymeric and proven to be beneficial in pain management. Conclusion: Overall, new nano based preparations and new ways to utilize existing medications in a variety of circumstances is a multimodal approach to pain relief, have resulted in recent advancements in the pharmacological management of pain.

The safety and efficacy of diclofenac sodium suppository as adjunctive opioids in the treatment of cancer pain: A prospective, multi-center, real-world study.

12055 Background: Cancer pain is one of the most common and unbearable symptoms for cancer patients (pts), seriously affecting their quality of life. Diclofenac sodium is a potent third-generation non-steroidal anti-inflammatory drug known for its significant analgesic, anti-inflammatory, and antipyretic effects. It is commonly used to treat different types of cancer pain. The objective of this study was to assess the safety and effectiveness of diclofenac sodium suppository when used alongside opioids for managing cancer pain in pts with solid tumors. Methods: In this prospective, multi-center, real-world study, we enrolled pts diagnosed with malignancy, Eastern Cooperative Oncology Group (ECOG) performance status of 0-3, numeric rating scale (NRS) score ≥ 3, and sustained cancer pain, who required additional analgesic medication were enrolled. Diclofenac sodium suppository is an anal administration suppository, prescribed once a day at a dosage of 50 mg. This study was conducted across 20 centers to observe the clinical characteristics of pain relief in pts with cancer pain . The primary endpoint of the study was to assess the safety of the medication. The secondary endpoints included evaluating the incidence of breakthrough pain (BP), NRS score, and Brief Pain Inventory (BPI) score on the second and sixth days of medication. Results: Of the 506 pts that were screened, 437 pts met the inclusion criteria. This included 10 pts who did not receive planned treatment and 2 pts who did not undergo post-baseline efficacy evaluation. Among the 425 pts in the full analysis set (FAS), 261 were man, and 169 (39.8%) had baseline BP. The mean age was 63.0±11.3 years old. Among 425 response-evaluable pts, compared to the baseline, the incidence of BP was reduced on the second (20.0% vs 39.8%), and sixth days (14.8% vs 39.8%) of medication and the difference was statistically significant ( P < 0.001, P < 0.001). For pts with baseline BP, 56.2% and 66.9% pts achieved BP relief on the second and sixth days of medication, respectively. From the baseline evaluation, the mean NRS scores for the three visits (baseline, second day, sixth day) were 5.28 ± 1.71, 3.73 ± 1.71, and 2.91 ± 1.88, respectively. The mean pain intensity at each visit was decreased compared to the baseline, and the difference was statistically significant ( P < 0.001, P < 0.001). 427 pts were included for safety analysis and 5 pts experienced any grade treatment emergent adverse events (TEAEs). All TEAEs were grade 1-2. TEAE leading to treatment discontinuation was occurred in one pt. Conclusions: This study demonstrated that diclofenac sodium suppository was an effective treatment option for managing breakthrough pain in patients with persistent cancer pain who required additional analgesic therapy. Moreover, diclofenac sodium suppository was found to be well tolerated when administered anally.

Use of electronic health record data to examine administrations of pro re nata analgesics during hip fracture post-acute care.

Medications prescribed to older adults in US skilled nursing facilities (SNF) and administrations of pro re nata (PRN) "as needed" medications are unobservable in Medicare insurance claims. There is an ongoing deficit in our understanding of medication use during post-acute care. Using SNF electronic health record (EHR) datasets, including medication orders and barcode medication administration records, we described patterns of PRN analgesic prescribing and administrations among SNF residents with hip fracture. Eligible participants resided in SNFs owned by 11 chains, had a diagnosis of hip fracture between January 1, 2018 to August 2, 2021, and received at least one administration of an analgesic medication in the 100 days after the hip fracture. We described the scheduling of analgesics, the proportion of available PRN doses administered, and the proportion of days with at least one PRN analgesic administration. Among 24 038 residents, 57.3% had orders for PRN acetaminophen, 67.4% PRN opioids, 4.2% PRN non-steroidal anti-inflammatory drugs, and 18.6% PRN combination products. The median proportion of available PRN doses administered per drug was 3%-50% and the median proportion of days where one or more doses of an ordered PRN analgesic was administered was 25%-75%. Results differed by analgesic class and the number of administrations ordered per day. EHRs can be leveraged to ascertain precise analgesic exposures during SNF stays. Future pharmacoepidemiology studies should consider linking SNF EHRs to insurance claims to construct a longitudinal history of medication use and healthcare utilization prior to and during episodes of SNF care.

Constipation in Women with High-Grade Intraepithelial Neoplasia and Cervical Cancer: Does the Extent of Cervical Lesion Invasion Influence the Severity of Constipation and Compromise Quality of Life?

Abstract Introduction Constipation is a common clinical condition, particularly among cancer patients. Objective To assess the prevalence and severity of CF in women with high-grade intraepithelial neoplasia (HSIL) and cervical cancer (CC), as well as the impact of this condition on their daily lives. Methods A cross-sectional study was conducted at a tertiary cancer center. To assess the presence and severity of constipation, the Rome IV criteria, and the Constipation Scoring System (CSS) were used. To assess the impact of constipation on daily life, the Visual Analogue Scale (VAS) was used. Results The study included 153 patients with HSIL or CC, with a median age of 44 (IQR 35–56) years. Constipation was reported in 54 (35.3%) patients, 33 (61.1%) of those with HSIL, and 21 (38.9%) of those with CC. In constipated patients, the median number of positive Rome IV criteria items was 3 (IQR 2–5). "Irregular or hard stools" was the most common complaint, affecting 41 (75.9%) of the patients. In patients with CC, the use of analgesic medications was associated with constipation (p = 0.016). There is no link between constipation and invasive cancer (p = 0.492). Constipation had a daily impact of 7.5 (IQR 4.75–9), with no relationship between VAS and clinical diagnosis (HSIL or CC) [7 (IQR 3-9) X 8 (5-9.5), p-value = 0.536] The more severe the constipation, the more disturbing it is to these women's daily lives. Conclusion Constipation is common in women with cervical lesions, affecting their daily lives regardless of their severity.

How is postoperative pain after hip and knee replacement managed? An analysis of two large hospitals in Australia

BackgroundMultimodal analgesia regimens are recommended for the postoperative period after hip and knee replacement surgeries. However, there are no data on practice patterns for analgesic use in the immediate postoperative period after hip and knee replacements in Australia.ObjectivesTo describe analgesic prescribing patterns in the inpatient postoperative phase for patients undergoing hip and knee replacement.MethodsRetrospective study of electronic medical record data from two major hospitals in Sydney, Australia. We identified analgesic medication prescriptions for all patients aged 18 years and older who underwent hip or knee replacement surgery in 2019. We extracted data on pain medications prescribed while in the ward up until discharge. These were grouped into distinct categories based on the Anatomical Therapeutic Chemical classification. We described the frequency (%) of pain medications used by category and computed the average oral morphine equivalent daily dose (OMEDD) during hospitalisation.ResultsWe identified 1282 surgeries in 1225 patients. Patients had a mean (SD) age of 69 (11.8) years; most (57.1%) were female. Over 99% of patients were prescribed opioid analgesics and paracetamol during their hospital stay. Most patients (61.4%) were managed with paracetamol and opioids only. The most common prescribed opioid was oxycodone (87.3% of patients). Only 19% of patients were prescribed nonsteroidal anti-inflammatories (NSAIDs). The median (IQR) average daily OMEDD was 50.2 mg (30.3–77.9).ConclusionWe identified high use of opioids analgesics as the main strategies for pain control after hip and knee replacement in hospital. Other analgesics were much less frequently used, such as NSAIDs, and always in combination with opioids and paracetamol.

Brain health in preterm infants: importance of early-life pain and analgesia exposure.

"Everyday" exposures in the neonatal period, such as pain, may impact brain health in preterm infants. Specifically, greater exposure to painful procedures in the initial weeks after birth have been related to abnormalities in brain maturation and growth and poorer neurodevelopmental outcomes in preterm infants. Despite an increasing focus on the importance of treating pain in preterm infants, there is a lack of consensus of optimal approaches to managing pain in this population. This may be due to recent findings suggesting that commonly used analgesic and sedative medications in preterm infants may also have adverse effects of brain maturation and neurodevelopmental outcomes. This review provides an overview of potential impacts of pain and analgesia exposure on preterm brain health while highlighting research areas in need of additional investigations for the development of optimal pain management strategies in this population.

Discomfort/pain due to peri-implant probing at titanium and zirconium implants: A cross-sectional study.

This study was designed to compare discomfort/pain after periodontal and peri-implant probing in patients with titanium compared with zirconium implants. One examiner recruited and examined 70 patients, each of whom had a dental implant with a contralateral tooth; 37 patients had titanium implants of various types and 33 patients had zirconium implants; one implant was analyzed for each patient. Periodontal and peri-implant probing pocket depth (PPD) and clinical attachment level (CAL) were assessed. Immediately after probing, patients rated their discomfort/pain with a visual analog scale (VAS). The emergence profiles of implant crowns were assessed on periapical radiographs of the implants. Seventy patients with a median age of 55 years (interquartile range [IQR]: 42-65 years), including 43 females and 16 current smokers, were examined. The mean PPD and bleeding on probing (BOP) were higher around implants than around teeth (p < .001). CAL and suppuration were well-balanced between implants and teeth. Peri-implant probing caused significantly more discomfort/pain than periodontal probing [median VAS score: 12.5 (IQR 4-22) vs. 9 (2-15); p < .001]. Logistic regression revealed that discomfort/pain after peri-implant probing was less intense in patients who had taken analgesic medication (p = .021) and around titanium implants (p = .037). Peri-implant probing caused significantly more discomfort/pain than periodontal probing. Patients who had taken analgesic medication experienced less discomfort and pain with peri-implant probing than those who had not; furthermore, titanium implants were associated with less pain than zirconium implants.

Referred pain is associated with greater odontogenic spontaneous pain and a heightened pain sensitivity in patients with symptomatic irreversible pulpitis.

Symptomatic irreversible pulpitis often results in heightened reactions to thermal stimuli such as pain evoked by a cold stimulus, and spontaneous odontogenic pain (unprovoked pain). This study primarily compared the clinical manifestations of odontogenic spontaneous pain and pain provoked by cold stimulus specifically focusing on their sensory discriminative characteristics (intensity, duration and quality) between symptomatic irreversible pulpitis patients with and without referred pain. Twenty-three patients with symptomatic irreversible pulpitis with referred pain and 12 patients without referred pain were included in this cross-sectional study. The following outcomes were assessed: odontogenic spontaneous pain and its descriptors; pain evoked by cold stimulus and qualitative sensory testing before and after local anaesthesia; referred pain location; use of analgesic medication; complementary anaesthesia efficacy. T-test, chi-squared and McNemar tests were applied to the data (p < .50). Patients with referred pain presented a greater odontogenic pain intensity (p < .05) when considered the average of the last 24 h. These patients also showed higher pain rating and pain descriptors (p < .05). Intensity and duration of the pain evoked by cold stimulus in the non-affected contralateral tooth at baseline were higher for patients with referred pain (p < .05). Symptomatic irreversible pulpitis patients with referred pain present greater odontogenic spontaneous pain and a heightened pain sensitivity. Therefore, patients with referred pain seem more complex from a pain severity perspective, supporting the clinical utility of discriminating symptomatic irreversible pulpitis with and without referred pain.

Use of Fish Skin Grafts for Wound Management: Report of 5 Pediatric Cases

Abstract Background Managing wounds and scars in children presents a significant challenge for surgical and rehabilitation teams. Studies have already explored the potential of fish skin grafts with Omega-3 in hard-to-heal lower extremity chronic ulcers and deep-burn management. Aims The purpose of this study is to assess the safety and outcome of intact fish skin grafts with Omega-3 when used as skin replacement therapy in the pediatric population. Methods This article was conducted in adherence to our hospital's ethical guidelines. Patients enrolled in this study were identified retrospectively. Their medical records were reviewed, and data was collected concerning patient demographics, initial mode of injury, indication for fish skin placement, operative data, postoperative care, complications and outcomes. The acellular dermal matrix was obtained from North Atlantic codfish skin (Gadus morhua) farmed in Isafjordur, Iceland. Results All patients underwent meticulous wound debridement and patch application under general anesthesia and were discharged the same day. Wound surface ranged between 10 and 110 cm2 (mean: 53 cm2). Standard analgesic medications were taken for a maximum period of 48 hours in all patients. Upon follow-up at our outpatient clinic, shrinkage in the wound surface was observed in all patients after a few days, followed by early wound granulation. Two patients underwent subsequent split-thickness grafting to achieve healing. The mean time required to achieve complete epithelialization was 48.6 days (range: 29 – 62 days). No hypersensitivity or allergic reaction was reported. The definitive outcome was satisfactory in all wounds, meaning complete wound coverage. Conclusion The findings from this case series reveal that fish skin grafts with Omega-3 can be an effective and a safe scaffold in the process of repairing damaged tissues in the pediatric population. We have been able to accomplish a quality skin replacement therapy, with no donor site morbidity.

The Multifaceted Effects of Non-Steroidal and Non-Opioid Anti-Inflammatory and Analgesic Drugs on Platelets: Current Knowledge, Limitations, and Future Perspectives.

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely utilized pharmaceuticals worldwide. Besides their recognized anti-inflammatory effects, these drugs exhibit various other pleiotropic effects in several cells, including platelets. Within this article, the multifaceted properties of NSAIDs on platelet functions, activation and viability, as well as their interaction(s) with established antiplatelet medications, by hindering several platelet agonists' pathways and receptors, are thoroughly reviewed. The efficacy and safety of NSAIDs as adjunctive therapies for conditions involving inflammation and platelet activation are also discussed. Emphasis is given to the antiplatelet potential of commonly administered NSAIDs medications, such as ibuprofen, diclofenac, naproxen and ketoprofen, alongside non-opioid analgesic and antipyretic medications like paracetamol. This article delves into their mechanisms of action against different pathways of platelet activation, aggregation and overall platelet functions, highlighting additional health-promoting properties of these anti-inflammatory and analgesic agents, without neglecting the induced by these drugs' side-effects on platelets' functionality and thrombocytopenia. Environmental issues emerging from the ever-increased subscription of these drugs are also discussed, along with the need for novel water treatment methodologies for their appropriate elimination from water and wastewater samples. Despite being efficiently eliminated during wastewater treatment processes on occasion, NSAIDs remain prevalent and are found at significant concentrations in water bodies that receive effluents from wastewater treatment plants (WWTPs), since there is no one-size-fits-all solution for removing all contaminants from wastewater, depending on the specific characteristics of the wastewater. Several novel methods have been studied, with adsorption being proposed as a cost-effective and environmentally friendly method for wastewater purification from such drugs. This article also presents limitations and future prospects regarding the observed antiplatelet effects of NSAIDs, as well as the potential of novel derivatives of these compounds, with benefits in other important platelet functions.

Most commonly prescribed analgesic among 6 to 12-year-olds after extraction in paediatric dentistry - A retrospective study

Background: Using their expertise in analgesics, the dentist should recommend the best prescription at the right dosage to reduce pain without going overboard. Aim: To determine the most commonly prescribed analgesics which are used post-extraction for 6 to 12-year-old children Materials &amp; Methods: A total of 4160 patient data was collected from OPD data from the Department of Pediatric Dentistry, Saveetha Dental College &amp; Hospital of 6 to 12-year-old children who have gotten dental treatment and have received analgesic medication. The dentist should use his or her knowledge of analgesics to prescribe the most effective drug and appropriate dose to alleviate pain while avoiding overmedication. The treatment records of these patients were assessed and data was analyzed. Descriptive analysis and chi-square tests were performed. Results: The majority of the patients (16.7%) were 9 years old. The most commonly prescribed analgesic was found to be paracetamol (56.6%). The most common combination drug prescribed to children was Paracetamol and Ibuprofen (19.5%). P value for the comparison between gender and age with different types of analgesics [0.0005 (&lt;0.05)] was found to be statistically significant. Conclusion: In both males and females, paracetamol was the most prescribed analgesic and most commonly prescribed analgesic, a combination drug; Paracetamol &amp; Ibuprofen.

Analgesia for the treatment of acute pancreatitis: a protocol for a systematic review and network meta-analysis

IntroductionGastrointestinal hospitalisations in the USA cause over US$130 billion in expenditures, and acute pancreatitis is a leading cause of these hospitalisations. Adequate pain control is one of the primary treatment...

Keep Calm: Does parental preoperative anxiety affect post-tonsillectomy pain scores in children?

PurposeTo understand if high parental anxiety leads to increased post-tonsillectomy pain in children.MethodsProspective study including parents of children aged 3–10 years old submitted to tonsillectomy with or without adenoidectomy. To evaluate anxiety, parents were asked to fill the State-Trait Anxiety Inventory form-Y, with postoperative pain being evaluated with the Wong-Baker FACES pain scale at postoperative days 1, 3 and 7. Parents were also asked to register the number of days during which children took analgesic and the number of analgesic intakes needed.Results41 parents were enrolled, of which 95.1% (n = 39) were female with a mean age of 35.64 years (SD 5.751), with 41 children also being enrolled, of which 85.4% of children (n = 35) underwent tonsillectomy and adenoidectomy. 43.9% (n = 18) of parents presented State anxiety scores above the cut-off level and 53.7% (n = 22) above the Trait anxiety scores above the cut-off. Children of parents with high State anxiety presented statistically higher pain scores in both the third (p = 0.035) and the seventh postoperative days (p = 0.006), with significantly longer use of analgesic medication (p = 0.043) being found, as well as a statistically higher number of analgesic intakes (p = 0.045) (Table 4).ConclusionThe present study establishes an association between preoperative parental anxiety, postoperative pain scores and the need for longer analgesic use in children undergoing tonsillectomy. This reinforces the importance of reducing parental anxiety and opens the door for further strategies to better post-tonsillectomy outcomes.

Analgesia in Pregnant Patients: A Literature Review

Pregnant patients physiologically undergo various changes in their bodies due to hormonal actions. The oral cavity is not exempt from these alterations, and repercussions on oral health are also identified. It is essential to provide safe and appropriate dental care during pregnancy, taking into account the gestational trimester and the patient's overall health. Analgesia in pregnant patients remains a taboo for many professionals, especially for newly graduated dental surgeons. The use of local anesthetics in the office as a pain control method makes the procedure safer and more efficient. Regarding orally administered analgesics, acetaminophen is considered the first choice, with dipyrone as the second option. Aspirin, ibuprofen, and corticosteroids may be an option, but their use should be rationalized and when the benefits outweigh the risks to the maintenance of pregnancy and maternal health. The use of analgesia or reduction of the pain protocol in a pregnant patient in the office can be performed with 2% lidocaine with epinephrine, as it is considered safe. However, certain anesthetics, such as benzocaine and procaine, should be avoided due to risks of methemoglobinemia. Nonetheless, the professional must always weigh the risks and benefits of using analgesic medications for the pregnant patient and the fetus when choosing the medication.

Tramadol/Diclofenac Fixed-Dose Combination for Acute Pain Management: Bioavailability Assessment of a Generic Product.

The multimodal analgesia strategy for acute pain involves using 2 or more analgesic medications with distinct mechanisms of action. This study assessed the bioavailability and tolerability of 2 tramadol hydrochloride (50mg)/diclofenac sodium (50mg) fixed-dose combination formulations under fed conditions to attend the Brazilian regulatory requirements for generic product registration. An open-label, randomized, single-dose, 2-period, 2-way crossover trial was conducted, including healthy subjects of both sexes. Subjects received a single dose of either the test or reference formulation of tramadol/diclofenac fixed-dose combination tablets with a 7-day washout period. Blood samples were collected up to 36hours after dosing for tramadol and 12hours for diclofenac and quantified using a validated liquid chromatography-tandem mass spectrometry method. Of 56 subjects enrolled, 53 completed the study. The 90% confidence intervals for maximum plasma concentration and area under the concentration-time curve from time 0 to the last quantifiable concentration were within acceptable bioequivalence limits of 80%-125%. Considering the results presented in this study, the test formulation is bioequivalent to the reference formulation and could be interchangeable in medical practice.

Maternal opioid use during pregnancy and the risk of neonatal opioid withdrawal syndrome in the offspring.

Neonatal opioid withdrawal syndrome (NOWS) is caused by sudden cessation from in utero exposure to opioids. The indications for opioid use during pregnancy are diverse including medication for opioid use disorder and analgesia. The opioid dose typically depends on the indication, with higher doses used for medication for opioid use disorder and lower doses used for analgesia. The aim of this study was to investigate the relationship between maternal opioid dose during pregnancy and the risk of NOWS. We conducted a historical multicenter cohort study of neonates prenatally exposed to opioids in Eastern Denmark during a six-year period from 2013 to 2018. The data was extracted from reviewing the individual's medical record(s), which were identified through a search of the Danish National Patient Register. Four groups (quartiles) according to maternal opioid dose during the last four weeks prior to delivery were compared. Unadjusted and adjusted logistic regression analyses were conducted to examine the risk of NOWS while controlling for relevant covariates. A total of 130 in utero opioid exposed neonates were included. The majority of the pregnant patients (88%) were treated with opioids for analgesic purposes. Overall, 52% of neonates developed NOWS. The cumulative incidence of NOWS was 21%, 28%, 67% and 91% at maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery of 0.7-14 (group I), 14.3-38.6 (group II), 40-90 (group III) and 90.9-1440 (group IV), respectively. Compared to group I the adjusted odds (aOR) of NOWS increased significantly in group III (aOR 10.6 [2.9-39.1]) and group IV (aOR 37.8 [7.6-188.2]) but not in group II (aOR 1.5 [0.4-5.2]). No cases of NOWS were reported at maternal dose less than an average daily dose of five morphine milligram equivalent during the last four weeks prior to delivery. No significant changes in the incidence of NOWS were observed between 2013 and 2018. The odds of neonatal opioid withdrawal syndrome increased significantly as the maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery surpassed 40.

Dexmedetomidine for analgesia and sedation in newborn infants receiving mechanical ventilation.

Dexmedetomidine is a selective alpha-2 agonist with minimal impact on the haemodynamic profile. It is thought to be safer than morphine or stronger opioids, which are drugs currently used for analgesia and sedation in newborn infants. Dexmedetomidine is increasingly being used in children and infants despite not being licenced for analgesia in this group. To determine the overall effectiveness and safety of dexmedetomidine for sedation and analgesia in newborn infants receiving mechanical ventilation compared with other non-opioids, opioids, or placebo. We searched CENTRAL, MEDLINE, Embase, CINAHL, and two trial registries in September 2023. We planned to include randomised controlled trials (RCTs) and quasi-RCTs evaluating the effectiveness of dexmedetomidine compared with other non-opioids, opioids, or placebo for sedation and analgesia in neonates (aged under four weeks) requiring mechanical ventilation. We used standard Cochrane methods. Our primary outcomes were level of sedation and level of analgesia. Our secondary outcomes included days on mechanical ventilation, number of infants requiring additional medication for sedation or analgesia (or both), hypotension, neonatal mortality, and neurodevelopmental outcomes. We planned to use GRADE to assess the certainty of evidence for each outcome. We identified no eligible studies for inclusion. We identified four ongoing studies, two of which appear to be eligible for inclusion; they will compare dexmedetomidine with fentanyl in newborn infants requiring surgery. We listed the other two studies as awaiting classification pending assessment of full reports. One study will compare dexmedetomidine with morphine in asphyxiated newborns undergoing hypothermia, and the other (mixed population, age up to three years) will evaluate dexmedetomidine versus ketamine plus dexmedetomidine for echocardiography. The planned sample size of the four studies ranges from 40 to 200 neonates. Data from these studies may provide some evidence for dexmedetomidine efficacy and safety. Despite the increasing use of dexmedetomidine, there is insufficient evidence supporting its routine use for analgesia and sedation in newborn infants on mechanical ventilation. Furthermore, data on dexmedetomidine safety are scarce, and there are no data available on its long-term effects. Future studies should address the efficacy, safety, and long-term effects of dexmedetomidine as a single drug therapy for sedation and analgesia in newborn infants.

Treatment Effect Modifiers for Return-to-Work in Patients With Musculoskeletal Disorders

Investigating how individual characteristics modify treatment effects can improve understanding, interpretation, and translation of trial findings. The purpose of this secondary analysis was to identify treatment effect modifiers of the MI-NAV trial, a 3 arm, parallel randomized controlled trial which compared motivational interviewing and stratified vocational advice intervention in addition to usual case management (UC), to UC alone. This study included (n = 514) participants with musculoskeletal disorders on sick leave for at least 50% of their contracted work hours for at least 7 consecutive weeks with the Norwegian Labour and Welfare Administration. Sickness absence days was the primary outcome, measured from baseline assessment date until the 6-month follow-up. Potential treatment effect modifiers, identified a priori and informed by expert consultation and literature, were evaluated using linear regression models and statistical interaction tests. For motivational interviewing versus UC, age (mean difference [MD] −.7, 95% confidence interval [CI] −1.5 to .2; P = .13) and self-perceived health status (MD −.3, 95% CI −.7 to .1; P = .19) were identified as potential effect modifiers (P ≤ .2). For stratified vocational advice intervention versus UC, analgesic medication use (MD −26.2, 95% CI −45.7 to −6.7; P = .009) was identified as a treatment effect modifier (P ≤ .05). These findings may assist in more targeted treatment adaptation and translation as well as the planning of future clinical trials. PerspectiveThis secondary analysis of the MI-NAV trial found that analgesic medication use, age, and self-perceived health may modify the effect of 2 vocational interventions on reducing sickness absence in people with musculoskeletal disorders.