Ondansetron for the Prevention of Pruritus in Women Undergoing Cesarean Delivery With Intrathecal Opioid: A Systematic Review and Meta-Analysis.

BACKGROUND: Pruritus is a frequently reported and unpleasant side effect following intrathecal opioid use with frequency further increased among parturients. We have performed a systematic review to assess the overall efficacy of ondansetron for the prevention of pruritus in patients receiving intrathecal opioid as part of spinal anesthesia for cesarean delivery. METHODS: A literature search of MEDLINE, Embase, Cochrane, and Web of Science databases was conducted from date of inception to September 2022. Studies that included patients undergoing cesarean delivery with spinal anesthesia using intrathecal opioid were included. The primary outcome was the presence of pruritus, and the secondary outcome was time to onset of pruritus. Data from included studies were pooled for analysis using an appropriately determined random-effects model. Outcomes were presented using forest plots and 95% confidence intervals. Additional sensitivity and subgroup analysis were performed. Trial sequential analysis was conducted for the primary outcome. RESULTS: Twenty-three randomized controlled trials with a total of 2586 patients were included: 1219 received ondansetron, 1030 received a placebo, and a further 337 received a different study drug and were excluded from analysis. Opioids used in the included studies were morphine, fentanyl, and sufentanil. Patients who received ondansetron showed a significant reduction in the incidence of pruritus compared to the control group (RR, 0.81; 95% confidence interval [CI], 0.71-0.92; I 2 = 64%). There was no significant difference in pruritus onset between the groups (mean difference [MD], 17.54 minutes; 95% CI, -2.18 to 37.26; I 2 = 83%). The overall Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessment of quality of evidence was low. CONCLUSIONS: This systematic review has demonstrated a significant reduction in the incidence of pruritus following the use of ondansetron. This is in contrast to previously published meta-analyses. Studies included were of varying quality and some at high risk of bias with a high degree of statistical heterogeneity. Furthermore, high-quality and well-powered studies are required to confirm these findings.

Pressure-garment therapy for preventing hypertrophic scarring after burn injury.

BACKGROUND: Burn damage to skin often results in scarring; however in some individuals the failure of normal wound-healing processes results in excessive scar tissue formation, termed 'hypertrophic scarring'. The most commonly used method for the prevention and treatment of hypertrophic scarring is pressure-garment therapy (PGT). PGT is considered standard care globally; however, there is continued uncertainty around its effectiveness. OBJECTIVES: To evaluate the benefits and harms of pressure-garment therapy for the prevention of hypertrophic scarring after burn injury. SEARCH METHODS: We used standard, extensive Cochrane search methods. We searched CENTRAL, MEDLINE, Embase, two other databases, and two trials registers on 8 June 2023 with reference checking, citation searching, and contact with study authors to identify additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing PGT (alone or in combination with other scar-management therapies) with scar management therapies not including PGT, or comparing different PGT pressures or different types of PGT. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected trials for inclusion using predetermined inclusion criteria, extracted data, and assessed risk of bias using the Cochrane RoB 1 tool. We assessed the certainty of evidence using GRADE. MAIN RESULTS: We included 15 studies in this review (1179 participants), 14 of which (1057 participants) presented useable data. The sample size of included studies ranged from 17 to 159 participants. Most studies included both adults and children. Eight studies compared a pressure garment (with or without another scar management therapy) with scar management therapy alone, five studies compared the same pressure garment at a higher pressure versus a lower pressure, and two studies compared two different types of pressure garments. Studies used a variety of pressure garments (e.g. in-house manufactured or a commercial brand). Types of scar management therapies included were lanolin massage, topical silicone gel, silicone sheet/dressing, and heparin sodium ointment. Meta-analysis was not possible as there was significant clinical and methodological heterogeneity between studies. Main outcome measures were scar improvement assessed using the Vancouver Scar Scale (VSS) or the Patient and Observer Scar Assessment Scale (POSAS) (or both), pain, pruritus, quality of life, adverse events, and adherence to therapy. Studies additionally reported a further 14 outcomes, mostly individual scar parameters, some of which contributed to global scores on the VSS or POSAS. The amount of evidence for each individual outcome was limited. Most studies had a short follow-up, which may have affected results as the full effect of any therapy on scar healing may not be seen until around 18 months. PGT versus no treatment/lanolin We included five studies (378 participants). The evidence is very uncertain on whether PGT improves scars as assessed by the VSS compared with no treatment/lanolin. The evidence is also very uncertain for pain, pruritus, adverse events, and adherence. No study used the POSAS or assessed quality of life. One additional study (122 participants) did not report useable data. PGT versus silicone We included three studies (359 participants). The evidence is very uncertain on the effect of PGT compared with silicone, as assessed by the VSS and POSAS. The evidence is also very uncertain for pain, pruritus, quality of life, adverse events, adherence, and other scar parameters. It is possible that silicone may result in fewer adverse events or better adherence compared with PGT but this was also based on very low-certainty evidence. PGT plus silicone versus no treatment/lanolin We included two studies (200 participants). The evidence is very uncertain on whether PGT plus silicone improves scars as assessed by the VSS compared with no treatment/lanolin. The evidence is also very uncertain for pain, pruritus, and adverse events. No study used the POSAS or assessed quality of life or adherence. PGT plus silicone versus silicone We included three studies (359 participants). The evidence is very uncertain on the effect of PGT plus silicone compared with silicone, as assessed by the VSS and POSAS. The evidence is also very uncertain for pain, pruritus, quality of life, adverse events, and adherence. PGT plus scar management therapy including silicone versus scar management therapy including silicone We included one study (88 participants). The evidence is very uncertain on the effect of PGT plus scar management therapy including silicone versus scar management therapy including silicone, as assessed by the VSS and POSAS. The evidence is also very uncertain for pain, pruritus, quality of life, adverse events, and adherence. High-pressure versus low-pressure garments We included five studies (262 participants). The evidence is very uncertain on the effect of high pressure versus low pressure PGT on adverse events and adherence. No study used the VSS or the POSAS or assessed pain, pruritus, or quality of life. Different types of PGT (Caroskin Tricot + an adhesive silicone gel sheet versus Gecko Nanoplast (silicone gel bandage)) We included one study (60 participants). The evidence is very uncertain on the effect of Caroskin Tricot versus Gecko Nanoplast on the POSAS, pain, pruritus, and adverse events. The study did not use the VSS or assess quality of life or adherence. Different types of pressure garments (Jobst versus Tubigrip) We included one study (110 participants). The evidence is very uncertain on the adherence to either Jobst or Tubigrip. This study did not report any other outcomes. AUTHORS' CONCLUSIONS: There is insufficient evidence to recommend using either PGT or an alternative for preventing hypertrophic scarring after burn injury. PGT is already commonly used in practice and it is possible that continuing to do so may provide some benefit to some people. However, until more evidence becomes available, it may be appropriate to allow patient preference to guide therapy.

Pharmacological agents for prevention of pruritus in women undergoing Caesarean delivery with neuraxial morphine: a systematic review and Bayesian network meta-analysis.

BACKGROUND: Neuraxial opioids provide effective analgesia for Caesarean delivery, however, pruritus can be a troubling side-effect. Effective agents to prevent pruritus are needed. Our objective was to perform an updated systematic review and network meta-analysis to provide clinicians with a comparison of relative efficacy of available interventions to reduce the incidence of pruritus, induced by either intrathecal or epidural single-shot morphine, in women undergoing Caesarean delivery. METHODS: Databases systematically searched (up to January 2022) included PubMed MEDLINE, Web of Science, EBSCO CINAHL, Embase, LILACS, and two Cochrane databases. We included randomised, controlled trials involving adult female patients undergoing Caesarean delivery. We pooled trials comparing interventions used for preventing pruritus after Caesarean delivery and performed a Bayesian model network meta-analysis. RESULTS: The final primary network included data from comparisons of 14 distinct interventions (including placebo) used to reduce the incidence of pruritus in 6185 participants. We judged five interventions to be 'definitely superior' to placebo: propofol, opioid agonist-antagonists (neuraxial), opioid antagonists, opioid agonist-antagonists (systemic), and serotonin antagonists. For the network evaluating the incidence of severe pruritus (warranting additional therapeutic treatment of pruritus), data were available for 14 interventions (including placebo) in 4489 patients. For this outcome, we judged three interventions to be 'definitely superior' to placebo: dopamine antagonists (neuraxial) and systemic and neuraxial opioid agonist-antagonists. CONCLUSION: Our analysis found several interventions to be effective in reducing the incidence of pruritus. Although sub-hypnotic doses of propofol appear to have an antipruritic effect, replication of this finding and further investigation of optimal dosing are warranted. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42022367058).

Crisaborole Inhibits Itch and Pain by Preventing Neutrophil Infiltration in a Mouse Model of Atopic Dermatitis.

Crisaborole, a phosphodiesterase 4 (PDE4) inhibitor, has been approved for the treatment of mild to moderate atopic dermatitis. Atopic dermatitis is often associated with increased pain. Using a mouse model, this study investigated whether crisaborole suppresses pain associated with atopic dermatitis and the potential mechanisms underlying it. The mouse model for atopic dermatitis was developed by repeatedly applying MC903. MC903-treated mice had increased spontaneous scratching (itch-related behaviour) and wiping behaviour (pain-related behaviour). Crisaborole was topically applied to the cheek skin of MC903-treated mice, and it reduced both itch- and pain-related behaviours in these mice. Immunofluorescence staining revealed that crisaborole reduced neutrophil infiltration and interaction of neutrophils with sensory neurones. Intradermal injection of S100A8/A9, proinflammatory neutrophil mediator, enhanced not only itch-related behaviours evoked by histamine or chloroquine, but also pain-related behaviours evoked by capsaicin. Calcium imaging of mouse dorsal root ganglion neurones revealed that pretreatment with S100A8/A9 significantly increased calcium responses to histamine and capsaicin, and the proportion of chloroquine-sensitive neurones. These findings suggest that the PDE4 inhibitor reduces itch and pain, in part by inhibiting infiltration of S100A8/A9-containing neutrophils in a mouse model of MC903-induced atopic dermatitis.

A structurally optimized FXR agonist, MET409, reduced liver fat content over 12 weeks in patients with non-alcoholic steatohepatitis.

BACKGROUND & AIMS: The benefits of farnesoid X receptor (FXR) agonists in patients with non-alcoholic steatohepatitis (NASH) have been validated, although improvements in efficacy and/or tolerability remain elusive. Herein, we aimed to assess the performance of a structurally optimized FXR agonist in patients with NASH. METHODS: In this 12-week, randomized, placebo-controlled study, we evaluated MET409 - a non-bile acid agonist with a unique chemical scaffold - in patients with NASH. Patients were randomized to receive either 80 mg (n = 20) or 50 mg (n = 19) of MET409, or placebo (n = 19). RESULTS: At Week 12, MET409 lowered liver fat content (LFC), with mean relative reductions of 55% (80 mg) and 38% (50 mg) vs. 6% in placebo (p <0.001). MET409 achieved ≥30% relative LFC reduction in 93% (80 mg) and 75% (50 mg) of patients vs. 11% in placebo (p <0.001) and normalized LFC (≤5%) in 29% (80 mg) and 31% (50 mg) of patients vs. 0% in placebo (p <0.05). An increase in alanine aminotransferase (ALT) was observed with MET409, confounding Week 12 changes from baseline (-25% for 80 mg, 28% for 50 mg). Nonetheless, MET409 achieved ≥30% relative ALT reduction in 50% (80 mg) and 31% (50 mg) of patients vs. 17% in placebo. MET409 was associated with on-target high-density lipoprotein cholesterol decreases (mean changes of -23.4% for 80 mg and -20.3% for 50 mg vs. 2.6% in placebo) and low-density lipoprotein cholesterol (LDL-C) increases (mean changes of 23.7% for 80 mg and 6.8% for 50 mg vs. -1.5% in placebo). Pruritus (mild-moderate) occurred in 16% (50 mg) and 40% (80 mg) of MET409-treated patients. CONCLUSION: MET409 lowered LFC over 12 weeks in patients with NASH and delivered a differentiated pruritus and LDL-C profile at 50 mg, providing the first clinical evidence that the risk-benefit profile of FXR agonists can be enhanced through structural optimization. LAY SUMMARY: Activation of the farnesoid X receptor (FXR) is a clinically validated approach for treating non-alcoholic steatohepatitis (NASH), although side effects such as itching or increases in low-density lipoprotein cholesterol are frequently dose-limiting. MET409, an FXR agonist with a unique chemical structure, led to significant liver fat reduction and delivered a favorable side effect profile after 12 weeks of treatment in patients with NASH. These results provide the first clinical evidence that the risk-benefit profile of FXR agonists can be enhanced.

Onset Mechanism and Pharmaceutical Management of Dry Skin.

Dry skin is a common symptom of various conditions, and elderly individuals commonly exhibit this physiological symptom. Dry skin develops owing to sebum deficiency; however, the use of moisturizers can typically overcome this issue, particularly in patients in whom there are no other skin problems. If dry skin is left untreated, itching and eczema can occur, resulting in skin damage. Additionally, hemodialysis patients exhibit reduced barrier function and can experience pain associated with repeated needle insertion; the repeated use of lidocaine tape to manage the pain can cause further skin damage. To reduce the occurrence of dry skin, the skin is hydrated using moisturizers. Dry skin is also prominent in patients with varicose veins in the lower extremities, and many biochemical studies have shown that skin immunity is altered in patients with dry skin. Moreover, the incidences of dry skin and pruritus differ in male and female patients. Furthermore, in elderly patients, zinc deficiency is likely to cause dry skin, and zinc supplementation may maintain skin hydration. To date, few reports have described dry skin from a clinical point of view. In this review, research on dry skin is presented, and the findings of basic research studies are integrated.

Antipruritic Effect of Nalbuphine, a Kappa Opioid Receptor Agonist, in Mice: A Pan Antipruritic.

Antipruritic effects of kappa opioid receptor (KOR) agonists have been shown in rodent models of acute and chronic scratching (itchlike behavior). Three KOR agonists, nalfurafine, difelikefalin, and nalbuphine, are in clinical studies for antipruritic effects in chronic itch of systemic and skin diseases. Nalfurafine (in Japan) and difelikefalin (in the USA) were approved to be used in the treatment of chronic itch in hemodialysis patients. The FDA-approved nalbuphine has been used in clinic for over 40 years, and it is the only narcotic agonist that is not scheduled. We aimed to study (a) antiscratch activity of nalbuphine against TAT-HIV-1 protein (controls HIV transcription)-, deoxycholic acid (DCA, bile acid)-, and chloroquine (CQ)-induced scratching in a mouse model of acute itch; and (b) whether the effect of nalbuphine is produced via KORs. First, dose-responses were developed for pruritogens. Mice were pretreated with nalbuphine (0.3-10 mg/kg) and then a submaximal dose of pruritogens were administered and the number of scratching bouts was counted. To study if the antiscratch effect of nalbuphine is produced via KOR, we used KOR knock out mice and pharmacologic inhibition of KORs using nor-binaltorphimine, a KOR antagonist. For this aim, we used CQ as a pruritogen. We found that: (a) TAT-HIV-1 protein elicits scratching in a dose-dependent manner; (b) nalbuphine inhibits scratching induced by TAT-HIV-1, DCA, and CQ dose-dependently; and (c) nalbuphine inhibits scratching induced by CQ through KORs. In conclusion, nalbuphine inhibits scratching elicited by multiple pruritogens.

Ondansetron versus ondansetron with dexamethasone to prevent intrathecal-morphine pruritus for caesarean patients: randomised double-blind trial.

The objective of this randomised, double blinded clinical trial was to evaluate the efficacy of prophylactic administration of 4 mg ondansetron as monotherapy versus combination therapy of 4 mg ondansetron plus 8 mg dexamethasone for the prevention of intrathecal morphine-associated pruritus in caesarean section within 24 h. A total of 194 patients were included, 96 patients in the monotherapy group and 98 in the combination group. One hour after the operation, 11.5% of patients in ondansetron group had failure of prophylaxis for pruritus compared to 13.5% of patients in the combination group (p = .66). This decreased throughout the follow-up to reach 0.0% and 1.0% at 24 h in the ondansetron vs. the combination groups respectively. There was no superiority of combining ondansetron with dexamethasone over the use of ondansetron as prophylactic antipruritic in parturients receiving intrathecal morphine for caesarean section.IMPACT STATEMENTWhat is already known on this subject? The incidence of pruritus has been reported to be between 36% and 60% in patients undergoing caesarean section with intrathecal morphine. Ondansetron has been identified as possible antipruritic agent while the antipruritic effect of dexamethasone is inconclusive.What do the results of this study add? The study demonstrated that there was no superiority of combining ondansetron with dexamethasone over the use of ondansetron as prophylactic antipruritic in parturients receiving intrathecal morphine for caesarean section. Moreover, it seems that there is no effect of combining ondansetron with dexamethasone over ondansetron alone on antiemetic consequences.What are the implications of these findings for clinical practice and/or further research? Ondansetron could be an effective antipruritic if used solely for patients undergoing caesarean section.

Ursodeoxycholic acid versus placebo in women with intrahepatic cholestasis of pregnancy (PITCHES): a randomised controlled trial.

BACKGROUND: Intrahepatic cholestasis of pregnancy, characterised by maternal pruritus and increased serum bile acid concentrations, is associated with increased rates of stillbirth, preterm birth, and neonatal unit admission. Ursodeoxycholic acid is widely used as a treatment without an adequate evidence base. We aimed to evaluate whether ursodeoxycholic acid reduces adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy. METHODS: We did a double-blind, multicentre, randomised placebo-controlled trial at 33 hospital maternity units in England and Wales. We recruited women with intrahepatic cholestasis of pregnancy, who were aged 18 years or older and with a gestational age between 20 weeks and 40 weeks and 6 days, with a singleton or twin pregnancy and no known lethal fetal anomaly. Participants were randomly assigned 1:1 to ursodeoxycholic acid or placebo, given as two oral tablets a day at an equivalent dose of 500 mg twice a day. The dose could be increased or decreased at the clinician's discretion, to a maximum of four tablets and a minimum of one tablet a day. We recommended that treatment should be continued from enrolment until the infant's birth. The primary outcome was a composite of perinatal death (in-utero fetal death after randomisation or known neonatal death up to 7 days after birth), preterm delivery (<37 weeks' gestation), or neonatal unit admission for at least 4 h (from birth until hospital discharge). Each infant was counted once within this composite. All analyses were done according to the intention-to-treat principle. The trial was prospectively registered with the ISRCTN registry, number 91918806. FINDINGS: Between Dec 23, 2015, and Aug 7, 2018, 605 women were enrolled and randomly allocated to receive ursodeoxycholic acid (n=305) or placebo (n=300). The primary outcome analysis included 304 women and 322 infants in the ursodeoxycholic acid group, and 300 women and 318 infants in the placebo group (consent to use data was withdrawn for 1 woman and 2 infants). The primary composite outcome occurred in 74 (23%) of 322 infants in the ursodeoxycholic acid group and 85 (27%) of 318 infants in the placebo group (adjusted risk ratio 0·85 [95% CI 0·62-1·15]). Two serious adverse events were reported in the ursodeoxycholic acid group and six serious adverse events were reported in the placebo group; no serious adverse events were regarded as being related to treatment. INTERPRETATION: Treatment with ursodeoxycholic acid does not reduce adverse perinatal outcomes in women with intrahepatic cholestasis of pregnancy. Therefore, its routine use for this condition should be reconsidered. FUNDING: National Institute for Health Research Efficacy and Mechanism Evaluation Programme.

Thymol activates TRPM8-mediated Ca2+ influx for its antipruritic effects and alleviates inflammatory response in Imiquimod-induced mice.

Psoriasis is a highly prevalent chronic dermatitis, characterized by widespread skin inflammation and spontaneous itch. Given the adverse reactions and drug dependence of current treatment, new drugs for psoriasis therapy are urgently needed. This study aims to explore the anti-psoriatic effects of thymol in imiquimod (IMQ) induced mice, and elucidate the potential mechanisms for its therapeutic activities. Thymol reduced the scratching behavior in IMQ mice, and activated Ca2+ response in cervical DRG neurons via TRPM8 channel. Also, thymol alleviated psoriasis-like skin lesions, and attenuated the enhanced infiltration of dermal neutrophils, dendritic cells (DCs) and Th17 cells. In addition, it reversed the upregulated expression of pro-inflammatory cytokines in the skin (TNF-α, IL-22, IL-23, IL-17A, IL-17F, IL-17C, IL-6, IL-1ß and IFN-γ) and serum (TNF-α, IL-6, IL-1ß, IL-17A and IFN-γ). Our results indicated that thymol can effectively ameliorate pruritus and the symptoms of psoriasis-like inflammation induced by IMQ, which makes it a promising drug for the treatment of psoriasis.

Hygiene and emollient interventions for maintaining skin integrity in older people in hospital and residential care settings.

BACKGROUND: Ageing has a degenerative effect on the skin, leaving it more vulnerable to damage. Hygiene and emollient interventions may help maintain skin integrity in older people in hospital and residential care settings; however, at present, most care is based on "tried and tested" practice, rather than on evidence. OBJECTIVES: To assess the effects of hygiene and emollient interventions for maintaining skin integrity in older people in hospital and residential care settings. SEARCH METHODS: We searched the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL, up to January 2019. We also searched five trials registers. SELECTION CRITERIA: Randomised controlled trials comparing hygiene and emollient interventions versus placebo, no intervention, or standard practices for older people aged ≥ 60 years in hospital or residential care settings. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane. Primary outcomes were frequency of skin damage, for example, complete loss of integrity (tears or ulceration) or partial loss of integrity (fissuring), and side effects. Secondary outcomes included transepidermal water loss (TEWL), stratum corneum hydration (SCH), erythema, and clinical scores of dryness or itch. We used GRADE to assess the quality of evidence. MAIN RESULTS: We included six trials involving 1598 residential care home residents; no included trial had a hospital setting. Most participants had a mean age of 80+ years; when specified, more women were recruited than men. Two studies included only people with diagnosed dry skin. Studies were conducted in Asia, Australasia, Europe, and North America. A range of hygiene and emollient interventions were assessed: a moisturising soap bar; combinations of water soak, oil soak, and lotion; regular application of a commercially available moisturiser; use of two different standardised skin care regimens comprising a body wash and leave-on body lotion; bed bath with "wash gloves" containing numerous ingredients; and application of a hot towel after usual care bed bath. In five studies, treatment duration ranged from five days to six months; only one study had post-treatment follow-up (one to eight days from end of treatment). Outcomes in the hot towel study were measured 15 minutes after the skin was wiped with a dry towel. Three studies each had high risk of attrition, detection, and performance bias. Only one trial (n = 984) assessed frequency of skin damage via average monthly incidence of skin tears during six months of treatment. The emollient group (usual care plus twice-daily application of moisturiser) had 5.76 tears per month per 1000 occupied bed-days compared with 10.57 tears in the usual care only group (ad hoc or no standardised skin-moisturising regimen) (P = 0.004), but this is based on very low-quality evidence, so we are uncertain of this result. Only one trial (n = 133) reported measuring side effects. At 56 ± 4 days from baseline, there were three undesirable effects (itch (mild), redness (mild/moderate), and irritation (severe)) in intervention group 1 (regimen consisting of a moisturising body wash and a moisturising leave-on lotion) and one event (mild skin dryness) in intervention group 2 (regimen consisting of body wash and a water-in-oil emulsion containing emollients and 4% urea). In both groups, the body wash was used daily and the emollient twice daily for eight weeks. There were zero adverse events in the usual care group. This result is based on very low-quality evidence. This same study also measured TEWL at 56 ± 4 days in the mid-volar forearm (n = 106) and the lower leg (n = 105). Compared to usual care, there may be no difference in TEWL between intervention groups, but evidence quality is low. One study, which compared application of a hot towel for 10 seconds after a usual care bed bath versus usual care bed bath only, also measured TEWL at 15 minutes after the skin was wiped with a dry towel for one second. The mean TEWL was 8.6 g/m²/h (standard deviation (SD) 3.2) in the hot towel group compared with 8.9 g/m²/h (SD 4.1) in the usual care group (low-quality evidence; n = 42), showing there may be little or no difference between groups. A lower score is more favourable. Three studies (266 participants) measured SCH, but all evidence is of very low quality; we did not combine these studies due to differences in treatments (different skin care regimens for eight weeks; wash gloves for 12 weeks; and single application of hot towel to the skin) and differences in outcome reporting. All three studies showed no clear difference in SCH at follow-up (ranging from 15 minutes after the intervention to 12 weeks from baseline), when compared with usual care. A clinical score of dryness was measured by three studies (including 245 participants); pooling was not appropriate. The treatment groups (different skin care regimens for eight weeks; a moisturising soap bar used for five days; and combinations of water soak, oil soak, and lotion for 12 days) may reduce dryness compared to standard care or no intervention (results measured at 5, 8, and 56 ± 4 days after treatment was initiated). However, the quality of evidence for this outcome is low. Outcomes of erythema and clinical score of itch were not assessed in any included studies. AUTHORS' CONCLUSIONS: Current evidence about the effects of hygiene and emollients in maintaining skin integrity in older people in residential and hospital settings is inadequate. We cannot draw conclusions regarding frequency of skin damage or side effects due to very low-quality evidence. Low-quality evidence suggests that in residential care settings for older people, certain types of hygiene and emollient interventions (two different standardised skin care regimens; moisturising soap bar; combinations of water soak, oil soak, and lotion) may be more effective in terms of clinical score of dryness when compared with no intervention or standard care. Studies were small and generally lacked methodological rigour, and information on effect sizes and precision was absent. More clinical trials are needed to guide practice; future studies should use a standard approach to measuring treatment effects and should include patient-reported outcomes, such as comfort and acceptability.

Cross-talk between Human Spinal Cord µ-opioid Receptor 1Y Isoform and Gastrin-releasing Peptide Receptor Mediates Opioid-induced Scratching Behavior.

BACKGROUND: Although spinal opioids are safe and effective, pruritus is common and distressing. The authors previously demonstrated in mouse spinal cord that interactions between µ-opioid receptor isoform 1D and gastrin releasing peptide receptor mediate morphine-induced scratch. The C-terminal of 1D inhibits morphine-induced scratch without affecting analgesia. The authors hypothesize that human spinal cord also contains itch-specific µ-opioid receptor isoforms which interact with gastrin releasing peptide receptor. METHODS: Reverse transcription polymerase chain reaction was performed on human spinal cord complimentary DNA from two human cadavers. Calcium responses to morphine (1 µM) were examined using calcium imaging microscopy on human cells (HEK293) coexpressing gastrin releasing peptide receptor and different human µ-opioid receptor isoforms. The authors assessed morphine-induced scratching behavior and thermal analgesia in mice following intrathecal injection of morphine (0.3 nmol) and a transactivator of transcription peptide designed from C-terminal sequences of 1Y isoform (0, 0.1, and 0.4 nmol). RESULTS: The authors demonstrated 1Y expression in the spinal cord dorsal horn. Morphine administration evoked a calcium response (mean ± SD) (57 ± 13 nM) in cells coexpressing both gastrin releasing peptide receptor and the 1Y isomer. This was blocked by 10 µM naltrexone (0.7 ± 0.4 nM; P < 0.0001), 1 µM gastrin-releasing peptide receptor antagonist (3 ± 2 nM; P < 0.0001), or 200 µM 1Y-peptide (2 + 2 nM; P < 0.0001). In mice, 0.4 nmol 1Y-peptide significantly attenuated morphine-induced scratching behaviors (scratching bouts, vehicle vs. 1Y-peptide) (92 ± 31 vs. 38 ± 29; P = 0.011; n = 6 to 7 mice per group), without affecting morphine antinociception in warm water tail immersion test (% of maximum possible effect) (70 ± 21 vs. 67 ± 22; P = 0.80; n = 6 mice per group). CONCLUSIONS: Human µ-opioid receptor 1Y isomer is a C-terminal splicing variant of Oprm1 gene identified in human spinal cord. Cross-talk between 1Y and gastrin releasing peptide receptor is required for mediating opioid-induced pruritus. Disrupting the cross talk may have implications for therapeutic uncoupling of desired analgesic effects from side effects of opioids.

Antipruritic Effects of Janus Kinase Inhibitor Tofacitinib in a Mouse Model of Psoriasis.

The Janus kinase 1/3 inhibitor tofacitinib has demonstrated an antipruritic effect in two phase III studies in psoriasis. However, the mechanisms behind this antipruritic effect are still unknown. We presently investigated whether tofacitinib affects spontaneous itch as well as expression of itch-related cytokines and epidermal nerve fiber density (ENFD) in the imiquimod-induced mouse model of psoriasis. Psoriasis-like skin lesions were produced by daily topical application of imiquimod to the back skin. Imiquimod treatment resulted in spontaneous scratching, which was significantly inhibited by tofacitinib treatment. Imiquimod treatment significantly increased mRNA expression of Il22, Il23, and Il31, reduced peptidergic ENFD, and increased nonpeptidergic ENFD compared to naive mice. Tofacitinib significantly decreased the expression of those cytokines and increased peptidergic ENFD without a significant effect on nonpeptidergic ENFD. Tofacitinib may inhibit psoriatic itch through inhibition of cytokine expression as well as modulation of epidermal innervation.

Lifestyle changes for treating psoriasis.

BACKGROUND: Psoriasis is an inflammatory skin disease that presents with itching, red, scaling plaques; its worsening has been associated with obesity, drinking, smoking, lack of sleep, and a sedentary lifestyle. Lifestyle changes may improve psoriasis. OBJECTIVES: To assess the effects of lifestyle changes for psoriasis, including weight reduction, alcohol abstinence, smoking cessation, dietary modification, exercise, and other lifestyle change interventions. SEARCH METHODS: We searched the following databases up to July 2018: the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched the China National Knowledge Infrastructure, the Airiti Library, and five trials registers up to July 2018. We checked the references of included trials for further relevant trials, and we asked the authors of the included trials if they were aware of any relevant unpublished data. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of lifestyle changes (either alone or in combination) for treating psoriasis in people diagnosed by a healthcare professional. Treatment had to be given for at least 12 weeks. Eligible comparisons were no lifestyle changes or another active intervention. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The primary outcome measures were 'Severity of psoriasis' and 'Adherence to the intervention'. Secondary outcomes were 'Quality of life', 'Time to relapse', and 'Reduction in comorbidities'. We used GRADE to assess the quality of the evidence for each outcome. MAIN RESULTS: We included 10 RCTs with 1163 participants (mean age: 43 to 61 years; 656 men and 478 women were reported). Six trials examined the effects of dietary intervention (low-calorie diet) in 499 obese participants (mean age: 44.3 to 61 years; where reported, 395 had moderate-to-severe psoriasis). One trial assessed a combined dietary intervention and exercise programme in 303 obese participants with moderate-to-severe psoriasis who had started a systemic therapy for psoriasis and had not achieved clearance after four weeks of continuous treatment (median age: 53 years). Another trial assessed a walking exercise and continuous health education in 200 participants (mean age: 43.1 years, severity not reported). Finally, two trials included education programmes promoting a healthy lifestyle in 161 participants (aged 18 to 78 years), with one trial on mild psoriasis and the other trial not reporting severity.Comparisons included information only; no intervention; medical therapy alone; and usual care (such as continuing healthy eating).All trials were conducted in hospitals and treated participants for between 12 weeks and three years. One trial did not report the treatment period. Seven trials measured the outcomes at the end of treatment and there was no additional follow-up. In two trials, there was follow-up after the treatment ended. Five trials had a high risk of performance bias, and four trials had a high risk of attrition bias.We found no trials assessing interventions for alcohol abstinence or smoking cessation. No trials assessed time to relapse. Only two trials assessed adverse events; in one trial these were caused by the add-on therapy ciclosporin (given in both groups). The trial comparing two dietary interventions to a no-treatment group observed no adverse events.The results presented in this abstract are based on trials of obese participants.Outcomes for dietary interventions versus usual care were measured 24 weeks to six months from baseline. Compared to usual care, dietary intervention (strict caloric restriction) may lead to 75% or greater improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) (risk ratio (RR) 1.66, 95% confidence interval (CI) 1.07 to 2.58; 2 trials, 323 participants; low-quality evidence). Adherence to the intervention may be greater with the dietary intervention than usual care, but the 95% CI indicates that the dietary intervention might also make little or no difference (RR 1.26, 95% CI 0.76 to 2.09; 2 trials, 105 participants; low-quality evidence). Dietary intervention probably achieves a greater improvement in dermatology quality-of-life index (DLQI) score compared to usual care (MD -12.20, 95% CI -13.92 to -10.48; 1 trial, 36 participants; moderate-quality evidence), and probably reduces the BMI compared to usual care (MD -4.65, 95% CI -5.93 to -3.36; 2 trials, 78 participants; moderate-quality evidence).Outcomes for dietary interventions plus exercise programme were measured 16 weeks from baseline and are based on one trial (303 participants). Compared to information only (on reducing weight to improve psoriasis), combined dietary intervention and exercise programme (dietetic plan and physical activities) probably improves psoriasis severity, but the 95% CI indicates that the intervention might make little or no difference (PASI 75: RR 1.28, 95% CI 0.83 to 1.98). This combined intervention probably results in a greater reduction in BMI (median change -1.10 kg/m², P = 0.002), but there is probably no difference in adherence (RR 0.95, 95% CI 0.89 to 1.01; 137/151 and 145/152 participants adhered in the treatment and control group, respectively). There were no data on quality of life. These outcomes are based on moderate-quality evidence. AUTHORS' CONCLUSIONS: Dietary intervention may reduce the severity of psoriasis (low-quality evidence) and probably improves quality of life and reduces BMI (moderate-quality evidence) in obese people when compared with usual care, while combined dietary intervention and exercise programme probably improves psoriasis severity and BMI when compared with information only (moderate-quality evidence). None of the trials measured quality of life.We did not detect a clear difference in treatment adherence between those in the combined dietary intervention and exercise programme group and those given information only (moderate-quality evidence). Adherence may be improved through dietary intervention compared with usual care (low-quality evidence). Participants generally adhered well to the lifestyle interventions assessed in the review.No trials assessed the time to relapse. Trial limitations included unblinded participants and high dropout rate.Future trials should reduce dropouts and include comprehensive outcome measures; they should examine whether dietary intervention with or without an exercise programme is effective in non-obese people with psoriasis, whether an additional exercise programme is more effective than dietary intervention alone, whether the time to relapse prolongs in people who receive dietary intervention with or without exercise programme, and whether smoking cessation and alcohol abstinence are effective in treating psoriasis.

Prophylactic granisetron for post-spinal anesthesia shivering in cesarean section: A randomized controlled clinical study.

BACKGROUND: The serotonergic system is known to be involved in control of post-anesthetic shivering. Our hypothesis was that prophylactic granisetrone (serotonin antagonist) might reduce incidence of post-spinal anesthesia shivering in cesarean section. METHODS: Parturient scheduled for elective cesarean delivery under spinal anesthesia were allocated to receive 0.9% saline (Group I, n = 71), 1 mg granisetron (Group II, n = 69), or 0.7 mg granisetron (Group III, n = 72) before the spinal block. Assessment parameters included; hemodynamics, tympanic membrane temperature, neonatal Apgar score, shivering score, patient satisfaction scores about shivering prophylaxis and adverse effects. RESULTS: Clinically significant shivering was recorded in 55/71 patients (77.5%) in group I, 11/69 (15.9%) in group II and 21/72 (29.2%) in group III (P = 0.000). The intensity of shivering was significantly lower in patients who received granisetron 1 mg compared with granisetron 0.7 mg or saline (P = 0.000). Patients who received prophylactic granisetron 1 mg reported lower mean intraoperative arterial pressure and heart rate values and consumed higher doses of iv ephedrine compared with 0.7 mg granisetron or saline placebo (P < 0.05). Pruritus significantly decreased from (22.5%) in control group to (0%) in granisetron groups (P = 0.000). Nausea was reported in 8 vs 10 and four in group I, II and III, respectively (P < 0.03). Sixteen vs eight and six patients vomited in group I, II, and III, respectively (P < 0.03). Higher patient satisfaction scores were recorded in group II (9.83 ± 0.29, P < 0.03) and III (9.14 ± 1.04, P < 0.04), compared with control group (8.23 ± 1.14). CONCLUSION: Prophylactic granisetron effectively reduced incidence and severity of perioperative shivering in a dose dependent manner, compared to placebo controls.

Narrowband ultraviolet B phototherapy improves quality of life of psoriasis and atopic dermatitis patients up to 3 months: Results from an observational multicenter study.

BACKGROUND/PURPOSE: Narrowband UVB phototherapy is a common treatment modality in psoriasis and atopic dermatitis, but evidence of its actual effect in clinical setting is sparse. Our aim was to assess the effectiveness and costs of narrowband UVB phototherapy in psoriasis and atopic dermatitis in clinical setting. METHODS: We observed 207 psoriasis patients and 144 atopic dermatitis patients in eight centers. SAPASI, PO-SCORAD, and VAS measures were used at baseline, at the end, and 3 months after the narrowband UVB phototherapy course. Quality of life was measured using Dermatology Life Quality Index (DLQI), and costs were assessed using a questionnaire. RESULTS: In both psoriasis and atopic dermatitis, the DLQI and Self-Administrated PASI (SAPASI)/Patient-Oriented SCORAD (PO-SCORAD) improved significantly and the results remained improved for at least 3 months in both groups. Alleviation of pruritus correlated with better quality of life in both patient groups. We reported slight redness and burning side effects which were due to lack of MED testing. Self-administered tools proved to be useful in evaluating pruritus and severity of the disease in psoriasis and atopic dermatitis. Mean patient costs were 310 € and 21 hours of time, and mean costs for the healthcare provider were 810 €. CONCLUSION: In psoriasis, narrowband UVB is a very efficient treatment in clinical setting, whereas in atopic dermatitis, more studies are needed to determine the best dosage.

Sub-hypnotic dose of propofol as antiemetic prophylaxis attenuates intrathecal morphine-induced postoperative nausea and vomiting, and pruritus in parturient undergoing cesarean section - a randomized control trial.

BACKGROUND: Postoperative Nausea and Vomiting (PONV) is a dreadful and uncomfortable experience that significantly detracts patients' quality of life after surgery. This study aimed to examine the antiemetic effect of a single sub-hypnotic dose of propofol as prophylaxis for PONV. METHOD: In this prospective, double-blind, randomized control trial, 345 parturients presented for elective cesarean section at the Obstetric unit of Tamale Teaching Hospital were recruited. Each recruited parturient was randomly assigned to one of three groups; Propofol group (n = 115) represented those who received propofol 0.5 mg/kg, Metoclopramide group (n = 115) represented those who received metoclopramide 10 mg and, Control group (n = 115) represented those who received 0.9% saline. Spinal anesthesia with 0.5% hyperbaric bupivacaine 7.5-10 mg, and intrathecal morphine 0.2 mg was employed for the anesthesia. RESULTS: The data indicate that 108 (93.9%) parturients from the control group, 10 (8.7%) from the propofol group and 8 (7.0%) from the metoclopramide group experienced some incidence of PONV. There was no significant difference in the incidence of PONV (nausea, vomiting, and none) between the propofol and the metoclopramide groups (P = 0.99; 0.31; and 0.35 respectively). Parturients who received antiemetic agents were 105 (97.2%), 1 (10.0%) and 3 (37.5%) from the control, propofol and metoclopramide groups respectively. The data indicated that 98 (85.2%) parturients from the control, 3 (2.6%) from propofol group, and 100 (87.0%) from the metoclopramide group experienced some levels of pruritus. There was a significant difference in the incidence of pruritus (mild, moderate, and no pruritus) between the metoclopramide and propofol groups (P <  0.01; P <  0.01; and P <  0.01 respectively). CONCLUSION: A sub-hypnotic dose of propofol is effective as metoclopramide in the prevention of PONV in parturient undergoing cesarean section under spinal anesthesia with intrathecal morphine. Sub-hypnotic dose of propofol significantly reduces the incidence of postoperative pruritus following intrathecal morphine use. TRIAL REGISTRATION: Current control trial, registered at ISRCTN trial registry: ISRCTN15475205 . Date registered: 03/04/2019. Retrospectively registered.

Long-term omalizumab outcomes in chronic idiopathic urticaria: a real-world study.

Background: Although clinical trials documented omalizumab's efficacy in U.S. patients with chronic idiopathic urticaria (CIU), the real-world evidence on its long-term effectiveness is lacking. Objective: To assess omalizumab use and the long-term response in a large sample of U.S. real-world patients. Methods: Patients with CIU and ≥ 12 years old who were initiated on omalizumab (index date) and with ≥ 6 months of postindex data were identified in an electronic medical record system (2007-2018). Omalizumab use was described. Provider assessments of disease control and course, and patient-reported symptoms were compared at 6-month intervals postindex versus baseline in the patients with values available at both time points. Results: A total of 1096 patients (mean age, 44.1 years; 74.7% women) were followed up for a mean of 19 months postindex. Patients, predominantly initiated on a 300-mg dose, received a mean of 15 omalizumab administrations and were treated continuously for a mean of 14.2 months. At 6 months postindex versus baseline, the patients (n = 708) were more likely to be well controlled (odds ratio [OR] 31.68 [95% confidence interval {CI}, 17.20-58.36]) with an improved disease course (OR 15.73 [95% CI, 11.33-21.85]). Moreover, the patients (n = 373) were less likely to report itching (OR 0.39 [95% CI, 0.21-0.76]), rash (OR 0.59 [95% CI, 0.45-0.78]), and swelling (OR 0.46 [95% CI, 0.36-0.59]). Benefits associated with omalizumab treatment were sustained through month 24 and beyond. Conclusion: This real-world study showed that the patients who received a mean of 15 omalizumab administrations over a mean of 14.2 months experienced, starting at 6 and through 24 months after omalizumab initiation and beyond, improved CIU control, course, and symptoms.

Prophylactic Nalbuphine to Prevent Neuraxial Opioid-Induced Pruritus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PURPOSE: Evaluate the efficacy of prophylactic nalbuphine in preventing neuraxial opioid-induced pruritus. DESIGN: Systematic review and meta-analysis. METHODS: Following the PRISMA statement, PubMed, CINAHL, Cochrane and EMBASE were searched for eligible studies. FINDINGS: A total of 17 trials consisting of 1,052 patients were evaluated. Compared to placebo, there is low quality of evidence that nalbuphine was effective in reducing the incidence of pruritus in all patient population (RR, 0.66; 95% CI, 0.52 to 0.83; P = .0004) and obstetrics (RR, 0.81; 95% CI, 0.67 to 0.98; P = .03). We also found moderate quality of evidence that nalbuphine lowered pruritus in non-obstetrics, the number of rescue pruritus therapy and severity of pruritus episodes. However, nalbuphine did not cause sedation and affect pain scores. CONCLUSIONS: Prophylactic nalbuphine decreased the incidence and severity of pruritus without adverse effects on sedation and analgesic effect of opioids.