Hybridized quantum dot, silica, and gold nanoparticles for targeted chemo-radiotherapy in colorectal cancer theranostics.

Multimodal nanoparticles, utilizing quantum dots (QDs), mesoporous silica nanoparticles (MSNs), and gold nanoparticles (Au NPs), offer substantial potential as a smart and targeted drug delivery system for simultaneous cancer therapy and imaging. This method entails coating magnetic GZCIS/ZnS QDs with mesoporous silica, loading epirubicin into the pores, capping with Au NPs, PEGylation, and conjugating with epithelial cell adhesion molecule (EpCAM) aptamers to actively target colorectal cancer (CRC) cells. This study showcases the hybrid QD@MSN-EPI-Au-PEG-Apt nanocarriers (size ~65 nm) with comprehensive characterizations post-synthesis. In vitro studies demonstrate the selective cytotoxicity of these targeted nanocarriers towards HT-29 cells compared to CHO cells, leading to a significant reduction in HT-29 cell survival when combined with irradiation. Targeted delivery of nanocarriers in vivo is validated by enhanced anti-tumor effects with reduced side effects following chemo-radiotherapy, along with imaging in a CRC mouse model. This approach holds promise for improved CRC theranostics.

Enhanced theranostic efficacy of epirubicin-loaded SPION@MSN through co-delivery of an anti-miR-21-expressing plasmid and ZIF-8 hybridization to target colon adenocarcinoma.

Using targeted drug delivery systems has emerged as a promising approach to increase the efficacy of chemotherapy, particularly in combination with gene therapy. The overexpression of miR-21 plays a crucial role in colorectal cancer (CRC) progression, and targeted inhibition of miR-21 offers significant potential for enhancing CRC chemotherapy outcomes. In this study, a theranostic system based on mesoporous silica and superparamagnetic iron oxide nanoparticles (SPION@MSNs) was synthesized as a core-shell structure. After loading epirubicin (EPI) in the open pores of MSN, the plasmid expressing anti-miR-21 (pDNA) covered the outer surface with the help of a ZIF-8 (zeolitic imidazolate framework-8) film. Afterward, polyethylene glycol (PEG) and AS1411 aptamer were conjugated to the surface to improve the protective, biocompatibility, and targeting abilities of the nanocarrier. Moreover, the physicochemical characteristics as well as the loading capacity and release profile of EPI and pDNA were fully evaluated. The uptake of the nanoparticles by CRC and normal cell lines in addition to the anticancer effects related to targeted combinational therapy were investigated in vitro. Finally, in vivo tests were performed on BALB/c mice bearing colorectal tumors to evaluate the effectiveness of the targeted nanoparticles, their possible side effects, and also their application in fluorescence and magnetic imaging in vivo. The successful synthesis of SPION@MSN-EPI/pDNA-ZIF-8-PEG-Apt nanoparticles (∼68 nm) and good loading efficiency and controlled release of EPI and pDNA were confirmed. Moreover, hemolysis and gel retardation assays demonstrated the biocompatibility and plasmid protection. Cellular uptake and expression of copGFP illustrated selective entry and transient transfection of targeted nanoparticles, consistent with the cytotoxicity results that indicated the synergistic effects of chemo-gene therapy. The results of animal studies proved the high antitumor efficiency of targeted nanoparticles with minimal tissue damage, which was in line with fluorescence and magnetic imaging results. The novel synthesized nanoparticles containing SPION@MSN-ZIF-8 were suitable for CRC theranostics, and the combined approach of chemo-gene therapy suppressed the tumor more effectively.

Real-world effectiveness of repeated ketamine infusions for treatment resistant depression during the COVID-19 pandemic.

Herein we evaluate the impact of COVID-19 restrictions on antidepressant effectiveness of intravenous (IV) ketamine in adults with treatment-resistant depression (TRD). We conducted a case series analysis of adults with TRD (n = 267) who received four ketamine infusions at an outpatient clinic in Ontario, Canada, during COVID-19 restrictions (from March 2020 - February 2021; n = 107), compared to patients who received treatment in the previous year (March 2019 - February 2020; n = 160). Both groups experienced significant and comparable improvements in depressive symptoms, suicidal ideation, and anxiety with repeated ketamine infusions. Effectiveness of IV ketamine was not attenuated during the COVID-19 period.

Interventions to reduce medication errors in anesthesia: a systematic review.

BACKGROUND: The objective of this study was to provide a synthesis of the interventions designed to reduce medication errors in anesthetized patients. METHODS: We electronically searched major databases using index and free-text keywords related to anesthesia and medication errors. We included cohort studies exploring interventions to reduce anesthetic medication errors in both adult and pediatric patients. The risk of bias for each study was assessed using the Newcastle-Ottawa Scale. RESULTS: One thousand five-hundred and fifty-eight titles or abstracts were screened, and 56 full-text studies were assessed for eligibility; eight studies were included in the final analysis. Case reports and retrospective studies were excluded. The quality of most studies (n = 6) was graded as "low". There were three categories of interventions: I) multimodal interventions (6 studies, n = 900,170 medication administrations) showed a reduction in rates of errors of 21-35% per administration and 37-41% per anesthetic; II) improved labels (1 study, n = 55,426 medication administrations) resulted in a 37% reduction in rates of errors per anesthetic; and III) the effect of education was assessed in one study and showed no effect. CONCLUSION: Multimodal interventions and improved labelling reduce medication errors in anesthetized patients.

RéSUMé: CONTEXTE: L'objectif de cette étude était de fournir une synthèse des interventions visant à réduire les erreurs de médicaments chez les patients anesthésiés. MéTHODE: Nous avons fait une recherche électronique dans les principales bases de données à l'aide de l'index et de mots clés en texte libre liés à l'anesthésie et aux erreurs de médicaments. Nous avons inclus les études de cohorte explorant des interventions pour réduire des erreurs de médicaments en anesthésie chez des patients adultes et pédiatriques. Le risque de biais de chaque étude a été évalué à l'aide de l'échelle de Newcastle-Ottawa. RéSULTATS: Mille cinq cent cinquante-huit titres ou résumés ont été passés en revue, et 56 études en texte intégral ont été évaluées pour en déterminer l'admissibilité; huit études ont été incluses dans l'analyse finale. Les présentations de cas et les études rétrospectives ont été exclues. La qualité de la plupart des études (n = 6) a été classée comme « faible ¼. Il y avait trois catégories d'interventions : I) les interventions multimodales (6 études, n = 900 170 administrations de médicaments) ont montré une réduction des taux d'erreurs de 21 à 35 % par administration et de 37 à 41 % par anesthésique; II) l'amélioration des étiquettes (1 étude, n = 55 426 administrations de médicaments) a entraîné une réduction de 37 % des taux d'erreurs par anesthésique; et III) l'effet de la formation a été évalué dans une étude et n'a montré aucun effet. CONCLUSION: Les interventions multimodales et l'amélioration de l'étiquetage réduisent les erreurs de médicaments chez les patients anesthésiés.

The effectiveness of repeated intravenous ketamine on depressive symptoms, suicidal ideation and functional disability in adults with major depressive disorder and bipolar disorder: Results from the Canadian Rapid Treatment Center of Excellence.

BACKGROUND: The effectiveness, tolerability, and safety of intravenous (IV) ketamine in adults with treatment resistant depression (TRD) receiving care in real-word settings is insufficiently characterized. Herein, results from a naturalistic, retrospective study are presented from a Canadian outpatient IV ketamine clinic. METHODS: Adults (N = 213; Mage = 45) with Major Depressive Disorder or Bipolar Disorder, with a minimum of Stage 2 antidepressant resistance, received IV ketamine at a community-based multi-disciplinary clinic. The primary outcome measure was change from baseline to post-infusion 4 on the Quick Inventory for Depression Symptomatology-Self Report-16 (QIDS-SR16; n = 190). Secondary measures included QIDS-SR16-measured response and remission rates, changes from baseline to endpoint in Generalized Anxiety Disorder-7 Scale (GAD-7; n = 188) and the Sheehan Disability Scale (SDS; n = 168). RESULTS: Significant improvement in total depressive symptoms severity (p < 0.0001) was observed after four infusions of IV ketamine 0.5-0.75 mg/kg. Moreover, the response rate (QIDS-SR16 total score change ≥ 50%) was 27% and remission (QIDS-SR16 total score ≤5) rate was 13%. Patients receiving IV ketamine exhibited anxiolytic effects (p < 0.0001,), improved overall psychosocial function (p < 0.0001), and reduced suicidal ideation (p < 0.0001). Compared to the baseline infusion, dissociation severity significantly reduced in subsequent infusions. LIMITATIONS: This was a naturalistic, retrospective study, without a control group. CONCLUSIONS: IV ketamine was safe, well-tolerated, and effective at improving depressive, anxiety, and functional impairment symptoms in a well-characterized cohort of adults with TRD.

A Perioperative Smoking Cessation Intervention With Varenicline, Counseling, and Fax Referral to a Telephone Quitline Versus a Brief Intervention: A Randomized Controlled Trial.

BACKGROUND: The effectiveness of perioperative interventions to quit smoking with varenicline has not been compared with brief interventions. Our objective was to determine the efficacy of a comprehensive smoking cessation program versus a brief intervention for smoking cessation. METHODS: In this prospective, multicenter study, 296 patients were randomized to participate in a smoking cessation program (one 10- to 15-minute counseling session, pharmacotherapy with varenicline, an educational pamphlet, and a fax referral to a telephone quitline); or brief advice and self-referral to a telephone quitline. The primary outcome was the 7-day point prevalence (PP) abstinence at 12 months after surgery. Secondary outcomes included abstinence at 1, 3, and 6 months. Multivariable generalized linear regression was used to identify independent variables related to abstinence. RESULTS: The 7-day PP abstinence for the smoking cessation program versus brief advice group was 42.4% vs 26.2% (relative risk [RR], 1.62; 95% confidence interval [CI], 1.16-2.25; P = .003) at 12 months. The 7-day PP abstinence at 1, 3, and 6 months was higher in the smoking cessation group versus the brief advice group: 45.7% vs 25.5% (RR, 1.79; 95% CI, 1.29-2.49; P < .001), 46.4% vs 26.9% (RR, 1.72; 95% CI, 1.25-2.37; P< .001), and 45.0% vs 26.2% (RR, 1.72; 95% CI, 1.24-2.38; P < .001), respectively. Participating in the smoking cessation group predicted abstinence at 12 months (RR, 1.58; 95% CI, 1.12-2.21; P = .0087). CONCLUSIONS: A perioperative smoking cessation program with counseling, pharmacotherapy with varenicline, an educational pamphlet, and a fax referral to a quitline increased abstinence from smoking 1, 3, 6, and 12 months after surgery versus a brief intervention.

Surgical resection versus liver transplant for patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma is a major worldwide health problem, involving more than half a million new patients yearly, with a different incidence in different parts of the world. Hepatocellular carcinoma develops in about 80% of cirrhotic patients, and cirrhosis is considered the strongest predisposing factor for it. Surgical resection and liver transplantation are conventional treatment modalities that can offer long-term survival for patients with hepatocellular carcinoma. OBJECTIVES: To assess the benefits and harms of surgical resection compared with those of liver transplantation in patients with hepatocellular carcinoma. SEARCH METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded (SCI-EXPANDED) at ISI Web of Science (last search February 2013). We also searched the abstracts from annual meetings of the American Society of Clinical Oncology, the American Association for the Study of Liver Diseases (AASLD), and the European Association for the Study of the Liver (EASL), provided through The Cochrane Hepato-Biliary Group until February 2013. SELECTION CRITERIA: Randomised clinical trials comparing surgical resection and hepatic transplantation. DATA COLLECTION AND ANALYSIS: The search strategies were run and two authors individually evaluated whether the retrieved studies fulfilled the inclusion criteria. MAIN RESULTS: No randomised clinical trials comparing surgical resection and liver transplantation as the major methods of treating hepatocellular carcinoma were found. AUTHORS' CONCLUSIONS: There are no randomised clinical trials comparing surgical resection and liver transplantation for hepatocellular carcinoma treatment.

The facilitatory effects of intravenous dexmedetomidine on the duration of spinal anesthesia: a systematic review and meta-analysis.

BACKGROUND: Central mechanisms have been proposed to explain the prolongation of effect reported with the off-label use of dexmedetomidine as an adjuvant in local anesthetic admixtures. We evaluated whether IV dexmedetomidine can prolong the duration of sensory block associated with spinal anesthesia. METHODS: The authors searched MEDLINE, Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials databases for randomized controlled trials investigating the facilitatory effects of IV administration of dexmedetomidine (dexmedetomidine group) compared with placebo (control group) on single-injection local anesthetic-based spinal anesthesia. Durations of sensory and motor block, sensory and motor block onset times, postoperative pain scores, time to first analgesic request, analgesic consumption, and dexmedetomidine-related side effects were evaluated. Results were combined using random effects modeling when appropriate. RESULTS: A total of 364 patients were analyzed from 7 intermediate to high-quality randomized controlled trials. When IV dexmedetomidine accompanied spinal anesthesia, sensory block duration was prolonged by at least 34% (point estimate: 38%), P < 0.00001, motor block duration was prolonged by at least 17% (point estimate: 21%), P < 0.00001, and time to first analgesic request was increased by at least 53% (point estimate: 60%), P < 0.00001. The use of dexmedetomidine was associated with a 3.7-fold increase (95% confidence interval, 1.53-8.82, P = 0.004) in transient reversible bradycardia. There was no difference in the incidence of hypotension or postoperative sedation, and none of the patients experienced respiratory depression. CONCLUSION: IV dexmedetomidine can prolong the duration of sensory block, motor block, and time to first analgesic request associated with spinal anesthesia.

A perioperative smoking cessation intervention with varenicline: a double-blind, randomized, placebo-controlled trial.

BACKGROUND: The efficacy of perioperative tobacco interventions on long-term abstinence and the safety of smoking cessation less than 4 weeks before surgery is unclear. Our objective was to determine the efficacy and safety of a perioperative smoking cessation intervention with varenicline to reduce smoking in elective surgical patients. METHODS: In a prospective, multicenter, double-blind, placebo-controlled trial, 286 patients were randomized to receive varenicline or placebo. Both groups received in-hospital and telephone counseling during 12 months. The primary outcome was the 7-day point prevalence abstinence rate 12 months after surgery. Secondary outcomes included abstinence at 3 and 6 months after surgery. Multivariable logistic regression was used to identify independent variables related to abstinence. RESULTS: The 7-day point prevalence abstinence at 12 months for varenicline versus placebo was 36.4% versus 25.2% (relative risk: 1.45; 95%: CI: 1.01-2.07; P = 0.04). At 3 and 6 months, the 7-day point prevalence abstinence was 43.7% versus 31.9% (relative risk: 1.37; 95% CI: 1.01 to 1.86; P = 0.04), and 35.8% versus 25.9% (relative risk: 1.43; 95%: CI 1.01-2.04; P = 0.04) for varenicline versus placebo, respectively. Treatment with varenicline (odds ratio: 1.76; 95% CI: 1.03-3.01; P = 0.04), and preoperative nicotine dependence (odds ratio: 0.82, 95% CI: 0.68 to 0.98; P = 0.03) predicted abstinence at 12 months. The adverse events profile in both groups was similar except for nausea, which occurred more frequently for varenicline versus placebo (13.3% vs. 3.7%, P = 0.004). CONCLUSIONS: A perioperative smoking cessation intervention with varenicline increased abstinence from smoking 3, 6, and 12 months after elective noncardiac surgery with no increase in serious adverse events.

Short-term preoperative smoking cessation and postoperative complications: a systematic review and meta-analysis.

PURPOSE: The literature was reviewed to determine the risks or benefits of short-term (less than four weeks) smoking cessation on postoperative complications and to derive the minimum duration of preoperative abstinence from smoking required to reduce such complications in adult surgical patients. SOURCE: We searched MEDLINE, EMBASE, Cochrane, and other relevant databases for cohort studies and randomized controlled trials that reported postoperative complications (i.e., respiratory, cardiovascular, wound-healing) and mortality in patients who quit smoking within six months of surgery. Using a random effects model, meta-analyses were conducted to compare the relative risks of complications in ex-smokers with varying intervals of smoking cessation vs the risks in current smokers. PRINCIPAL FINDINGS: We included 25 studies. Compared with current smokers, the risk of respiratory complications was similar in smokers who quit less than two or two to four weeks before surgery (risk ratio [RR] 1.20; 95% confidence interval [CI] 0.96 to 1.50 vs RR 1.14; CI 0.90 to 1.45, respectively). Smokers who quit more than four and more than eight weeks before surgery had lower risks of respiratory complications than current smokers (RR 0.77; 95% CI 0.61 to 0.96 and RR 0.53; 95% CI 0.37 to 0.76, respectively). For wound-healing complications, the risk was less in smokers who quit more than three to four weeks before surgery than in current smokers (RR 0.69; 95% CI 0.56 to 0.84). Few studies reported cardiovascular complications and there were few deaths. CONCLUSION: At least four weeks of abstinence from smoking reduces respiratory complications, and abstinence of at least three to four weeks reduces wound-healing complications. Short-term (less than four weeks) smoking cessation does not appear to increase or reduce the risk of postoperative respiratory complications.

Preoperative pain sensitivity and its correlation with postoperative pain and analgesic consumption: a qualitative systematic review.

Pain perception to minor physical stimuli has been hypothesized to be related to subsequent pain ratings after surgery. The objective of this systematic review was to evaluate the correlation between preoperative pain sensitivity and postoperative pain intensity. After a literature search of MEDLINE, EMBASE, and meeting abstracts, we identified 15 studies (n = 948 patients) with univariate and/or multivariate analysis on the topic. In these studies, three types of pain stimuli were applied: thermal, pressure, and electrical pain. The intensity of suprathreshold heat pain (i.e., pain beyond patient threshold) was most consistently shown to correlate with postoperative pain. The most common limitation of the included studies was the method of statistical analysis and lack of multivariate analysis. More research is required to establish the correlation of other pain sensitivity variables with postoperative pain outcomes.

Percutaneous needle aspiration, injection, and re-aspiration with or without benzimidazole coverage for uncomplicated hepatic hydatid cysts.

BACKGROUND: Hepatic hydatid cyst is an important public health problem in parts of the world where dogs are used for cattle breeding. Management of uncomplicated hepatic hydatid cysts is currently surgical. However, the puncture, aspiration, injection, and re-aspiration (PAIR) method with or without benzimidazole coverage has appeared as an alternative over the past decade. OBJECTIVES: To assess the benefits and harms of PAIR with or without benzimidazole coverage for patients with uncomplicated hepatic hydatid cyst in comparison with sham/no intervention, surgery, or medical treatment. SEARCH STRATEGY: The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, DARE, and ACP Journal Club and full text searches were combined (all searched October 2010). Reference lists of pertinent studies and other identified literature were scanned. Researchers in the field were contacted. SELECTION CRITERIA: Only randomised clinical trials using the PAIR method with or without benzimidazole coverage as the experimental treatment of uncomplicated hepatic hydatid cyst (ie, hepatic hydatid cysts, which are not infected and do not have any communication with the biliary tree or other viscera) versus no intervention, sham puncture (ie, performing all steps for puncture, pretending PAIR being performed, but actually not performing the procedure), surgery, or chemotherapy were included. DATA COLLECTION AND ANALYSIS: Data were independently extracted, and the risk of bias in each trial was assessed by the authors. Principal authors of the trials were contacted to retrieve missing data. MAIN RESULTS: We found no randomised clinical trials comparing PAIR versus no or sham intervention. We identified only two randomised clinical trials, one comparing PAIR versus surgical treatment (n = 50 participants) and the other comparing PAIR (with or without albendazole) versus albendazole alone (n = 30 participants). Both trials were graded as 'adequate' for allocation concealment; however, generation of allocation sequence and blinding methods were 'unclear' in both. Compared to surgery, PAIR plus albendazole obtained similar cyst disappearance and mean cyst diameter with fewer adverse events (32% versus 84%, P < 0.001) and fewer days in hospital (mean + SD) ( 4.2 + 1.5 versus 12.7 + 6.5 days, P < 0.001). Compared to albendazole, PAIR with or without albendazole obtained significantly more (P < 0.01) cyst reduction and symptomatic relief. AUTHORS' CONCLUSIONS: PAIR seems promising, but there is insufficient evidence to support or refute PAIR with or without benzimidazole coverage for treating patients with uncomplicated hepatic hydatid cyst. Further well-designed randomised clinical trials are necessary to address the topic.

Topical application of tranexamic acid reduces postoperative blood loss in total knee arthroplasty: a randomized, controlled trial.

BACKGROUND: Topical application of tranexamic acid to bleeding wound surfaces reduces blood loss in patients undergoing some major surgeries, without systemic complications. The objective of the present trial was to assess the efficacy and safety of the topical application of tranexamic acid on postoperative blood loss in patients undergoing primary unilateral total knee arthroplasty with cement. METHODS: In a prospective, double-blind, placebo-controlled trial, 124 patients were randomized to receive 1.5 or 3.0 g of tranexamic acid in 100 mL of normal saline solution or an equivalent volume of placebo (normal saline solution) applied into the joint for five minutes at the end of surgery. The primary outcome was blood loss calculated from the difference between the preoperative hemoglobin level and the corresponding lowest postoperative value or hemoglobin level prior to transfusion. The safety outcomes included Doppler ultrasound in all patients and measurement of plasma levels of tranexamic acid one hour after release of the tourniquet. RESULTS: Twenty-five patients were withdrawn for various reasons; therefore, ninety-nine patients were included in the intention-to-treat analysis. The postoperative blood loss was reduced in the 1.5 and 3-g tranexamic acid groups (1295 mL [95% confidence interval, 1167 to 1422 mL] and 1208 mL [95% confidence interval, 1078 to 1339 mL], respectively) in comparison with the placebo group (1610 mL [95% confidence interval, 1480 to 1738 mL]) (p < 0.017). The postoperative hemoglobin levels were higher in the 1.5 and 3.0-g tranexamic acid groups (10.0 g/dL [95% confidence interval, 9.5 to 10.4 g/dL] and 10.1 g/dL [95% confidence interval, 9.8 to 10.5 g/dL], respectively) in comparison with the placebo group (8.6 g/dL [95% confidence interval, 8.2 to 9 g/dL]) (p < 0.017). With the numbers studied, there was no difference in the rates of deep-vein thrombosis or pulmonary embolism between the three groups. Minimal systemic absorption of tranexamic acid was observed. CONCLUSIONS: At the conclusion of a total knee arthroplasty with cement, topical application of tranexamic acid directly into the surgical wound reduced postoperative bleeding by 20% to 25%, or 300 to 400 mL, resulting in 16% to 17% higher postoperative hemoglobin levels compared with placebo, with no clinically important increase in complications being identified in the treatment groups.

Brief review: Airway rescue with insertion of laryngeal mask airway devices with patients in the prone position.

PURPOSE: Unintentional extubation of the trachea while the anesthetized patient is in the prone position is a potentially life-threatening situation that is usually managed by turning the patient supine for emergent re-intubation. However, this approach may delay definitive airway management and lead to irreversible complications. This review evaluates the efficacy of insertion of a laryngeal mask airway device (LMAD) with the patient in the prone position as a rescue method in airway management for unintentional tracheal extubation. PRINCIPAL FINDINGS: We searched MEDLINE and EMBASE databases in the English language for the period 1980 to October 2009 in order to identify observational studies and case reports describing insertion of the LMAD with the patient in the prone position. We found 12 such articles (n = 526 patients) consisting of four retrospective studies, one prospective cohort with a control group, one non-controlled prospective study, and six case reports. On the first attempt, the LMAD was inserted successfully in 87.5-100% of the patients involved in the included reports. On the second attempt, the LMAD was inserted successfully in all patients, with or without laryngoscopy. Ventilation was maintained successfully in the lungs of 83.3-100% of the patients involved in the reported articles. Following insertion of the LMAD with patients in the prone position, the most common complications reported were sore throat, bleeding, bradycardia, and laryngospasm. CONCLUSIONS: Cumulative experience from published reports suggests the feasibility of placing the LMAD with the patient in the prone position in the elective setting; however, the evidence is lacking regarding the use of this method for emergency management of unintended tracheal extubation with the patient in the prone position.

Efficacy and safety of melatonin as an anxiolytic and analgesic in the perioperative period: a qualitative systematic review of randomized trials.

Melatonin possesses sedative, hypnotic, analgesic, antiinflammatory, antioxidative, and chronobiotic properties that distinguish it as an attractive alternative premedicant. A qualitative systematic review of the literature concerning the perioperative use of melatonin as an anxiolytic or analgesic in adult patients was carried out using the recommended guidelines provided by the Cochrane Handbook for Systematic Reviews of Interventions. Nine of the 10 studies showed statistically significant reduction of preoperative anxiety with melatonin premedication compared with placebo. An opioid-sparing effect or reduced pain scores were evident in five studies whereas three studies were contradictory. Thus, melatonin premedication is effective in ameliorating preoperative anxiety in adults, but its analgesic effects remain controversial in the perioperative period. Additional well designed randomized controlled trials are necessary to compare melatonin premedication with other pharmacological interventions, investigate its effect on more varied surgical populations, and to delineate its optimal dosing regimen.

Cochrane corner: sugammadex, a selective reversal medication for preventing postoperative residual neuromuscular blockade.

BACKGROUND: Sugammadex is the first selective relaxant binding agent that has been studied for reversal of neuromuscular blockade induced by rocuronium and other steroidal non-depolarizing neuromuscular blocking agents (NMBAs). OBJECTIVES: To assess the efficacy and safety of sugammadex in reversing neuromuscular blockade induced by steroidal non-depolarizing NMBAs and in preventing postoperative residual neuromuscular blockade. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 3), MEDLINE (1950 to August 2008), and EMBASE (1980 to August 2008). In addition, we handsearched reference lists of relevant articles and meeting abstracts. Furthermore, we contacted the medication's manufacturer for more information. SELECTION CRITERIA: All randomized controlled trials (RCTs) on adult patients (> or = 18 years old) in which sugammadex was compared with placebo or other medications, or in which different doses of sugammadex were compared with each other. We excluded non-randomized trials and studies on healthy volunteers. DATA COLLECTION AND ANALYSIS: We independently performed determination of trial inclusion, quality assessment, and data extraction. We applied standard meta- analytic techniques. MAIN RESULTS: We included18 RCTs (n=1321 patients). Seven trials were published as full-text papers, and 11 trials only as meeting abstracts. All the included trials had adequate methods of randomization and allocation concealment. The results suggest that, compared with placebo or neostigmine, sugammadex can more rapidly reverse rocuronium-induced neuromuscular blockade regardless of the depth of the block. We identified 2, 4, and 16 mg/kg of sugammadex for reversal of rocuronium-induced neuromuscular blockade at T2 reappearance , 1 to 2 post-tetanic counts, and 3 to 5 minutes after rocuronium, respectively. The number of trials are very limited regarding vecuronium and pancuronium. Serious adverse events occurred in < 1% of all patients who received the medication. There was no significant difference between sugammadex and placebo in terms of the prevalence of drug-related adverse events (RR 1.20, 95% CI 0.61 to 2.37; P=0.59, I2=0%, 5 RCTs). Also, no significant difference was found between sugammadex and neostigmine for adverse events (RR 0.98, 95% CI 0.48 to1.98; P=0.95, I2=43%, 3 RCTs). AUTHORS' CONCLUSIONS: Sugammadex was shown to be effective in reversing rocuronium-induced neuromuscular blockade. This review has found no evidence of a difference in the instance of unwanted effects between sugammadex, placebo or neostigmine. These results need to be confirmed by future trials on larger patient populations and with more focus on patient-related outcomes.

A systematic review of screening questionnaires for obstructive sleep apnea.

PURPOSE: Obstructive sleep apnea (OSA) may lead to life-threatening problems if it is left undiagnosed. Polysomnography is the "gold standard" for OSA diagnosis; however, it is expensive and not widely available. The objective of this systematic review is to identify and evaluate the available questionnaires for screening OSA. SOURCE: We carried out a literature search through MEDLINE, EMBASE, and CINAHL to identify eligible studies. The methodological validity of each study was assessed using the Cochrane Methods Group's guideline. PRINCIPAL FINDINGS: Ten studies (n = 1,484 patients) met the inclusion criteria. The Berlin questionnaire was the most common questionnaire (four studies) followed by the Wisconsin sleep questionnaire (two studies). Four studies were conducted exclusively on "sleep-disorder patients", and six studies were conducted on "patients without history of sleep disorders". For the first group, pooled sensitivity was 72.0% (95% confidence interval [CI]: 66.0-78.0%; I(2) = 23.0%) and pooled specificity was 61.0% (95% CI: 55.0-67.0%; I(2) = 43.8%). For the second group, pooled sensitivity was 77.0% (95% CI: 73.0-80.0%; I(2) = 78.1%) and pooled specificity was 53.0% (95% CI: 50-57%; I(2) = 88.8%). The risk of verification bias could not be eliminated in eight studies due to insufficient reporting. Studies on snoring, tiredness, observed apnea, and high blood pressure (STOP) and STOP including body mass index, age, neck circumference, gender (Bang) questionnaires had the highest methodological quality. CONCLUSION: The existing evidence regarding the accuracy of OSA questionnaires is associated with promising but inconsistent results. This inconsistency could be due to studies with heterogeneous design (population, questionnaire type, validity). STOP and STOP-Bang questionnaires for screening of OSA in the surgical population are suggested due to their higher methodological quality and easy-to-use features.

Sugammadex, a selective reversal medication for preventing postoperative residual neuromuscular blockade.

BACKGROUND: Sugammadex is the first selective relaxant binding agent that has been studied for reversal of neuromuscular blockade induced by rocuronium and other steroidal non-depolarizing neuromuscular blocking agents (NMBAs). OBJECTIVES: To assess the efficacy and safety of sugammadex in reversing neuromuscular blockade induced by steroidal non-depolarizing NMBAs and in preventing postoperative residual neuromuscular blockade. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 3), MEDLINE (1950 to August 2008), and EMBASE (1980 to August 2008). In addition, we handsearched reference lists of relevant articles and meeting abstracts. Furthermore, we contacted the medication's manufacturer for more information. SELECTION CRITERIA: All randomized controlled trials (RCTs) on adult patients (>/= 18 years old) in which sugammadex was compared with placebo or other medications, or in which different doses of sugammadex were compared with each other. We excluded non-randomized trials and studies on healthy volunteers. DATA COLLECTION AND ANALYSIS: We independently performed determination of trial inclusion, quality assessment, and data extraction. We applied standard meta-analytic techniques. MAIN RESULTS: We included18 RCTs (n = 1321 patients). Seven trials were published as full-text papers, and 11 trials only as meeting abstracts. All the included trials had adequate methods of randomization and allocation concealment. The results suggest that, compared with placebo or neostigmine, sugammadex can more rapidly reverse rocuronium-induced neuromuscular blockade regardless of the depth of the block. We identified 2, 4, and 16 mg/kg of sugammadex for reversal of rocuronium-induced neuromuscular blockade at T(2) reappearance , 1 to 2 post-tetanic counts, and 3 to 5 minutes after rocuronium, respectively. The number of trials are very limited regarding vecuronium and pancuronium. Serious adverse events occurred in < 1% of all patients who received the medication. There was no significant difference between sugammadex and placebo in terms of the prevalence of drug-related adverse events (RR 1.20, 95% CI 0.61 to 2.37; P = 0.59, I(2) = 0%, 5 RCTs). Also, no significant difference was found between sugammadex and neostigmine for adverse events (RR 0.98, 95% CI 0.48 to1.98; P = 0.95, I(2) = 43%, 3 RCTs). AUTHORS' CONCLUSIONS: Sugammadex was shown to be effective in reversing rocuronium-induced neuromuscular blockade. This review has found no evidence of a difference in the instance of unwanted effects between sugammadex, placebo or neostigmine. These results need to be confirmed by future trials on larger patient populations and with more focus on patient-related outcomes.

Predictors of postoperative pain and analgesic consumption: a qualitative systematic review.

Pain is a subjective and multidimensional experience that is often inadequately managed in clinical practice. Effective control of postoperative pain is important after anesthesia and surgery. A systematic review was conducted to identify the independent predictive factors for postoperative pain and analgesic consumption. The authors identified 48 eligible studies with 23,037 patients included in the final analysis. Preoperative pain, anxiety, age, and type of surgery were four significant predictors for postoperative pain. Type of surgery, age, and psychological distress were the significant predictors for analgesic consumption. Gender was not found to be a consistent predictor as traditionally believed. Early identification of the predictors in patients at risk of postoperative pain will allow more effective intervention and better management. The coefficient of determination of the predictive models was less than 54%. More vigorous studies with robust statistics and validated designs are needed to investigate this field of interest.