Effect of Volatile Anesthetics on Myocardial Infarction After Coronary Artery Surgery: A Post Hoc Analysis of a Randomized Trial.

OBJECTIVE: To investigate the effect of volatile anesthetics on the rates of postoperative myocardial infarction (MI) and cardiac death after coronary artery bypass graft (CABG). DESIGN: A post hoc analysis of a randomized trial. SETTING: Cardiac surgical operating rooms. PARTICIPANTS: Patients undergoing elective, isolated CABG. INTERVENTIONS: Patients were randomized to receive a volatile anesthetic (desflurane, isoflurane, or sevoflurane) or total intravenous anesthesia (TIVA). The primary outcome was hemodynamically relevant MI (MI requiring high-dose inotropic support or prolonged intensive care unit stay) occurring within 48 hours from surgery. The secondary outcome was 1-year death due to cardiac causes. MEASUREMENTS AND MAIN RESULTS: A total of 5,400 patients were enrolled between April 2014 and September 2017 (2,709 patients randomized to the volatile anesthetics group and 2,691 to TIVA). The mean age was 62 ± 8.4 years, and the median baseline ejection fraction was 57% (50-67), without differences between the 2 groups. Patients in the volatile group had a lower incidence of MI with hemodynamic complications both in the per-protocol (14 of 2,530 [0.6%] v 27 of 2,501 [1.1%] in the TIVA group; p = 0.038) and as-treated analyses (16 of 2,708 [0.6%] v 29 of 2,617 [1.1%] in the TIVA group; p = 0.039), but not in the intention-to-treat analysis (17 of 2,663 [0.6%] v 28 of 2,667 [1.0%] in the TIVA group; p = 0.10). Overall, deaths due to cardiac causes were lower in the volatile group (23 of 2,685 [0.9%] v 40 of 2,668 [1.5%] than in the TIVA group; p = 0.03). CONCLUSIONS: An anesthetic regimen, including volatile agents, may be associated with a lower rate of postoperative MI with hemodynamic complication in patients undergoing CABG. Furthermore, it may reduce long-term cardiac mortality.

Acute Kidney Injury and Risk of Death After Elective Surgery: Prospective Analysis of Data From an International Cohort Study.

BACKGROUND: Postoperative acute kidney injury (AKI) is associated with a high mortality rate. However, the relationship among AKI, its associations, and mortality is not well understood. METHODS: Planned analysis of data was collected during an international 7-day cohort study of adults undergoing elective in-patient surgery. AKI was defined using Kidney Disease Improving Global Outcomes criteria. Patients missing preoperative creatinine data were excluded. We used multivariable logistic regression to examine the relationships among preoperative creatinine-based estimated glomerular filtration rate (eGFR), postoperative AKI, and hospital mortality, accounting for the effects of age, major comorbid diseases, and nature and severity of surgical intervention on outcomes. We similarly modeled preoperative associations of AKI. Data are presented as n (%) or odds ratios (ORs) with 95% confidence intervals. RESULTS: A total of 36,357 patients were included, 743 (2.0%) of whom developed AKI with 73 (9.8%) deaths in hospital. AKI affected 73 of 196 (37.2%) of all patients who died. Mortality was strongly associated with the severity of AKI (stage 1: OR, 2.57 [1.3-5.0]; stage 2: OR, 8.6 [5.0-15.1]; stage 3: OR, 30.1 [18.5-49.0]). Low preoperative eGFR was strongly associated with AKI. However, in our model, lower eGFR was not associated with increasing mortality in patients who did not develop AKI. Conversely, in older patients, high preoperative eGFR (>90 mL·minute·1.73 m) was associated with an increasing risk of death, potentially reflecting poor muscle mass. CONCLUSIONS: The occurrence and severity of AKI are strongly associated with risk of death after surgery. However, the relationship between preoperative renal function as assessed by serum creatinine-based eGFR and risk of death dependent on patient age and whether AKI develops postoperatively.

Beta Adrenergic Receptors Stimulation Attenuates Phosphorylation of NF-κB and IκBα in Hyperglycemic Endothelial Cells.

BACKGROUND/AIMS: NF-κB induces transcription of a number of genes, associated with inflammation and apoptosis. In this study, we have investigated the effect of ß-adrenergic receptor stimulation on NF-κB and IκBα in HUVECs. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured in high and low glucose concentrations. All HUVECs were treated with different concentrations of isoproterenol and propranolol for different time periods. The analytical procedures consisted of Western Blot, ELISA, DCFH-DA and TUNEL assays. RESULTS: Isoproterenol (agonist of a beta-adrenergic receptor) significantly reduced phosphorylation at Ser-536 of NF-κB; and Ser-32 and Ser-36 of IκBα in hyperglycemic HUVECs. Isoproterenol also significantly reduced apoptosis and ROS generation. No effect of IκBα was observed on Tyr-42 phosphorylation. The effect of isoproterenol was reversed by the antagonist propranolol. We also checked if NF-κB inhibitor MG132 causes any change at the level of apoptosis. However, we observed an almost similar effect. CONCLUSION: Given data demonstrates that beta-adrenergic receptors stimulation has a protective effect on HUVECs that might be occuring via NF-κß and IκBα pathway.

Continuous Infusion versus Intermittent Bolus Injection of Furosemide in Critically Ill Patients: A Systematic Review and Meta-analysis.

OBJECTIVE: Fluid overload is a common phenomenon seen in intensive care units (ICUs). However, there is no general consensus on whether continuous or bolus furosemide is safer or more effective in these hemodynamically unstable ICU patients. The aim of this meta-analysis was to examine the clinical outcomes of continuous versus bolus furosemide in a critically ill population in ICUs. DATA SOURCES: MEDLINE, EMBASE, PubMed, and the Cochrane Database of Systematic reviews were searched from their inception until June 2017. REVIEW METHODS: All randomized controlled trials, observational studies, and case-control studies were included. Case reports, case series, nonsystematic reviews, and studies that involved children were excluded. RESULTS: Nine studies (n = 464) were eligible in the data synthesis. Both continuous and bolus furosemide resulted in no difference in all-cause mortality (7 studies; n = 396; I2 = 0%; fixed-effect model [FEM]: odds ratio [OR] 1.15 [95% confidence interval (CI) 0.67-1.96]; p = 0.64). Continuous furosemide was associated with significant greater total urine output (n = 132; I2 = 70%; random-effect model: OR 811.19 [95% CI 99.84-1,522.53]; p = 0.03), but longer length of hospital stay (n = 290; I2 = 40%; FEM: OR 2.84 [95% CI 1.74-3.94]; p < 0.01) in comparison to the bolus group. No statistical significance was found in the changes of creatinine and estimated glomerular filtration rate between both groups. CONCLUSIONS: In this meta-analysis, continuous furosemide was associated with greater diuretic effect in total urine output as compared with bolus. Neither had any differences in mortality and changes of renal function tests. However, a large adequately powered randomized clinical trial is required to fill this knowledge gap.

Kidney Function Alters the Relationship between Postoperative Troponin T Level and Death.

Cardiac troponin T (cTnT), even at low concentrations, is a risk factor for 30-day mortality in patients undergoing noncardiac surgery, but it is uncertain whether that risk is generalizable to patients with poor kidney function. We, therefore, evaluated the relationship between cTnT concentration and kidney function on the outcome of 30-day mortality in a post hoc analysis of a prospective cohort study of patients undergoing noncardiac surgery. cTnT was measured for 3 days after surgery and considered abnormal if the peak was ≥0.02 ng/ml. Of the included 14,037 patients, 267 (1.9%) patients died within 30 days of surgery. The adjusted hazard ratios for death with an abnormal cTnT concentration were 4.37 (95% confidence intervals [95% CI], 3.21 to 6.22), 6.15 (95% CI, 2.95 to 140.9), 6.30 (95% CI, 3.12 to 21.23), 1.33 (95% CI, 0.56 to 4.85), and 1.46 (95% CI, 0.46 to 9.21) for eGFR≥60, 45 to <60, 30 to <45, 15 to <30, and <15 ml/min per 1.73 m(2) or on dialysis, respectively. Compared with patients with eGFR≥60 ml/min per 1.73 m(2), the adjusted hazard ratio was significantly lower for patients with eGFR=15 to <30 ml/min per 1.73 m(2) (interaction P value=0.02). Redefining abnormal cTnT concentration as ≥0.03 ng/ml or a change of ≥0.02 ng/ml did not alter results. Because the risk associated with postoperative cTnT levels may be different for patients with eGFR<30 ml/min per 1.73 m(2), additional research is required to determine how to interpret perioperative cTnT values for patients with low kidney function.

Antifilarial and Antibiotic Activities of Methanolic Extracts of Melaleuca cajuputi Flowers.

We evaluated the activity of methanolic extracts of Melaleuca cajuputi flowers against the filarial worm Brugia pahangi and its bacterial endosymbiont Wolbachia. Anti-Wolbachia activity was measured in worms and in Aedes albopictus Aa23 cells by PCR, electron microscopy, and other biological assays. In particular, microfilarial release, worm motility, and viability were determined. M. cajuputi flower extracts were found to significantly reduce Wolbachia endosymbionts in Aa23 cells, Wolbachia surface protein, and microfilarial release, as well as the viability and motility of adult worms. Anti-Wolbachia activity was further confirmed by observation of degraded and phagocytized Wolbachia in worms treated with the flower extracts. The data provided in vitro and in vivo evidence that M. cajuputi flower extracts inhibit Wolbachia, an activity that may be exploited as an alternative strategy to treat human lymphatic filariasis.

Antioxidant, antibacterial activity, and phytochemical characterization of Melaleuca cajuputi extract.

BACKGROUND: The threat posed by drug-resistant pathogens has resulted in the increasing momentum in research and development for effective alternative medications. The antioxidant and antibacterial properties of phytochemical extracts makes them attractive alternative complementary medicines. Therefore, this study evaluated the phytochemical constituents of Melaleuca cajuputi flower and leaf (GF and GL, respectively) extracts and their antioxidant and antibacterial activities. METHODS: Radical scavenging capacity of the extracts was estimated using 2,2-diphenyl-2-picrylhydrazyl and Fe(2+)-chelating activity. Total antioxidant activity was determined using ferric reducing antioxidant power assay. Well diffusion, minimum inhibitory concentration, and minimum bactericidal concentration assays were used to determine antibacterial activity against eight pathogens, namely Staphylococcus aureus, Escherichia coli, Bacillus cereus, Staphylococcus epidermidis, Salmonella typhimurium, Klebsiella pneumonia, Streptococcus pneumoniae, and Pasteurella multocida. We identified and quantified the phytochemical constituents in methanol extracts using liquid chromatography/mass spectrometry (LC/MS) and gas chromatography (GC)/MS. RESULTS: This study reports the antioxidant and radical scavenging activity of M. cajuputi methanolic extracts. The GF extract showed better efficacy than that of the GL extract. The total phenolic contents were higher in the flower extract than they were in the leaf extract (0.55 ± 0.05 and 0.37 ± 0.05 gallic acid equivalent per mg extract dry weight, respectively). As expected, the percentage radical inhibition by GF was higher than that by the GL extract (81 and 75 %, respectively). A similar trend was observed in Fe(2+)-chelating activity and ß-carotene bleaching tests. The antibacterial assay of the extracts revealed no inhibition zones with the Gram-negative bacteria tested. However, the extracts demonstrated activity against B. cereus, S. aureus, and S. epidermidis. CONCLUSIONS: In this study, we found that M. cajuputi extracts possess antioxidant and antibacterial activities. The results revealed that both extracts had significant antioxidant and free radical-scavenging activity. Both extracts had antibacterial activity against S. aureus, S. epidermidis, and B. cereus. The antioxidant and antimicrobial activities could be attributed to high flavonoid and phenolic contents identified using GC/MS and LC/MS. Therefore, M. cajuputi could be an excellent source for natural antioxidant and antibacterial agents for medical and nutraceutical applications.

Partial vs full glottic view with CMACTM D blade intubation of airway with simulated cervical spine injury: a randomized controlled trial.

PURPOSE: A previous study reported a shorter time to tracheal intubation by reducing percentage of glottic opening (POGO) view to <50% when intubating a normal adult airway using the GlidescopeTM blade. We evaluate the efficacy of reducing POGO to <50% when intubating patients with rigid cervical immobilization using CMACTM D blade. METHODS: One hundred and four adult patients were randomized to group POGO 100% or POGO <50% . Laryngoscopy was performed by advancing tip of the D blade at vallecula. POGO 100% was achieved by exerting upward force to displace epiglottis until glottic opening from the anterior commissure to inter arytenoid notch. POGO < 50% was acquired by withdrawing the D blade tip dorsally from vallecula. The primary outcome was time to intubation. RESULTS: The median time (IQR) to successful intubation was 29 (25-35) seconds for group POGO < 50% and 34 (28-40) seconds for group with POGO 100% (difference in medians, 5 seconds; 95% confidence interval, 2 to 8, p = 0.003). Complications were minor. CONCLUSION: Using the CMACTM D blade with a reduced POGO in patients with cervical spine immobilization resulted in faster tracheal intubation. TRIAL REGISTRATION: The trial is registered at ClinicalTrial.gov (CT.gov identifier: NCT04833166).

Gelam honey scavenges peroxynitrite during the immune response.

Monocytes and macrophages are part of the first-line defense against bacterial, fungal, and viral infections during host immune responses; they express high levels of proinflammatory cytokines and cytotoxic molecules, including nitric oxide, reactive oxygen species, and their reaction product peroxynitrite. Peroxynitrite is a short-lived oxidant and a potent inducer of cell death. Honey, in addition to its well-known sweetening properties, is a natural antioxidant that has been used since ancient times in traditional medicine. We examined the ability of Gelam honey, derived from the Gelam tree (Melaleuca spp.), to scavenge peroxynitrite during immune responses mounted in the murine macrophage cell line RAW 264.7 when stimulated with lipopolysaccharide/interferon-γ (LPS/IFN-γ) and in LPS-treated rats. Gelam honey significantly improved the viability of LPS/IFN-γ-treated RAW 264.7 cells and inhibited nitric oxide production-similar to the effects observed with an inhibitor of inducible nitric oxide synthase (1400W). Furthermore, honey, but not 1400W, inhibited peroxynitrite production from the synthetic substrate 3-morpholinosydnonimine (SIN-1) and prevented the peroxynitrite-mediated conversion of dihydrorhodamine 123 to its fluorescent oxidation product rhodamine 123. Honey inhibited peroxynitrite synthesis in LPS-treated rats. Thus, honey may attenuate inflammatory responses that lead to cell damage and death, suggesting its therapeutic uses for several inflammatory disorders.

Gelam honey has a protective effect against lipopolysaccharide (LPS)-induced organ failure.

Gelam honey exerts anti-inflammatory and antioxidant activities and is thought to have potent effects in reducing infections and healing wounds. The aim of this study was to investigate the effects of intravenously-injected Gelam honey in protecting organs from lethal doses of lipopolysaccharide (LPS). Six groups of rabbits (N = 6) were used in this study. Two groups acted as controls and received only saline and no LPS injections. For the test groups, 1 mL honey (500 mg/kg in saline) was intravenously injected into two groups (treated), while saline (1 mL) was injected into the other two groups (untreated); after 1 h, all four test groups were intravenously-injected with LPS (0.5 mg/kg). Eight hours after the LPS injection, blood and organs were collected from three groups (one from each treatment stream) and blood parameters were measured and biochemical tests, histopathology, and myeloperoxidase assessment were performed. For survival rate tests, rabbits from the remaining three groups were monitored over a 2-week period. Treatment with honey showed protective effects on organs through the improvement of organ blood parameters, reduced infiltration of neutrophils, and decreased myeloperoxidase activity. Honey-treated rabbits also showed reduced mortality after LPS injection compared with untreated rabbits. Honey may have a therapeutic effect in protecting organs during inflammatory diseases.

Music therapy for reducing anxiety in patients undergoing total knee replacement surgery under subarachnoid anesthesia.

BACKGROUND: Non-pharmacological interventions such as music are being increasingly used in clinical settings. OBJECTIVE: To assess the effects of music on patients undergoing total knee replacement (TKR) surgery under subarachnoid anesthesia. METHODS: This randomized controlled trial examined participants (45/group) in a music and non-music group. Anxiety was measured in both the groups using (1) the adapted hospital anxiety and depression scale (HADS), (2) Spielberger state trait anxiety inventory (STAI-S), (3) visual analog scale (VAS), (4) cortisol levels, and (5) blood pressure. Music was delivered using an MP3 player and headphones. Hemodynamic data was collected before, during, and after music therapy. Cortisol and stress levels were measured postoperatively. VAS was assessed 30 min before surgery, 30 min after the administration of anesthesia, and 30 min after the surgery ended in the recovery room to obtain comparative data on pain levels at 3 different phases using a numeric rating scale. RESULTS: Changes in the mean VAS scores from the pre-to postoperative phase were significantly different between the music and non-music groups (p = .001). The mean (±standard deviation [SD]) HADS and STAI-S scores of the non-music group were higher than those in the music group (HADS:15.58 ± 2.231 vs 11.91 ± 3.218; STAI-S: 54.04 ± 2.899 vs 48.87 ± 4.595). There were significant differences in the mean systolic and diastolic blood pressure and mean heart rate between the groups based on time (both, p < .001). Correlation regression analysis for the cortisol level revealed a certain relationship between age and cortisol level (p < .05). CONCLUSIONS: These results suggest that music can reduce patients' anxiety level in the operating room. Studies on music therapy for patients undergoing lower limb orthopedic surgery, especially under subarachnoid anesthesia, are extremely limited. Therefore, this study can serve as a reference regarding the application of music therapy in the medical field.

Development of conventional and real-time multiplex PCR assays for the detection of nosocomial pathogens.

Nosocomial infections are major clinical threats to hospitalised patients and represent an important source of morbidity and mortality. It is necessary to develop rapid detection assays of nosocomial pathogens for better prognosis and initiation of antimicrobial therapy in patients. In this study, we present the development of molecular methods for the detection of six common nosocomial pathogens including Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter spp. Conventional multiplex PCR and SYBR Green based real time PCR assays were performed using genus and species specific primers. Blind testing with 300 clinical samples was also carried out. The two assays were found to be sensitive and specific. Eubacterial PCR assay exhibited positive results for 46 clinical isolates from which 43 samples were detected by real time PCR assay. The sensitivity of the assay is about 93.7% in blind test isolates. The PCR results were reconfirmed using the conventional culture method. This assay has the potential to be a rapid, accurate and highly sensitive molecular diagnostic tool for simultaneous detection of Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter spp. This assay has the potential to detect nosocomial pathogens within 5 to 6 hours, helping to initiate infection control measures and appropriate treatment in paediatric and elderly (old aged) patients, pre-and post surgery patients and organ transplant patients and thus reduces their hospitalization duration.

Inhibitory effects of biofeedback electrostimulation therapy on pain and cortisol levels in chronic neuropathic pain: A randomized-controlled trial.

OBJECTIVES: This study aims to investigate the effectiveness of biofeedback electrostimulation therapy (BEST) in chronic neuropathic pain and to evaluate changes in perceived level of pain and level of blood cortisol before and after treatment. PATIENTS AND METHODS: This single-blind, prospective, randomized-controlled study included a total of 20 patients (8 males, 12 females; mean age: 53.5±13.8; range, 31 to 82 years) with chronic neuropathic pain between January 2014 and June 2014. The patients were randomized to BEST (n=10) or placebo (n=10) group. Pain was measured using the Visual Analog Scale, and serum cortisol levels were measured before and after treatment. RESULTS: There was no significant difference in the baseline demographics, diagnosis, and treatment modalities between the groups. Approximately 50% patients in the treatment group reported that the treatment was effective, compared to 30% in the placebo group. Pain score reduction after treatment in the BEST group was significant (p<0.05), while it was not significant in the placebo group (p=0.4). Cortisol levels significantly reduced only in the BEST group after treatment (p=0.013). CONCLUSION: The BEST yields reduction in pain severity and cortisol levels. Based on these results, it seems to be effective in the treatment of chronic neuropathic pain after a single treatment and may be more effective for long-term management.

Baska mask versus endotracheal tube in laparoscopic cholecystectomy surgery: a prospective randomized trial.

Background: Supraglottic airway devices have increasingly been used as the airway technique of choice in laparoscopic surgeries. This study compared the efficacy and safety of the Baska Mask with endotracheal tube (ETT) in patients undergoing elective laparoscopic cholecystectomy.Research design and methods: This single-center, prospective, randomized controlled trial recruited 60 patients aged 18-75 years with American Society of Anesthesiologists' classifications I to III. The time taken to achieve effective airway, number of attempts, ease of insertion, ventilation parameters, hemodynamics data, and pharyngolaryngeal complications were recorded.Results: The time taken to achieve effective airway was shorter for the Baska group (26.6 ± 4.7 vs. 47.2 ± 11.8 s; p < 0.001), although the first-time insertion success rate was ≥90% for both groups. The ETT group experienced more pharyngolaryngeal complications, including cough, trauma, spasm, dysphonia, and sore throat, during device insertion and removal and had higher systolic and diastolic blood pressures during intubation (p = 0.001). The Baska Mask achieved significantly lower peak airway pressure (p = 0.024) with stable oropharyngeal leak pressure ≥33 cmH2O throughout the surgery.Conclusions: The Baska Mask is a suitable alternative to endotracheal intubation in selected patients undergoing laparoscopic cholecystectomy, with shorter insertion times, fewer perioperative complications, and improved ventilatory performance and hemodynamic response.Trial registration: The trial is registered at ClinicalTrials.gov (NCT03045835), 8 February 2017.

Iron regulated outer membrane proteins (IROMPs) as potential targets against carbapenem-resistant Acinetobacter spp. isolated from a Medical Centre in Malaysia.

BACKGROUND & OBJECTIVES: Carbapenem-resistant Acinetobacter spp. have gained increasing significance as opportunistic pathogens in hospitalized patients. Carbapenem resistance is often associated with the loss and/or decrease in outer membrane proteins (OMP) and overexpression of multidrug efflux systems. However, carbapenem-hydrolysing beta-lactamases of Ambler Class B (metallo-enzymes) and Ambler Class D (oxacillinases) have also been detected in Acinetobacter spp. In this study we have investigated the role of the iron regulated outer membrane protein (IROMPs) and the loss of a 29-kDa OMP in carbapenem resistance of Acinetobacter calcoaceticus. METHODS: Carbapenem resistant clinical isolates (n=39) of Acinetobacter baumannii / calcoaceticus were used. Identification of Acinetobacter spp. at species level was done by amplified ribosomal DNA restriction analysis (ARDRA). MIC was evaluated using agar dilution method according to CLSI standards. Presence of outer membrane proteins were determined by SDS-PAGE. A representative strain of A. calcoaceticus, S26 with the loss of 29-kDa OMP was selected for further analysis as strain S26 had unique resistance mechanism, that is, the presence of IMP-4 metallo-beta-lactamases. IROMPs were expressed under iron deficit conditions. Bands corresponding to IROMPs were excised from SDS-PAGE and used to immunize rabbits for the production of polyclonal antibodies. The antibodies raised against IROMPs were detected by an in-house ELISA and then used for bactericidal activity against carbapenem resistant A. baumannii / calcoaceticus. RESULTS: All isolates were resistant to all antibiotics including imipenem and meropenem and had loss of a 29-kDa OMP. The polyclonal antibodies showed bactericidal effect against the organism tested and it specifically killed the bacteria grown in iron deficit medium. INTERPRETATION & CONCLUSIONS: In this study, a 29-kDa OMP has been identified to be the major outer membrane protein in A. baumannii / calcoaceticus and loss of this porin and overexpression of IROMPs have contributed to carbapenem resistance. Polyclonal antibodies raised against IROMPs may have a role in antimicrobial therapy in these isolates.

Analgesic Prescription Patterns and Pain Outcomes in Southeast Asia: Findings From the Analgesic Treatment of Cancer Pain in Southeast Asia Study.

PURPOSE: To identify patterns of analgesic prescription and to explore patient-reported pain intensity, sleep disturbance, and quality of life among cancer patients with pain in Southeast Asia (SEA). METHODS: This cross-sectional observational study included 465 adult outpatients prescribed analgesics for cancer pain for 1 month or longer at 22 sites in Indonesia, Malaysia, Philippines, Singapore, Thailand, and Vietnam. Data on analgesic prescription and cancer characteristics were extracted from medical records. Pain intensity, sleep disturbance, and quality of life measures were recorded via questionnaires. RESULTS: Most patients (84.4%) had stage III or IV cancer. A total of 419 patients (90.7%) were prescribed opioids; of these, 42.2% received only weak opioids, whereas 57.8% received at least one strong opioid. The mean worst pain intensity during the past 24 hours was 4.76 (standard deviation [SD], 2.47) on a scale of 0 (no pain) to 10 (worst possible pain); the mean current pain intensity was 4.10 (SD, 2.61). More than half of patients (54.8%) reported sleep disturbance caused by pain in the past 7 days. The majority of patients reported problems with pain/discomfort (82.3%), usual activities (65.8%), mobility (58.2%), and anxiety/depression (56.3%). The median daily dose prescribed in oral morphine equivalents was 30 mg for both morphine and tramadol. CONCLUSION: Despite unrelieved pain, sleep disturbance, and issues with quality of life, a notable proportion of patients were prescribed only weak opioids, and opioid doses prescribed were generally low. Efforts focused on encouragement of prescriptions with analgesic strength and/or doses proportional to the pain management needs of patients are vital to improve the status of cancer pain management in the region.

Patient and Physician Satisfaction with Analgesic Treatment: Findings from the Analgesic Treatment for Cancer Pain in Southeast Asia (ACE) Study.

Aim: The aim of this study was to examine patients' and physicians' satisfaction, and concordance of patient-physician satisfaction with patients' pain control status. Methods: This cross-sectional observational study involved 465 adults prescribed analgesics for cancer-related pain from 22 sites across Indonesia, Malaysia, Philippines, Singapore, Thailand, and Vietnam. Pain intensity, pain control satisfaction, and adequacy of analgesics for pain control were documented using questionnaires. Results: Most patients (84.4%) had stage III or IV cancer. On a scale of 0 (no pain) to 10 (worse pain), patients' mean worst pain intensity over 24 hours was 4.76 (SD 2.47). More physicians (19.0%) than patients (8.0%) reported dissatisfaction with patient's pain control. Concordance of patient-physician satisfaction was low (weighted kappa 0.36; 95% CI 0.03-0.24). Most physicians (71.2%) found analgesics to be adequate for pain control. Patients' and physicians' satisfaction with pain control and physician-assessed analgesic adequacy were significantly different across countries (P < 0.001 for all). Conclusions: Despite pain-related problems with sleep and quality of life, patients were generally satisfied with their pain control status. Interestingly, physicians were more likely to be dissatisfied with patients' pain control. Enhanced patient-physician communication, physicians' proactivity in managing opioid-induced adverse effects, and accessibility of analgesics have been identified to be crucial for successful cancer pain management. This study was registered at ClinicalTrials.gov (identifier NCT02664987).

Antifilarial activity of caffeic acid phenethyl ester on Brugia pahangi in vitro and in vivo.

Lymphatic filariasis (LF) is a vector borne disease caused by parasitic worms such as Wuchereria bancrofti, Brugia malayi and B. timori, which are transmitted by mosquitoes. Current therapeutics to treat LF are mainly microfilarcidal, and lack activity against adult worms. This set back, poses a challenge for the control and elimination of filariasis. Thus, in this study the activities of caffeic acid phenethyl ester (CAPE) against the filarial worm B. pahangi and its bacterial endosymbiont, Wolbachia were evaluated. Different concentrations (2, 5, 10, 15, 20 µg/ml) of CAPE were used to assess its effects on motility, viability and microfilarial (mf) production of B. pahangi in vitro. Anti-Wolbachial activity of CAPE was measured in worms by quantification of Wolbachial wsp gene copy number using real-time polymerase chain reaction. Our findings show that CAPE was found to significantly reduce adult worm motility, viability, and mf release both in vitro and in vivo. 20 µg/ml of CAPE halts the release of mf in vitro by day 6 of post treatment. Also, the number of adult worms recovered in vivo were reduced significantly during and after treatment with 50 mg/kg of CAPE relative to control drugs, diethylcarbamazine and doxycycline. Real time PCR based on the Wolbachia ftsZ gene revealed a significant reduction in Wolbachia copy number upon treatment. Anti-Wolbachia and antifilarial properties of CAPE require further investigation as an alternative strategy to treat LF.

Cancer Pain Management Insights and Reality in Southeast Asia: Expert Perspectives From Six Countries.

This expert opinion report examines the current realities of the cancer pain management landscape and the various factors that hinder optimal pain control in six countries in Southeast Asia, describes ongoing efforts to advance patient care, and discusses approaches for improving cancer pain management. Information was gathered from leading experts in the field of cancer pain management in each country through an initial meeting and subsequent e-mail discussions. Overall, there are vast disparities in cancer pain management practices and access to opioids in the Southeast Asian countries. The experts considered cancer pain as being generally undermanaged. Access to opioids is inadequate in most countries, and opioid use for analgesia remains inadequate in the region. Several system-, physician-, and patient-related barriers to adequate pain relief were identified, including widespread over-regulation of opioid use, shortage of trained health care workers, inadequacies in pain assessment and knowledge about managing pain, and widespread resistance among patients and physicians toward opioid treatment. According to the experts, many of the ongoing initiatives in the Southeast Asian countries are related to educating patients and physicians on cancer pain management and opioid use. Efforts to improve opioid availability and reduce regulatory barriers in the region are limited, and much work is still needed to improve the status of cancer pain management in the region. Enacting necessary change will require recognition of the unique needs and resources of each country and collaboration across interdisciplinary professional teams to improve cancer pain care in this region.