Postoperative acute pain management with duloxetine as compared to placebo: A systematic review with meta-analysis of randomized clinical trials.

BACKGROUND: Duloxetine has been used as an adjunct in multimodal analgesia for acute postoperative pain in clinical studies. This meta-analysis aims to conclude whether oral duloxetine, when given perioperatively, is any better than a placebo in managing postoperative pain. Effects of duloxetine on postoperative pain scores, time to first rescue analgesia, postoperative rescue analgesia consumption, side effects attributable to duloxetine, and patient satisfaction profile were assessed. METHOD: MEDLINE, Web of Science, EMBASE, Scholar Google, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched with keywords including "Duloxetine" AND "postoperative pain", "Duloxetine" AND "acute pain" and with "Duloxetine" till October 2022. This meta-analysis included randomized clinical trials in which perioperative duloxetine 60 mg per oral was administered not more than 7 days before surgery and for at least 24 after surgery but not more than 14 days after surgery. All RCTs in which the comparator is placebo and outcomes related to analgesic efficacy like pain scores, opioid consumption, and side effects of duloxetine until 48 h postoperatively were included. Data were extracted from the studies and a risk of bias summary was formed using the Cochrane Collaboration tool. Effect sizes were given as standardized mean differences for continuous outcomes and risk ratios (RR) by the Mantel-Haenszel test for the categorical outcome. Confirmation of publication bias was done by Egger's regression test (p < 0.05). If publication bias or heterogeneity was detected, the trim-and-fill method was used to calculate the adjusted effect size. Sensitivity analysis was done by leaving one out method after excluding the study with a high risk of bias. Subgroup analysis was done based on the type of surgery and gender. The study was prospectively registered in the PROSPERO under the registration number CRD42019139559. FINDINGS: 29 studies with 2043 patients met the inclusion criteria and were reviewed for this meta-analysis. Postoperative pain scores at 24 h [Std. Mean Difference (95% CI); -0.69 (-1.07, -0.32)] and at 48 h [-1.13 (-1.68, -0.58)] are significantly less with duloxetine (p-value < 0.05). Time to first rescue analgesia was significantly more in patients where duloxetine was administered [1.27 (1.10, 1.45); p-value > 0.05]. Opioid consumption up to 24 h [-1.82 (-2.46, -1.18)] and 48 h [-2.48 (-3.46, -1.50)] was significantly less (p-value < 0.05) in patients who received duloxetine. Complications and recovery profiles were similar in patients receiving either duloxetine or a placebo. INTERPRETATION: Based on GRADE findings, we conclude that there is low to moderate evidence to advocate the use of duloxetine for managing postoperative pain. Further trials are needed to replicate or refute these results based on robust methodology.

A case of spontaneous pneumothorax due to paragonimiasis in North America with literature review.

The species, Paragonimus kellicotti , causes human paragonimiasis in North America. As a foodborne disease, human infection with P. kellicotti occurs after eating raw or undercooked crayfish containing metacercariae. Many risk factors have been described in the literature, including young adult age, male, alcohol consumption, outdoor activities involving rivers within Missouri, and ingesting raw or partially cooked crayfish. Here, we report a case of a 41-year-old male with a 5-year history of cough who presented with acute shortness of breath. Further workup showed mild eosinophilia and spontaneous pneumothorax. A definitive diagnosis was made with a lung biopsy, which showed P. kellicotti eggs. Further questioning revealed that the patient took a hunting and river rafting trip on a river in Missouri 5 years ago, though the history was negative for any crayfish consumption. Paragonimiasis should be considered in those with associated clinical features, including cough and eosinophilia, with a history of a river raft float trip in Missouri, even if the history is negative for crayfish ingestion or travel.

Catabolic profiling of selective enzymes in the saccharification of non-food lignocellulose parts of biomass into functional edible sugars and bioenergy: An in silico bioprospecting.

Objectives: The research aims to analyze the catabolic strength of different hydrolytic enzymes in assessing the biological conversion potential of lignocellulose parts of agricultural biomass wastes into functional edible sugars and biofuels. Materials and Methods: The enzymes' hydrolytic properties-versatile peroxidase, manganese peroxidase, and lignin peroxidase were used to identify their complexing strength with the lignin substrate, whereas endoglucanase cel12A, acidocaldarius cellulase, and Melanocarpus albomyces endoglucanase were tested on the cellulose gel substrate. Because the biodegradation properties are heavily influenced by the "enzyme-substrate complexing energy level," proper molecular optimization and energy minimization of the enzymes and substrates were carried out, as well as the identification of the enzyme's active sites prior to complexing.comprehensive molecular dynamic simulation was run to study their-alpha carbon, root-mean-square deviation (Å), molecular surface area (Å2), root-mean-square fluctuation (Å), radius of gyration (nm), hydrogen bonds with hydrophobic interactions, and solvent accessible surface area (Å2) values for 50 ns. The simulated data mining was conducted using advanced programming algorithms to establish the final enzyme-substrate complexing strength in binding and catalysis. Results: Among the lignin-degrading enzymes, versatile peroxidase shows promising catalytic activity with the best docking pose and significant values in all the dynamic simulation parameters. Similarly, Melanocarpus albomyces endoglucanase shows the best activity in all aspects of molecular docking and dynamics among the cellulose-degrading enzymes. Conclusion: The lignin content of biomass wastes can be degraded into cellulose and hemicellulose using lignin-degrading enzymes. The cellulose can be further degraded into glucose and xylose sugars following the cellulose-degrading enzyme activity. These sugars can be further degraded into biofuel through anaerobic fermentation. Systematic bioconversion of the lignocellulosic components can ensure sustainable biomass management, creating an alternative food and energy source for human beings to face the challenges of global hunger where the enzymes can pave the way.

Comparative evaluation of analgesic efficacy of buprenorphine transdermal patch and fentanyl patch in management of postoperative pain after arthroscopic lower limb surgery: A randomized controlled trial.

BACKGROUND AND AIMS: Transdermal opioids are newer modality in use for the control of postoperative pain, because of its noninvasiveness, longer duration of action, sustained blood levels, and with minimal side effects. The study was aimed to evaluate the efficacy of analgesia of buprenorphine patch 10, 20 µg·h-1 and fentanyl patch 25 µg·h-1 for relief of pain in the postoperative period in patients undergoing arthroscopic lower limb surgeries. MATERIALS AND METHODS: It was a randomized, double-blinded, prospective study in which adult patients undergoing lower limb arthroscopic surgery were randomly segregated into three groups. In Group 1 (fentanyl patch 25 µg·h-1), Group 2 (buprenorphine patch 10 µg·h-1), and Group 3 (buprenorphine patch 20 µg·h-1), transdermal patches were applied 12 h prior to surgery. Mean NRS score, total rescue analgesic requirement, drug-related adverse effects, and hemodynamic status were evaluated till 72 h in the postoperative period. RESULTS: Out of 175 screened patients, 150 patients were finally analyzed. Baseline characteristics were the same among all the three groups. Median NRS score was lowest in Group 3 [P value < 0.05 at 2, 4, 8, 12, and 24 h after surgery (Kruskal Wallis test). The total consumption of postoperative rescue analgesic diclofenac was the lowest in Group 3 as compared to other groups without any significant increase in adverse events. CONCLUSIONS: In arthroscopic lower limb surgery, buprenorphine patch (20 µg·h-1) applied 12 h prior to surgery is an effective postoperative analgesic and it is not associated with any significant adverse effects.

Molecular optimization, docking, and dynamic simulation profiling of selective aromatic phytochemical ligands in blocking the SARS-CoV-2 S protein attachment to ACE2 receptor: an in silico approach of targeted drug designing.

OBJECTIVES: The comprehensive in silico study aims to figure out the most effective aromatic phytochemical ligands among a number from a library, considering their pharmacokinetic efficacies in blocking "angiotensin-converting enzyme 2 (ACE2) receptor-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S protein" complex formation as part of a target-specific drug designing. MATERIALS AND METHODS: A library of 57 aromatic pharmacophore phytochemical ligands was prepared from where the top five ligands depending on Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) and quantitative structure-activity relationship (QSAR)-based pharmacokinetic properties were considered. The selected ligands were optimized for commencing molecular docking and dynamic simulation as a complex with the ACE2 receptor to compare their blocking efficacy with the control drug. The ligand-receptor complexes' accuracy in preventing the Spike (S) protein of SARS-CoV-2 penetration inside the host cells has been analyzed through hydrogen-hydrophobic bond interactions, principal component analysis (PCA), root mean square deviation (RMSD), root mean square fluctuation (RMSF), and B-Factor. Advanced in silico programming language and bioanalytical software were used for high throughput and authentic results. RESULTS: ADMET and QSAR revealed Rhamnetin, Lactupicrin, Rhinacanthin D, Flemiflavanone D, and Exiguaflavanone A as the ligands of our interest to be compared with the control Cassiarin D. According to the molecular docking binding affinity to block ACE2 receptor, the efficiency mountings were Rhinacanthin D > Flemiflavanone D > Lactupicrin > Exiguaflavanone A > Rhamnetin. The binding affinity of the Cassiarin D-ACE2 complex was (-10.2 KJ/mol) found inferior to the Rhinacanthin D-ACE2 complex (-10.8 KJ/mol), referring to Rhinacanthin D as a more stable candidate to use as drugs. The RMSD values of protein-ligand complexes evaluated according to their structural conformation and stable binding pose ranged between 0.1~2.1 Å. The B-factor showed that very few loops were present in the protein structure. The RMSF peak fluctuation regions ranged 5-250, predicting efficient ligand-receptor interactions. CONCLUSION: The experiment sequentially measures all the parameters required in referring to any pharmacophore as a drug, considering which all aromatic components analyzed in the study can strongly be predicted as target-specific medication against the novel coronavirus 2019 infection.

Translation, cultural adaptation, and validation of the duke activity status index in the hindi language.

Background: The Duke Activity Status Index (DASI) is a validated questionnaire in English to assess the functional capacity (FC) of patients with cardiovascular disease (CVD). Aim: The aim of the study is to translate, cross-culturally adapt, and validate the DASI in Hindi. Settings and Study Design: Observational validation study. Methodology: Different translators translated the DASI into Hindi and then back-translated it into English. Validation for feasibility and psychometric properties of translated questionnaire was done on 200 adults, Hindi-speaking patients with CVD, who were advised exercise testing by a cardiologist. Statistical Analysis: Internal consistency (Cronbach's α) and test-retest reliability (Pearson's correlation coefficient) were calculated. Construct (correlation with the Canadian Cardiovascular Society Classification [CCSC] for angina and exercise capacity with treadmill testing [TMT]) and content validity (time taken to fill the questionnaire, ease of understanding the questionnaire items, and comprehensibility) were calculated.P < 0.05 was considered significant. Results: The Cronbach's α for internal consistency was 0.78, which indicates adequate relatedness among the items of questionnaire, and the test-retest reliability was 0.65 (P < 0.05). A significant correlation between CCSC (r = -0.60) and TMT (r = 0.56) was found. The median time taken by the respondents to fill the questionnaire was 4 min. Of all the respondents, 95.74% of the respondents agreed that the Hindi questionnaire was easy to comprehend and 97.87% patients correlated the translated items to their daily physical activity. Conclusions: The Hindi translated and culturally adapted version of the DASI is reliable, valid, and feasible to assess the FC in the Hindi-speaking CVD patients.

Perioperative duloxetine as part of a multimodal analgesia regime reduces postoperative pain in lumbar canal stenosis surgery: a randomized, triple blind, and placebo-controlled trial.

BACKGROUND: Duloxetine is an antidepressant that is also useful in chronic neuropathic and central origin pain. In this study, the role of duloxetine in decreasing acute postoperative pain after lumbar canal stenosis surgery is explored. METHODS: In this single center, triple blinded, and placebo-controlled trial, 96 patients were randomized for statistical analysis. The intervention group received oral duloxetine 30 mg once a day (OD) for 2 days before surgery, 60 mg OD from the day of surgery to the postoperative second day and 30 mg OD for the next 2 days (a total duration of 7 days). A placebo capsule was given in the other group for a similar time and schedule. The same standard perioperative analgesia protocols were followed in both groups. RESULTS: Total morphine consumption up to 24 hours was significantly decreased in the duloxetine group (P < 0.01). The time to the first analgesia requirement was similar in both groups but the time to the second and third dose of rescue analgesia increased significantly in the duloxetine group. The time to ambulation was decreased significantly (P < 0.01) in the duloxetine group as compared to the placebo group. Pain scores remained similar during most of the time interval. No significant difference was observed in the complication rate and patient satisfaction score recorded. CONCLUSIONS: Duloxetine reduces postoperative pain after lumbar canal stenosis surgery with no increase in adverse effects.

Intraoperative Comparison and Evaluation of Intrathecal Bupivacaine Combined with Clonidine versus Fentanyl in Children Undergoing Hernia Repair or Genital Surgery: A Prospective, Randomized Controlled Trial.

BACKGROUND: Nowadays, spinal anesthesia is commonly being used in infants and children for infraumblical surgeries. Intrathecal adjuvants such as clonidine and fentanyl are used with local anesthetics for additive effects. AIM: The present study aims to assess and compare the effects of adding clonidine versus fentanyl to bupivacaine intrathecally in terms of propofol consumption, hemodynamic profile, adverse events, and complications intraoperatively in pediatric patients. SETTINGS AND DESIGN: A prospective randomized controlled trial was conducted between June 2016 and October 2018 in pediatric patients aged 3-8 years undergoing hernia repair or genital surgery under spinal anesthesia after approval of the Institutional Ethical Committee (Reference No: SGRR/IEC/04/16). MATERIALS AND METHODS: Patients were randomly divided into two equal sized (n = 42) study groups, while analysis was done in (n = 40) each group. Group 1 (BC) received clonidine 1 µg/kg with 0.5% bupivacaine (heavy) and Group 2 (BF) received fentanyl 0.5 µg/kg with 0.5% bupivacaine (heavy). STATISTICAL ANALYSIS: Quantitative data were expressed in mean and standard deviation. Qualitative data were expressed in proportion and percentages. Independent t-test was applied to compare the means of quantitative data, and Chi-square test was used to compare categorical data. P < 0.05 was considered statistically significant. RESULTS: Patient characteristics regarding age, weight, and surgical time were comparable in the two groups. The maintenance dose and bolus dose of propofol consumed during surgery were less in Group 1 than that in the Group 2 and were found to be statistically insignificant. The values of hemodynamic parameters such as heart rate, systolic blood pressure, and diastolic blood pressure were less in Group 1 and were statistically significant at different time intervals. Sedation scores were comparable in both groups. Intraoperative incidence of bradycardia, systolic hypotension, and diastolic hypotension were high in Group 1, whereas the incidence of desaturation was high in Group 2. Intraoperative complications such as apnea and respiratory obstruction were high in Group 2, but were statistically insignificant. CONCLUSION: We conclude that intrathecal adjuvant fentanyl maintains a better hemodynamic profile in terms of adverse events such as bradycardia, systolic hypotension, and diastolic hypotension. Intrathecal clonidine maintains a better sedation level requiring less propofol for sedation. Complications such as apnea and respiratory obstruction can be attributed more to the deep sedation caused by bolus of propofol rather than the inherent properties of intrathecal adjuvant clonidine or fentanyl.

Comparison of Subcostal Transversus Abdominis Block with Intraperitoneal Instillation of Levobupivacaine for Pain Relief after Laparoscopic Cholecystectomy: A Prospective Study.

BACKGROUND: There are several methods employed in the management of postoperative pain after laparoscopic cholecystectomy such as conventional systemic analgesics, including paracetamol, non-steroidal anti-inflammatory drugs, systemic opioids, and thoracic epidural analgesia with all having its limitations and side effects. AIMS: The present study aims to compare ultrasound-guided subcostal transversus abdominis (STA) block with intraperitoneal instillation of levobupivacaine in reducing postoperative pain, total analgesic consumption, nausea and vomiting, and recovery time in patients after elective laparoscopic cholecystectomy. SETTINGS AND DESIGN: A prospective study was conducted between January 2017 and December 2017 in 80 patients undergoing elective laparoscopic cholecystectomy after approval of the Institutional Ethical Committee (Reference No: SGRR/IEC/05/16). MATERIALS AND METHODS: Patients were randomly divided into two equal-sized (n = 40) study groups. Group 1 patients received ultrasonography-guided STA block with 0.25% levobupivacaine both sides and Group 2 patients received 0.25% levobupivacaine through intraperitoneal route. STATISTICAL ANALYSIS: Quantitative data were expressed in mean and standard deviation. Qualitative data were expressed in proportion and percentages. Independent t-test was applied to compare the means of quantitative data and the Chi-square test was used to compare categorical data. P < 0.05 was considered to be statistically significant. Survival curve was drawn using the log-rank test for comparing two groups. RESULTS: Patient characteristics regarding age, gender, and weight were comparable in the two groups. The mean Numerical Rating Scale scores were less in Group 1 than in Group 2 in the first 6 h, which was found to be statistically significant. There was no significant difference noted in pain scores after 6 h up to 24 h in postoperative area among the two groups. Pain scores for shoulder tip pain were lower in Group 2 as compared to Group 1 in the first 24 h, which was not significant statistically. CONCLUSION: STA block is a better modality for analgesia compared to intraperitoneal instillation in patients undergoing elective laparoscopic cholecystectomy.

A global reference database of crowdsourced cropland data collected using the Geo-Wiki platform.

A global reference data set on cropland was collected through a crowdsourcing campaign using the Geo-Wiki crowdsourcing tool. The campaign lasted three weeks, with over 80 participants from around the world reviewing almost 36,000 sample units, focussing on cropland identification. For quality assessment purposes, two additional data sets are provided. The first is a control set of 1,793 sample locations validated by students trained in satellite image interpretation. This data set was used to assess the quality of the crowd as the campaign progressed. The second data set contains 60 expert validations for additional evaluation of the quality of the contributions. All data sets are split into two parts: the first part shows all areas classified as cropland and the second part shows cropland average per location and user. After further processing, the data presented here might be suitable to validate and compare medium and high resolution cropland maps generated using remote sensing. These could also be used to train classification algorithms for developing new maps of land cover and cropland extent.

Stability at the half pin-frame interface on external fixation constructs.

A mechanical study investigating the use of two different methods (grub and bolt screws) to secure external fixation half pins to circular frames. A four part experiment: (1) Grub and bolt screws were used to secure half pins in Taylor Spatial frames. Loosening torques were measured using a calibrated torque wrench. (2) Using universal testing machine (UTM), axial loading was applied to establish thresholds for loosening in grub and bolt screw constructs. (3) We established the application torque to produce failure at the head-driver interface using these two methods. (4) Grub and bolt screw constructs were created controlling torque. Using UTM, axial loading was applied to establish thresholds for loosening. Statistical analysis was conducted using SPSS v20.0.0. (1) Higher torque is employed when bolt rather than grub screws is used to secure half pins on Rancho cubes (p < 0.05). (2) Loading threshold for loosening is higher in bolt screw constructs when the torque applied to secure the constructs is not controlled (p < 0.05). (3) Torque required for failure at the head-driver interface was 5.3 Nm for grub screws and 9.9 Nm for bolts. (4) Loading threshold for loosening is higher in grub screw constructs when the same torque was applied to secure them (p < 0.05). Bolt screws can be employed to secure the half pin-frame interface. They offer good stability and reduce failure at the head-driver interface. Further research is needed to determine the mechanical properties of such constructs in vivo.

The non-operative treatment of anterior knee pain.

Anterior knee pain is a common presenting complaint, and in many cases no identifiable cause can be found. In these circumstances it is commonly known as anterior knee pain syndrome or patellofemoral pain syndrome. The management for this condition is most commonly non-operative. Treatment strategies include physiotherapy, pharmacotherapy, orthoses and combinations of the above. There are many described methods in the literature with a wide spectrum of outcomes, which in itself is testimony to the lack of any generally accepted gold standard of care for these patients. It is thus unclear to the health care professional treating these patients which is the best treatment to offer. In this review we aim to summarise historical and most up to date literature on the subject and in so doing allow the health care professional pick whichever treatment strategy they feel most beneficial and also provide a guide for appropriate patient education.

The operative management of patella malalignment.

Management of patellofemoral joint pathology is challenging as a result of the unique and complex organization of static forces and dynamic factors contributing to its functional capacity. Anterior knee pain is a common musculoskeletal complaint seen daily in the practices of primary care physicians, rheumatologists, and orthopedic surgeons. The key to successful treatment lies not only in the correct diagnosis of a chondral defect, but more importantly, in the accurate identification of associated pathomechanical factors. Appreciating the pathoanatomic basis of the disease and addressing imbalances and anatomical abnormalities should guide treatment.Despite the complexity of the interplay of various components it is essential to attempt to describe patellar malalignement as a clinical entity in order to proceed with appropriate surgical management and successful outcomes. The goals of patellofemoral re- alignment surgery should be to create both a stable environment for optimal extensor mechanism performance and an appropriate load transmission for optimal cartilage wear and joint loading. In the context of this article we will review the operative management of patellofemoral malalignment; the indications for surgery, the different techniques available and the evidence regarding their effectiveness.A large number of procedures have been employed and they have all undergone various modifications over the course of the years. The majority of publications are retrospective series in poorly defined population groups. There are significant methodological inconsistencies and as a result there is lack of strong evidence base for the majority of these procedures.