Using the nociception level index to compare the intraoperative antinociceptive effect of propofol and sevoflurane during clinical and experimental noxious stimulus in patients under general anesthesia.

STUDY: Propofol and sevoflurane are two anesthetic agents widely used to induce and maintain general anesthesia (GA). Their intrinsic antinociceptive properties remain unclear and are still debated. OBJECTIVE: To determine whether propofol presents stronger antinociceptive properties than sevoflurane using intraoperative clinical and experimental noxious stimulations and evaluating postoperative pain outcomes. DESIGN: A prospective randomized monocentric trial. SETTING: Perioperative care. PATIENTS: 60 adult patients with ASA status I to III who underwent elective abdominal laparoscopic surgery under GA were randomized either in propofol or sevoflurane group to induce and maintain GA. INTERVENTIONS: We used clinical and experimental noxious stimulations (intubation, tetanic stimulation) to assess the antinociceptive properties of propofol and sevoflurane in patients under GA and monitored using the NOL index, BIS index, heart rate, and mean arterial blood pressure. MEASUREMENTS: We measured the difference in the NOL index alterations after intubation and tetanic stimulation during either intravenous anesthesia (propofol) or inhaled anesthesia (sevoflurane). We also intraoperatively measured the NOL index and remifentanil consumption and recorded postoperative pain scores and opioid consumption in the post-anesthesia care unit. Intraoperative management was standardized by targeting similar values of depth of anesthesia (BIS index), hemodynamic (HR and MAP), NOL index values (below the threshold of 20), same multimodal analgesia and type of surgery. MAIN RESULTS: We found the antinociceptive properties of propofol and sevoflurane similar. The only minor difference was after tetanic stimulation: the delta NOL was higher in the sevoflurane group (39 ± 13 for the propofol group versus 47 ± 15 for sevoflurane; P = 0.04). Intraoperative and postoperative pain outcomes and opioid consumption were similar between groups. CONCLUSIONS: Despite a precise intraoperative experimental and clinical protocol using the NOL index, propofol does not provide a higher level of antinociception during anesthesia or analgesia after surgery when compared to sevoflurane. Anesthesiologists may prefer propofol over sevoflurane to reduce PONV or anesthesia-related pollution, but not for superior antinociceptive properties.

Make me more comfortable: effects of a hypnosis session on pain perception in chronic pain patients.

Introduction: Approximately one-quarter of Canadians experience chronic pain, a debilitating condition often necessitating opioid use, which raises concerns regarding dependency and overdose risks. As an alternative, we developed the HYlaDO program (Hypnose de la Douleur, hypnosis of Pain in French), a novel self-hypnosis approach for chronic pain management. The development of this program followed the ORBIT model, a comprehensive framework for designing interventions encompassing several phases ranging from design to efficacy assessment. Methods: In the present work, we conducted a preliminary evaluation of the HYlaDO program with 21 participants (18 of the 21 patients were included in the analysis). The primary objective was to determine one session of the program's effectiveness in altering pain, anxiety and relaxation via pre-post analysis. The secondary goal was to examine the long-term effects across the same measures, in addition to the overall quality of life. Results: The results highlight the benefits of our approach, while participants reported short-term significant pain reduction, decreased anxiety, and increased relaxation. Additionally, preliminary trends suggest improvements in physical activity and quality of life metrics. Discussion: These positive outcomes highlight HYlaDO's potential as an alternative to opioid therapy for chronic pain. Encouraged by these results, we aim to extend our research to a broader and more diverse cohort, paving the way for comprehensive randomized controlled trials. This expansion will further validate HYlaDO's efficacy and its role in transforming chronic pain management.

Practicing self-hypnosis to reduce chronic pain: A qualitative exploratory study of HYlaDO.

Background: Nearly a quarter of Canada's population suffers from chronic pain, a long-lasting medical condition marked by physical pain and psychological suffering. Opioids are the primary treatment for pain management in this condition; yet, this approach involves several undesirable side effects. In contrast to this established approach, non-pharmacological interventions, such as medical hypnosis, represent an efficient alternative for pain management in the context of chronic pain. HYlaDO is a self-hypnosis program designed to improve pain management for people with chronic pain. Purpose: This research aimed to evaluate the HYlaDO program based on the proof-of-concept level of the ORBIT model and investigated participants' subjective experience. Research design: Qualitative study. Study sample: Seventeen participants with chronic pain took part in this study. Data collection: We conducted individual semi-structured interviews with patients who had participated in HYlaDO to identify the three targets of desired change: pain, anxiety and autonomy in self-hypnosis practice. Results: Thematic analysis revealed that the practice of hetero-hypnosis and self-hypnosis decreased (i) pain and (ii) anxiety. Also, it (iii) indicated the development of an independent and beneficial self-hypnosis practice by having integrated the techniques taught. Conclusion: These results confirm that the established targets were reached and support further development, implementation and scaling up of this program. Consequently, we believe it is justified to move to the next step of program development.

Prediction of acute postoperative pain based on intraoperative nociception level (NOL) index values: the impact of machine learning-based analysis.

The relationship between intraoperative nociception and acute postoperative pain is still not well established. The nociception level (NOL) Index (Medasense, Ramat Gan, Israel) uses a multiparametric approach to provide a 0-100 nociception score. The objective of the ancillary analysis of the NOLGYN study was to evaluate the ability of a machine-learning aglorithm to predict moderate to severe acute postoperative pain based on intraoperative NOL values. Our study uses the data from the NOLGYN study, a randomized controlled trial that evaluated the impact of NOL-guided intraoperative administration of fentanyl on overall fentanyl consumption compared to standard of care. Seventy patients (ASA class I-III, aged 18-75 years) scheduled for gynecological laparoscopic surgery were enrolled. Variables included baseline demographics, NOL reaction to incision or intubation, median NOL during surgery, NOL time-weighted average (TWA) above or under manufacturers' recommended thresholds (10-25), and percentage of surgical time spent with NOL > 25 or < 10. We evaluated different machine learning algorithms to predict postoperative pain. Performance was assessed using cross-validated area under the ROC curve (CV-AUC). Of the 66 patients analyzed, 42 (63.6%) experienced moderate to severe pain. NOL post-intubation (42.8 (31.8-50.6) vs. 34.8 (25.6-41.3), p = 0.05), median NOL during surgery (13 (11-15) vs. 11 (8-13), p = 0.027), percentage of surgical time spent with NOL > 25 (23% (18-18) vs. 20% (15-24), p = 0.036), NOL TWA < 10 (2.54 (2.1-3.0) vs. 2.86 (2.48-3.62), p = 0.044) and percentage of surgical time spent with NOL < 10 (41% (36-47) vs. 47% (40-55), p = 0.022) were associated with moderate to severe PACU pain. Corresponding ROC AUC for the prediction of moderate to severe PACU pain were 0.65 [0.51-0.79], 0.66 [0.52-0.81], 0.66 [0.52-0.79], 0.65 [0.51-0.79] and 0.67 [0.53-0.81]. Penalized logistic regression achieved the best performance with a 0.753 (0.718-0.788) CV-AUC. Our results, even if limited by the small number of patients, suggest that acute postoperative pain is better predicted by a multivariate machine-learning algorithm rather than individual intraoperative nociception variables. Further larger multicentric trials are highly recommended to better understand the relationship between intraoperative nociception and acute postoperative pain.Trial registration Registered on ClinicalTrials.gov in October 2018 (NCT03776838).

Effect of combined intraoperative use of the Nociception Level (NOL) and bispectral (BIS) indexes on desflurane administration.

BACKGROUND: Currently, nociception monitors are not part of standard anaesthesia care. We investigated whether combined intraoperative nociception (NOL index) and anaesthesia (BIS index) monitoring during general anaesthesia would reduce anaesthetics consumption and enhance intraoperative safety and postoperative recovery when compared to standard of care monitoring (SOC). METHODS: In this randomised study, we included 60 patients undergoing colonic surgery under desflurane/remifentanil anaesthesia and epidural analgesia. Patients received either standard monitoring or combined BIS + NOL index monitoring. In the monitored group, remifentanil infusion was titrated to achieve a NOL index below 20. Desflurane was adjusted to BIS values (45-55). In the SOC group, remifentanil and desflurane were titrated on vital signs and MAC. The primary outcome was intraoperative desflurane consumption. RESULTS: Fifty-five patients were analysed. Desflurane administration was reduced in the monitored group from 0.25 ± 0.05 to 0.20 ± 0.06 mL kg-1 h-1 (p < 0.001). The cumulative time with a BIS under 40 was significantly higher in the SOC group with a median time of 12.6 min (95% CI: 0.6-80.0) versus 2.0 min (95% CI: 0.3-5.83) (p = 0.023). Time for extubation was significantly shorter in the monitored group: 4.4 min (95% CI: 2.4-4.9) versus 6.28 min (95% IC: 5.0-8.2) (p = 0.003). We observed no differences in remifentanil or phenylephrine requirements during anaesthesia or in postoperative outcome measures, such as postoperative pain, opioid consumption, neurocognitive recovery. CONCLUSION: Combined intraoperative monitoring of anaesthesia and nociception during colonic surgery resulted in less desflurane consumption and quicker extubation time compared to standard clinical care monitoring.

Changes in Inequality in Use of Maternal Health Care Services: Evidence from Skilled Birth Attendance in Mauritania for the Period 2007-2015.

Skilled birth attendance is critical to reduce infant and maternal mortality. Health development plans and strategies, especially in developing countries, consider equity in access to maternal health care services as a priority. This study aimed to measure and analyze the inequality in the use of skilled birth attendance services in Mauritania. The study identifies the inequality determinants and explores its changes over the period 2007−2015. The concentration curve, concentration index, decomposition of the concentration index, and Oaxaca-type decomposition technique were performed to measure socioeconomically-based inequalities in skilled birth attendance services utilization, and to identify the contribution of different determinants to such inequality as well as the changes in inequality overtime using data from Mauritania Multiple Indicator Cluster Surveys (MICS) 2007 and 2015. The concentration index for skilled birth attendance services use dropped from 0.6324 (p < 0.001) in 2007 to 0.5852 (p < 0.001) in 2015. Prenatal care, household wealth level, and rural−urban residence contributed most to socioeconomic inequality. The concentration index decomposition and the Oaxaca-type decomposition revealed that changes in prenatal care and rural−urban residence contributed positively to lower inequality, but household economic status had an opposite contribution. Clearly, the pro-rich inequality in skilled birth attendance is high in Mauritania, despite a slight decrease during the study period. Policy actions on eliminating geographical and socioeconomic inequalities should target increased access to skilled birth attendance. Multisectoral policy action is needed to improve social determinants of health and to remove health system bottlenecks. This will include the socioeconomic empowerment of women and girls, while enhancing the availability and affordability of reproductive and maternal health commodities. This policy action can be achieved through improving the availability of obstetric service providers in rural areas; ensuring better distribution and quality of health infrastructure, particularly health posts and health centers; and, ensuring user fees removal for equitable, efficient, and sustainable financial protection in line with the universal health coverage objectives.

Intrapandemic regional anesthesia as practice: a historical cohort study in patients undergoing breast cancer surgery.

BACKGROUND: The COVID-19 pandemic has markedly increased delays in oncologic surgeries because of the virus's impact on traditional anesthetic management. Novel protocols, developed to protect patients and medical professionals, have altered the ways and instances in which general anesthesia (GA) can be safely performed. To reduce virus exposure related to aerosol-generating procedures, it is now recommended to avoid GA when feasible and promote regional anesthesia instead. At our institution, we observed faster postoperative recovery in patients who received paravertebral blocks for breast cancer surgery instead of GA. This led us to formally evaluate whether regional anesthesia instead of GA helped improve time to hospital discharge. METHODS: We conducted a historical cohort study to retrospectively analyze two cohorts of patients: prepandemic vs intrapandemic. We obtained approval from our institutional ethics committee to review files of consecutive patients who underwent breast cancer surgery between 30 March 2020 and 30 June 2020 (intrapandemic group; N = 106) and consecutive patients-moving backwards-from 28 February 2020 to 6 December 2019 (prepandemic group; N = 104). The primary outcome was the length of time between the end of surgery to readiness for hospital discharge. Secondary outcomes included the incidence of postoperative nausea and vomiting (PONV), the need for postoperative analgesia, and the duration of stay in the postanesthesia care unit (PACU). RESULTS: The median [interquartile range (IQR)] time to readiness for hospital discharge was significantly lower in patients who received paravertebral blocks for breast cancer surgery compared with GA (intrapandemic group, 119 [99-170] min vs prepandemic group, 191 [164-234] min; P < 0.001) as was the incidence of PONV (3% vs 11%; P = 0.03) and median [IQR] PACU durations of stay (29 [21-39] min vs 46 [37-63] min; P < 0.001). CONCLUSIONS: Patients who received paravertebral blocks for breast cancer surgery in the intrapandemic group were ready for hospital discharge earlier, spent less time in the PACU, and experienced less PONV than those who received GA in the prepandemic group. With growing surgical wait times, concerns related to aerosol-generating procedures, and recommendations to avoid GA when feasible, paravertebral blocks as the principal anesthetic modality for breast cancer surgery offered benefits for patients and medical teams.

RéSUMé: CONTEXTE: La pandémie de COVID-19 a considérablement augmenté les retards dans les chirurgies oncologiques en raison de l'impact du virus sur la prise en charge anesthésique traditionnelle. De nouveaux protocoles, mis au point pour protéger les patients et les professionnels de la santé, ont modifié les façons et les cas dans lesquels une anesthésie générale (AG) peut être réalisée en toute sécurité. Afin de réduire l'exposition au virus liée aux interventions génératrices d'aérosols, il est maintenant recommandé d'éviter l'AG lorsque possible et de privilégier l'anesthésie régionale. Dans notre établissement, nous avons observé une récupération postopératoire plus rapide chez les patientes ayant reçu des blocs paravertébraux pour une chirurgie de cancer du sein au lieu d'une AG. Cela nous a menés à évaluer de façon formelle si l'anesthésie régionale au lieu de l'AG avait contribué à réduire les délais jusqu'au congé de l'hôpital. MéTHODE: Nous avons réalisé une étude de cohorte historique afin d'analyser rétrospectivement deux cohortes de patientes : prépandémie vs intrapandémie. Nous avons obtenu l'approbation de notre comité d'éthique institutionnel pour examiner les dossiers de patientes consécutives ayant bénéficié d'une chirurgie de cancer du sein entre le 30 mars 2020 et le 30 juin 2020 (groupe intrapandémie; n = 106) et des patientes consécutives ­ en reculant ­ du 28 février 2020 au 6 décembre 2019 (groupe prépandémie; n = 104). Le critère d'évaluation principal était le délai entre la fin de la chirurgie et le moment où les patientes étaient prêtes à recevoir leur congé de l'hôpital. Les critères d'évaluation secondaires comprenaient l'incidence de nausées et vomissements postopératoires (NVPO), la nécessité d'une analgésie postopératoire et la durée de séjour en salle de réveil (SDR). RéSULTATS: Le délai médian [écart interquartile (ÉIQ)] jusqu'à la disposition au congé de l'hôpital était significativement plus court chez les patientes ayant reçu des blocs paravertébraux pour une chirurgie de cancer du sein plutôt qu'une AG (groupe intrapandémie, 119 [99-170] min vs groupe prépandémie, 191 [164­234] min; P < 0,001), tout comme l'incidence de NVPO (3 % vs 11 %; P = 0,03) et les durées médianes [ÉIQ] de séjour en salle de réveil (29 [21­39] min vs 46 [37­63] min; P < 0,001). CONCLUSION: Les patientes qui ont reçu des blocs paravertébraux pour une chirurgie de cancer du sein dans le groupe intrapandémie étaient prêtes à quitter l'hôpital plus tôt, ont passé moins de temps en salle de réveil et ont ressenti moins de NVPO que celles qui ont reçu une AG dans le groupe prépandémie. Avec des temps d'attente pour accès à la chirurgie de plus en plus longs, des préoccupations liées aux interventions génératrices d'aérosols et les recommandations d'éviter l'AG lorsque possible, les blocs paravertébraux ont offert des avantages aux patientes et aux équipes médicales en tant que principale modalité anesthésique pour la chirurgie de cancer du sein.

"Impact of Nociception Level (NOL) index intraoperative guidance of fentanyl administration on opioid consumption, postoperative pain scores and recovery in patients undergoing gynecological laparoscopic surgery. A randomized controlled trial".

STUDY OBJECTIVE: The Nociception Level (NOL) index uses a multiparametric approach to measure the balance between sympathetic and parasympathetic systems activity. Recently, a strong correlation between the NOL index response to nociceptive stimuli and the level of opioid analgesia during surgery was reported. Others observed that intraoperative doses of remifentanil and sufentanil were reduced when the NOL index was used. So far, no study has evaluated the impact of NOL-guided fentanyl antinociception in laparoscopic gynecological surgery. The primary hypothesis of this present study was to evaluate whether intraoperative NOL-guided fentanyl administration would reduce intra-operative opioid consumption. Secondary hypotheses were to assess whether this would lead to lower postoperative opioid consumption and pain scores, as well as improved postoperative outcomes. SETTING: University hospital, operating room. PATIENTS: 70 adult patients, ASA 1-3, scheduled for total laparoscopic hysterectomy. INTERVENTIONS: Patients were randomized into 2 groups: SOC (standardization of care) and NOL (using the NOL index to guide the administration of fentanyl). The depth of anesthesia was monitored with BIS™. Intraoperative fentanyl boluses were administered based on heart rate and mean arterial pressure variations in the SOC group, and NOL index for the NOL group. MEASUREMENTS: Fentanyl total intraoperative dose administered was collected and also averaged per hour. Pain scores and hydromorphone consumption were assessed in the post-anesthesia care unit and up to 24 h. MAIN RESULTS: Sixty-six patients completed the study, 33 in each group. Total intraoperative fentanyl administration was not different between the two groups (217 (70) in the NOL group vs 280 (210) in the SOC group (P = 0.11)). Nevertheless, intraoperative fentanyl administration per hour was reduced by 25% in the NOL-guided group compared to the SOC group: 81 (24) vs 108 (66) µg.h-1, respectively (P = 0.03). Hydromorphone consumption and pain scores in the post-anesthesia care unit and at 24 h were not significantly different between the two groups. CONCLUSION: NOL-guided analgesia allowed for a 22% reduction of the total amount of intraoperative fentanyl which was not significant. Nevertheless, results reported a significant reduction by 25% in the doses of fentanyl averaged per hour of surgery and administered in the NOL-guided group compared with the standardized practice in laparoscopic gynecological surgery. The pain measured postoperatively was similar in the two groups while the average postoperative consumption of opioids to achieve the same level of pain scores in post-anesthesia care unit and at 24 h was not significantly reduced. Further larger multicenter studies centered towards postoperative outcomes are needed.

The impact of bolus versus continuous infusion of intravenous ketamine on bispectral index variations and desflurane administration during major surgery: The KETABIS study.

BACKGROUND: Although ketamine, a NMDA-receptor antagonist, tends to increase the bispectral index (BIS), it remains a widely used analgesic whenever administered in low doses during major surgery. OBJECTIVE: The objective of this study was to compare the impact of intravenous ketamine (given either as a continuous infusion or as a bolus) on BIS and to compare desflurane administration and postoperative outcomes between the groups. DESIGN: Prospective, randomised, parallel-group, open-label study. SETTING: University hospital, operating room. PARTICIPANTS: Fifty patients, scheduled for major abdominal surgery. INTERVENTIONS AND MAIN OUTCOMES MEASURES: Patients were randomised into two groups: ketamine by intravenous continuous infusion - group (KI) and ketamine by i.v. bolus - group (KB). In the KI group, ketamine at a rate of 0.25 mg kg-1 h-1 was commenced at skin incision (T0) and maintained at this rate for the duration of surgery. In group KB, a ketamine bolus of 0.25 mg kg-1was administered at T0 and repeated every hour. The difference in BIS between the groups was compared from T0 onwards. The amount of desflurane administered to keep BIS within the usual recommended range (40-60) was compared, as were the doses of phenylephrine and remifentanil. Postoperative pain and recovery outcomes were also assessed. RESULTS: After T0, the BIS increased significantly from baseline in group KB compared with group KI: the rise in BIS was 20 ±â€Š8 vs. 11 ±â€Š6, respectively (P = 0.0001). The between-group mean difference (95% confidence interval (CI), was 9 (5 to 13). In group KB, desflurane administration significantly increased for the first 15 min after T0: 6.3 ±â€Š1.8 vs. 3.8 ±â€Š1.3 ml (P < 0.0001) with a mean intergroup group difference (95% CI) of 2.4 (1.5 to 3.4) ml. There was no difference in desflurane administration when considering the full hour from T0 to T60 min: 16 ±â€Š9 vs. 15 ±â€Š5 ml (P = 0.63) with a mean intergroup difference (95% CI) of 1 (-3 to 5) ml. After surgery, pain scores, opioid consumption, incidence of nausea and vomiting and recovery scores were similar between groups. CONCLUSION: Compared with a continuous ketamine infusion, a ketamine bolus significantly increased the BIS after T0. In order to keep the BIS below 60, significantly more desflurane was administered from T0 to T15 min in group KB. To prevent such higher desflurane administration and its related atmospheric pollution, our results suggest administering intra-operative intravenous ketamine as an infusion rather than a bolus. TRIAL REGISTRATION: Clinicaltrials.gov registration identifier: NCT03781635.

Assessing the antinociceptive effect of nitrous oxide to tetanic stimulation in anaesthetised patients with new intra-operative nociception monitors: An observational study.

BACKGROUND: Nitrous oxide (N2O) has been used since the 19th century for its analgesic, antinociceptive and anxiolytic effects during surgical procedures in awake and anaesthetised patients. However, quantification of noxious stimuli that occur under general anaesthesia is a constant challenge for anaesthesiologists, and recently two new indices have been developed to assess intra-operative nociception. OBJECTIVE: The aim of this study was to quantify with new indices as well as with more classical clinical parameters the antinociceptive effect of N2O during general anaesthesia. DESIGN: Prospective, open label, patient-blinded, observational and descriptive trial. SETTING: Single-centre academic hospital. PARTICIPANTS: Forty American Society of Anesthesiologists' physical status 1 to 3 patients undergoing general anaesthesia for elective abdominal surgery via laparotomy were recruited. MAIN OUTCOMES MEASURES: Intra-operative pain was assessed using a standardised electrical stimulation of the forearm (tetanic stimulation at 70 mA, 100 Hz for 30 s), at 0, 25 and 50% inhaled N2O/O2. Heart rate (HR), mean arterial blood pressure, bispectral index, the analgesia nociception index and the nociception level (NOL) index were used to evaluate intra-operative nociception before and after each standardised tetanic stimulation. RESULTS: There was a 16% reduction of the analgesia nociception index reaction, a 31% reduction of the NOL reaction and a 51% reduction of the HR reaction to a standardised electrical tetanic nociceptive stimulation during administration of 50% N2O. Administration of 50 or 25% inhaled N2O produced the same quality of antinociception based on HR and NOL index analyses. HR and the NOL index were the best parameters to identify the antinociceptive effect of intra-operatively administered N2O. CONCLUSION: In anaesthetised patients, our study demonstrated clinically significant antinociceptive properties of N2O. Our results showed that low concentrations of N2O (25%) are as effective as higher concentrations (50%) to achieve a significant antinociceptive effect. These findings may help decrease negative effects of using higher concentrations of N2O, including its side effects and its environmental pollution. TRIAL REGISTRATION: ClinicalTrials.gov registration identifier: NCT02701478.

Impact of anesthesia management during cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy for the treatment of colorectal peritoneal carcinomatosis on intra- and postoperative outcomes: A systematic review protocol.

BACKGROUND: The impact of the anesthesia management during cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of colorectal peritoneal carcinomatosis (CRPC) on postoperative outcomes might be of major importance in the process of postoperative recovery. It might have a significant impact on intra- and postoperative outcomes, but the evaluation of this impact seems to be under-reported. To investigate the question whether the anesthesia management was reported in previous studies done in this population and if it had any impact on postoperative outcomes, we propose to conduct a systematic review of the published literature. METHODS: For this review, we will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P). Medline/PubMed, Embase, EBM Reviews and the Cochrane Database of Systematic Reviews (CDSR) will be systematically consulted for eligible studies without age, gender, ethnic, and language restriction. The goal of this review will be to assess whether anesthesia monitoring, dosing, and analgesia protocols were reported in this literature on this specific procedure and whether the impact of the anesthesia management on intraoperative safety and postoperative recovery was evaluated. RESULTS: The results of this systematic review will allow to answer the initial question: has the impact of anesthesia management on intraoperative safety and patients' postoperative recovery already been studied and reported in the past for this type of major surgery? And does anesthesia have any impact on postoperative outcomes? DISCUSSION: In the hypothesis that the impact of anesthesia management on patients' postoperative recovery has never been studied, or very little reported in previous studies in this type of major surgery, it would be justified to conduct a randomized controlled trial on this specific objective. REGISTRATION: This systematic review protocol was registered in PROSPERO, under the registration number CRD42019124162.

Measuring and understanding the effects of a performance based financing scheme applied to nutrition services in Burundi-a mixed method impact evaluation design.

BACKGROUND: Malnutrition is a huge problem in Burundi. In order to improve the provision of services at hospital, health centre and community levels, the Ministry of Health is piloting the introduction of malnutrition prevention and care indicators within its performance based financing (PBF) scheme. Paying for units of services and for qualitative indicators is expected to enhance provision and quality of these nutrition services, as PBF has done, in Burundi and elsewhere, for several other services. METHODS: This paper presents the protocol for the impact evaluation of the PBF scheme applied to malnutrition. The research design consists in a mixed methods model adopting a sequential explanatory design. The quantitative component is a cluster-randomized controlled evaluation design: among the 90 health centres selected for the study, half receive payment related to their results in malnutrition activities, while the other half get a budget allocation. Qualitative research will be carried out both during the intervention period and at the end of the quantitative evaluation. Data are collected from 1) baseline and follow-up surveys of 90 health centres and 6,480 households with children aged 6 to 23 months, 2) logbooks filled in weekly in health centres, and 3) in-depth interviews and focus group discussions. The evaluation aims to provide the best estimate of the impact of the project on malnutrition outcomes in the community as well as outputs at the health centre level (malnutrition care outputs) and to describe quantitatively and qualitatively the changes that took place (or did not take place) within health centres as a result of the program. DISCUSSION: Although PBF schemes are blooming in low in-come countries, there is still a need for evidence, especially on the impact of revising the list of remunerated indicators. It is expected that this impact evaluation will be helpful for the national policy dialogue in Burundi, but it will also provide key evidence for countries with an existing PBF scheme and confronted with malnutrition problems on the appropriateness to extend the strategy to nutrition services. TRIAL REGISTRATION: ClinicalTrials.gov PRS Identifier: NCT02721160; registered March 2016.

Discovery of thiadiazoles as a novel structural class of potent and selective PDE7 inhibitors. Part 1: design, synthesis and structure-activity relationship studies.

The synthesis and SAR studies of a series of structurally novel small molecule inhibitors of PDE7 are discussed. The best compounds from the series displayed low nanomolar inhibitory activity and are selective versus PDE4.

Discovery of thiadiazoles as a novel structural class of potent and selective PDE7 inhibitors. Part 2: metabolism-directed optimization studies towards orally bioavailable derivatives.

The synthesis and optimization of pharmacokinetic parameters of structurally novel small PDE7 inhibitors is discussed.

Spiroquinazolinones as novel, potent, and selective PDE7 inhibitors. Part 1.

The synthesis and SAR studies of spiroquinazolinones as novel PDE7 inhibitors are discussed. The best compounds from the series displayed nanomolar inhibitory affinity and were selective versus other PDE isoenzymes.

Spiroquinazolinones as novel, potent, and selective PDE7 inhibitors. Part 2: Optimization of 5,8-disubstituted derivatives.

The optimization of 5,8-disubstituted spirocyclohexane-quinazolinones into potent, selective, soluble PDE7 inhibitors with acceptable in vivo pharmacokinetic parameters is presented.