Intravenous versus perineural dexamethasone to prolong analgesia after interscalene brachial plexus block: a systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: The efficacy of perineural vs intravenous dexamethasone as a local anaesthetic adjunct to increase duration of analgesia could be particular to specific peripheral nerve blocks because of differences in systemic absorption depending on the injection site. Given this uncertainty, we performed a systematic review with meta-analysis and trial sequential analysis comparing dexamethasone administered perineurally or intravenously combined with local anaesthetic for interscalene brachial plexus block. METHODS: Following a search of various electronic databases, we included 11 trials (1145 patients). The primary outcome was the duration of analgesia defined as the time between peripheral nerve block or onset of sensory blockade and the time to first analgesic request or initial report of pain. RESULTS: The primary outcome, duration of analgesia, was greater in the perineural dexamethasone group, with a mean difference (95% confidence interval) of 122 (62-183) min, I2=73%, P<0.0001. Trial sequential analysis indicated that firm evidence had been reached. The quality of evidence was downgraded to low, mainly because of moderate inconsistency and serious publication bias. No significant differences were present for any of the secondary outcomes, except for onset time of sensory and motor blockade and resting pain score at 12 h, but the magnitude of differences was not clinically relevant. CONCLUSIONS: There is low-quality evidence that perineural administration of dexamethasone as a local anaesthetic adjunct increases duration of analgesia by an average of 2 h compared with intravenous injection for interscalene brachial plexus block. Given the limited clinical relevance of this difference, the off-label use of perineural administration, and the risk of drug crystallisation, we recommend intravenous dexamethasone administration. SYSTEMATIC REVIEW PROTOCOL: PROSPERO (CRD42023466147).

Influence of different volumes and frequency of programmed intermittent epidural bolus in labor on maternal and neonatal outcomes: A systematic review and network meta-analysis.

STUDY OBJECTIVE: In labor, programmed intermittent epidural bolus (PIEB) can be defined as the bolus administration of epidural solution at scheduled time intervals. Compared to continuous epidural infusion (CEI) with or without patient controlled epidural analgesia (PCEA), PIEB has been associated with decreased pain scores and need for rescue analgesia and increased maternal satisfaction. The optimal volume and dosing interval of PIEB, however, has still not been determined. DESIGN: Systematic review and network meta-analysis registered with PROSPERO (CRD42022362708). SETTINGS: Labor. PATIENTS: Pregnant patients. INTERVENTIONS: Central, CINAHL, Global Health, Ovid Embase, Ovid Medline and Web of Science were searched for randomized controlled trials that examined pregnant patients in labor who received CEI or PIEB with or without a PCEA component. Network meta-analysis was performed with a frequentist method, facilitating the indirect comparison of PIEB with different volumes and dosing intervals through the common comparator of CEI and substituting or supplementing direct comparisons with these indirect ones. Continuous and dichotomous outcomes were presented as mean differences and odds ratios, respectively, with 95% confidence intervals. The risk of bias was evaluated using the Cochrane risk of bias 2 tool. MAIN RESULTS: Overall, 30 trials were included. For the first primary endpoint, need for rescue analgesia, PIEB delivered at a volume of 4 ml and frequency of 45 min (4/45) was inferior to PIEB 8/45 (OR 3.55; 95% CI 1.12-11.33), PIEB 10/60 was superior to PIEB 2.5/15 (OR 0.36; 95% CI 0.16-0.82), PIEB 4/45 (OR 0.14; 95% CI 0.03-0.71) and PIEB 5/60 (OR 0.23; 95% CI 0.08-0.70), and PIEB 5/30 was not inferior to PIEB 10/60 (OR 0.61; 95% CI 0.31-1.19). For the second primary endpoint, maternal satisfaction, no differences were present between the various PIEB regimens. The quality of evidence for these multiple primary endpoints was low owing to the presence of serious limitations and imprecision. Importantly, PIEB 5/30 decreased the pain score at 4 h compared to PIEB 2.5/15 (MD 2.45; 95% CI 0.13-4.76), PIEB 5/60 (MD -2.28; 95% CI -4.18--0.38) and PIEB 10/60 (MD 1.73; 95% CI 0.31-3.16). Mean ranking of interventions demonstrated PIEB 10/60 followed by PIEB 5/30 to be best placed to reduce the cumulative dose of local anesthetic, and this resulted in an improved incidence of lower limb motor blockade for PIEB 10/60 in comparison to CEI (OR 0.30; 95% CI 0.14-0.67). No differences in neonatal outcomes were found. Some concerns were present for the risk of bias in two thirds of trials and the risk of bias was shown to be high in the remaining one third of trials. CONCLUSIONS: Future research should focus on PIEB 5/30 and PIEB 10/60 and how the method of analgesia initiation, nature and concentration of local anesthetic, design of epidural catheter and rate of administration might influence outcomes related to the mother and neonate.

Local anaesthetic adjuncts for peripheral nerve blockade.

PURPOSE OF REVIEW: Moderate-to-severe pain is common and remains a significant problem. Compared with opioid analgesia alone, single-shot peripheral nerve blockade has been associated with improved pain relief and the potential of decreased side effects. Single-shot nerve blockade, however, is limited by its relatively short duration of action. In this review, we aim to summarize the evidence related to local anaesthetic adjuncts for peripheral nerve blockade. RECENT FINDINGS: Dexamethasone and dexmedetomidine exhibit characteristics that most closely resemble the ideal local anaesthetic adjunct. In upper limb block, dexamethasone has been demonstrated to be superior to dexmedetomidine regardless of administration route for the duration of sensory and motor blockade as well as the duration of analgesia. No clinically significant differences between intravenous and perineural dexamethasone were found. Perineural and intravenous dexamethasone have the potential to prolong sensory blockade to a greater extent than motor blockade. The evidence indicates that the mechanism of action of perineural dexamethasone in upper limb block is systemic in nature. Unlike perineural dexmedetomidine, intravenous dexmedetomidine has not been shown to result in differences in the characteristics of regional blockade compared with local anaesthetic alone. SUMMARY: Intravenous dexamethasone is the local anaesthetic adjunct of choice, increasing the duration of sensory and motor blockade as well as the duration of analgesia by 477, 289 and 478 min, respectively. In view of this, we recommend consideration of the intravenous administration of dexamethasone at a dose of 0.1-0.2 mg/kg for all patients undergoing surgery whatever the level of postoperative pain, mild, moderate or severe. Further research should focus on the potential synergism of action between intravenous dexamethasone and perineural dexmedetomidine.

Comparison of different nonsteroidal anti-inflammatory drugs for cesarean section: a systematic review and network meta-analysis.

BACKGROUND: Cesarean section is associated with moderate to severe pain and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly employed. The optimal NSAID, however, has not been elucidated. In this network meta-analysis and systematic review, we compared the influence of control and individual NSAIDs on the indices of analgesia, side effects, and quality of recovery. METHODS: CDSR, CINAHL, CRCT, Embase, LILACS, PubMed, and Web of Science were searched for randomized controlled trials comparing a specific NSAID to either control or another NSAID in elective or emergency cesarean section under general or neuraxial anesthesia. Network plots and league tables were constructed, and the quality of evidence was evaluated with Grading of Recommendations Assessment, Development and Evaluation (GRADE) analysis. RESULTS: We included 47 trials. Cumulative intravenous morphine equivalent consumption at 24 h, the primary outcome, was examined in 1,228 patients and 18 trials, and control was found to be inferior to diclofenac, indomethacin, ketorolac, and tenoxicam (very low quality evidence owing to serious limitations, imprecision, and publication bias). Indomethacin was superior to celecoxib for pain score at rest at 8-12 h and celecoxib + parecoxib, diclofenac, and ketorolac for pain score on movement at 48 h. In regard to the need for and time to rescue analgesia COX-2 inhibitors such as celecoxib were inferior to other NSAIDs. CONCLUSIONS: Our review suggests the presence of minimal differences among the NSAIDs studied. Nonselective NSAIDs may be more effective than selective NSAIDs, and some NSAIDs such as indomethacin might be preferable to other NSAIDs.

Use of Cryopreserved Amniotic Membrane During Pterygium Excision: Health Economic Analysis.

Purpose: To determine the health economic opportunity cost or gain associated with performing pterygium excision surgery using the TissueTuck technique with cryopreserved amniotic membrane (AM) instead of conjunctival autograft (CAU). Methods: We performed a literature review to determine the average surgical duration of pterygium surgery using CAU with fibrin glue or sutures to calculate the average time saved with the TissueTuck technique. Such time savings was then used to determine the opportunity revenue gain per national average Medicare reimbursement if adjusted to the average surgical duration of cataract surgery. Results: The time savings achieved using the TissueTuck technique over CAU with fibrin glue is 8.9 min per procedure, which can be applied to additional MSICS or phacoemulsification procedures to generate an opportunity revenue gain of $1167 or $762 per 2022 National Average Medicare reimbursement, respectively. After subtracting the current list cost of AmnioGraft (ie, $645), the opportunity gain is $522 or $117 if the time saving is applied to the above procedures, respectively. Alternatively, the time savings achieved by using the TissueTuck technique over CAU with sutures is 23.4 min per procedure, which can be applied to additional MSICS or phacoemulsification procedures to generate an opportunity revenue gain of $3068 and $2004 per TissueTuck procedure or $2423 or $1359 when accounting for the list cost of AmnioGraft, respectively. Conclusion: The TissueTuck surgical technique using cryopreserved AM for pterygium takes less time, has lower recurrence rates, and provides an opportunity gain compared to pterygium excision with CAU.

Increased complications rates and inferior patient reported outcomes following total knee arthroplasty due to post-traumatic osteoarthritis with previous fracture treatment: a systematic review.

PURPOSE: This study aims to present the existing literature relating to patient-reported outcome measures (PROMs) and complications in patients undergoing total knee arthroplasty (TKA) due to posttraumatic osteoarthritis (PTOA) with prior fracture treatment around the knee compared with patients who underwent TKA because of primary osteoarthritis (OA). METHODS: A systematic review was undertaken and synthesised in accordance with the PRISMA guidelines by searching existing literature in the following databases: PubMed, Scopus, Cochrane Library and EMBASE. A search string according to the PECO was used. After analysing 2781 studies, 18 studies (5729 PTOA patients/149,843 OA patients) were included for a final review. An analysis revealed that 12 (67%) were retrospective cohort studies, four (22%) were register studies and the remaining two (11%) were prospective cohort studies. The mean Critical Appraisal Skills Programme (CASP) score was 23.6 out of 28, signifying studies of moderate quality. RESULTS: The most frequently reported outcome measure were postoperative complications, reported in all eighteen studies. Intraoperative complications were reported in ten (4165 PTOA/124.511 OA) and patient-reported outcome measures (PROMs) in six studies (210 PTOA/2768 OA). A total of nine different PROMs were evaluated. As far as PROMs were concerned, the scores were inferior for PTOA but did not differ statistically from OA, except for one study, which favoured the OA group. Across all studies, postoperative complications were higher in the PTOA group, reporting infections as the most common complication. Furthermore, a higher revision rate was reported in the PTOA group. CONCLUSION: PROM analysis suggests that both patient groups benefit from a TKA in terms of functional outcome and pain relief, however, patient-reported outcomes could be inferior for PTOA patients. There is consistent evidence for increased complication rates following PTOA TKA. Patients undergoing TKA due to PTOA after fracture treatment should be informed about the risk for inferior results and refrain from comparing their knee function to patients with TKA after OA. Surgeons should be aware of the challenges that PTOA TKA poses. LEVEL OF EVIDENCE: Level III.

High-level soccer players have a low rate of return to performance after hip arthroscopy for femoroacetabular impingement syndrome.

PURPOSE: Femoroacetabular impingement syndrome (FAIS) is a known cause of impaired sports performance in athletes and the relationship between FAIS and soccer players has previously been described. Hip arthroscopy is a viable treatment option that can facilitate athletes' return to sport (RTS). The aim of this study was to evaluate the RTS and return to performance (RTP) with objective measurements in high-level soccer players after hip arthroscopy for FAIS. METHOD: Soccer players, with a hip sports activity scale (HSAS) level of 7 or 8 before symptom onset and undergoing hip arthroscopy for FAIS between 2011 and 2019 were identified in the Gothenburg hip arthroscopic registry. A total of 83 high-level soccer players, with a mean age of 23.9 (SD 4.4) years at surgery, were included. To verify the activity level and further stratify players as elite or sub-elite, player statistics were collected from soccer-specific scout webpages and the Swedish national soccer association. The return to sport was defined as return to one game of soccer. Return to performance was defined as playing at the same level, or higher, and participating in at least 80% of the number of games played the season before symptom onset or the season before surgery either the first or second season after hip arthroscopy. RESULTS: In total, 71 (85.5%, 95% confidence interval (CI) 76.1-92.3%) of the players returned to sport the first or second season after surgery. Compared to the season before symptom onset, 31 (37.3%, 95% CI 27.0-48.7%) players returned to performance the first or second season after surgery, and 32 (38.6%, 95% CI 28.1-49.9%) players returned to performance the first or second season after surgery compared to the season before surgery. CONCLUSION: A high rate of elite and sub-elite soccer players return to soccer after hip arthroscopy for FAIS. However, less than half of the players RTP when evaluating performance through level of play and number of games played. LEVEL OF EVIDENCE: Level IV.

Comparison of different delivery modalities of epidural analgesia and intravenous analgesia in labour: a systematic review and network meta-analysis.

PURPOSE: In labour, neuraxial analgesia is the standard in the provision of pain relief. However, the optimal mode of delivering epidural solution has not been determined, and some parturients may need an alternative to epidural analgesia. We sought to conduct a systematic review and network meta-analysis to compare continuous epidural infusion (CEI), programmed intermittent epidural bolus (PIEB), computer-integrated CEI, computer-integrated PIEB, patient-controlled epidural bolus (PCEA), fentanyl patient-controlled analgesia (PCA), and remifentanil PCA, either alone or in combination. METHODS: We searched CENTRAL, CINAHL, Ovid Embase, Ovid Medline, and Web of Science for randomized controlled trials that included nulliparous and/or multiparous parturients in spontaneous or induced labour. The maintenance epidural solution had to include a low concentration local anesthetic and an opioid. Specific subgroups in the obstetric population such as preeclampsia were excluded. Network meta-analysis was performed with a frequentist method, and continuous and dichotomous outcomes are presented as mean differences and odds ratios, respectively, with 95% confidence intervals. RESULTS: Overall, 73 trials were included. For the first coprimary outcome, the need for rescue analgesia, CEI was inferior to PIEB and PIEB + PCEA was superior to PCEA alone, with a low certainty of evidence given the presence of serious limitations and imprecision. The second coprimary outcome, the maternal satisfaction, was improved by PIEB + PCEA compared with CEI + PCEA and PCEA alone, with a low quality of evidence in view of the presence of serious limitations and imprecision. Fentanyl PCA increased the requirement for rescue analgesia and decreased maternal satisfaction relative to many methods of delivering epidural solution. In terms of secondary outcomes, PIEB increased analgesic efficacy compared with CEI, and PCEA reduced local anesthetic consumption at the expense of inferior analgesia relative to CEI and PIEB. PIEB + PCEA was superior to CEI + PCEA in regard to the pain score at 2 h and 4 h, consumption of local anesthetic, incidence of lower lower limb motor blockade and the rate of spontaneous vaginal delivery. Fentanyl and remifentanil PCA did not provide the same level of analgesia as all epidural methods, resulted in increasing analgesic ineffectiveness with time spent in labour, and predisposed to a higher incidence of side effects such as nausea and/or vomiting and sedation. Remifentanil PCA was superior to fentanyl PCA for analgesia at an early time point, and it increased the incidence of oxygen desaturation relative to other strategies of delivering epidural solution. CONCLUSIONS: Opioid PCA did not provide the same level of analgesia as epidural methods with a higher incidence of side effects. We interpret the findings of our systematic review and network meta-analysis as suggesting PIEB + PCEA to be the optimal delivery mode of epidural solution. Nevertheless, the potential differing importance of the various maternal, fetal, and neonatal outcomes in determining which is optimal has not, to our knowledge, been elucidated yet. STUDY REGISTRATION: PROSPERO (CRD42021254978); registered 27 May 2021.

RéSUMé: OBJECTIF: Pendant le travail obstétrical, l'analgésie neuraxiale constitue la norme de soins pour soulager la douleur. Néanmoins, le mode optimal d'administration de la solution péridurale n'a pas été déterminé et certaines parturientes pourraient avoir besoin d'une alternative à l'analgésie péridurale. Nous avons cherché à réaliser une revue systématique et une méta-analyse en réseau pour comparer l'analgésie péridurale par perfusion continue (APPC), l'administration programmée de bolus périduraux (PIEB), l'APPC intégrée par ordinateur, l'analgésie péridurale contrôlée par la patiente (l'APCP), l'analgésie contrôlée par la patiente (ACP) de fentanyl et l'ACP de rémifentanil, soit seules ou en combinaison. MéTHODE: Nous avons effectué des recherches dans les bases de données CENTRAL, CINAHL, Ovid Embase, Ovid Medline et Web of Science pour en tirer les études randomisées contrôlées incluant des parturientes nullipares et/ou multipares en travail spontané ou induit. La solution péridurale de maintien devait inclure un anesthésique local à faible concentration et un opioïde. Des sous-groupes spécifiques dans la population obstétricale, comme par exemple les parturientes atteintes de prééclampsie, ont été exclus. Une méta-analyse en réseau a été réalisée à l'aide d'une méthode fréquentiste, et les résultats continus et dichotomiques sont présentés sous forme de différences moyennes et de rapports de cotes, respectivement, avec des intervalles de confiance à 95 %. RéSULTATS: Au total, 73 études ont été incluses. Concernant le premier critère d'évaluation coprincipal, soit le besoin d'analgésie de secours, l'APPC était inférieure à la PIEB, et la PIEB + APCP était supérieure à l'APCP seule, avec un faible niveau de fiabilité des données probantes compte tenu de la présence de limitations et d'imprécisions importantes. Le deuxième critère d'évaluation coprincipal, soit la satisfaction maternelle, a été amélioré avec la PIEB + APCP comparativement à l'APPC + APCP et à l'APCP seule, avec une faible qualité de données probantes compte tenu de la présence de limitations et d'imprécisions importantes. L'ACP à base de fentanyl a augmenté le besoin d'analgésie de secours et diminué la satisfaction maternelle par rapport à de nombreuses méthodes d'administration de la solution péridurale. En termes de critères d'évaluation secondaires, la PIEB a amélioré l'efficacité analgésique par rapport à l'APPC, et l'APCP a diminué la consommation d'anesthésiques locaux au détriment d'une analgésie inférieure par rapport à l'APPC et à la PIEB. La PIEB + APCP était supérieure à l'APPC + APCP en ce qui a trait aux scores de douleur à 2 h et 4 h, à la consommation d'anesthésiques locaux, à l'incidence de bloc moteur des membres inférieurs et au taux d'accouchement vaginal spontané. Les ACP de fentanyl et de rémifentanil n'ont pas fourni le même niveau d'analgésie que toutes les méthodes péridurales et ont entraîné une augmentation de l'inefficacité analgésique avec le temps passé en travail actif, en plus de prédisposer les parturientes à une incidence plus élevée d'effets secondaires tels que les nausées et/ou vomissements et la sédation. L'ACP de rémifentanil était supérieure à l'ACP de fentanyl en début d'analgésie mais a augmenté l'incidence de désaturation en oxygène par rapport aux stratégies de livraison de la solution péridurale. CONCLUSION: L'ACP à base d'opioïdes n'a pas fourni le même niveau d'analgésie que les méthodes péridurales, avec une incidence plus élevée d'effets secondaires. Nous interprétons les résultats de notre revue systématique et de notre méta-analyse en réseau comme suggérant que la PIEB + APCP constitue le mode d'administration optimal de la solution péridurale. Néanmoins, la différence potentielle en importance des divers devenirs maternels, fœtaux et néonataux pour déterminer la modalité optimale n'a pas encore été élucidée, à notre connaissance. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021254978); enregistrée le 27 mai 2021.

Cryopreserved Amniotic Membrane Using the TissueTuck Technique: A Sutureless Approach for Pterygium Surgery.

PURPOSE: The purpose of this study was to evaluate the clinical outcomes of the TissueTuck technique in the management of pterygium. METHODS: This was a single-center, retrospective review of patients with primary or recurrent pterygium that underwent surgical excision followed by application of cryopreserved amniotic membrane (AM) using the TissueTuck technique. All patients underwent surgery between January 2012 and May 2019. Patient profile, surgical time, complications, and rates of pterygium recurrence were analyzed. RESULTS: A total of 582 eyes of 453 patients (328 female patients; 65.1 ± 13.9 years) were included for analysis and initially presented with primary (92%) pterygium. The average duration of pterygium excision surgery was 14.7 ± 5.2 minutes (median: 14, range: 4-39 minutes) with mitomycin C administration in 257 (45%) eyes. At the last follow-up of 30.2 ± 22.2 months (median: 24.5, range: 3-94 months), BCVA significantly improved from logMAR 0.23 at baseline to logMAR 0.19 ( P < 0.0001). Recurrence rate was 2.3% but only 0.7% (2/274) in those cases with primary, single-headed pterygium without mitomycin C treatment. Other postoperative complications in that cohort included granuloma (7.9%), scarring (3.8%), and diplopia in extreme lateral gaze (2.5%). The AM remained secured to the ocular surface throughout the postoperative period. CONCLUSIONS: The TissueTuck surgical technique with cryopreserved AM can be performed in minimal time and result in a low recurrence and complication rate after pterygium surgery.

Anatomic Double-Bundle Anterior Cruciate Ligament Reconstruction Is Not Superior to Anatomic Single-Bundle Reconstruction at 10-Year Follow-up: A Randomized Clinical Trial.

BACKGROUND: The anatomic double-bundle (DB) technique is purported to be a superior technique due to its mimicking of the double-stranded anatomic formation of the anterior cruciate ligament (ACL). Previous studies with 2-, 5- and 10-year follow-up are conflicted as to whether this technique is superior to the previous gold standard method of ACL reconstruction, the anatomic single-bundle (SB) reconstruction. PURPOSE/HYPOTHESIS: The aim of this prospective randomized study was to compare the outcomes of the anatomic DB technique and anatomic SB technique with independent drilling at 10 years after anterior cruciate ligament (ACL) reconstruction. We hypothesized that DB ACL reconstruction would result in a better outcome in terms of the pivot-shift test. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 105 patients (33 women, 72 men; median age, 27 years [range, 18-52 years]) were randomized and underwent ACL reconstruction (DB group: n = 53; SB group: n = 52). All reconstruction procedures were performed anatomically by identifying the ACL footprint, using the anteromedial portal for femoral tunnel drilling, and utilizing interference screws for tibial and femoral fixation. One blinded observer examined the patients both preoperatively and at follow-up (median, 120 months [range, 112-134 months]). Multiple subjective and objective clinical evaluations were used to assess the outcomes. Radiographic assessments of osteoarthritis were performed using the Ahlbäck, Kellgren-Lawrence, and Fairbank classification systems early postoperatively and at the final follow-up. RESULTS: Preoperatively, no differences were found between the study groups. Overall, 70 patients (67%; DB group: n = 39; SB group: n = 31) were available for analysis at 10-year follow-up. No significant difference could be shown between the groups in terms of the pivot-shift grade, knee laxity measurements using the KT-1000 arthrometer, manual Lachman grade, single-leg hop test result, range of motion measurements, Lysholm knee score, Tegner activity score, and Knee injury and Osteoarthritis Outcome Score (KOOS) score. Correspondingly, no differences were found between the groups regarding the presence of radiographic osteoarthritis at follow-up. Both groups improved at follow-up compared with preoperatively in terms of the pivot-shift grade, knee laxity measurements using the KT-1000 arthrometer, manual Lachman grade, Lysholm knee score, and KOOS score (P < .05 [highest P value for any comparison]). CONCLUSION: The anatomic DB technique was not superior to the anatomic SB technique with independent drilling at 10-year follow-up in regard to objective and subjective measurements. As such, one could argue that there is no need for the continued use of the anatomic DB technique in an unselected population.

NetCellMatch: Multiscale Network-Based Matching of Cancer Cell Lines to Patients Using Graphical Wavelets.

Cancer cell lines serve as model in vitro systems for investigating therapeutic interventions. Recent advances in high-throughput genomic profiling have enabled the systematic comparison between cell lines and patient tumor samples. The highly interconnected nature of biological data, however, presents a challenge when mapping patient tumors to cell lines. Standard clustering methods can be particularly susceptible to the high level of noise present in these datasets and only output clusters at one unknown scale of the data. In light of these challenges, we present NetCellMatch, a robust framework for network-based matching of cell lines to patient tumors. NetCellMatch first constructs a global network across all cell line-patient samples using their genomic similarity. Then, a multi-scale community detection algorithm integrates information across topologically meaningful (clustering) scales to obtain Network-Based Matching Scores (NBMS). NBMS are measures of cluster robustness which map patient tumors to cell lines. We use NBMS to determine representative "avatar" cell lines for subgroups of patients. We apply NetCellMatch to reverse-phase protein array data obtained from The Cancer Genome Atlas for patients and the MD Anderson Cell Line Project for cell lines. Along with avatar cell line identification, we evaluate connectivity patterns for breast, lung, and colon cancer and explore the proteomic profiles of avatars and their corresponding top matching patients. Our results demonstrate our framework's ability to identify both patient-cell line matches and potential proteomic drivers of similarity. Our methods are general and can be easily adapted to other'omic datasets.

Scent-delivery devices as a digital healthcare tool for olfactory training: A pilot focus group study in Parkinson's disease patients.

Parkinson's disease (PD) patients display a combination of motor and non-motor symptoms. The most common non-motor symptom is scent (olfactory) impairment, occurring at least four years prior to motor symptom onset. Recent and growing interest in digital healthcare technology used in PD has resulted in more technologies developed for motor rather than non-motor symptoms. Human-computer interaction (HCI), which uses computer technology to explore human activity and work, could be combined with digital healthcare technologies to better understand and support olfaction via scent training - leading to the development of a scent-delivery device (SDD). In this pilot study, three PD patients were invited to an online focus group to explore the association between PD and olfaction, understand HCI and sensory technologies and were demonstrated a new multichannel SDD with an associated mobile app. Participants had a preconceived link, a result of personal experience, between olfactory impairment and PD. Participants felt that healthcare professionals did not take olfactory dysfunction concerns seriously prior to PD diagnosis. Two were not comfortable with sharing scent loss experiences with others. Participants expected the multichannel SDD to be small, portable and easy-to-use, with customisable cartridges to deliver chosen scents and the mobile app to create a sense of community. None of the participants regularly performed scent training but would consider doing so if some scent function could be regained. Standardised digital SDDs for regular healthcare check-ups may facilitate improvement in olfactory senses in PD patients and potential earlier PD diagnosis, allowing earlier therapeutic and symptomatic PD management.

Most Elite Athletes Who Underwent Hip Arthroscopy for Femoroacetabular Impingement Syndrome Did Not Return to the Same Level of Sport, but the Majority Were Satisfied With the Outcome of Surgery.

Purpose: To evaluate the 2-year outcomes after arthroscopic surgical treatment for femoroacetabular impingement syndrome (FAIS) using validated patient-reported outcome measurements in young elite athletes and to report the rate of return to sport. Methods: Young elite athletes undergoing arthroscopic surgery for FAIS with 2 years of follow-up were included. A young elite athlete was defined as an athlete aged 18 to 22 years at the time of surgery with a Hip Sports Activity Scale (HSAS) level greater than 6 before the onset of symptoms. The following patient-reported outcome measurements were collected prospectively: Copenhagen Hip and Groin Outcome Score, 12-item International Hip Outcome Tool, HSAS, visual analog scale (VAS), European Quality of Life (EQ) 5 Dimensions questionnaire, and EQ VAS. Furthermore, the patients answered a question related to satisfaction with surgery at follow-up. Results: A total of 84 athletes (67 male and 17 female athletes), with a mean age of 19.8 ± 1.5 years, completed the 2-year follow-up. Bilateral hip arthroscopy was performed in 57 athletes, generating a total of 141 included hips. The improvements in the Copenhagen Hip and Groin Outcome Score subscales, 12-item International Hip Outcome Tool, EQ 5 Dimensions questionnaire, EQ VAS, and VAS for overall hip function were statistically significant (P < .001). At the 2-year follow-up, 42% of the athletes reported an HSAS level of either 7 or 8 whereas 28% reported an HSAS level of 5 or 6. In total, 79% of the athletes were satisfied with the surgical procedure. Conclusions: There are significant improvements in outcome measurements at the 2-year follow-up in elite young athletes undergoing arthroscopic hip surgery for FAIS. Although many of the athletes remained in high-level sports 2 years after surgery, only 30% of the athletes returned to sport at the same level. Level of Evidence: Level IV, therapeutic case series.

Intense pulsed light improves signs and symptoms of dry eye disease due to meibomian gland dysfunction: A randomized controlled study.

PURPOSE: To compare the safety and efficacy of intense pulsed light (IPL) followed by meibomian gland expression (MGX), against monotherapy of MGX. METHODS: Patients with moderate to severe meibomian gland dysfunction (MGD) were 1:1 randomized to 4 sessions of intense pulse light + MGX at 2-week intervals, or 4 sessions of Sham + MGX at 2-week intervals. Both patients and examiners were blinded to the allocation. Outcome measures, evaluated at the baseline (BL) and at a follow-up (FU) conducted 4 weeks after the last IPL session, included fluorescein tear breakup time (TBUT) as the primary outcome measure, OSDI (Ocular Surface Disease Index) questionnaire, Eye Dryness Score (EDS, a visual analog scale (VAS)-based questionnaire), Meibomian gland score (MGS, a score of meibum expressibility and quality in 15 glands on the lower eyelid), daily use of artificial tears, and daily use of warm compresses. In addition, during each treatment session, the number of expressible glands was counted in both eyelids, the predominant quality of meibum was estimated in both eyelids, and the level of pain/discomfort due to MGX and IPL was recorded. RESULTS: TBUT increased from 3.8±0.2 (µ±standard error of mean (SEM)) to 4.5±0.3 seconds in the control arm, and from 4.0±0.2 to 6.0±0.3 in the study arm. The difference between arms was statistically significant (P < .01). Other signs/symptoms which improved in both arms but were greater in the study arm included MGS (P < .001), EDS (P < .01), the number of expressible glands in the lower eyelids (P < .0001) and upper eyelid (P < .0001), the predominant meibum quality in the lower eyelid (P < .0001) and upper eyelid (P < .0001), and the level of pain due to MGX (P < .0001). Outcome measures which improved in both arms with no significant differences between the two were OSDI (P = .9984), and the daily use of artificial tears (P = .8216). Meibography, daily use of warm compresses, and severity of skin rosacea did not show statistically significant changes in either arm. No serious adverse events were observed. There was a slight tendency for more adverse events in the control group (P = 0.06). CONCLUSIONS: The results of this study suggest that, in patients with moderate to severe symptoms, combination therapy of intense pulse light (IPL) and meibomian gland expression (MGX) could be a safe and useful approach for improving signs of dry eye disease (DED) due to meibomian gland dysfunction (MGD). Future studies are needed to elucidate if and how such improvements can be generalized to different severity levels of MGD.

Modernising Orodispersible Film Characterisation to Improve Palatability and Acceptability Using a Toolbox of Techniques.

Orodispersible films (ODFs) have been widely used in paediatric, geriatric and dysphagic patients due to ease of administration and precise and flexible dose adjustments. ODF fabrication has seen significant advancements with the move towards more technologically advanced production methods. The acceptability of ODFs is dependent upon film composition and process of formation, which affects disintegration, taste, texture and mouthfeel. There is currently a lack of testing to accurately assess ODFs for these important acceptability sensory perceptions. This study produced four ODFs formed of polyvinyl alcohol and sodium carboxymethylcellulose using 3D printing. These were assessed using three in vitro methods: Petri dish and oral cavity model (OCM) methods for disintegration and bio-tribology for disintegration and oral perception. Increasing polymer molecular weight (MW) exponentially increased disintegration time in the Petri dish and OCM methods. Higher MW films adhered to the OCM upper palate. Bio-tribology analysis showed that films of higher MW disintegrated quickest and had lower coefficient of friction, perhaps demonstrating good oral perception but also stickiness, with higher viscosity. These techniques, part of a toolbox, may enable formulators to design, test and reformulate ODFs that both disintegrate rapidly and may be better perceived when consumed, improving overall treatment acceptability.

Protocol for a multicenter prospective cohort study evaluating arthroscopic and non-surgical treatment for microinstability of the hip joint.

BACKGROUND: Microinstability of the hip joint is a proposed cause of hip pain and reduced function in young individuals. The underlying mechanism is thought to be extraphysiological hip motion due to bony deficiency and/or soft tissue deficiency or decreased soft tissue function. Recently, the condition has gained increased attention, and despite the fact that treatment today includes both non-surgical and surgical approaches, there is limited evidence on diagnostic specificity and treatment effects. The aim of this study is to evaluate clinical outcomes of both non-surgical and surgical treatment for microinstability of the hip joint. METHODS: A multicenter prospective cohort study is planned to evaluating the outcome of physical therapy aimed at stabilizing the hip joint, as well as arthroscopic plication of the hip joint capsule, if the physical therapy fails. Outcomes will be evaluated using hip-specific patient-reported outcome measures: the short version of the International Hip Outcome Tool and the Copenhagen Hip and Groin Outcome Score, strength and function tests, health-related quality of life as determined using the European Quality of Life-5 Dimensions and the European Quality of Life-Visual Analog Scale, sports activity levels according to the Hip Sport Activity Scale, and reported complications. Patients will be evaluated at 6, 12 and 24 months after each treatment. DISCUSSION: It is important to evaluate the clinical outcomes of both non-surgical and surgical treatment for suspected microinstability of the hip joint, and the planned prospective evaluation will contribute to the understanding of non-surgical as well as surgical treatment outcomes, including complications. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04934462 . Registered June 22 2021.

Influence of perioperative dexmedetomidine on the incidence of postoperative delirium in adult patients undergoing cardiac surgery.

BACKGROUND: Delirium is a common neurocognitive complication after cardiac surgery. The aim of this systematic review was to determine whether the administration of dexmedetomidine in the perioperative period decreases the incidence of postoperative delirium in adult patients undergoing cardiac surgery. METHODS: Central, CINAHL, Ovid Embase, Ovid Medline, and Web of Science databases were searched for RCTs of adult patients undergoing cardiac surgery where participants received i.v. dexmedetomidine or control in the perioperative period. The methods included systematic review, meta-analysis, and trial sequential analysis. The primary outcome was the incidence of postoperative delirium. Dichotomous outcomes were presented as risk ratio (RR) using the Mantel-Haenszel method, and continuous variables were presented as mean difference with the inverse variance method. RESULTS: Thirty trials, comprising 4090 patients, were included. With unselected inclusion of trials, dexmedetomidine vs control was associated with decreased incidence of postoperative delirium (12.4% vs 16.2%; RR=0.62; 95% confidence interval 0.44-0.86; P=0.005; I2=61%). If trials at high risk of bias were excluded, the incidence of postoperative delirium was not significantly different between groups (RR=0.71; 95% confidence interval 0.49-1.03; P=0.070; I2=58%). Postoperative delirium was not a reliably determined outcome across trials because of methodological and reporting limitations, including the heterogeneity of delirium diagnostic approach. Trial sequential analysis revealed that the optimal information size was not reached, and the Z-curve did not cross the trial sequential boundaries for benefit or futility. With respect to safety concerns, dexmedetomidine was not significantly associated with incident bradycardia or hypotension, or with the duration of mechanical ventilation. CONCLUSIONS: When trials at high risk of bias were excluded, the use of perioperative dexmedetomidine was not associated with decreased incidence of postoperative delirium. PROSPERO REGISTRATION NUMBER: CRD 42021252779.

Comparison of analgesic modalities for patients undergoing midline laparotomy: a systematic review and network meta-analysis.

BACKGROUND: Midline laparotomy is associated with severe pain. Epidural analgesia has been the established standard, but multiple alternative regional anesthesia modalities are now available. We aimed to compare continuous and single-shot regional anesthesia techniques in this systematic review and network meta-analysis. METHODS: We included randomized controlled trials on adults who were scheduled for laparotomy with solely a midline incision under general anesthesia and received neuraxial or regional anesthesia for pain. Network meta-analysis was performed with a frequentist method, and continuous and dichotomous outcomes were presented as mean differences and odds ratios, respectively, with 95% confidence intervals. The quality of evidence was rated with the  grading of recommendations, assessment, development, and evaluation system. RESULTS: Overall, 36 trials with 2,056 patients were included. None of the trials assessed erector spinae plane or quadratus lumborum block, and rectus sheath blocks and transversus abdominis plane blocks were combined into abdominal wall blocks (AWB). For the co-primary outcome of pain score at rest at 24 hr, with a minimal clinically important difference (MCID) of 1, epidural was clinically superior to control and single-shot AWB; epidural was statistically but not clinically superior to continuous wound infiltration (WI); and no statistical or clinical difference was found between control and single-shot AWB. For the co-primary outcome of cumulative morphine consumption at 24 hr, with a MCID of 10 mg, epidural and continuous AWB were clinically superior to control; epidural was clinically superior to continuous WI, single-shot AWB, single-shot WI, and spinal; and continuous AWB was clinically superior to single-shot AWB. The quality of evidence was low in view of serious limitations and imprecision. Other results of importance included: single-shot AWB did not provide clinically relevant analgesic benefit beyond two hr; continuous WI was clinically superior to single-shot WI by 8-12 hr; and clinical equivalence was found between epidural, continuous AWB, and continuous WI for the pain score at rest, and epidural and continuous WI for the cumulative morphine consumption at 48 hr. CONCLUSIONS: Single-shot AWB were only clinically effective for analgesia in the early postoperative period. Continuous regional anesthesia modalities increased the duration of analgesia relative to their single-shot counterparts. Epidural analgesia remained clinically superior to alternative continuous regional anesthesia techniques for the first 24 hr, but reached equivalence, at least with respect to static pain, with continuous AWB and WI by 48 hr. TRIAL REGISTRATION: PROSPERO (CRD42021238916); registered 25 February 2021.

RéSUMé: CONTEXTE: La laparotomie médiane est associée à une douleur sévère. L'analgésie péridurale est la norme de soins établie, mais plusieurs modalités alternatives d'anesthésie régionale sont aujourd'hui disponibles. Dans cette revue systématique et méta-analyse en réseau, nous avons cherché à comparer les techniques d'anesthésie régionale continue et par injection unique. MéTHODE: Nous avons inclus les études randomisées contrôlées portant sur des adultes devant bénéficier d'une laparotomie avec une simple incision médiane sous anesthésie générale et qui ont reçu une anesthésie neuraxiale ou régionale pour la douleur. Une méta-analyse en réseau a été réalisée avec une méthode fréquentiste, et les résultats continus et dichotomiques ont été présentés sous forme de différences moyennes et de rapports de cotes, respectivement, avec des intervalles de confiance à 95 %. La qualité des données probantes a été évaluée avec le système GRADE (Grading of Recommendations Assessment, Development and Evaluation). RéSULTATS: Au total, 36 études portant sur 2056 patients ont été incluses. Aucune des études n'a évalué le bloc du plan des muscles érecteurs du rachis ou du carré des lombes. Les blocs de la gaine des grands droits et du plan des muscles transverses de l'abdomen ont été combinés en blocs de la paroi abdominale (BPA). Concernant le critère d'évaluation principal de score de douleur au repos à 24 heures, avec une différence minimale cliniquement pertinente (DMCP) de 1, l'analgésie péridurale était cliniquement supérieure au BPA de contrôle et par injection unique; l'analgésie péridurale était statistiquement mais non cliniquement supérieure à l'infiltration continue de la plaie; et aucune différence statistique ou clinique n'a été constatée entre le BPA de contrôle et par injection unique. Pour le deuxième critère d'évaluation principal portant sur la consommation cumulative de morphine à 24 heures, avec une DMCP de 10 mg, la péridurale et le BPA continu étaient cliniquement supérieurs au groupe contrôle; la péridurale était cliniquement supérieure à l'infusion continue de la plaie, au BPA par injection unique, à l'infiltration par injection unique de la plaie et à la rachianesthésie; et le BPA continu était cliniquement supérieur au BPA par injection unique. La qualité des données probantes était faible compte tenu d'importantes limites et d'imprécisions. De plus, le BPA par injection unique n'a fourni aucun avantage analgésique cliniquement pertinent au-delà de deux heures; l'infiltration continue de la plaie était cliniquement supérieure de 8 à 12 heures à l'infiltration de la plaie en injection unique; et une équivalence clinique a été observée entre la péridurale, le BPA continu et l'infiltration continue de la plaie en ce qui avait trait au score de douleur au repos, et entre la péridurale et l'infiltration continue de la plaie en ce qui touchait à la consommation cumulative de morphine à 48 heures. CONCLUSION: Les BPA par injection unique n'étaient cliniquement efficaces pour procurer une analgésie qu'au début de la période postopératoire. Les modalités d'anesthésie régionale continue ont augmenté la durée de l'analgésie par rapport aux modalités équivalentes par injection unique. L'analgésie péridurale est demeurée cliniquement supérieure aux techniques alternatives d'anesthésie régionale continue pendant les 24 premières heures, mais a atteint l'équivalence, au moins en ce qui concerne la douleur statique, avec les BPA et les infiltrations de lésions continus à 48 heures. Enregistrement de l'étude : PROSPERO (CRD42021238916); enregistrée le 25 février 2021.