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Praveen Chahar, Kenneth C Cummings IIIAnesthesiology Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USAAbstract: Many attempts have been made to increase the duration of local anesthetic action. One avenue of investigation has focused on encapsulating local anesthetics within carrier molecules to increase their residence time at the site of action. This article aims to review the literature surrounding the recently approved formulation of bupivacaine, which consists of bupivacaine loaded in multivesicular liposomes. This preparation increases the duration of local anesthetic action by slow release from the liposome and delays the peak plasma concentration when compared to plain bupivacaine administration. Liposomal bupivacaine has been approved by the US Food and Drug Administration for local infiltration for pain relief after bunionectomy and hemorrhoidectomy. Studies have shown it to be an effective tool for postoperative pain relief with opioid sparing effects and it has also been found to have an acceptable adverse effect profile. Its kinetics are favorable even in patients with moderate hepatic impairment, and it has been found not to delay wound healing after orthopedic surgery. More studies are needed to establish its safety and efficacy for use via intrathecal, epidural, or perineural routes. In conclusion, liposomal bupivacaine is effective for treating postoperative pain when used via local infiltration when compared to placebo with a prolonged duration of action, predictable kinetics, and an acceptable side effect profile. However, more adequately powered trials are needed to establish its superiority over plain bupivacaine.Keywords: liposomal bupivacaine, postoperative pain, pharmacokinetics, pharmacodynamics, efficacy, safety

Introduction: Depressive symptoms, goal progress, and goal characteristics are interrelated, but the directionality of these relationships is unclear., Methods: In a 6-wave longitudinal study (N = 431; 2002 total surveys), we examine the bidirectionality of the relationships between depressive symptoms, goal characteristics (commitment, self-efficacy, and perception of other's support), and goal progress for academic and interpersonal goals at 2-week intervals. Separate random-intercept cross-lagged panel models were tested for each goal characteristic across both goals., Results: At the within-person level, goal progress significantly positively predicted commitment, self-efficacy, and perception of others' support for the goal. Most of the other hypothesized paths were nonsignificant, including paths between depressive symptoms and progress. At the between-person level, all variables were significantly correlated, with some effects significantly larger for the interpersonal than the academic goal., Discussion: The results suggest that when it comes to depressive symptoms and goal pursuit, general tendencies may be more important than variations over 2-week intervals., (© 2024 The Author(s). Journal of Clinical Psychology published by Wiley Periodicals LLC.)

Objectives: Thrombocytopenia following Perceval aortic valve replacement has been described previously with variable outcome. Studies have lacked a robust analysis of platelet fluctuation and factors affecting it. We aimed to statistically describe the trend in thrombocyte variability as compared with conventional aortic valve replacement, and to assess predictors as well as impact on associated outcomes., Methods: One hundred consecutive patients with first-time Perceval were retrospectively compared to 219 patients after Perimount Magna Ease valve replacement. The primary outcome was the serial thrombocyte count on day 0-6. Generalized estimating equations were used to analyse the data using fixed-effect models: for the effect of the post-operative day on platelet count, and random-effect models estimating both time-variant (platelets) and time in-variant variables (valve type, age, LV function, pre-op platelet level)., Results: Perceval patients were older (72 ± 1 vs 68 ± 1 years, p < 0.01) with higher NYHA status (3(2-3) vs 2(1-2), p < 0.001). Mean platelet count in the sutureless group was lowest on day 2 (91.9 ± 31.6 vs 121.7 ± 53.8 × 10 3  µl -1 ), and lower on day 4 (97.9 ± 44) and 6 (110.6 ± 61) compared to the conventional group (157.2 ± 60 and 181.7 ± 79) but did not result in a higher number of transfusions, bleeding or longer hospital stay (p > 0.05). Reduced platelet count was a strong predictor of red cell transfusion in the conventional (p = 0.016), but not in the sutureless group (p = 0.457). Age (Coef -1.025, 95%CI-1.649--0.401, p < 0.001) and CPB-time (Coef 0.186, 95%CI-0.371--0.001, p = 0.048) were predictors for lower platelet levels., Conclusion: Considering the older patient profile treated with Perceval, postoperative thrombocytopenia does not impact on outcome in terms of transfusions, complications or hospital stay., (© 2024. The Author(s).)

Objective: This retrospective study aimed to compare the outcomes of sutureless aortic valve replacement (su-AVR) and conventional bioprosthetic sutured AVR (cAVR) in high-risk patients undergoing redo surgery., Methods: A total of 79 patients who underwent redo AVR between 2014 and 2021 were included in the study. Of these, 27 patients underwent su-AVR and 52 underwent cAVR. Patient characteristics and clinical outcomes were analysed using multivariate regression and Kaplan Meier survival test., Results: The groups were similar in terms of age, gender, left ventricular function, and number of previous sternotomies. In cases of isolated AVR, su-AVR had significantly lower cross clamp times than cAVR (71 vs. 86 min, p = 0.03). Postoperatively, 4 cAVR patients required pacemaker compared to zero patients in the su-AVR group. There were no significant differences between the two groups in terms of postoperative complications, intrahospital stay (median 9 days, IQR 7-20), or in-hospital mortality (1 su-AVR; 2 cAVR). The long-term survival rate was similar between the su-AVR (90%) and cAVR (92%) groups (log rank p = 0.8). The transvalvular gradients at follow-up were not affected by the type of valve used, regardless of the valve size (coef 2.68, 95%CI -3.14-8.50, p = 0.36)., Conclusion: The study suggests that su-AVR is a feasible and safe alternative to cAVR in high-risk patients undergoing redo surgery. The use of su-AVR offers comparable outcomes to cAVR, with reduced cross clamp times and a lower incidence of postoperative pacemaker requirement in isolated AVR cases. The results of this study contribute to the growing body of evidence supporting the use of su-AVR in high-risk patients, highlighting its feasibility and safety in redo surgeries., (© 2023. The Author(s).)

Surgery for endocarditis of the aorto-mitral continuity can be a challenge in case of extensive tissue destruction. We report two cases of a modified monobloc reconstruction of the aortic and mitral valves and of the aorto-mitral fibrous body. Two valve bioprostheses were sutured to each other and implanted as a composite graft. A pericardial patch sutured to the valves was employed to reconstruct both the noncoronary sinus and the left atrial roof. This technical adjustment allows adaptation to variable anatomical conditions in these particularly difficult cases.

Background. Despite the abundance and proximity of edible marine resources, coastal communities along the St. Lawrence in Eastern Québec rarely consume these resources. Within a community-based food sovereignty project, Manger notre Saint-Laurent ("Sustenance from our St. Lawrence"), members of participating communities (3 non-Indigenous, 1 Indigenous) identified a need for a web-based decision tool to help make informed consumption choices. Methods. We thus aimed to co-design a prototype website that facilitates informed choices about consuming local edible marine resources based on seasonal and regional availability, food safety, nutrition, and sustainability, with community members, regional stakeholders, and experts in user experience design and web development. We conducted 48 interviews with a variety of people over 3 iterative cycles, assessing the prototype's ease of use with a validated measure, the System Usability Scale. Results. Community members, regional stakeholders, and other experts identified problematic elements in initial versions of the website (e.g., confusing symbols). We resolved issues and added features people identified as useful. Usability scores reached "best imaginable" for both the second and the third versions and did not differ significantly between sociodemographic groups. The final prototype includes a tool to explore each species and index cards to regroup accurate evidence relevant to each species. Conclusions. Engaging co-designers with different sociodemographic characteristics brought together a variety of perspectives. Several components would not have been included without co-designers' input; other components were greatly improved thanks to their feedback. Co-design approaches in research and intervention development are preferable to foster the inclusion of a variety of people. Once the prototype is programmed and available online, we hope to evaluate the website to determine its effects on food choices., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Financial support for this study was provided entirely by the Sustenance from our St. Lawrence project, which was funded by Réseau Québec Maritime (principal investigator Lemire), by the Littoral Research Chair (Sentinel North Partnership Research Chair in Ecosystem Approaches to Health funded by Sentinel North and the Northern Contaminant Program of the Crown-Indigenous Relations and Northern Affairs Canada [CIRNAC], chairholder Lemire), and the Canadian Institutes of Health Research Foundation grant FDN-148426 (principal investigator Witteman). The funding agreement ensured the authors’ independence in designing the study, interpreting the data, writing, and publishing the report. ML receives salary support from the Fonds de recherche en santé du Québec. HOW receives salary support from a Tier 2 Canada Research Chair in Human-Centred Digital Health., (© The Author(s) 2022.)

Objectives: The intermediate-term all-cause mortality rate of real-world patients with multivessel disease (MVD) treated with percutaneous coronary intervention (PCI) with new-generation drug-eluting stents or coronary artery bypass grafting (CABG) remains unknown. We sought to compare the intermediate-term all-cause mortality rates of real-world patients with MVD including left main stem disease, treated with CABG or PCI., Methods: All consecutive all-comer patients with MVD undergoing CABG or PCI with second/third generation drug-eluting stents from 2007 to 2015 in Harefield Hospital, UK were included in this study. The revascularization modality was based on heart team discussions. Primary outcome was all-cause mortality. Mean follow-up of the study was 3.3 years. Cox regression analysis and propensity matching were used., Results: Of 6383 patients with MVD, 4230 underwent CABG, whereas 2153 had PCI with new-generation stents. In the CABG group, the mean age was 66.4 ± 10 years, whereas in the PCI group it was 65.3 ± 12.1 years (P < 0.001). Fewer female patients with MVD were treated with CABG than were treated with PCI (18.5% vs 20.5%; P = 0.026). There was a higher 5-year estimated survival rate among patients having CABG (88% vs 78.3%; Plog-rank < 0.001). The adjusted hazard ratio (HR) for PCI over CABG was 1.74 [95% confidence interval (CI) 1.41-2.16; P < 0.001]. A total of 653 patients having CABG and 653 having PCI were included in the propensity-matched groups. At mean follow-up, PCI was associated with a higher adjusted HR for all-cause mortality (2.18, 95% CI 1.54-3.1; P < 0.001)., Conclusions: In this contemporary cohort of real-world patients with MVD, CABG was associated with increased intermediate-term survival compared to PCI with new-generation drug-eluting stents., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: The Leisure Time Physical Activity Questionnaire (LTPAQ) measures the duration of physical activities performed during the past 7 days, and results are expressed in minutes. This study aimed to translate this questionnaire into Canadian-French and to evaluate the content validity and its test-retest reliability in people with physical disabilities., Methods: The LTPAQ was translated from English to French by forward and backward translation. To assess content validity, 9 adults with physical disabilities read and provided comments regarding the relevance, wording and understanding of the items of the preliminary Canadian-French version of the questionnaire. For test-retest reliability, 37 adults with physical disabilities completed the questionnaire 2 or 3 times at T1 (baseline), T2 (2 days from baseline) and T3 (7 days from baseline). The test-retest reliability was investigated by intra-class correlation coefficients (ICCs), paired t test and Bland and Altman tests., Results: The translation and the content validation process resulted in a Canadian-French version of the LTPAQ (LTPAQ-CF). Total LTPAQ-CF scores between T1-T2 and T1-T3 featured strong ICCs, 0.90 and 0.75 (P≤0.01). Paired t tests and Bland and Altman analyses confirmed the good reproducibility of results., Conclusion: The LTPAQ-CF has good test-retest reliability when self-administered or administered by interview to people with physical disabilities., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Purpose: In Canada, two counseling services are offered to facilitate physical activity participation among persons with physical disabilities, yet both have encountered concerns related to the recruitment and retainment of clients. The purpose of this paper is to explore factors related to service adoption among nonusers, and the barriers and facilitators to maintaining service participation among adopters., Methods: Individuals who had never enrolled in the services (nonusers, n = 13) as well as current/previous service clients (adopters, n = 26) participated in interviews based on the Theoretical Domains Framework. Transcripts were subjected to deductive thematic analysis according to participant group., Results: Fifteen themes relating to service adoption within 10 of the 12 theoretical domains were identified for nonusers, while 23 themes relating to maintenence of service participation were identified across all 12 theoretical domains for adopters., Conclusions: The findings provide strategies to improve recruitment, adoption, and retention of clients in counseling services and to enhance the experiences of targeted service users. Implications for Rehabiliation Peer support and education for equipment use should be built into physical activity programs to encourage participation among persons with physical disabilities. Programs that encourage physical activity among individuals with disabilities should be designed by practitioners to be responsive to a variety of needs, which are addressed in the program's advertisements and offerings. The Theoretical Domains Framework is a useful framework for providing valuable insight about clients' experiences of adoption and maintenance of a behavior change service, suggesting merit in other rehabilitation settings.

Closure of the pericardium is important to protect bypass grafts, the great vessels, and the heart from injury due to sternal dehiscence. Furthermore, it is reported to reduce the formation of pericardial adhesions and thus facilitate entry into the chest at resternotomy. We here describe a simple, reproducible, and effective technique for tension-free approximation of the upper pericardium by applying small hemostatic clips to the preserved thymic fascia overlying the pericardium.

Purpose of Review: Tuberculosis (TB) remains a global emergency and continues to kill 1.7 million people globally each year. In the UK, figures for TB are increasing especially in urban areas. There have been advances in imaging techniques as well as increasingly invasive medical interventions in both the diagnosis and treatment of this complex disease. Surgery continues to play an evolving and more challenging role in TB management as minimally invasive procedures can be increasingly used in diagnosis and treatment. Open surgical procedures continue to prove an important adjunct in the management of multidrug-resistant TB (MDR-TB) and the complications of TB., Recent Findings: Since the peak of surgical treatment for TB in the 1950s, surgery is currently mainly reserved for 'difficult-to-diagnose' or indeed 'difficult-to-treat' cases of TB. Improved diagnostics, medical imaging and invasive medical interventions have all enabled alternatives to early surgical intervention. As improving minimally invasive surgical techniques provide diagnostic and treatment options, older methods of surgically managing complex TB have been revisited. To date most of the studies are retrospective and observatory but large studies and meta-analyses are showing the continued role surgery has to play in the treatment of TB., Summary: This review will focus on new diagnostic imaging techniques and medical interventions which may become increasingly available in both developing countries and in the Western world. It will also highlight the continued role of minimally invasive video-assisted thoracoscopic surgery as well as open surgery in managing TB and MDR-TB.

Objectives: We have previously demonstrated the functionality and growth of autologous, living, tissue-engineered vascular grafts (TEVGs) in long-term animal studies. These grafts showed substantial in vivo tissue remodeling and approximation to native arterial wall characteristics. Based on this, in vitro and in vivo matrix metalloproteinase (MMP) activity of TEVGs is investigated as a key marker of matrix remodeling., Methods: TEVGs fabricated from biodegradable scaffolds (polyglycolic-acid/poly-4-hydroxybutyrate, PGA/P4HB) seeded with autologous vascular cells were cultured in static and dynamic in vitro conditions. Thereafter, TEVGs were implanted as pulmonary artery replacements in lambs and followed up for 2 years. Gelatin gel zymography to detect MMP-2 and -9 was performed and collagen content quantified (n=5). Latent (pro) and active MMP-2 and -9 were detected., Results: Comparable levels of active MMP-9 and pro-MMP-2 were detected in static and dynamic culture. Higher levels of active MMP-2 were detected in dynamic cultures. Expression of MMP-2 and -9 was minimal in native grafts but was increased in implanted TEVG. Pro-MMP-9 was expressed 20 weeks post implantation and persisted up to 80 weeks post implantation. Collagen content in vitro was increased in dynamically conditioned TEVG as compared with static constructs and was increased in vivo compared with the corresponding native pulmonary artery., Conclusions: MMPs are up-regulated in vitro by dynamic culture conditions and could contribute to increased matrix remodeling, native analogous tissue formation and functional growth of TEVGs in vivo. Monitoring of MMP activity, for example, by molecular imaging techniques, may enable the non-invasive assessment of functional tissue quality in future clinical tissue-engineering applications.

By learning lessons from weed science we have adopted three approaches to make plants more effective in phytoremediation: (1) The application of functional genomics to identify key components involved in the detoxification of, or tolerance to, xenobiotics for use in subsequent genetic engineering/breeding programmes. (2) The rational metabolic engineering of plants through the use of forced evolution of protective enzymes, or alternatively transgenesis of detoxification pathways. (3) The use of chemical treatments which protect plants from herbicide injury. In this paper we examine the regulation of the xenome by herbicide safeners, which are chemicals widely used in crop protection due to their ability to enhance herbicide selectivity in cereals. We demonstrate that these chemicals act to enhance two major groups of phase 2 detoxification enzymes, notably the glutathione transferases and glucosyltransferases, in both cereals and the model plant Arabidopsis thaliana, with the safeners acting in a chemical- and species-specific manner. Our results demonstrate that by choosing the right combination of safener and plant it should be possible to enhance the tolerance of diverse plants to a wide range of xenobiotics including pollutants.

Background: Continuity of primary care is known to be associated with both improved processes and outcomes of care. Despite continuity being a desired attribute of end-of-life care and despite the desire by most patients with cancer to die at home, there has been no health services research examining this relationship., Aim: To examine the association between family physician continuity of care and the location of death for patients with cancer., Design of Study: A retrospective population-based study involving secondary data analysis of four linked administrative health databases spanning 6 years of information (1992-1997)., Setting: Nova Scotia, Canada Participants: All those who died of cancer from 1992 to 1997 and had made at least three ambulatory visits to a family physician., Methods: The relationship of provider continuity of care and an out-of-hospital death was examined using logistic regression., Results: Out-of-hospital deaths accounted for 31.6% of the 9714 deaths in the study population. The mean provider continuity of care was 0.78 (standard deviation [SD] 0.22). Those who died out-of-hospital had a greater odds of having received high provider continuity (adjusted odds ratio [OR] = 1.54, 95% confidence interval [CI] = 1.22, 1.93) when compared to those who died in-hospital. There appears to be a modification of this effect by gender with a significant association found for males and not for females. The trends in the point estimates are, however, similar for both sexes., Conclusions: This study demonstrates an association between family physician continuity of care and the location of death for those with advanced cancer. Such continuity should be fostered in the development of models of integrated service delivery for end-of-life care.

Objective: To explore issues family physicians face in providing community-based palliative care to their patients in the context of a changing health care system., Design: Focus groups., Setting: Small (< 10,000 population), medium-sized (10,000 to 50,000), and large (> 50,000) communities in Nova Scotia., Participants: Twenty-five men and women physicians with varying years of practice experience in both solo and group practices., Method: A semistructured approach was used, asking physicians to reflect on recent palliative care experiences in order to explore issues of care., Main Findings: Five themes emerged from the discussions: resources needed, availability of family support, time and money supporting physicians' activities, symptom control for patients, and physicians' emotional reactions to caring for dying patients., Conclusion: With downsizing of hospitals and greater emphasis on community-based care, the issues identified in this study will need attention, particularly in designing an integrated service delivery model for palliative care.

The medical management of end-of-life symptoms, and the psychosocial care of the dying and their families have not been a specific part of the curriculum for undergraduate medical students or residency training programs. The purpose of our research was to assess family medicine residents' knowledge of and attitudes toward care of the dying. All entering (PGY1) and exiting (PGY2) residents of the Dalhousie University Family Medicine Residency Program were given a 50-item survey on end-of-life care. They survey contains two 25-item subscales concerning attitudes/opinions toward end-of-life care, and knowledge about care. Thirty-one of the 33 entering PGY1s 94%) and 26 of the 30 exiting PGY2s (86%) completed the surveys. Overall attitude scores were felt to be high among both groups, with little difference between them. Areas of concern regarding the adequacy of knowledge were found in relation to managing opioid drugs and the symptom of dyspnea. Interventions are now in development to address these issues in the residency program. In an era of subspecialties, the challenge of integrating these areas into the curriculum without creating rotations in specialist palliative care is an issue faced by most family medicine residency programs.

Objective: To assess the degree to which Nova Scotia cancer patients who may need palliative care are being referred to the comprehensive Halifax-based Palliative Care Program (PCP)., Methods: The authors conducted a retrospective, population-based study using administrative health data for all adults in Nova Scotia who died of cancer from 1988 to 1994. Proportions and odds ratios (ORs) were used to determine where there were differences in age, sex, place of residence, cancer cause of death, year of death and use of palliative radiotherapy between those who were referred to the PCP at the Halifax Infirmary and those who were not, and between those who were referred late (within 14 days of death) and those who were referred earlier., Results: Of the 14,494 adults who died of cancer during the study period, 2057 (14.2%) were registered in the PCP. Within Halifax County, 1582 (36.4%) of the 4340 patients with terminal cancer were seen in the PCP. Predictors of PCP registration were residence in Halifax County (OR 19.2, 95% confidence interval [CI] 15.4-23.9), younger age compared with those 85 years of age or older (for those 20-54 years of age, OR 4.9, 95% CI 3.2-7.6; 55-64 years, OR 3.4, 95% CI 2.2-5.1; 65-74 years, OR 3.1, 95% CI 2.1-4.5; 75-84 years, OR 2.1, 95% CI 1.4-3.1), and having received palliative radiation (OR 1.8, 95% CI 1.5-2.2). PCP referral was associated directly with head and neck cancer (OR 5.4, 95% CI 3.0-9.7) and inversely with hematopoietic (OR 0.2, 95% CI 0.4-0.9), lymph node (OR 0.3, 95% CI 0.1-0.4) and lung (OR 0.6, 95% CI 0.4-0.9) cancer. Predictors of late referral (being referred to the PCP within 14 days of death) were age 65-84 years (OR 1.4, 95% CI 1.1-1.8) and 85 years and over (OR 1.8, 95% CI 1.1-3.0), no palliative radiation (OR 2.0, 95% CI 1.4-3.1) and cancer cause of death. People dying within 6 months of diagnosis were somewhat less likely to have been referred to the PCP (OR 0.8, 95% CI 0.6-0.9), but those who were referred were more likely to have been referred late (OR 2.6, 95% CI 2.0-3.5)., Interpretation: Referral to the PCP and earlier rather than late referral were more likely for younger people with terminal cancer, those who received palliative radiation and those living closer to the PCP. Referral rates also varied by cancer cause of death and the time between diagnosis and death.

We present a computer method utilizing published values for base pairing energies to compute the most energetically favorable secondary structure of an RNA from its primary nucleotide sequence. After listing all possible double-helical regions, every pair of mutally incompatible regions (whose nucleotides overlap) is examined to determine whether parts of those two regions can be combined by branch migration to form a pair of compatible new subregions which together are more stable than either of the original regions separately. These subregions are added to the list of base pairing regions which will compete to form the best overall structure. Then, a 'hyperstructure matrix' is generated, containing the unique topological relationship between every pair of regions. We have shown that the best structure can be chosen directly from this matrix, without the necessity of creating and examing every possible secondary structure. We have included the results from our solution of the 5S rRNA of the cyanobacterium Anacystis nidulans as an example of our program's capabilities.