Intravenous Lidocaine for the Management of Chronic Pain: A Narrative Review of Randomized Clinical Trials.

Background: Chronic pain remains a serious health problem with significant impact on morbidity and well-being. Available treatments have only resulted in relatively modest efficacy. Thus, novel therapeutic treatments with different mechanisms have recently generated empirical interest. Lidocaine is postulated to provide anti-inflammatory and anti-nociceptive effect through its action at the N-methyl-D-aspartate (NMDA) and voltage gated calcium receptors. Emerging research indicates that lidocaine could be a reasonable alternative for treating chronic pain. Objective: Considering the evidence surrounding lidocaine's potential as a therapeutic modality for chronic pain, we conducted a narrative review on the evidence of lidocaine's therapeutic effects in chronic pain. Methods: A review of the PubMed, and Google scholar databases was undertaken in May 2022 to identify completed studies that investigated the effectiveness of lidocaine in the treatment of chronic pain from database inception to June 2022. Results: A total of 25 studies were included in the narrative review. Findings on available studies suggest that intravenous infusion of lidocaine is an emerging and promising option that may alleviate pain in some clinical populations. Our narrative synthesis showed that evidence for intravenous lidocaine is currently mixed for a variety of chronic pain syndromes. Findings indicate that evidence for efficacy is limited for: CRPS, and cancer pain. However, there is good evidence supporting the efficacy of intravenous lidocaine as augmentation in chronic post-surgical pain. Conclusion: Lidocaine may be a promising pharmacologic solution for chronic pain. Future investigation is warranted on elucidating the neurobiological mechanisms of lidocaine in attenuating pain signaling pathways.

The many "costs" of transportation: Examining what cancer caregivers experience as transportation obstacles.

BACKGROUND: Transportation has been identified as a specific source of burden for cancer caregivers. This study examined cancer caregivers' subjective experiences and objectives costs associated with transportation over a 6-month period of providing end-of-life care to a family member or friend. METHODS: This was a multi-site longitudinal, prospective cohort study that followed 223 caregiver-patient dyads. Data were collected using biweekly, semi-structured interviews for up to 6 months and collection of all caregiving related receipts. Interviews were coded and analyzed using a comparative, iterative analysis and actual out of pockets costs were described using descriptive statistics. RESULTS: Over the 6-month study period most caregivers (n = 143; 74%) discussed transportation at one or more timepoints. Average biweekly transportations costs to caregivers were $43.6. Caregivers described (n = 56; 39%) multiple direct and indirect costs of transportation, and 58% (n = 84) discussed the need for transportations services or assistance at the institutional level. CONCLUSIONS: Caregivers described the multifaceted costs of transportation they experienced which are in line with previous work. Alongside descriptions of direct costs, caregivers described key opportunity costs, such as personal and work time forgone to transporting patients. Caregivers also made suggestions for institutional and/or civic based solutions to facilitate reliable modes of transportation, rather than individual-level intervention.

The Impact of COVID-19 on Academic Cancer Clinical Trials in Canada and the Initial Response from Cancer Centers.

The COVID-19 pandemic resulted in temporary holds placed on new trial startups, patient recruitment and follow up visits for trials which contributed to major disruptions in cancer center trial unit operations. To assess the impact, the Canadian Cancer Clinical Trials Network (3CTN) members participated in regional meetings and a survey to understand the impact of the pandemic to academic cancer clinical trials (ACCT) activity, cancer trial unit operations and supports needed for post-pandemic recovery. Trial performance and recruitment data collected from 1 April 2020-31 March 2021 was compared to the same period in previous years. From 1 April-30 June 2020, patient recruitment decreased by 67.5% and trial site activations decreased by 81% compared to the same period in 2019. Recovery to reopening and recruitment of ACCTs began after three months, which was faster than initially projected. However, ongoing COVID-19 impacts on trial unit staffing and operations continue to contribute to delayed trial activations, lower patient recruitment and may further strain centers' capacity for participation in academic-sponsored trials.

A call to bridge the divide in breast reconstruction research: A systematic review.

PURPOSE: Breast reconstruction is an important component of comprehensive breast cancer care. Although reconstructive plans require multidisciplinary clinical-decision making, research in cross-discipline collaborations is often limited. This study aims to evaluate multidisciplinary involvement in breast reconstruction outcomes research. METHODS: A systematic review of breast reconstruction literature published from 2000 to 2019 using Ovid MEDLINE, Ovid EMBASE, and PubMed databases was conducted. English language articles published in North America or Europe with n ≥ 12 nonpediatric patients were included. Articles concerning procedures not performed in the context of breast cancer care or articles that did not evaluate at least one outcome, diagnostic test, or risk factor were excluded. Authors' affiliations were used to define multidisciplinary involvement. Quality of research was evaluated using the level of evidence,  journal impact factor (IF), and altmetrics. RESULTS: Of the 1679 articles screened, 784 met the stated eligibility criteria. Only half (50.6%) of these articles involved an author outside the discipline of plastic surgery. Compared to nonmultidisciplinary studies, multidisciplinary studies were more likely to be designated with a higher level of evidence (I or II) (p<0.001), published in journals with higher IF (p<0.05), have higher usage (p = 0.03), and mentions (p = 0.02). There was no difference in citations, captures, and social media posts (p>0.05). CONCLUSION: Breast reconstruction outcomes research often fails to offer author collaborations from nonplastic surgery disciplines. Multidisciplinary involvement in breast cancer care research is strongly recommended to improve the quality and impact of clinical studies in breast reconstruction.

Advancing Academic Cancer Clinical Trials Recruitment in Canada.

The Canadian Cancer Clinical Trials Network (3CTN) was established in 2014 to address the decline in academic cancer clinical trials (ACCT) activity. Funding was provided to cancer centres to conduct a Portfolio of ACCTs. Larger centres received core funding and were paired with smaller centres to enable support and sharing of resources. All centres were eligible for incentive-based funding for recruitment above pre-3CTN baseline. Established performance measures were collected and tracked. The overall recruitment target was 50% above pre-3CTN baseline by Year 4. An analysis was completed to identify predictive success factors and descriptive statistics were used to summarize site characteristics and outcomes. From 2014-2018, a total of 11,275 patients were recruited to 559 Portfolio trials, an overall increase of 59.6% above pre-3CTN baseline was observed in Year 4. Twenty-five (51%) adult centres met the Year 4 recruitment target and the overall recruitment target was met within three years. Three factors that correlated with sites' achieving recruitment targets were: time period, region and number of baseline trials. 3CTN was successful in meeting its objectives and will continue to support ACCTs and member cancer centres, monitor performance over time and seek continued funding to ensure success, better trial access and outcomes for patients.

Diastereoselective Synthesis of P-Stereogenic Secondary Phosphine Oxides (SPOs) Bearing a Chiral Substituent by Ring Opening of (+)-Limonene Oxide with Primary Phosphido Nucleophiles.

Kinetic separation of the commercially available cis/trans-(+)-limonene oxide mixture by ring opening with primary phosphido nucleophiles LiPHR (R = ferrocenyl, Ph, Cy, t-Bu, Mes* (Mes* = 2,4,6-(t-Bu)3C6H2)), followed by treatment with aqueous NH4Cl and H2O2, gave unreacted cis-(+)-limonene oxide and diastereoenriched mixtures of the secondary phosphine oxides (SPOs) PHR(trans-(+)-Lim-OH)(O), which could be separated by chromatography and/or recrystallization. This one-pot synthesis uses a cheap chiral material and commercially available primary phosphines to control the configuration of the new P-stereogenic SPOs, which are potentially useful as ligands for metal complexes in asymmetric catalysis.

Resource utilization of intraoperative cultures for pediatric deep neck space abscesses.

INTRODUCTION: Peritonsillar (PT), parapharyngeal (PP), and retropharyngeal (RP) abscesses are common pediatric deep neck space infections (DNSI). Despite established literature on DNSI microbiology, obtaining intraoperative cultures remains commonplace. The objective was to evaluate the resource utilization of intraoperative cultures when draining PT, PP, and RP abscesses. METHODS: Pediatric patients (age <18.0 years) who underwent surgical drainage of a PT, PP, or RP abscess between January 2013 and June 2018 were retrospectively reviewed. Changes in antimicrobials based on intraoperative culture results were assessed by use of Fisher's exact tests or Wilcoxon rank-sum tests, as appropriate. Multivariable linear regression was used to model the association between factors of interest and number of cultures obtained. RESULTS: Eighty-eight patients underwent surgical drainage, of which 80 patients (median age 6.96 years) had intraoperative bacterial cultures (32 PT, 21 PP, and 27 RP). There were no positive fungal or acid-fast bacilli cultures. Seven patients had culture-directed changes in treatment; none of these patients had a PT abscess. Age was inversely associated with culture-directed changes (p = 0.006) while the use of blood cultures (p = 0.012) was positively associated with culture-directed treatment changes. Hospital length of stay (p < 0.001) and history of prior DNSI (p = 0.001) were associated with number of cultures obtained. CONCLUSIONS: Younger children with PP and RP abscesses are most likely to benefit from intraoperative bacterial cultures. Cultures of PT abscesses are unlikely to change clinical management. Fungal and acid-fast bacilli cultures are unlikely to yield clinically useful information. Prudent use of intraoperative cultures may decrease the use of hospital resources and admission-related costs.

Ask PCOS: Identifying Need to Inform Evidence-Based App Development for Polycystic Ovary Syndrome.

BACKGROUND: People are increasingly seeking health information and managing their health through electronic technologies. We aimed to determine if women with polycystic ovary syndrome (PCOS) identified a need for PCOS-related mobile health apps and to evaluate related apps currently available. DESIGN: A national survey of women and a review of apps available on the iOS and Android platforms. SETTING: Community recruitment in Australia in 2016 and review of mobile apps available in 2017. SAMPLE: The survey received 264 responses. Sixteen apps related to PCOS were evaluated. MAIN OUTCOME MEASURES: Survey: Women's likeliness to use mobile health apps, specifically a PCOS-related app and preferred features of apps. App review: Mapping of available apps and evaluation using the Mobile Application Rating Scale (MARS). RESULTS: Of 264 respondents, almost all women had a smartphone (98%), 72% had previously used an app to manage their health, and most (91%) would use a PCOS-specific app if available. The most important feature was the availability of current, evidence-based information. Current apps on PCOS lack provision of quality information. CONCLUSION: Women with PCOS would use a PCOS-specific app of good quality that responds to their needs and facilitates self-care; however, currently available apps are unlikely to meet their information needs.

Phosphodiesterase-5 inhibition reduces postoperative metastatic disease by targeting surgery-induced myeloid derived suppressor cell-dependent inhibition of Natural Killer cell cytotoxicity.

Cancer surgery while necessary for primary tumor removal, has been shown to induce immune suppression and promote metastases in preclinical models and human cancer surgery patients. Activating the immune system and reversing immunosuppression have emerged as promising ways to treat cancer and they can be safely employed in the perioperative period. In this study, we evaluated the immunotherapeutic potential of phosphodiesterase-5 (PDE-5) inhibitors to target surgery-induced myeloid-derived suppressor cells (MDSC) and restore natural killer (NK) cell function in the clinically relevant perioperative period. Immunocompetent murine tumor models of major surgery were used to characterize the functional suppression of surgery-induced MDSC and to assess the in vivo efficacy of perioperative PDE5 inhibition. In cancer surgery patients with abdominal malignancies, we assessed postoperative NK cell function following co-culture with MDSC and PDE5 inhibition. Perioperative PDE5 inhibition reverses surgery-induced immunosuppression. In particular, sildenafil reduces surgery-derived granulocytic-MDSC (gMDSC) function through downregulation of arginase 1 (ARG1), IL4Ra and reactive oxygen species (ROS) expression, enabling NK cell antitumor cytotoxicity and reducing postoperative disease recurrence. By removing surgery-derived immunosuppressive mechanisms of MDSCs, sildenafil can be combined with the administration of perioperative influenza vaccination which targets NK cells to reduce postoperative metastasis. Importantly, sildenafil reverses MDSC suppression in cancer surgery patients. These findings demonstrate that PDE5 inhibitors reduce postoperative metastasis by their ability to inhibit surgery-induced MDSC. Further clinical studies are warranted to investigate the immunotherapeutic role of PDE5 inhibitors in combination with cancer surgery.

Dysfunctional Natural Killer Cells in the Aftermath of Cancer Surgery.

The physiological changes that occur immediately following cancer surgeries initiate a chain of events that ultimately result in a short pro-, followed by a prolonged anti-, inflammatory period. Natural Killer (NK) cells are severely affected during this period in the recovering cancer patient. NK cells play a crucial role in anti-tumour immunity because of their innate ability to differentiate between malignant versus normal cells. Therefore, an opportunity arises in the aftermath of cancer surgery for residual cancer cells, including distant metastases, to gain a foothold in the absence of NK cell surveillance. Here, we describe the post-operative environment and how the release of sympathetic stress-related factors (e.g., cortisol, prostaglandins, catecholamines), anti-inflammatory cytokines (e.g., IL-6, TGF-ß), and myeloid derived suppressor cells, mediate NK cell dysfunction. A snapshot of current and recently completed clinical trials specifically addressing NK cell dysfunction post-surgery is also discussed. In collecting and summarizing results from these different aspects of the surgical stress response, a comprehensive view of the NK cell suppressive effects of surgery is presented. Peri-operative therapies to mitigate NK cell suppression in the post-operative period could improve curative outcomes following cancer surgery.

Funding oncology clinical trials: are cooperative group trials sustainable?

PURPOSE: Many oncology clinical trials departments (CTDs) are in serious fiscal deficit and their sustainability is in jeopardy. This study investigates whether the payment models used to fund industry versus cooperative group trials contribute to the fiscal deficit of a CTD. METHODS: We examined the lifetime costs of all cooperative group and industry trials activated in the CTD of a cancer center between 2007 and 2011. A trial's lifetime is defined as being from the date the first patient was accrued until the last patient's actual or projected final follow-up visit. For each trial, we calculated the lifetime monthly net income, which was defined as monthly revenue minus monthly costs. Data sources included study protocols, trial budgets, and accrual data. RESULTS: Of the 97 trials analyzed, 64 (66%) were cooperative group trials. The pattern of lifetime net income for cooperative group trials has a positive peak during patient accrual followed by a negative trough during follow-up. In contrast, the pattern for industry trials resembled an "l" shape. The patterns reflect the differing payment models: upfront lump-sum payments (cooperative group) versus milestone payments (industry). CONCLUSION: The negative trough in the lifetime net income of a cooperative group trial occurs because follow-up costs are typically not funded or are underfunded. CTDs accrue more patients in new trials to offset that deficit. The CTD uses revenue from accrual to existing trials to cross-subsidize past trials in follow-up. As the number of patients on follow-up increases, the fiscal deficit grows larger each year, perpetuating the cycle.