Developing a Sustainable Renal Transplant Program in Low- and Middle-Income Countries: Outcome, Challenges, and Solutions.

INTRODUCTION: The initiation of a kidney transplant program, in a low- and middle-income country, while striving to maintain excellent outcomes and adhere to high ethical, legal standards, is a formidable task. Herein, we review the outcomes and challenges of a living donor kidney transplant program from its inception to sustainability, in Guyana, South America. METHODS: This is a retrospective review of a living donor kidney transplant program instituted in Guyana in 2008. Data included recipient and donor demographics, cause of renal failure, donor-recipient matching and relationship, perioperative complications, timing and cause of death, graft failure, surgical technique, and laterality of organ procured. Patient and donor data were compared by phases and additionally compared to United States Renal Data Base System. Survival outcomes were compared by phases and by Kaplan-Meier curves. RESULTS: To date, 45 kidney transplants have been completed. Phase I (2007-2008) was the initiation of the program, which was comprised of upgrading hospital and operating rooms, obtaining antirejection medications, educating local providers, fostering a relationship with the government, and screening patients and living donors. We also began vascular access and peritoneal dialysis in the country, as well as introduced the companion public health service initiative: the SEVAK program. Phase II (2008-2014) involved completion of 25 living donor kidney transplants, of which there have been 11 confirmed deaths and 10 lost to follow-up. In Phase III (2015-present), 20 transplants have been completed to date, of whom only 1 died and none were lost to follow-up. In the third phase, we also introduced corneal transplantation to Guyana and have performed over 100 transplants. CONCLUSION: Kidney transplantation can be safely and ethically performed in a low- and middle-income country. We applied lessons learnt from the first two phases to improve follow-up by appointing a local coordinator who goes to patient's homes in remote villages. Currently, there is a stable local team that is performing transplants and following the patients. We believe that our model of public-private partnership can sustain kidney, as well as corneal, transplantation and could be replicated in other countries.

Behavioral transcriptomic effects of triploidy and probiotic therapy (Bifidobacterium, Lactobacillus, and Lactococcus mixture) on juvenile Chinook salmon (Oncorhynchus tshawytscha).

Aquaculturists use polyploid fish to maximize production albeit with some unintended consequences including compromised behaviors and physiological function. Given benefits of probiotic therapies (e.g., improved immune response, growth, and metabolism), we explored probiotic supplementation (mixture of Bifidobacterium, Lactobacillus, and Lactococcus), to overcome drawbacks. We first examined fish gut bacterial community composition using 16S metabarcoding (via principal coordinate analyses and PERMANOVA) and determined probiotics significantly impacted gut bacteria composition (p = 0.001). Secondly, we examined how a genomic disruptor (triploidy) and diet supplements (probiotics) impact gene transcription and behavioral profiles of hatchery-reared Chinook salmon (Oncorhynchus tshawytscha). Juveniles from four treatment groups (diploid-regular feed, diploid-probiotic feed, triploid-regular feed, and triploid-probiotic feed; n = 360) underwent behavioral assays to test activity, exploration, neophobia, predator evasion, aggression/sociality, behavioral sensitivity, and flexibility. In these fish, transcriptional profiles for genes associated with neural functions (neurogenesis/synaptic plasticity) and biomarkers for stress response and development (growth/appetite) were (i) examined across treatments and (ii) used to describe behavioral phenotypes via principal component analyses and general linear mixed models. Triploids exhibited a more active behavioral profile (p = 0.002), and those on a regular diet had greater Neuropeptide Y transcription (p = 0.02). A growth gene (early growth response protein 1, p = 0.02) and long-term neural development genes (neurogenic differentiation factor, p = 0.003 and synaptysomal-associated protein 25-a, p = 0.005) impacted activity and reactionary profiles, respectively. Overall, our probiotic treatment did not compensate for triploidy. Our research highlights novel applications of behavioral transcriptomics for identifying candidate genes and dynamic, mechanistic associations with complex behavioral repertoires.

Ketamine For Acute Pain After Trauma (KAPT): A Pragmatic, Randomized Clinical Trial.

INTRODUCTION: Non-narcotic intravenous medications may be a beneficial adjunct to oral multimodal pain regimens (MMPRs) which reduce but do not eliminate opioid exposure and prescribing after trauma. We hypothesized that the addition of a sub-dissociative ketamine infusion (KI) to a standardized oral MMPR reduces inpatient opioid exposure. METHODS: Eligible adult trauma patients admitted to the intermediate or intensive care unit were randomized upon admission to our institutional MMPR per usual care (UC) or UC plus sub-dissociative KI for 24 to 72 hours after arrival. The primary outcome was morphine milligram equivalents per day (MME/d) and secondary outcomes included total MME, discharge with an opioid prescription (OP%), and rates of ketamine side effects. Bayesian posterior probabilities (pp) were calculated using neutral priors. RESULTS: A total of 300 patients were included in the final analysis with 144 randomized to KI and 156 to UC. Baseline characteristics were similar between groups. The injury severity scores for KI were 19 [14, 29] versus UC 22 [14, 29]. The KI group had a lower rate of long-bone fracture (37% versus 49%) and laparotomy (16% versus 24%). Patients receiving KI had an absolute reduction of 7 MME/day, 96 total MME, and 5% in OP%. Additionally, KI had a relative risk (RR) reduction of 19% in MME/day (RR 0.81 [0.69 - 0.95], pp = 99%), 20% in total MME (RR 0.80 [0.64, 0.99], pp = 98%), and 8% in OP% (RR 0.92 [0.76, 1.11], pp = 81%). The KI group had a higher rate of delirium (11% versus 6%); however, rates of other side effects such as arrythmias and unplanned intubations were similar between groups. CONCLUSION: Addition of a sub-dissociative ketamine infusion to an oral MMPR resulted in a decrease in opioid exposure in severely injured patients. Sub-dissociative ketamine infusions can be used as a safe adjunct to decrease opioid exposure in monitored settings. LEVEL OF EVIDENCE: I; Therapeutic/Care Management.

Impact of Intra-Operative Shock and Resuscitation on Surgical Site Infections After Trauma Laparotomy.

Background: Patients undergoing trauma laparotomy experience high rates of surgical site infection (SSI). Although intra-operative shock is a likely contributor to SSI risk, little is known about the relation between shock, intra-operative restoration of physiologic normalcy, and SSI development. Patients and Methods: A retrospective review of trauma patients who underwent emergent definitive laparotomy was performed. Using shock index and base excess at the beginning and end of laparotomy, patients were classified as normal, persistent shock, resuscitated, or new shock. Univariable and multivariable analyses were performed to identify predictors of organ/space SSI, superficial/deep SSI, and any SSI. Results: Of 1,191 included patients, 600 (50%) were categorized as no shock, 248 (21%) as resuscitated, 109 (9%) as new shock, and 236 (20%) as persistent shock, with incidence of any SSI as 51 (9%), 28 (11%), 26 (24%), and 32 (14%), respectively. These rates were similar in organ/space and superficial/deep SSIs. On multivariable analysis, resuscitated, new shock, and persistent shock were associated with increased odds of organ/space SSI (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.3-3.5; p < 0.001) and any SSI (OR, 2.0; 95% CI, 1.4-3.2; p < 0.001), but no increased risk of superficial/deep SSI (OR, 1.4; 95% CI, 0.8-2.6; p = 0.331). Conclusions: Although the trajectory of physiologic status influenced SSI, the presence of shock at any time during trauma laparotomy, regardless of restoration of physiologic normalcy, was associated with increased odds of SSI. Further investigation is warranted to determine the relation between peri-operative shock and SSI in trauma patients.

Poor Oral Health in Trauma Intensive Care Unit Patients: Application of a Novel Oral Health Score.

Background: Although oral hygiene in patients in the intensive care unit (ICU) has been shown to reduce hospital-associated infections, baseline and progressive oral health are often not reported because of lack of a standardized tool. The Oral Health Risk Assessment Value Index (OHRAVI) is a comprehensive oral assessment validated by dental providers. This study hypothesizes that non-dental providers can use OHRAVI in trauma ICU patients with minimal training and acceptable inter-rater reliability (IRR). Patients and Methods: Dentulous adult patients in the ICU at a level 1 trauma center were scored, excluding those with severe orofacial trauma. The eight categories of the OHRAVI were scored 0 to 3 (best to worst) with summed total and index (average) score. Index scores 1 or less need routine oral care; greater than 1-2 require moderate care; and greater than 2-3 require extensive oromaxillofacial care. Inter-rater reliability was assessed by two to three raters with Krippendorff's α (≥0.80 for good and ≥0.667 for acceptable). Results: Eighty-four ratings were completed across 34 patients, with 16 patients (47%) scored by all three raters. Ten patients (29%) had an index score <1. The average index score for patients was 1.28 (median, 1.34; range, 0.63-2). Krippendorff's α for index score was 0.86. For individual categories, α ranged from 0.44 to 1, with six of the eight categories achieving an α ≥ 0.667. Conclusions: With minimal training, non-dental providers were able to use OHRAVI with a good IRR for index score and an acceptable/good IRR for most individual categories. This novel, simple, comprehensive oral health score could help standardize oral assessment and facilitate future studies of peri-operative oral hygiene interventions.

Challenges in the control of neglected insect vector diseases of human importance in the Anglo-Caribbean.

INTRODUCTION: Neglected tropical diseases (NTDs) in developing countries like the Caribbean, negatively affect multiple income-generating sectors, including the tourism industry upon which island states are highly dependent. Insect-transmitted NTDs include, but are not limited to, malaria, dengue and lymphatic filariasis. Control measures for these disease, are often ignored because of the associated cost. Many of the developing country members are thus retained in a financially crippling cycle, balancing the cost of prophylactic measures with that of controlling an outbreak.The purpose of the paper is to bring awareness to NTDs transmitted by insects of importance to humans, and to assess factors affecting such control, in the English-speaking Caribbean. METHOD: Comprehensive literature review on reports pertaining to NTDs transmitted by insects in the Caribbean and Latin America was conducted. Data search was carried out on PubMed, and WHO and PAHO websites. RESULTS AND CONCLUSION: Potential risk factors for NTDs transmitted by arthropods in the English-speaking Caribbean are summarised. The mosquito appears to be the main insect-vector of human importance within the region of concern. Arthropod-vectors of diseases of veterinary importance are also relevant because they affect the livelihood of farmers, in highly agriculture based economies. Other NTDs may also be in circulation gauged by the presence of antibodies in Caribbean individuals. However, routine diagnostic tests for specific diseases are expensive and tests may not be conducted when diseases are not prevalent in the population. It appears that only a few English-speaking Caribbean countries have examined secondary reservoirs of pathogens or assessed the effectivity of their insect control methods. As such, disease risk assessment appears incomplete. Although continuous control is financially demanding, an integrated and multisectoral approach might help to deflect the cost. Such interventions are now being promoted by health agencies within the region and various countries are creating and exploring the use of novel tools to be incorporated in their insect-vector control programmes.