13 research outputs found
Epidemiological characteristics of deaths related to surgical emergencies in Sub-Saharan Africa: case of Parakou, Benin
No full textBackground: Emergency and resuscitation departments, often on the front lines of the hospital care system, are sadly the site of many deaths. Author aim to study the epidemiological characteristics of deaths related to surgical emergencies at Parakou Teaching Hospital in Benin.Methods: This was a prospective, descriptive study covering 6 months from January 1st to June 31st 2016. It focused on patients admitted to the emergency department and hospitalized in general surgery or resuscitation department during the study period. Three criteria were defined: admission for a surgical emergency, clinical classification of emergency patients (known as CCMU: Classification Clinique des Malades aux Urgences) between 1 and 5 and evolution marked by death.Results: A total of 54 deaths were recorded out of 379 surgical emergencies (14.2%). The sex-ratio was 2.2. The average age was 31±18.8 years old. The average admission time was 75.7±95.2 hours. The CCMU 4 and 5 were the most numerous (77. 7%). Traumatic emergencies were the most likely cause of death (56.6%), with cranio-encephalic trauma being the leading cause (38.9%). for non-traumatic emergencies (44.4%), acute generalized peritonitis is the leading cause of death (18.5%). The average time to surgical management was 87.4 hours, mainly related to the indigence of patients.Conclusions: The reduction of deaths related to surgical emergencies requires the adapted equipment of the different services involved in the care, the continuous training of staff and the creation of a health insurance.</jats:p
Exploring the cost-effectiveness of high versus low perioperative fraction of inspired oxygen in the prevention of surgical site infections among abdominal surgery patients in three low- and middle-income countries
No full textBackground: This study assessed the potential cost-effectiveness of high (80–100%) vs low (21–35%) fraction of inspired oxygen (FiO2) at preventing surgical site infections (SSIs) after abdominal surgery in Nigeria, India, and South Africa. Methods: Decision-analytic models were constructed using best available evidence sourced from unbundled data of an ongoing pilot trial assessing the effectiveness of high FiO2, published literature, and a cost survey in Nigeria, India, and South Africa. Effectiveness was measured as percentage of SSIs at 30 days after surgery, a healthcare perspective was adopted, and costs were reported in US dollars (216 compared with 6 (95% confidence interval [CI]: −1) difference in costs. In India, the average cost for high FiO2 was 195 for low FiO2 leading to a −15 to −1164 compared with 93 (95% CI: −65) difference in costs. The high FiO2 arm had few SSIs, 7.33% compared with 8.38% for low FiO2, leading to a −1.05 (95% CI: −1.14 to −0.90) percentage point reduction in SSIs. Conclusion: High FiO2 could be cost-effective at preventing SSIs in the three countries but further data from large clinical trials are required to confirm this. © 2023 The Author
The regulation of tau-dependent neurodegeneration by Brain Selective/SAD kinases
No full textBrain-selective kinases (BRSK1 and BRSK2) are serine/threonine kinase members
of the AMPK-related family of protein kinases, the majority of which are regulated
by the upstream kinase LKB1 whilst AMPK itself is regulated by CaMKK. The
BRSKs are highly expressed in brain and have been implicated in neuronal
polarization and the regulation of neurotransmitter release. They have also been
shown to be involved in the basal phosphorylation of tau at the Alzheimer‟s disease
(AD) related residue, serine 262, and are highly expressed in areas of the brain
affected by AD, namely the hippocampus and the cortex. I have utilised the model
organism Drosophila melanogaster to investigate interactions between transgenically
expressed human tau, human BRSKs and upstream regulators
Selective over-expression of 0N4R human tau in the Drosophila eye resulted in a
disruption of eye morphology. In contrast, over-expression of human wild type
BRSK2 (B-WT) had no obvious effect on the eye. However, co-expression of both
tau and B-WT resulted in a neurodegenerative phenotype more severe than tau alone.
This enhancement of phenotype was not observed when BRSK2 was expressed that
either lacked the activating phosphorylation site (non-phosphorylatable, B-NP) or
that is unable to bind ATP (kinase dead, B-KD). Co-expression of human tau and BWT
significantly elevated tau phosphorylation at S262, suggesting that S262 is a key
residue for tau-induced toxic phenotypes and the BRSK/tau interaction I observe. In
support of this, no phenotype was observed in flies expressing the S262A variant of
human tau with or without B-WT.
To establish the upstream kinases responsible for activating human BRSK2 in
Drosophila I removed endogenous Drosophila LKB1 by RNAi. This prevented the
enhanced degeneration of the eye caused by tau/B-WT co-expression, demonstrating
that LKB1 is a key upstream regulator of BRSK2. I also found that down regulation
of the Drosophila CaMKK homologue, CG17698, by the same method, ameliorated
B-WT induced eye degeneration implicating a calcium-dependent pathway in the
regulation of BRSK. Over-expression of human CaMKKα in the CG17698 RNAi
background prevented the rescue seen with CG17698 RNAi. Over-expression of
cac1, a calcium channel subunit, in the presence of B-WT and human tau
exacerbated the B-WT induced eye phenotype in a B-WT dependent manner,
supporting the hypothesis that the human tau and B-WT interaction can be regulated
in a calcium-dependent manner.
Expression of total BRSK2, LKB1 and CaMKK were not altered in human postmortem
AD brain tissue when compared to control. However, with the exception of
LKB1, due to limited reagents and time constraints I was unable to investigate the
proportion of phosphorylated (and thus active) to total kinase.
This study defines a novel Ca2+ -dependent regulatory pathway to tau, which may
contribute to AD and other tauopathies
Functional analysis of the tomato Ve resistance locus against Verticillium wilt
No full text Verticillium dahliae, V. albo-atrum and V. longisporum are soil-borne plant pathogens that are responsible for Verticillium wilt diseases in temperate and subtropical regions. Collectively they can infect over 200 hosts, including many economically important crops. Chapter 1 is a “pathogen profile” which describes the most important aspects of the biology of the Verticillium wilt pathogens. They colonize the xylem vessels of their host plants and cause symptoms such as wilting, chlorosis, stunting, necrosis and vein clearing. Verticillium species are notoriously difficult to control as there are no fungicides available to cure plants once they are infected. Therefore, genetic resistance is the preferred method for disease control. Chapter 2 describes the functional characterization of the tomato (Solanum lycopersicum) Ve locus. This locus is responsible for resistance against race 1 strains of V. dahliae and V. albo-atrum and comprises two closely linked inversely oriented genes, Ve1 and Ve2. Both genes encode cell surface receptor proteins of the extracellular leucine-rich repeat (eLRR) receptor-like protein (RLP) class of disease resistance proteins. In chapter 2, it is demonstrated that Ve1, but not Ve2, provides resistance in tomato against race 1 but not against race 2 strains of V. dahliae and V. albo-atrum. Using virus-induced gene silencing in tomato, the signaling cascade downstream of Ve1 was shown to require both EDS1 (enhanced disease susceptibility1) and NDR1 (non-race-specific disease resistance1). In addition, also NRC1 (NB-LRR protein required for hypersensitive response-associated cell death1), ACIF (Avr9/Cf-9–induced F-box1), MEK2 (MAP/ERK kinase2), and SERK3/BAK1 (somatic embryogenesis receptor kinase 3/brassinosteroid-associated kinase 1) act as positive regulators of Ve1 in tomato. In conclusion, Ve1-mediated resistance signaling only partially overlaps with signaling mediated by Cf proteins, type members of the eLRR-RLP-class of resistance proteins. In chapter 3 an attempt to introduce Nicotiana benthamiana as a model to facilitate the study of Ve1-mediated resistance is described. Challenge of wild type plants with several race 1 and race 2 strains of V. dahliae and V. albo-atrum demonstrated that N. benthamiana is susceptible to both Verticillium species. To obtain Verticillium wilt resistant plants, N. benthamiana was engineered to express the tomato Ve1 coding sequence. However, out of thirteen transgenic lines, six showed clear phenotypic aberrancies that included severe stunting and malformed leaves when compared to wild type plants. The seven Ve1-transgenic lines that did not show any phenotypic alterations were challenged with race 1 and race 2 strains. Although the pathogenicity assays indicated that in few lines Ve1 expression temporarily reduced disease development, most lines were as susceptible as wild type parental line. In conclusion, in chapter 3 it is demonstrated that the Ve1-transgenic N. benthamiana lines could not be used to study Ve1-mediated resistance signaling. In chapter 4, the use of Arabidopsis (Arabidopsis thaliana) as model to facilitate the study of Ve1-mediated resistance is presented. To this end, tomato Ve1 was expressed in susceptible Arabidopsis plants. Upon challenge with race 1 strains of V. dahliae or V. albo-atrum, Ve1-expressing plants were found to be resistant. In contrast, Ve1-expressing plants were susceptible to race 2 strains of both V. dahliae and V. albo-atrum. Furthermore, expression of Ve1 in Arabidopsis plants did not prevent colonization by V. longisporum strains. Through Ve1-expression in Arabidopsis defense signaling mutants, it was demonstrated that signaling downstream of Ve1 is highly conserved between tomato and Arabidopsis. In previous chapters it was shown that the receptor kinase SERK3/BAK1 is required for Ve1-mediated resistance in tomato as well as in Arabidopsis. In Arabidopsis, SERK3/BAK1 belongs to a gene family consisting of five members. In chapter 5, the requirement of the different SERK family members in Ve1-mediated resistance in Arabidopsis is investigated, revealing the requirement of SERK1 and, although to a lesser extent, SERK4 for resistance. Using virus-induced gene silencing, it was subsequently shown that SERK1 is also required for Ve1-mediated resistance in tomato. In conclusion, the results of chapter 5 demonstrate that Arabidopsis can be used as model to unravel the molecular mechanisms of Ve1-mediated resistance. In chapter 6, the recognition specificity of Ve1 was further investigated by performing domain-swaps with Ve2 and expressing the chimeric Ve proteins in Arabidopsis. Various domain swaps in which eLRRs from Ve1 were replaced by those of Ve2 suggest that the region between eLRR22 and eLRR35 is required for full Ve1-mediated resistance. However, plants expressing a Ve chimera in which eLRR1 to eLRR30 of Ve1 was replaced with those of Ve2 were resistant against Verticillium. Overall, these results suggest that Ve2 may still bind the elicitor in the eLRR domain, but its C-terminal domain is not able to activate a successful defense response. Finally in Chapter 7, highlights of this thesis are discussed and placed in a broader perspective. </p
Management and Outcomes Following Surgery for Gastrointestinal Typhoid: An International, Prospective, Multicentre Cohort Study
No full textBackground: Gastrointestinal perforation is the most serious complication of typhoid fever, with a high disease burden in low-income countries. Reliable, prospective, contemporary surgical outcome data are scarce in these settings. This study aimed to investigate surgical outcomes following surgery for intestinal typhoid. Methods: Two multicentre, international prospective cohort studies of consecutive patients undergoing surgery for gastrointestinal typhoid perforation were conducted. Outcomes were measured at 30 days and included mortality, surgical site infection, organ space infection and reintervention rate. Multilevel logistic regression models were used to adjust for clinically plausible explanatory variables. Effect estimates are expressed as odds ratios (ORs) alongside their corresponding 95% confidence intervals. Results: A total of 88 patients across the GlobalSurg 1 and GlobalSurg 2 studies were included, from 11 countries. Children comprised 38.6% (34/88) of included patients. Most patients (87/88) had intestinal perforation. The 30-day mortality rate was 9.1% (8/88), which was higher in children (14.7 vs. 5.6%). Surgical site infection was common, at 67.0% (59/88). Organ site infection was common, with 10.2% of patients affected. An ASA grade of III and above was a strong predictor of 30-day post-operative mortality, at the univariable level and following adjustment for explanatory variables (OR 15.82, 95% CI 1.53–163.57, p = 0.021). Conclusions: With high mortality and complication rates, outcomes from surgery for intestinal typhoid remain poor. Future studies in this area should focus on sustainable interventions which can reduce perioperative morbidity. At a policy level, improving these outcomes will require both surgical and public health system advances
Use of Telemedicine for Post-discharge Assessment of the Surgical Wound: International Cohort Study, and Systematic Review with Meta-analysis
No full textObjective: This study aimed to determine whether remote wound reviews using telemedicine can be safely upscaled, and if standardised assessment tools are needed. Summary background data: Surgical site infection is the most common complication of surgery worldwide, and frequently occurs after hospital discharge. Evidence to support implementation of telemedicine during postoperative recovery will be an essential component of pandemic recovery. Methods: The primary outcome of this study was surgical site infection reported up to 30-days after surgery (SSI), comparing rates reported using telemedicine (telephone and/or video assessment) to those with in-person review. The first part of this study analysed primary data from an international cohort study of adult patients undergoing abdominal surgery who were discharged from hospital before 30-days after surgery. The second part combined this data with the results of a systematic review to perform a meta-analysis of all available data conducted in accordance with PRIMSA guidelines (PROSPERO:192596). Results: The cohort study included 15,358 patients from 66 countries (8069 high, 4448 middle, 1744 low income). Of these, 6907 (45.0%) were followed up using telemedicine. The SSI rate reported using telemedicine was slightly lower than with in-person follow-up (13.4% vs. 11.1%, P<0.001), which persisted after risk adjustment in a mixed-effects model (adjusted odds ratio: 0.73, 95% confidence interval 0.63-0.84, P<0.001). This association was consistent across sensitivity and subgroup analyses, including a propensity-score matched model. In nine eligible non-randomised studies identified, a pooled mean of 64% of patients underwent telemedicine follow-up. Upon meta-analysis, the SSI rate reported was lower with telemedicine (odds ratio: 0.67, 0.47-0.94) than in-person (reference) follow-up (I2=0.45, P=0.12), although there a high risk of bias in included studies. Conclusions: Use of telemedicine to assess the surgical wound post-discharge is feasible, but risks underreporting of SSI. Standardised tools for remote assessment of SSI must be evaluated and adopted as telemedicine is upscaled globally
Surgical site infection after gastrointestinal surgery in children: An international, multicentre, prospective cohort study
No full textSurgical site infection (SSI) is one of the most common healthcare-associated infections (HAIs). However, there is a lack of data available about SSI in children worldwide, especially from low-income and middle-income countries. This study aimed to estimate the incidence of SSI in children and associations between SSI and morbidity across human development settings
Exploring the cost-effectiveness of high versus low perioperative fraction of inspired oxygen in the prevention of surgical site infections among abdominal surgery patients in three low- and middle-income countries
No full textUse of Telemedicine for Postdischarge Assessment of the Surgical Wound: International Cohort Study, and Systematic Review With Meta-analysis
No full textObjective:
This study aimed to determine whether remote wound reviews using telemedicine can be safely upscaled, and if standardized assessment tools are needed.
//
Background:
Surgical site infection (SSI) is the most common complication of surgery worldwide, and frequently occurs after hospital discharge. Evidence to support implementation of telemedicine during postoperative recovery will be an essential component of pandemic recovery.
//
Methods:
The primary outcome of this study was SSI reported up to 30 days after surgery (SSI), comparing rates reported using telemedicine (telephone and/or video assessment) to those with in-person review. The first part of this study analyzed primary data from an international cohort study of adult patients undergoing abdominal surgery who were discharged from hospital before 30 days after surgery. The second part combined this data with the results of a systematic review to perform a meta-analysis of all available data conducted in accordance with PRIMSA guidelines (PROSPERO:192596).
//
Results:
The cohort study included 15,358 patients from 66 countries (8069 high, 4448 middle, 1744 low income). Of these, 6907 (45.0%) were followed up using telemedicine. The SSI rate reported using telemedicine was slightly lower than with in-person follow-up (13.4% vs 11.1%, P<0.001), which persisted after risk adjustment in a mixed-effects model (adjusted odds ratio: 0.73, 95% confidence interval: 0.63–0.84, P<0.001). This association was consistent across sensitivity and subgroup analyses, including a propensity-score matched model. In 9 eligible nonrandomized studies identified, a pooled mean of 64% of patients underwent telemedicine follow-up. Upon meta-analysis, the SSI rate reported was lower with telemedicine (odds ratio: 0.67, 0.47–0.94) than in-person (reference) follow-up (I2=0.45, P=0.12), although there a high risk of bias in included studies.
//
Conclusions:
Use of telemedicine to assess the surgical wound postdischarge is feasible, but risks underreporting of SSI. Standardized tools for remote assessment of SSI must be evaluated and adopted as telemedicine is upscaled globally
Accuracy of the Wound Healing Questionnaire in the diagnosis of surgical-site infection after abdominal surgery in low- and middle-income countries
No full textIntroductionTelemedicine is being adopted for postoperative surveillance but requires evaluation for efficacy. This study tested a telephone Wound Healing Questionnaire (WHQ) to diagnose surgical site infection (SSI) after abdominal surgery in low- and middle-income countries.MethodA multi-centre, international, prospective study was embedded in the FALCON trial; a factorial RCT testing measures to reduce SSI in seven low- and middle-income countries (NCT03700749). It was conducted according to a pre-registered protocol (SWAT126) and reported according to STARD guidelines. The reference test was in-person review by a trained clinician at 30 postoperative days according to US Centres for Disease Control criteria. The index test was telephone administration of an adapted WHQ at 27 to 30 postoperative days by a researcher blinded to the outcome of in-person review. The sum of item response scores generated an overall score between 0 and 29. The primary outcome was the diagnostic accuracy of the WHQ, defined as the proportion of SSI correctly identified by the telephone WHQ, and summarized using the area under the receiving operator characteristic curve (AUROC) and diagnostic test accuracy statistics.ResultsPatients were included from three upper-middle income (396 patients, 13 hospitals), three lower-middle income (746 patients, 19 hospitals), and one low-income country (54 patients, 4 hospitals). 90.3% (1088 of 1196) patients were successfully contacted. Those with non-midline incisions (adjusted odds ratio: 0.36, 95% c.i. 0.17 to 0.73, P=0.005) or a confirmed diagnosis of SSI on in-person assessment (odds ratio: 0.42, 95% c.i. 0.20 to 0.92, P=0.006) were harder to reach. The questionnaire correctly discriminated between most patients with and without SSI (AUROC 0.869, 95% c.i. 0.824 to 0.914), which was consistent across subgroups. A representative cut-off score of ≥4 displayed a sensitivity of 0.701 (0.610-0.792), specificity of 0.911 (0.878-0.943), positive predictive value of 0.723 (0.633-0.814) and negative predictive value of 0.901 (0.867-0.935).ConclusionSSI can be diagnosed using a telephone questionnaire (obviating in-person assessment) in low resource settings
