GALA: an international multicentre randomised trial comparing general anaesthesia versus local anaesthesia for carotid surgery

Background: Patients who have severe narrowing at or near the origin of the internal carotid artery as a result of atherosclerosis have a high risk of ischaemic stroke ipsilateral to the arterial lesion. Previous trials have shown that carotid endarterectomy improves long-term outcomes, particularly when performed soon after a prior transient ischaemic attack or mild ischaemic stroke. However, complications may occur during or soon after surgery, the most serious of which is stroke, which can be fatal. It has been suggested that performing the operation under local anaesthesia, rather than general anaesthesia, may be safer. Therefore, a prospective, randomised trial of local versus general anaesthesia for carotid endarterectomy was proposed to determine whether type of anaesthesia influences peri-operative morbidity and mortality, quality of life and longer term outcome in terms of stroke-free survival. Methods/design: A two-arm, parallel group, multicentre randomised controlled trial with a recruitment target of 5000 patients. For entry into the study, in the opinion of the responsible clinician, the patient requiring an endarterectomy must be suitable for either local or general anaesthesia, and have no clear indication for either type. All patients with symptomatic or asymptomatic internal carotid stenosis for whom open surgery is advised are eligible. There is no upper age limit. Exclusion criteria are: no informed consent; definite preference for local or general anaesthetic by the clinician or patient; patient unlikely to be able to co-operate with awake testing during local anaesthesia; patient requiring simultaneous bilateral carotid endarterectomy; carotid endarterectomy combined with another operation such as coronary bypass surgery; and, the patient has been randomised into the trial previously. Patients are randomised to local or general anaesthesia by the central trial office. The primary outcome is the proportion of patients alive, stroke free ( including retinal infarction) and without myocardial infarction 30 days post-surgery. Secondary outcomes include the proportion of patients alive and stroke free at one year; health related quality of life at 30 days; surgical adverse events, re-operation and re-admission rates; the relative cost of the two methods of anaesthesia; length of stay and intensive and high dependency bed occupancy

Latent class evaluation of the performance of serological tests for exposure to Brucella spp. in cattle, sheep, and goats in Tanzania

Background: Brucellosis is a neglected zoonosis endemic in many countries, including regions of sub-Saharan Africa. Evaluated diagnostic tools for the detection of exposure to Brucella spp. are important for disease surveillance and guiding prevention and control activities. Methods and findings: Bayesian latent class analysis was used to evaluate performance of the Rose Bengal plate test (RBT) and a competitive ELISA (cELISA) in detecting Brucella spp. exposure at the individual animal-level for cattle, sheep, and goats in Tanzania. Median posterior estimates of RBT sensitivity were: 0.779 (95% Bayesian credibility interval (BCI): 0.570–0.894), 0.893 (0.636–0.989), and 0.807 (0.575–0.966), and for cELISA were: 0.623 (0.443–0.790), 0.409 (0.241–0.644), and 0.561 (0.376–0.713), for cattle, sheep, and goats, respectively. Sensitivity BCIs were wide, with the widest for cELISA in sheep. RBT and cELISA median posterior estimates of specificity were high across species models: RBT ranged between 0.989 (0.980–0.998) and 0.995 (0.985–0.999), and cELISA between 0.984 (0.974–0.995) and 0.996 (0.988–1). Each species model generated seroprevalence estimates for two livestock subpopulations, pastoralist and non-pastoralist. Pastoralist seroprevalence estimates were: 0.063 (0.045–0.090), 0.033 (0.018–0.049), and 0.051 (0.034–0.076), for cattle, sheep, and goats, respectively. Non-pastoralist seroprevalence estimates were below 0.01 for all species models. Series and parallel diagnostic approaches were evaluated. Parallel outperformed a series approach. Median posterior estimates for parallel testing were ≥0.920 (0.760–0.986) for sensitivity and ≥0.973 (0.955–0.992) for specificity, for all species models. Conclusions: Our findings indicate that Brucella spp. surveillance in Tanzania using RBT and cELISA in parallel at the animal-level would give high test performance. There is a need to evaluate strategies for implementing parallel testing at the herd- and flock-level. Our findings can assist in generating robust Brucella spp. exposure estimates for livestock in Tanzania and wider sub-Saharan Africa. The adoption of locally evaluated robust diagnostic tests in setting-specific surveillance is an important step towards brucellosis prevention and control

Percutaneous versus surgical strategy for tracheostomy: protocol for a systematic review and meta-analysis of perioperative and postoperative complications

Background: Tracheostomy is one of the most frequently performed procedures in intensive care medicine. The two main approaches to form a tracheostoma are the open surgical tracheotomy (ST) and the interventional strategy of percutaneous dilatational tracheotomy (PDT). It is particularly important to the critically ill patients that both procedures are performed with high success rates and low complication frequencies. Therefore, the aim of this systematic review is to summarize and analyze existing and relevant evidence for peri- and postoperative parameters of safety. Methods/design: A systematic literature search will be conducted in The Cochrane Library, MEDLINE, LILACS, and Embase to identify all randomized controlled trials (RCTs) comparing peri- and postoperative complications between the two strategies and to define the strategy with the lower risk of potentially life-threatening events. A priori defined data will be extracted from included studies, and methodological quality will be assessed according to the recommendations of the Cochrane Collaboration. Discussion: The findings of this systematic review with proportional meta-analysis will help to identify the strategy with the lowest frequency of potentially life-threatening events. This may influence daily practice, and the data may be implemented in treatment guidelines or serve as the basis for planning further randomized controlled trials. Considering the critical health of these patients, they will particularly benefit from evidence-based treatment. Systematic review registration: PROSPERO CRD4201502196

Performance characteristics and costs of serological tests for brucellosis in a pastoralist community of northern Tanzania

The control of brucellosis across sub-Saharan Africa is hampered by the lack of standardized testing and the use of tests with poor performance. This study evaluated the performance and costs of serological assays for human brucellosis in a pastoralist community in northern Tanzania. Serum collected from 218 febrile hospital patients was used to evaluate the performance of seven index tests, selected based on international recommendation or current use. We evaluated the Rose Bengal test (RBT) using two protocols, four commercial agglutination tests and a competitive enzyme-linked immunosorbent assay (cELISA). The sensitivity, specificity, positive predictive value, negative predictive value, Youden’s index, diagnostic accuracy, and per-sample cost of each index test were estimated. The diagnostic accuracy estimates ranged from 95.9 to 97.7% for the RBT, 55.0 to 72.0% for the commercial plate tests, and 89.4% for the cELISA. The per-sample cost range was $0.69–$0.79 for the RBT, $1.03–$1.14 for the commercial plate tests, and $2.51 for the cELISA. The widely used commercial plate tests performed poorly and cost more than the RBT. These findings provide evidence for the public health value of discontinuing the use of commercial agglutination tests for human brucellosis in Tanzania

Prevalence and risk factors for human leptospirosis at a hospital serving a pastoralist community, Endulen, Tanzania

Background: Leptospirosis is suspected to be a major cause of illness in rural Tanzania associated with close contact with livestock. We sought to determine leptospirosis prevalence, identify infecting Leptospira serogroups, and investigate risk factors for leptospirosis in a rural area of Tanzania where pastoralist animal husbandry practices and sustained livestock contact are common. Methods: We enrolled participants at Endulen Hospital, Tanzania. Patients with a history of fever within 72 hours, or a tympanic temperature of ≥38.0°C were eligible. Serum samples were collected at presentation and 4–6 weeks later. Sera were tested using microscopic agglutination testing with 20 Leptospira serovars from 17 serogroups. Acute leptospirosis cases were defined by a ≥four-fold rise in antibody titre between acute and convalescent serum samples or a reciprocal titre ≥400 in either sample. Leptospira seropositivity was defined by a single reciprocal antibody titre ≥100 in either sample. We defined the predominant reactive serogroup as that with the highest titre. We explored risk factors for acute leptospirosis and Leptospira seropositivity using logistic regression modelling. Results: Of 229 participants, 99 (43.2%) were male and the median (range) age was 27 (0, 78) years. Participation in at least one animal husbandry practice was reported by 160 (69.9%). We identified 18 (7.9%) cases of acute leptospirosis, with Djasiman 8 (44.4%) and Australis 7 (38.9%) the most common predominant reactive serogroups. Overall, 69 (30.1%) participants were Leptospira seropositive and the most common predominant reactive serogroups were Icterohaemorrhagiae (n = 20, 29.0%), Djasiman (n = 19, 27.5%), and Australis (n = 17, 24.6%). Milking cattle (OR 6.27, 95% CI 2.24–7.52) was a risk factor for acute leptospirosis, and milking goats (OR 2.35, 95% CI 1.07–5.16) was a risk factor for Leptospira seropositivity. Conclusions: We identified leptospirosis in approximately one in twelve patients attending hospital with fever from this rural community. Interventions that reduce risks associated with milking livestock may reduce human infections

Latent class evaluation of the performance of serological tests for exposure to Brucella spp. in cattle, sheep, and goats in Tanzania

BACKGROUND : Brucellosis is a neglected zoonosis endemic in many countries, including regions of sub-Saharan Africa. Evaluated diagnostic tools for the detection of exposure to Brucella spp. are important for disease surveillance and guiding prevention and control activities. METHODS AND FINDINGS : Bayesian latent class analysis was used to evaluate performance of the Rose Bengal plate test (RBT) and a competitive ELISA (cELISA) in detecting Brucella spp. exposure at the individual animal-level for cattle, sheep, and goats in Tanzania. Median posterior estimates of RBT sensitivity were: 0.779 (95% Bayesian credibility interval (BCI): 0.570–0.894), 0.893 (0.636–0.989), and 0.807 (0.575–0.966), and for cELISA were: 0.623 (0.443–0.790), 0.409 (0.241–0.644), and 0.561 (0.376–0.713), for cattle, sheep, and goats, respectively. Sensitivity BCIs were wide, with the widest for cELISA in sheep. RBT and cELISA median posterior estimates of specificity were high across species models: RBT ranged between 0.989 (0.980–0.998) and 0.995 (0.985–0.999), and cELISA between 0.984 (0.974–0.995) and 0.996 (0.988–1). Each species model generated seroprevalence estimates for two livestock subpopulations, pastoralist and non-pastoralist. Pastoralist seroprevalence estimates were: 0.063 (0.045–0.090), 0.033 (0.018–0.049), and 0.051 (0.034–0.076), for cattle, sheep, and goats, respectively. Non-pastoralist seroprevalence estimates were below 0.01 for all species models. Series and parallel diagnostic approaches were evaluated. Parallel outperformed a series approach. Median posterior estimates for parallel testing were ≥0.920 (0.760-0.986) for sensitivity and ≥0.973 (0.955-0.992) for specificity, for all species models. CONCLUSIONS : Our findings indicate that Brucella spp. surveillance in Tanzania using RBT and cELISA in parallel at the animal-level would give high test performance. There is a need to evaluate strategies for implementing parallel testing at the herd- and flock-level. Our findings can assist in generating robust Brucella spp. exposure estimates for livestock in Tanzania and wider sub-Saharan Africa. The adoption of locally evaluated robust diagnostic tests in setting-specific surveillance is an important step towards brucellosis prevention and control.The UK Biotechnology and Biological Sciences Research Council (BBSRC), Department for International Development (DFID), the Economic & Social Research Council (ESRC), the Medical Research Council (MRC), the Natural Environment Research Council (NERC) and the Defence Science & Technology Laboratory under the Zoonoses and Emerging Livestock Systems programme, Zoonoses and Emerging Livestock Systems – Associated Studentship programme, US National Institutes of Health-National (NIH) Science Foundation Ecology and Evolution of Infectious Disease program, UK BBSRC , the US NIH, National Institute of Allergy and Infectious Diseases through Investigating Febrile Deaths in Tanzania (INDITe) and the BBSRC Institute Strategic Programme Grants.https://journals.plos.org/plosntdspm2022Veterinary Tropical Disease