Safety of equine tetanus antitoxin for prophylactic use in Ethiopia: a retrospective multi-center study.

BACKGROUND: Tetanus remains a severe life-threatening infectious disease and neurological disorder in many parts of the world, where immunization programs are suboptimal. Any human injury or trauma has the possibility of getting infected with Clostridium tetani which is the sole causative bacterium of tetanus. Evidence is available that TAT may cause anaphylaxis and late serum sickness, while there has been no study conducted in Ethiopia. The Ethiopian Ministry of Health standard treatment guideline recommends tetanus prophylaxis for all tetanus-prone wounds. This study aimed to evaluate the safety of TAT administration in adults exposed to tetanus-prone wounds in Ethiopia. METHODS: The target product of this study was the equine tetanus antitoxin developed and manufactured by the ViNS Bioproducts Limited, India (Code: 130202084, A.W.No: 15/AAW/PI/02.00, DT: 25.04.2016). The product is delivered with the dose of 1000/1500 IU intramuscularly or subcutaneously to individuals at risk of tetanus infection for prophylactic purposes. The study was carried out in 11 healthcare facilities in Addis Ababa, Ethiopia, that had a relatively high clients load for tetanus-prone wounds. Medical records of patients with tetanus-prone wounds who received the equine TAT were reviewed retrospectively for any adverse events following immunization according to the World Health Organization (WHO) definition for adverse events following immunization (AEFI). RESULTS: There were more than 20,000 patients treated for trauma in the facilities from 2015 to 2019. Upon revision of available registration books, we identified 6000 charts to be eligible for the study, of which 1213 charts that had complete and reliable data on the AEFI profile of the TAT were included in the final analysis. The median age of the study participants was 26 years (IQR = 11 years, age range: 18-91 years) and 78% (949) were male. The tetanus-prone wounds resulted mainly from stab (44%, 535) and blunt force (30%, 362), and the most common sites of wounds were hand (22%, 270) and head (21%, 253). The most and least frequently occurring types of wounds were open wounds (77%, 930) and organ system injury (0.003%, 4), respectively. The mean time of presenting at health facilities from the onset of trauma was 2.96 h. Of the total 1231 participants, one male participant who presented within 3 h after experiencing a wound on his nose at the workplace had a severe local reaction immediately after injection of the TAT. No AEFI was recorded for the other participants. CONCLUSIONS: The adverse event following immunization of the equine tetanus antitoxin produced by the ViNS Bioproducts Limited was very rare. A regular review of the product's safety performance and systematic collection and analysis of adverse event reports are important to ensure the safety of the product.

Inpatient Teleneurology Follow-up Has Comparable Outcomes to In-Person Neurology Follow-up.

Background and Objectives: Community emergency departments often transfer patients for lack of neurology coverage, potentially burdening patients and accepting facilities. Telestroke improves access to acute stroke care, but there is a lack of data on inpatient teleneurology and telestroke care. Methods: From our prospective telestroke registry, we retrospectively reviewed 3702 consecutive patients who were seen via telestroke between September 2015 and December 2018. Patients who required transfer after initial telestroke evaluation or who were kept at hospitals without consistent neurology coverage were excluded from analysis. We compared baseline demographics, clinical characteristics, and hospital outcomes in patients who were subsequently followed remotely by a teleneurology neurohospitalist and those followed in person by a neurohospitalist. Results: There were 447 (23%) patients followed by a teleneurology neurohospitalist and 1459 (77%) patients followed in person by a neurohospitalist. Both groups presented with similar stroke severity. In multivariate analysis, there were no significant differences in discharge disposition, stroke readmission rates, or 90-day modified Rankin Scale (mRS) scores. Length of stay was shorter with teleneurology follow-up. In the subgroup of patients who received tissue plasminogen activator, patients showed no differences in outcomes and had similar complication rates. Teleneurology follow-up resulted in a 3% transfer rate for higher level of care after admission. There remained no difference in outcomes in a subanalysis without Comprehensive Stroke Centers. A higher proportion of non-Hispanic Black patients and a lower proportion of Hispanic patients in the teleneurology follow-up group were possibly due to spoke location demographics. Discussion: Teleneurology follow-up resulted in comparable outcomes to in-person neurology follow-up, with few transfers after admission. For select neurology and ischemic stroke patients, teleneurology follow-up provides an alternative to transfer for hospitals lacking neurology coverage.

Thrombolytic Refusal Over Telestroke.

BACKGROUND: Tissue plasminogen activator (tPA) refusal is 4%-6% for acute ischemic stroke (AIS) in the emergency department. Telestroke (TS) has increased the use of tPA for AIS but is accompanied by barriers in communication that can affect tPA consent. We characterized the incidence of tPA refusal in our TS network and its associated reasons. METHODS: Patients with AIS who were offered tPA within 4.5 hours from symptom onset according to American Heart Association guidelines were identified within our Lone Star Stroke Consortium Telestroke Registry from September 2015 to December 2018. We compared baseline characteristics and clinical outcomes between patients who refused tPA and patients who accepted tPA. RESULTS: Among the 1,242 patients who qualified for tPA and were offered treatment, 8% refused tPA. Female and non-Hispanic Black patients and patients with a prior history of stroke were more likely to decline tPA. Patients who refused tPA presented with a lower NIHSS and were associated with a final diagnosis of stroke mimic (odds ratio [OR] 0.23; 95% confidence interval [CI] 0.15-0.36). Good outcome (90-day modified Rankin Scale 0-2) was the same among patients who received tPA and those who refused (OR 0.80; 95% CI 0.42-1.54). The most common reasons for refusal were rapidly improving and mild/nondisabling symptoms and concern for potential side effects. CONCLUSION: tPA refusal over TS is comparable to previously reported rates; there was no difference in outcomes among patients who received tPA compared with those who refused. Sex and racial differences associated with an increased tPA refusal warrant further investigation in efforts to achieve equity/parity in tPA decisions.

Pyrosequencing for diagnosis of multidrug and extensively drug-resistant tuberculosis: A systemic review and meta-analysis.

BACKGROUND: Multidrug and extensively drug-resistant tuberculosis (M/XDR-TB) pose major threats to global health. Diagnosis accuracy and delay have been the major drivers for the upsurge of M/XDR-TB. Pyrosequencing (PSQ) is a novel, real-time DNA sequencing for rapid detection of mutations associated with M/XDR-TB. We aimed to systematically synthesize the evidence on the diagnostic accuracy of PSQ for M/XDR-TB. METHODS: We conducted an electronic search of PubMed, Embase, Biosis, Web of Science, and Google Scholar up to March 2020. We used the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool to assess the quality of studies, the BRMA (bivariate random-effects meta-analysis) model to synthesize diagnostic accuracies, and the Rev-Man 5.4 software to perform the meta-analyses. We analyzed dichotomous data using the risk ratio (RR) with a 95% confidence interval. PROSPERO Registration ID: CRD42020200817. RESULTS: The analysis included seven studies, with a total sample of 3,165. At 95% confidence interval, the pooled sensitivity and specificity of PSQ were 89.7 (CI: 83.5-93.8) and 97.8 (CI: 94.9-99.1) for Isoniazid, 94.6 (CI: 90.9-96.8) and 98.5 (CI: 96.5-99.3) for Rifampicin, 87.9 (CI: 81.2-92.4) and 98.8 (CI: 97.2-99.5) for Fluoroquinolone, 83.5 (CI: 72.8-90.5) and 99.4 (CI: 98.3-99.8) for Amikacin, 79 (CI: 67-8-87) and 97.9 (CI: 95.5-99) for Capreomycin, and 69.6 (CI: 57-79.8) and 98.2 (CI: 95.9-99.2) for Kanamycin. The overall pooled sensitivity and specificity were 85.8 (CI: 76.7-91.7) and 98.5 (CI: 96.5-99.3), respectively. CONCLUSION: According to the pooled data, PSQ is highly sensitive and specific for detecting M/XDR-TB, both from clinical specimens and culture isolates, and within a shorter turnaround time. We suggest a continued synthesis of the evidence on the cost-effectiveness and technical feasibilities of PSQ in low-income countries context, including sub-Saharan Africa.

Human papillomavirus self-sampling versus standard clinician-sampling for cervical cancer screening in sub-Saharan Africa: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Human papillomavirus (HPV) infection remains a major health threat in sub-Saharan Africa (SSA). HPV self-sampling could help find and treat cervical cancer at an early stage. We aimed to evaluate the effectiveness of HPV self-sampling over the standard health facility-based clinician-sampling for cervical cancer screening through a systematic review and meta-analysis of available randomized controlled trials. METHOD: We searched PubMed, Cochrane Central Register of Controlled Trials, ClinicalTrial.gov, and the WHO Global Health Library for articles in SSA published as of 31 May 2020. We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 guidelines for the design and reporting of the results. We included randomized control trials that compared HPV self-sampling with the standard of care. The primary endpoint was uptake of cervical cancer screening service. The secondary endpoints were linkage to care, acceptability, screening frequency, and adverse events. We used RevMan V.5.3 software for statistical analysis. We computed random-effect model to provide pooled estimates of available data and I-squared (I2) test to assess heterogeneity. RESULT: Of 77 citations, we included four trials from Nigeria, Ethiopia, Kenya, and Uganda, encompassing 8200 participants with age ranging from 25 to 65 years. The pooled analysis showed significantly higher uptake of cervical cancer screening in women who used HPV self-sampling (risk ratio [RR] 1.72, 95% CI 1.58-1.87; p = 0.01), while this had a considerable heterogeneity as explained by subgroup analysis. Uptake was higher in women who were offered sampling kit at home or work (RR 2.05, 95% CI 1.80-2.33) and those who's kit was mailed to or invited to a nearby health center (RR 1.65, 95% CI 1.58-1.72, I2 = 0%) than those screened with the standard of care. There was no difference between the two groups in the rate of linkage to care of positive cases (RR 1.30, 95% CI 0.90-2.74, I2 = 91%). HPV self-sampling was acceptable and easy to use. None of the trials compared the frequency of screening or adverse events. CONCLUSION: HPV self-sampling is an effective and feasible alternative to the standard health facility-based clinician-sampling for cervical cancer screening in SSA. It could improve the uptake of cervical cancer screening and harness the global strategy towards elimination of cervical cancer by 2030.

Efficacy and safety of dihydroartemisinin-piperaquine versus artemether-lumefantrine for treatment of uncomplicated Plasmodium falciparum malaria in Ugandan children: a systematic review and meta-analysis of randomized control trials.

BACKGROUND: The emergence of artemisinin resistance in Southeast Asia and Plasmodium falciparum kelch13 propeller gene mutations in sub-Saharan African pose the greatest threat to global efforts to control malaria. This is a critical concern in Uganda, where artemisinin-based combination therapy (ACT) is the first-line treatment for uncomplicated falciparum. The objective of this study was to compare the efficacy and safety of dihydroartemisinin-piperaquine (DHA-PQ) and artemether-lumefantrine (AL) for the treatment of uncomplicated falciparum malaria in Ugandan children. METHODS: A search of PubMed and the Cochrane Central Register of Controlled Trials for retrieving randomized controlled trials comparing the efficacy and safety of DHA-PQ and AL for treatment of uncomplicated falciparum malaria in Ugandan children was done. The search was performed up to 31 August 2020. The data extracted from eligible studies and pooled as risk ratio (RR) with a 95% confidence interval (CI), using Rev Man Software (5.4). The protocol was registered in PROSPERO, ID: CRD42020182354. RESULTS: Eleven trials were included in this review and two of them only included under safety outcome. Total 3798 participants were enrolled. The PCR unadjusted treatment failure was significantly lower with DHA-PQ at day 28 (RR 0.30, 95% CI 0.19-0.49; participants = 7863; studies = 5; I2 = 93%, low quality evidence) and at day 42 (RR 0.53, 95% CI 0.38-0.76; participants = 1618; studies = 4; I2 = 79%, moderate quality of evidence). The PCR adjusted treatment failure at day 42 was significantly lower with DHA-PQ treatment group (RR 0.45, 95% CI 0.28 to 0.72; participants = 1370; studies = 5, high quality of evidence), and it was below 5% in both arms at day 28 (moderate quality of evidence). AL showed a longer prophylactic effect on new infections which may last for up to 63 days (PCR-adjusted treatment failure: RR 2.04, 95% CI 1.13-3.70; participants = 1311; studies = 2, moderate quality of evidence). Compared to AL, DHA-PQ was associated with a slightly higher frequency of cough (RR 1.07, 95% CI 1.01 to 1.13; 2575 participants; six studies; high quality of evidence). In both treatment groups, the risk of recurrent parasitaemia due to possible recrudescence was less than 5% at day 28. The appearance of gametocyte between 29 and 42 days was also significantly lower in DHA-PQ than AL (RR 0.26, 95% CI 0.12 to 0.56; participants = 623; studies = 2; I2 = 0%). CONCLUSION: Compared to AL, DHA-PQ appeared to reduce treatment failure and gametocyte carriage in Ugandan children. This may trigger DHA-PQ to become the first-line treatment option. Both treatments were safe and well-tolerated.

Tenofovir disoproxil fumarate for prevention of mother-to-child transmission of hepatitis B virus: A systematic review and meta-analysis of randomised control trials.

Hepatitis B virus (HBV) infection caused by mother-to-child transmission (MTCT) continues to pose challenges to global health. This study aimed to assess the efficacy and safety of tenofovir disoproxil fumarate (TDF) for preventing HBV MTCT. PubMed and the Cochrane Central Register of Controlled Trials were searched through August 2020. Randomised controlled trials (RCTs) were selected that evaluated the efficacy and safety of TDF for preventing MTCT of HBV compared with the standard of care, placebo or other HBV therapies. The primary outcomes were HBV MTCT rate and maternal HBV DNA level. Secondary outcomes were infant and maternal safety outcomes. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines, and prospectively registered on PROSPERO (CRD42020186275). Of 240 citations, three RCTs that involved 651 participants were included. The pooled result showed that TDF can reduce the risk of HBV MTCT after 6 months postpartum by 80% (risk ratio [RR] 0.2, 95% confidence interval [CI 0.06-0.7], n = 584) with low heterogeneity (I2  = 0%). TDF demonstrated HBV DNA suppression at delivery, though there was heterogeneity among individual studies (RR 0.13, 95% CI [0.08-0.20] and (RR 0.36, 95% CI [0.27-0.49]). Maternal and infant safety outcomes were comparable among treated and untreated mothers and infants born to them. The quality of evidence varied from high to very low. There is evidence that TDF effectively interrupted MTCT of HBV and suppressed HBV DNA level. Available studies on safety are very limited and heterogeneous, emphasising the need for additional RCTs with complete safety indicators.

IAT-TiMeS: Intra-Arterial Thrombectomy Transfer Metric Study in Texas.

OBJECTIVE: We aim to report intra-arterial thrombectomy transfer metrics for ischemic stroke patients that were transferred to hub hospitals for possible intra-arterial thrombectomy in multiple geographic regions throughout the state of Texas and to identify potential barriers and delays in the intra-arterial thrombectomy transfer process. METHOD: We prospectively collected data from 8 participating Texas comprehensive stroke/thrombectomy capable centers from 7 major regions in the State of Texas. We collected baseline clinical and imaging data related to the pre-transfer evaluation, transfer metrics, and post-transfer clinical and imaging data. RESULTS: A total of 103 acute ischemic stroke patients suspected/confirmed to have large vessel occlusions between December 2016 to May 2019 that were transferred to hubs as possible intra-arterial thrombectomy candidates were enrolled. A total of 56 (54%) patients were sent from the spoke to the hub via ground ambulance with 47 (46%) patients traveling via air ambulance. The median spoke arrival to hub arrival time was 174 min, median spoke arrival to departure from spoke was 131 min, and median travel time was 39 min. The spoke arrival time to transfer initiation was 68 min. CT-perfusion obtained at the spoke and earlier initiation of transfer were statistically associated with shorter transfer times. CONCLUSION: Transfer of intra-arterial thrombectomy patients in Texas may take over 4 h from spoke arrival to hub arrival. This time may be shortened by earlier transfer initiation and acceptance.

Uni- and interdisciplinary effects on round and handover content in intensive care units.

OBJECTIVE: The aim of this study was to explore differences in the verbal content of handovers and rounds conducted in uni- and interdisciplinary social contexts. We expected higher proportions of goals to be articulated during interdisciplinary rounds. BACKGROUND: Lack of explanatory connections between round improvement initiatives and outcomes suggest insufficient understanding about health care communications, especially the role of social interaction. METHODS: The recognition-primed abstract decomposition space (RP-ADS) was used to analyze the information content of nurse handovers and morning rounds in a unidisciplinary- (physicians only) and an interdisciplinary-round intensive care unit (ICU). Data were collected using audio recordings of rounds and handovers for five patients for 5 days each in both ICUs. RESULTS: Hierarchical log-linear analyses show strong associations between events (medical rounds vs. nurses' shift handovers), type (uni- vs. interdisciplinary), and focus (levels of the RP-ADS) with highly significant combined two-way and higher-order interactions, LRchi2(df=4) = 30.91, p < .0001. All tests of partial association were also highly significant. Differences among levels of the variables were evaluated using standardized residuals. CONCLUSION: Nurses focused on RP-ADS data and intervention levels, whereas physicians focused on diagnoses and expectations. Clinical goals that integrate these orientations emerged to a greater extent in interdisciplinary rounds. In addition, social context of rounds appears to influence nurse handovers. Unidisciplinary ICU nurse handovers consisted of a series of data- and intervention-related observations, whereas ICU nurse handovers in interdisciplinary ICUs tended to integrate data, interventions and clinical goals. APPLICATION: These results are relevant to the design and implementation of clinical communication improvement initiatives and support tools.

Coordination and continuity of intensive care unit patient care.

OBJECTIVE: Using Klein's model of team coordination, we explored the null hypothesis that intensive care unit (ICU) care coordination unfolds as a linear sequence. Our intent was to generate hypotheses for further research and to provide interim recommendations for improving care coordination. We also explored factors contributing to care coordination (e.g., role responsibilities, support tools). BACKGROUND: Although the body of clinical communications research is considerable, few studies address broader team processes in real-world environments; hence, these processes are not well understood. METHODS: All bedside communications for 5 ICU patients were recorded for 5 days per patient and were coded using Klein's model. Markov analysis was used to describe the care coordination process. Multivariate contingency table analysis and standardized parameter estimates described important contributing factors, and support tools were described using descriptive statistics. RESULTS: First-, second-, and third-order Markov analyses show that care coordination does not unfold as a linear sequence; however, Markov diagrams suggest some process structure. Standardized parameter estimates of factors contributing to care coordination were calculated from a statistically significant three-way model (chi2[df= 18] = 36.95, p < .005). Role-based differences depend on context, with important differences in contributions to care coordination occurring within rounds. Tools supported only 48% of conversations. CONCLUSION: Three alternative research hypotheses were defined with at least a minimal level of support. Testing these hypotheses present substantial theoretical, methodological, and data analysis challenges. APPLICATION: Within a research framework, recommendations for change could achieve significant gains for understanding and for reducing breakdowns in care coordination.

Information environments for supporting consistent registrar medical handover.

This study was two-fold in nature. Initially, it examined the information environment and the use of customary information tools to support medical handovers in a large metropolitan teaching hospital on four weekends (i.e. Friday night to Monday morning). Weekend medical handovers were found to involve sequences of handovers where patients were discussed at the discretion of the doctor handing over; no reliable discussion of all patients of concern occurred at any one handover, with few information tools being used; and after a set of weekend handovers, there was no complete picture on a Monday morning without an analysis of all patient progress notes. In a subsequent case study, three information tools specifically designed as intervention that attempted to enrich the information environment were evaluated. Results indicate that these tools did support greater continuity in who was discussed but not in what was discussed at handover. After the intervention, if a doctor discussed a patient at handover, that patient was more likely to be discussed at subsequent handovers. However, the picture at Monday morning remained fragmentary. The results are discussed in terms of the complexities inherent in the handover process.

Making patient safety the focus: crisis resource management in the undergraduate curriculum.

BACKGROUND: This paper examines the role of high fidelity simulation and crisis resource management in bridging the gap between theory and practice. Patient safety is fundamental to healthcare professional practice and is a common goal for healthcare providers. It provides a focus to motivate practitioners. Patient safety issues are not a priority in undergraduate curricula. Raising the profile at this level is crucial to improving the safety and quality of healthcare delivery. This paper explores the role of simulation in providing a realistic, safe environment for participants with different levels of experience to manage evolving crises in the context of their work environment. METHODS: The Southern Health Simulation and Skills Centre uses a patient safety focus in delivering a specialised educational programme adapted from aviation to healthcare. The programme, crisis resource management, enables participants to consolidate knowledge, attitudes and skills to achieve a deeper understanding of how their performance impacts on patient safety and the quality of healthcare provided. Self-reported written evaluation data was collected from participants of three different courses at Southern Health. RESULTS: Participants consistently report that these courses offer unique learning experiences that address aspects of workplace learning in ways that have not previously been possible. A video-assisted reflective process powerfully reinforces learning. CONCLUSION: Crisis resource management courses demonstrate the value of simulation in bridging the gap between 'knowing' and 'doing' and keeping the focus on patient safety. Recommendations are made for ways in which the core elements of crisis resource management philosophy can influence the conceptualization of a new medical curriculum.