Effi cacy and safety of single-dose liposomal amphotericin B for visceral leishmaniasis in a rural public hospital in Bangladesh: a feasibility study

Background To rapidly reduce the burden of visceral leishmaniasis for national elimination programmes, an acceptable, safe, and eff ective treatment is needed that can be delivered at primary health-care centres. We aimed to assess the tolerability, safety, and cure rate of single-dose liposomal amphotericin B (AmBisome, Gilead, USA) for visceral leishmaniasis treatment in such a setting in Bangladesh. Methods We enrolled patients who had been diagnosed with visceral leishmaniasis at Muktagacha upazila (subdistrict) hospital, Bangladesh. Eligible participants were at least 5 years old and had a history of fever for more than 2 weeks, splenomegaly, rK39 rapid test positivity, and haemoglobin concentrations of at least 50 g/L. Participants were provided a one-off intravenous infusion of liposomal amphotericin B (10 mg/kg bodyweight). Clinical assessments were done during treatment, before hospital discharge, and on days 30 and 180 after treatment. Cure was defi ned as resolution of fever, decrease in spleen size, and an increase in haemoglobin by 10% compared with baseline or to at least 100 g/L. We estimated effi cacy in terms of initial cure (at day 30) and fi nal cure (at 6 months), and safety in all patients who were enrolled (intention-to-treat analysis). We also assessed effi cacy in all patients who completed treatment and 6 month follow-up after treatment with or without visceral leishmaniasis relapse (per protocol analysis). We assessed acceptability in terms of proportion of patients who consented to treatment. This study was registered with the Australian New Zealand Clinical Trial Registry, number CTRN12612000367842. Findings Between March 5, and Aug 14, 2012, 329 (55%) of 594 cases of suspected visceral leishmaniasis were confi rmed. Of these cases, fi ve patients did not consent to treatment and 24 were ineligible for treatment. In the intention-to-treat analysis, 261 (87%) of 300 patients achieved initial cure and 290 (97%) achieved fi nal cure. In the per-protocol analysis, 260 (88%) of 296 patients achieved initial cure and 289 (98%) achieved fi nal cure. One patient did not start treatment owing to an allergic reaction to liposomal amphotericin B. During treatment or within 2 h afterwards, 79 (26%) patients developed fever, 109 (36%) had fever with rigor, and 56 (19%) had hypotension. No patients needed referral to a tertiary hospital for management of adverse events. Interpretation Treatment of visceral leishmaniasis in a primary health-care facility with single-dose liposomal amphotericin B could safely and eff ectively be adopted by the national visceral leishmaniasis elimination programme in Bangladesh

Can a multicomponent multidisciplinary implementation package change physicians' and nurses' perceptions and practices regarding thrombolysis for acute ischemic stroke? : an exploratory analysis of a cluster-randomized trial

Background: The Thrombolysis ImPlementation in Stroke (TIPS) trial tested the effect of a multicomponent, multidisciplinary, collaborative intervention designed to increase the rates of intravenous thrombolysis via a cluster randomized controlled trial at 20 Australian hospitals (ten intervention, ten control). This sub-study investigated changes in self-reported perceptions and practices of physicians and nurses working in acute stroke care at the participating hospitals. Methods: A survey with 74 statements was administered during the pre-and post-intervention periods to staff at 19 of the 20 hospitals. An exploratory factor analysis identified the structure of the survey items and linear mixed modeling was applied to the final survey domain scores to explore the differences between groups over time. Result: The response rate was 45% for both the pre-(503 out of 1127 eligible staff from 19 hospitals) and post-intervention (414 out of 919 eligible staff from 18 hospitals) period. Four survey domains were identified: (1) hospital performance indicators, feedback, and training; (2) personal perceptions about thrombolysis evidence and implementation; (3) personal stroke skills and hospital stroke care policies; and (4) emergency and ambulance procedures. There was a significant pre-to post-intervention mean increase (0.21 95% CI 0.09; 0.34; p < 0.01) in scores relating to hospital performance indicators, feedback, and training; for the intervention hospitals compared to control hospitals. There was a corresponding increase in mean scores regarding perceptions about the thrombolysis evidence and implementation (0.21, 95% CI 0.06; 0.36; p < 0.05). Sub-group analysis indicated that the improvements were restricted to nurses' responses. Conclusion: TIPS resulted in changes in some aspects of nurses' perceptions relating to the evidence for intravenous thrombolysis and its implementation and hospital performance indicators, feedback, and training. However, there is a need to explore further strategies for influencing the views of physicians given limited statistical power in the physician sample

Thrombolysis implementation intervention and clinical outcome : a secondary analysis of a cluster randomized trial

Background: Multiple studies have attempted to increase the rate of intravenous thrombolysis for ischemic stroke using interventions to promote adherence to guidelines. Still, many of them did not measure individual-level impact. This study aimed to make a posthoc comparison of the clinical outcomes of patients in the "Thrombolysis ImPlementation in Stroke (TIPS)"study, which aimed to improve rates of intravenous thrombolysis in Australia. Methods: A posthoc analysis was conducted using individual-level patient data. Excellent (Three-month post treatment modified Rankin Score 0-2) and poor clinical outcome (Three-month post treatment modified Rankin Score 5-6) and post treatment parenchymal haematoma were the three main outcomes, and a mixed logistic regression model was used to assess the difference between the intervention and control groups. Results: There was a non-significant higher odds of having an excellent clinical outcome of 57% (odds ratio: 1.57; 95% CI: 0.73-3.39) and 33% (odds ratio: 1.33; 95% CI: 0.73-2.44) during the active-And post-intervention period respectively, for the intervention compared to the control group. A non-significant lower odds of having a poor clinical outcome was also found in the intervention, relative to control group of 4% (odds ratio: 0.96; 95% CI: 0.56-2.07) and higher odds of having poor outcome of 44% (odds ratio: 1.44 95% CI: 0.61-3.41) during both active and post-intervention period respectively. Similarly, a non-significant lower odds of parenchymal haematoma was also found for the intervention group during the both active-(odds ratio: 0.53; 95% CI: 0.21-1.32) and post-intervention period (odds ratio: 0.96; 95% CI: 0.36-2.52). Conclusion: The TIPS multi-component implementation approach was not effective in reducing the odds of post-Treatment severe disability at 90 days, or post-thrombolysis hemorrhage

Quality Assessment of Dried Blood Spots from Tuberculosis Patients from Four Countries

BACKGROUND: Dried blood spot (DBS) sampling is a blood collection tool that uses a finger prick to obtain a blood drop on a DBS card. It can be used for therapeutic drug monitoring, a method that uses blood drug concentrations to optimize individual treatment. DBS sampling is believed to be a simpler way of blood collection compared with venous sampling. The aim of this study was to evaluate the quality of DBSs from patients with tuberculosis all around the world based on quality indicators in a structured assessment procedure. METHODS: Total 464 DBS cards were obtained from 4 countries: Bangladesh, Belarus, Indonesia, and Paraguay. The quality of the DBS cards was assessed using a checklist consisting of 19 questions divided into 4 categories: the integrity of the DBS materials, appropriate drying time, blood volume, and blood spot collection. RESULTS: After examination, 859 of 1856 (46%) blood spots did not comply with present quality criteria. In 625 cases (34%), this was due to incorrect blood spot collection. The DBS cards from Bangladesh, Indonesia, and Paraguay seemed to be affected by air humidity, causing the blood spots not to dry appropriately. CONCLUSIONS: New tools to help obtain blood spots of sufficient quality are necessary and environmental specific recommendations to determine plasma concentration correctly. In addition, 3% of the DBS cards were rejected because the integrity of the materials suggesting that the quality of plastic ziplock bags currently used to protect the DBS cards against contamination and humidity may not be sufficient

Similarity Check: Quality Assessment of Dried Blood Spots from Patients With Tuberculosis from 4 Countries

Background: Dried blood spot (DBS) sampling is a blood collection tool that uses a finger prick to obtain a blood drop on a DBS card. It can be used for therapeutic drug monitoring, a method that uses blood drug concentrations to optimize individual treatment. DBS sampling is believed to be a simpler way of blood collection compared with venous sampling. The aim of this study was to evaluate the quality of DBSs from patients with tuberculosis all around the world based on quality indicators in a structured assessment procedure. Methods: Total 464 DBS cards were obtained from 4 countries: Bangladesh, Belarus, Indonesia, and Paraguay. The quality of the DBS cards was assessed using a checklist consisting of 19 questions divided into 4 categories: the integrity of the DBS materials, appropriate drying time, blood volume, and blood spot collection. Results: After examination, 859 of 1856 (46%) blood spots did not comply with present quality criteria. In 625 cases (34%), this was due to incorrect blood spot collection. The DBS cards from Bangladesh, Indonesia, and Paraguay seemed to be affected by air humidity, causing the blood spots not to dry appropriately. Conclusions: New tools to help obtain blood spots of sufficient quality are necessary and environmental specific recommendations to determine plasma concentration correctly. In addition, 3% of the DBS cards were rejected because the integrity of the materials suggesting that the quality of plastic ziplock bags currently used to protect the DBS cards against contamination and humidity may not be sufficient. Key Words: DBS, TB, quality, TDM, plasma concentration

Gauging the skin resident Leishmania parasites through a loop mediated isothermal amplification (LAMP) assay in post-kala-azar dermal leishmaniasis

Despite the availability of highly sensitive polymerase chain reaction (PCR)-based methods, the dearth of remotely deployable diagnostic tools circumvents the early and accurate detection of individuals with post-kala-azar dermal leishmaniasis (PKDL). Here, we evaluate a design-locked loop-mediated isothermal amplification (LAMP) assay to diagnose PKDL. A total of 76 snip-skin samples collected from individuals with probable PKDL (clinical presentation and a positive rK39 rapid diagnostic test (RDT)) were assessed by microscopy, qPCR, and LAMP. An equal number of age and sex-matched healthy controls were included to determine the specificity of the LAMP assay. The LAMP assay with a Qiagen DNA extraction (Q-LAMP) showed a promising sensitivity of 72.37% (95% CI: 60.91–82.01%) for identifying the PKDL cases. LAMP assay sensitivity declined when the DNA was extracted using a boil-spin method. Q-qPCR showed 68.42% (56.75–78.61%) sensitivity, comparable to LAMP and with an excellent agreement, whereas the microscopy exhibited a weak sensitivity of 39.47% (28.44–51.35%). When microscopy and/or qPCR were considered the gold standard, Q-LAMP exhibited an elevated sensitivity of 89.7% (95% CI: 78.83–96.11%) for detection of PKDL cases and Bayesian latent class modeling substantiated the excellent sensitivity of the assay. All healthy controls were found to be negative. Notwithstanding the optimum efficiency of the LAMP assay towards the detection of PKDL cases, further optimization of the boil-spin method is warranted to permit remote use of the assay

Rollout of a statewide Australian telestroke network including virtual reality training is associated with improved hyperacute stroke workflow metrics and thrombolysis rate

BackgroundTelestroke networks aim to address variability in both quality and access to stroke care in rural areas, by providing remote access to expert stroke neurologists. Implementation of telestroke requires adaptation of workflow processes and education. We previously developed virtual reality (VR) workflow training and documented acceptability, utility and feasibility. The effects on acute stroke treatment metrics have not been previously described.AimsThe overall aim was to improve hyperacute stroke metrics and shorten the time-to-reperfusion therapy administration in rural settings.MethodsThis study applies a natural experiment approach, collecting stroke metric data during transition from a pre-existing pilot to a statewide telestroke service at five rural hospitals. Pre- and post-intervention data included baseline patient demographics and assessment, diagnosis, and treatment delivery metrics. The primary study outcome was door-to-decision time (thrombolysis and endovascular thrombectomy). Secondary outcomes included door-to-computerized tomography time, door-to-thrombolysis time and proportion of patients receiving thrombolysis or thrombectomy treatment. Usage data relating to the VR stroke workflow training of interprofessional healthcare professionals was automatically captured via Wi-Fi. Statistical comparisons of clinical metrics between the pre- and post-intervention time periods, defined as the timeframes before and after VR deployment, were performed.ResultsA total of 2,683 patients were included (April 2013–December 2022); 1910 pre- and 773 post-intervention. All acute stroke time metrics significantly improved post-intervention. The primary outcome, door-to-decision time, decreased from 80 min [56–118] to 54 min [40–76; P &lt; 0.001]. Secondary outcomes also improved, including door-to-thrombolysis time (90 min [68–114] vs. 68.5 min [54–90]; P &lt; 0.001) and proportion of patients thrombolysed (11 vs. 16%; P &lt; 0.001). The proportion of patients transferred for thrombectomy was unchanged (6 vs. 7%; P = 0.69). Seventy VR sessions totaling 15 h 39 min of training time were logged. VR training usage varied across sites (3–31 sessions per site).ConclusionsDelivery of a multi-factorial intervention including infrastructure, funding, education and training (with VR workflow training) as part of a state-wide telestroke rollout was associated with improved acute stroke treatment metrics. Additional work is required to identify the contribution of each intervention component on clinical outcomes and to increase training uptake and sustainment

Amphotericin B deoxycholate for relapse visceral leishmaniasis in Bangladesh: a cross-sectional study

Abstract Objective Based on studies in India (as there was no studies from outside India) amphotericin B deoxycholate has been considered as a backup drug for treatment of visceral leishmaniasis. However, treatment response and adverse effect to anti-leishmanial drugs may vary across different populations and in Bangladesh the effect to amphotericin B deoxycholate for treatment of visceral leishmaniasis is still unknown. Therefore, there is a need to explore cure rate and adverse effects to amphotericin B deoxycholate to justify its use on visceral leishmaniasis patients in Bangladesh. Result Here we report 34 visceral leishmaniasis patients who received treatment with amphotericin B deoxycholate in the Surya Kanta Kala-azar Research Centre from December 2011 to June 2015. The dose of the treatment was 1 mg/kg body weight for 15 days followed up until 12 months after treatment. Response to amphotericin B deoxycholate treatment was excellent as all 34 patients achieved a final cure. Hypokalaemia (47%), shivering (47%), vomiting (35%) and acidity (15%) were most common adverse events. However, we did not observe any serious adverse events. Amphotericin B deoxycholate for relapse visceral leishmaniasis was found to be highly effective and safe. Our study justified to include amphotericin B deoxycholate as a second line drug for visceral leishmaniasis in Bangladesh

A comparative evaluation of the performance of commercially available rapid immunochromatographic tests for the diagnosis of visceral leishmaniasis in Bangladesh

Abstract Background Accurate and early diagnosis of Visceral Leishmaniasis (VL) is a prerequisite for proper treatment and restricting disease propagation in enldemic foci. An rK39 antigen-based immunochromatographic test is now recommended for its diagnostic accuracy and operational feasibility at point of care. In endemic regions of Bangladesh, rK39 or rKE16 antigen-based Rapid Diagnostic Tests (RDTs) are routinely performed on whole blood for diagnosis of VL. However, manufacturer’s instructions require use of serum. Therefore, we wanted to assess whether the diagnostic accuracy of these RDTs is as good on whole blood as on serum. Methods We evaluated and compared the sensitivity and specificity of five different commercially available RDTs on whole blood and on serum. We enrolled 30 VL patients, 35 endemic healthy controls and 30 Tuberculosis (TB) patients in our study from Mymensingh, a hyper-endemic region in Bangladesh. Results The sensitivity of all RDTs ranged between 96.67 % (95 % CI: 82.72-99.44 %) and 100 % (95 % CI: 96.34-100 %). The specificity ranged between 93.85 % (95 % CI: 84.97-98.26 %) and 98.46 % (95 % CI: 91.69-99.74 %), except for the Onsite leishmania Ab (Rev B) kit which showed markedly lower specificity (31.25-58.46 %). There was no significant difference in sensitivity and specificity between blood and serum. The Cohen kappa index (k >0.97) indicated excellent agreement. Conclusions We conclude from the study that the use of blood for RDT in lieu of serum is appropriate for diagnosis of VL in peripheral endemic regions provided the manufacturer recommendations are followed and the RDT is of good quality