Evaluating the Impact of a Pharmacist-Led Antimicrobial Stewardship Intervention at Discharge in a Community, Nonteaching Hospital.

INTRODUCTION: Approximately 30% to 50% of hospital discharge antimicrobials are inappropriate. Limited data exist on approaches to improve antimicrobial prescribing practices at the time of discharge from a community hospital. Objective: To assess the impact of a comprehensive pharmacist-led antimicrobial stewardship intervention at discharge. METHODS: We conducted a quasi-experimental, pre-post study. A biphasic intervention took place on 2 medicine units from November 2019 to May 2020 at a community hospital. Baseline data were collected, followed by prescriber education on antimicrobial stewardship to both units (education phase). Next, a pharmacist-led intervention took place on one unit (intervention phase). The primary outcome was composite appropriateness of an oral antimicrobial prescribed to an adult at the time of discharge, defined by narrow spectrum of activity, dosing, and duration of therapy. The primary outcome was assessed using Fisher exact test. RESULTS: Baseline composite appropriateness was 30% (n = 12) on the control unit and 30.8% (n = 20) on the intervention unit. From baseline to posteducation, no significant change in composite appropriateness was found on the control (30% to 26.7%, P = 0.256) or intervention (30.8% to 19.4%, P = 0.09) unit. There was no significant difference between the education to intervention phase (26.7% vs 35%, P = 0.254) on the control unit. On the intervention unit, a significant difference in composite appropriateness was found from the education to intervention phase (19.4% vs 47.8%, P = 0.017). CONCLUSION AND RELEVANCE: A pharmacist-led intervention improved appropriateness of oral antimicrobials prescribed at discharge. One-time education was insufficient for improving antimicrobial stewardship.

Healthcare professional and community preferences in deceased donor kidney allocation: A best-worst scaling survey.

Deceased donor kidneys are a scarce community resource; therefore, the principles underpinning organ allocation should reflect societal values. This study aimed to elicit community and healthcare professional preferences for principles guiding the allocation of kidneys from deceased donors and compare how these differed across the populations. A best-worst scaling survey including 29 principles in a balanced incomplete block design was conducted among a representative sample of the general community (n = 1237) and healthcare professionals working in transplantation (n = 206). Sequential best-worst multinomial logistic regression was used to derive scaled preference scores (PS) (range 0-100). Thematic analysis of free text responses was performed. Five of the six most valued principles among members of the community related to equity, including priority for the longest waiting (PS 100), difficult to transplant (PS 94.5) and sickest (PS 93.9), and equitable access for men and women (PS 94.0), whereas the top four principles for healthcare professional focused on maximizing utility (PS 89.9-100). Latent class analysis identified unmeasured class membership among community members. There are discordant views between community members and healthcare professionals. These should be considered in the design, evaluation, and implementation of deceased donor kidney allocation protocols.

Emotional Contagion Scale and Mental Health Status during the First Wave of COVID-19 Pandemic, National Assessment.

Background: This great pandemic of COVID-19 has been a unique stressor that affected all communities in 2020. This study aims to examine the prevalence of anxiety and depression due to the COVID-19 pandemic in Saudi Arabia and to study the emotional cognition scale in the Kingdom of Saudi Arabia (KSA) in relation to the COVID-19 pandemic. Methodology: A descriptive cross-sectional study was conducted on 857 inhabitants randomly selected from the 13 administrative regions of Saudi Arabia, using a validated self-administrated questionnaire comprising six sections. The collected data were summarized and analyzed. Results: Among the majority of the studied participants, 377 (44.0%) were aged from 35 to less than 50 y. There were 489 (57.1%) females and 368 (42.9%) males, 616 (71.9%) Saudi nationals, 715 (83.4%) university-educated or postgraduate, 619 (72.2%) unmarried and 238 (27.8%) married, and 663 (77.4%) living in areas under partial lockdown. The resultant elevated total depression score was statistically significant (p<0.05) for the following: participants younger than 35y, females, Saudis, those with lower education levels, those who were married, students, those with work suspension during the COVID-19 pandemic, and amongst those who experienced complete lockdown. Among the majority of the studied participants, 355 (41.2%) showed mild depression, and 281(32.6) showed moderate anxiety, and were in the growth zone. In addition, the elevated total anxiety score was statistically significant (p<0.05) amongst the following; younger participants, females, Saudi nationals, those with lower educational levels, those who were unmarried, students, those with telework, and those with no curfew. Conclusion: The adverse mental health effects were more prevalent among particular groups of the population, such as females, adults under 35 years old, students, those with lower educational attainments, and those suffering from chronic illnesses. Anxiety was significantly correlated with depression. The practice of preventive measures, e.g., wearing masks, and social distancing to prevent the spread of COVID-19, may have had psychological benefits during the pandemic. Summary: We assessed the mental health status in Saudi Arabia during the first wave of the COVID-19 pandemic. Mild depression and moderate anxiety were prevalent problems, with many determinants and interrelations. Fear was the most infectious emotion, while happiness was the highest.

A Continuing Education Activity Durably Addressed Knowledge Gaps Related to Penicillin Allergies Among Pharmacists and Pharmacy Technicians.

Background: Penicillin allergy is one of the most frequent self-reported allergies; however, only about 10% of reported allergies are accurate. Objectives: Through the creation of a continuing pharmacy education (CPE) activity, we sought to assess knowledge gaps and comfort levels in the management of penicillin allergies. Methods: A 1-hour enduring-content CPE activity was offered as an interactive course from September 20, 2019, to September 20, 2020. Participants completed 3 surveys (pre-survey, post-survey, and follow-up survey). Participants were pharmacists and pharmacy technicians who completed, at a minimum, the activity and both pre- and post-surveys. The primary outcome was the percentage of participants scoring >80% on knowledge-based questions on the post-survey compared with the pre-survey. Secondary outcomes included pre-post comparisons on knowledge-based questions, participants' self-report of an allergy, and comfort levels dispensing cephalosporins in a patient with a self-reported penicillin allergy. Results: A total of 389 participants completed the CPE activity, with 176 included for analysis. Significantly more participants scored >80% on knowledge-based questions on the post-survey compared with the pre-survey (71.6% vs 22.7%, P < .001). There was no significant difference between the percentage of participants scoring >80% on the post-survey and the follow-up survey (71.6% vs 65%, P = .119). The majority of participants (74%) felt comfortable dispensing a cephalosporin in a patient with a penicillin allergy on the pre-survey, with similar percentages on the post- and follow-up surveys (77% and 90%, respectively). Conclusion: A targeted continuing education program improved overall knowledge, which was sustained for up to 2 months.

Prolonged immunosuppression does not improve risk of sensitization or likelihood of retransplantation after kidney transplant graft failure.

The optimum approach towards immunosuppression withdrawal following kidney transplant failure is unclear. Prolonged weaning may be associated with reduced sensitization, less graft nephrectomy and greater likelihood of retransplantation, but conversely increased risk of infection, malignancy and death. We conducted a single-centre retrospective analysis of patients experiencing graft failure between 2007 and 2017, comparing rates of sensitization, retransplantation, nephrectomy, infection, malignancy and death between patients who had immunosuppression weaned over <90 vs. 90-180 vs. >180 days. Patient survival after immunosuppression withdrawal over <90 vs. 90-180 vs. >180 days was 73.3%, 72.1% and 80.4%, respectively (P = 0.35), with no differences in cPRA (80.06 vs. 81.21 vs. 85.42, P = 0.66) or retransplantation rate [24/31 (77.4%) vs. 21/35 (60.0%) vs. 22/36 (61.1%), P = 0.13]. There was significantly less nephrectomy after late immunosuppression cessation [10/42 (23.8%) vs. 7/42 (16.7%) vs. 3/43 (7.0%), P = 0.01] but no differences in infections or malignancy. On competing risk regression (death as competing risk) controlling for cofactors including age, nephrectomy and rejection, prolonged immunosuppression did not predict likelihood of retransplantation (SHR 1.000, P = 0.88). Prolonged immunosuppression withdrawal does not reduce sensitization or improve retransplantation rates but is associated with less nephrectomy. Immunosuppression withdrawal should be tailored to individual circumstances after graft failure.

Very late-onset cytomegalovirus disease with ganciclovir resistance >15 years following renal transplantation.

Cytomegalovirus (CMV) infection is a significant cause of morbidity and mortality after solid organ transplantation. There has been a significant shift in disease epidemiology with the introduction of antiviral prophylaxis, with CMV disease occurring later and clinical presentations more atypical. We describe two cases of very late-onset CMV disease where first disease occurred 15 and 18 years post-renal transplantation, with both cases complicated by antiviral drug resistance. We subsequently review the published cases and literature of very late-onset CMV disease (onset > 10 years post-solid organ transplantation) as an increasingly recognized phenomenon which is emerging as an important aspect in improving long-term patient outcomes in the current era of renal transplantation.

Paediatric deceased donor kidney transplant in Australia: A 30-year review-What have paediatric bonuses achieved and where to from here?

BACKGROUND: In this 30-year national review, we describe trends in DD transplantation for paediatric recipients, assess the impact of paediatric allocation bonuses and identify outstanding areas of need for this population. METHODS: A retrospective review of all DD kidney only transplants to paediatric recipients (<18 years old) in Australia between 1989 and 2018 was conducted using deidentified extracts from the ANZDATA. RESULTS: Of the 1011 kidney only transplants performed in paediatric recipients during the study period, 426 (42%) were from deceased donors. Paediatric candidates on the DD waiting list had consistently higher rates of transplantation and shorter time from dialysis initiation to transplantation compared with adult candidates (median 372 vs 832 days in 2018, for example). Donor characteristics remained more favourable for paediatric recipients, despite a decline in the overall quality of the donor pool. The mean number of HLA antigen mismatches for paediatric recipients of DD transplants increased each decade (2.86 [1989-1998], 3.85 [1999-2008], 4.01 [2009-2018]). Both patient and graft survival have improved for paediatric DD transplant recipients in the most recent era (5-year graft and patient survival 85% vs 65% and 99% vs 94%, respectively, for 2009-2018 vs 1999-2008). CONCLUSIONS: The current DD kidney allocation system in Australia provides rapid access to high-quality organs for paediatric recipients, and early graft loss has decreased significantly in recent years; however, additional targeted interventions to address HLA matching may improve long-term outcomes in this population.

Insights into the labeling effect of Kidney Donor Performance Index reporting: The Australian experience.

In 2016, Australia began reporting the Kidney Donor Performance Index (KDPI) with all deceased donor kidney transplant offers despite this not being used in organ allocation rules, offering a unique opportunity to explore the "labeling effect" of KDPI reporting. We reviewed all kidneys retrieved for transplant in Australia from 2015 to 2018 and analyzed the association of KDPI reporting with organ nonutilization, number of offer declines, and donor/recipient age and longevity matching. Analyses were stratified by organ failure risk: higher risk (KDPI > 80%), standard risk (KDPI 20% to 79%), and lower risk (KDPI 0% to 20%). There was no significant difference in organ nonutilization post KDPI reporting either overall or for higher-risk kidneys. KDPI reporting was associated with an increase in offer declines for both higher-risk (incidence risk ratio 1.45, P = .007) and standard-risk (incidence risk ratio 1.22, P = .021) kidneys but not for lower-risk organs. There was a significant increase in recipient age and expected posttransplant survival score for higher-risk kidneys but no differences among other groups. We conclude that although KDPI reporting in Australia has been associated with an increased number of offer declines for higher-risk kidneys, this has not resulted in increased nonutilization and may have contributed to more appropriate use of these organs.

The potential role of antibodies against minor blood group antigens in renal transplantation.

Blood group antigens are red blood cell (RBC) surface markers comprising specific carbohydrate moieties attached to the glycolipids and glycoproteins within the membrane. In addition to the major ABO blood group antigens, at least 35 minor blood group antigens have been defined to date. These antigens have immunogenic potential and may cause a transfusion reaction. There is evidence for renal expression of antigens from the Kidd, MNS, Duffy and Lewis groups and therefore the potential for antibodies directed against these antigens to cross-react in a transplanted kidney. In individuals lacking a specific RBC antigen, antibodies may develop after de novo exposure to that antigen, in addition to the potential presence of pre-existing innate antibodies. Relatively little attention has been paid to non-ABO system antibodies, with most reports in the literature focusing on transfusion reactions rather than on any putative role in allograft rejection. Here, we review each of these antigens in the context of renal transplantation and what limited evidence there is on how such immunological risk may be assessed and managed.

Human leukocyte antigen eplet mismatches and long-term clinical outcomes in pediatric renal transplantation: A pragmatic, registry-based study.

BACKGROUND: HLA epitope-based matching offers the potential to improve immunological risk prediction and management in children receiving renal allografts; however, studies demonstrating the association between systems for defining epitope mismatches and clinical end-points are lacking in this population. METHODS: We conducted a pragmatic, retrospective, registry-based study of pediatric recipients of primary renal allografts in Victoria, Australia between 1990 and 2014 to determine the association between HLA EpMM and clinical outcomes including graft failure, re-transplantation and dnDSA formation. RESULTS: A total of 196 patients were included in the analysis with a median age of 11 years. Median follow-up period was 15 years during which time 108 (55%) primary grafts failed and 72 patients were re-transplanted. HLA class I but not class II EpMM was a significant predictor of graft failure on univariate analysis but not in adjusted models. EpMM was associated with reduced likelihood of re-transplantation in univariate but not adjusted analysis. Within the limitations of the study, class-specific EpMM was a strong predictor of dnDSA formation. Associations were stronger when considering only the subset of antibody-verified EpMM. CONCLUSION: Associations between HLA EpMM and clinical outcomes in pediatric renal allograft recipients seen on univariate analysis were attenuated following adjustment for confounders. These findings are inconclusive but suggest that HLA EpMM may provide one tool for assessing long-term risk in this population while highlighting the need for further clinical studies.

Baseline characteristics of patients with atypical haemolytic uraemic syndrome (aHUS): The Australian cohort in a global aHUS registry.

AIMS: To describe the baseline characteristics and treatment of Australian patients diagnosed with atypical haemolytic uraemic syndrome (aHUS) reported to the Global aHUS Registry. METHODS: Descriptive analysis of the Australian cohort with aHUS (n = 106) was undertaken for demographics, disease characteristics and prior treatment with eculizumab; comparing with the global cohort (n = 1688) for certain pre-specified disease characteristics. RESULTS: In Australia, almost two-thirds of patients diagnosed with aHUS were female and over 80% of patients were Caucasians, with similar proportions reported in the global cohort. Less than 6% of patients in the Australia and global cohorts were reported to have a history of autoimmune disease (4% vs 2%, respectively; P = .21) or cancer (5% vs 5%, respectively; P = .93), conditions that have been associated with secondary HUS. In the Australian cohort, 26% had received a kidney transplant and 68% of patients had received eculizumab. Kidneys were the most common organ involvement, followed by gastrointestinal tract (26%) and cardiovascular system (19%), with 35% of patients reported to have had at least two organs involved within 6 months prior to baseline visit or entry into the registry. Complement factor H was the most common pathogenic complement gene variant in the Australian patients. CONCLUSION: Data from the aHUS registry confirms and defines region-specific disease characteristics among a selected group of Australian children and adults with aHUS reported to the registry. Ongoing and more inclusive data will provide further information about temporal trends and treatment outcomes, representing a unique opportunity for clinicians and researchers to further develop knowledge surrounding this rare disease.

External validation of the US and UK kidney donor risk indices for deceased donor kidney transplant survival in the Australian and New Zealand population.

BACKGROUND: The US Kidney Donor Risk Index (KDRI) and the UK KDRI were developed to estimate the risk of graft failure following kidney transplantation. Neither score has been validated in the Australian and New Zealand (ANZ) population. METHODS: Using data from the Australia and New Zealand Organ Donor (ANZOD) and Dialysis and Transplant (ANZDATA) Registries, we included all adult deceased donor kidney-only transplants performed in ANZ from 2005 to 2016 (n = 6405). The KDRI was calculated using both the US donor-only and UK formulae. Three Cox models were constructed (Model 1: KDRI only; Model 2: Model 1 + transplant characteristics; Model 3: Model 2 + recipient characteristics) and compared using Harrell's C-statistics for the outcomes of death-censored graft survival and overall graft survival. RESULTS: Both scores were strongly associated with death-censored and overall graft survival (P < 0.0001 in all models). In the KDRI-only models, discrimination of death-censored graft survival was moderately good with C-statistics of 0.63 and 0.59 for the US and UK scores, respectively. Adjusting for transplant characteristics resulted in marginal improvements of the US KDRI to 0.65 and the UK KDRI to 0.63. The addition of recipient characteristics again resulted in marginal improvements of the US KDRI to 0.70 and the UK KDRI to 0.68. Similar trends were seen for the discrimination of overall graft survival. CONCLUSIONS: The US and UK KDRI scores were moderately good at discriminating death-censored and overall graft survival in the ANZ population, with the US score performing slightly better in all models.

Pre- and postdonation kidney function in donors of a kidney paired donation with unique criteria for donor glomerular filtration rate - a longitudinal cohort analysis.

Baseline predonation estimated GFR (eGFR) appears to predict the risk of postdonation chronic kidney disease in live donors. New KIDGO guidelines recommend an eGFR ≥90 ml/min/1.73 m2 as an acceptable level of glomerular filtration rate (GFR) for kidney donation. In the Australian Paired Kidney Exchange (AKX) program, all donors with a raw measured GFR (mGFR) ≥80 ml/min are deemed suitable for donation, but the significance of this selection indicator is unclear. We analysed the first 129 live donors in the AKX program with at least 1-year follow-up linking records in the AKX database and ANZDATA. There were 73 male and 56 female donors; mean (±SD) age was 53 ± 11 years. Predonation eGFR was 94 ± 13 ml/min/1.73 m2 , mGFR 99 ± 17 ml/min/1.73 m2 and raw mGFR 108 ± 18 ml/min. Baseline eGFR was <80 ml/min/1.73 m2 in 19 donors, and <90 ml/min/1.73 m2 in 42 donors. At 1 year postdonation eGFR was 68 ± 15 ml/min/1.73 m2 and the predicted eGFR at 30 years postdonation was on average 50 (29-83) ml/min/1.73 m2 . The hypothetical mean age at end-stage kidney disease was estimated to be 145 (95% CI 120-263) years. Over 30% of AKX live donors would have been excluded from donation using KDIGO guidelines. Using AKX donor guidelines, the majority of donors with predicted eGFR <30 ml/min/1.73 m2 30-year postdonation were aged ≥50 years. Long-term outcome data on AKX donors with low eGFR will need careful monitoring.

An examination of opioid prescription for Medicare Part D patients among family practice prescribers.

BACKGROUND: In the USA, opioid overdose accounted for more than 60% of drug overdose deaths in 2015. Of these deaths, 40% were due to use of prescription opioids. OBJECTIVES: The aims of the study were to (i) study family medicine physician opioid-prescribing rate and duration of prescription, (ii) study the distribution of prescription by medication potency, (iii) study opioid-prescribing trends in health care shortage areas and (iv) study the association between extreme high prescribing rates and medical board discipline. METHODS: This is a retrospective cross-sectional study of the 2015 Medicare Part D claim data. RESULTS: Family practitioners have opioid prescription rates (5.6%) similar to medical subspecialists (6.0%), but lower than pain specialists (53.2%) and surgical specialists (36.6%). Family practitioners have an average opioid prescription duration (21.5 days) similar to medical subspecialists (23.1 days) and pain specialists (27.1 days), but longer than surgical specialists (8.9 days). Family practitioners tend to prescribe lower potency opioids. Family practitioners in rural health care shortage areas have a higher opioid prescription rate than other family practitioners (6.5% versus 5.6%). Among the 52 family practitioners who prescribed opioids as frequently as pain specialists, 26 of the 52 (50%) were certified in pain management or worked with a partner certified in pain management. Of the other 26 family practitioners, 3 (12%) had medical board disciplinary actions regarding opioid prescription. CONCLUSIONS: While monitoring extreme prescribers is important and needs to be continued, the next step in policies to reduce prescription opioids will require systemic change, especially providing support for family practitioners in rural health care shortage areas.

Why do not all living kidney donor candidates proceed to donation?

There are national and international guidelines for donor workup and acceptance criteria of potential living kidney donor candidates (LKDC), but there is significant variation in clinical practice. We examined our local practice in assessing potential LKDC against current guidelines; nearly all of our accepted donors met these guidelines. LKDC who did not proceed to donation had an identified health issue (60%), the presence of risk factors for long-term end-stage kidney disease (17%), social (13%) or immunological reasons (7%).

Frequency and outcomes of kidney donation from intensive care patients with acute renal failure requiring renal replacement therapy.

BACKGROUND: Kidney transplantation is the preferred treatment for end-stage renal failure. Unfortunately, donor organ shortages prevent many individuals receiving a renal transplant and there is a need to increase the pool of appropriate donors. The presence of acute kidney injury (AKI) in deceased donors has traditionally been a relative contraindication to renal transplantation, even though renal recovery may be favorable in the absence of chronic renal disease. METHODS: We undertook an 8 years retrospective observational study of potential deceased organ donors with AKI requiring renal replacement therapy (RRT). We evaluated the rate of successful transplantation as well as short term and outcomes at a median of 19.5 (13.0-52.7) months after donation. RESULTS: Amongst 1058 consented potential organ donors, 39 patients had AKI requiring RRT, of which 19 became donors (13 not medically suitable, 7 did not proceed to donation). The median (interquartile range (IQR)) donor age was 41 (34-50) years and norepinephrine, epinephrine and vasopressin were given to 18, 14 and 9 donors, respectively. From the 38 donated kidneys 34 were transplanted. The median (IQR) age of recipients was 53 (42.8-58.5) years and they were dialysis free in a median (IQR) of 5.5 (2.3-10.8) days. Only minor abnormalities were found at 3 and 6 months renal biopsies, and two patients experienced graft failure in the first 12 months. CONCLUSION: Amongst deceased donors with AKI receiving RRT and vasoactive medications outcomes of renal transplantation seems acceptable in the absence of pre-existing renal failure and other donor co-morbidity. Such patients may be an important additional source of kidney donation.

Access to waitlisting for deceased donor kidney transplantation in Australia.

AIM: A detailed analysis of waitlisting for deceased donor kidney transplantation in Australia has not previously been reported. We aimed to determine if patient characteristics associated with waitlisting identify areas of potential inequality in access to transplantation in Australia. METHODS: A competing risk time-to-event model was used to determine predictors of waitlisting for all adult incident renal replacement therapy patients in Australia between 2006 and 2015. Secondary analysis was performed to determine predictors of overall access to transplantation (using a combined outcome of waitlisting and living donor transplantation). RESULTS: The cohort consisted of 21 231 patients with a median age of 63 years. Overall, 4361 (20.5%) were waitlisted and 1239 (5.8%) received a living donor transplant without being previously waitlisted. Primary analysis revealed that medical comorbidities, older age, smoking status and body mass index were all significant predictors of waitlisting and that and there was variation in waitlisting practice across states Despite adjustment for the above factors, demographic characteristics, including Indigenous ethnicity (subdistribution hazard ratios (SHR) 0.46 (95% confidence interval (CI) 0.38-0.55)), female gender (SHR 0.85 (95% CI 0.80, 0.91)) and residence in a regional area (SHR 0.88 (95% CI 0.81-0.95)) were also associated with a lower likelihood of waitlisting. Secondary analysis showed younger age and higher socio-economic advantage were additional predictors of overall access to transplantation, driven by higher rates of living donor transplantation. CONCLUSION: Demographic as well as clinical characteristics are associated with reduced likelihood of waitlisting for kidney transplantation in Australia. Further analysis and auditing should be considered to determine if this reflects other unmeasured factors or highlights a need to address inequality.

HLA Epitope Matching in Kidney Transplantation: An Overview for the General Nephrologist.

Rapid changes in tissue-typing technology, including the widespread availability of highly specific molecular typing methods and solid-phase assays for the detection of allele-specific anti-HLA antibodies, make it increasingly challenging to remain up to date with developments in organ matching. Terms such as epitopes and eplets abound in the transplantation literature, but often it can be difficult to see what they might mean for the patient awaiting transplantation. In this review, we provide the historical context for current practice in tissue typing and explore the potential role of HLA epitopes in kidney transplantation. Despite impressive gains in preventing and managing T-cell-mediated rejection and the associated improvements in graft survival, the challenge of the humoral alloresponse remains largely unmet and is the major cause of late graft loss. Describing HLA antigens as a series of antibody targets, or epitopes, rather than based on broad seroreactivity patterns or precise amino acid sequences may provide a more practical and clinically relevant system to help avoid antibody-mediated rejection, reduce sensitization, and select the most appropriate organs in the setting of pre-existing alloantibodies. We explain the systems proposed to define HLA epitopes, summarize the evidence to date for their role in transplantation, and explore the potential benefits of incorporating HLA epitopes into clinical practice as this field continues to evolve toward everyday practice.

Evaluation of HIV-1 rapid tests and identification of alternative testing algorithms for use in Uganda.

INTRODUCTION: The World Health Organization recommends that countries conduct two phase evaluations of HIV rapid tests (RTs) in order to come up with the best algorithms. In this report, we present the first ever such evaluation in Uganda, involving both blood and oral based RTs. The role of weak positive (WP) bands on the accuracy of the individual RT and on the algorithms was also investigated. METHODS: In total 11 blood based and 3 oral transudate kits were evaluated. All together 2746 participants from seven sites, covering the four different regions of Uganda participated. Two enzyme immunoassays (EIAs) run in parallel were used as the gold standard. The performance and cost of the different algorithms was calculated, with a pre-determined price cut-off of either cheaper or within 20% price of the current algorithm of Determine + Statpak + Unigold. In the second phase, the three best algorithms selected in phase I were used at the point of care for purposes of quality control using finger stick whole blood. RESULTS: We identified three algorithms; Determine + SD Bioline + Statpak; Determine + Statpak + SD Bioline, both with the same sensitivity and specificity of 99.2% and 99.1% respectively and Determine + Statpak + Insti, with sensitivity and specificity of 99.1% and 99% respectively as having performed better and met the cost requirements. There were 15 other algorithms that performed better than the current one but rated more than the 20% price. None of the 3 oral mucosal transudate kits were suitable for inclusion in an algorithm because of their low sensitivities. Band intensity affected the performance of individual RTs but not the final algorithms. CONCLUSION: We have come up with three algorithms we recommend for public or Government procurement based on accuracy and cost. In case one algorithm is preferred, we recommend to replace Unigold, the current tie breaker with SD Bioline. We further recommend that all the 18 algorithms that have shown better performance than the current one are made available to the private sector where cost may not be a limiting factor.

Consensus opinion on diagnosis and management of thrombotic microangiopathy in Australia and New Zealand.

Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. Although TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all adults, urgent, empirical plasma exchange (PE) should be started within 4-8 h of presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 (a disintegrin and metalloprotease thrombospondin, number 13) activity. A sodium citrate plasma sample should be collected for ADAMTS13 testing prior to any plasma therapy. In children, Shiga toxin-associated haemolytic uraemic syndrome due to infection with Escherichia coli (STEC-HUS) is the commonest cause of TMA, and is managed supportively. If TTP and STEC-HUS have been excluded, a diagnosis of aHUS should be considered, for which treatment is with the monoclonal complement C5 inhibitor, eculizumab. Although early confirmation of aHUS is often not possible, except in the minority of patients in whom auto-antibodies against factor H are identified, genetic testing ultimately reveals a complement-related mutation in a significant proportion of aHUS cases. The presence of other TMA-associated conditions (e.g. infection, pregnancy/postpartum and malignant hypertension) does not exclude TTP or aHUS as the underlying cause of TMA.