Renal allograft procurement from living unrelated donors in Iran: What falls under the eclipse.

Renal transplantation is the treatment of choice for end stage kidney disease. However, despite all the efforts to expand the donor pool, the shortage of donors is increasing and as a consequence, there has been a significant increase in the number of patients on transplant waiting lists globally. Societies worldwide have employed different methods to address this, each with specific ethical concerns surrounding them. Over three decades ago, a governmentally regulated program of kidney transplantation from living unrelated donors was introduced in Iran and since practiced which has been the subject of hot debate in the literature. Nevertheless, despite all these extensive discussions and publications, several key aspects of the program have still not been properly elucidated and addressed. In this article, the author aims to illuminate some dark corners related to this issue that have largely escaped the notice of ethicists.

Efficacy and safety of booster vaccination against SARS-CoV-2 in dialysis and renal transplant patients: systematic review and meta-analysis.

INTRODUCTION: Patients under renal replacement therapy are at an increased risk of severe infection with SARS-CoV-2, and have been known to have impaired response to standard vaccination. This systematic review and meta-analysis aims at evaluating the efficacy of booster dose vaccination in this population. METHODS: A systematic review has been conducted to find trials on the booster dose vaccination in kidney transplant recipients (KTRs) or patients under dialysis. Data of seroconversion rates at different timepoints, especially 1 month prior and post-booster dose vaccination have been collected and analyzed. Effects of different factors including type of renal replacement therapy (RRT), vaccine type and brands, magnitude of response to the standard vaccination, and immunosuppression drugs on the response rates have been investigated. Meta-analyses were performed using software Stata v.17. RESULTS: Overall 58 studies were included. Both RRT patient subgroups represented significant seroconversion, post- (versus pre-) booster dose vaccination, but only in KTRs the booster dose seroconversion surpassed that of the standard protocol. T-cell response was also significantly augmented after booster vaccination, with no difference between the RRT subgroups. mRNA and vector vaccine types had comparable immunogenicity when employed as boosters, both significantly higher than the inactivated virus vaccine, with no significant disparity regarding the vaccine brands. Patients with poor response to standard vaccination had a significant response to booster dose, with dialysis patients having stronger response. The differential effects of vaccine types and brands in the poor responders was similar to that of the overall RRT population. No rejection episodes or graft failure post-booster vaccination was reported. CONCLUSION: In patients under RRT, booster dose vaccination against SARS-CoV-2 is safe and efficacious determined by significant seroconversion, and therefore, it should be considered to be implemented in all these patients. Since in the KTR patients, the third dose vaccination significantly increased the seroconversion rates even beyond that of the standard protocol, three dose vaccine doses is recommended to be recognized as the standard vaccination protocol in this population. The same recommendation could be considered for dialysis patients, due to their augmented risk of breakthrough infection.

A Cost-effectiveness Analysis of Adding Cetuximab to the First-line Treatment of Metastatic Colorectal Carcinoma in Iran; Considering Genetic Screening for Precision Medicine.

PURPOSE: This study aimed to evaluate the cost-effectiveness of cetuximab in different genetic populations of metastatic colorectal carcinoma patients, including KRAS and RAS wild types and mutants, when added to FOLFIRI treatment regimens for evidence-based disease management in Iran. METHOD: A Markov decision model was designed in TreeAge software with the three states of stable, progress, and death. Clinical outcomes were extracted from published clinical studies, and costs were extracted from the Iranian local data. The primary outcome was an incremental cost-effectiveness ratio (ICER) in the simulated population. RESULTS: The cost-utility model from the perspective of the health system indicated that the average direct medical costs of a patient that has not been genetically screened are $56,985.27 and $20,767.74 in FOLFIRI + cetuximab and FOLFIRI regimens, respectively. However, costs per patient in the KRAS wild-type population were $21,845.52 in FOLFIRI and $78,321.22 in FOLFIRI + cetuximab. In RAS wild-type patients, FOLFIRI and FOLFIRI + cetuximab costs per patient were $23,111.62 and $84,976.39, respectively. Incremental QALYs for the above scenarios were 0.069, 0.193, and 0.285, respectively. Therefore, the ICER of add-on cetuximab in Iran compared to the treatment alternatives in the scenarios with and without KRAS screening was $520,771.55/QALY, $292,768.16/QALY, and $217,460.51/QALY. CONCLUSION: Although genetic screening in precision medicine reduces costs per outcome, according to the willingness-to-pay threshold of $4349.50 in the Iranian health system, add-on cetuximab to the FOLFIRI regimen is not a cost-effective strategy even with genetic screening and a 20% price reduction.

Heterogeneity in cardiorenal protection by Sodium glucose cotransporter 2 inhibitors in heart failure across the ejection fraction strata: Systematic review and meta-analysis.

BACKGROUND: Gliflozins or Sodium glucose cotransporter 2 inhibitors (SGLT2i) are relatively novel antidiabetic medications that have recently been shown to represent favorable effects on patients' cardiorenal outcomes. However, there is shortage of data on potential disparities in this therapeutic effect across different patient subpopulations. AIM: To investigate differential effects of SGLT2i on the cardiorenal outcomes of heart failure patients across left ventricular ejection fraction (LVEF) levels. METHODS: Literature was searched systematically for the large randomized double-blind controlled trials with long enough follow up periods reporting cardiovascular and renal outcomes in their patients regarding heart failure status and LVEF levels. Data were then meta-analyzed after stratification of the pooled data across the LVEF strata and New York Heart Associations (NYHA) classifications for heart failure using Stata software version 17.0. RESULTS: The literature search returned 13 Large clinical trials and 13 post hoc analysis reports. Meta-analysis of the effects of gliflozins on the primary composite outcome showed no significant difference in efficacy across the heart failure subtypes, but higher efficacy were detected in patient groups at lower NYHA classifications (I2 = 46%, P = 0.02). Meta-analyses across the LVEF stratums revealed that a baseline LVEF lower than 30% was associated with enhanced improvement in the primary composite outcome compared to patients with higher LVEF levels at the borderline statistical significance (HR: 0.70, 95%CI: 0.60 to 0.79 vs 0.81, 95%CI: 0.75 to 0.87; respectively, P = 0.06). Composite renal outcome was improved significantly higher in patients with no heart failure than in heart failure patients with preserved ejection fraction (HFpEF) (HR: 0.60, 95%CI: 0.49 to 0.72 vs 0.94, 95%CI: 0.74 to 1.13; P = 0.04). Acute renal injury occurred significantly less frequently in heart failure patients with reduced ejection fraction who received gliflozins than in HFpEF (HR: 0.67, 95%CI: 51 to 0.82 vs 0.94, 95%CI: 0.82 to 1.06; P = 0.01). Volume depletion was consistently increased in response to SGLT2i in all the subgroups. CONCLUSION: Heart failure patients with lower LVEF and lower NYHA sub-classifications were found to be generally more likely to benefit from therapy with gliflozins. Further research are required to identify patient subgroups representing the highest benefits or adverse events in response to SGLT2i.

Cost-Effectiveness of Dulaglutide Versus Liraglutide for Management of Type 2 Diabetes Mellitus in Iran.

OBJECTIVES: Diabetes mellitus (DM), as one of the most common metabolic diseases, is the ninth leading cause of death globally and imposes heavy costs on the health systems including both costs of treatment and management of secondary complications. This study intended to investigate the cost-effectiveness of dulaglutide compared with liraglutide in the management of patients with type 2 DM in Iran. METHOD: We conducted a cost-utility analysis using a 5-state Markov model from the health system perspective, over a 10-year time horizon, in 2018 in Iran. Sensitivity of the model has been evaluated through tornado diagram and using one-way sensitivity analysis. In addition, probabilistic sensitivity analysis has been accomplished using Monte Carlo simulation. RESULTS: The average costs of treatment of patients with type 2 DM using the dulaglutide and liraglutide treatment regimens are 17 577.09 and 18 517.54 US dollars per patient, respectively, over a 10-year time horizon. In terms of effectiveness, the average discounted quality-adjusted life-year rates are estimated at 5.560 and 5.403 for the dulaglutide and liraglutide treatment regimens, respectively. The model is mostly sensitive to the price of dulaglutide and liraglutide, the hemoglobin A1c reduction of liraglutide, and the utility resulting from less injection frequency of dulaglutide, respectively. CONCLUSION: Dulaglutide, in addition to being more effective, providing 0.156 more quality-adjusted life-years for the patients, reduces costs by 940.45 US dollars per patient over a 10-year time horizon. Therefore, due to the greater effectiveness and lower cost, it is concludable that dulaglutide is the cost-effective (incremental cost-effectiveness ratio = -6028.52) treatment alternative from the health system perspective.

Efficacy and safety of insulin detemir versus glargine in patients with diabetes: a systematic review and meta-analysis.

OBJECTIVES: Performing an updated meta-analysis to compare the safety and efficacy of insulin glargine and insulin detemir in adults with type 1 and type 2 diabetes. METHODS: Electronic databases were searched up to 18 August 2021. A random-effects model was applied to pool data from included studies to calculate the standardized mean differences (SMDs) for the continuous variables and relative risks (RRs) for the dichotomous variable. RESULTS: Nine studies compared insulin detemir and insulin glargine in type 2 diabetes and three studies in patients with type 1 diabetes. The pooled SMD of weight gain was -0.59 (95% CI -1.05 to -0.14; P=0.01; I2=98%) in patients with type 2 diabetes. The pooled RR of severe hypoglycemia was 0.28 (95% CI 0.12 to 0.63; P=0.002; I2=0%) in patients with type 1 diabetes. The effects of detemir and glargine on HbA1c, fasting plasma glucose, nocturnal hypoglycemia, and overall hypoglycemia were not statistically different (P>0.05). CONCLUSIONS: It was found that there is no clinically considerable difference between the impacts of insulin detemir and insulin glargine in diabetic patients. The only statistically significant differences were less weight gain in type 2 diabetes and fewer episodes of severe hypoglycemia in type 1 diabetes with insulin detemir.

Renal biopsy reports in nephritic syndrome: Update.

BACKGROUND: Nephritic syndrome (NiS) is a major indicator of serious renal diseases necessitating kidney biopsies for histopathological evaluations, but due to the lack of comprehensive reviews in the literature, the current understanding of the syndrome and its significance is limited. AIM: To collect all the evidence retrievable from the literature on the diagnoses made on the renal biopsies performed for NiS as the indication to the procedure. METHODS: A literature search was conducted to find studies reporting final diagnoses on renal biopsies in NiS patients. Data were pooled and analyzed with stratifications on age and regions. Meta-analyzes were performed using Stata v.9. RESULTS: Overall, 26414 NiS patients from the total number of 96738 kidney biopsy diagnoses reported by 47 studies from 23 countries from all continents (except sub-Saharan Africa) were found and analyzed. NiS was the indication for renal biopsy in 21% of the patient populations across the reviewed studies. Immunoglobulin A (IgA) nephropathy was the single most frequent diagnosis in these patients (approximately 38%) followed by lupus nephritis (approximately 8%) and Henoch Schönlein purpura (approximately 7%). IgA nephropathy was the most frequent diagnosis reported for the NiS patients from the East Asia, comprising half of all the cases, and least prevalent in South Asia. Considering the age subgroups, adult (vs pediatric or elderly) patients were by far the most likely age group to be diagnosed with the IgA nephropathy. A myriad of such regional and age disparities have been found and reported. CONCLUSION: As the indication for renal biopsy, NiS represents a very distinctive epidemiology of final renal disease diagnoses compared to the other major syndromes.

Cytokine Release Syndrome after Chimeric Antigen Receptor Transduced T-Cell Therapy in Cancers: A Systematic Review.

Patients with refractory or relapsed malignant disorders are in desperate condition, with few therapeutic options left, if any. Chimeric antigen receptor (CAR) transduced T-cell transplantation is a novel approach that has shown promising results as well as serious adverse events. This study aimed to systematically review the current data on the cytokine release syndrome (CRS) as a major side effect of CAR therapy. A systematic literature review was conducted to find reports of CAR T-cell therapy in the context of cancer patients and to extract reports of severe CRS. The factors that could significantly affect the incidence of CRS were investigated. Mortality rates were also compared regarding the occurrence of CRS. The incidence of severe CRS was 9.4% (95% confidence interval: 8.3-10.5) in the reviewed studies. Younger and older patients (vs. adults), higher doses of CAR T-cell infusions, lymphodepletion (LD) before CAR T-cell infusions, specific LD regimens, the source of allogeneic cells for the construction of CAR, chronic lymphocytic leukemia as the tumor type (vs. lymphoma), and CD28 as costimulatory domain in the structure of CAR were significantly associated with CRS events. Patients experiencing severe CRS had a significantly higher mortality rate within 2 and 3 months after transplantation. In conclusion, this study found many factors that could predict severe CRS and future clinical trials could reveal the relevance of appropriate interventions to the incidence and outcomes of CRS in cancer patients undergoing CAR T-cell transduced infusions.

Cost-effectiveness of ocrelizumab for treatment of Iranian patients with relapsing multiple sclerosis.

Background: The current study desired to conduct an economic analysis on ocrelizumab (OCR), a new relapsing multiple sclerosis (RMS) treatment strategy, in comparison to natalizumab (NTL), as one of the mostly-used disease-modifying therapies (DMTs) in Iran. Methods: A 31-health-state Markov model, based on Expanded Disability Status Scale (EDSS), containing patients on- and off-treatment with annual cycles was developed. Baseline demographics and utility scores were extracted from OPERA 1 and 2 trials. Confirmed disability progression (CDP) and annualized relapse rates (ARR) were extracted from the literature. Mortality was calculated based on age, sex, and disease state. Quality-adjusted life years (QALYs) and life years gained (LYG) were measurements of efficacy. Direct and indirect costs were identified and calculated based on the national book of tariffs in Iranian Rial (IRR) rates, then converted to the 2020 United States Dollar (USD). Final results were reported in terms of incremental cost-effectiveness ratio (ICER), which showed extra costs required for one additional QALY. Robustness of the model was analyzed through deterministic sensitivity analysis (DSA) and probabilistic sensitivity analysis (PSA). Results: OCR dominated NTL and was associated with cost-savings of 6971 USD, longer LYG (0.004), and higher QALYs (0.27). Although OCR had higher acquisition costs, which was the main component in both comparator arms, it was associated with lower total costs, due to lower disability progression and productivity loss. Results remained robust in DSA and PSA (93.5% cost-effectiveness in Iran's pharmacoeconomic threshold, 2709 USD). Conclusion: Results suggested that OCR was a more cost-effective option than NTL for the treatment of patients with RMS in Iran.

Cost-effectiveness analysis of tofacitinib compared with adalimumab and etanercept in the treatment of severe active rheumatoid arthritis; Iranian experience.

BACKGROUND AND OBJECTIVE: This study aimed to evaluate the cost-utility of Tofacitinib (TFC) in patients with severe rheumatoid arthritis (RA) who had not responded well to methotrexate from the Iranian payer's perspective. METHODS: An individual microsimulation Markov model was developed to compare TFC with etanercept (ETN) and Adalimumab (ADA) over a life-time horizon. Treatment efficacy was estimated based on the American College of Rheumatology (ACR) response improvement criteria in 6 months. Changes in the Health Assessment Questionnaire (HAQ) scores were mapped onto utility values to calculate outcomes in terms of QALYs. Direct medical costs were taken from national databases. Uncertainty in model parameters was evaluated by sensitivity analyses. RESULTS: This study demonstrated that TFC was cost-effective in both scenarios. Although TFC was associated with lower QALYs than ETN (6.664 versus 6.876), it was also associated with lower costs over a life-time horizon ($42,565.04 versus $58,696.29). Additionally, TFC was found to be the dominant strategy with a lower cost ($50,299.91 versus $51,550.29) and higher QALYs gained (6.900 versus 6.687) compared to ADA. CONCLUSION: TFC was found to be cost-effective in patients with severe RA who do not respond well to methotrexate compared to ADA, ETN in Iran.

Teriparatide in the Treatment of Severe Postmenopausal Osteoporosis: A Cost-Utility Analysis.

Teriparatide is a new agent serves as a treatment of choice for severe post-menopausal osteoporotic patients who are at high risk of fracture or have failed or been intolerant of previous osteoporosis therapy. The objective of this study is to estimate the cost-utility of teriparatide compared with no treatment from health system perspective in Iran. A micro-simulation model was developed for a cohort of hypothetical Iranian patient population (women aged 70 years, T-score -2.5 with previous fracture or T-score -3.0 without prior fracture) over a lifetime horizon. The model consisted of the seven health states. During each cycle, patients could have a fracture, remain healthy, remain in a post-fracture state or die. Background fracture risks, mortality rates, persistence rates, utilities, medical and drug costs were derived using published sources. Total accumulated life-time costs and quality-adjusted life years (QALYs) were estimated. Teriparatide was associated with 4.786 QALYs and total direct costs of IRR 143,168,259 over a lifetime horizon. Compared to no treatment, teriparatide provided an additional 0.145 QALY at an incremental cost of IRR 33,511,013. The resulting incremental cost-effectiveness ratio was IRR 230,333,030/QALYs gained. The probabilistic analysis showed that accepting a willingness-to-pay 2 and 3 GDP/capita in Iran, the probability of teriparatide being cost-effective were 51% and 83%, respectively. Compared to no treatment, teriparatide was indicated to be more costly and associated with fewer fractures, more life-years, and more QALYs. The result showed that teriparatide may be considered a cost-effective intervention when targeted to the appropriate patients.

Cost-effectiveness of alemtuzumab and natalizumab for relapsing-remitting multiple sclerosis treatment in Iran: decision analysis based on an indirect comparison.

BACKGROUND: Alemtuzumab and natalizumab are approved as second-line therapies for relapsing-remitting multiple sclerosis (RRMS) patients in Iran who have shown an inadequate response to other disease-modifying therapy (DMT). In the absence of head-to-head trials, evaluations based on decision analytic modeling may be a suitable alternative to compare alemtuzumab and natalizumab in RRMS. PURPOSE: To evaluate the cost-effectiveness of alemtuzumab compared with natalizumab in RRMS in Iran, based on an indirect comparison of clinical trial data. METHODS: A cost-utility analysis was conducted using a cohort-based Markov model to analyze cost-utility in a cohort of 1,000 RRMS patients treated with alemtuzumab or natalizumab who had failed at least one previous DMT. Costs were measured in 2018 US Dollars, and were estimated from both the societal and National Healthcare Service (NHS) perspective over a 20-year time horizon in Iran. One-way deterministic sensitivity analyses were carried out to investigate the impact of individual variables on model results. RESULTS: Alemtuzumab dominated natalizumab in both NHS and societal perspective analyses. From the NHS perspective, the total discounted costs per patient were estimated at $147,417 and $150,579 for alemtuzumab and natalizumab, respectively, over 20 years. The discounted quality-adjusted life years were estimated to be 7.07 and 6.05, respectively. Results were similar for the societal perspective analysis. Results were most sensitive to acquisition costs and the time horizon, while no sensitivity was observed for Expanded Disability Status Scale (EDSS) health-states utility, relapse relative risk, adverse event or EDSS-related costs, and laboratory/monitoring costs. CONCLUSION: Alemtuzumab was dominant in the treatment of RRMS compared with natalizumab due to lower total cost, greater efficacy and slowing of disease progression, and lower rate of relapses over a 20-year time horizon in Iran. Comparative head-to-head trials and long-term follow-up are needed to confirm these results.

Efficacy and Safety of Dulaglutide Compared to Liraglutide: A Systematic Review and Meta-analysis in Patients with Type 2 Diabetes Mellitus.

Diabetes mellitus has been always one of the most prevalent chronic diseases in the last decades. There exist a wide range of pharmacological agents for controlling this disease. However, these agents fare differently in terms of efficacy and safety. Hence, the aim of this study was to compare dulaglutide and liraglutide, two glucagon-like peptide-1 receptor agonists, in terms of efficacy and safety, drawing on a systematic review and meta-analysis. A systematic review and meta-analysis were carried out in January 2018. The articles were evaluated by two independent investigators and their quality was evaluated using Jadad scale and the Cochrane Collaboration's tools. Finally, the eligible articles entered the study. HbA1c and FBS were considered as efficacy outcomes. Safety profile was evaluated based on several outcomes such as serious side effects and vital signs. Three articles met the inclusion and exclusion criteria. The results indicated that the mean difference (MD) of HbA1c reduction was -0.10% (95% CI, -0.20% to -0.01%, P=0.03) in the patients who received dulaglutide in comparison with the patients who received liraglutide. In addition, dulaglutide was safer than liraglutide in terms of gastrointestinal problems (RR=0.85, 95% CI, 0.73 to 0.99, P=0.04, I2=55%) and heart rate (RR=-1.14, 95% CI, -1.90 to -0.38, P=0.003, I2=0%). Once-weekly dulaglutide showed a further reduction in HbA1c compared to once-daily liraglutide. However, comparisons between these regimens indicated no significant difference between groups in either FBS reduction or safety profile. Similarly, no statistically significant difference was observed in treatment discontinuation, hypoglycemia events, and vital signs.

COST-EFFECTIVENESS ANALYSIS OF IVABRADINE IN TREATMENT OF PATIENTS WITH HEART FAILURE IN IRAN.

OBJECTIVES: This study aimed to assess the cost-effectiveness of ivabradine plus standard of care (SoC) in comparison with current SoC alone from the Iranian payer perspective. METHODS: A cohort-based Markov model was developed to assess the incremental cost-effectiveness ratio (ICER) over a 10-year time horizon in a cohort of 1,000 patients. The baseline transition probabilities between New York Heart Association (NYHA), mortality rate, and hospitalization rate were extracted from the literature. The effect of ivabradine on mortality, hospitalization, and NYHA improvement or worsening were retrieved from the SHIFT study. The effectiveness was measured as quality-adjusted life-years (QALYs) using the utility values derived from Iranian Heart Failure Quality of Life study. Direct medical costs were obtained from hospital records and national tariffs. Deterministic and probabilistic sensitivity analyses were conducted to show the robustness of the model. RESULTS: Ivabradine therapy was associated with an incremental cost per QALY of USD $5,437 (incremental cost of USD $2,207 and QALYs gained 0.41) versus SoC. The probabilistic sensitivity analysis showed that ivabradine is expected to have a 60 percent chance of being cost-effective accepting a threshold of USD $6,550 per QALY. Furthermore, deterministic sensitivity analysis indicated that the model is sensitive to the ivabradine drug acquisition cost. CONCLUSIONS: The cost-effectiveness model suggested that the addition of ivabradine to SoC therapy was associated with improved clinical outcomes along with increased costs. The analysis indicates that the clinical benefit of ivabradine can be achieved at a reasonable cost in eligible heart failure patients with sinus rhythm and a baseline heart rate ≥ 75 beats per minute (bpm).

A Systematic Review of Clinical Practice Guidelines for Castration-Resistant Prostate Cancer.

Cancer constitutes a huge burden on societies in countries with any level of economic development. Prostate cancer is the first most diagnosed cancer of men in developed countries and the forth one in developing countries in terms of incidence rate. It is also the third incident cancer of men in Iran along with a prevalence of about 10,000 cases. Castration-resistant prostate cancer (CRPC) is a severe stage of the disease with a number of newly discovered treatment options. These therapeutic alternatives including abiraterone acetate, enzalutamide, cabazitaxel, immunotherapy with sipuleucel-T, radiopharmaceuticals and bone-targeted therapies (zoledronic acid, denosumab) along with docetaxel have made the decision making process complex and challenging for clinicians. In addition to the challenges of selecting the best-fit treatment, high costs of new pharmaceuticals and technologies necessitates the health policy-makers to develop practice guidelines in adaptation with local resources and limitations. The aim of this paper is to review the clinical guidelines for the management of CRPC. For better comprehension of guideline recommendations, the main clinical trials on new treatments were also identified. The efficacy and safety outcomes including but not limited to overall survival, progression free survival, quality of life and adverse effects were summarized. The guidelines of American Urological Association (AUA), National Comprehensive Cancer Network (NCCN), European Association of Urology (EUA), Spanish Oncology Genitourinary Group (SOGG), Asian Oncology Summit, Saudi Oncology Society-Saudi Urology Association combined guideline, National Institute for Health and Care Excellence (NICE) and Canadian Urological Association-Canadian Urologic Oncology Group (CUA-CUOG) were covered in this paper.

Interim Study: Comparison Of Safety And Efficacy of Levofloxacin Plus Colistin Regimen With Levofloxacin Plus High Dose Ampicillin/Sulbactam Infusion In Treatment of Ventilator-Associated Pneumonia Due To Multi Drug Resistant Acinetobacter.

Due to the emerging antibiotic resistance of Acinetobacter, which is the leading cause of ventilator-associated pneumonia (VAP) in critically ill patients, there is an urgent need for studies comparing various antibiotic regimens for its treatment. In this single blinded randomized clinical trial, adult patients with VAP due to multi drug resistant Acinetobacter (MDRA), were randomly assigned to receive 9×109 unit loading dose of colistin followed by 4.5×109 unit intravenously twice daily plus 750 mg intravenous levofloxacin daily or continuous infusion of ampicillin/sulbactam, 24g daily plus 750mg IV levofloxacin daily. Dose and dosing interval were adjusted according to serum creatinine levels during the study. Clinical and microbiological cure, inflammatory biomarkers, and possible adverse effects were recorded in participants. Twenty-nine patients were recruited (14 in colistin and 15 in ampicillin/sulbactam groups). Three patients were excluded in each group. Clinical response occurred in 3 (27%) and 10 (83%) in colistin and ampicillin-sulbactam arms, respectively (P = 0.007). Nephrotoxicity happened in 6 (54%) and 1 (8%) of cases in colistin and ampicillin-sulbactam groups, (P = 0.016). 14-day and 28-day survival rate were significantly higher in ampicillin-sulbactam group compared to colistin arm with P values of 0.002 and 0.049, respectively. This study revealed that levofloxacin plus high dose ampicillin/sulbactam as continuous infusion is more effective than levofloxacin plus colistin in patients with MDR Acinetobacter VAP with significantly lower risk of nephrotoxicity.

Cardiovascular manifestations of allograft dysfunction in renal transplant recipients: a review.

INTRODUCTION: Cardiovascular complications are the leading cause of death among renal transplant recipients; renal graft dysfunction has special effects on cardiovascular morbidity and mortality. REVIEW: Several studies have demonstrated a significant correlation between creatinine level and major coronary events, congestive heart failure and cerebrovascular events. Cardiovascular mortality has been related in different reports to serum creatinine levels and duration on renal replacement therapy. A low estimated glomerular filtration rate (eGFR) was also found to be a significant predictor of death in the pediatric kidney transplant population. Immunosuppressive therapy is also associated with several adverse effects. It has been shown that earlier withdrawal of steroids is associated with less cardiovascular effects, especially via reduction in the incidence of hypertension, hyperlipidemia, weight gain, and post-transplant diabetes. The introduction of calcineurin inhibitors (CNIs) has led to an increase in the number of renal transplant patients dying with a functioning graft, mainly because of cardiovascular disease. Compared to CNIs, mycophenolate mofetil has been proposed to reduce infiltration of circulating lymphocytes to the atherosclerotic plaque. Sirolimus is known to be associated with higher incidence of hyperlipidemia and hyperglycemia but lower incidence of hypertension. CONCLUSION: Dialysis duration, renal allograft dysfunction and the immunosuppressive agents used enhance cardiovascular risk among the renal transplantation population. Transplanted children are at a particularly high risk of cardiovascular events post-transplantation.

Pediatric patients with renal disease and cardiovascular complications: A literature review.

The cardiovascular burden of end stage renal disease (ESRD) in children has recently received more attention, and some authors have recommended that the origins of the increase in cardiovascular morbidity and mortality be found in childhood. In this comprehensive review of the literature, we aim to review the main and most recent studies evaluating cardiovascular risk factors in pediatric kidney disease patients. The literature suggests that ESRD, even in the pediatric population, is associated with a high rate of cardiovascular morbidity and mortality, and needs serious attention. Unfortunately, there is extreme scarcity of data on the efficacy of preventive strategies on cardiovascular morbidity and mortality in pediatric patients with renal disease. Therefore, authors of the current article recommend future studies to be directed to find beneficial and/or potential harmful effects of different interventions conventionally used in this population, including lifestyle modifications and pharmaceutical therapy on cardiovascular indices. Moreover, the effects of these drugs on the renal function of children with minimal kidney disease should be evaluated.