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Papers by Donald Molony

Dialysis & Transplantation, Mar 1, 2010

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Nephrology Dialysis Transplantation, 2012

Introduction and Aims: KAI-4169, a novel long acting peptide agonist of the calcium sensing recep... more Introduction and Aims: KAI-4169, a novel long acting peptide agonist of the calcium sensing receptor (CaSR), is being evaluated in hemodialysis (HD) subjects as a thrice weekly intravenous (IV) treatment for chronic kidney disease-mineral and mineral bone disorder (CKD-MBD). This Phase 2 randomized, double-blind, placebo-controlled, dose escalation study, evaluated the efficacy of KAI-4169 on serum intact parathyroid hormone (iPTH), FGF-23 and bone markers for formation (bone specific alkaline phosphatase; BSAP) and resorption (tartrate-resistant acid phosphatase 5b; TRAP5b). Methods: Sixty-eight subjects were randomized (1:1 to receive either KAI-4169 or placebo) and treated for 4 weeks (42 in 10 mg cohort and 26 in 5 mg cohort). Serum chemistries, iPTH, FGF-23 and BSAP and plasma TRAP5b were determined at selected time points. Results: KAI-4169 was well tolerated. No subject developed symptomatic hypocalcemia or discontinued due to adverse events. KAI-4169 treatment resulted in mean 33% and 49% reductions from baseline in iPTH at the end of the treatment phase in subjects treated with KAI-4169 5 mg and 10 mg, respectively (P<0.01 for comparison to placebo). At the end of treatment mean log FGF-23 levels were reduced from baseline by 7.0% and 11.3% in subjects treated with KAI-4169 5 mg and 10 mg, respectively (P<0.05 for comparison to placebo). Exploratory analyses showed that 4-week treatment with KAI-4169 was associated with an initial dose-dependent increase in BSAP at the end of treatment followed by a dosedependent reduction during the 4-week follow-up phase. Dose-dependent reductions in TRAP5b were observed at the end of treatment, and then tended to return toward baseline during the 4-week follow-up phase. At the end of treatment, median BSAP levels increased by 17.7% and TRAP5b levels decreased by 22.3% in subjects treated with KAI-4169 10 mg. Conclusions: Over a 4-week treatment period, KAI-4169 5 mg and 10 mg doses were associated with profound, dose-dependent reductions in iPTH and FGF-23. Preliminary data shows beneficial effects on bone markers of bone formation and resorption. These initial changes in bone markers are consistent with early changes observed following parathyroidectomy. KAI-4169 was well tolerated and represents a novel intravenous therapeutic approach for the treatment of CKD-MBD in hemodialysis patients with SHPT.

European Psychiatry, 2017

IntroductionElectroconvulsive therapy (ECT) is an efficacious treatment for many mental disorders... more IntroductionElectroconvulsive therapy (ECT) is an efficacious treatment for many mental disorders, but is underutilized because of fears of adverse effects, including the risk of death.Objectives and aimsTo provide a full picture of the magnitude of ECT-related mortality worldwide.MethodsWe performed a systematic review and meta-analysis (PubMed and Embase) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Only publications reporting on a specific number of ECT treatments as well as specific number of ECT-related deaths were included in our analysis. The ECT-related mortality rate was calculated by dividing the total number of ECT-related deaths by the total number of ECT treatments. The 95% confidence interval (95% CI) of this estimate was calculated using Bernoullis principle of distribution.ResultsFourteen studies with data from 32 countries reporting on a total of 757,662 ECT treatments met the predefined inclusion crit...

American Journal of Kidney Diseases, 1998

Dialysis & Transplantation, 2011

Annals of Internal Medicine

SOURCE CITATION Heerspink HJ, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in patients wi... more SOURCE CITATION Heerspink HJ, Stefánsson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383:1436-46. 32970396.

Annals of Internal Medicine, 2021

SOURCE CITATION Drekonja DM, Trautner B, Amundson C, et al. Effect of 7 vs 14 days of antibiotic ... more SOURCE CITATION Drekonja DM, Trautner B, Amundson C, et al. Effect of 7 vs 14 days of antibiotic therapy on resolution of symptoms among afebrile men with urinary tract infection: a randomized clinical trial. JAMA. 2021;326:324-31. 34313686.

Tienda online donde Comprar Evidence-Based Nephrology al precio 277,20 € de John Hubley | June Co... more Tienda online donde Comprar Evidence-Based Nephrology al precio 277,20 € de John Hubley | June Copeman | Donald A. Molony, M.D. | Jonathan C. Craig, tienda de Libros de Medicina, Libros de Epidemiologia, Salud Publica y Estadistica - Salud Publica

Chronic Kidney Disease, Dialysis, & Transplantation, 2005

American Journal of Kidney Diseases, 1997

American Journal of Kidney Diseases, Dec 1, 1996

• We report the first series demonstrating effective clearance of methotrexate using acute interm... more • We report the first series demonstrating effective clearance of methotrexate using acute intermittent hemodialysis with a high-flux dialyzer. The study was performed on six patients, two females and four males aged 13 to 72 years. All were patients at M.D. Anderson Cancer Center. Patients were dialyzed for 4 to 6 hours daily using a Fresenius F-80 membrane (Fresenius Inc, Walnut Creek, CA). Following the initiation of dialysis, there was a reduction in arterial and venous serum concentration of methotrexate with time. Mean plasma clearance of methotrexate during dialysis in these six patients was 92.1 ± 10.3 mL/min. One patient who was nearly functionally anephric was studied in detail. In this patient, following a high dose of methotrexate (7.2 g/m2), approximately 63% of this dose was cleared with 6 hours of hemodialysis. With subsequent dialysis performed daily for 6 hours, the drug was cleared completely in 5.6 ± 0.3 days (n = 7 separate methotrexate treatments). A reduction in plasma methotrexate concentration from 1,733 ± 40/~mol/L 1 hour postinfusion to less than 0.3/~mol/L in 5 to 6 days was observed for these seven separate treatments. We conclude that significant clearance of methotrexate can be achieved with high-flux dialyzers, making methotrexate therapy a viable treatment option in patients with responsive malignancies despite the presence of renal failure.

Cochrane Database of Systematic Reviews, Jan 20, 2003

IgA nephropathy (IgAN) is the most common primary glomerular disease with approximately 30% to 40... more IgA nephropathy (IgAN) is the most common primary glomerular disease with approximately 30% to 40% of patients progressing to end-stage kidney disease (ESKD) within 20 years. The most common regimens include immunosuppressive agents, however the risks of long-term treatment often outweigh the potential benefits. Non-immunosuppressive options, including fish oils, anticoagulants, antihypertensive agents and tonsillectomy have also been examined but not reviewed systematically. To assess the benefits and harms of non-immunosuppressive treatments for treating IgAN in adults and children. In July 2010 we searched the Cochrane Renal Group&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s specialised register, CENTRAL (in The Cochrane Library), MEDLINE (from 1966) and EMBASE (from 1980). We also searched reference lists of included studies, review articles and contacted local and international experts. Randomised controlled trials (RCTs) of non-immunosuppressive agents in adults and children with biopsy-proven IgAN were included. Two authors independently reviewed search results, extracted data and assessed study quality. Results were expressed as mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CI) using a random-effects model. We included 56 studies (2838 participants). Antihypertensive agents were the most beneficial non-immunosuppressive intervention for IgAN. The antihypertensives examined were predominantly angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB) or combinations of both, versus other antihypertensives and other agents. The benefits of antihypertensive agents, particularly inhibitors of the renin angiotensin system, appear to potentially outweigh the harms in patients with IgAN. The benefits are largely manifest as a reduction in proteinuria, a surrogate outcome. There is no evidence that treatment with any of the antihypertensive agents evaluated affect major renal and/or cardiovascular endpoints or long-term mortality risk beyond the benefit that arises from controlling hypertension in patients with IgAN. The RCT evidence is insufficiently robust to demonstrate efficacy for any of the other non-immunosuppressive therapies evaluated here. IgAN remains a disease in search of adequately powered RCTs to reliably inform clinical practice. More and better evidence is needed to understand the magnitude of benefit and the possible risks of anti-hypertensive or more specifically of ACEi/ARB therapy alone or in combination and which specific types of patients with the IgAN might have the greatest potential for benefit. For other non-immunosuppressive therapies, where neither benefit nor significant harm has yet to be demonstrated, there remains some justification for further exploration of the potential benefits.

Toxicology and Applied Pharmacology, Jul 1, 1993

Advances in Pediatrics, 1978

This review has necessarily been incomplete. We have not considered the potentially important int... more This review has necessarily been incomplete. We have not considered the potentially important interplay between PGs and male and female reproductive functions or the well-documented relationships between PGs and inflammation. We have examined the evidence for the influence of PGs on the pulmonary and peripheral vascular circulations and the interaction between PGs and the kidney and the autonomic nervous system. Emphasis has been placed on the role of PGs in the control of the circulation of the ductus arteriosus, and our recent experiences with indomethacin in sick, preterm infants with large left-to-right ductal shunting have been outlined. Existing information has been reviewed concerning PGs and the fetal-placental and fetal-maternal units. It should be clear that a host of proposed functions exists for PGs; many remain tentative in light of the conflicting and often bewildering results of animal experimentation.

Clinical Journal of The American Society of Nephrology, Aug 1, 2011

Background and objectives Although Henoch-Schö nlein purpura (HSP) is the most common form of ren... more Background and objectives Although Henoch-Schö nlein purpura (HSP) is the most common form of renal vasculitis in childhood, progression to ESRD is rare, and there are few data on outcomes of renal transplantation in patients with HSP. Design, setting, participants, & measurements This is a matched retrospective cohort study of renal allografts using the United Network of Organ Sharing database (1987 to 2005). Of the 189,211 primary renal allografts, there were 339 with a diagnosis of HSP. The primary end point was allograft survival. Results Compared with the remainder of the database, the HSP population was younger (25 years versus 46 years), and had a higher proportion of women (47% versus 40%), live donors (50% versus 35%), and Caucasians (77% versus 60%). Controlling for age, gender, donor source, ethnicity, and year of transplantation, death-censored graft survival for patients with HSP was 80.0% at 5 years and 58.8% at 10 years compared with 79.0% at 5 years and 55.4% at 10 years in the non-HSP population. Among patients with reported causes of graft loss, failure from recurrent disease occurred in 13.6% of patients with HSP, compared with 6.6% in the non-HSP population. When analyzing allograft survival in recipients with HSP compared with those with IgA nephropathy, there was no difference in 10-year allograft survival (58.4% and 59.3%, respectively). Conclusions These data indicate that although there is an increased risk of graft failure attributable to recurrent disease in patients with HSP, a diagnosis of HSP has little effect on overall renal allograft survival.

Annals of Internal Medicine, Jun 1, 2023

Healthcare, Nov 6, 2019

The n-of-1 trial can utilized in clinical practice as a decision support tool, which may improve ... more The n-of-1 trial can utilized in clinical practice as a decision support tool, which may improve patient outcomes by providing both the patient and the clinician with objective evidence to inform personalized treatment decisions. As its use broadens, it will be important to study whether the added time and effort of an n-of-1 trial results in measurable improvements in important patient outcomes compared to usual clinical practice. Parallel-group randomized clinical trials testing the n-of-1 approach versus usual care have been undertaken in a number of medical settings. A systematic review will be performed according to PRISMA guidelines, using MEDLINE, Embase, Cochrane, CINAHL, PsycINFO, Scopus, and Web of Science to search for randomized clinical trials in humans, without date or language restriction. Reports from the gray literature and ongoing studies in trial registries will be included. Articles will be screened by two independent reviewers with a third reviewer consulted to adjudicate disagreement. The quality of included studies will be assessed using the Cochrane Collaboration's tool for assessing risk of bias. A narrative synthesis will explore the differing methodological approaches of the included studies. The protocol will be registered in the PROSPERO registry, and the results of the review will be published in a peer-reviewed journal. To our knowledge, this systematic review will be the first to comprehensively assess the existing research on randomized trials testing the n-of-1 trial approach in clinical practice.

PLOS ONE, Jun 2, 2022

Background The single patient (n-of-1) trial can be used to resolve therapeutic uncertainty for t... more Background The single patient (n-of-1) trial can be used to resolve therapeutic uncertainty for the individual patient. Treatment alternatives are systematically tested against each other, generating patient-specific data used to inform an individualized treatment plan. We hypothesize that clinical decisions informed by n-of-1 trials improve patient outcomes compared to usual care. Our objective was to provide an overview of the clinical trial evidence on the effect of n-of-1 trials on clinical outcomes. Methods A systematic search of medical databases, trial registries, and gray literature was performed to identify trials assessing clinical outcomes in a group of patients undergoing an n-of-1 trial compared to those receiving usual care for any clinical condition. We abstracted elements related to study design and results and assessed risk of bias for both the overall randomized trials and the n-of-1 trials. The review was registered on PROSPERO. (CRD: 42020166490). Findings Twelve randomized trials of the n-of-1 approach were identified in conditions spanning chronic pain, osteoarthritis, chronic irreversible airflow limitation, attention-deficit hyperactivity disorder, hyperlipidemia, atrial fibrillation, statin intolerance, and hypertension. One trial showed a statistically significant benefit in the primary outcome. Only one reached the prespecified sample size target. Secondary outcomes showed modest benefits, including decreasing medication use, fewer atrial fibrillation episodes, and improved patient satisfaction. Interpretation Very few trials have been undertaken to assess the effectiveness of n-of-1 trials in improving clinical outcomes, and most trials were underpowered for the primary outcome. Barriers to

Advances in Chronic Kidney Disease, 2012

Nephrologists rely on valid clinical studies to inform their health care decisions. Knowledge of ... more Nephrologists rely on valid clinical studies to inform their health care decisions. Knowledge of simple statistical principles equips the prudent nephrologist with the skills that allow him or her to critically evaluate clinical studies and to determine the validity of the results. Important in this process is knowing when certain statistical tests are used appropriately and if their application in interpreting research data will most likely lead to the most robust or valid conclusions. The research team bears the responsibility for determining the statistical analysis during the design phase of the study and subsequently for carrying out the appropriate analysis. This will ensure that bias is minimized and &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;valid&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; results are reported. We have summarized the important caveats and components in correctly choosing a statistical test with a series of tables. With this format, we wish to provide a tool for the nephrologist/researcher that he or she can use when required to decide if an appropriate statistical analysis plan was implemented for any particular study. We have included in these tables the types of statistical tests that might be used best for analysis of different types of comparisons on small and on larger patient samples.

Journal of Nephrology, Jul 16, 2014

The recent multicenter, randomized, open-label INDEPENDENT study demonstrated that sevelamer impr... more The recent multicenter, randomized, open-label INDEPENDENT study demonstrated that sevelamer improves survival in new to hemodialysis (HD) patients compared with calcium carbonate. The objective of this study was to determine the cost-effectiveness of sevelamer versus calcium carbonate for patients new to HD, using patient-level data from the INDEPENDENT study. Cost-effectiveness analysis. Adult patients new to HD in Italy. A patient-level cost-effectiveness analysis was conducted from the perspective of the Servizio Sanitario Nazionale, Italy&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s national health service. The analysis was conducted for a 3-year time horizon. The cost of dialysis was excluded from the base case analysis. Sevelamer was compared to calcium carbonate. Total life years (LYs), total costs, and the incremental cost per LY gained were calculated. Bootstrapping was used to estimate confidence intervals around LYs, costs, and cost-effectiveness and to calculate the cost-effectiveness acceptability curve. Sevelamer was associated with a gain of 0.26 in LYs compared to calcium carbonate, over the 3-year time horizon. Total drug costs were &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;euro&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;3,282 higher for sevelamer versus calcium carbonate, while total hospitalization costs were &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;euro&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;2,020 lower for sevelamer versus calcium carbonate. The total incremental cost of sevelamer versus calcium carbonate was…