Research Spotlight

Rahn, D.D., Richter, H.E., Sung, V.W., Larsen, W.I. and Hynan, L.S. (2021). “Design of a Randomized Clinical Trial of Perioperative Vaginal Estrogen Versus Placebo With Transvaginal Native Tissue Apical Prolapse Repair (Investigation to Minimize Prolapse Recurrence of the Vagina using Estrogen: IMPROVE).” Female Pelvic Med Reconstr Surg 27(1): e227-e233.

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OBJECTIVES: To provide the rationale and design for a randomized, double-blind clinical trial of conjugated estrogen vaginal cream (applied for at least 5 weeks preoperatively and continued twice-weekly through 12 months postoperatively) compared with placebo in postmenopausal women with symptomatic pelvic organ prolapse undergoing a standardized transvaginal native tissue apical repair. METHODS: Study population, randomization process, study cream intervention, masking of participants and evaluators, placebo cream manufacture, standardized surgical intervention, and collection of adverse events are described. The primary outcome of surgical success is a composite of objectively no prolapse beyond the hymen and the vaginal cuff descending no more than one third the vaginal length; subjectively, no sense of vaginal pressure or bulging; and no retreatment for prolapse at 12 months. Time-to-failure postoperatively will be compared in the 2 groups with continued surveillance to 36 months. Secondary outcomes assessed at baseline, preoperatively (ie, after at least 5 weeks of study cream), and postoperatively at 6 month intervals include validated condition-specific and general quality-of-life metrics, overall impression of improvement, sexual function, vaginal atrophy symptoms, and body image. Challenges unique to this study include design and manufacture of placebo and defining and measuring study drug adherence. RESULTS: Recruitment of 204 women is complete with 197 randomized. There have been 174 surgeries completed with 15 more pending; 111 have completed their 12 month postoperative visit. CONCLUSIONS: This trial will contribute evidence-based information regarding the effect of perioperative vaginal estrogen as an adjunct therapy to standardized transvaginal native tissue prolapse surgical repair.

Procter, B.C., Ross, C., Pickard, V., Smith, E., Hanson, C. and McCullough, P.A. (2020). “Clinical outcomes after early ambulatory multidrug therapy for high-risk SARS-CoV-2 (COVID-19) infection.” Rev Cardiovasc Med 21(4): 611-614.

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There is an emergency need for early ambulatory treatment of Coronavirus Disease 2019 (COVID-19) in acutely ill patients in an attempt to reduce disease progression and the risks of hospitalization and death. Such management should be applied in high-risk patients age > 50 years or with one or more medical problems including cardiovascular disease. We evaluated a total of 922 outpatients from March to September 2020. All patients underwent contemporary real-time polymerase chain reaction (PCR) assay tests from anterior nasal swab samples. Patients age 50.5 ± 13.7 years (range 12 to 89), 61.6% women, at moderate or high risk for COVID-19 received empiric management via telemedicine. At least two agents with antiviral activity against SARS-CoV-2 (zinc, hydroxychloroquine, ivermectin) and one antibiotic (azithromycin, doxycycline, ceftriaxone) were used along with inhaled budesonide and/or intramuscular dexamethasone consistent with the emergent science on early COVID-19 treatment. For patients with high severity of symptoms, urgent in-clinic administration of albuterol nebulizer, inhaled budesonide, and intravenous volume expansion with supplemental parenteral thiamine 500 mg, magnesium sulfate 4 grams, folic acid 1 gram, vitamin B12 1 mg. A total of 320/922 (34.7%) were treated resulting in 6/320 (1.9%) and 1/320 (0.3%) patients that were hospitalized and died, respectively. We conclude that early ambulatory (not hospitalized, treated at home), multidrug therapy is safe, feasible, and associated with low rates of hospitalization and death. Early treatment should be considered for high-risk patients as an emergency measure while we await randomized trials and guidelines for ambulatory management.

Potter, S.R., Hinojosa, R., Miles, C.D., O’Brien, D. and Ross, D.J. (2020). “Remote monitoring using donor-derived, cell-free DNA after kidney transplantation during the coronavirus disease 2019 pandemic.” Kidney Res Clin Pract 39(4): 495-500.

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BACKGROUND: Donor-derived, cell-free DNA (dd-cfDNA) level correlates with allograft injury with clinical validity and utility for quiescence and active acute rejection (AR) in kidney transplant recipients. We analyzed trends in dd-cfDNA level immediately preceding and during the coronavirus disease 2019 (COVID-19) pandemic with implemented “shelter in place” and a tele-health strategy with remote home phlebotomy to limit COVID-19 exposure. METHODS: During COVID-19 in the United States (US), we surveyed weekly (January 6, 2020-May 25, 2020) metrics for dd-cfDNA corresponding to both a low risk for active rejection (dd-cfDNA < 0.5%) and cohorts with indeterminate levels of 0.5% to 1.0% and > 1.0%. During the study timeframe, over 11,000 patient samples (67%) from 150 kidney transplantation centers were transitioned from standard facility-based to remote phlebotomy. RESULTS: The proportion of dd-cfDNA samples, analyzed in 21 weekly aggregated cohorts by risk-stratification category, was unchanged during the COVID-19 escalation in the US. Linearized slopes for numbers of samples corresponding to indeterminate risk for AR cohorts of > 1.0% and 0.5% to 1.0% were -0.31 and -0.12, respectively; indicating that prevalence of these “at risk for AR cohorts” decreased during remote surveillance. Approximately 73% of samples corresponded to low risk of AR (dd-cfDNA < 0.5%), while an additional 15% of samples had dd-cfDNA level ≤ 1.0%. CONCLUSION: The combination of remote home phlebotomy including dd-cfDNA analysis and a tele-health program offer a new paradigm that may substantially improve patient compliance and assuage anxiety regarding the state of kidney allograft health during the COVID-19 pandemic. Further prospective multi-center studies with robust outcomes data are warranted.

Pham, P.H., Stalter, L.N., Martinez, E.J., Wang, J.F., Welch, B.M., Leverson, G., Marka, N., Al-Qaoud, T., Mandelbrot, D., Parajuli, S., Sollinger, H.W., Kaufman, D., Redfield, R.R., 3rd and Odorico, J.S. (2020). “Large Single Center Results of Simultaneous Pancreas-Kidney Transplantation in Patients with Type 2 Diabetes.” Am J Transplant Dec 22. [Epub ahead of print].

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Studies have found similar outcomes of Simultaneous Pancreas-Kidney transplantation (SPKT) in patients with Type 2 (T2D) and Type 1 diabetes (T1D). However, there are few data evaluating the association of recipient factors such as age, BMI, or pre-transplant insulin requirements with outcomes, thus the criteria for the optimal recipient selection remains unclear. In this study, 284 T1D and 39 T2D patients, who underwent SPKT between 2006-2017 with 1 year of follow-up at minimum, were assessed for potential relationship of pre-transplant BMI and insulin requirements with post-transplant diabetes and pancreatic graft failure. Kaplan-Meier analysis showed similar rates of freedom from post-transplant diabetes (94.7% T2D vs. 92.3% T1D at 1 yr, and 88.1% T2D vs. 81.1% T1D at 5 yrs) and graft survival (89.7% T2D vs. 90.4% T1D at 1 yr, and 89.7% T2D vs. 81.2% T1D at 5 yrs). There was no significant association between BMI or pre-transplant insulin requirements with post-transplant diabetes occurrence in either T1D (p = 0.10, 0.43, respectively) or T2D (p = 0.12, 0.63) patients in the cohort; or with graft failure (T1D: p = 0.40, 0.09; T2D: p = 0.71, 0.28). These observations suggest a less restricted approach to selective use of SPKT in patients with T2D.

Pennington, M.L., Ylitalo, K.R., Lanning, B.A., Dolan, S.L. and Gulliver, S.B. (2021). “An epidemiologic study of suicide among firefighters: Findings from the National Violent Death Reporting System, 2003 – 2017.” Psychiatry Res 295: 113594

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Suicide is a significant concern among fire service due to high rates of suicide behaviors. The aim of this study was to describe suicides among firefighters using national suicide death data. Data from the National Violent Death Reporting System for 722 firefighters and 192,430 non-firefighters were analyzed to compare sociodemographics and risk factors between firefighter and non-firefighter decedents; and among firefighters based on suicide means. A greater proportion of firefighter decedents died by firearm compared to non-firefighters. Firefighter decedents were less likely to have been diagnosed with depression, but more likely to have been diagnosed with post-traumatic stress disorder compared to non-firefighters. A greater percentage of firefighter decedents had a relationship or physical health problem prior to death, but a lower percentage had a history of suicide thoughts/attempts. Among firefighter decedents, multivariate analysis showed physical health problems and disclosing suicide intent predicted death by firearm. Greater awareness of risk factors, reduced access to lethal means, and ensuring access to behavioral health services may aide in decreasing suicide mortality in this population. These findings should be interpreted with caution due to limitations concerning report accuracy, generalizability, small female sample size, and inclusion of data only for lethal suicide attempts.