Real-World Effectiveness of Preventive Pharmacological Therapy in Patients With Urolithiasis: A Retrospective Cohort Study.

RATIONALE & OBJECTIVE: Data supporting the efficacy of preventive pharmacological therapy (PPT) to reduce urolithiasis recurrence are based on clinical trials with composite outcomes that incorporate imaging findings and have uncertain clinical significance. This study evaluated whether the use of PPT leads to fewer symptomatic stone events. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Medicare enrollees with urolithiasis who completed 24-hour urine collections that revealed hypercalciuria, hypocitraturia, low urine pH, or hyperuricosuria. EXPOSURE: PPT (thiazide diuretics for hypercalciuria, alkali for hypocitraturia or low urine pH, or uric acid lowering drugs for hyperuricosuria) categorized as (1) adherent to guideline-concordant PPT, (2) nonadherent to guideline-concordant PPT, or (3) untreated. OUTCOME: Symptomatic stone event occurrence (emergency department [ED] visit or hospitalization for urolithiasis or stone-directed surgery). ANALYTICAL APPROACH: Cox proportional hazards regression. RESULTS: Among 13,942 patients, 31.0% were prescribed PPT. Compared with no treatment, concordant/adherent PPT use was associated with a significantly lower hazard of symptomatic stone events for patients with hypercalciuria (HR, 0.736 [95% CI, 0.593-0.915]) and low urine pH (HR, 0.804 [95% CI, 0.650-0.996]) but not for patients with hypocitraturia or hyperuricosuria. These associations were largely driven by significantly lower rates of ED visits after initiating PPT among the concordant/adherent group versus untreated patients. Patients with hypercalciuria had adjusted 2-year predicted probabilities of a visit of 3.8% [95% CI, 2.5%-5.2%%] and 6.9% [95% CI, 6.0%-7.7%] for the concordant/adherent PPT and no-treatment groups, respectively. Among patients with low urine pH, these probabilities were 4.3% (95% CI, 2.9%-5.7%) and 7.3% (95% CI, 6.5%-8.0%) for the concordant/adherent PPT and no-treatment groups, respectively. LIMITATIONS: Potential bias from the possibility that patients prescribed PPT had more severe disease than untreated patients. CONCLUSIONS: Patients with urolithiasis and hypercalciuria who were adherent to treatment with thiazide diuretics as well as those with low urine pH adherent to prescribed alkali therapy had fewer symptomatic stone events than untreated patients. PLAIN-LANGUAGE SUMMARY: Despite multiple clinical trials demonstrating the efficacy of thiazide diuretics and alkali for secondary prevention of kidney stones, they are infrequently prescribed due in part to a lack of data about their effectiveness in real-world settings. We analyzed medical claims from older adults with kidney stones for whom urine chemistry data were available. We found that patients who took prescribed thiazide diuretics for elevated urine calcium levels or alkali for low urinary pH were less likely to experience symptomatic stone recurrences than untreated patients. This benefit was expressed as lower rates of emergency department visits after initiating therapy. Our findings should inform the prescription of and adherence to treatment with thiazide diuretics and alkali for the prevention of recurrent kidney stones.

Understanding the Barriers to Preventive Pharmacological Therapy Use in Older Patients With Urinary Stone Disease.

INTRODUCTION: Despite compelling clinical trial evidence and professional society guideline recommendations, prescription rates of preventative pharmacological therapy (PPT) for urinary stone disease are low. We sought to understand how patient- and clinician-level factors contribute to the decision to prescribe PPT after an index stone event. METHODS: We identified Medicare beneficiaries with urinary stone disease who had a 24-hour urine collection processed by a central laboratory. Among the subset with a urine chemistry abnormality (ie, hypercalciuria, hypocitraturia, hyperuricosuria, or low urine pH), we determined whether PPT was prescribed within 6 months of their collection. After assigning patients to the clinicians who ordered their collection, we fit multilevel models to determine how much of the variation in PPT prescription was attributable to patient vs clinician factors. RESULTS: Of the 11,563 patients meeting inclusion criteria, 33.6% were prescribed PPT. There was nearly sevenfold variation between the treating clinician with the lowest prescription rate (11%) and the one with the highest (75%). Nineteen percent of this variation was attributable to clinician factors. After accounting for measured patient differences and clinician volume, patients had twice the odds of being prescribed PPT if they were treated by a nephrologist (odds ratio [OR], 2.15; 95% CI, 1.79-2.57) or a primary care physician (OR, 1.78; 95% CI, 1.22-2.58) compared to being treated by a urologist. CONCLUSIONS: These findings suggest that the type of clinician whom a patient sees for his stone care determines, to a large extent, whether PPT will be prescribed.

Health care delivery system contributions to management of newly diagnosed prostate cancer.

BACKGROUND: Despite clinical guidelines advocating for use of conservative management in specific clinical scenarios for men with prostate cancer, there continues to be tremendous variation in its uptake. This variation may be amplified among men with competing health risks, for whom treatment decisions are not straightforward. The degree to which characteristics of the health care delivery system explain this variation remains unclear. METHODS: Using national Medicare data, men with newly diagnosed prostate cancer between 2014 and 2019 were identified. Hierarchical logistic regression models were used to assess the association between use of treatment and health care delivery system determinants operating at the practice level, which included measures of financial incentives (i.e., radiation vault ownership), practice organization (i.e., single specialty vs. multispecialty groups), and the health care market (i.e., competition). Variance was partitioned to estimate the relative influence of patient and practice characteristics on the variation in use of treatment within strata of noncancer mortality risk groups. RESULTS: Among 62,507 men with newly diagnosed prostate cancer, the largest variation in the use of treatment between practices was observed for men with high and very high-risk of noncancer mortality (range of practice-level rates of treatment for high: 57%-71% and very high: 41%-61%). Addition of health care delivery system determinants measured at the practice level explained 13% and 15% of the variation in use of treatment among men with low and intermediate risk of noncancer mortality in 10 years, respectively. Conversely, these characteristics explained a larger share of the variation in use of treatment among men with high and very high-risk of noncancer mortality (26% and 40%, respectively). CONCLUSIONS: Variation among urology practices in use of treatment was highest for men with high and very high-risk noncancer mortality. Practice characteristics explained a large share of this variation.

T cell activation is insufficient to drive SIV disease progression.

Resolution of T cell activation and inflammation is a key determinant of the lack of SIV disease progression in African green monkeys (AGMs). Although frequently considered together, T cell activation occurs in response to viral stimulation of acquired immunity, while inflammation reflects innate immune responses to mucosal injury. We dissociated T cell activation from inflammation through regulatory T cell (Treg) depletion with Ontak (interleukin-2 coupled with diphtheria toxin) during early SIV infection of AGMs. This intervention abolished control of T cell immune activation beyond the transition from acute to chronic infection. Ontak had no effect on gut barrier integrity, microbial translocation, inflammation, and hypercoagulation, despite increasing T cell activation. Ontak administration increased macrophage counts yet decreased their activation. Persistent T cell activation influenced SIV pathogenesis, shifting the ramp-up in viral replication to earlier time points, prolonging the high levels of replication, and delaying CD4+ T cell restoration yet without any clinical or biological sign of disease progression in Treg-depleted AGMs. Thus, by inducing T cell activation without damaging mucosal barrier integrity, we showed that systemic T cell activation per se is not sufficient to drive disease progression, which suggests that control of systemic inflammation (likely through maintenance of gut integrity) is the key determinant of lack of disease progression in natural hosts of SIVs.

Potential for Urolithiasis-related Research Using the Novel Medicare-Litholink Database.

INTRODUCTION: To overcome the data availability hurdle of observational studies on urolithiasis, we linked claims data with 24-hour urine results from a large cohort of adults with urolithiasis. This database contains the sample size, clinical granularity, and long-term follow-up needed to study urolithiasis on a broad level. METHODS: We identified adults enrolled in Medicare with urolithiasis who had a 24-hour urine collection processed by Litholink (2011 to 2016). We created a linkage of their collections results and paid Medicare claims. We characterized them across a variety of sociodemographic and clinical factors. We measured frequencies of prescription fills for medications used to prevent stone recurrence, as well as frequencies of symptomatic stone events, among these patients. RESULTS: In total, there were 11,460 patients who performed 18,922 urine collections in the Medicare-Litholink cohort. The majority were male (57%), White (93.2%), and lived in a metropolitan county (51.5%). Results from their initial urine collections revealed abnormal pH to be the most common abnormality (77.2%), followed by low volume (63.8%), hypocitraturia (45.6%), hyperoxaluria (31.1%), hypercalciuria (28.4%), and hyperuricosuria (11.8%). Seventeen percent had prescription fills for alkali monotherapy, and 7.6% had prescription fills for thiazide diuretic monotherapy. Symptomatic stone events occurred in 23.1% at 2 years of follow-up. CONCLUSIONS: We successfully linked Medicare claims with results from 24-hour urine collections performed by adults that were processed by Litholink. The resulting database is a unique resource for future studies on the clinical effectiveness of stone prevention strategies and urolithiasis more broadly.

Merit-based Incentive Payment System Quality Reporting in Urology Practices.

INTRODUCTION: Most urologists are required to participate in Merit-based Incentive Payment System-an alternative payment model in which physicians must track and report quality measures. However, Merit-based Incentive Payment System measures are urology-specific, and it remains unclear what measures urologists are choosing to track and report. METHODS: We performed a cross-sectional analysis of Merit-based Incentive Payment System measures reported by urologists for the most recent performance year. Urologists were categorized by their reporting affiliation (ie, individual, group, or alternative payment model). We identified the measures most frequently reported by urologists. Among reported measures, we identified those that were specific to urological conditions and those that were "topped out" (ie, measures considered indiscriminate by Medicare because high performance is easily achieved). RESULTS: A total of 6,937 urologists reported in Merit-based Incentive Payment System during the 2020 performance year, of whom 14% reported as an individual, 56% as a group, and 30% as an alternative payment model. Among the top 10 most frequently reported measures, none were urology-specific. Eleven percent of urologists reported measures that were directly specific to urological conditions; 65% of individual urologists, 58% of those in groups, and 92% in alternative payment models reported at least 1 or more "topped out" measures. CONCLUSIONS: Most measures reported by urologists are not specific to urological conditions, and therefore performance within Merit-based Incentive Payment System may be a poor indicator of the quality of urological care provided. As Medicare transitions Merit-based Incentive Payment System to implement specific quality measures, the urological community will need to develop and submit measures that will be most impactful for urology patients.

Evaluating novel methods of outcome assessment following cardiac arrest.

INTRODUCTION: We compared novel methods of long-term follow-up after resuscitation from cardiac arrest to a query of the National Death Index (NDI). We hypothesized use of the electronic health record (EHR), and internet-based sources would have high sensitivity for identifying decedents identified by the NDI. METHODS: We performed a retrospective study including patients treated after cardiac arrest at a single academic center from 2010 to 2018. We evaluated two novel methods to ascertain long-term survival and modified Rankin Scale (mRS): 1) a structured chart review of our health system's EHR; and 2) an internet-based search of: a) local newspapers, b) Ancestry.com, c) Facebook, d) Twitter, e) Instagram, and f) Google. If a patient was not reported deceased by any source, we considered them to be alive. We compared results of these novel methods to the NDI to calculate sensitivity. We queried the NDI for 200 in-hospital decedents to evaluate sensitivity against a true criterion standard. RESULTS: We included 1,097 patients, 897 (82%) alive at discharge and 200 known decedents (18%). NDI identified 197/200 (99%) of known decedents. The EHR and local newspapers had highest sensitivity compared to the NDI (87% and 86% sensitivity, respectively). Online sources identified 10 likely decedents not identified by the NDI. Functional status estimated from EHR, and internet sources at follow up agreed in 38% of alive patients. CONCLUSIONS: Novel methods of outcome assessment are an alternative to NDI for determining patients' vital status. These methods are less reliable for estimating functional status.

Systemic lupus erythematous after Pfizer COVID-19 vaccine: a case report.

The Pfizer-BioNTech COVID-19 vaccine has been authorized by the U.S. Food and Drug Administration as it demonstrated 95% effectiveness against the SARS-CoV-2 virus. Although the initial vaccine trials showed a favorable side effect profile, there have been concerns regarding activation of aberrant immune responses, triggering autoimmunity. This is a case report of a 68-year-old woman without history of autoimmune conditions, who presented to our emergency department 7 days after receiving the Pfizer-BioNTech COVID-19 vaccine. Her initial symptoms were suggestive of polymyalgia rheumatica, and she had nearly complete response to steroids. Interestingly, she later met criteria for classified systemic lupus erythematous given the development of inflammatory arthritis, positive ANA, and positive dsDNA. The temporal relationship of her symptoms that started 2 days after vaccine administration could suggest a possible association between the Pfizer-BioNTech COVID-19 and the development of systemic lupus erythematous.

Comparing demographics of organ donor referrals from the intensive care unit and outside units.

The Spanish organ donation system is a world leader in organ recovery. One of Spain's strategies is the identification of organ donor referrals outside of the intensive care unit (ICU) for intensive care to facilitate organ donation (ICOD). There are limited data comparing the profiles of ICU-based and non-ICU ICOD referrals. This single-center retrospective chart review analyzed organ donor referrals of ICU and non-ICU patients to better understand the demographic and clinical differences between cohorts. The primary outcome was to understand if organ donation conversion rates were similar between ICU and non-ICU referrals. We collected data from 745 organ donor referral candidates, 235 (32%) of whom entered ICOD protocols. Out of this cohort, 144 (61%) became actual organ donors, 37 of whom (26%) were referred from non-ICU units. The ICU had the highest organ donor conversion rate (66% of ICU ICOD patients became actual organ donors) whereas non-ICU referrals had a 51% conversion rate. Non-ICU unit donors contributed to 21% and 26% of all kidney and liver donations, respectively. Though organ referral candidates from non-ICU units contribute to a small proportion of actual donors, their donated organs are important to sustaining organ donation and transplant activity.

High-fat diet exacerbates SIV pathogenesis and accelerates disease progression.

Consuming a high-fat diet (HFD) is a risk factor for obesity and diabetes; both of these diseases are also associated with systemic inflammation, similar to HIV infection. A HFD induces intestinal dysbiosis and impairs liver function and coagulation, with a potential negative impact on HIV/SIV pathogenesis. We administered a HFD rich in saturated fats and cholesterol to nonpathogenic (African green monkeys) and pathogenic (pigtailed macaques) SIV hosts. The HFD had a negative impact on SIV disease progression in both species. Thus, increased cell-associated SIV DNA and RNA occurred in the HFD-receiving nonhuman primates, indicating a potential reservoir expansion. The HFD induced prominent immune cell infiltration in the adipose tissue, an important SIV reservoir, and heightened systemic immune activation and inflammation, altering the intestinal immune environment and triggering gut damage and microbial translocation. Furthermore, HFD altered lipid metabolism and HDL oxidation and also induced liver steatosis and fibrosis. These metabolic disturbances triggered incipient atherosclerosis and heightened cardiovascular risk in the SIV-infected HFD-receiving nonhuman primates. Our study demonstrates that dietary intake has a discernable impact on the natural history of HIV/SIV infections and suggests that dietary changes can be used as adjuvant approaches for HIV-infected subjects, to reduce inflammation and the risk of non-AIDS comorbidities and possibly other infectious diseases.

Neutrophil extracellular trap production contributes to pathogenesis in SIV-infected nonhuman primates.

Neutrophil extracellular traps (NETs) are involved in the pathogenesis of many infectious diseases, yet their dynamics and impact on HIV/SIV infection have not yet been assessed. We hypothesized that SIV infection and the related microbial translocation trigger NET activation and release (NETosis), and we investigated the interactions between NETs and immune cell populations and platelets. We compared and contrasted the levels of NETs between SIV-uninfected, SIV-infected, and SIV-infected antiretroviral-treated nonhuman primates. We also cocultured neutrophils from these animals with either peripheral blood mononuclear cells or platelets. Increased NET production was observed throughout SIV infection. In chronically infected animals, NETs were found in the gut, lung, and liver, and in the blood vessels of kidney and heart. Antiretroviral therapy (ART) decreased NETosis, albeit above preinfection levels. NETs captured CD4+ and CD8+ T cells, B cells, and monocytes, irrespective of their infection status, potentially contributing to the indiscriminate generalized immune cell loss characteristic to HIV/SIV infection, and limiting the CD4+ T cell recovery under ART. By capturing and facilitating aggregation of platelets, and through expression of increased tissue factor levels, NETs may also enhance HIV/SIV-related coagulopathy and promote cardiovascular comorbidities.