COUNTY-LEVEL ANALYSIS OF EYE EXAM ACCESS AND UTILIZATION IN THE UNITED STATES.

PURPOSE: The eye exam is a critical tool for the prevention, screening, and diagnosis of ocular and systemic conditions. In this study, we characterize county-level variation in eye exam access and utilization for Medicare patients in the United States. METHODS: This nationwide study uses the Medicare Physician & Other Practitioners - by Provider and Service dataset. We included all ophthalmologists and optometrists who performed eye exams on Medicare beneficiaries within a United States county in 2019. For every county where exams were performed, we calculated the number of practicing vision testing providers, percentage of providers classified as ophthalmologists, and the number of exams per 100 Medicare beneficiaries. Multiple linear regression was used to characterize associations between these variables and county characteristics, including measures of poverty, education, and income. RESULTS: In 2019, 28937,540 eye exams were performed by 46,000 providers in 2,291 U.S. counties. In the median county, 34.9 eye exams were provided per 100 Medicare beneficiaries. The average county had 20.1 exam providers, 16.5% of whom were ophthalmologists. There were a median 6.6 eye exam providers for every 10,000 Medicare beneficiaries in the average county. The average provider performed 517.8 exams. Regression showed counties with lower median household incomes, higher poverty rates, or fewer high-school graduates had fewer eye exam providers per 10,000 Medicare beneficiaries and fewer eye exams performed per 100 Medicare beneficiaries. CONCLUSIONS: We find significant county-level variation in eye exam utilization and provider availability. This reflects broader, well-recognized trends in socioeconomic health disparities in the U.S.

Associations between Hospital Setting and Outcomes after Pediatric Appendectomy.

Prior studies of associations between hospital location and outcomes for pediatric appendectomy have not adjusted for significant differences in patient and treatment patterns between settings. This was a cross-sectional analysis of pediatric appendectomies in the 2016 Kids' Inpatient Database (KID). Weighted multiple linear and logistic regression models compared hospital location (urban or rural) and academic status against total admission cost (TAC), length of stay (LOS), and postoperative complications. Patients were stratified by laparoscopic (LA) or open (OA) appendectomy. Among 54,836 patients, 39,454 (73%) were performed at an urban academic center, 11,642 (21%) were performed at an urban non-academic center, and 3740 (7%) were performed at a rural center. LA was utilized for 49,011 (89%) of all 54,386 patients: 36,049 (91%) of 39,454 patients at urban academic hospitals, 10,191 (87%) of 11,642 patients at urban non-academic centers, and 2771 (74%) of 3740 patients at rural centers (p < 0.001). On adjusted analysis, urban academic centers were associated with an 18% decreased TAC (95% CI -0.193--0.165; p < 0.001) despite an 11% increased LOS (95% CI 0.087-0.134; p < 0.001) compared to rural centers. Urban academic centers were associated with a decreased odds of complication among patients who underwent LA (OR 0.787, 95% CI 0.650-0.952) but not after OA. After adjusting for relevant patient and disease-related factors, urban academic centers were associated with lower costs despite longer lengths of stay compared to rural centers. Urban academic centers utilized LA more frequently and were associated with decreased odds of postoperative complications after LA.

Mortality in the Emergency Department and the Effectiveness of Conventional Safety Event Reporting.

Background Patient mortality reviews identify care, system, and process deficiencies. Patient deaths undergo quarterly review in our academic emergency department (ED), whereas in other departments, mortality reviews are requested by the pronouncing physician within 24 hours. In the ED, individual physicians encounter barriers to 24-hour reviews, including feasibility, the perception of futility, re-exposure to traumatic events, and a high frequency of pre-hospital and non-preventable deaths. This quality review aimed to determine the preventable death rate, contributing factors to ED patient mortality, cases requiring further review, and the capture rate of individual case submissions into the patient safety reporting system. Methods A retrospective chart review was performed on all patient deaths occurring in our ED from July 2019 to February 2020. All patients 18 years or older who were pronounced dead in the ED during our data collection period were included. Patients declared deceased pre-hospital, on an inpatient floor, or in the operating room were excluded. Deaths were assessed for characteristics such as sex, presence of a pulse upon arrival, diagnostics and interventions performed, and whether the cause of death was traumatic or medical. Deaths were categorized on a 5-point Likert scale ranging from "not preventable" to "likely preventable." The presence or absence of contributing factors and the need for further review were recorded. Results Of the 166 reviewed cases, 87% (n=144) were non-preventable due to a terminal condition upon arrival, 12% (n=20) were non-preventable despite maximal efforts, 0.6% (n=1) were non-preventable despite a medical or systems error, and 0.6% (n=1) were possibly preventable due to a medical or systems error. No cases were definitively preventable. Only 1.2% (n=2) of cases required further safety review. In 55% (n=91) of cases, the patient arrived without a pulse. Medical deaths (60%, n=100) outnumbered traumatic deaths (39%, n=64). The most utilized diagnostic test was ultrasound (67%, n=111), and the most utilized intervention was advanced cardiac life support (59%, n=98). Conclusion There is a high prevalence of unpreventable deaths in the ED (99%, n=164). Only two cases (1.2%) were identified for further patient safety review. Standard safety event reporting practices correctly identified all possibly preventable ED deaths.

Market Competition and Anemia Management in the United States Following Dialysis Payment Reform.

BACKGROUND: Whether market competition influences health care provider responses to national reimbursement reforms is unknown. OBJECTIVES: We examined whether changes in anemia management after the expansion of Medicare's dialysis payment bundle varied with market competition. RESEARCH DESIGN: With data from the US dialysis registry, we used a difference-in-differences (DID) design to estimate the independent associations of market competition with changes in anemia management after dialysis reimbursement reform. SUBJECTS: A total of 326,150 patients underwent in-center hemodialysis in 2009 and 2012, representing periods before and after reimbursement reform. MEASURES: Outcomes were erythropoiesis-stimulating agent (ESA) and intravenous iron dosage, the probability of hemoglobin <9 g/dL, hospitalizations, and mortality. We also examined serum ferritin concentration, an indicator of body iron stores. We used a dichotomous market competition index, with less competitive areas defined as effectively having <2 competing dialysis providers. RESULTS: Compared with areas with more competition, patients in less competitive areas had slightly more pronounced declines in ESA dose (60% vs. 57%) following reimbursement reform (DID estimate: -3%; 95% CI, -5% to -1%) and less pronounced declines in intravenous iron dose (-14% vs. -19%; DID estimate: 5%; 95% CI, 1%-9%). The likelihoods of hemoglobin <9 g/dL, hospitalization, and mortality did not vary with market competition. Serum ferritin concentrations in 2012 were 4% (95% CI, 3%-6%) higher in less competitive areas. CONCLUSIONS: After the expansion of Medicare's dialysis payment bundle, ESA use declined by more, and intravenous iron use declined by less in concentrated markets. More aggressive cost-reduction strategies may be implemented in less competitive markets.

Risk Factors for Multiple Sclerosis Development After Optic Neuritis Diagnosis Using a Nationwide Health Records Database.

Multiple sclerosis (MS) is an autoimmune demyelinating disease that often initially presents with optic neuritis (ON). Little is known about the demographic factors and familial histories that may be associated with the development of MS after a diagnosis of ON. We utilised a nationwide database to characterise specific potential drivers of MS following ON as well as analyse barriers to healthcare access and utilisation. The All of Us database was queried for all patients who were diagnosed with ON and for all patients diagnosed with MS after an initial diagnosis of ON. Demographic factors, family histories, and survey data were analysed. Multivariable logistic regression was performed to analyse the potential association between these variables of interest with the development of MS following a diagnosis of ON. Out of 369,297 self-enrolled patients, 1,152 were identified to have a diagnosis of ON, while 152 of these patients were diagnosed with MS after ON. ON patients with a family history of obesity were more likely to develop MS (obesity odd ratio: 2.46; p < .01). Over 60% of racial minority ON patients reported concern about affording healthcare compared with 45% of White ON patients (p < .01). We have identified a possible risk factor of developing MS after an initial diagnosis of ON as well as alarming discrepancies in healthcare access and utilisation for minority patients. These findings bring attention to clinical and socioeconomic risk factors for patients that could enable earlier diagnosis and treatment of MS to improve outcomes, particularly in racial minorities.

Hemodialysis Versus Peritoneal Dialysis Drug Expenditures: A Comparison Within the Private Insurance Market.

Rationale and Objective: Recent initiatives aim to improve patient satisfaction and autonomy by increasing the use of peritoneal dialysis (PD) in the United States. However, limited knowledge is available about the costs of different dialysis modalities, particularly those incurred by private insurers. In this study, we compared the costs of injectable dialysis drugs (and their oral equivalents) paid by insurers between privately insured patients receiving hemodialysis and PD. Study Design: A retrospective cohort study. Setting and Participants: From a private insurance claims database, we identified patients who started receiving PD or in-center hemodialysis between January 1, 2017, and December 31, 2020. Exposure: Patients started receiving PD. Outcomes: Average annual injectable drug and aggregate expenditures and expenditure subcategories. Analytical Approach: Patients who started receiving PD were propensity matched to similar patients who started receiving hemodialysis based on the year of dialysis initiation, patient demographics, health, geography, and comorbidities. Cost ratios (CRs) were estimated from generalized linear models. Results: We matched 284 privately insured patients who started receiving PD 1:1 with patients started receiving in-center hemodialysis. The average annual injectable drug expenditures for hemodialysis were 2-fold higher (CR: 1.99; 95% CI, 1.62-2.44) than that for PD. Compared those receiving PD, patients receiving hemodialysis incurred significantly lower nondrug dialysis-related expenditures (0.85; 95% CI, 0.76-0.94). The average annual expenditures for non-dialysis-dependent outpatient services were significantly higher among patients who underwent in-center hemodialysis (CR: 1.44; 95% CI, 1.10-1.90). Although aggregate and inpatient hospitalization expenditures were higher for in-center hemodialysis, these differences did not reach statistical significance. Limitations: Small sample sizes may have restricted our ability to identify differences in some cost categories. Conclusions: Compared with privately insured patients who started receiving PD, patients starting in-center hemodialysis incurred higher expenditures for injectable dialysis drugs, whereas differences in other expenditure categories varied. Recent increases in the use of PD may lead to reductions in injectable dialysis drug costs among privately insured patients. Plain Language Summary: Recent initiatives aim to improve patient satisfaction and autonomy by increasing the use of peritoneal dialysis (PD) in the United States. However, limited knowledge is available about the costs of different dialysis modalities, particularly those incurred by private insurers. In this study, we compared the costs of injectable dialysis drugs (and their oral equivalents) provided by insurers between privately insured patients receiving hemodialysis and PD. We found that the average annual injectable drug expenditures for hemodialysis were 2.0-fold higher compared with those for PD. These findings suggest that the recent increase in the use of PD may lead to reductions in injectable dialysis drug costs among privately insured patients.

Demographic and applicant-specific predictors of medical school research productivity in a national cohort of dermatology residents.

Research is a crucial aspect of medical advancement, and applicants applying to dermatology often have high research outputs. With United States Medical Licensing Examination (USMLE) Step 1 becoming pass/fail, research productivity may be more emphasized. We primarily sought to assess predictors of medical school research productivity. Class of 2023 dermatology residents publicly listed on Accreditation Council for Graduate Medical Education-accredited programs were included. Their medical school bibliography and demographics were assessed using PubMed and other platforms (eg, Doximity, LinkedIn). By multivariable analysis, students who attended a top 25 medical school (ranked by US News and World Report) or were PhD graduates had significantly higher H-indices, average impact factors, and total years of research activity (P < .01). Top 25 medical school graduates also had significantly higher total peer-reviewed publications, first authorships, and clinical research papers (P < .01). PhD graduates had significantly more clinical research and fewer dermatology-related papers (P < .03). Graduates of osteopathic medical schools had significantly fewer review papers (P = .02). Gender and graduation from an international medical school had no relationship with research productivity. Our study demonstrates a correlation between applicant-specific factors and research productivity. Because the emphasis on research productivity may increase, understanding the mechanisms behind these relationships may guide future dermatology applicants or their mentors.

Transplanting hepatitis B surface antigen-positive livers in the United States: Outcomes and opportunities.

Livers from donors with positive hepatitis B surface antigens (HBsAg+) have been used to expand the donor pool; however, outcome data are limited. We aim to evaluate survival following liver transplant (LT) from HBsAg+ donors. Using the United Network for Organ Sharing registry, we identified HBsAg+ donors used for LT from 2009 to 2020. We used Kaplan-Meier survival and Cox proportional hazards regression to compare post-LT survival in hepatitis B virus-negative recipients who utilized HBsAg+ donors to propensity-matched cohorts who utilized other types of donors. From 2009-2020, 70 patients received HBsAg+ livers, and 58 of them did not carry a diagnosis of chronic hepatitis B virus. The 1- and 3-year post-LT survival for hepatitis B virus-negative patients who received livers from HBsAg+ donors were 96.6% and 91.4%, respectively, with no statistical differences compared with patients who received livers from hepatitis C virus viremic donors (96.5%/93.0%, P = .961/.427), donation after cardiac death donors (93.0%/86.0%, P = .651/.598), average-risk donors (89.5%/86.0%, P = 0.264/0.617), and a combination of extended-criteria donors, including donation after cardiac death, donor age over 70, and graft with greater than 30% steatosis (93.0%/91.2%, P = .621/.785). Recipients of HBsAg+ livers have similar post-LT survival compared with those receiving other types of grafts. Increasing the utilization of HBsAg+ livers could safely expand the donor pool.

Epidemiology of Retinopathy of Prematurity in the US From 2003 to 2019.

Importance: Retinopathy of prematurity (ROP) is a potentially blinding retinal disease with poorly defined epidemiology. Understanding of which infants are most at risk for developing ROP may foster targeted detection and prevention efforts. Objective: To identify changes in ROP incidence in the US from 2003 to 2019. Design, Setting, and Participants: This retrospective database cohort study used the Healthcare Cost and Utilization Project Kids' Inpatient Databases. These nationwide databases are produced every 3 years, include data from over 4000 hospitals, and are designed to generate national estimates of health care trends in the US. Participants included pediatric newborns at risk for ROP development between 2003 and 2019. Data were analyzed from September 30, 2021, to January 13, 2022. Exposures: Premature or low-birth-weight infants with relevant International Classification of Diseases, Ninth Revision or Tenth Revision codes were considered ROP candidates. Infants with ROP were identified using relevant codes. Main Outcomes and Measures: ROP incidence in selected subpopulations (based on database-reported race and ethnicity, sex, location, income) was measured. To determine whether incidences varied across time or subpopulations, χ2 tests of independence were used. Results: This study included 125 212 ROP discharges (64 715 male infants [51.7%]) from 23 187 683 births. The proportion of premature infants diagnosed with ROP increased from 4.4% (11 720 of 265 650) in 2003 to 8.1% (27 160 of 336 117) in 2019. Premature infants from the lowest median household income quartile had the greatest proportional increase of ROP diagnoses from 4.9% (3244 of 66 871) to 9.0% (9386 of 104 235; P < .001). Premature Black infants experienced the largest increase from 5.8% (2124 of 36 476) to 11.6% (7430 of 63 925; P < .001) relative to other groups (2.71%; 95% CI, 2.56%-2.87%; P < .001). Hispanic infants experienced the second largest increase from 4.6% (1796 of 39 106) to 8.2% (4675 of 57 298; P < .001) relative to other groups (-0.16%; 95% CI, -0.29% to -0.03%; P = .02). The Southern US experienced the greatest proportional growth of ROP diagnoses, increasing from 3.7% (3930 of 106 772) to 8.3% (11 952 of 144 013; P < .001) relative to other groups (1.61%; 95% CI, 1.51%-1.71%; P < .001). ROP diagnoses proportionally increased in urban areas and decreased in rural areas. Conclusions and Relevance: This cohort study found that ROP incidence among premature infants increased from 2003 to 2019, especially among Black and Hispanic infants. Infants from the lowest-income areas persistently had the highest proportional incidence of ROP, and all regions experienced a significant increase in ROP incidence with the most drastic changes occurring in the South. These trends suggest that ROP is a growing problem in the US and may be disproportionately affecting historically marginalized groups.

Long-term outcomes and trends in liver transplantation for hereditary hemochromatosis in the United States.

There have been conflicting data regarding liver transplantation (LT) outcomes for hereditary hemochromatosis (HH), with no recent data on LT outcomes in patients with HH in the past decade. Using the United Network for Organ Sharing registry, we evaluated waitlist and post-LT survival in all adult patients listed for HH without concomitant liver disease from 2003 to 2019. Post-LT survival for HH was compared with a propensity-matched (recipient and donor factors) cohort of recipients with chronic liver disease (CLD). From 2003 to 2019, 862 patients with HH were listed for LT, of which 55.6% ( n = 479) patients underwent LT. The 1- and 5-year post-LT survival rates in patients with HH were 88.7% (95% confidence interval [CI], 85.4%-91.4%) and 77.5% (95% CI, 72.8%-81.4%), respectively, and were comparable with those in the propensity-matched CLD cohort ( p value = 0.96). Post-LT survival for HH was lower than for Wilson's disease, another hereditary metabolic liver disease with similar LT volume ( n = 365). Predictors for long-term (5-year) post-LT mortality included presence of portal vein thrombosis (hazard ratio [HR], 1.96; 95% CI, 1.07-3.58), obesity measurements greater than Class II (HR, 1.98; 95% CI, 1.16-3.39), and Karnofsky performance status (HR, 0.98; 95% CI, 0.97-0.99) at the time of LT. The leading cause of post-LT death ( n = 145) was malignancy (25.5%), whereas cardiac disease was the cause in less than 10% of recipients. In conclusion, short- and long-term survival rates for HH are excellent and comparable with those of other LT recipients. Improving extrahepatic metabolic factors and functional status in patients with HH prior to LT may improve outcomes.

Successful Nonextracorporeal Life Support Resuscitation and Rewarming of a Patient with Hypothermia in Cardiac Arrest.

We report full recovery of a patient with hypothermia in cardiac arrest following continuous and prolonged cardiopulmonary resuscitation (CPR) and conventional, nonextracorporeal life support (non-ECLS) methods. A 57-y-old man presented with unwitnessed cardiac arrest and a core temperature of 23°C (73°F). The presenting cardiac rhythm was ventricular fibrillation. The team administered epinephrine and performed defibrillation and CPR. Because ECLS was unavailable at the facility, the medical team externally and internally rewarmed the patient using heated blankets, forced warmed air, thoracic lavage, and warmed IV fluids. The patient achieved return of spontaneous circulation after 4 h 56 min of continuous CPR and rewarming. The medical team admitted the patient to the intensive care unit. He achieved full neurologic recovery the following day. When ECLS is not available and transfer is not appropriate because of patient instability or hospital location, conventional rewarming methods and continuous, prolonged CPR can lead to successful outcomes in patients with hypothermia in cardiac arrest. This case demonstrates that CPR in patients with hypothermia-associated cardiac arrest can lead to full recovery.

Chloropsia in the Charles Bonnet syndrome.

Purpose: Chloropsia (green-colored vision) is an extremely uncommon and relatively unstudied clinical finding. We report a case where cerebral chloropsia was the presenting symptom of the Charles Bonnet syndrome. Observations: A 66-year-old male physician with a previous ocular history of advanced bilateral primary open-angle glaucoma presented with acute, diffuse chloropsia, which he described as "light green and oval-shaped." The patient was not taking any drugs that commonly cause altered color perception and did not have a previously diagnosed psychiatric disorder. Ophthalmic examination findings showed poor visual acuity, central visual field loss, and altered color perception in both eyes. Common laboratory tests and visual imaging showed no abnormalities that could be associated with the patient's symptoms. Conclusions and Importance: Our patient meets all diagnostic criteria for Charles Bonnet syndrome, even though, to the best of our knowledge, chloropsia has never been previously associated with this disorder. Physicians should monitor patients for altered color perception, which cannot be explained by other ocular, psychiatric, or systemic mechanisms, as this could be a sign of Charles Bonnet syndrome.

Role of Volumetric Modulated Arc Technique Radiotherapy in a Rare Case of Intraductal Apocrine Carcinoma of Parotid Gland.

Introduction Apocrine carcinoma, a cancer of sweat glands, is very rare, with a global incidence of 0.0049 to 0.0173 cases per 100,000 persons annually. It is usually found in axilla and anogenital areas. The intraductal apocrine variety of salivary duct carcinoma in the parotid gland is very rare and aggressive and may be due to ectopic sweat glands in the parotid gland duct or metaplastic change of the salivary duct epithelium. It usually presents in an advanced stage. Even though surgery is the standard of care in most head and neck cancers, there are no standard guidelines for the treatment of intraductal apocrine parotid carcinoma, which is different from other head and neck cancers due to its rare incidence, aggressive behavior, and poor prognosis. Case presentation We present a rare case of intraductal apocrine salivary duct carcinoma of the left parotid gland, presented in a locally advanced stage with very high chances of recurrence after surgery, and discuss the role of volumetric modulated arc technique radiotherapy in its management. Conclusion Intraductal apocrine salivary duct carcinoma usually has androgen receptor expression, and lack of expression is associated poor prognosis. Even with complete resection, it has a high recurrence rate. Volumetric modulated arc technique radiotherapy (VMAT) decreases recurrence and increases survival by irradiating the areas more likely of recurrence, with minimal toxicity to surrounding normal tissues.

Social Media Impact of Articles Published by Dermatology Residents During Medical School: Cross-sectional Study.

BACKGROUND: The Altmetric score (AS) is a novel measure of publication impact that is calculated by the number of mentions across various social media websites. This method may have advantages over traditional bibliometrics in the context of research by medical students. OBJECTIVE: This study aimed to determine whether dermatology matriculants who graduated from higher-ranked medical schools published more articles with greater impact (ie, a higher AS) than those from lower-ranked institutions. METHODS: A PubMed search for articles published by dermatology residents who started medical school in 2020 was conducted. Demographic information and Altmetric data were collected, and medical schools were sorted according to US News' top-25 and non-top-25 categories. RESULTS: Residents who completed their medical training at a top-25 institution published more papers (mean 4.93, SD 4.18 vs mean 3.11, SD 3.32; P<.001) and accrued a significantly higher total AS (mean 67.9, SD 160 vs mean 22.9, SD 75.9; P<.001) and average AS (mean 13.1, SD 23.7 vs mean 6.71, SD 32.3; P<.001) per article than those who graduated from non-top-25 schools. CONCLUSIONS: Our results indicate that students in top-25 schools may have greater access to research resources and opportunities. With a pass/fail United States Medical Licensing Examination Step 1 exam that may increasingly shift focus toward scholarly output from medical students, further discussion on how to create a more equitable dermatology match is essential.

Nodal volume as a prognostic factor in locally advanced head and neck cancer: Identifying candidates for elective neck dissection after chemoradiation with IGRT from a single institutional prospective series from the Indian subcontinent.

OBJECTIVE: Nodal volume as a prognostic factor has been extensively evaluated in head and neck cancer, however there is still no consensus. We attempted to analyze nodal volume as a prognostic factor in head and neck cancer treated with chemoradiation (CCRT) without an elective neck dissection with image guided intensity modulated radiotherapy (IG-IMRT). MATERIAL AND METHODS: We prospectively analysed 87 patients of Stage III-IV cancer of the oropharynx (57), and hypopharynx (30), who subsequently received definitive concurrent chemoradiation. Total Nodal volume (TNV) was the sum of all lymph node volumes calculated by volume algorithm from the planning CT. The impact of TNV on overall survival (OS) & regional control (RC) was assessed. Survival analysis was done using SPSS version 20.0 (SPSS, Chicago, Illinois). A receiver operating characteristics (ROC) curve analysis was done for estimation of cut offs. RESULTS: The 2 year OS & RC were 64% and 83% respectively. On multivariate analysis, the TNV was a significant prognostic factor for OS &RC. ROC curve analysis found an optimal volumetric cut off of 15cc for OS & RC. The 2 year OS & RC for <15cc/>15cc group were 78% /30% (p = 0.001) & 100%/52% (p = 0.001). Similar results were obtained on subset analysis of our oropharyngeal patients with 2 year OS 75%/24% for the <15cc and >15cc group (p = 0.001). CONCLUSION: TNV is an independent prognostic factor for OS & RC in head and neck cancer. TNV can identify patients for consideration of elective neck dissection post CCRT ie for patients with TNV > 15CC.

Isolation of a chiral anthracene cation radical: X-ray crystallography and computational interrogation of its racemization.

Chiral cation-radical salts hold significant promise as charge-transfer materials, chiroptical switches, and electron-transfer catalysts for enantioselective synthesis. Herein we demonstrate that the readily-available chiral 9,10-diphenyleanthracene derivative (i.e.SANT) forms a robust cation radical, whose structure was elucidated by X-ray crystallography and DFT calculations. While SANT was observed to racemize on a timescale (t1/2) of 1.1 hours, a computational conformational search and kinetic analysis of the racemization pathway led us to identify a simple methyl substituted SANT derivative, which does not racemize (racemization t1/2 1013-1017 years).