Clinical and genetic factors affecting diagnostic timeline of amyotrophic lateral sclerosis: a 15-year retrospective study.

OBJECTIVES: Amyotrophic Lateral Sclerosis (ALS) diagnosis can take 10-16 months from symptom onset, leading to delays in treatment and patient counselling. We studied the impact of clinical and genetic risk factors on the diagnostic timeline of ALS. METHODS: Baseline characteristics, family history, gene testing, onset location, time from symptom onset to diagnosis, and time from first doctor visit to suspected ALS was collected. We used multiple regression to assess the interaction of these factors on ALS diagnostic timeline. We analysed a subgroup of patients with genetic testing and compared positive or negative tests, sporadic or familial and ALS-related genes to time for diagnosis. RESULTS: Four hundred and forty-eight patients diagnosed with ALS at the University of Massachusetts Chan Medical Center between January 2007 and December 2021 were analysed. The median time to ALS diagnosis was 12 months and remained unchanged from 2007 to 2021 (p = 0.20). Diagnosis was delayed in patients with sporadic compared with familial ALS (mean months [standard deviation], 16.5[13.5] and 11.2[8.5], p < 0.001); cognitive onset (41[21.26]) had longer time to diagnosis than bulbar (11.9[8.2]), limb (15.9[13.2]), respiratory (19.7[13.9]) and ALS with multiple onset locations (20.77[15.71], p < 0.001). One hundred and thirty-four patients had gene testing and 32 tested positive (23.8%). Gene testing (p = 0.23), a positive genetic test (p = 0.16), different ALS genes (p = 0.25) and sporadic (p = 0.92) or familial (p = 0.85) ALS testing positive for ALS genes did not influence time to diagnosis. DISCUSSION: Time for ALS diagnosis remained unchanged from 2007 to 2021, bulbar-onset and familial ALS made for faster diagnosis.

Effect of Hospital Safety Net Burden on Survival for Patients With Sinonasal Squamous Cell Carcinoma.

OBJECTIVE: To examine factors associated with hospital safety net burden and its impact on survival for patients with sinonasal squamous cell carcinoma (SNSCC). STUDY DESIGN: Retrospective database study. SETTING: National Cancer Database from 2004 to 2016. METHODS: SNSCC cases were identified in the National Cancer Database. Hospital safety net burden was defined by percentage of uninsured/Medicaid patients treated, namely ≤25% for low-burden hospitals, 26% to 75% for medium-burden hospitals, and >75% for high-burden hospitals (HBHs). Univariate and multivariate analyses were used to investigate patient demographics, clinical characteristics, and overall survival. RESULTS: An overall 6556 SNSCC cases were identified, with 1807 (27.6%) patients treated at low-burden hospitals, 3314 (50.5%) at medium-burden hospitals, and 1435 (21.9%) at HBHs. On multivariate analysis, Black race (odds ratio [OR], 1.39; 95% CI, 1.028-1.868), maxillary sinus primary site (OR, 1.31; 95% CI, 1.036-1.643), treatment at an academic/research program (OR, 20.63; 95% CI, 8.868-47.980), and treatment at a higher-volume facility (P < .001) resulted in increased odds of being treated at HBHs. Patients with grade III/IV tumor (OR, 0.70; 95% CI, 0.513-0.949), higher income (P < .05), or treatment modalities other than surgery alone (P < .05) had lower odds. Survival analysis showed that hospital safety net burden status was not significantly associated with overall survival (log-rank P = .727). CONCLUSION: In patients with SNSCC, certain clinicopathologic factors, including Black race, lower income, treatment at an academic/research program, and treatment at facilities in the West region, were associated with treatment at HBHs. Hospital safety net burden status was not associated with differences in overall survival.

Gene Therapy in Amyotrophic Lateral Sclerosis.

Since the discovery of Cu/Zn superoxide dismutase (SOD1) gene mutation, in 1993, as the first genetic abnormality in amyotrophic lateral sclerosis (ALS), over 50 genes have been identified as either cause or modifier in ALS and ALS/frontotemporal dementia (FTD) spectrum disease. Mutations in C9orf72, SOD1, TAR DNA binding protein 43 (TARDBP), and fused in sarcoma (FUS) genes are the four most common ones. During the last three decades, tremendous effort has been made worldwide to reveal biological pathways underlying the pathogenesis of these gene mutations in ALS/FTD. Accordingly, targeting etiologic genes (i.e., gene therapies) to suppress their toxic effects have been investigated widely. It includes four major strategies: (i) removal or inhibition of abnormal transcribed RNA using microRNA or antisense oligonucleotides (ASOs), (ii) degradation of abnormal mRNA using RNA interference (RNAi), (iii) decrease or inhibition of mutant proteins (e.g., using antibodies against misfolded proteins), and (iv) DNA genome editing with methods such as clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (CRISPR/Cas). The promising results of these studies have led to the application of some of these strategies into ALS clinical trials, especially for C9orf72 and SOD1. In this paper, we will overview advances in gene therapy in ALS/FTD, focusing on C9orf72, SOD1, TARDBP, and FUS genes.

Analysis of the Treatment and Survival of Sinonasal Extramedullary Plasmacytoma.

BACKGROUND: While extramedullary plasmacytomas are infrequently encountered plasma cell malignancies, most cases occur in the head and neck, with a predilection for the sinonasal cavity. Due to the rarity of this disease, the majority of studies on sinonasal extramedullary plasmacytoma (SN-EMP) are case reports or small retrospective case series. OBJECTIVE: To investigate the impact of patient, disease, and treatment factors on the survival of patients with SN-EMP. METHODS: The National Cancer Database was queried for all patients with SN-EMP between 2004-2016 (N = 381 cases). Univariate and multivariate analyses were used to examine patient demographics, tumor characteristics, and survival. RESULTS: The majority of SN-EMP patients were over 60 years old (57.0%), male (69.8%), and white (86.2%). The most common treatment modality was radiotherapy alone (38.6%), followed by surgery plus radiotherapy (37.8%). Five-year overall survival was 74.0% and median survival was 9.1 years. Accounting for patient demographics and tumor characteristics in a multivariate model, the following groups had worse prognosis: 60 and older (HR 1.99, p = 0.031) and frontal sinus primary site (HR 11.56, p = 0.001). Patients who received no treatment (HR 3.89, p = 0.013), chemotherapy alone (HR 5.57, p = 0.008) or radiotherapy plus chemotherapy (HR 2.82, p = 0.005) had significantly lower survival than patients who received radiotherapy alone. Patients who received surgery with radiotherapy (HR 0.57, p = 0.039) had significantly higher survival than patients who received radiotherapy alone. CONCLUSION: In patients with SN-EMP five-year overall survival was found to be 74.0% with decreased survival associated with a frontal sinus primary site and being aged 60 or older. Patients receiving no treatment, chemotherapy alone, or radiotherapy with chemotherapy was associated with lower survival. Receiving surgery plus radiotherapy was associated with the highest five-year overall survival.

Trends in HPV Testing for Patients With Sinonasal Squamous Cell Carcinoma: A National Analysis.

OBJECTIVE: The objective of this study was to analyze national trends in human papillomavirus (HPV) testing for patients diagnosed with sinonasal squamous cell carcinoma (SNSCC). STUDY DESIGN: Retrospective database study. SETTING: National Cancer Database (2010-2016). METHODS: Cases from 2010 to 2016 with a primary SNSCC diagnosis and known HPV testing status were extracted from the National Cancer Database. Univariate and multivariate analyses were then performed to assess differences in socioeconomic, hospital, and tumor characteristics between tested and nontested patients. RESULTS: A total of 2308 SNSCC cases were collected, with 1210 (52.4%) HPV tested and 1098 (47.6%) not tested. On univariate analyses, patient age, insurance, income quartile, population density, treatment facility location, and tumor grade were significantly associated with HPV testing status. After multivariate logistic regression modeling, living in a suburban area had lower odds of HPV testing as compared with living in urban areas (odds ratio, 0.74 [95% CI, 0.55-0.99]; P = .041), while tumor grade III/IV had higher odds than grade I (odds ratio, 1.73 [95% CI, 1.29-2.33]; P < .001). HPV-tested patients had a similar 5-year overall survival to nontested patients (48.3% vs 45.3%, log-rank P = .405). A sharp increase in HPV testing rates was observed after 2010 (P < .001). CONCLUSION: Among patients with SNSCC, those with high-grade tumors were more likely to be tested for HPV, while patients with a suburban area of residence were less likely. Additionally, there was no significant survival benefit to HPV testing, with tested and nontested groups having similar overall survival. LEVEL OF EVIDENCE: 4.

Inpatient Sinus Surgery Patient Morbidity and Outcomes: A National Analysis.

OBJECTIVES/HYPOTHESIS: To investigate the morbidity and mortality of patients undergoing endoscopic sinus surgery (ESS) in the inpatient setting. STUDY DESIGN: Retrospective database review. METHODS: The Nationwide Inpatient Sample was queried for all ESS between 2008 and 2014. Using All Patients Refined Diagnosis Related Groups (APR-DRG) codes, cases with APR-DRG codes under Major Diagnostic Category 3 (Diseases and Disorders of the Ear, Nose, Mouth, and Throat) were designated as patients with primary otolaryngology diagnoses undergoing ESS (ORL), and all other codes were designated as patients with non-otolaryngology pathologies as their primary reason for admission but undergoing ESS (non-ORL). A univariate analysis and a logistic regression were used to compare patient demographics, comorbidities, disease severity, and mortality. RESULTS: There were 8,305 ORL patients and 6,342 non-ORL patients. ORL patients were more likely to be elective admissions (61.3% vs. 48.5%, P < .001), have a deviated nasal septum (17.9% vs. 12.3%, P < .001), nasal polyps (15.8% vs. 5.0%, P < .001), obstructive sleep apnea (10.7% vs. 5.2%, P < .001), and pulmonary disease (15.9% vs. 10.5%, P < .001). Non-ORL patients had a higher likelihood of in-hospital mortality (odds ratio [OR] 6.22, 95% confidence interval [CI] 3.29-11.78, P < .001), length of stay in the highest quartile (OR 2.43, 95% CI 2.16-2.74, P < .001), and a higher proportion had APR-DRG subclasses indicating extreme severity of illness (19.3% vs. 4.3%, P < .001) or extreme risk of mortality (12.5% vs. 2.0%, P < .001). CONCLUSION: Patients undergoing ESS in the inpatient setting have a higher than expected mortality rate which can be associated with a non-otolaryngology pathology as the primary reason for their admission. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1523-1529, 2022.

A Machine Learning Approach in Predicting Mortality Following Emergency General Surgery.

BACKGROUND: There is a significant mortality burden associated with emergency general surgery (EGS) procedures. The objective of this study was to develop and validate the use of a machine learning approach to predict mortality following EGS. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for patients who underwent EGS between 2012 and 2017. We developed a machine learning algorithm to predict mortality following EGS and compared its performance with existing risk-prediction models of American Society of Anesthesiologists (ASA) classification, American College of Surgeon Surgical Risk Calculator (ACS-SRC), and the modified frailty index (mFI) using the area under receiver operative curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: The machine learning algorithm had a very high performance for predicting mortality following EGS, and it had superior performance compared to the ASA classification, ACS-SRC, and the mFI, as measured by the AUC, sensitivity, specificity, PPV, and NPV. DISCUSSION: Machine learning approaches may be a promising tool to predict outcomes for EGS, aiding clinicians in surgical decision-making and counseling of patients and family, improving clinical outcomes by identifying modifiable risk factors than can be optimized, and decreasing treatment costs through resource allocation.

Exploratory analysis on the association of mental health disorders with in-hospital postoperative complications and mortality in head and neck cancer surgery.

BACKGROUND: The objective was to assess the association of mental health disorders with in-hospital complication and mortality rates in patients undergoing head and neck cancer surgery. METHODS: In this exploratory retrospective study, the Nationwide Inpatient Sample was queried from 2003 to 2014 for all patients with a diagnosis of head and neck cancer who underwent surgery. Univariate cross-tabulation, logistic regression, and propensity score matching (PSM) were used to compare demographics, procedure-related variables, and in-hospital postoperative complications and mortality between patients with and without selected comorbid mental health disorders. RESULTS: Of 39 600 included patients, 3390 (8.6%) had a selected comorbid mental health disorder diagnosis. After PSM, patients with selected mental health disorders had increased risk of overall medical complications on multivariable analysis (OR 1.28 [CI 1.12-1.46], P < 0.001) but not overall surgical complications or mortality. CONCLUSIONS: Patients with a mental health disorder diagnosis have increased risk of in-hospital medical, certain surgical, and total complications.

Characterizing Patient Questions Before and After Rhinoplasty on Social Media: A Big Data Approach.

BACKGROUND: As an aesthetic surgery, a successful rhinoplasty is often assessed by patient satisfaction, subject to a diverse array of qualitative factors including patient expectations and happiness with care provided. While substantial effort has been dedicated to understanding patients' post-operative concerns, addressing patients' pre-operative questions has been comparatively less studied. This study analysed pre- and post-operative questions about rhinoplasty on social media to gain insights into patients' concerns and develop targeted educational material. METHODS: The most viewed rhinoplasty questions on Realself.com, a social media platform for discussions about cosmetic surgeries, were collected and analysed. Questions were then stratified into pre- and post-operative and further assigned categories based on common topics found in the data. Using a machine learning approach, the most common pre- and post-operative questions were determined. RESULTS: 2014 rhinoplasty questions were collected in total, with 957 pre-operative and 1057 post-operative. The most commonly asked pre-operative questions were about appearance (n = 441, 46.1%), function (n = 102, 10.7%), and cost (n = 94, 9.8%). The most commonly asked post-operative questions were about appearance (n = 502, 47.5%), behaviour allowed/disallowed (n = 283, 26.8%), and symptoms after surgery (n = 235, 22.2%). An educational handout with the 10 most common pre- and post-operative questions was developed using machine learning analysis, with the majority of questions about appearance. CONCLUSIONS: Patients primarily expressed concern about appearance when asking questions about rhinoplasty on social media, along with other aspects of their pre- and post-operative course. The educational handout developed by this study can be applied to address commonly asked patient questions during pre-operative education. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Extranodal Extension as an Indicator for Sinonasal Squamous Cell Carcinoma Prognosis.

OBJECTIVE: Although extranodal extension (ENE) is a known indicator of poor prognosis for head and neck malignancies, its value as an indicator for sinonasal squamous cell carcinoma (SCC) has not been well characterized. This study seeks to assess the usefulness of ENE as a prognostic marker for sinonasal SCC. STUDY DESIGN: Retrospective database review. SETTING: National Cancer Database from 2010 to 2015. METHODS: The National Cancer Database was queried from 2010 to 2015 for all patients with sinonasal SCC with available ENE status (n = 355). These cases were divided into those with pathologically confirmed ENE (n = 146) and those without ENE (n = 209). Univariate and multivariate analyses were used to examine survival differences and predictors of ENE status. RESULTS: Most patients with ENE were ≥60 years old (61.7%), male (61.6%), and white (83.6%). Patients aged 60 to 69 and 80+ years were more likely to have ENE than those under 60 years (P < .05). Patients with ENE had worse 1-year overall survival than those without ENE (58.2% vs 70.8%, log-rank P = .008). After multivariate regression, however, there was no survival difference detected between ENE-positive and ENE-negative cases (hazard ratio, 1.14 [0.775-1.672], P = .508). CONCLUSION: ENE status did not have a significant effect on survival in patients with sinonasal SCC. Thus, ENE alone may not necessarily be a helpful indicator for sinonasal SCC prognosis.

The Use of Artificial Neural Network to Predict Surgical Outcomes After Inguinal Hernia Repair.

BACKGROUND: Inguinal hernia repair is one of the most commonly performed surgical procedures. We developed and validated an artificial neural network (ANN) model for the prediction of surgical outcomes and the analysis of risk factors for inguinal hernia repair. MATERIALS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program was used to find patients who underwent inguinal hernia repair. Using logistic regression and ANN models, we evaluated morbidity, readmission, and mortality using the area under the receiver operating characteristic curves, true-positive rate, true-negative rate, false-positive rate, and false-negative rates. RESULTS: There was no significant difference in the power of the ANN and logistic regression for predicting mortality, readmission, and all morbidities after inguinal hernia repair. Risk factors for morbidity, readmission, and mortality outcomes identified using ANN were consistent with logistic regression analysis. CONCLUSIONS: ANNs perform comparably to logistic regression models in the prediction of outcomes after inguinal hernia repair. ANNs may be a useful tool in risk factor analysis of hernia surgery and clinical applications.

Damage Evolution in Complex-Phase and Dual-Phase Steels during Edge Stretching.

The role of microstructural damage in controlling the edge stretchability of Complex-Phase (CP) and Dual-Phase (DP) steels was evaluated using hole tension experiments. The experiments considered a tensile specimen with a hole at the center of specimen that is either sheared (sheared edge condition) or drilled and then reamed (reamed edge condition). The damage mechanism and accumulation in the CP and DP steels were systematically characterized by interrupting the hole tension tests at different strain levels using scanning electron microscope (SEM) analysis and optical microscopy. Martensite cracking and decohesion of ferrite-martensite interfaces are the dominant nucleation mechanisms in the DP780. The primary source of void nucleation in the CP800 is nucleation at TiN particles, with secondary void formation at martensite/bainite interfaces near the failure strain. The rate of damage evolution is considerably higher for the sheared edge in contrast with the reamed edge since the shearing process alters the microstructure in the shear affected zone (SAZ) by introducing work-hardening and initial damage behind the sheared edge. The CP microstructures were shown to be less prone to shear-induced damage than the DP materials resulting in much higher sheared edge formability. Microstructural damage in the CP and DP steels was characterized to understand the interaction between microstructure, damage evolution and edge formability during edge stretching. An analytical model for void evolution and coalescence was developed and applied to predict the damage rate in these rather diverse microstructures.

Management of fibromyalgia syndrome in 2016.

Fibromyalgia syndrome is a chronic pain disorder and defies definitively efficacious therapy. In this review, we summarize the results from the early treatment research as well as recent research evaluating the pharmacological, interventional and nonpharmacological therapies. We further discuss future directions of fibromyalgia syndrome management; we specifically focus on the issues that are associated with currently available treatments, such as the need for personalized approach, new technologically oriented and interventional treatments, the importance of understanding and harnessing placebo effects and enhancement of patient engagement in therapy.

Cryoablation for the treatment of occipital neuralgia.

BACKGROUND: Treatment of occipital neuralgia (ON) can be complex, though many treatment options exist. Cryoablation (CA) is an interventional modality that has been used successfully in chronic neuropathic conditions and is one such option. OBJECTIVE: To study and evaluate the efficacy and safety of cryoablation for treatment of ON. STUDY DESIGN: Retrospective evaluation. SETTING: Academic university-based pain management center. METHODS: All patients received local anesthetic injections for ON. Patients with greater than or equal to 50% relief and less than 2 week duration of relief were treated with CA. RESULTS: Thirty-eight patients with an average age of 49.6 years were included. Of the 38 patients, 20 were treated for unilateral greater ON, 10 for unilateral greater and lesser ON, and 8 for bilateral greater ON. There were 10 men and 28 women, with an average age of 45.2 years and 51.1 years, respectively. The average relief for all local anesthetic injections was 71.2%, 58.3% for patients who reported 50 - 74% relief (Group 1) and 82.75% for patients who reported greater than 75% relief (Group 2). The average improvement of pain relief with CA was 57.9% with an average duration of 6.1 months overall. Group 1 reported an average of 45.2% relief for an average of 4.1 months with CA. In comparison, Group 2 reported an average of 70.5% relief for 8.1 months. The percentage of relief (P = 0.007) and duration of relief (P = 0.0006) was significantly improved in those reporting at least 75% relief of pain with local anesthetic injections (Group 2 vs Group 1). Though no significance in improvement from CA was found in men, significance was seen in women with at least 75% benefit with local anesthetic injections in terms of duration (P = 0.03) and percentage (P = 0.001) of pain relief with CA. The average pain score prior to CA was 8 (0 - 10 visual analog scale, VAS), this improved to 4.2, improvement of 3.8 following CA at 6 months (P = 0.03). Of the 38 patients, 3 (7.8%) adverse effects were seen. Two patients reported post procedure neuritis and one was monitored for procedure-related hematoma. LIMITATIONS: Study limitations include the retrospective nature of the study. Additionally, only the percentage of relief, pain score, and duration of relief were collected. CONCLUSIONS: CA is safe, and should be considered in patients with ON. KEY WORDS: Cryoablation, cryoanalgesia, occipital neuralgia, treatment, adverse effects.

Studying dissolution with a model integrating solid-liquid interface kinetics and diffusion kinetics.

A dissolution model that integrates the solid-liquid interface kinetics and the mass transport kinetics is introduced. Such a model reduces to the Noyes-Whitney equation under special conditions, but offers expanded range of applicability and flexibility fitting dissolution profiles when interfacial kinetics and interfacial concentration deviate from the assumptions implied in the Noyes-Whitney equation. General solutions to the integrated dissolution model derived for noninteractive solutes as well as for solutes participating in ionization equilibrium are discussed. Parameters defining the integrated dissolution model are explained conceptually along with practical ways for their determinations. Conditions under which the model exhibits supersaturation features are elaborated. Simulated dissolution profiles using the integrated dissolution model for published experimental data exhibiting supersaturation features are illustrated.

Efficacy and safety of donepezil in patients with Alzheimer's disease in assisted living facilities.

The aim of this 12-week, open-label study was to determine the safety and efficacy of donepezil in participants with Alzheimer's disease (AD) residing in assisted living facilities (ALFs). Participants received 5 mg donepezil daily for 6 weeks followed by 10 mg daily for 6 weeks. Primary and secondary outcomes were change from baseline in Mini-Mental State Examination (MMSE) and Neuropsychiatric Inventory 8 (NPI-8) scores, respectively. Safety was assessed by adverse events (AEs) and laboratory tests. Of the 97 participants, 76 completed the study. Mean MMSE score (18.7 at baseline) improved 1.8 points (P < .0001) at study end. Total NPI-8 score improved 1.8 points (P = .043). The most frequent AEs were nausea and diarrhea. Donepezil improved cognition and behavior and was safe and well tolerated. The results suggest a need for proactive screening and diagnosis of AD and support the value of treatment and use of donepezil in participants residing in ALFs.

Safety and tolerability of donepezil in mild cognitive impairment: open-label extension study.

Following a 48-week, double-blind, randomized, placebo-controlled trial of donepezil in 821 patients with amnestic mild cognitive impairment (aMCI), safety and tolerability of donepezil (10 mg) were further evaluated in a 28-week extension study. Of 499 participants who completed the double-blind phase, 145 enrolled in the open-label study. Adverse events (AEs) were recorded throughout. Overall, 57.4% of participants in the donepezil/donepezil group and 62.3% in the placebo/donepezil group experienced an AE, with the most frequent treatment-emergent AEs being diarrhea, muscle spasms, insomnia, and nausea. Most were mild to moderate in severity and were more common in the first several weeks after treatment initiation. More participants in the placebo/donepezil group (22.1%) discontinued donepezil due to an AE compared with the donepezil/donepezil group (10.3%). These findings support the safety of donepezil in patients with aMCI. When compared with other studies, however, the data suggest that patients with Alzheimer's tolerate donepezil better than patients with MCI.

Optimizing tacrolimus therapy in the maintenance of renal allografts: 12-month results.

BACKGROUND: The determination of optimal tacrolimus (TAC) trough levels is needed to prevent adverse effects of calcineurin inhibitors. METHODS: Stable transplant recipients currently receiving cyclosporine (CsA) were assigned randomly (1:1:1) to continue CsA (target trough level of 50-250 ng/mL); or convert to "reduced" TAC (target trough level 3.0-5.9 ng/mL) or "standard" TAC (target trough level 6.0-8.9 ng/mL). RESULTS: At 12 months, there was a significant improvement in renal function in the reduced TAC versus CsA group with lower serum creatinine (P=0.004) and cystatin C (P<0.001), and higher estimated creatinine clearance (P=0.017). However, there were no statistically significant differences in any renal parameter in the standard TAC versus CsA group. Total and low-density lipoprotein cholesterol were significantly reduced in both TAC groups versus the CsA group (P<0.001). Patient and graft survival and episodes of biopsy-confirmed acute rejection were similar for all treatment groups, and no statistically significant differences were observed between groups in the incidence of new-onset diabetes or cardiac conditions, or in the prevalence of hyperglycemia, hypertension, or hyperlipidemia among patients who did not have these conditions at baseline. Alopecia developed more commonly among TAC-treated patients than CsA-treated patients (P<0.001). CONCLUSIONS: Compared with CsA continuation, conversion to reduced TAC target trough concentrations resulted in significantly improved renal function without increasing the risk of rejection. Conversion to TAC, regardless of target concentration, resulted in improved serum lipid profiles in kidney transplant recipients at 12 months.