Effectiveness of the 2023-2024 Formulation of the Coronavirus Disease 2019 mRNA Vaccine.

BACKGROUND: The purpose of this study was to evaluate whether the 2023-2024 formulation of the COVID-19 mRNA vaccine protects against COVID-19. METHODS: Employees of Cleveland Clinic in employment when the 2023-2024 formulation of the COVID-19 mRNA vaccine became available to employees, were included. Cumulative incidence of COVID-19 over the following 17 weeks was examined prospectively. Protection provided by vaccination (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression, with time-dependent coefficients used to separate effects before and after the JN.1 lineage became dominant. The analysis was adjusted for the propensity to get tested, age, sex, pandemic phase when the last prior COVID-19 episode occurred, and the number of prior vaccine doses. RESULTS: Among 48210 employees, COVID-19 occurred in 2462 (5.1%) during the 17 weeks of observation. In multivariable analysis, the 2023-2024 formula vaccinated state was associated with a significantly lower risk of COVID-19 before the JN.1 lineage became dominant (HR, .58; 95% C.I., .49-.68, p-value < .001), and lower risk but one that did not reach statistical significance after (HR, .81; 95% C.I., .65-1.01, p-value 0.06). Estimated vaccine effectiveness (VE) was 42% (95% C.I., 32%-51%) before the JN.1 lineage became dominant, and 19% (C.I., -1%-35%) after. Risk of COVID-19 was lower among those previously infected with an XBB or more recent lineage, and increased with the number of vaccine doses previously received. CONCLUSIONS: The 2023-2024 formula COVID-19 vaccine given to working-aged adults afforded modest protection overall against COVID-19 before the JN.1 lineage became dominant, and less protection after.

Body morphometry may predict parastomal hernia following radical cystectomy with ileal conduit.

OBJECTIVE: To investigate whether preoperative body morphometry analysis can identify patients at risk of parastomal hernia (PH), which is a common complication after radical cystectomy (RC). PATIENTS AND METHODS: All patients who underwent RC between 2010 and 2020 with available cross-sectional imaging preoperatively and at 1 and 2 years postoperatively were included. Skeletal muscle mass and total fat mass (FM) were determined from preoperative axial computed tomography images obtained at the level of the L3 vertebral body using Aquarius Intuition software. Sarcopenia and obesity were assigned based on consensus definitions of skeletal muscle index (SMI) and FM index (FMI). PH were graded using both the Moreno-Matias and European Hernia Society criteria. Binary logistic regression and recursive partitioning were used to identify patients at risk of PH. The Kaplan-Meier method with log-rank and Cox proportional hazards models included clinical and image-based parameters to identify predictors of PH-free survival. RESULTS: A total of 367 patients were included in the final analysis, with 159 (43%) developing a PH. When utilising binary logistic regression, high FMI (odds ratio [OR] 1.63, P < 0.001) and low SMI (OR 0.96, P = 0.039) were primary drivers of risk of PH. A simplified model that only relied upon FMI, SMI, and preoperative albumin improved the classification of patients at risk of PH. On Kaplan-Meier analysis, patients who were obese or obese and sarcopenic had significantly worse PH-free survival (P < 0.001). CONCLUSION: Body morphometry analysis identified FMI and SMI to be the most consistent predictors of PH after RC.

Clinical and immunological outcomes of HIV-exposed uninfected and HIV-unexposed uninfected children in the first 24 months of life in Western Kenya.

BACKGROUND: Previous studies show increased morbidity in children who are HIV-exposed but uninfected (HEU) compared to children who are HIV-unexposed uninfected (HUU). We sought to evaluate the effects of prenatal HIV exposure on clinical and immunological outcomes in the first 24 months of life. METHODS: Eighty-five HEU and 168 HUU children from Kenya were followed from birth to 24 months. All mothers living with HIV received combination antiretroviral therapy. Children who were HEU received standard-of-care cotrimoxazole prophylaxis through 18 months. Episodes of acute illness were identified through a combination of active and passive follow up. Trajectories of plasma cytokines, vaccine-specific antibodies, and antimalarial antibodies were examined. RESULTS: Children who were HEU and children who were HUU had similar growth curves. Children who were HEU had lower rates of malaria (rate ratio 0.54, 95% CI 0.38, 0.77) and respiratory illness (rate ratio 0.80, 95% CI 0.68, 0.93). Trajectories of plasma cytokines and vaccine-specific antibodies were similar in children who were HEU and HUU. There were subtle differences in antimalarial antibody dynamics, in which children who were HEU had overall lower antibody levels against five of the 14 malaria antigens tested. CONCLUSIONS: Children who were HEU and born to optimally treated mothers living with HIV had similar growth characteristics and immune profiles compared to children who were HUU. Children who were HEU had reduced risk for malaria and respiratory illness, which may be secondary to cotrimoxazole prophylaxis.

Crohn's Disease Is Associated with Liver Fibrosis in Patients with Nonalcoholic Fatty Liver Disease.

BACKGROUND: Chronic inflammation in IBD is postulated to drive NAFLD progression from steatosis to fibrosis. AIMS: To study the histopathological spectrum of NAFLD in Crohn disease (CD) and Ulcerative colitis (UC). METHODS: Patients with biopsy proven NAFLD at a quaternary center from 2008 to 2018 were included in this retrospective analysis. Inflammatory bowel disease (IBD) diagnosed either clinically and/or endoscopically at the time of liver biopsy. Multivariable regression and propensity score (PS) weighted analysis were conducted. Statistical analysis were performed using SAS statistical software. RESULTS: Among 1009 patients with NAFLD a diagnosis of IBD was identified in 50 cases (34 CD and 16 UC). On multivariable analysis; CD was independently associated with significantly higher odds of advanced fibrosis (AF) on liver biopsy (adjusted OR = 4.09, 95% CI = 1.40-11.94) compared to NAFLD patients without IBD. Similar results were obtained with both the overlap PS weighted model (OR = 3.17, 95% CI = 1.55-6.49) and the PS matched model (OR = 3.49, 95% CI = 1.50-8.13). CONCLUSION: In a large cohort of patients with histologically well characterized NAFLD, AF was more common in CD patients than NAFLD patients without IBD. These findings must be confirmed in a larger cohort, but suggest CD patients with NAFLD could be at greater risk for liver fibrosis.

Risk of Complications in Combined Plastic Surgery Procedures Using the Tracking Operations and Outcomes for Plastic Surgeons Database.

BACKGROUND: Combining multiple surgical procedures into a single operative session is widespread in the field of plastic surgery; however, the implications of this practice are not fully understood. OBJECTIVES: This study compared 30-day complication rates associated with combined plastic surgery procedures with the rates for index procedures. METHODS: This retrospective cohort analysis utilized the Tracking Operations and Outcomes for Plastic Surgeons database from 2016 to 2020 to identify the 3 most frequent combinations of augmentation mammaplasty, reduction mammaplasty, trunk liposuction, mastopexy, and abdominoplasty. RESULTS: The 30-day overall complication rate was 5.0% (1400 of 26,771 patients), with a higher complication rate for combined procedures compared with index (7.6% vs 4.2%, adjusted odd ratio [aOR], 1.91 [95% CI, 1.61-2.27], P < .001). There were no significant differences in complication rates for abdominoplasty or mastopexy combinations compared with index. Complication rates for reduction mammaplasty combinations compared with index were not statistically different after controlling for demographics (aOR, 1.02 [95% CI, 0.61-1.64], P = .93). Higher rates of minor and major complications were observed for combinations of trunk liposuction (aOR, 4.84 [95% CI, 3.31-7.21), P < .001) and augmentation mammaplasty (aOR, 1.60 [95% CI 1.13-2.22], P = .007) compared with index. CONCLUSIONS: Combinations with trunk liposuction or augmentation mammaplasty present with increased risk of complications compared with index, controlling for demographics. Abdominoplasty and mastopexy may be combined with other plastic surgery procedures without increased risk to patients. The complication risk of reduction mammaplasty combinations is mediated by other variables, suggesting the need for shared surgical decision-making when recommending these combinations to patients.

Coronavirus Disease 2019 Vaccine Boosting in Previously Infected or Vaccinated Individuals.

BACKGROUND: The purpose of this study was to determine whether boosting previously infected or vaccinated individuals with a vaccine developed for an earlier variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protects against the Omicron variant. METHODS: Employees of Cleveland Clinic, previously infected with or vaccinated against coronavirus disease 2019 (COVID-19) and working the day the Omicron variant was declared a variant of concern, were included. The cumulative incidence of COVID-19 was examined over 2 months during an Omicron variant surge. Protection provided by boosting was evaluated using Cox proportional hazards regression. Analyses were adjusted for time since proximate SARS-CoV-2 exposure. RESULTS: Among 39 766 employees, 8037 (20%) previously infected and the remaining previously vaccinated, COVID-19 occurred in 6230 (16%) during the study. Risk of COVID-19 increased with time since proximate SARS-CoV-2 exposure, and boosting protected those >6 months since prior infection or vaccination. In multivariable analysis, boosting was independently associated with lower risk of COVID-19 among those vaccinated but not previously infected (hazard ratio [HR], .43; 95% confidence interval [CI], .41-.46) as well as those previously infected (HR, .66; 95% CI, .58-.76). Among those previously infected, receipt of 2 compared with 1 dose of vaccine was associated with higher risk of COVID-19 (HR, 1.54; 95% CI, 1.21-1.97). CONCLUSIONS: Administering a COVID-19 vaccine not designed for the Omicron variant >6 months after prior infection or vaccination protects against Omicron variant infection. There is no advantage to administering more than 1 dose of vaccine to previously infected persons.

Necessity of Coronavirus Disease 2019 (COVID-19) Vaccination in Persons Who Have Already Had COVID-19.

BACKGROUND: The aim was to evaluate the necessity of coronavirus disease 2019 (COVID-19) vaccination in persons with prior COVID-19. METHODS: Employees of the Cleveland Clinic working in Ohio on 16 December 2020, the day COVID-19 vaccination was started, were included. Anyone who tested positive for COVID-19 at least once before the study start date was considered previously infected. One was considered vaccinated 14 days after receiving the second dose of COVID-19 mRNA vaccine. Cumulative incidences of COVID-19, symptomatic COVID-19, and hospitalizations for COVID-19 were examined over the next year. RESULTS: Among 52 238 employees, 4718 (9%) were previously infected and 36 922 (71%) were vaccinated by the study's end. Cumulative incidence of COVID-19 was substantially higher throughout for those previously uninfected who remained unvaccinated than for all other groups, lower for the vaccinated than unvaccinated, and lower for those previously infected than those not. Incidence of COVID-19 increased dramatically in all groups after the Omicron variant emerged. In multivariable Cox proportional hazards regression, both prior COVID-19 and vaccination were independently associated with significantly lower risk of COVID-19. Among previously infected subjects, a lower risk of COVID-19 overall was not demonstrated, but vaccination was associated with a significantly lower risk of symptomatic COVID-19 in both pre-Omicron (HR, .60; 95% CI, .40-.90) and Omicron (HR, .36; 95% CI, .23-.57) phases. CONCLUSIONS: Both previous infection and vaccination provide substantial protection against COVID-19. Vaccination of previously infected individuals does not provide additional protection against COVID-19 for several months, but after that provides significant protection at least against symptomatic COVID-19.

Prolactin-to-Testosterone Ratio Predicts Pituitary Abnormalities in Mildly Hyperprolactinemic Men with Symptoms of Hypogonadism.

PURPOSE: We aimed to identify predictor variables associated with pituitary abnormalities in hypogonadal men with mild hyperprolactinemia. We also sought to develop a decision-making aid to select patients for evaluation with pituitary magnetic resonance imaging. MATERIALS AND METHODS: We retrospectively examined men with mild hyperprolactinemia (15.1-50.0 ng/ml) who presented with symptoms of hypogonadism and underwent pituitary magnetic resonance imaging. Demographics, laboratory values and clinical data were obtained from the electronic medical record. Selected predictor variables were included in multivariable logistic regression and partitioning models. Cost avoidance analysis was performed on models achieving sensitivities ≥90%. RESULTS: A total of 141 men were included in the study, of whom 40 (28%) displayed abnormalities on pituitary magnetic resonance imaging. Patients with pituitary abnormalities exhibited higher prolactin (p=0.01), lower testosterone (p=0.0001) and lower luteinizing hormone (p=0.03) levels than those with normal anatomy, as well as higher prolactin-to-testosterone ratios (p <0.0001) and lower luteinizing hormone-to-follicle-stimulating hormone ratios (p=0.0001). These serological variables were identified as the best performing predictor variables. The partition incorporating a prolactin-to-testosterone ratio cutoff of 0.10 and prolactin cutoff of 25 ng/ml achieved 90% sensitivity and 48% specificity, and reduced diagnostic expenses by 28%. CONCLUSIONS: Hypogonadal men presenting with mild hyperprolactinemia and pituitary abnormalities declare themselves via endocrine studies routinely ordered to evaluate these conditions. The prolactin-to-testosterone ratio is the best independent predictor of finding a pituitary abnormality on magnetic resonance imaging, although sensitivity improves by referencing additional serological parameters. Significant cost avoidance may result from screening this population prior to ordering pituitary magnetic resonance imaging.

Predicting mood decline following temporal lobe epilepsy surgery in adults.

OBJECTIVE: To develop a model to predict the probability of mood decline in adults following temporal lobe resection for the treatment of pharmacoresistant epilepsy. METHODS: Variable selection was performed on 492 patients from the Cleveland Clinic using best subsets regression. After completing variable selection, a subset of variables was requested from four epilepsy surgery centers across North America (n = 100). All data were combined to develop a final model to predict postoperative mood decline (N = 592). Internal validation with bootstrap resampling was performed. A clinically significant increase in depressive symptoms was defined as a 15% increase in Beck Depression Inventory-Second Edition score and a postoperative raw score > 11. RESULTS: Fourteen percent of patients in the Cleveland Clinic cohort and 22% of patients in the external cohort experienced clinically significant increases in depressive symptoms following surgery. The final prediction model included six predictor variables: psychiatric history, resection side, relationship status, verbal fluency score, age at preoperative testing, and presence/absence of malformation of cortical development on magnetic resonance imaging. The model had an optimism-adjusted c-statistic of .70 and good calibration, with slight probability overestimation in higher risk patients. SIGNIFICANCE: Clinicians can utilize our nomogram via a paper tool or online calculator to estimate the risk of postoperative mood decline for individual patients prior to temporal lobe epilepsy surgery.

D-dimer can help differentiate suspected pulmonary embolism patients that require anti-coagulation.

OBJECTIVES: Determine whether D-dimer concentration in the absence of imaging can differentiate patients that require anti-coagulation from patients who do not require anti-coagulation. METHODS: Data was obtained retrospectively from 366 hemodynamically stable adult ED patients with suspected pulmonary embolism (PE). Patients were categorized by largest occluded artery and aggregated into: 'Require anti-coagulation' (main, lobar, and segmental PE), 'Does not require anti-coagulation' (sub-segmental and No PE), 'High risk of deterioration' (main and lobar PE), and 'Not high risk of deterioration' (segmental, sub-segmental, and No PE) groups. Wilcoxon rank-sum test was used for 2 sample comparisons of median D-dimer concentrations. Receiver operating characteristic (ROC) curve analysis was utilized to determine a D-dimer cut-off that could differentiate 'Require anti-coagulation' from 'Does not require anti-coagulation' and 'High risk of deterioration' from 'Low risk of deterioration' groups. RESULTS: The 'Require anti-coagulation' group had a maximum area under the curve (AUC) of 0.92 at an age-adjusted D-dimer cut-off of 1540 with a specificity of 86% (95% CI, 81-91%), and sensitivity of 84% (79-90%). The 'High risk of deterioration' group had a maximum AUC of 0.93 at an age-adjusted D-dimer cut-off of 2500 with a specificity of 90% (85-93%) and sensitivity of 83% (77-90%). CONCLUSIONS: An age-adjusted D-dimer cut-off of 1540 ng/mL differentiates suspected PE patients requiring anti-coagulation from those not requiring anti-coagulation. A cut-off of 2500 differentiates those with high risk of clinical deterioration from those not at high risk of deterioration. When correlated with clinical outcomes, these cut-offs can provide an objective method for clinical decision making when imaging is unavailable.

Fifteen Years' Experience With Safe and Effective Procedural Sedation in Infants and Children in a General Emergency Department.

OBJECTIVE: To evaluate procedural sedation (PS) in infants/children, performed by emergency physicians in a general (nonpediatric) emergency department (ED). METHODS: Procedural sedation prospectively recorded on a standardized form over 15 years. Demographics, sedatives, and analgesia associations with adverse events were explored with logistic regressions. RESULTS: Of 3274 consecutive PS, 1177 were pediatric: 2 months to 21 years, mean age (±SD) 8.7 ± 5.2 years, 63% boys, 717 White, 435 Black, 25 other. Eight hundred and seventy were American Society of Anesthesiology (ASA) 1, 256 ASA 2, 39 ASA 3, 11 ASA 4, 1 ASA 5. Procedural sedation indications are as follows: fracture reduction (n = 649), dislocation reduction (n = 114), suturing/wound care (n = 244), lumbar puncture (n = 49), incision and drainage (n = 37), foreign body removal (n = 28), other (n = 56). Sedatives were ketamine (n = 762), propofol ( = 354), benzodiazepines (n = 157), etomidate (n = 39), barbiturates (n = 39). There were 47.4% that received an intravenous opioid. Success rate was 100%. Side effects included nausea/vomiting, itching/rash, emergence reaction, myoclonus, paradoxical reaction, cough, hiccups. Complications were oxygen desaturation less than 90%, bradypnea respiratory rate less than 8, apnea, tachypnea, hypotension, hypertension, bradycardia, tachycardia. Normal range of vital signs was age-dependent. Seventy-four PS (6.3%) resulted in a side effect and 8 PS (3.2%) a complication. No one died, required hospital admission, intubation, or any invasive procedure. CONCLUSIONS: Adverse events in infants/children undergoing PS in a general ED are low and comparable to a pediatric ED at a children's hospital. Pediatric PS can be done safely and effectively in a general ED by nonpediatric EM physicians for a wide array of procedures.

Distribution of Transmission Potential During Nonsevere COVID-19 Illness.

BACKGROUND: Patients recovering from coronavirus disease 2019 (COVID-19) often continue to test positive for the causative virus by polymerase chain reaction (PCR) even after clinical recovery, thereby complicating return-to-work plans. The purpose of this study was to evaluate transmission potential of COVID-19 by examining viral load with respect to time. METHODS: Health care personnel (HCP) at Cleveland Clinic diagnosed with COVID-19, who recovered without needing hospitalization, were identified. Threshold cycles (Ct) for positive PCR tests were obtained and viral loads calculated. The association of viral load with days since symptom onset was examined in a multivariable regression model, which was reduced by stepwise backward selection to only keep variables significant at a level of .05. Viral loads by day since symptom onset were predicted using the model and transmission potential evaluated by examination of a viral load-time curve. RESULTS: Over 6 weeks, 230 HCP had 528 tests performed. Viral loads declined by orders of magnitude within a few days of symptom onset. The only variable significantly associated with viral load was time since onset of symptoms. Of the area under the curve (AUC) spanning symptom onset to 30 days, 96.9% lay within the first 7 days, and 99.7% within 10 days. Findings were very similar when validated using split-sample and 10-fold cross-validation. CONCLUSIONS: Among patients with nonsevere COVID-19, viral loads in upper respiratory specimens peak by 2 or 3 days from symptom onset and decrease rapidly thereafter. The vast majority of the viral load-time AUC lies within 10 days of symptom onset.

Paediatric haematologists' attitudes regarding haematopoietic cell transplantation as treatment for sickle cell disease.

Beginning early in childhood, patients with sickle cell disease [SCD; a group of genetic haemoglobin disorders characterized by the sickle or HbS mutation (HBB E7V)] are at risk of life-threatening and debilitating health events. Despite the high morbidity and mortality of this disease, haematopoietic cell transplantation (HCT), a curative therapy for SCD, remains underutilized. A variety of factors, including the limited availability of suitable donors, play a role in this trend, but do not fully explain the low frequency with which this therapy is employed. The objective of this study was to identify paediatric haematologists' attitudes about HCT as a treatment option for SCD, and to describe the impact of these attitudes on their practices of discussing HCT with families of children affected by this disease. A nationwide survey of paediatric haematologists in the United States was conducted between February and May 2016. Two hundred and eighty-seven surveys were included in the final analysis (response rate 20%). On average, respondents reported informing 42% of families about HCT as a treatment option (N = 248, 95% confidence interval: 38-46). Clinician attitudes about the cost and safety of HCT were associated with practices of discussing this therapy with families. These findings suggest that clinician attitudes and referral practices may play a role in the underutilization of this therapy in the SCD population.

Impact of the COVID-19 Pandemic on Healthcare Workers' Risk of Infection and Outcomes in a Large, Integrated Health System.

BACKGROUND: Understanding the impact of the COVID-19 pandemic on healthcare workers (HCW) is crucial. OBJECTIVE: Utilizing a health system COVID-19 research registry, we assessed HCW risk for COVID-19 infection, hospitalization, and intensive care unit (ICU) admission. DESIGN: Retrospective cohort study with overlap propensity score weighting. PARTICIPANTS: Individuals tested for SARS-CoV-2 infection in a large academic healthcare system (N = 72,909) from March 8-June 9, 2020, stratified by HCW and patient-facing status. MAIN MEASURES: SARS-CoV-2 test result, hospitalization, and ICU admission for COVID-19 infection. KEY RESULTS: Of 72,909 individuals tested, 9.0% (551) of 6145 HCW tested positive for SARS-CoV-2 compared to 6.5% (4353) of 66,764 non-HCW. The HCW were younger than the non-HCW (median age 39.7 vs. 57.5, p < 0.001) with more females (proportion of males 21.5 vs. 44.9%, p < 0.001), higher reporting of COVID-19 exposure (72 vs. 17%, p < 0.001), and fewer comorbidities. However, the overlap propensity score weighted proportions were 8.9 vs. 7.7 for HCW vs. non-HCW having a positive test with weighted odds ratio (OR) 1.17, 95% confidence interval (CI) 0.99-1.38. Among those testing positive, weighted proportions for hospitalization were 7.4 vs. 15.9 for HCW vs. non-HCW with OR of 0.42 (CI 0.26-0.66) and for ICU admission: 2.2 vs. 4.5 for HCW vs. non-HCW with OR of 0.48 (CI 0.20-1.04). Those HCW identified as patient facing compared to not had increased odds of a positive SARS-CoV-2 test (OR 1.60, CI 1.08-2.39, proportions 8.6 vs. 5.5), but no statistically significant increase in hospitalization (OR 0.88, CI 0.20-3.66, proportions 10.2 vs. 11.4) and ICU admission (OR 0.34, CI 0.01-3.97, proportions 1.8 vs. 5.2). CONCLUSIONS: In a large healthcare system, HCW had similar odds for testing SARS-CoV-2 positive, but lower odds of hospitalization compared to non-HCW. Patient-facing HCW had higher odds of a positive test. These results are key to understanding HCW risk mitigation during the COVID-19 pandemic.

Family history of psoriasis, psychological stressors, and tobacco use are associated with the development of tumor necrosis factor-α inhibitor-induced psoriasis: A case-control study.

BACKGROUND: Tumor necrosis factor-α inhibitor-induced psoriasis (TNFI psoriasis) is a paradoxical reaction characterized by development of a psoriasiform rash that mimics psoriasis vulgaris. Temporal onset variability and low incidence rates suggest that underlying risk factors or outside triggers have a role in TNFI psoriasis initiation. OBJECTIVES: We aimed to identify underlying risk factors and outside triggers associated with TNFI psoriasis onset. METHODS: This case-control study included 97 patients at a tertiary care center between 2003 and 2013 who developed TNFI psoriasis. Ninety-seven control patients were matched to age, sex, disease, TNF-α inhibitor, and length of time on treatment before TNFI psoriasis onset. Patient medical records were reviewed ≥6 months immediately preceding TNFI psoriasis onset (similar equivalent time point for matched controls) for information about potential risk factors and outside factors categorized as: (1) serologic abnormalities, (2) acute events, and (3) social factors. RESULTS: Compared with those of matched controls, odds ratios (ORs) were significantly higher in the TNFI psoriasis group for psoriasis family history (OR, 16.0) and acute psychological stressors (OR, 3.14) and marginally associated with tobacco use (OR, 1.76). CONCLUSIONS: Our results suggest that psoriasis family history, psychological stressors, and tobacco use might be risk factors for developing TNFI psoriasis. Performing detailed patient histories when considering TNFI therapy may be useful in identifying patients at risk for TNFI-psoriasis.

Parent and Guardian Knowledge of Hematopoietic Cell Transplantation as a Treatment Option for Sickle Cell Disease.

Beginning early in childhood, patients with sickle cell disease (SCD) are at risk of life-threatening and debilitating health events. Despite the high morbidity and mortality of this disease, hematopoietic cell transplantation (HCT), a curative treatment for SCD, remains underutilized. In the literature there is a paucity of data concerning medical decision maker (MDM) awareness of HCT as a treatment option for SCD. The objective of this study was to estimate the proportion of parents/guardians of children with SCD who are aware of HCT as a treatment option, and to identify the demographic factors associated with knowledge of this therapy's curative potential. Between November 2015 and December 2016, 327 parents/guardians were surveyed across 4 clinical sites in 3 Midwestern US cities. Although 82% of parents/guardians had heard of HCT in the past and 78% were aware of the therapy's curative potential, nearly half indicated that they did not know whether HCT could specifically cure their child of the disease. Respondents who had discussed HCT with their child's physician had 5 times higher odds of being aware of HCT's curative potential than those who had not. These findings suggest that additional efforts to enhance MDM knowledge of HCT as well as shared decision making in the use of this therapy, is warranted.

Frequency, Timing, and Types of Medication Ordering Errors Made by Residents in the Electronic Medical Records Era.

OBJECTIVES: To describe associations between resident level of training, timing of medication orders, and the types of inpatient medication ordering errors made by internal medicine residents. METHODS: This study reviewed all inpatient medication orders placed by internal medicine residents at a tertiary care academic medical center from July 2011 to June 2015. Medication order errors were measured by pharmacists' reporting of an error via the electronic medical record during real-time surveillance of orders. Multivariable regression models were constructed to assess associations between resident training level (postgraduate year [PGY]), medication order timing (time of day and month of year), and rates of medication ordering errors. RESULTS: Of 1,772,462 medication orders placed by 335 residents, 68,545 (3.9%) triggered a pharmacist intervention in the electronic medical record. Overall and for each PGY level, renal dose monitoring/adjustment was the most common order error (40%). Ordering errors were less frequent during the night and transition periods versus daytime (adjusted odds ratio [aOR] 0.93, 95% confidence interval [CI] 0.91-0.96, and aOR 0.93, 95% CI 0.90-0.95, respectively). Errors were more common in July and August compared with other months (aOR 1.05, 95% CI 1.01-1.09). Compared with PGY2 residents, both PGY1 (aOR 1.06, 95% CI 1.03-1.10), and PGY3 residents (aOR 1.07, 95% CI, 1.03-1.10) were more likely to make medication ordering errors. Throughout the course of the academic year, the odds of a medication ordering error decreased by 16% (aOR 0.84, 95% CI 0.80-0.89). CONCLUSIONS: Despite electronic medical records, medication ordering errors by trainees remain common. Additional supervision and resident education regarding medication orders may be necessary.

The impact of resection margin on overall survival for patients with colon cancer liver metastasis varied according to the primary cancer location.

INTRODUCTION: Investigation into right and left-sided primary colon liver metastasis (CLM) has revealed differences in the tumor biology and prognosis. This indicates that preoperative and operative factors may affect outcomes of right-sided primary CLM differently than left. This retrospective analysis investigated the effects of resection margin stratified by left and right-sided primary CLM on overall survival (OS) for patients undergoing hepatectomy. METHODS: A total of 732 patients undergoing hepatic resection for CLM at the Cleveland Clinic and Johns Hopkins were identified between 2002 and 2016. Clinically significant variables were analyzed using Cox proportional hazard regression. The cohort was then divided into patients with right and left-sided CLM and analyzed separately using Kaplan Meier analysis and Cox proportional hazard regression. RESULTS: Cox proportional hazard regression showed that left-sided CLM with an R0 margin was a statistically significant predictor of OS even after controlling for other important factors (HR = 0.629, P = 0.024) but right-sided CLM with R0 margin was not (HR = 0.788, P = 0.245). Kaplan-Meier analysis demonstrated that patients with a left-sided CLM and R0 margin had the best prognosis (P = 0.037). CONCLUSION: Surgical margin is an important prognostic factor for left-sided primary CLM but tumor biology may override surgical technique for right-sided CLM.

Expression of LC3B and FIP200/Atg17 in brain metastases of breast cancer.

BACKGROUND: Macroautophagy/autophagy is considered to play key roles in tumor cell evasion of therapy and establishment of metastases in breast cancer. High expression of LC3, a residual autophagy marker, in primary breast tumors has been associated with metastatic disease and poor outcome. FIP200/Atg17, a multi-functional pro-survival molecule required for autophagy, has been implicated in brain metastases in experimental models. However, expression of these proteins has not been examined in brain metastases from patients with breast cancer. METHODS: In this retrospective study, specimens from 44 patients with brain metastases of infiltrating ductal carcinoma of the breast (IDC), unpaired samples from 52 patients with primary IDC (primary-BC) and 16 matched-paired samples were analyzed for LC3 puncta, expression of FIP200/Atg17, and p62 staining. RESULTS: LC3-puncta+ tumor cells and FIP200/Atg17 expression were detected in greater than 90% of brain metastases but there were considerable intra- and inter-tumor differences in expression levels. High numbers of LC3-puncta+ tumor cells in brain metastases correlated with a significantly shorter survival time in triple-negative breast cancer. FIP200/Atg17 protein levels were significantly higher in metastases that subsequently recurred following therapy. The percentages of LC3 puncta+ tumor cells and FIP200/Atg17 protein expression levels, but not mRNA levels, were significantly higher in metastases than primary-BC. Meta-analysis of gene expression datasets revealed a significant correlation between higher FIP200(RB1CC1)/Atg17 mRNA levels in primary-BC tumors and shorter disease-free survival. CONCLUSIONS: These results support assessments of precision medicine-guided targeting of autophagy in treatment of brain metastases in breast cancer patients.

Health Literacy (HL) & Health-Related Quality of Life (HRQL) Among Minority Men.

Health literacy remains a key factor in the continuance of health disparities in our society as health related quality of life can be negatively affected by limited health literacy. This study explores how limited health literacy among minority men, attending a community health fair, correlates with their health related quality of life. Findings reflect that minority men who possess lower levels of health literacy experience lower self-reported quality of life. Directions for healthcare providers, community health educators and future research approaches are provided.