Comparison of retention of monolithic zirconia crowns with alumina airborne-particle abraded and nonabraded intaglio using three different cements: A clinical simulation.

STATEMENT OF PROBLEM: The necessity of roughening the intaglio surface of zirconia crowns to achieve adequate retention is unclear. PURPOSE: The purpose of this clinical simulation study was to evaluate the retention of airborne-particle-abraded and nonabraded monolithic zirconia crowns using 3 different cement types. MATERIAL AND METHODS: Extracted human molars were used and prepared with a 10-degree taper. Impressions were made of the prepared teeth with a polyvinyl siloxane (PVS) material, and dies were made with Type 4 gypsum. Each die was scanned with a NobelProcera 1G Scanner, and the standard tessellation language (STL) files were transferred electronically to the Nobel Biocare production site, where a bar was added virtually on top of each crown and parameters were set for milling. Seventy-two Procera zirconia crowns were generated, of which half were airborne-particle abraded on the intaglio surface with 50-µm alumina particles at 400 to 500 kPa for 15 seconds. The other 36 received no intaglio treatment other than cleaning. Both groups of 36 crowns were divided into 3 subgroups of 12 specimens. The area of each preparation was calculated using a computer-aided design software program. The specimens were distributed to attain similar mean surface areas among the cementation groups. The crowns were cemented onto the specimen with a controlled force of 196 N. The 3 cements used were self-adhesive, modified resin RelyX Unicem Aplicap, resin-modified glass ionomer RelyX Luting, and a composite resin, Panavia F2.0 with ED Primer A & B. All specimens were thermocycled (5 °C to 55 °C) for 5000 cycles and then removed axially with a universal testing machine (Instron Model 5585H) at a crosshead speed of 0.5 mm/min. The removal force was recorded, and stress of dislodgement was calculated for each crown. A 2-way analysis of variance was used for statistical analyses. The type of failure was analyzed with the chi-squared test of association for independent samples (α=.05 for all tests). RESULTS: The mean dislodging force for crowns with airborne-particle abraded intaglio was 5.4 MPa, which was statistically greater than the mean of 3.2 MPa for nonabraded specimens (P<.001). No significant differences related to the dislodging stresses were detected among the 3 cements (P=.109). The mode of failure was similar whether abraded or not, with 50% of specimens retaining cement in the crown after separation. CONCLUSIONS: Alumina airborne-particle abrasion of the intaglio of zirconia to create surface roughness is beneficial in retaining the crowns, regardless of the cement type. The nonabraded crowns demonstrated significantly lower retentive stress with crown removal. The principal mode of failure was similar whether the zirconia intaglio was airborne-particle abraded or not. The most common mode of failure (>50% of specimens) was at least three-fourths of the cement remaining within the crown.

No Drain, No Problem: Serum-Based Marker Prediction of Clinically Relevant Postoperative Pancreatic Fistula.

BACKGROUND: Postoperative day (POD) 1 drain amylase concentration (DAC) is considered the most accurate predictor for the development of a clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy (PD). Recent studies have associated drain placement with negative postoperative outcomes. This study aims to evaluate multiple biochemical markers and their associations with CR-POPF development in order to identify a reliable, non-drain dependent alternative to DAC. METHODS: This is a review of 53 consecutive PD patients between 2021 and 2022. Albumin, C-reactive protein (CRP), C-reactive protein-to-albumin ratio (CAR), DAC, white blood cell count, and procalcitonin values were compared by CR-POPF status. The discriminatory abilities of CAR, CRP, and DAC for CR-POPF were compared using receiver operating characteristic (ROC) curves. RESULTS: Six of 51 included patients developed a CR-POPF. Receiver operating characteristic curve analysis produced an area under the curve of .977 for POD 1 DAC (cut-off 5131.0 IU/L, sensitivity 100%, specificity 95.5%), .858 for POD 1 CRP (cut-off 52.5 mg/L, sensitivity 100%, specificity 72.7%), and 1.000 for POD 3 CAR (cut-off 99.2, sensitivity and specificity 100%). POD 3 CAR produced a positive and negative predictive value of 100%. CONCLUSION: The CAR and CRP provide early and accurate identification of patients with post-PD CR-POPFs. These markers offer a method of safe CR-POPF detection, when the gold standard DAC is unavailable, ultimately allowing for early intervention and patient rescue.

A multi-site phase I trial of Veliparib with standard radiation and temozolomide in patients with newly diagnosed glioblastoma multiforme (GBM).

PURPOSE: A multi-site Phase I trial was conducted to determine the safety, maximum tolerated dose, and pharmacokinetics (PK) of Veliparib, a Poly (ADP-ribose) polymerase [PARP] enzyme inhibitor, when administered with temozolomide (TMZ) alone and then with temozolomide and radiation (RT) in patients with newly diagnosed glioblastoma. METHODS: Given the potential for myelosuppression when a PARP inhibitor is combined with chemotherapy, the first 6 patients accrued were given Veliparib 10 mg bid and TMZ 75 mg/m2/d daily for six weeks. If this was well tolerated, the same doses of Veliparib and TMZ would be tested along with standard radiation with plans to dose escalate the Veliparib in subsequent patient cohorts. Once a maximal tolerated dose was determined, a 78 patient phase II study was planned. Peripheral blood pharmacokinetics were assessed. RESULTS: Twenty-four patients were enrolled. In the first 6 patients who received 6 weeks of TMZ with Veliparib only one dose limiting toxicity (DLT) occurred. The next 12 patients received 6 weeks of RT + TMZ + veliparib and 4/12 (33%) had dose limiting hematologic toxicities. As a result, Veliparib was reduced by 50% to 10 mg BID every other week, but again 3/3 patients had dose limiting hematologic toxicities. The trial was then terminated. The mean clearance (± SD) CL/F of Veliparib for the initial dose (27.0 ± 9.0 L/h, n = 16) and at steady-state for 10 mg BID (23.5 ± 10.4 L/h, n = 18) were similar. Accumulation for BID dosing was 56% (± 33%). CONCLUSIONS: Although Veliparib 10 mg BID administered with TMZ 75 mg/m2 for six weeks was well tolerated, when this regimen was combined with standard partial brain irradiation it was severely myelosuppressive even when the dose was reduced by 50%. This study again highlights the potential of localized cranial radiotherapy to significantly increase hematologic toxicity of marginally myelosuppressive systemic therapies.

18F-fluciclovine PET/CT to distinguish radiation necrosis from tumor progression for brain metastases treated with radiosurgery: results of a prospective pilot study.

PURPOSE: Distinguishing radiation necrosis from tumor progression among patients with brain metastases previously treated with stereotactic radiosurgery represents a common diagnostic challenge. We performed a prospective pilot study to determine whether PET/CT with 18F-fluciclovine, a widely available amino acid PET radiotracer, repurposed intracranially, can accurately diagnose equivocal lesions. METHODS: Adults with brain metastases previously treated with radiosurgery presenting with a follow-up tumor-protocol MRI brain equivocal for radiation necrosis versus tumor progression underwent an 18F-fluciclovine PET/CT of the brain within 30 days. The reference standard for final diagnosis consisted of clinical follow-up until multidisciplinary consensus or tissue confirmation. RESULTS: Of 16 patients imaged from 7/2019 to 11/2020, 15 subjects were evaluable with 20 lesions (radiation necrosis, n = 16; tumor progression, n = 4). Higher SUVmax statistically significantly predicted tumor progression (AUC = 0.875; p = 0.011). Lesion SUVmean (AUC = 0.875; p = 0.018), SUVpeak (AUC = 0.813; p = 0.007), and SUVpeak-to-normal-brain (AUC = 0.859; p = 0.002) also predicted tumor progression, whereas SUVmax-to-normal-brain (p = 0.1) and SUVmean-to-normal-brain (p = 0.5) did not. Qualitative visual scores were significant predictors for readers 1 (AUC = 0.750; p < 0.001) and 3 (AUC = 0.781; p = 0.045), but not for reader 2 (p = 0.3). Visual interpretations were significant predictors for reader 1 (AUC = 0.898; p = 0.012) but not for reader 2 (p = 0.3) or 3 (p = 0.2). CONCLUSIONS: In this prospective pilot study of patients with brain metastases previously treated with radiosurgery presenting with a contemporary MRI brain with a lesion equivocal for radiation necrosis versus tumor progression, 18F-fluciclovine PET/CT repurposed intracranially demonstrated encouraging diagnostic accuracy, supporting the pursuit of larger clinical trials which will be necessary to establish diagnostic criteria and performance.

Studying social change in human lives: a conversation.

This commentary reinforces a central commitment of life course research: to make visible how social change matters in human lives. This paper captures a moderated conversation with four senior scholars about how they came to study the intersection between social change and life experience, why this intersection is so important to life course studies, and theoretical and methodological imperatives and challenges that come with it.

Effect of vaccination on the case fatality rate for COVID-19 infections 2020-2021: multivariate modelling of data from the US Department of Veterans Affairs.

OBJECTIVES: To evaluate the benefits of vaccination on the case fatality rate (CFR) for COVID-19 infections. DESIGN, SETTING AND PARTICIPANTS: The US Department of Veterans Affairs has 130 medical centres. We created multivariate models from these data-339 772 patients with COVID-19-as of 30 September 2021. OUTCOME MEASURES: The primary outcome for all models was death within 60 days of the diagnosis. Logistic regression was used to derive adjusted ORs for vaccination and infection with Delta versus earlier variants. Models were adjusted for confounding factors, including demographics, comorbidity indices and novel parameters representing prior diagnoses, vital signs/baseline laboratory tests and outpatient treatments. Patients with a Delta infection were divided into eight cohorts based on the time from vaccination to diagnosis. A common model was used to estimate the odds of death associated with vaccination for each cohort relative to that of unvaccinated patients. RESULTS: 9.1% of subjects were vaccinated. 21.5% had the Delta variant. 18 120 patients (5.33%) died within 60 days of their diagnoses. The adjusted OR for a Delta infection was 1.87±0.05, which corresponds to a relative risk (RR) of 1.78. The overall adjusted OR for prior vaccination was 0.280±0.011 corresponding to an RR of 0.291. Raw CFR rose steadily after 10-14 weeks. The OR for vaccination remained stable for 10-34 weeks. CONCLUSIONS: Our CFR model controls for the severity of confounding factors and priority of vaccination, rather than solely using the presence of comorbidities. Our results confirm that Delta was more lethal than earlier variants and that vaccination is an effective means of preventing death. After adjusting for major selection biases, we found no evidence that the benefits of vaccination on CFR declined over 34 weeks. We suggest that this model can be used to evaluate vaccines designed for emerging variants.

A novel method for handling pre-existing conditions in multivariate prediction model development for COVID-19 death in the Department of Veterans Affairs.

Many mathematical models have been proposed to predict death following the Coronavirus Disease 2019 (COVID-19); all started with comorbidity subsets for this still-little understood disease. Thus, we derived a novel predicted probability of death model (PDeathDx) upon all diagnostic codes documented in the Department of Veterans Affairs. We present the conceptual underpinnings and analytic approach in estimating the independent contribution of pre-existing conditions. This is the largest study to-date following patients with COVID-19 to predict mortality. Cases were identified with at least one positive nucleic acid amplification test. Starting in 1997, we use diagnoses from the first time a patient sought care until 14 days before a positive nucleic acid amplification test. We demonstrate the clear advantage of using an unrestricted set of pre-existing conditions to model COVID-19 mortality, as models using conventional comorbidity indices often assign little weight or usually do not include some of the highest risk conditions; the same is true of conditions associated with COVID-19 severity. Our findings suggest that it is risky to pick comorbidities for analysis without a systematic review of all those experienced by the cohort. Unlike conventional approaches, our comprehensive methodology provides the flexibility that has been advocated for comorbidity indices since 1993; such an approach can be readily adapted for other diseases and outcomes. With our comorbidity risk adjustment approach outperforming conventional indices for predicting COVID-19 mortality, it shows promise for predicting outcomes for other conditions of interest.

Sex-Specific Differences in Low-Grade Glioma Presentation and Outcome.

PURPOSE: In addition to established prognostic factors in low-grade glioma (LGG), studies suggest a sexual dimorphism with male sex portending worse prognosis. Our objective was to identify the effect of sex on presentation and outcomes in LGG. METHODS AND MATERIALS: We conducted a retrospective cohort study of adults (aged ≥18 years) diagnosed with LGG (World Health Organization 2016 grade 2 glioma). Patients with IDH wild-type tumors were excluded. Patients were matched between male and female sex by age, treatment, and surgery via propensity score matching. Patient, tumor, and treatment characteristics were analyzed by sex. Endpoints included overall survival (OS), next intervention-free survival (NIFS), progression-free survival, and malignant transformation-free survival. Kaplan-Meier analyses and Cox proportional hazards regression multivariable analysis with backward elimination were completed. RESULTS: Of the 532 patients identified, 258 (48%) were men. Men were more likely to present with seizure (69.38% vs 56.57%, P = .002), but no other statistically significant differences between sexes at presentation were identified. Five-year OS was higher in women at 87% (95% confidence interval [CI], 83%-91%) versus 78% (95% CI, 73%-84%) in men (P = .0045). NIFS was significantly higher in female patients at 68% (95% CI, 62%-74%) versus 57% (95% CI, 51%-64%) in men (P = .009). On multivariable analysis, female sex was independently associated with improved OS (hazard ratio [HR], 1.54; 95% CI, 1.16-2.05; P = .002), NIFS (HR, 1.42; 95% CI, 1.42; P = .004), and malignant transformation-free survival (HR, 1.62; 95% CI, 1.24-2.12; P = .0004). In patients with molecularly defined LGG (IDH and 1p19q status; n = 291), female sex remained independently associated with improved OS (HR, 1.79; 95% CI, 1.16-2.77; P = .008) and NIFS (HR, 1.45; 95% CI, 1.07-1.96; P = .016). CONCLUSIONS: In this study, female sex was independently associated with improved outcomes. These findings support intrinsic sex-specific differences in LGG behavior, justifying further studies to optimize management and therapeutics based on sex.

Radiation Therapy for Brain Metastases: ASCO Guideline Endorsement of ASTRO Guideline.

PURPOSE: American Society of Radiation Oncology (ASTRO) has developed a guideline on appropriate radiation therapy for brain metastases. ASCO has a policy and set of procedures for endorsing clinical practice guidelines that have been developed by other professional organizations. METHODS: "Radiation Therapy for Brain Metastases: An ASTRO Clinical Practice Guideline"2 was reviewed for developmental rigor by methodologists. An ASCO Endorsement Panel subsequently reviewed the content and the recommendations. RESULTS: The ASCO Endorsement Panel determined that the recommendations from the ASTRO guideline, published May 6, 2022, are clear, thorough, and based upon the most relevant scientific evidence. ASCO endorses "Radiation Therapy for Brain Metastases: An ASTRO Clinical Practice Guideline."2. RECOMMENDATIONS: Within the guideline, stereotactic radiosurgery (SRS) is recommended for patients with Eastern Cooperative Oncology Group performance status of 0-2 and up to four intact brain metastases, and conditionally recommended for patients with up to 10 intact brain metastases. The guideline provides detailed dosing and fractionation recommendations on the basis of the size of the metastases. For patients with resected brain metastases, radiation therapy (SRS or whole-brain radiation therapy [WBRT]) is recommended to improve intracranial disease control; if there are limited additional brain metastases, SRS is recommended over WBRT. For patients with favorable prognosis and brain metastases ineligible for surgery and/or SRS, WBRT is recommended with hippocampal avoidance where possible and the addition of memantine is recommended. For patients with brain metastases, limiting the single-fraction V12Gy to brain tissue to ≤ 10 cm3 is conditionally recommended.Additional information is available at www.asco.org/neurooncology-guidelines.

Cognitive function after concurrent temozolomide-based chemoradiation therapy in low-grade gliomas.

PURPOSE: We sought to evaluate the effects of concurrent temozolomide-based chemoradiation therapy on neurocognitive function in patients with low-grade glioma (LGG). MATERIALS/METHODS: We included adult patients with LGG who were treated postoperatively with radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ). Patients were evaluated with comprehensive psychometric tests at baseline (prior to RT + TMZ) and at various time intervals following RT + TMZ. Baseline cognitive performance was analyzed by sex, age, education history, history of seizures, IDH mutation status, and 1p/19q codeletion status. Changes in neurocognitive performance were evaluated over time. RESULTS: Thirty-seven LGG patients (mean age 43.6, 59.5% male) had baseline neurocognitive evaluation. Patients with an age > 40 years old at diagnosis and those with an education > 16 years demonstrated superior baseline verbal memory as assessed by HVLT. No other cognitive domains showed differences when stratified by the variables mentioned above. A total of 22 LGG patients had baseline and post RT + TMZ neurocognitive evaluation. Overall, patients showed no statistical difference between group mean test scores prior to and following RT + TMZ on all psychometric measures (with the exception of HVLT Discrimination). CONCLUSION: Cognitive function remained stable following RT + TMZ in LGG patients evaluated prospectively up to 2 years. The anticipated analysis of RTOG 0424 will provide valuable neurocognitive outcomes specifically for high risk LGG patients treated with RT + TMZ.

Quality of life following concurrent temozolomide-based chemoradiation therapy or observation in low-grade glioma.

PURPOSE: Low-grade glioma (LGG) exhibits longer median survival than high-grade brain tumors, and thus impact of our therapies on patient quality of life remains a crucial consideration. This study evaluated the effects of concurrent temozolomide-based chemoradiation (RT + TMZ) or observation on quality of life (QOL) in patients with low-grade glioma. METHODS: We completed a retrospective cross-sectional study of adults with LGG who underwent surgery with known molecular classification from 1980 to 2018. Postoperatively, patients were either observed or received adjuvant concurrent temozolomide-based chemoradiation. EQ-5D and PHQ-9 depression screen were completed before outpatient visits every 2-3 months. Baseline score was defined as ± 30 days within initial operation. RESULTS: Of the 63 patients (mean age 44 ± 17 years, 51% female) with baseline EQ-5D or PHQ-9 depression screen data and at least one follow-up measure, 30 (48%) were observed and 33 (52%) received RT + TMZ. No significant decline was seen in EQ-5D or PHQ-9 scores at 3, 6, 9, 12, and 24 months compared to baseline scores for all patients. At each time point, there was no significant difference between those who were observed or received adjuvant therapy. The linear mixed model estimating PHQ-9 value or EQ-5D index demonstrated that there was no significant difference in PHQ-9 or EQ-5D index between treatment groups (p = 0.42 and p = 0.54, respectively) or time points (p = 0.24 and p = 0.99, respectively). CONCLUSION: Our study found no significant decline in patient QOL or depression scores as assessed by patient- reported outcome measures for patients with low-grade glioma up to 2 years following surgery. We found no difference between RT + TMZ compared to observation during this time frame. Additional follow-up can help identify the longer-term impact of treatment strategy on patient experience.

BASELINE METABOLIC PROFILING AND RISK OF DEATH FROM COVID-19

ObjectiveTo derive a predicted probability of death (PDeathLabs) based upon complete value sets for 11 clinical measurements (CM) obtained on patients prior to their diagnosis of coronavirus disease (COVID-19). PDeathLabs is intended for use as a summary metric for baseline metabolic status in multivariate models for COVID-19 death. MethodsCases were identified through the COVID-19 Shared Data Resource (CSDR) of the Department of Veterans Affairs. The diagnosis required at least one positive nucleic acid amplification test (NAAT). The primary outcome was death within 60 days of the first positive test. We retrieved all values for systolic blood pressure (SBP), diastolic blood pressure (DBP), oxygen saturation (O2SAT), body mass index (BMI), estimated glomerular filtration rate (EGFR), alanine aminotransferase (ALT), serum albumin (ALB), hematocrit (HCT), LDL cholesterol (LDL) hemoglobin A1c (A1C), and HDL cholesterol (HDL) if they were done at least 14 days prior to the NAAT. Clinicians evaluate several attributes of CM that are of critical importance: metabolic control, disease burden, chronicity, refractoriness, tendency to relapse, temporal trends, and lability. We derived 1-3 parameters for each of these attributes: the most recent value (metabolic control); time-weighted average and abnormal area under a severity versus time curve (disease burden); time and number of readings above or below goal (chronicity); longest abnormal cluster and time/number of consecutive readings above goal if the last value was abnormal (refractoriness); number of abnormal clusters (tendency to relapse); long- and short-term changes (temporal trends); and coefficient of variation and mean deviation between consecutive readings (lability). We created computer programs to derive cumulative values for these 13 parameters for all 11 CM as each new value is added. A fitted logistic model was developed for each CM to determine which of the 13 parameters contributed to the risk of death. A main logistic model was developed to determine which of the 13 x 11 = 143 metabolic parameters were independently predictive of death. The resulting model was used to derive PDeathLabs for each patient and the area under its receiver operating characteristic (ROC) curve calculated. Single variable logistic models were also derived for age at diagnosis, the Charlson 2-year (Charl2Yr) and lifetime (CharlEver) scores, and the Elixhauser 2-year (Elix2Yrs) and lifetime (ElixEver) scores. Stata was used to compare the ROCs for PDeathDx and each of the other metrics. ResultsOn September 30, 2021, there were 347,220 COVID-19 patients in the CSDR. 329,491 (94.9%) patients had CM performed at least 14 days prior to the COVID-19 diagnosis and form the basis for this report. 17,934 (5.44%) died within 60 days of the diagnosis. On the subset regressions, the number of significant parameters ranged from all 13 for SBP to 7 for HDL. 239,393 patients had complete sets of data for developing the main model. Of 143 candidate predictors, 49 parameters were identified as statistically significant, independent predictors of death. The most influential domains were the most recent value, disease burden, temporal trends, and tendency to relapse. The ROC area for PDeathLabs was 0.785 +/- 0.002. No difference was found in the ROC areas of PDeathLabs and age at diagnosis (0.783 +/- 0.002; P = NS). However, the ROC area for PDeathLabs was significantly greater than that of Charl2Yrs (0.704 +/- 0.002; P < 0.001), CharlEver (0.729 +/- 0.002; P < 0.001), Elix2Yrs (0.675 {+/-} 0.002; P < 0.001), and ElixEver (0.707 +/- 0.002; P < 0.001). A poor prognosis was found for chronic systolic hypertension. On the other hand, a higher BMI was protective once SBP, DBP, HDL, LDL and A1C were considered. ConclusionsOur study confirms that parameters derived for 11 CM are significant determinants of COVID-19 death. The most recent value should not be selected over other parameters for multivariate modeling unless there is a physiologic basis for doing so. PDeathLabs has the same discriminating power as age at diagnosis and outperforms comorbidity indices as a summary metric for pre-existing conditions. If validated by others, this approach provides a robust approach to handling CM in multivariate models.

A NOVEL METHOD FOR HANDLING PRE-EXISTING CONDITIONS IN PREDICTION MODELS FOR COVID-19 DEATH

ObjectiveTo derive a predicted probability of death (PDeathDx) based upon complete sets of ICD-10 codes assigned to patients prior to their diagnosis of COVID-19. PDeathDx is intended for use as a summary metric for pre-existing conditions in multivariate models for COVID-19 death. MethodsCases were identified through the COVID-19 Shared Data Resource (CSDR) of the Department of Veterans Affairs. The diagnosis required at least one positive nucleic acid amplification test (NAAT). The primary outcome was death within 60 days of the first positive test. We retrieved all diagnoses entered into the electronic medical record for visits, on problem lists, and at the time of hospital discharge if they were at least 14 days prior to the NAAT. ICD-9 codes were converted to ICD-10 equivalents using a crosswalk provided by the Centers for Medicare/Medicaid Services. ICD-10 codes were converted to their category diagnoses defined as all columns to the left of the decimal point. Each patient was considered to have or not have each category diagnosis prior to the NAAT. A computer program calculated the number of cases for each category diagnosis, the relative risk (RR) of death, and its confidence interval (CI) using a Bonferroni adjustment for multiple comparisons. RRs were re-centered by subtracting 1 so that high-risk conditions had a positive value while protective conditions had a negative one. Diagnoses found to be significant were entered into a logistic model for death in a stepwise fashion. Each patient was assigned (RR-1) to each category diagnosis if they had the condition or 0 otherwise. The resulting model was used to derive PDeathDx for each patient and the area under its receiver operating characteristic (ROC) curve calculated. Single variable logistic models were also derived for age at diagnosis, the Charlson 2-year (Charl2Yr) and lifetime (CharlEver) scores, and the Elixhauser 2-year (Elix2Yrs) and lifetime (ElixEver) scores. Stata was used to compare the ROCs for PDeathDx and each of the other metrics. ResultsOn September 30, 2021 there were 347,220 COVID-19 patients in the CSDR. 18,120 patients (5.33%) died within 60 days of their diagnosis. After consolidating ICD-9 and ICD-10 codes, 29,162,710 separate diagnoses were given to the subjects representing 41,341 ICD-10 codes. This set was reduced to 1,890 category diagnoses assigned to the group for the first time on 19,184,437 occasions. Of the 1,890 category diagnoses, 425 involved >= 100 subjects and had a lower boundary for the CI >= 1.50 (a high-risk condition) or upper boundary <= 0.80 (a protective condition). Stepwise logistic regression showed that 153 were statistically significant, independent predictors of death. PDeathDx was slightly less powerful than age as a discriminator (ROC = 0.811 +/- 0.002 vs 0.812 +/- 0.001, respectively; P < 0.001) but was superior to the Charl2Yr (ROC = 0.727 +/- 0.002; P < 0.001), CharlEver (ROC = 0.753 +/- 0.002; P <= 0.001), Elix2Yr (ROC = 0.694 +/- 0.002; P < 0.001); and ElixEver (ROC = 0.731 +/- 0.002; P < 0.001). Univariate analysis and multivariate modeling showed that many of the most high-risk conditions are under-represented or not included in the Charlson Index. These include hypertension, dementia, degenerative neurologic disease, or diagnoses associated with severe physical disability. ConclusionsOur method for handling pre-existing conditions in multivariate analysis has many advantages over conventional comorbidity indices. The approach can be applied to any condition or outcome, can use any categorical predictors including medications, creates its own condition weights, handles rare as well as protective conditions, and returns actionable information to providers. The latter include the specific ICD-10 groups, their contribution to the risk, and their rank order of importance. Finally, PDeathDx is equivalent to age as a discriminator of outcomes and outperforms 4 other comorbidity scores. If validated by others, this approach provides an alternative and more robust approach to handling comorbidities in multivariate models.

ESTIMATING THE EFFECT OF VACCINATION ON THE CASE-FATALITY RATE FOR COVID-19

ObjectiveTo evaluate the benefits of vaccination on the case fatality rate (CFR) for COVID-19 infections. DesignMultivariate modeling of data from electronic medical records Setting130 medical centers of the United States Department of Veterans Affairs Participants339,772 patients with COVID-19 confirmed by nucleic acid amplification testing as of September 30, 2021 MethodsThe primary outcome was death within 60 days of the diagnosis. Patients were considered vaccinated if they had completed a full series >= 14 days prior to diagnosis. Cases presenting in July - September of 2021 were considered to have the delta variant. Logistic regression was used to derive adjusted odds ratios (OR) for vaccination and infection with delta versus earlier variants. Models were adjusted for demographic traits, standard comorbidity indices, selected clinical terms, and 3 novel parameters representing all prior diagnoses, all prior vital signs/ baseline laboratory tests, and current outpatient treatment. Patients with a delta infection were divided into 8 cohorts based upon the time from vaccination to diagnosis (in 4-week blocks). A common model was used to estimate the odds of death associated with vaccination for each cohort relative that of all unvaccinated patients. Results9.1% of subjects had been fully vaccinated, and 21.5% were presumed to have the delta variant. 18,120 patients (5.33%) died within 60 days of their diagnoses. The adjusted OR for delta infection was 1.87 +/- 0.05 which corresponds to a relative risk of 1.78. The overall adjusted OR for prior vaccination was 0.280 +/- 0.011 corresponding to a relative risk of 0.291. The study of vaccine cohorts with a delta infection showed that the raw CFR rose steadily after 10-14 weeks. However, the OR for vaccination remained stable for 10-34 weeks. ConclusionsOur study confirms that delta is substantially more lethal than earlier variants and that vaccination is an effective means of preventing COVID death. After adjusting for major selection biases, we found no evidence that the benefits of vaccination on CFR declined over 34 weeks.

Health-Enhancing Physical Activity in Europe-Combined Aerobic Physical Activity and Muscle-Strengthening Exercise Guideline Adherence Among 280,605 Adults From 28 European Countries.

BACKGROUND: Compared with engaging in aerobic physical activity (aerobic PA; eg, walking, running, cycling) or muscle-strengthening exercise (MSE; eg, weight/resistance training) alone, epidemiological evidence suggests that combining both is linked to better health. However, the assessment of both PA modes is rare in health surveillance. This article provides the first multicountry study on the descriptive epidemiology of combined moderate to vigorous PA-MSE guideline adherence. METHODS: Data were drawn from the European Health Interview Survey wave 2 (2013-2014), comprising samples from 28 European countries (n = 280,605). Self-reported aerobic PA and MSE were assessed using the validated European Health Interview Survey Physical Activity Questionnaire. The authors calculated the weighted proportions meeting the health-enhancing PA guideline (aerobic PA ≥ 150 min/wk and MSE ≥ 2 sessions/wk). Poisson regression assessed the prevalence ratios for meeting the combined guideline across sociodemographic factors and by country. RESULTS: A total of 15.0% met the health-enhancing PA guideline. The lowest prevalence was from respondents from Southern and Central European countries (Romania, Poland, and Croatia, range: 0.5%-5.7%). Poorer self-rated health, older age, lower income, being female, and being obese had a lower likelihood of meeting the combined guideline. CONCLUSIONS: Most European adults do not meet the health-enhancing PA guideline that includes both aerobic PA and MSE.

Consensus-based Standards and Indicators to strengthen trauma center injury and violence prevention programs.

For decades, the American College of Surgeons Committee on Trauma (ACSCOT) has published Resources for Optimal Care of the Injured Patient, which outlines specific criteria necessary to be verified by the college as a trauma center, including having an organized and effective approach to prevention of trauma. However, the document provides little public health-specific guidance to assist trauma centers with developing these approaches. An advisory panel was convened in 2017 with representatives from national trauma and public health organizations with the purpose of identifying strategies to support trauma centers in the development of a public health approach to injury and violence prevention and to better integrate these efforts with those of local and state public health departments. This panel developed the Standards and Indicators for Model Level I and II Trauma Center Injury and Violence Prevention Programs. The document outlines five, consensus-based core components of a model injury and violence prevention program: (1) leadership, (2) resources, (3) data, (4) effective interventions, and (5) partnerships. We think this document provides the missing public health guidance and is an essential resource to trauma centers for effectively addressing injury and violence in our communities. We recommend the Standards and Indicators be referenced in the injury prevention chapter of the upcoming revision of ACSCOT's Resources for Optimal Care of the Injured Patient as guidance for the development, implementation and evaluation of injury prevention programs and be used as a framework for program presentation during ACSCOT verification visits.

SNO and EANO practice guideline update: Anticonvulsant prophylaxis in patients with newly diagnosed brain tumors.

OBJECTIVE: To update the 2000 American Academy of Neurology (AAN) practice parameter on anticonvulsant prophylaxis in patients with newly diagnosed brain tumors. METHODS: Following the 2017 AAN methodologies, a systematic literature review utilizing PubMed, EMBASE Library, Cochrane, and Web of Science databases was performed. The studies were rated based on the AAN therapeutic or causation classification of evidence (class I-IV). RESULTS: Thirty-seven articles were selected for final analysis. There were limited high-level, class I studies and mostly class II and III studies. The AAN affirmed the value of these guidelines. RECOMMENDATIONS: In patients with newly diagnosed brain tumors who have not had a seizure, clinicians should not prescribe antiepileptic drugs (AEDs) to reduce the risk of seizures (level A). In brain tumor patients undergoing surgery, there is insufficient evidence to recommend prescribing AEDs to reduce the risk of seizures in the peri- or postoperative period (level C). There is insufficient evidence to support prescribing valproic acid or levetiracetam with the intent to prolong progression-free or overall survival (level C). Physicians may consider the use of levetiracetam over older AEDs to reduce side effects (level C). There is insufficient evidence to support using tumor location, histology, grade, molecular/imaging features when deciding whether or not to prescribe prophylactic AEDs (level U).

Long-term retention of lithium disilicate crowns with a current bioactive cement.

OBJECTIVE: To determine if a recent bioactive cement provides acceptable lithium disilicate crown retention after long-term aging with monthly thermocycling. MATERIALS AND METHODS: Extracted molars prepared with flat occlusal, 20° taper, ~4 mm axial. Prepared teeth assigned to two groups for equal mean surface areas per group. Lithium disilicate crowns fabricated with occlusal bar to facilitate removal. Crowns etched with 9.5%HF and cleaned. Cements were Ceramir Crown & Bridge QuikCap (CM) and Ketac Cem Maxicap (KC). Before cementation, specimens stored in 37°C water. Crowns cemented with 196 N force, placed in 37°C, 100% humidity oven for setting. Specimens thermocycled (5-55°C) 5000 cycles monthly for 6 months; otherwise stored in phosphate buffered saline solution. Crowns removed axially at 0.5 mm/min. Removal forces recorded and stresses calculated using areas. Independent t-test (α = 0.05). RESULTS: Levene test not significant (P = 0.649). CM removal stresses and forces (P < 0.001) were higher (1.93 MPa, 261.4 N) compared to KC (1.06 MPa, 139.4 N). CM cement found principally on crown intaglio, KC found with most cement on prepared tooth. Chi-square significant (P < 0.001). CONCLUSIONS: Following long-term aging with monthly thermocycling, lithium disilicate crowns were best retained by CM cement, however both cements are capable of retaining lithium disilicate crowns with preparations of ideal taper and length. CLINICAL SIGNIFICANCE: Results serve as a basis for bioactive cement selection for retaining lithium disilicate crowns. Without optimal axial length, taper of preparation or retentive features, Ceramir Crown and Bridge QuikCap offers a bioactive cement with improved long-term retention when compared to Ketac Cem Maxicap for lithium disilicate crowns.

Long-term retention of zirconia crowns cemented with current automixed cements.

STATEMENT OF PROBLEM: Automixing and dispensing cements is a straightforward approach with consistent dosing. Previous studies have demonstrated clinically significant differences in crown retention between power-liquid and paste-paste forms of the same cement, as the composition between the 2 differs. A self-adhesive modified-resin (SAMR) and a resin-modified glass ionomer (RMGI) cement, originally offered as a powder-liquid, are now in common use as paste-paste automixed cements. With the increased use of zirconia restorations, the long-term retention of zirconia crowns for these 2 automixed cements should be evaluated. PURPOSE: The purpose of this in vitro study was to determine whether zirconia crowns cemented with 2 automixed cements provided clinically acceptable retention after 6 months of aging with monthly thermocycling. MATERIAL AND METHODS: Extracted molars were mounted in resin and prepared with a flat occlusal surface, 20-degree taper, approximately 4-mm axial length, and with the axio-occlusal line angle slightly rounded. Prepared teeth were equally distributed into 3 cementation groups (n=12) to achieve nearly equal mean preparation surface areas for each group. Zirconia crowns (IPS ZirCAD LT) were fabricated with an added occlusal bar to facilitate removal of the cemented crowns. Cement space was set at 45 µm axially and 55 µm occlusally. After sintering and before delivery, the intaglio surfaces were airborne-particle abraded with 50-µm alumina at 275-kPa pressure for 3 seconds and then steam cleaned. Cements were the original powder-liquid RelyX Luting (RMGI; RXL) as the control, paste-paste, automixed systems RelyX Luting Plus Automix (RMGI; RXLA), and RelyX Unicem 2 Automix (SAMR; RXUA). Crowns were cemented under 196 N force, placed in an oven at 37 °C and 100% humidity during setting and then thermocycled (5 °C-55 °C) for 5000 cycles monthly for 6 months. The crowns were removed axially with a universal testing machine at 0.5 mm/min. Removal forces were recorded and dislodgement stress calculated by using the surface area of each preparation. One-way ANOVA was used for dislodgement stress and force. Chi-square test was used for cement location after testing (α=.05). RESULTS: RXLA demonstrated considerably lower crown retention (1.3 MPa) and differed significantly (P<.001) from RXUA (3.1 MPa) and RXL (3.1 MPa). Modes of failure showed most of the cement remaining only in the crown intaglio for RXLA for all specimens, whereas half of the crowns for RXL and RXUA demonstrated cement adhesion to both dentin and the intaglio surface, indicating cohesive failure of the cement at separation. As the Levene test was significant, the Games-Howell test was used for mean differences. The χ2 analysis was significant. CONCLUSIONS: After long-term aging with monthly thermocycling, high-strength zirconia crowns were strongly retained by 2 (RXL, RXUA) of the 3 cements. Crown retention for RelyX Luting Plus Automix was less than half in comparison and with cement found only on the intaglio surface after separation.