ABSTRACT
BACKGROUND: Randomized clinical trials (RCTs) are the gold standard for assessing treatment effectiveness; however, they have been criticized for generalizability issues such as how well trial participants represent those who receive the treatments in clinical practice. We assessed the representativeness of participants from eight RCTs for chronic spine pain in the U.S., which were used for an individual participant data meta-analysis on the cost-effectiveness of spinal manipulation for spine pain. In these clinical trials, spinal manipulation was performed by chiropractors. METHODS: We conducted a retrospective secondary analysis of RCT data to compare trial participants' socio-demographic characteristics, clinical features, and health outcomes to a representative sample of (a) U.S. adults with chronic spine pain and (b) U.S. adults with chronic spine pain receiving chiropractic care, using secondary data from the National Health Interview Survey (NHIS) and Medical Expenditure Panel Survey (MEPS). We assessed differences between trial and U.S. spine populations using independent t-tests for means and z-tests for proportions, accounting for the complex multi-stage survey design of the NHIS and MEPS. RESULTS: We found the clinical trials had an under-representation of individuals from health disparity populations with lower percentages of racial and ethnic minority groups (Black/African American 7% lower, Hispanic 8% lower), less educated (No high school degree 19% lower, high school degree 11% lower), and unemployed adults (25% lower) with worse health outcomes (physical health scores 2.5 lower and mental health scores 5.3 lower using the SF-12/36) relative to the U.S. population with spine pain. While the odds of chiropractic use in the U.S. are lower for individuals from health disparity populations, the trials also under-represented these populations relative to U.S. adults with chronic spine pain who visit a chiropractor. CONCLUSIONS: Health disparity populations are not well represented in spine pain clinical trials. Embracing key community-based approaches, which have shown promise for increasing participation of underserved communities, is needed.
Subject(s)
Back Pain , Chronic Pain , Neck Pain , Randomized Controlled Trials as Topic , Humans , United States , Neck Pain/therapy , Adult , Chronic Pain/therapy , Chronic Pain/diagnosis , Male , Female , Middle Aged , Back Pain/therapy , Back Pain/diagnosis , Retrospective Studies , Aged , Manipulation, Chiropractic/statistics & numerical data , Patient Selection , Treatment Outcome , Manipulation, Spinal/statistics & numerical dataABSTRACT
OBJECTIVES: Total pancreatectomy and islet autotransplantation (TPIAT) for pancreatitis may induce risk for essential fatty acid deficiency (EFAD) due to exocrine pancreatic insufficiency and intestinal alterations. The prevalence of EFAD post-TPIAT is currently unknown. METHODS: We abstracted essential fatty acid (EFA) profiles (n = 332 samples) for 197 TPIAT recipients (72% adult, 33% male). Statistical analyses determined the prevalence of, and associations with, EFAD post-operatively. EFAD was defined as a Triene-to-Tetraene ratio ≥0.05 if <18 years old, or ≥0.038 if ≥18 years old. RESULTS: Prevalence of EFAD was 33%, 49%, and 53.5% at 1, 2, and ≥3 years. At 1-year post-TPIAT, older age at transplant ( P = 0.03), being an adult versus a child ( P = 0.0024), and obstructive etiology ( P = 0.0004) were significant predictors of EFAD. Only 6% of children had EFAD 1-year post-TPIAT versus 46% of adults. The alpha-linolenic acid levels were lower with lower body mass index at transplant ( P = 0.011). EFAD was associated with the presence of other intestinal diseases ( P < 0.0001). CONCLUSIONS: One-third of individuals had EFAD 1-year post-TPIAT, highlighting the need for systematic monitoring. Older age at transplant increased risk and adults were more affected than children. Other diagnoses affecting intestinal health may further increase risk for EFAD.
Subject(s)
Fatty Acids, Essential , Islets of Langerhans Transplantation , Pancreatectomy , Transplantation, Autologous , Humans , Male , Pancreatectomy/adverse effects , Pancreatectomy/methods , Female , Islets of Langerhans Transplantation/adverse effects , Islets of Langerhans Transplantation/methods , Adult , Fatty Acids, Essential/deficiency , Child , Transplantation, Autologous/adverse effects , Adolescent , Middle Aged , Young Adult , Prevalence , Risk Factors , Child, Preschool , Pancreatitis/etiology , Exocrine Pancreatic Insufficiency/etiology , Exocrine Pancreatic Insufficiency/epidemiology , Exocrine Pancreatic Insufficiency/diagnosis , Age FactorsABSTRACT
BACKGROUND: Single-tier newborn screening (NBS) for CAH using 17-hydroxyprogesterone (17OHP) measured by fluoroimmunoassay (FIA) in samples collected at 24-48 hours produces a high false-positive rate (FPR). 2nd tier steroid testing can reduce the FPR and has been widely implemented. We investigated the accuracy of an alternative multi-tier CAH NBS protocol that incorporates molecular testing of the CYP21A2 gene and reduces the 1st tier 17OHP cutoff to minimize missed cases. METHODS: Created a Minnesota-specific CYP21A2 pathogenic variants panel; develop a rapid, high-throughput multiplex, allele-specific-primer-extension assay; perform 1-year retrospective analysis of Minnesota NBS results comparing metrics between a conventional steroid-based two-tier protocol and a molecular-based multi-tier NBS protocol, applied post-hoc. RESULTS: CYP21A2 gene sequencing of 103 Minnesota families resulted in a Minnesota-specific panel of 21 pathogenic variants. Centers for Disease Control and Prevention (CDC) created a molecular assay with 100% accuracy and reproducibility. Two-tier steroid-based screening of 68,659 live births during 2015 resulted in 2 false negatives (FNs), 91 FPs, and 1 true positive (TP). A three-tier protocol with a lower 1st-tier steroid cutoff, 2nd-tier 21-variant CYP21A2 panel and 3rd-tier CYP21A2 sequencing would have resulted in 0 FNs, 52 FPs and 3 TPs. CONCLUSIONS: Incorporation of molecular testing could improve the accuracy of CAH NBS, although some distinct challenges of molecular testing may need to be considered before implementation by NBS programs.
ABSTRACT
Background: Although research suggests that early-life adversity (ELA) and cannabis use are linked, researchers have not established factors that mediate or modify this relationship. Identifying such factors could help in developing targeted interventions. We explored chronic pain as a potential mediator or moderator of this relationship. Methods: Using an online study, we collected cross-sectional data about ELA, cannabis use, and chronic pain to test whether ELA (adverse childhood experiences total score) is associated with cannabis use, and to examine pain as a potential mediator or moderator. Cannabis use was examined two ways: times used per day, and categorized as non-, some, or regular use. Chronic pain was measured as present/absent and as the number of painful body locations (0-8). Analyses used linear and multinomial regression. Results: ELA, chronic pain, and cannabis use were common among respondents. ELA was strongly associated with both measures of cannabis use. The number of painful body locations modestly mediated the association of ELA with cannabis use, reducing the magnitude of regression coefficients by about 1/7. The number of painful body locations modified the association between ELA and cannabis use (p≤0.006), while chronic pain presence/absence (a less-informative measure) had only a nonsignificant modification effect (p≥0.10). When either ELA or pain was high, the other was not associated with cannabis use; when either ELA or pain was low, more painful locations or higher ELA (respectively) was associated with more intense cannabis use. Conclusion: These exploratory findings suggest the importance of ELA and chronic pain as factors contributing to cannabis use, and of accounting for these factors in developing treatment and prevention strategies addressing cannabis use.
ABSTRACT
The instant blood-mediated inflammatory response (IBMIR) causes islet loss and compromises diabetes outcomes after total pancreatectomy with islet autotransplant (TPIAT). We previously reported a possible benefit of etanercept in maintaining insulin secretion 3 months post-TPIAT. Here, we report 2-year diabetes outcomes and peri-operative inflammatory profiles from a randomized trial of etanercept and alpha-1 antitrypsin (A1AT) in TPIAT. We randomized 43 TPIAT recipients to A1AT (90 mg/kg IV x6 doses, n = 13), etanercept (50 mg then 25 mg SQ x 5 doses, n = 14), or standard care (n = 16). Inflammatory cytokines, serum A1AT and unmethylated insulin DNA were drawn multiple times in the perioperative period. Islet function was assessed 2 years after TPIAT with mixed meal tolerance test, intravenous glucose tolerance test and glucose-potentiated arginine induced insulin secretion. Cytokines, especially IL-6, IL-8, IL-10, and MCP-1, were elevated during and after TPIAT. However, only TNFα differed significantly between groups, with highest levels in the etanercept group (p = 0.027). A1AT increased after IAT in all groups (p < 0.001), suggesting endogenous upregulation. Unmethylated insulin DNA ratios (a marker of islet loss) and 2 years islet function testing were similar in the three groups. To conclude, we found no sustained benefit from administering etanercept or A1AT in the perioperative period.
Subject(s)
Diabetes Mellitus , Islets of Langerhans Transplantation , Humans , Etanercept/therapeutic use , Autografts , Transplantation, Autologous , Insulin , Inflammation , Cytokines , DNA , Pancreatectomy , Treatment OutcomeABSTRACT
BACKGROUND: Co-use of cannabis is increasing in nicotine users and presents additional challenges in addressing nicotine dependence. This study examined the links between regular co-use of cannabis and nicotine with biobehavioral and affective changes in response to stress during nicotine withdrawal and ad libitum use. METHODS: Participants (N = 79) who regularly used nicotine-only, cannabis-only, both substances, or neither substance were invited to attend two laboratory stress assessment sessions. For nicotine users, one session occurred during ad libitum nicotine use and one occurred after abstinence from nicotine. During the stress sessions, participants provided saliva samples for cortisol assay and completed measures of subjective states. Cardiovascular measures were collected during resting baseline, exposure to acute stressors, and a recovery rest period. RESULTS: Nicotine-only users had higher average cortisol levels in the second lab session (nicotine withdrawal) relative to the first lab session (ad libitum nicotine use). Compared to nicotine non-users, nicotine users reported less positive affect and exhibited attenuated cortisol and systolic blood pressure (BP) stress responses. Cannabis users exhibited exaggerated diastolic BP responses to stress compared to cannabis non-users, and co-users of nicotine and cannabis had higher levels of cannabis craving than cannabis-only users (p < .01). CONCLUSIONS: This study partially replicated earlier findings on the effects of chronic nicotine use and provided novel results regarding the influence of cannabis co-use on physiological and affective responses to stress in nicotine users during nicotine withdrawal.
Subject(s)
Cannabis , Hallucinogens , Substance Withdrawal Syndrome , Tobacco Use Disorder , Humans , Nicotine/adverse effects , Cannabis/adverse effects , Hydrocortisone , Substance Withdrawal Syndrome/psychology , Cannabinoid Receptor AgonistsABSTRACT
BACKGROUND: During third molar removal, the mandible is supported by a dental assistant (DA) to counter downward forces during surgery, and with sedation, to maintain airway patency. The Restful Jaw device (PEP Design; Saint Paul) provides this support instead of the DA. PURPOSE: This study compared the occurrence of postoperative preauricular and masticatory muscle pain symptoms (PMMPS) between the device and DAs providing mandibular support, using two outcome measures. Secondary aims identify predictors of outcome and providers' opinions of the device. STUDY DESIGN, SETTING, SAMPLE: In this multisite, single-blind, two-arm parallel randomized trial, participants without preoperative PMMPS had surgical removal of third molars, with sedation and bite blocks were randomly assigned to manual support or the device. EXPOSURE VARIABLE: The exposed group was randomly assigned to the device and the nonexposed group to manual support. MAIN OUTCOME VARIABLE(S): The primary outcome was patient-reported PMMPS. Two secondary outcomes were pain assessed with the temporomandibular disorder Pain Screener and providers' views on the device. Outcomes were assessed at 1-, 3-, and 6-month postsurgery. COVARIATES: The covariates are baseline demographics (eg, sex), clinical characteristics (eg, eruption status), and third molar surgeries. ANALYSES: For occurrence of pain, generalized estimating equations assessed differences between groups. Logistic regression analysis assessed predictors of pain at 1 month, per the Screener. The level for statistical significance was 5%. RESULTS: Enrollment was 86 and 83 participants in the device and DA groups, respectively. The average age was 20.8 years; the majority were female (65%) and Caucasian (66%). The retention rate was ≥95.9%. The groups did not differ significantly for occurrence of pain using the primary and secondary outcome measures at any follow-up (P ≥ .46). Fully impacted molars were associated with occurrence of pain (odds ratio = 3.44; 95% confidence interval 1.49-7.92; P = .004). CONCLUSION AND RELEVANCE: Occurrence of pain using the primary and secondary outcome measures did not differ significantly between groups at any follow-up and was associated with removal of fully impacted third molars. Four out of five surgeons reported wanting to use the device on a regular basis when performing this procedure in sedated patients.
Subject(s)
Molar, Third , Tooth, Impacted , Female , Humans , Male , Young Adult , Dental Assistants , Mandible/surgery , Masticatory Muscles , Molar, Third/surgery , Pain, Postoperative/etiology , Single-Blind Method , Tooth Extraction/methods , Tooth, Impacted/surgeryABSTRACT
Meta-analysis is commonly used to combine results from multiple clinical trials, but traditional meta-analysis methods do not refer explicitly to a population of individuals to whom the results apply and it is not clear how to use their results to assess a treatment's effect for a population of interest. We describe recently-introduced causally interpretable meta-analysis methods and apply their treatment effect estimators to two individual-participant data sets. These estimators transport estimated treatment effects from studies in the meta-analysis to a specified target population using the individuals' potentially effect-modifying covariates. We consider different regression and weighting methods within this approach and compare the results to traditional aggregated-data meta-analysis methods. In our applications, certain versions of the causally interpretable methods performed somewhat better than the traditional methods, but the latter generally did well. The causally interpretable methods offer the most promise when covariates modify treatment effects and our results suggest that traditional methods work well when there is little effect heterogeneity. The causally interpretable approach gives meta-analysis an appealing theoretical framework by relating an estimator directly to a specific population and lays a solid foundation for future developments.
Subject(s)
Meta-Analysis as Topic , Research Design , HumansABSTRACT
Background: Although diabetes after total pancreatectomy and islet autotransplantation (TP-IAT) is one of the biggest concerns for TP-IAT recipients and physicians, reliable prediction of post-TP-IAT glycemic control remains unestablished. This study was conducted to identify early predictors of insulin independence and goal glycemic control by hemoglobin A1c (HbA1c) ≤ 6.5% after TP-IAT. Methods: In this single-center, retrospective study, patients who underwent TP-IAT (nâ =â 227) were reviewed for simple metabolic markers or surrogate indices of ß-cell function obtained 3 mo after TP-IAT as part of standard clinical testing. Long-term metabolic success was defined as (1) insulin independence and (2) HbA1c ≤ 6.5% 1, 3, and 5 y after TP-IAT. Single- and multivariate modeling used 3-mo markers to predict successful outcomes. Results: Of the 227 recipients, median age 31 y, 30% male, 1 y after TP-IAT insulin independence, and HbA1c ≤ 6.5% were present in 39.6% and 72.5%, respectively. In single-predictor analyses, most of the metabolic markers successfully discriminated between those attaining and not attaining metabolic goals. Using the best model selected by random forests analysis, we accurately predicted 1-y insulin independence and goal HbA1c control in 77.3% and 86.4% of the patients, respectively. A simpler "clinically feasible" model using only transplanted islet dose and BETA-2 score allowed easier prediction at a small accuracy loss (74.1% and 82.9%, respectively). Conclusions: Metabolic testing measures performed 3 mo after TP-IAT were highly associated with later diabetes outcomes and provided a reliable prediction model, giving valuable prognostic insight early after TP-IAT and help to identify recipients who require early intervention.
ABSTRACT
BACKGROUND: Iron deficiency (ID) and environmental exposure to metals frequently co-occur among Ugandan children, but little is known about their associations, although iron and other divalent metals share the same intestinal absorption transporter, divalent metal transporter 1 (DMT1). OBJECTIVES: We examined associations between iron status and blood concentrations of lead, manganese (Mn), cobalt (Co), and cadmium, both singly and as a mixture. METHODS: We used data on sociodemographic status, iron biomarkers, and blood concentrations of heavy metals collected from a cross-sectional survey of 100 children aged 6-59 mo in Kampala, Uganda. We compared blood concentrations of metals in ID with iron-sufficient children. We examined associations between a metal mixture and iron biomarkers using multiple linear regression and weighted quintile sum regression. RESULTS: The median (interquartile range) blood Mn (µg/L) was higher in ID children defined by soluble transferrin receptor (sTfR) and ferritin (ID compared with iron-sufficient children): (sTfR [21.3 {15.1, 28.8}, 11.2 {8.6, 18.5}], ferritin [19.5 {15.0, 27.2}, 11.2 {8.8, 19.6}]; P < 0.001 for both). Similarly, the median (interquartile range) blood Co (µg/L) was higher in ID children by ferritin ([0.5 {0.4, 0.9}, 0.4 {0.3, 0.5}], P = 0.05). Based on the multiple linear regression results, higher blood Co and Mn were associated with poorer iron status (defined by all 4 iron indicators for Co and by sTfR for Mn). The weighted quintile sum regression result showed that higher blood concentrations of a metal mixture were associated with poorer iron status represented by sTfR, ferritin, and hepcidin, mainly driven by Co and Mn. CONCLUSIONS: Our study findings suggest that poorer iron status is associated with overall heavy metal burden, predominantly Co and Mn, among Ugandan children. Further prospective studies should confirm our primary findings and investigate the combined effects of coexposures to neurotoxicants on the neurodevelopment of young children.
Subject(s)
Anemia, Iron-Deficiency , Iron Deficiencies , Metals, Heavy , Humans , Child , Child, Preschool , Iron/metabolism , Cross-Sectional Studies , Uganda , Prospective Studies , Ferritins , Manganese , Biomarkers , Receptors, TransferrinABSTRACT
Children with intractable chronic pancreatitis may require total pancreatectomy with islet autotransplantation (TPIAT) for pain relief. The IAT reduces the severity of post- pancreatectomy diabetes. We analyzed 635 mixed meal tolerance tests (MMTT) in 134 children undergoing TPIAT to determine whether superior survival of islet grafts explains higher rates of insulin independence previously reported in young children (n = 52, age 3-11 years) versus adolescents (n = 82, age 12-18 years). For MMTT, children consumed Boost HP and we sampled C-peptide and glucose repeatedly over 2 h. The trajectory of outcomes before and after TPIAT was compared between children and adolescents using data from pre-TPIAT and 3, 6 months, 1, 2, 3, and 4 years post-TPIAT and mixed linear models with a random effect for child. Cox regression was used to analyze time outcomes (e.g., time to first off insulin). Islet mass transplanted, measured as islet equivalents (IEQ), was higher in adolescents (p = .003) but IEQ/kg was higher in young children (p < .001) because of their lower weight. AUC C-peptide in young children increased somewhat over 4 years, but was stable in adolescents (p = .0013). AUC glucose increased more in adolescents over time post-TPIAT (p = .0024). Islet function by AUC C-peptide:AUC glucose ratio was better preserved in young children (p < .001). Adolescents were less likely to wean off insulin (hazard ratio .44 [95% CI .28, .69]). These data support an advantage of young age in islet graft survival after TPIAT. The greater likelihood of insulin independence in young children may be driven by better islet survival after transplant.
Subject(s)
Islets of Langerhans Transplantation , Child , Adolescent , Humans , Child, Preschool , Transplantation, Autologous , Pancreatectomy , C-Peptide , Insulin , Glucose , Treatment OutcomeABSTRACT
AIMS: To assess differences in biopsychosocial factors between participants with masticatory myofascial pain with referral (MFPwR), with myalgia without referral (Mw/oR), and community controls without TMDs. METHODS: Study participants were diagnosed with MFPwR (n = 196), Mw/oR (n = 299), or as a non-TMD community control (n = 87) by two calibrated examiners at each of three study sites. Pain chronicity, pain on palpation of masticatory muscle sites, and pressure pain thresholds (PPT) at 12 masticatory muscle, 2 trigeminal, and 2 nontrigeminal control sites were recorded. Psychosocial factors assessed included anxiety, depression, and nonspecific physical symptoms (Symptom Checklist-90 Revised); stress (Perceived Stress Scale); and health-related quality of life (Short Form Health Survey). Comparisons among the three groups were adjusted for age, sex, race, education, and income using multivariable linear regression. The significance threshold was set at P = .017 (.05 / 3) for subsequent pairwise comparisons. RESULTS: Compared to the Mw/oR group, the MFPwR group had significantly greater pain chronicity, number of painful muscle sites, anxiety, depression, nonspecific physical symptoms, and impaired physical health (P < .017). The MFPwR group also had significantly lower PPTs for masticatory sites (P < .017). Both muscle pain groups differed significantly from the non-TMD community control group for all outcome measures (P < .017). CONCLUSION: These findings support the clinical utility of separating MFPwR from Mw/oR. Patients with MFPwR are more complex from a biopsychosocial perspective than Mw/oR patients, which likely affects prognosis and supports consideration of these factors in case management.
Subject(s)
Myalgia , Myofascial Pain Syndromes , Humans , Quality of Life , Research Design , Pain Threshold , Control GroupsABSTRACT
BACKGROUND: The objective of this study was to identify tooth-level risk factors for use during preradiation dental care management to predict risk of tooth failure (tooth lost or declared hopeless) and exposed bone after radiation therapy (RT) for head and neck cancer (HNC). METHODS: The authors conducted a prospective observational multicenter cohort study of 572 patients receiving RT for HNC. Participants were examined by calibrated examiners before RT and then every 6 months until 2 years after RT. Analyses considered time to tooth failure and chance of exposed bone at a tooth location. RESULTS: The following pre-RT characteristics predicted tooth failure within 2 years after RT: hopeless teeth not extracted pre-RT (hazard ratio [HR], 17.1; P < .0001), untreated caries (HR, 5.0; P < .0001), periodontal pocket 6 mm or greater (HR, 3.4; P = .001) or equaling 5 mm (HR, 2.2; P = .006), recession over 2 mm (HR, 2.8; P = .002), furcation score of 2 (HR, 3.3; P = .003), and any mobility (HR, 2.2; P = .008). The following pre-RT characteristics predicted occurrence of exposed bone at a tooth location: hopeless teeth not extracted before RT (risk ratio [RR], 18.7; P = .0002) and pocket depth 6 mm or greater (RR, 5.4; P = .003) or equaling 5 mm (RR, 4.7; P = .016). Participants with exposed bone at the site of a pre-RT dental extraction averaged 19.6 days between extraction and start of RT compared with 26.2 days for participants without exposed bone (P = .21). CONCLUSIONS: Individual teeth with the risk factors identified in this study should be considered for extraction before RT for HNC, with adequate healing time before start of RT. PRACTICAL IMPLICATIONS: The findings of this trial will facilitate evidence-based dental management of the care of patients receiving RT for HNC. This clinical trial was registered at Clinicaltrials.gov. The registration number is NCT02057510.
Subject(s)
Dental Caries , Head and Neck Neoplasms , Tooth Loss , Humans , Tooth Loss/etiology , Tooth Loss/epidemiology , Cohort Studies , Dental Caries/etiology , Risk Factors , Head and Neck Neoplasms/radiotherapyABSTRACT
BACKGROUND: In total pancreatectomy with islet auto-transplantation, successful diabetes outcomes are limited by islet loss from the instant blood mediated inflammatory response. We hypothesized that blockade of the inflammatory response with either etanercept or alpha-1-antitrypsin would improve islet function and insulin independence. METHODS: We randomized 43 participants to receive A1AT (90 mg/kg x 6 doses, n = 13), or etanercept (50 mg then 25 mg x 5 doses, n = 14), or standard care (n = 16), aiming to reduce detrimental effects of innate inflammation on early islet survival. Islet graft function was assessed using mixed meal tolerance testing, intravenous glucose tolerance testing, glucose-potentiated arginine-induced insulin secretion studies, HbA1c, and insulin dose 3 months and 1 year post-TPIAT. RESULTS: We observed the most robust acute insulin response (AIRglu) and acute C-peptide response to glucose (ACRglu) at 3 months after TPIAT in the etanercept-treated group (p ≤ 0.02), but no differences in other efficacy measures. The groups did not differ overall at 1 year but when adjusted by sex, there was a trend towards a sex-specific treatment effect in females (AIRglu p = 0.05, ACRglu p = 0.06), with insulin secretion measures highest in A1AT-treated females. CONCLUSION: Our randomized trial supports a potential role for etanercept in optimizing early islet engraftment but it is unclear whether this benefit is sustained. Further studies are needed to evaluate possible sex-specific responses to either treatment. CLINICAL TRIAL NOTATION: This study was performed under an Investigational New Drug Application (IND #119828) from the Food and Drug Administration and was registered on clinicaltrials.gov (NCT#02713997).
Subject(s)
Diabetes Mellitus , Islets of Langerhans Transplantation , Pancreatitis, Chronic , Female , Humans , Male , Diabetes Mellitus/surgery , Etanercept/pharmacology , Etanercept/therapeutic use , Glucose , Insulin/therapeutic use , Pancreatectomy , Pancreatitis, Chronic/surgery , Pilot Projects , Transplantation, Autologous , Treatment Outcome , ThymalfasinABSTRACT
Meta-regression is widely used in systematic reviews to investigate sources of heterogeneity and the association of study-level covariates with treatment effectiveness. Existing meta-regression approaches are successful in adjusting for baseline covariates, which include real study-level covariates (e.g., publication year) that are invariant within a study and aggregated baseline covariates (e.g., mean age) that differ for each participant but are measured before randomization within a study. However, these methods have several limitations in adjusting for post-randomization variables. Although post-randomization variables share a handful of similarities with baseline covariates, they differ in several aspects. First, baseline covariates can be aggregated at the study level presumably because they are assumed to be balanced by the randomization, while post-randomization variables are not balanced across arms within a study and are commonly aggregated at the arm level. Second, post-randomization variables may interact dynamically with the primary outcome. Third, unlike baseline covariates, post-randomization variables are themselves often important outcomes under investigation. In light of these differences, we propose a Bayesian joint meta-regression approach adjusting for post-randomization variables. The proposed method simultaneously estimates the treatment effect on the primary outcome and on the post-randomization variables. It takes into consideration both between- and within-study variability in post-randomization variables. Studies with missing data in either the primary outcome or the post-randomization variables are included in the joint model to improve estimation. Our method is evaluated by simulations and a real meta-analysis of major depression disorder treatments.
Subject(s)
Random Allocation , Humans , Bayes Theorem , Systematic Reviews as Topic , Treatment OutcomeABSTRACT
Purpose: To assess whether the poor prognosis of triple-negative breast cancer (TNBC) necessitates a more aggressive surgical approach. Methods: We examined the association of: breast-conserving surgery (BCS); BCS plus radiotherapy; mastectomy; and mastectomy plus radiotherapy with overall and breast cancer-specific survival of stage I-III TNBC patients aged 66 years and older. We used unweighted and inverse probability of treatment weighted Cox proportional hazards regression and the Fine and Gray sub-distribution model. Results: Among 4333 women, individuals who were selected for BCS, mastectomy or mastectomy plus radiotherapy had lower adjusted overall and breast cancer-specific survival compared with women who had BCS plus radiotherapy. Conclusion: In this population-based study, women with TNBC treated with BCS plus radiotherapy have a better prognosis than those treated with BCS, mastectomy or mastectomy plus radiotherapy. Given the poor prognosis of TNBC and selection bias inherent in observational studies, these findings should be confirmed in further studies such as randomized clinical trials.
Subject(s)
Breast Neoplasms , Triple Negative Breast Neoplasms , Aged , Female , Humans , Mastectomy , Mastectomy, Segmental , Neoplasm Staging , Prognosis , Radiotherapy, Adjuvant , Triple Negative Breast Neoplasms/surgeryABSTRACT
PURPOSE: To elucidate long-term sequelae of radiation therapy (RT) in head and neck cancer (HNC) patients, a multicenter, prospective study, Clinical Registry of Dental Outcomes in Head and Neck Cancer Patients (OraRad), was established with tooth failure as its primary outcome. We report tooth failure and associated risk factors. METHODS AND MATERIALS: Demographics and cancer and dental disease characteristics were documented in 572 HNC patients at baseline and 6, 12, 18, and 24 months after RT. Eligible patients were aged 18 or older, diagnosed with HNC, and receiving RT to treat HNC. Tooth failure during follow-up was defined as losing a tooth or having a tooth deemed hopeless. Analyses of time to first tooth-failure event and number of teeth that failed used Kaplan-Meier estimators, Cox regression, and generalized linear models. RESULTS: At 2 years, the estimated fraction of tooth failure was 17.8% (95% confidence interval, 14.3%-21.3%). The number of teeth that failed was higher for those with fewer teeth at baseline (P < .0001), greater reduction in salivary flow rate (P = .013), and noncompliance with daily oral hygiene (P = .03). Patients with dental caries at baseline had a higher risk of tooth failure with decreased salivary flow. Patients who were oral-hygiene noncompliant at baseline but compliant at all follow-up visits had the fewest teeth that failed; greatest tooth failure occurred in participants who were noncompliant at baseline and follow-up. CONCLUSIONS: Despite pre-RT dental management, substantial tooth failure occurs within 2 years after RT for HNC. Identified factors may help to predict or reduce risk of post-RT tooth failure.
Subject(s)
Dental Caries , Head and Neck Neoplasms , Dental Caries/epidemiology , Dental Caries/etiology , Head and Neck Neoplasms/radiotherapy , Humans , Prospective Studies , Registries , Risk FactorsABSTRACT
PURPOSE: This study aims to develop and test feasibility of a colorectal cancer (CRC) education video appropriate for Somali immigrants. DESIGN: One-group pretest-posttest design. SETTING: Minneapolis, MN. SAMPLE: Thirty-one Somali men (mean age = 60.6; SD = 13.0). INTERVENTION: A CRC education video was developed in the Somali language with Somali community partners. Participants were invited to a workshop and watched the video. MEASURES: Levels of understanding about CRC and screening were assessed before vs after the video. ANALYSIS: Binomial tests were conducted to examine changes in level of understanding. RESULTS: Analysis on pre-post, within-person changes in understanding about cancer, and CRC screening showed that proportions with a positive change in understanding risks of cancer (80%) and benefits of CRC screening (90%) were significantly higher than expected if the video had no effect (50%; P = .012, P < .001, respectively). Ninety-three percent of participants agreed that the video contained useful information. CONCLUSION: These results provide evidence of usefulness of culturally tailored videos to facilitate CRC screening in the Somali community. Results of this study were limited by a small sample size and lack of a control group.