Examining crossover and postprotocol therapies in first-line immunotherapy trials in non-small cell lung cancer (NSCLC).

BACKGROUND: Immune checkpoint inhibitor (ICI) therapy has led to significant improvement in outcomes for patients with nononcogene-driven advanced non-small cell lung cancer (NSCLC). The rate of crossover and receipt of postprotocol ICI in frontline trials for advanced NSCLC has not been systematically evaluated. METHODS: ClinicalTrials.gov was used to identify phase 3 studies evaluating the use of immunotherapy or combination chemoimmunotherapy against chemotherapy alone in the frontline management of advanced NSCLC. Data on outcomes, rate of crossover and/or subsequent post-protocol receipt of immunotherapy, and the start dates of these clinical trials were then extracted. RESULTS: Twenty-three frontline trials in nononcogene-driven advanced NSCLC were identified. Six trials with ICI monotherapy/dual ICI therapy and 17 trials evaluating chemotherapy/ICI in first-line advanced NSCLC were included in the analysis. The crossover rate ranged 0% to 54% in ICI monotherapy/dual ICI trials and 0% to 52% in chemotherapy/ICI trials. Nineteen of 23 trials provided information on subsequent postprotocol therapies. Among the trials not allowing crossover, postprotocol ICI was administered to 17% to 45.8% of patients. Information regarding the eventual receipt of ICI therapy was available for 22 of 23 trials. Of 6631 patients, 2507 (37.8%) randomized to the control arm eventually received ICI therapy. CONCLUSION: The rate of crossover and postprotocol ICI use was low in frontline trials for first-line NSCLC incorporating ICI. Given the proven survival overall survival of ICI in a broad population, there is a need to ensure availability of this life-prolonging therapy in future trials, either by crossover treatment or postprotocol administration.

Assessment of Rehabilitation Journal Requirements for the Use of Reporting Guidelines and Clinical Trial Registration.

OBJECTIVE: To assess reporting guideline and clinical trial registration requirements in rehabilitation journals. DESIGN: We examined rehabilitation journals with 5-year impact factors exceeding 1.00 from the 2021 Scopus CiteScore tool, alongside the 28 journals included in the 2014 rehabilitation and disability quality improvement initiative. Journals outside the traditional rehabilitation scope were excluded. SETTING: A publicly-funded academic health center in the United States. PARTICIPANTS AND INTERVENTIONS: N/A. MAIN OUTCOME MEASURE(S): The proportion of journals requiring/recommending reporting guideline use and clinical trial registration. RESULTS: Over 90% (57/63) of journals required/recommended clinical trial reporting guidelines, while 68% (39/57) specified guideline requirements for systematic review/meta-analysis protocols. The 2014 collaborative initiative journals demonstrated higher rates of requiring/recommending reporting guidelines for clinical trials (24/26; 92.3%), systematic reviews/meta-analyses (23/26; 88.5%), observational studies in epidemiology (22/25; 88%), and diagnostic accuracy studies (20/24; 83.3%). Conversely, the 2021 Scopus CiteScore journals displayed higher rates for the remaining study designs. Overall, 52/63 (82.5%) journals required/recommended trial registration. Trial registration policies were comparable, with a slight advantage favoring the 2021 Scopus CiteScore journals. CONCLUSION: Rehabilitation journals variably promoted reporting guideline use and clinical trial registration. Common study designs like clinical trials, observational studies in epidemiology, and diagnostic accuracy studies demonstrated robust requirement/recommendation rates, while less common designs like economic evaluations and animal research had suboptimal rates. Journals can enhance reporting guideline use and trial registration by directing authors to the EQUATOR Network, requiring adherence to registration and reporting standards, and clarifying language in author instructions.

Endorsement of reporting guidelines and clinical trial registration across Scopus-indexed rheumatology journals: a cross-sectional analysis.

The purpose of this study was to investigate the instructions for authors of rheumatology journals and analyze their endorsement of reporting guidelines and clinical trial registration. Sixty rheumatology journals were selected by a research librarian and an investigator through the 2021 Scopus CiteScore tool. The instructions for authors' subsection of each journal was assessed to determine endorsement of study design-specific reporting guidelines or clinical trial registration. Descriptive statistics were calculated using R (version 4.2.1) and RStudio. Of the 58 journals analyzed, 34 (34/58; 59%) mentioned the EQUATOR Network: an online compendium of best practice reporting guidelines. The most commonly mentioned reporting guidelines were CONSORT with 44 journals (44/58; 75%), and PRISMA with 35 journals (35/58; 60%). The least mentioned guidelines were QUOROM with 56 journals not mentioning the guideline (56/58; 97%), and SRQR with 53 journals not mentioning the guideline (53/57, 93%). Clinical trial registration was required by 38 journals (38/58; 66%) and recommended by 8 journals (8/58; 14%). Our study found that endorsement of reporting guidelines and clinical trial registration within rheumatology journals was suboptimal with great room for improvement. Endorsement of reporting guidelines have shown to not only mitigate bias, but also improve research methodologies. Therefore, we recommend rheumatology journals broadly expand their endorsement of reporting guidelines and clinical trial registration to improve the quality of evidence they publish.

Brainstem astrocytes control homeostatic regulation of caloric intake.

Prolonged high-fat diet (HFD) exposure is associated with hyperphagia, excess caloric intake and weight gain. After initial exposure to a HFD, a brief (24-48 h) period of hyperphagia is followed by the regulation of caloric intake and restoration of energy balance within an acute (3-5 day) period. Previous studies have demonstrated this occurs via a vagally mediated signalling cascade that increases glutamatergic transmission via activation of NMDA receptors located on gastric-projecting neurons of the dorsal motor nucleus of the vagus (DMV). The present study used electrophysiological recordings from thin brainstem slice preparations, in vivo recordings of gastric motility and tone, measurement of gastric emptying rates, and food intake studies to investigate the hypothesis that activation of brainstem astrocytes in response to acute HFD exposure is responsible for the increased glutamatergic drive to DMV neurons and the restoration of caloric balance. Pharmacological and chemogenetic inhibition of brainstem astrocytes reduced glutamatergic signalling and DMV excitability, dysregulated gastric tone and motility, attenuated the homeostatic delay in gastric emptying, and prevented the decrease in food intake that is observed during the period of energy regulation following initial exposure to HFD. Understanding the mechanisms involved in caloric regulation may provide critical insights into energy balance as well as into the hyperphagia that develops as these mechanisms are overcome. KEY POINTS: Initial exposure to a high fat diet is associated with a brief period of hyperphagia before caloric intake and energy balance is restored. This period of homeostatic regulation is associated with a vagally mediated signalling cascade that increases glutamatergic transmission to dorsal motor nucleus of the vagus (DMV) neurons via activation of synaptic NMDA receptors. The present study demonstrates that pharmacological and chemogenetic inhibition of brainstem astrocytes reduced glutamatergic signalling and DMV neuronal excitability, dysregulated gastric motility and tone and emptying, and prevented the regulation of food intake following high-fat diet exposure. Astrocyte regulation of glutamatergic transmission to DMV neurons appears to involve release of the gliotransmitters glutamate and ATP. Understanding the mechanisms involved in caloric regulation may provide critical insights into energy balance as well as into the hyperphagia that develops as these mechanisms are overcome.

Evaluating a Tobacco Treatment Program's Transition to Telehealth Using a Social Determinants of Health Lens.

INTRODUCTION: While strong associations exist between social determinants of health (SDOH), socioeconomic status, and smoking, these factors are not routinely assessed in tobacco treatment programs (TTP). This study addresses this gap by evaluating a composite metric of SDOH and a measure of access to care to determine program reach before and after the implementation of telehealth tobacco treatment delivery. AIMS AND METHODS: We examined inpatient data from a large TTP during two comparable time periods from April 1, 2019 to September 30, 2019 (pre-telehealth) and from April 1, 2020 to September 30, 2020 (telehealth). The populations were compared using point-of-care data, including 5-digit zip codes mapped to the CDC's Social Vulnerability Index (SVI) and driving distance (in 60-min increments) to the study hospital. Chi-square tests for homogeneity were performed for SVI and driving distance comparisons. RESULTS: While distance distributions were significantly different between the pre-telehealth and telehealth populations (χ 2 = 13.5 (df = 3, N = 3234), p = .004, no significant differences existed in the proportion of SVI categories between the two populations (χ 2 = 5.8 (df = 3, N = 3234), p = .12). In the telehealth population, patients with the highest SVI vulnerability had the greatest proportions living >1 h from the hospital. CONCLUSIONS: This study offers a novel evaluation of tobacco treatment in relation to an SDOH metric (SVI) and care access (distance to the hospital) for inpatient populations. Patient reach, including to those with high vulnerabilities, remained consistent in a transition to telehealth. These methods can inform future reach and engagement of patients who use tobacco products, including patients with high vulnerability or who reside at greater distances from treatment programs. IMPLICATIONS: This study provides the first analysis of inpatient tobacco use treatment (TUT) transition to telehealth delivery of care during the COVID-19 pandemic using the CDC's SVI metric and patient distance to the hospital. The transition resulted in consistent reach to patients at the highest vulnerability. These findings can inform efforts to evaluate SDOH measures and improve reach, engagement, and research on telehealth delivery of inpatient TUT.

An Analysis of Inpatient Tobacco Use Treatment Transition to Telehealth.

INTRODUCTION: During the COVID-19 pandemic, many tobacco users increased their tobacco use, and calls to quitlines decreased. Among inpatients, the pandemic also necessitated a rapid transition of intensive tobacco use counseling to telehealth counseling. No data exist comparing the outcomes of telehealth inpatient counseling with in-person (pre-telehealth) counseling. AIMS AND METHODS: We examined inpatient data from a large tobacco treatment program (TTP) during two comparable time periods 04/01/2019-09/30/2019 (pre-telehealth) and 04/01/2020-09/30/2020 (telehealth). The pre-telehealth and telehealth populations were compared using Pearson's chi-square test for homogeneity on each populations' patient, visit, and medication acceptance characteristics. Reach to "current tobacco users" was analyzed using TTP flowsheet and electronic health record (EHR) data in relation to aggregate EHR data in the data warehouse. RESULTS: Mean monthly tobacco treatment inpatient counseling and outreach visits increased 38.9% in the telehealth period (M = 376, SD = 36.7) compared with the pre-telehealth period (M = 271, SD = 50.0) (t(10) = 3.8, p = .004). Reach significantly increased from 32.8% to 65.9% among all "current tobacco users" admitted, including 31.8% to 66.6% in races at higher risk for COVID-19 severe disease. Pearson's chi-square tests for homogeneity showed significant differences in the pre-telehealth and telehealth population distributions for age, visit type, ethnicity, and medication acceptance. CONCLUSIONS: This study offers the first understanding of characteristics of patients, visits, and medication acceptances in pre-telehealth and telehealth tobacco use treatment for inpatient populations. Larger reach and counseling were identified in the telehealth population. This study's findings on inpatient tobacco use treatment can inform future reach and engagement of large numbers of patients who use tobacco products. IMPLICATIONS: This study provides the first analysis of inpatient tobacco use treatment transition to telehealth delivery of care during the COVID-19 pandemic. The transition resulted in increases in reach and cessation counseling. These findings can inform efforts to improve reach, engagement, and research on telehealth delivery of inpatient tobacco use treatment.

Designing More Effective Cigar Warnings: An Experiment Among Adult Cigar Smokers.

INTRODUCTION: Little systematic evidence exists about the effectiveness of cigar warnings. This study examined the perceived message effectiveness (PME) of warning statements about different health consequences caused by cigars. PME is a validated self-report scale of how effectively a health message discourages smoking. AIMS AND METHODS: We conducted an online study from April to May 2020 with adults in the United States who used cigars in the past 30 days (n = 777). Participants were randomly assigned to view and rate PME (three items, range 1-5) for seven out of 37 text warning statements about different health consequences from cigar use. Linear mixed effects models evaluated the most effective warning characteristics (eg, type of health consequence), controlling for repeated measures and participant demographics. RESULTS: Analyses showed that health consequences about the cardiovascular system (B = 0.38), mouth (B = 0.40), other digestive (B = 0.45), respiratory system (B = 0.36), and early death (B = 0.36) were associated with higher PME scores than reproductive health consequences (all p values <.001). Similar results were found for these health consequences compared with addiction (all p values p < .001). We also observed that awareness of the health consequence was associated with higher PME scores (B = 0.19, p < .001) and length of the warning message (number of characters) was associated with lower PME scores (B = -0.007, p = .03). No differences were observed between cancer and noncancer health consequences (p = .27) or health consequences that used plain language versus medical jargon (p = .94). CONCLUSIONS: Our study provides new evidence about the perceived effectiveness of different cigar health warning statements and identifies features that may strengthen statements. IMPLICATIONS: Our study with cigar smokers from across the United States provides much-needed evidence concerning the perceived effectiveness of different cigar health warning statements and features that may strengthen such statements. Mandated cigar warnings in the United States could be strengthened by including health consequences that were perceived as more effective in our study (eg, early death), using health consequences that participants were aware of, and using short warning statements.

Nanoliposomal irinotecan (Nal-IRI)-based chemotherapy after irinotecan -based chemotherapy in patients with pancreas cancer.

BACKGROUND: Nanoliposomal irinotecan (Nal-IRI) is a preferred second-line treatment for metastatic pancreas cancer. It is unclear, however, whether patients who had received irinotecan derive benefit. METHODS: Medical records of metastatic pancreas cancer patients who had received irinotecan and then Nal-IRI were reviewed. The primary endpoint was overall survival after the initiation of Nal-IRI (an a priori threshold of >4 months defined success); adverse events and quotes from the medical record on decision-making were also recorded. RESULTS: Sixty four patients met eligibility criteria with a median age of 65 years (range: 36, 80 years). The median overall survival from initiation of Nal-IRI was 5.1 months (95% confidence interval (CI): 4.3, 5.6 months). An exploratory comparison, based on no cancer progression with irinotecan versus progression, showed improved survival with Nal-IRI in the former group: 6.1 months (95% CI: 5.1, 9.3 months) versus 4.3 months (95% CI: 2.3, 4.8 months); p = 0.0006. Nal-IRI adverse events occurred as expected. Qualitative data illustrate several themes, including "limited treatment options," which appeared to drive the decision to prescribe Nal-IRI. CONCLUSION: Nal-IRI might be considered in pancreas cancer patients who had received irinotecan, particularly in the absence of disease progression with the latter.

Rare Adverse Events with Programmed Death-1 and Programmed Death-1 Ligand Inhibitors: Justification and Rationale for a Systematic Review.

PURPOSE: Immune checkpoint inhibitors are a new class of cancer drug that spawn unusual adverse events that generate unusual and sometimes unexpected adverse events. Despite databases that track such adverse events, there remains a need to also generate systematic reviews to capture side effects from such agents. FINDINGS: We generated a systematic compendium of adverse event reports. Extensively reviewing the published literature of case reports and case series, we relied on the peer process to compile a resource for clinicians of rare adverse events associated with checkpoint inhibitors. We used this compendium as a platform to provide broad-based comments on the role of systematic reviews in gathering such adverse event data. This approach generated 265 types of rare adverse events that had been reported, the most frequent of which were autoimmune type I diabetes (n = 62), pneumonitis (n = 40), myocarditis (n = 39), and colitis (n = 36). More unusual adverse events were also catalogued. Some adverse events that initially seemed unusual turned out to be more frequently reported over time and thus lost their novelty-an important point which provides context for how adverse events should be viewed when new drugs become available. Additionally, in contrast to such resources as the FDA Adverse Event Reporting System (FAERS), this systematic review relied on peer-reviewed data-another important point which adds strength to such systematic reviews. This report provides a compendium of rare and usual adverse events, serves as a resource to cancer clinicians, and appears to be justified based on the reported findings.

Methodological quality of systematic reviews comprising clinical practice guidelines for cardiovascular risk assessment and management for noncardiac surgery.

BACKGROUND: Cardiac assessment in noncardiac surgery clinical practice guidelines should be supported by the highest-quality evidence such as that offered by systematic reviews. Currently, the methodological and reporting quality of these studies remains unknown. METHODS: We used PubMed to search for all clinical practice guidelines related to perioperative cardiovascular patients undergoing noncardiac surgery from 2010 to 2021. The included clinical practice guidelines were analysed for all systematic reviews and meta-analyses. The primary objective of this study was to determine reporting and methodological quality using the PRISMA (Preferred Reporting Instrument for Systematic Reviews and Meta-Analyses) and AMSTAR-2 (A Measurement Tool to Assess Systematic Reviews-2) instruments. Our secondary objective was to compare systematic reviews conducted by the Cochrane Collaboration with non-Cochrane studies. RESULTS: Three clinical practice guidelines were included in our study. Within these, 78 systematic reviews were included. PRISMA completion ranged from 34.8% to 100.0% with a mean of 76.9%. AMSTAR-2 completion ranged from 15.6% to 96.9% with a mean of 58.0%. Fifty-four systematic reviews underpinned a clinical practice guidelines recommendation, of which 25 were rated 'critically low' by AMSTAR-2 appraisal. Cochrane systematic reviews typically performed better than non-Cochrane studies, but were a minority of the included studies (10/78). CONCLUSION: We found deficiencies in several key areas regarding the methodological and reporting qualities of systematic reviews included in cardiac assessment in noncardiac surgery clinical practice guidelines. As these clinical practice guidelines are instrumental to clinical decision-making and patient care in cardiac assessment in noncardiac surgery, we advocate for improved reporting quality among systematic reviews cited as supportive evidence for these recommendations.

Assessing quality of randomized trials supporting guidelines for laparoscopic and endoscopic surgery.

BACKGROUND: Recent studies have highlighted the risk of bias and the fragility of results in randomized controlled trials (RCTs). The aim of our study was to evaluate the clinical practice guidelines created by the Society for Gastrointestinal and Endoscopic Surgeons (SAGES) for fragility, statistical power, and risk of bias. MATERIALS AND METHODS: We screened the SAGES clinical practice guideline references for qualifying RCTs. RCTs were assessed for risk of bias using the Cochrane Collaboration Risk of Bias tool 2.0. We used the fragility index and fragility quotient to evaluate the robustness of trial results and conducted a power analysis using G*Power to determine if trials were adequately powered. RESULTS: Twenty-two (40.7%) of the 54 trials that we assessed were rated as having a high risk of bias, 17 (31.5%) were rated as having a low risk of bias, and 15 (27.8%) were rated as having some concerns. The median fragility index was 2.5 (interquartile range 1-7). The median fragility quotient was 0.021 (interquartile range 0.003-0.045). Mean sample size was 108, and the mean loss to follow-up was eight patients. Eight of 33 trials (24.2%) were found to be underpowered according to the sample size used in the primary outcome. CONCLUSIONS: Guidelines created by SAGES are supported by RCTs that are frequently fragile or underpowered or have a high risk of bias. Future RCTs should utilize the Consolidated Standards of Reporting Trials statement, implement strategies to minimize loss to follow-up, and use properly powered sample sizes.

Analysis of the Five Unimolecular Reaction Pathways of CD2ClCHFCl with Emphasis on CD2Cl(F)C: and CD2Cl(Cl)C: Formed by 1,1-HCl and 1,1-HF Elimination.

The five unimolecular HX and DX (X = F, Cl) elimination pathways of CD2ClCHFCl* were examined using a chemical activation technique; the molecules were generated with 92 kcal mol-1 of vibrational energy in a room-temperature bath gas by a combination of CD2Cl and CHFCl radicals. The total unimolecular rate constant was 9.7 × 107 s-1, and branching fractions for each channel were 0.52 (2,1-DCl), 0.29 (1,1-HCl), 0.10 (2,1-DF), 0.07 (1,1-HF), and 0.02 (1,2-HCl). Comparison of the individual experimental rate constants to calculated statistical rate constants gave threshold energies for each process as 63, 72, 66, 73, and 70 kcal mol-1, listed in the same order as the branching fractions. The 1,1-HCl and 1,1-HF reactions gave carbenes, CD2Cl(F)C: and CD2Cl(Cl)C:, respectively, as products, which have hydrogen-bonded complexes with HCl or HF in the exit channel of the potential energy surface. These carbenes have energy in excess of the threshold energy for D atom migration to give CDCl═CDF and CDCl═CDCl, and the subsequent cis-trans isomerization rates of the dihaloethenes can provide information about energy disposal by the 1,1-HX elimination reactions. Electronic structure calculations provide information for transition states of CD2ClCHFCl and hydrogen-bonded complexes of carbenes with HF and HCl. In addition, D atom migration in both free carbenes and in complexes formed by the carbene hydrogen bonding to HCl or HF is explored.

The Unimolecular Reactions of CF3CHF2 Studied by Chemical Activation: Assignment of Rate Constants and Threshold Energies to the 1,2-H Atom Transfer, 1,1-HF and 1,2-HF Elimination Reactions, and the Dependence of Threshold Energies on the Number of F-Atom Substituents in the Fluoroethane Molecules.

The recombination of CF3 and CHF2 radicals in a room-temperature bath gas was used to prepare vibrationally excited CF3CHF2* molecules with 101 kcal mol-1 of vibrational energy. The subsequent 1,2-H atom transfer and 1,1-HF and 1,2-HF elimination reactions were observed as a function of bath gas pressure by following the CHF3, CF3(F)C: and C2F4 product concentrations by gas chromatography using a mass spectrometer as the detector. The singlet CF3(F)C: concentration was measured by trapping the carbene with trans-2-butene. The experimental rate constants are 3.6 × 104, 4.7 × 104, and 1.1 × 104 s-1 for the 1,2-H atom transfer and 1,1-HF and 1,2-HF elimination reactions, respectively. These experimental rate constants were matched to statistical RRKM calculated rate constants to assign threshold energies (E0) of 88 ± 2, 88 ± 2, and 87 ± 2 kcal mol-1 to the three reactions. Pentafluoroethane is the only fluoroethane that has a competitive H atom transfer decomposition reaction, and it is the only example with 1,1-HF elimination being more important than 1,2-HF elimination. The trend of increasing threshold energies for both 1,1-HF and 1,2-HF processes with the number of F atoms in the fluoroethane molecule is summarized and investigated with electronic-structure calculations. Examination of the intrinsic reaction coordinate associated with the 1,1-HF elimination reaction found an adduct between CF3(F)C: and HF in the exit channel with a dissociation energy of ∼5 kcal mol-1. Hydrogen-bonded complexes between HF and the H atom migration transition state of CH3(F)C: and the F atom migration transition state of CF3(F)C: also were found by the calculations. The role that these carbene-HF complexes could play in 1,1-HF elimination reactions is discussed.

Reinvestigation of the Unimolecular Reactions of CHF2CHF2: Identification of the 1,1-HF Elimination Component from Addition of :CFCHF2 to trans-2-Butene.

The recombination of ·CHF2 radicals in a room-temperature bath gas was used to generate CHF2CHF2* (where * indicates vibrational excitation) molecules with 96 kcal mol-1 of vibrational energy. The CHF2CHF2* molecules decompose by four-centered 1,2-HF elimination and by three-centered 1,1-HF elimination reactions to give HF and either CHF═CF2 or :CFCHF2, respectively. The 1,1-HF component was identified by trapping the :CFCHF2 carbene with trans-2-butene that forms 1-fluoro-1-difluoromethyl-2,3-dimethylcyclopropane. The total rate constant for the decomposition of CHF2CHF2* was 6.0 × 105 s-1, and the rate constant for the 1,1-HF pathway forming the carbene, as measured by the 1-fluoro-1-difluoromethyl-2,3-dimethylcyclopropane yield, was 1.4 × 105 s-1. On the basis of matching the experimental rate constants to calculated statistical rate constants, the threshold energies for the four-centered and three-centered reactions are 78 and ≤85 kcal mol-1, respectively.

Chemical Activation Study of the Unimolecular Reactions of CD3CD2CHCl2 and CHCl2CHCl2 with Analysis of the 1,1-HCl Elimination Pathway.

Chemically activated C2D5CHCl2 molecules were generated with 88 kcal mol-1 of vibrational energy by the recombination of C2D5 and CHCl2 radicals in a room temperature bath gas. The competing 2,1-DCl and 1,1-HCl unimolecular reactions were identified by the observation of the CD3CD═CHCl and CD3CD═CDCl products. The initial CD3CD2C-Cl carbene product from 1,1-HCl elimination rearranges to CD3CD═CDCl under the conditions of the experiments. The experimental rate constants were 2.7 × 107 and 0.47 × 107 s-1 for 2,1-DCl and 1,1-HCl elimination reactions, respectively, which corresponds to branching fractions of 0.84 and 0.16. The experimental rate constants were compared to calculated statistical rate constants to assign threshold energies of 54 and ≈66 kcal mol-1 for the 1,2-DCl and 1,1-HCl reactions, respectively. The statistical rate constants were obtained from models developed from electronic-structure calculations for the molecule and its transition states. The rate constant (5.3 × 107 s-1) for the unimolecular decomposition of CHCl2CHCl2 molecules formed with 82 kcal mol-1 of vibrational energy by the recombination of CHCl2 radicals also is reported. On the basis of the magnitude of the calculated rate constant, 1,1-HCl elimination must contribute less than 15% to the reaction; 1,2-HCl elimination is the major reaction and the threshold energy is 59 kcal mol-1. Calculations also were done to analyze previously published rate constants for chemically activated CD2ClCHCl2 molecules with 86 kcal mol-1 of energy to obtain a better overall description of the nature of the 1,1-HCl pathway for 1,1-dichloroalkanes. The interplay of the threshold energies for the 2,1-HCl and 1,1-HCl reactions and the available energy determines the product branching fractions for individual molecules. The unusual nature of the transition state for 1,1-HCl elimination is discussed.