Nevin Manimala

Int J Epidemiol. 2023 Sep 21:dyad127. doi: 10.1093/ije/dyad127. Online ahead of print.

ABSTRACT

Competing risks issues are common in clinical trials and epidemiological studies for patients in follow-up who may experience a variety of possible outcomes. Under such competing risks, two hazard-based statistical methods, cause-specific hazard (CSH) and subdistribution hazard (SDH), are frequently used to assess treatment effects among groups. However, the outcomes of the CSH-based and SDH-based methods have a close connection with the proportional hazards (CSH or SDH) assumption and may have an non-intuitive interpretation. Recently, restricted mean time lost (RMTL) has been used as an alternative summary measure for analysing competing risks, due to its clinical interpretability and robustness to the proportional hazards assumption. Considering the above approaches, we summarize the differences between hazard-based and RMTL-based methods from the aspects of practical interpretation, proportional hazards model assumption and the selection of restricted time points, and propose corresponding suggestions for the analysis of between-group differences under competing risks. Moreover, an R package ‘cRMTL’ and corresponding step-by-step guidance are available to help users for applying these approaches.

PMID:37738672 | DOI:10.1093/ije/dyad127

J Infect Dis. 2023 Sep 21:jiad412. doi: 10.1093/infdis/jiad412. Online ahead of print.

ABSTRACT

BACKGROUND: The value of the widely applied maternal cytomegalovirus (CMV) serological testing approach in predicting intrauterine transmission in highly seroprevalent regions remains unknown.

METHODS: A nested case‒control study was conducted based on a maternal-child cohort study. Newborns with congenital CMV (cCMV) infection were included, and each of them was matched to 3 newborns without cCMV infection. Retrospective samples were tested for immunoglobulin G (IgG) avidity and immunoglobulin M (IgM) antibodies in maternal serum and CMV DNA in maternal blood and urine to analyse their associations with cCMV infection.

RESULTS: Forty-eight newborns with cCMV infection and 144 matched newborns without infection were included in the study. Maternal IgM antibodies and IgG avidity during pregnancy were not statistically associated with intrauterine transmission. The presence of CMV DNAemia indicated a higher risk of cCMV infection, with the OR values as 5.7, 6.5 and 13.0 in early, middle and late pregnancy, respectively. However, the difference in CMV shedding rates in transmitters and nontransmitters was not significant in urine.

CONCLUSION: The value of current maternal CMV serological testing in regions with high seropositivity rates is very limited and should be reconsidered. The detection of DNAemia would be helpful in assessing the risk of intrauterine transmission.

PMID:37738651 | DOI:10.1093/infdis/jiad412

J Appl Clin Med Phys. 2023 Sep 22:e14143. doi: 10.1002/acm2.14143. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this study is to assess the quality of automatic planned O-Ring Halcyon linac SBRT plans for pelvic lymph node metastases and to establish an absolute PTV volume threshold as a plan quality prediction criterion. Compliance of the plans to institutional SBRT plan evaluation criteria and differences in plan quality and treatment delivery times between Halcyon Linac and CyberKnife robotic SBRT were evaluated.

METHODS: Twenty-one CyberKnife treatment plans were replanned for Halcyon. Prescription doses range was 26-40 Gy in mean three fractions. The mean/median planning target volume was 4.0/3.6 cm³ . Institutional criteria for the plan evaluation were: New Conformity Index (NCI), Conformity Index (CI), Modified Gradient Index (MGI), selectivity index reciprocal (PIV/TV_PIV ), and the target coverage by prescription isodose (%PIV). Statistical analysis based on the receiver operating characteristic (ROC) curve was used to determine a plan quality predictor threshold of the PTV volume. Comparative analysis of normal tissue complication probabilities (NTCP) was used to assess the risk of toxicity in healthy tissues.

RESULTS: Seventy-one percent (n = 15)/95% (n = 20) of Halcyon and 81% (n = 17)/100% (n = 21) of CK plans fulfilled all ideal/tolerance criteria. For PTVs above a found optimal threshold of 2.6 cm³ (71%, n = 15), no statistically significant difference was observed between the CI, NCI, PIV/TV_PIV , and MGI indexes of both groups, while the coverage (%PIV) was statistically but not clinically significantly different between cohorts. Significantly shorter delivery times are expected with Halcyon. No significant differences in NTCP were observed.

CONCLUSION: All but one automatically optimized Halcyon treatment plans demonstrated ideal or acceptable performance. PTV threshold of 2.6 cm³ can be used as decision criteria in clinical settings. The results of our study demonstrated the promising performance of the Halcyon for pelvic SBRT, although plan-specific QA is required to verify machine performance during plan delivery.

PMID:37738649 | DOI:10.1002/acm2.14143

Ann Behav Med. 2023 Sep 21:kaad052. doi: 10.1093/abm/kaad052. Online ahead of print.

ABSTRACT

BACKGROUND: Cigarette pack inserts with messages on cessation benefits and advice are a promising labeling policy that may help promote smoking cessation.

PURPOSE: To assess insert effects, with and without accompanying pictorial health warning labels(HWLs), on hypothesized psychosocial and behavioral outcomes.

METHODS: We conducted a 2 × 2 between-subject randomized trial (inserts with efficacy messages vs. no inserts; large pictorial HWLs vs. small text HWLs), with 367 adults who smoked at least 10 cigarettes a day. Participants received a 14-day supply of their preferred cigarettes with packs modified to reflect their experimental condition. Over 2 weeks, we surveyed participants approximately 4-5 times a day during their smoking sessions, querying feelings about smoking, level of worry about harms from smoking, self-efficacy to cut down on cigarettes, self-efficacy to quit, hopefulness about quitting, and motivation to quit. Each evening, participants reported their perceived susceptibility to smoking harms and, for the last 24 hr, their frequency of thinking about smoking harms and cessation benefits, conversations about smoking cessation or harms, and foregoing or stubbing out cigarettes before they finished smoking. Mixed-effects ordinal and logistic models were estimated to evaluate differences between groups.

RESULTS: Participants whose packs included inserts were more likely than those whose packs did not include inserts to report foregoing or stubbing out of cigarettes (OR = 2.39, 95% CI = 1.36, 4.20). Otherwise, no statistically significant associations were found between labeling conditions and outcomes.

CONCLUSIONS: This study provides some evidence, albeit limited, that pack inserts with efficacy messages can promote behaviors that predict smoking cessation attempts.

PMID:37738629 | DOI:10.1093/abm/kaad052

Inflamm Bowel Dis. 2023 Sep 21:izad215. doi: 10.1093/ibd/izad215. Online ahead of print.

NO ABSTRACT

PMID:37738577 | DOI:10.1093/ibd/izad215

Pain Med. 2023 Sep 21:pnad128. doi: 10.1093/pm/pnad128. Online ahead of print.

ABSTRACT

OBJECTIVE: This case series retrospectively reviewed the outcomes in patients implanted with combined, synchronous dorsal root ganglion stimulation (DRGS) and spinal cord stimulation (SCS) connected to a single implantable pulse generator (IPG) in a tertiary referral neuromodulation centre in the United Kingdom.

MATERIALS AND METHODS: Twenty-six patients underwent a trial of DRGS+SCS for treating focal neuropathic pain between January 2016 and December 2019, with a follow-up in February 2022. A Transgrade approach was employed for DRGS. Patients were provided with three possible stimulation programmes: DRGS-only, SCS-only, or DRGS+SCS. Patients were assessed for pain intensity, patients’ global impression of change (PGIC), preferred lead(s) and complications.

RESULTS: Twenty patients were successful and went on for full implantation. The most common diagnosis was Complex Regional Pain Syndrome. After an average of 3.1 years follow-up, one patient was lost to follow-up, and two were non-responders. Of the remaining 17 patients, 16 (94%) continued to report a PGIC of 7. The average pain intensity at Baseline was 8.5 on an NRS scale of 0-10. At the last follow-up, the average NRS reduction overall was 78.9% with no statistical difference between those preferring DRGS+SCS (n = 9), SCS-only (n = 3) and DRGS-only (n = 5). The combination of DRGS+SCS was preferred by 53% at the last follow-up. There were no serious neurological complications.

CONCLUSION: This retrospective case series demonstrates the potential effectiveness of combined DRGS+SCS with sustained analgesia observed at an average follow-up of over three years. Implanting combined DRGS+SCS may provide programming flexibility and therapeutic alternatives.

PMID:37738574 | DOI:10.1093/pm/pnad128

Clin Infect Dis. 2023 Sep 21:ciad552. doi: 10.1093/cid/ciad552. Online ahead of print.

ABSTRACT

BACKGROUND: Widespread outbreaks of person-to-person transmission of hepatitis A virus (HAV), particularly among people who inject drugs (PWID), continue across the United States and globally. However, the herd immunity threshold and vaccination coverage required to prevent outbreaks is unknown. We aimed to use surveillance data and dynamic modeling to estimate herd immunity thresholds among PWID in 16 U.S. states.

METHODS: We used a previously published dynamic transmission model of HAV transmission, calibrated to surveillance data from outbreaks involving PWID in 16 states. Using state-level calibrated models, we estimated the basic reproduction number (R0) and herd immunity threshold for PWID in each state. We performed a meta-analysis of herd immunity thresholds to determine the critical vaccination coverage required to prevent most HAV outbreaks among PWID.

RESULTS: Estimates of R0 for HAV infection ranged from 2.2 (95% CI 1.9-2.5) for North Carolina to 5.0 (95% CI 4.5-5.6) for West Virginia. Corresponding herd immunity thresholds ranged from 55% (95% CI 47-61%) for North Carolina to 80% (95% CI 78-82%) for West Virginia. Based on the meta-analysis, we estimated a pooled herd immunity threshold of 64% (95% CI 61-68%, 90% prediction interval 52-76%) among PWID. Using the prediction interval upper bound (76%) and assuming 95% vaccine efficacy, we estimate a vaccination coverage of 80% could prevent most HAV outbreaks.

CONCLUSIONS: Hepatitis A vaccination programs in the United States may need to achieve vaccination coverage of at least 80% among PWID in order to prevent most HAV outbreaks among this population.

PMID:37738564 | DOI:10.1093/cid/ciad552

Mol Biol Evol. 2023 Sep 21:msad212. doi: 10.1093/molbev/msad212. Online ahead of print.

ABSTRACT

Molecular evolutionary rate variation is a key aspect of the evolution of many organisms that can be modelled using molecular clock models. For example, fixed local clocks revealed the role of episodic evolution in the emergence of SARS-CoV-2 variants of concern. Like all statistical models, however, the reliability of such inferences is contingent on an assessment of statistical evidence. We present a novel Bayesian phylogenetic approach for detecting episodic evolution. It consists of computing Bayes factors, as the ratio of posterior and prior odds of evolutionary rate increases, effectively quantifying support for the effect size. We conducted an extensive simulation study to illustrate the power of this method and benchmarked it to formal model comparison of a range of molecular clock models using (log) marginal likelihood estimation, and to inference under a random local clock model. Quantifying support for the effect size has higher sensitivity than formal model testing and is straight-forward to compute, because it only needs samples from the posterior and prior distribution. However, formal model testing has the advantage of accommodating a wide range molecular clock models. We also assessed the ability of an automated approach, known as the random local clock, where branches under episodic evolution may be detected without their a priori definition. In an empirical analysis of a data set of SARS-CoV-2 genomes, we find ‘very strong’ evidence for episodic evolution. Our results provide guidelines and practical methods for Bayesian detection of episodic evolution, as well as avenues for further research into this phenomenon.

PMID:37738550 | DOI:10.1093/molbev/msad212

JCO Glob Oncol. 2023 Sep;9:e2200397. doi: 10.1200/GO.22.00397.

ABSTRACT

PURPOSE: Timely radiation treatment (RT) is critical in cervical cancer treatment, but patients in low- and middle-income countries (LMICs) in sub-Saharan Africa often face barriers that delay care. Time to care was benchmarked in a multidisciplinary team (MDT) setting in Botswana.

METHODS: Time intervals between steps in care were recorded for 230 patients reviewed at MDT between January 2016 and July 2018. Associations between RT delay and overall survival (OS) were evaluated using Kaplan-Meier curves and multivariable Cox proportional hazards models.

RESULTS: For patients who received RT (n = 187; 81.3%), the median biopsy to pathology reporting interval was 25 (IQR, 19-36) days and was 57 (IQR, 28-68) days for patients who did not (P = .003). Intervals in care did not differ between patients who did and did not receive RT. Among treated patients, the uppermost quartile interval from pathology reporting to RT initiation was ≥111 days and that from RT simulation to initiation was ≥12 days. Among patients receiving a RT dose of ≥65 Gy (n = 100), the delay from RT simulation to initiation of >12 days was associated with worse median OS (2.0 v 4.6 years; P = .048); this association trended toward, although did not meet, statistical significance on multivariable analysis (hazard ratio, 2.35; 95% CI, 0.95 to 5.85; P = .07).

CONCLUSION: The MDT-coordinated care model allows for systematic benchmarking of the patient treatment cascade. Barriers to timely treatment exist for this cohort in Botswana, and RT delay may be associated with OS of patients receiving curative treatment. Interventions to accelerate the timing of the radiation oncology care cascade may improve clinical outcomes in this LMIC setting.

PMID:37738538 | DOI:10.1200/GO.22.00397

JCO Oncol Pract. 2023 Sep 22:OP2300309. doi: 10.1200/OP.23.00309. Online ahead of print.

ABSTRACT

PURPOSE: Biosimilars are clinically equivalent to branded products yet cost significantly less. Interchangeability is a US Food and Drug Administration (FDA) designation that allows generic drugs to be substituted for reference drugs at the pharmacy, without a physician’s consent. Currently, no oncologic biosimilar has FDA approval for interchangeability.

METHODS: Building on pharmacy auto-substitution processes with therapeutic interchange, Plan-Do-Study-Act methodology was used to automate conversions from reference biological products to Pharmacy and Therapeutics-/Physician-approved biosimilars. After establishing the baseline metrics, cycle 1 focused on full staff education (completed July 2020) with systematic pharmacy-driven biosimilar conversion initiated in September 2020 for rituximab, trastuzumab, and bevacizumab. Physician-initiated conversion of Neulasta biosimilar products was encouraged but not mandated. During cycle 2 (May 1, 2021-November 30, 2021), pharmacy-driven Neulasta biosimilar conversion was mandated. In cycle 3 (December 1, 2021-April 30, 2023), stakeholder education was reinforced and the sustainability of conversions was confirmed.

RESULTS: Systematic pharmacy-driven conversion to biosimilar products improved over cycles 1 and 2 from baseline: 1.8% to 90.3% for rituximab, 9.2% to 89.7% for trastuzumab, and 20.5% to 96.1% for bevacizumab. Physician-driven biosimilar conversion for Neulasta was lower at 12.7% through April 2021. Pharmacy-driven Neulasta biosimilar conversion was initiated during cycle 2, resulting in a conversion rate of 39.7%. The conversion rates remained sustainable through April 2023.

CONCLUSION: Pharmacy-driven auto-substitution of biosimilar products results in rapid and statistically significant biosimilar adoption. The pharmacy-based substitution approach was found to be far more effective than physician-driven substitution. Rapid conversion from branded products to FDA-approved biosimilar is feasible, measurable, and sustainable and can be scaled. Barriers to Neulasta conversion warrant further investigation.

PMID:37738533 | DOI:10.1200/OP.23.00309