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Author contributions
A.-H.H. and W.-H.C. were the main authors of this manuscript and participated in all the study design. W.T.-J.W. participated in data interpretation and contributed to important intellectual content. Y.-F.S. and W.-Y.C. were responsible for designing the study, monitoring the study execution, and drafting and revising ...
PMC10317955
Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
PMC10317955
Competing interests
The authors declare no competing interests.
PMC10317955
References
PMC10317955
Key Points
PMC10492187
Question
Is adaptive pharmacotherapy effective for smoking cessation compared with nonadaptive standard pharmacotherapy?
PMC10492187
Findings
In this randomized clinical trial, 188 smokers chose between varenicline and nicotine patches and were then randomized to adaptive or standard treatment. Biochemically verified 30-day continuous smoking abstinence at 12 weeks after the target quit date was significantly higher for the adaptive treatment group than the ...
PMC10492187
Meaning
These findings suggest that adaptive pharmacotherapy was effective for smoking cessation.This randomized clinical trial assesses the efficacy of adaptive pharmacotherapy compared with standard pharmacotherapy using varenicline or nicotine patches for smoking cessation.
PMC10492187
Importance
Adaptive pharmacotherapy, ie, starting a medication regimen and then modifying that regimen based on patient response, is common in many medical domains but is not common in smoking cessation. Recently, studies have found that adaptive treatment using precessation nicotine patches is efficacious for smoking cessation; ...
PMC10492187
Objective
To determine whether adaptive pharmacotherapy leads to higher smoking abstinence rates than standard pharmacotherapy in a clinical practice setting.
PMC10492187
Design, Setting, and Participants
MAY
This double-blinded stratified placebo-controlled randomized clinical trial compared adaptive treatment with standard treatment for smoking cessation. The study was conducted at a university health system in Durham, North Carolina, from February 2018 to May 2020 and was stopped early due to COVID-19. Data were analyzed...
PMC10492187
Interventions
Participants were allowed to choose varenicline or nicotine patches and were then randomized to adaptive or nonadaptive (standard) treatment. Participants started on their chosen medication (adaptive) or placebo (standard) 4 weeks before their target quit day. Two weeks later, participants were assessed for treatment r...
PMC10492187
Main Outcome and Measures
The main outcome was biochemically verified 30-day continuous smoking abstinence 12 weeks after their target quit smoking day. Other measures included demographic characteristics, smoking history, and repeated smoking assessments.
PMC10492187
Results
Of the planned 300 participants, a total of 188 participants (mean [SD] age, 49.1 [12.5] years; 102 [54%] female) were enrolled before the trial was stopped because of the COVID-19 pandemic. A total of 127 participants chose to use varenicline, including 64 randomized to adaptive treatment and 63 randomized to standard...
PMC10492187
Conclusions and Relevance
This randomized clinical trial found that adaptive pharmacotherapy was efficacious for smoking cessation treatment in a practice setting.
PMC10492187
Trial Registration
ClinicalTrials.gov Identifier:
PMC10492187
Introduction
precessation smoking reduction
Adaptive treatment, ie, assessing the patient’s response to an initial medication and then modifying the medication regimen based on the patient’s response, is a common medical practice.Regarding extended precessation pharmacotherapy, trials have now shown that 4, 6, and 12 weeks of precessation varenicline all show hi...
PMC10492187
Methods
PMC10492187
Design, Funding, and Registration
This phase 2 double-blind placebo-controlled stratified randomized clinical trial was approved by the Duke University Health System Institutional Review Board, and all participants provided written informed consent prior to enrollment. The trial was designed to compare biochemically verified 12-week smoking abstinence ...
PMC10492187
Participants
psychiatric illness, allergy
ALLERGY
The study was conducted at Duke University Health System, a large university health system in central North Carolina. Potential participants were daily smokers who had been referred to a clinical smoking cessation program. Potential participants were offered free medications and compensation for study participation. In...
PMC10492187
Stratification, Randomization, and Blinding
After enrollment, participants were stratified by medication choice. Using FDA information, participants were asked to choose between using nicotine patches or varenicline. After stratification, participants in the varenicline and nicotine patch groups were randomized 1:1 to adaptive treatment or standard treatment gro...
PMC10492187
Interventions
PMC10492187
Behavioral Treatment
At the baseline visit, all participants were provided with 20 minutes of evidence-based smoking cessation counseling by a tobacco treatment specialist. Smoking cessation counseling including health education, motivational support, and instructions on medication use.
PMC10492187
Medication Treatment
Adaptive treatment participants were provided with their chosen medication (nicotine patch or varenicline) 4 weeks before the target quit day. Varenicline was up-titrated over the first week of treatment to 1 mg twice daily. The nicotine patch was started at 14 to 21 mg based on baseline cigarettes smoked per day. Stan...
PMC10492187
Outcome Measures
psychiatric
Study participants were asked to attend 4 study assessment visits: the baseline visit, medication response visit (2 weeks before the target quit day), and 2 post–quit day visits (2 and 12 weeks after the target quit day). Participants were paid $190 if they completed all 4 study visits. Baseline variables included age,...
PMC10492187
Sample Size
The sample size was based on a 2-tail significance test with 80% power and a 15% attrition rate (from our previous studies at our center). We referenced smoking abstinence rates from available trials that did not enroll a clinical population, and showed an adaptive treatment rate of 39.7%, and standard treatment of 23....
PMC10492187
Statistical Analysis
The primary outcome for the study was 30-day continuous smoking abstinence 12 weeks after the target quit day, verified by expired
PMC10492187
Results
PMC10492187
Participants
The first enrollment was February 15, 2018, and the last study visit was March 11, 2020. The study goal was to enroll 300 participants, but it was stopped early due to the COVID-19 pandemic. Of 307 individuals screened, 24 were not interested in the study, and 95 were excluded based on exclusion criteria. A total of 18...
PMC10492187
Baseline Variables in the Study Cohort
Abbreviation: FTND, Fagerstrom Nicotine Dependence Test.
PMC10492187
Participant Recruitment Flowchart
All enrolled participants were included in intention-to-treat analyses used to determine primary outcome.
PMC10492187
Efficacy
Among all participants, intent-to-treat 12-week postquit biochemically verified 30-day continuous smoking abstinence was 23 of 95 participants (24%) in the adaptive group and 8 of 93 participants (9%) in the standard treatment group (OR, 3.39; 95% CI, 1.43-7.99;
PMC10492187
Mean Expired Carbon Monoxide (
Significant group-by-time interaction across all postbaseline time points:
PMC10492187
Safety
cancer, death, disability
ADVERSE EVENTS, CANCER, EVENTS, ADVERSE EVENT
Among all 188 participants, we identified 1 serious adverse event: 1 participant (2%) in the varenicline standard treatment group died. This death was determined to be related to stage 4 cancer and not study-related. There were no other reports of death, life threatening events, hospitalization, persistent or significa...
PMC10492187
All Adverse Events Reported
anger, headaches, anxiety, constipation, dizziness, agitation, insomnia, nausea,, dry mouth
ADVERSE EVENTS, DRY MOUTH
Abbreviation: GI, gastrointestinal.Includes mild and nonstudy related adverse events.Includes constipation, dry mouth, nausea, vomiting, and gas.Includes anxiety and anger or agitation.Includes insomnia and vivid dreams.Includes dizziness and headaches.
PMC10492187
Discussion
psychiatric comorbidity, psychiatric illness
This randomized clinical trial found that adaptive treatment was more efficacious than standard treatment for daily smokers recruited from a smoking cessation clinic and allowed to choose between varenicline and nicotine patches. Additionally, the results suggest that adaptive treatment with extended (4-week) precessat...
PMC10492187
Limitations
This study has some limitations, including the exclusion of people with symptomatic alcohol dependence or substance use. Additionally, few or no Alaska Native, American Indian, Asian, Hispanic or Latinx, multiracial, or Pacific Islander people enrolled, limiting generalizability to these populations. Additionally, stud...
PMC10492187
Conclusions
This randomized clinical trial in daily smokers from a smoking cessation clinic with medication choice and limited exclusion criteria found higher smoking abstinence rates among participants randomized to adaptive compared with those randomized to nonadaptive pharmacotherapy. Specifically, these findings provide suppor...
PMC10492187
References
Trial Protocol and Statistical Analysis Plan Click here for additional data file. Data Sharing Statement Click here for additional data file.
PMC10492187
Background
pain, Varicocele
SECONDARY, VARICOCELE
Varicocele occurs as a result of dilatation of the pampiniform plexus in the spermatic veins. In this study, our primary aim was to evaluate the effect of Transversalis Fascia Plane Block (TFPB) on pain scores in the postoperative period in patients undergoing varicocelectomy surgery, and our secondary aim was to evalu...
PMC9903451
Methods
INFILTRATION, LOCAL INFILTRATION
The study was initiated following local ethics committee approval, and sixty ASA I-II patients > 18y scheduled to undergo varicocelectomy and who consented to participation were enrolled. Before the procedure, the patients were randomly assigned two groups: Transversalis Fascia Plan block group (Group TFPB) or surgical...
PMC9903451
Results
A total of 60 patients were included in the study. In terms of demographic data, there was no difference between the groups. At all hours, there was a statistically significant decrease in favor of Group TFPB in terms of active and passive VAS scores (
PMC9903451
Conclusion
INFILTRATION
This study has shown that TFPB can provide a more effective analgesia when compared to surgical site infiltration.
PMC9903451
Keywords
PMC9903451
Background
postoperative pain, pain, inguinal hernia, Varicocele
SECONDARY, VARICOCELE, VARICOCELE
Varicocele is caused by the dilatation of the pampiniform plexus in the spermatic veins and is observed in 15–20% of post-pubertal men [Many techniques exist for the surgical treatment of varicocele including, open techniques (retroperitoneal, inguinal and scrotal approaches), surgical ligation, laparoscopic approach a...
PMC9903451
Methods
PMC9903451
Study design
systemic disease, Postoperative pain, communication difficulties, liver insufficiency, cognitive problems, allergic reactions
SYSTEMIC DISEASE, CHRONIC RENAL FAILURE, INFILTRATION, ALLERGIC REACTION, CHRONIC OBSTRUCTIVE PULMONARY DISEASE, COAGULOPATHY, CHRONIC PAIN
This randomized, controlled study was registered with clinicaltrials.gov (ref: NCT05172882, first registration date was 29/12/2021) following local institutional review board of the Ethical Committee for Clinical Research of the Medical Faculty of Ataturk University, Erzurum, Turkey. The trial was conducted between Nov...
PMC9903451
Management of surgery, anesthesia and TFP block
STERILE, INFILTRATION, CAVITY, LOCAL ANESTHETICS
Patients were placed in the supine position. Following patient monitoring with electrocardiography (ECG), non-invasive blood pressure (NIBP) and peripheral oxygen saturation (SpOPostoperatively, TFPB and infiltration analgesia were performed by experienced anesthesiologists or urologists, respectively. TFPB was perform...
PMC9903451
Outcomes and postoperative analgesic management
pain
Patients' demographic data, such as age, weight, and height, ASA classification, duration of anesthesia and surgery, passive (at rest) and active (from supine to 45° sitting position) postoperative VAS scores at 1, 2, 4, 8, 12, and 24 h after surgery (VAS 0 = no pain, VAS 10 = worst pain imaginable) were recorded.The p...
PMC9903451
Sample size and statistical analyze
Data from a preliminary study taking into account average VAS score at 2Statistical analysis was performed using statistical program (SPSS Statistics version 20.0-IBM, Armonk, NY,USA). Data normality was evaluated using the Kolmogorov–Smirnov test. Mann Whitney-U test was used for continuous data that did not show norm...
PMC9903451
Discussion
hernia, nerve injuries, pain, decreases pain, somatic innervation
INFILTRATION, CREST, COMPLICATION, PNEUMOTHORAX
To the best of our knowledge, this is the first study to evaluate the effectiveness of TFBP block for postoperative analgesia after varicocelectomy surgery. Our study has shown that when compared to local anesthetic infiltration of the surgical site, TFBP block decreases pain scores, non-steroid analgesic requirement a...
PMC9903451
Acknowledgements
Not applicable
PMC9903451
Authors’ contributions
OI
MEA
ECC, OI, and MEA contributed to study conception and design. AMY, EOA, IHT, and AA contributed to study conduct. ECC and IHT contributed to data analysis. AMY, MEA, and AA contributed to manuscript preparation. ECC is a guarantor. The author(s) read and approved the final manuscript.
PMC9903451
Funding
Authors received no outside funding. The authors received no financial support for the research and/or authorship of this article. There are no any conflict of interests in this study.
PMC9903451
Availability of data and materials
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. Erkan Cem Celik e-mail:drerkancem@yahoo.com.
PMC9903451
Declarations
PMC9903451
Ethics approval and consent to participate
Ethics approval was approved with 16.01.2020–1/4 approval number from local ethic commitee (Ataturk University Ethic Commitee). After approval from ethic commitee it was registered with clinicaltrials.gov (ref: NCT05172882, first registration date was 29/12/2021). All patients enrolled in this study were evaluated befo...
PMC9903451
Consent for publication
Not applicable.
PMC9903451
Competing interests
The authors declare no competing interests.
PMC9903451
References
PMC9903451
Key Points
PMC10034574
Question
cancer
CANCER, ADVANCED CANCER
Can unsupervised machine learning identify older adults with advanced cancer who are at high risk of adverse outcomes based on patient-reported symptoms prior to cancer treatments?
PMC10034574
Findings
death
SECONDARY, ADVANCED CANCER
In this secondary analysis of a randomized clinical trial with 706 older adults with advanced cancer, a k-means algorithm identified 3 patient clusters characterized by symptom severity (low, moderate, and high) that were associated with increased risk of unplanned hospitalization and death.
PMC10034574
Meaning
death
SECONDARY, ADVANCED CANCER
These findings suggest that machine learning may be used to guide the development of risk stratification tools with the potential to assist clinicians in identifying older adults with high risk of hospitalization and death.This secondary analysis of a randomized clinical trial uses unsupervised machine learning to eval...
PMC10034574
Importance
cancer
ADVERSE EVENTS, CANCER, ADVANCED CANCER
Older adults with advanced cancer who have high pretreatment symptom severity often experience adverse events during cancer treatments. Unsupervised machine learning may help stratify patients into different risk groups.
PMC10034574
Objective
To evaluate whether clusters identified from baseline patient-reported symptom severity were associated with adverse outcomes.
PMC10034574
Design, Setting, and Participants
cancer, death, Toxicity, Cancer
ADVERSE EVENT, CANCER, ADVANCED CANCER, SECONDARY, CANCER
This secondary analysis of the Geriatric Assessment Intervention for Reducing Toxicity in Older Patients With Advanced Cancer (GAP70+) Trial (2014-2019) included patients who completed the National Cancer Institute Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) befor...
PMC10034574
Exposures
Symptom severity.
PMC10034574
Main Outcomes and Measures
Unplanned hospitalization over 3 months (primary), all-cause mortality over 1 year, and any clinician-rated grade 3 to 5 toxic effect over 3 months.
PMC10034574
Results
lung cancer
LUNG CANCER, GASTROINTESTINAL CANCER
Of 718 enrolled patients, 706 completed baseline PRO-CTCAE and were included (mean [SD] age, 77.2 [5.5] years, 401 [56.8%] male patients; 51 [7.2%] Black and 619 [87.8%] non-Hispanic White patients; 245 [34.7%] with gastrointestinal cancer; 175 [24.8%] with lung cancer; mean [SD] impaired Geriatric Assessment domains, ...
PMC10034574
Conclusions and Relevance
death
In this study, unsupervised machine learning partitioned patients into distinct symptom severity clusters; patients with higher pretreatment severity were more likely to experience hospitalization and death.
PMC10034574
Trial Registration
ClinicalTrials.gov Identifier:
PMC10034574
Introduction
fatigue, cancer, pain, insomnia, Cancer
CANCER, ADVANCED CANCER, CANCER
Older adults with advanced cancer usually present with a wide range of physical and psychological symptoms, such as insomnia, fatigue, and pain, prior to cancer treatments.In recent years, patient-reported outcomes (PROs) have been increasingly used as a measure to capture symptom burden in patients with cancer.To stan...
PMC10034574
Methods
PMC10034574
Data Source
cancer
CANCER, SECONDARY, ADVANCED CANCER
This secondary analysis used data from a nationwide, multicenter, cluster-randomized study that found that providing GA information to community oncologists reduced clinician-rated grade 3 to 5 toxic effects in older adults with advanced cancer starting a new cancer treatment regimen (GAP70+ study).
PMC10034574
Study Measures
death
SECONDARY
The GAP70+ trial collected 27 PRO-CTCAE symptom items with multiple attributes.The primary outcome of this study was whether a participant experienced unplanned hospitalization(s) within 3 months of starting a new treatment regimen. Any planned or scheduled admissions were excluded from the analysis. The secondary outc...
PMC10034574
Statistical Analysis
Our first step grouped patients into clusters with similar mixes of symptom severity using an unsupervised machine learning algorithm (k-means with Euclidean distance). We selected k-means because of its computational efficiency and intuitive visualization of the data points related to their respective clusters.After e...
PMC10034574
Results
Of the 706 older adults included in the analysis (eFigure in
PMC10034574
Clustering of Patient-Reported Outcome Version of the Common Terminology Criteria for Adverse Events Severity Items
Three clusters were found using the k-means method with Euclidean distance. For the purpose of data visualization, the x- and y-axes are principal components of the 24 PRO-CTCAE severity items.
PMC10034574
Associations of Symptom Severity Clusters With Longitudinal Adverse Outcomes
cancer type, cancer
CANCER
Abbreviations: HR, hazard ratio; NA, not applicable; RR, risk ratio.Models included practice site as random effect.Multivariable models adjusted for age, sex, cancer type, cancer treatment, number of Geriatric Assessment domain impairments, study group, Karnofsky performance status.Practice site random effect was exclu...
PMC10034574
Discussion
cancer, death
CANCER, SECONDARY, ADVANCED CANCER
In this secondary analysis of a large national randomized trial of more than 700 older adults with advanced cancer receiving active treatment, we identified 3 main symptom clusters (low, moderate, and high severity) using a clustering algorithm. The symptom severity score of patients in each cluster differed. Patients ...
PMC10034574
Limitations
Our study has limitations. Patients included were mostly non-Hispanic White with high levels of education; they do not represent the entire US population. The k-means algorithm is sensitive to outliers in the clustering variables, although all clustering variables ranged from 0 to 4. Euclidean distances might be distor...
PMC10034574
Conclusions
SECONDARY
In this secondary analysis of a cluster trial of more than 700 older adults, unsupervised machine learning effectively identified patients with similar characteristics and stratified patients into clusters based on symptom severity. Our findings reinforce the importance of routine symptom assessment prior to treatment ...
PMC10034574
Background
Participant feedback is an important consideration for increasing intervention acceptability, yet whether incorporating such feedback actually improves acceptability is rarely tested.
PMC10463387
Purpose
The present study describes a theory-based approach to assessing whether refining an intervention based on participant feedback increases acceptability.
PMC10463387
Methods
Three hundred and ninety-three UK adults who had previously self-harmed were exposed to the same intervention at baseline and, six months later, were randomly allocated to receive either: (a) the same version of the intervention (control group), or (b) a version of the intervention that had been refined following parti...
PMC10463387
Results
Mixed ANOVAs, with control versus experimental group as the between-participants factor and time (baseline versus follow-up) as the within participants factor showed no significant changes in acceptability.
PMC10463387
Conclusions
The null effects reported here imply that participants found both the original and modified versions of the intervention equally acceptable, and that our process of refining an intervention based on participant feedback did not impact on acceptability. Nevertheless, we have operationalised a robust approach for examini...
PMC10463387
Supplementary Information
The online version contains supplementary material available at 10.1186/s12889-023-16344-w.
PMC10463387
Keywords
PMC10463387
Background
Various factors affect the successful implementation of an intervention, such as its feasibility, desirability, and perceived appropriateness [Involving people in the design and modification of interventions is recognised as an important stage in ensuring acceptability [The first limitation concerns the lack of study m...
PMC10463387
Aims
The aims of the present study were to operationalise an approach to intervention acceptability that: (a) ensures that a large representative sample of people with lived experience is involved in the process of refining an intervention to increase acceptability; and (b) adopts a theory-driven, experimental approach to e...
PMC10463387
Methods
PMC10463387
Overview
Ethical approval was obtained from The University of Manchester Research Ethics Committee (ref: 2020-8446-15312). All methods were performed in accordance with the relevant guidelines and regulations (Declaration of Helsinki). The study was conducted in three phases as part of a larger six-month follow-up study examini...
PMC10463387
Phase 1: intervention development
PMC10463387
Development of the volitional help sheet for self-harm
The intervention is based on the concept of implementation intentions [Participant suggestions for refining the intervention were coded to the specific constructs of the TFA as part of our qualitative analyses conducted during our prior intervention development work on the original intervention [The original and modifi...
PMC10463387
Phase 2: main study
PMC10463387
Participants
A national community sample of people in the UK who had previously self-harmed were recruited via a survey panel company (YouGov), as part of a larger study (ClinicalTrials.gov Identifier: NCT04420546). Participants were incentivised in line with YouGov’s points system (respondents accumulate points for taking part in ...
PMC10463387
Design
A mixed-measures design was employed with one between-participants factor (
PMC10463387
Procedure
self-harm
At baseline, after participants gave informed consent, all were presented with the original intervention aimed at reducing self-harm. Participants were then randomised via online survey software to receive, at six-month follow-up, either: (a) the same version of the intervention, or (b) a version of the intervention th...
PMC10463387