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Procedures | stroke | STROKE, ATRIAL FIBRILLATION, PATHOPHYSIOLOGY | The original intervention was designed by J.G.K. and A.T. The development process is described elsewhere.The final intervention was a series of 4 videos: (1) “What is AF?” discussing cardiac anatomy, the ECG, and AF risk factors; (2) “Management of Atrial Fibrillation,” addressing the pathophysiology of AF, including the association with stroke risk and pharmacological and procedural management options; (3) “Lifestyle advice,” specifically addressing lifestyle modifications proven to reduce AF burden; and (4) “AF summary,” summarizing previous videos. Patients randomized to the intervention group were automatically directed to watch all 4 videos in order immediately after baseline data collection. The database recorded when videos were opened by participants, facilitating calculation of the number of videos watched. After their clinic appointment, intervention participants were emailed links to review the video series weekly. Ongoing engagement with the intervention was determined by participants and not a requirement of study participation. Videos are freely available elsewhere. | PMC10709770 |
Trial Procedures | RECRUITMENT | Participants underwent assessments at baseline (prior to the first clinic visit), 2 days after their clinic visit, and at 90 days after recruitment. At baseline, we collected demographic information, medication adherence, motivation to maintain medication adherence, and AF knowledge. Race and ethnicity were self-reported by study participants and categorized as Aboriginal or Torres Strait Islander, Asian (including North, East, and South-East Asian), Middle-East and North African, White, and other (including Central and South American, Pacific Islander, Polynesian, and Sub-Saharan African). Race and ethnicity were included in analysis to account for differences in intervention impact among participants of different sociocultural backgrounds. Time of AF diagnosis was not collected; hence, duration of AF could not be calculated. At the postclinic assessment (defined as 2 days postvisit), we collected information on satisfaction with clinical care, motivation to maintain medication adherence, and AF knowledge. At the 90-day follow-up, we collected information on medication adherence, motivation to maintain medication adherence, and AF knowledge. Patient characteristics and outcomes were collected with a combination of medical record review by trained research assistants and participant self-report. | PMC10709770 |
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Study Outcomes | nonadherence, Atrial Fibrillation | ATRIAL FIBRILLATION | The primary outcome was prospectively defined as the odds of correctly answering each Jessa Atrial Fibrillation Knowledge Questionnaire (JAFKQ) question in the intervention group compared with the control group at 90 days. The JAFKQ is a 16-item questionnaire that addresses general AF knowledge with anticoagulation-specific questions that are different depending on treatment with warfarin or direct oral anticoagulants. This was developed by Desteghe et alSecondary outcomes included medication adherence, measures of patient satisfaction, and JAFKQ score at the 2-day postclinic assessment. Medication adherence was calculated as the frequency of nonadherence in the intervention group compared with the control group based on responses to 3 questions previously validated in the Coronary Artery Risk Development in Young Adults study. | PMC10709770 |
Statistical Analysis | REGRESSION, SECONDARY, RECRUITMENT | The original intended sample size of 360 was revised to 200 due to recruitment limitations in the context of the COVID-19 pandemic. A sample size of 200 participants (100 participants per group) was calculated to have 90% power (2-sided, type 1 error 5) to detect a difference in 90-day JAFKQ score of 8.95%. This calculation allowed for 15% attrition and assumed an SD of 18, as previously observed.Due to the nature of the JAFKQ displaying a different number of questions depending on anticoagulant prescription, the primary outcome was analyzed in a log binomial logistic regression model. Age, sex, education, subtype of AF, and baseline JAFKQ score were included as covariates, due to a possible impact on AF knowledge. Resultant odds ratios (ORs) accompanied by 95% CIs describe the odds of a correct JAFKQ answer in intervention compared with control participants. The significance of difference between proportional secondary outcomes (satisfaction with care, education, motivation to maintain medication adherence, and reported medication adherence) was analyzed in a log binomial model adjusting for age, sex, education, subtype of AF, and baseline score where available. All analyses were completed according to principles of intention to treat. An as-treated analysis examining primary and secondary outcomes among highly engaged (watched videos on ≥3 additional occasions), moderately engaged (watched videos on 1-2 additional occasions) and poorly engaged (watched videos on 0 further occasions) participants was also conducted.Analyses were conducted using R statistical software version 4.1.2 (R Project for Statistical Computing). | PMC10709770 |
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Results | Between November 18, 2020, and July 18, 2022, 208 participants were recruited from 657 patients screened in cardiology outpatient clinics ( | PMC10709770 |
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Participant Baseline Characteristics | Atrial Fibrillation | ATRIAL FIBRILLATION, ATRIAL FIBRILLATION | Abbreviations: AF, atrial fibrillation; JAFKQ, Jessa Atrial Fibrillation Knowledge Questionnaire; NA, not applicable.Percentages calculated from available responses.Includes Central and South American, Pacific Islander, Polynesian, and Sub-Saharan African.Medical history was collected by clinical investigators from the electronic medical record.Mean scores baseline scores were weighted according to number of questions shown to patients.At the 90-day follow-up, intervention participants receiving clinician-created video education had significantly higher odds of correctly answering JAFKQ questions than control participants (OR, 1.23 [95% CI, 1.01-1.49]) ( | PMC10709770 |
Violin Plot of Knowledge Questionnaire Performance and Satisfaction With Individual Videos | The number of participants at each point in the y-axis is indicated by the width of the plot body. | PMC10709770 |
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Binomial Logistic Regression of Jessa Atrial Fibrillation Knowledge Questionnaire Performance | atrial fibrillation, Atrial Fibrillation | ATRIAL FIBRILLATION, ATRIAL FIBRILLATION | Abbreviation: OR, odds ratio.Adjusted by baseline Jessa Atrial Fibrillation Knowledge Questionnaire performance, atrial fibrillation diagnosis, education level, age, and sex.High engagement indicates watching videos on at least 3 separate occasions.There were no statistically significant differences between intervention and control participants in patient satisfaction with clinical care (OR, 1.15 [95% CI, 0.62-2.16]) or AF education (OR, 1.32 [95% CI, 0.71-2.44]). There remained no statistically significant differences among highly engaged intervention participants compared with control participants ( | PMC10709770 |
Satisfaction and Adherence Motivation by Treatment Group | ATRIAL FIBRILLATION | Abbreviations: AF, atrial fibrillation; OR, odds ratio.High engagement indicates watching videos on at least 3 separate occasions. The high engagement intervention subgroup is compared with the overall control group.There was also no statistically significant difference between intervention and control groups in motivation to maintain medication adherence at 90 days (relative risk, 1.04 [95% CI, 0.88-1.23]). At study completion, all patients reported adherence to AF-related medication. | PMC10709770 |
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Discussion | This randomized clinical trial found provision of clinician-developed, patient-targeted educational videos prior to and following clinic appointments increased patient-knowledge regarding AF at 3 months compared with usual care. Self-reported medication adherence in the selected population was too high to detect a clinically significant difference. These findings add to a developing evidence base supporting augmentation of outpatient care with opportunistic delivery of high-quality educational resources.Higher health literacy, facilitated through patient education, is associated with better cardiovascular outcomes.There is a large evidence base describing the potential role of video education to improve patient knowledge and clinical outcomes.There are several perceived barriers to wider adoption of clinician-created education. Limited time for clinicians to design and deliver patient-education is a commonly highlighted barrier. In this study, videos were developed over the course of 1 week, within working hours, narrated in a single take, and animated at a time-cost of 2 hours per video. Hence, the time required to develop the intervention was low. Second, clinicians often perceive a skill deficit (ie, assume they are unable to design their own videos) and do not pursue original content development. This leads to increased costs of content development when outsourced to paid third parties, which could have flow on effects in intellectual property ownership of content created. We addressed these issues by purchasing third-party software at low cost. This facilitated design of simple video animations reflective of commonly used sketching by clinicians to illustrate concepts to patients. Investigators D.M. and A.T. self-taught VideoScribe over 1 to 2 weeks, acquiring skills in parallel with video development. | PMC10709770 |
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Limitations | RECRUITMENT | This study has several limitations. The originally intended sample size of 360 participants was not achieved due to recruitment limitations during the COVID-19 pandemic, and we revised the sample size to 200 in consultation with the Western Sydney Local Health District Human Research Ethics Committee. This reduced the accuracy of findings, although the primary outcome was still achieved. The intervention was also consistent among all patients, with little personalization or variation. This kept costs low and facilitated scaled delivery, although it may have limited engagement with protracted delivery. The lack of discrimination among patients for medication adherence measures was disappointing and likely due to limitations of the 3-item scale selected to reduce survey burden. Furthermore, it is possible that contamination occurred in which control participants were exposed to the intervention, diluting intervention effect. Remote content delivery to personal devices reduced this risk. Additionally, time since AF diagnosis and CHA | PMC10709770 |
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Conclusions | The findings of this randomized clinical trial suggest that clinician-created educational videos could present a low-cost approach to augment patient-centered cardiovascular care. In this study, short clinician-created, patient-targeted educational videos offered weekly via email improved AF knowledge at 3 months after routine outpatient care. Highly engaged patients were more likely to correctly answer AF knowledge questions. An effect on medication adherence was not identified in this trial but should be investigated in larger studies. This study did not measure any cardiovascular outcomes, but this could be a logical progression of the concept. | PMC10709770 |
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Abstract | EDWARDS | Michelle Edwards Former employee of Pfizer. | PMC10712701 |
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Introduction | Activating | PMC10712701 |
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Methods | Phase Ib dose escalation started with binimetinib 45 mg twice daily plus panitumumab 6 mg/kg administered every 2 weeks. In the phase II study, patients with measurable mCRC were enrolled into 4 groups based on previous anti-EGFR monoclonal antibody therapy and | PMC10712701 |
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Results | No patients in the phase Ib portion ( | PMC10712701 |
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Conclusions | toxicity | MUTANT | The combination of binimetinib and panitumumab had substantial toxicity and limited clinical activity for patients with mutant or WT This article reports the results of a study that evaluated the combination of the MEK1/2 inhibitor binimetinib and the EGFR inhibitor panitumumab in patients with | PMC10712701 |
Implications for Practice | cancer, tumors | CANCER, METASTATIC COLORECTAL CANCER, TUMORS | Epidermal growth factor receptor (EGFR) protein and the MAPK pathway (including the proteins RAS, RAF, MEK1/2, and ERK) are involved in cell growth and survival; activation of any of these proteins can cause cells to divide more rapidly, allowing cancer to develop. People with metastatic colorectal cancer (mCRC) tumors with activated RAS are resistant to anticancer medicines targeting EGFR due to activation of the MAPK pathway, limiting treatment options. Therefore, we used a combination of medicines. We tested panitumumab, which blocks EGFR, with binimetinib, which blocks MEK1/2, to see if resistance could be overcome. Adding binimetinib to panitumumab did not improve outcomes for people with mCRC with activated or nonactivated RAS regardless of a person’s previous history with EGFR blockers. In addition, many people found this combination of medicines hard to tolerate. This work showed that binimetinib plus panitumumab has limited benefit for people with activated or nonactivated RAS mCRC. | PMC10712701 |
Introduction | tumors | METASTATIC COLORECTAL CANCER, TUMORS | Monoclonal antibodies targeting epidermal growth factor receptors (EGFRs) have led to significant improvements in survival for patients with metastatic colorectal cancer (mCRC).Studies of acquired resistance to EGFRi show that progressing tumors remain dependent on extracellular signal-regulated kinase (ERK) activation but that resistance alterations bypass EGFR inhibition to maintain ERK signaling.Binimetinib (MEK162) is a selective, potent allosteric inhibitor of MEK1/2 that has demonstrated antitumor activity in preclinical models.This trial evaluates the combination of binimetinib and the EGFR inhibitor panitumumab in patients with | PMC10712701 |
Materials and Methods | PMC10712701 |
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Study Design | This was a 2-part, open-label, multicenter study (NCT01927341) comprising a phase Ib dose escalation followed by a phase II clinical efficacy evaluation and safety assessment of the combination treatment binimetinib + panitumumab. For phase II, 4 patient populations were enrolled based on previous anti-EGFR monoclonal antibody (mAb) therapy and The study was conducted at 8 sites in the US, Belgium, Canada, France, Germany, Italy, Netherlands, and Spain. The study protocol was approved by the independent ethics committee or institutional review board at each site, and the study was conducted according to International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use guidelines concerning Good Clinical Practice. Written informed consent was obtained from all patients before screening. | PMC10712701 |
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Study Population | Tumors | TUMORS, DISEASE, ONCOLOGY | Both phases of the study enrolled adult patients (aged ≥18 years) with histologically or cytologically confirmed mCRC, evidence of measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), Eastern Cooperative Oncology Group performance status of 0 to 2, and written documentation of either For phase Ib, eligible patients had mCRC that had progressed on or following standard therapy or were determined to be patients for whom no standard therapy existed. For phase II, patients were eligible based on their previous anti-EGFR mAb therapy and | PMC10712701 |
Study Objectives and Endpoints | toxicities, DLTs, intercurrent illness | DISEASE PROGRESSION, ADVERSE EVENTS, DISEASE, SECONDARY, REGRESSION | The objective of phase Ib was to determine the maximum tolerated dose (MTD) of binimetinib + panitumumab. The MTD is defined as the highest combination drug dosage not causing medically unacceptable dose-limiting toxicities (DLTs) in more than 35% of treated patients in the first cycle of treatment, based on an adaptive 5-parameter Bayesian logistic regression model. DLTs were defined as adverse events (AEs) or clinically significant abnormal laboratory values assessed as unrelated to disease, disease progression, intercurrent illness, or concomitant medications that occurred within the first 28 days of treatment and met prespecified criteria. Infusion-related reactions were not considered DLTs.The primary endpoint in phase Ib was the incidence of DLTs in the first 28-day cycle of treatment (cycle 1). Secondary endpoints included frequency and severity of AEs, overall response rate (ORR) per RECIST 1.1, progression-free survival (PFS), duration of response (DOR), and disease control rate (DCR). In phase II, the primary endpoint was ORR, and secondary endpoints included frequency and severity of AEs, PFS, DOR, and DCR.AEs of special interest (AESI) were those for which there was a clinical interest related to the mechanism of action of the drug under investigation. These AESIs were defined on the basis of signals observed from previous studies in the binimetinib clinical development program and/or known class effects of other MEKi. | PMC10712701 |
Study Treatment and Procedures | loose stools, Tumor, diarrhea, toxicity, abdominal cramping, Toxicity, skin toxicity | DISEASE PROGRESSION, SKIN TOXICITY, ADVERSE EVENT, TUMOR | In phase Ib, patients received a starting dose of binimetinib 45 mg twice daily (BID) + panitumumab 6 mg/kg once every 2 weeks (Q2W), the US Food and Drug Administration approved doses of both agents at the time. Dose de-escalation was planned as needed until the MTD/recommended phase II dose (RP2D) was reached. In phase II, patients received the MTD/RP2D of binimetinib + panitumumab, as determined during phase Ib.Tumor response was evaluated locally by the investigator according to RECIST 1.1, using computed tomography scans and/or magnetic resonance imaging with intravenous contrast. Scans were performed at screening/baseline and then every 8 weeks (two 28-day cycles) until disease progression. Safety was assessed throughout the study, and AEs were coded using Medical Dictionary for Regulatory Activities version 18.1 terminology. Toxicity was assessed according to the Common Terminology Criteria for Adverse Events version 4.03. Per protocol, antidiarrheal medication was recommended at the first sign of abdominal cramping, loose stools, or overt diarrhea; skin toxicity prophylaxis was to be initiated 24 hours prior to first treatment with binimetinib or later as needed. Patients continued treatment until disease progression, development of unacceptable toxicity, or withdrawal of informed consent. | PMC10712701 |
Statistical Analyses | The MTD/RP2D of the combination treatment was estimated based on the anticipated probability of DLTs in cycle 1 for patients in the dose-determining set, which consisted of all phase Ib patients who met specified minimum exposure criteria and had sufficient safety evaluations during cycle 1 or who discontinued earlier due to a DLT during cycle 1.Efficacy analyses included all patients who received any dose of binimetinib or panitumumab. An estimation approach was to be used to assess exploratory efficacy for patient subgroups The safety analysis set included all patients who received ≥1 dose of binimetinib or panitumumab and had ≥1 valid postbaseline safety assessment. | PMC10712701 |
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Results | PMC10712701 |
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Patient Demographics and Disease Characteristics | ONCOLOGY, METASTATIC COLORECTAL CANCER, ADVERSE EVENT | In total, 53 patients were enrolled between November 19, 2013 and January 25, 2016: 10 in phase Ib and 43 in phase II (database lock: August 11, 2016; Patient flow diagram. Abbreviations: AE: adverse event; EGFRi: epidermal growth factor receptor inhibitor; mCRC: metastatic colorectal cancer; MUT: mutation; Overall, the median age at enrollment was 55.0 (range 30-79) years, and the majority of patients were White (85%; Patient demographics and baseline characteristics.Data are
Abbreviations: EGFRi: epidermal growth factor receptor inhibitor; EGFRi-naïve: naïve to epidermal growth factor receptor inhibitor (both monoclonal antibody and tyrosine kinase); ECOG: Eastern Cooperative Oncology Group; NS: not specified; PS: performance status; WT: wild type. | PMC10712701 |
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Maximum Tolerated Dose/Recommended Phase II Dose | DLTs | No DLTs were reported during phase Ib of the study. The MTD/RP2D was determined to be binimetinib 45 mg BID + panitumumab 6 mg/kg Q2W. | PMC10712701 |
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Efficacy | PD | DISEASE | In phase Ib, no patients had a response to combination therapy with binimetinib + panitumumab; 7 patients had stable disease for a DCR of 70% (95%CI, 34.8-93.3). In phase II, one patient in the Summary of confirmed response per local assessment.Abbreviations: CI: confidence interval; CR: complete response; DCR: disease control rate; EGFRi: epidermal growth factor receptor inhibitor; NE: not estimable; ORR: overall response rate; PD: progressive disease; PR: partial response; In phase II, the DCR was lowest in the PFS in months, per local assessment. Median PFS: phase Ib; 3.4 months (95%CI, 1.4-5.2). Phase II; all patients: 1.8 months (95%CI, 1.6-3.3); OS in months. Median OS: phase II; all patients: 5.5 months (95%CI, 3.6-7.6); | PMC10712701 |
Safety | gastrointestinal events, nausea, fatigue, diarrhea, vomiting, dermatitis acneiform, rash, fatigue/asthenia | ADVERSE EVENT | The median duration of exposure to binimetinib + panitumumab combination therapy was 9.1 (range 5.3-40.0) weeks in phase Ib and 6.1 (range 1.0-48.0) weeks in phase II of the study (Across both study phases, all patients experienced ≥1 AE, regardless of study drug relationship; the most common AEs were diarrhea (71.7%), vomiting (52.8%), nausea (50.9%), fatigue (49.1%), dermatitis acneiform (43.4%), and rash (41.5%) (AEs, regardless of study drug relationship, and select laboratory abnormalities occurring in ≥20% of patients across treatment groups.Data are Abbreviations: AE: adverse event; AESI: adverse event of special interest; CPK: creatine phosphokinase.In phase Ib, 8 patients (80.0%) reported ≥1 grade 3/4 AE, and 3 patients (30.0%) had serious AEs (SAEs; all grade 3/4). In phase II, 37 patients (86.0%) experienced grade 3/4 AEs and 22 (51.2%) had SAEs, including 17 patients (39.5%) who had grade 3/4 SAEs. Overall, the most common SAEs (>1 patient) included diarrhea (All patients experienced ≥1 AESI, most frequently dermatologic rash (90.6%), gastrointestinal events (88.7%), and fatigue/asthenia (62.3%). During phase Ib, 6 patients had a grade 3/4 AESI; in phase II, 29 patients experienced a grade 3/4 AESI. | PMC10712701 |
Discussion | right-sided colon cancer, DLTs | PRIMARY TUMOR, DISEASE | This phase Ib/II study aimed to determine the MTD and/or RP2D of the MEKi binimetinib given in combination with the EGFRi panitumumab and to investigate the efficacy and safety of the combination treatment in patients with mCRC. While there were no DLTs at the full dose of both agents, the combination was difficult to tolerate. There was limited clinical activity, and consequently, study enrollment was closed, and disease progression/survival follow-up were discontinued. The 30-day safety follow-up was not changed.The MTD/RP2D of the combination of binimetinib + panitumumab was determined to be binimetinib 45 mg BID + panitumumab 6 mg/kg Q2W. The treatment demonstrated limited clinical activity in adult patients with either In this study, patients were enrolled irrespective of primary tumor site. Patients with right-sided colon cancer primary sites are less likely to respond to EGFRi.The reversibility of acquired resistance to EGFRi upon withdrawal of treatment, and the subsequent restoration of drug sensitivity, has been documented in mCRC.The clinical development of binimetinib in combination with other therapeutic agents for patients with mCRC is ongoing. In the open-label, phase III BEACON study, the combination of encorafenib + cetuximab + binimetinib resulted in a significantly higher OS and ORR than standard therapy in patients with The similar rates of disease control between patient subgroups observed in the current study, regardless of prior EGFRi exposure, may help to further delineate the impact of Limitations of this study include the early closure of study enrollment due to a lack of clinical activity and the small number of patients enrolled into phase II, particularly in the acquired In conclusion, combination treatment with binimetinib + panitumumab exhibited limited clinical activity in adult patients with | PMC10712701 |
Acknowledgments | Cancer | CANCER | We thank the patients and their families, as well as the participating study teams, for making this study possible. Medical writing and editorial assistance were provided by Namiko Abe of Caudex and funded by Pfizer. In addition, the work was supported in part by a National Institutes of Health Cancer Center Support Grant to Memorial Sloan Kettering Cancer Center. | PMC10712701 |
Funding | Cancer | CANCER | This study was sponsored by Array Biopharma in collaboration with Novartis. Array Biopharma was acquired by Pfizer in July 2019. Medical writing and editorial assistance were provided by Namiko Abe of Caudex and were funded by Pfizer. Research was supported by the National Institutes of Health Cancer Center Core Grant P30 CA 008748. | PMC10712701 |
Conflict of Interest | Pierre, Diaccurate, Cancer | ONCOLOGY, CANCER | E.V.C. reports consulting or advisory roles with Array, AstraZeneca, Bayer, Biocartis, Bristol Myers Squibb, Celgene, Eli Lilly, Ipsen, MSD, Merck KGaA, Novartis, Pierre Fabre, Roche, Servier, Sirtex, and Taiho, and research funding to his institution from Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Eli Lilly, Ipsen, Merck, Merck KGaA, Novartis, Roche, and Servier. R.Y. reports consulting or advisory roles with Array BioPharma/Pfizer, Natera, and Mirati Therapeutics, and research funding from Pfizer, Boehringer Ingelheim, and Mirati Therapeutics. J.P.D. reports consulting or advisory roles, to the benefit of his institution, from AstraZeneca, Roche, Genentech, Bristol Myers Squibb, Diaccurate, Boehringer Ingleheim, MSD, Merch KGaA, Novartis, and Pierre Fabre, and research funding to his institution from MSD, Genentech, Transgene, BMS, and Debiopharm. J.T. reports personal financial interest in the form of a scientific consultancy role for Array Biopharma, AstraZeneca, Avvinity, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Ona Therapeutics, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Scandion Oncology, Servier, Taiho, Tessa Therapeutics, and TheraMyc. He also reports educational collaborations with Imedex, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education, and Physicians Education Resource (PER). He declares institutional financial interest in the form of financial support for clinical trials or contracted research for Amgen Inc, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Janssen-Cilag SA, MedImmune, Menarini, Merck Health KGAA, Merck Sharp & Dohme, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Pharma Mar, Sanofi Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc, Spanish Association Against Cancer Scientific Foundation, and Cancer Research UK. L.L.S. reports consulting or advisory roles with Merck, Pfizer, AstraZeneca/Medimmune, Morphosys, Roche, Oncorus, Symphogen, Seattle Genetics, GlaxoSmithKline, Voronoi, Treadwell Therapeutics, Arvinas, Tessa, Navire, Relay, Rubius, Janpix, and Daiichi Sankyo; and stock ownership in Agios (spouse); and a leadership position in Treadwell Therapeutics (spouse). M.D. reports consulting or advisory roles with Merck KGaA, MSD, Roche, Pierre Fabre, AstraZeneca, Bayer, HalioDX, Eli Lilly, Genentech, Servier, Daiichi Sankyo, and Amgen, and research funding to his institution from Bayer, Pfizer, and Roche. S.S. reports being an advisory board member for Agenus, AstraZeneca, Bayer, BMS, CheckmAb, Daiichi-Sankyo, GSK, Guardant Health, Menarini, Merck, Novartis, Pierre-Fabre, Roche-Genentech, Seagen, and T-One Therapeutics. E.E. reports advisory roles with Amgen, Bayer, Merck Serono, MSD, Pierre Fabre, Roche, Sanofi, and Servier. S.K. discloses honoraria (self) from Merck, Amgen, Roche, Sanofi-Aventis, Servier, Pierre Fabre, and Lilly; honoraria (institution) from Merck, Amgen, Roche, and Lilly; advisory/consultancy roles with Merck, Bristol Myers Squibb, Amgen, Roche, MSD, Sanofi-Aventis, Servier, and Lilly; research grants/funding (self) from Merck, Roche, Bristol Myers Squibb, and Lilly; research grants/funding (institution) from Merck, Roche, Bristol Myers Squibb, and Lilly; and travel/accommodation expenses from Merck, Amgen, Bristol Myers Squibb, Roche, Sanofi-Aventis, Servier, and Lilly. T.Z. reports consulting or advisory roles with Novartis, Bristol Myers Squibb, MSD, Pfizer, and Eli Lilly. N.S. reports advisory/consultancy roles for AIMM Therapeutics, Boehringer Ingelheim, Ellipses Pharma, and research grants for the institute from AB Science, AbbVie, Actuate Therapeutics, Amgen, Array, AstraZeneca/MedImmune, Bayer, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Cantargia, CellCentric, Cytovation, Deciphera, Genentech/Roche, GlaxoSmithKline, Incyte, Lilly, MSD, Merus, Molecular Partners, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi, Taiho, and Takeda (outside the submitted work). D.M. is an employee of Pfizer and is a Pfizer stockholder. M.E. was an employee of Pfizer and a Pfizer stockholder at the time of the study. Z.A.W. reports consulting/advisory roles with Daiichi, Arcus, Amgen, Ipsen, Array BioPharma, Novartis, Lilly, Merck, Merck KGaA, Pfizer, Bristol Myers Squibb, Bayer, AstraZeneca/MedImmune, and Macrogenics, and has been compensated for travel by Amgen, Lilly, Merck, and Bayer. His institution receives funding from Novartis, Plexxikon, Pfizer, Merck, and Arcus Therapeutics. | PMC10712701 |
Author Contributions | Conception/design: J.T., Z.A.W. Provision of study material or patients: E.V.C., J.P.D., J.T., M.D., S.S., E.E., T.Z., Z.A.W. Collection and/or assembly of data: R.Y., J.P.D., J.T., L.L.S., M.D., E.E., S.K., T.Z., N.S., Z.A.W. Data analysis and interpretation: E.V.C., J.P.D., J.T., M.D., S.S., T.Z., Z.A.W. Manuscript writing: R.Y., J.T., L.L.S., M.D., S.S., E.E., S.K., N.S., D.M., M.E., Z.A.W. Final approval of manuscript: all authors. | PMC10712701 |
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Data Availability | Upon request, and subject to review, Pfizer will provide the data supporting the findings of this study. Subject to certain criteria, conditions, and exceptions, Pfizer may also provide access to the related individual deidentified participant data. See | PMC10712701 |
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References | PMC10712701 |
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Objectives | Maximising the impact of community-based programmes requires understanding how supply of, and demand for, the intervention interact at the point of delivery. | PMC10410802 |
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Design | malaria | MALARIA | Post-hoc analysis from a large-scale community health worker (CHW) study designed to increase the uptake of malaria diagnostic testing. | PMC10410802 |
Setting | Respondents were identified during a household survey in western Kenya between July 2016 and April 2017. | PMC10410802 |
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Participants | fever | Household members with fever in the last 4 weeks were interviewed at 12 and 18 months post-implementation. We collected monthly testing data from 244 participating CHWs and conducted semistructured interviews with a random sample of 70 CHWs. | PMC10410802 |
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Primary and secondary outcome measures | fever | SECONDARY | The primary outcome measure was diagnostic testing before treatment for a recent fever. The secondary outcomes were receiving a test from a CHW and tests done per month by each CHW. | PMC10410802 |
Results | malaria | MALARIA | 55% (n=948 of 1738) reported having a malaria diagnostic test for their recent illness, of which 38.4% were tested by a CHW. Being aware of a local CHW (adjusted OR=1.50, 95% CI: 1.10 to 2.04) and belonging to the wealthiest households (vs least wealthy) were associated with higher testing (adjusted OR=1.53, 95% CI: 1.14 to 2.06). Wealthier households were | PMC10410802 |
Conclusion | malaria | MALARIA | Scale-up of community-based malaria testing is feasible and effective in increasing uptake among the poorest households. To maximise impact, it is important to recognise factors that may restrict delivery and demand for such services. | PMC10410802 |
Trial registration number | PMC10410802 |
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STRENGTHS AND LIMITATIONS OF THIS STUDY | malaria | MALARIA, SECONDARY | This analysis draws on a large multidimensional dataset describing uptake of community-based services (intervention recipients) and delivery of services (intervention providers) in the context of a cluster randomised implementation trial, thereby allowing us to examine the strengths and shortcomings of the intervention by triangulating data from two unique perspectives.These data were from a representative population sample which includes respondents who were successfully reached with the intervention as well as those who were not tested for malaria before taking antimalarials and may require alternative approaches in order to achieve adequate coverage of diagnostic testing before treatment with antimalarials.As a secondary analysis of trial data, we were limited in the scope of the data available and not able to fully explore the interaction between the community health workers and households nor the complex determinants of health-seeking behaviour. | PMC10410802 |
Introduction | malaria, fever | MALARIA, SECONDARY | Despite decades of control efforts, malaria remains a major public health problem. In 2019, an estimated 229 million cases of malaria occurred worldwide, most of which were in the WHO African Region (215 million or 94%).Prompt malaria diagnosis either by microscopy or rapid diagnostic tests (mRDTs) is recommended by WHO for all patients with suspected malaria before they are given treatment.The Kenya National Control Program adopted the Test and Treat policy in 2010 and this has been cascaded to the community level. The mRDTs are recommended for parasitological diagnosis in public health facilities where microscopy is not available and through community health workers (CHWs) in some regions. Despite these efforts, most people in rural Kenya still opt for self-treatment and seek care in the retail health sector.The deployment of mRDTs through trained CHWs could improve access to diagnostic testing for populations with limited access to health facilities. In a large, cluster randomised trial,Ideally, there should be adequate demand for the commodity or opportunity, and supply should be able to meet demand. In our cluster randomised trial, despite improvements in malaria testing before treatment of fever, we still observed that only 55% of those with recent illness reported having a malaria test before taking drugs and 21% still purchased antimalarials over the counter without a test,Here we report a secondary analysis of trial data collected at 12 and 18 months after the initiation of our cluster randomised trial of community-based diagnostic testing in western Kenya. | PMC10410802 |
Methods | PMC10410802 |
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Description of the main trial | malaria, febrile | MALARIA, SHOP | This is a post-hoc analysis of data collected within intervention clusters during a large community-based cluster randomised trial. The main results of the trial have been reported elsewhere.In Kenya, CHWs work on a volunteer basis and there are no formal education requirements. The ability to read and write are criteria for selection by the Ministry of Health (MOH). The role of CHWs as defined by the MOH is to promote good health through providing health education, basic treatments (such as first-aid) and referrals to healthcare facilities. The CHWs report to community health extension workers who are employees of MOH and are trained community health nurses mandated to supervise the activities of CHWs in the community units (CUs). In intervention areas, existing CHWs were trained to carry out the intervention. Two hundred seventy-two CHWs participated in offering testing, a median of 18 CHWs per cluster (range: 10–24).CareStart HRP2-based malaria mRDTs were used for testing. CareStart HRP2 detects The CHWs tested febrile patients at community level and issued AL vouchers to patients with positive results. This CHW model differs from other settings implementing community case management of malaria where the CHW is permitted to both perform the mRDT and provide antimalarials directly to the client. The voucher redemption period was 3 days whereby after that, the medicine shops were not allowed to collect the voucher. Patients with positive malaria results bought AL from medicine shops by redeeming their vouchers and leaving the voucher at the shop. The study team collected the redeemed vouchers from the medicine shops on a biweekly basis and reimbursed the difference in costs. | PMC10410802 |
Community surveys | malaria, fevers, fever | MALARIA | A community-based survey was conducted to collect individual-level study outcomes based on a population-based survey sampling strategy. This was a repeated cross-sectional household survey at four time points: baseline (pre-intervention), 6 months, 12 months and 18 months post-baseline. The survey was conducted in all the 32 CUs, 16 intervention and 16 control. Households were randomly selected by systematic random sampling and one person with fever in the last 4 weeks was interviewed in any household. If more than one eligible fever was found in a household, one participant would be selected based on alphabetical order of the given names. Details of community surveys’ sample size calculation are described elsewhere.Basic demographic information about the participants and the households was collected. Socioeconomic scores were calculated from an asset index and then grouped into quintiles as described previously. Euclidean distance from a household to the nearest health facility was calculated from Global Positioning System coordinates. In the final survey, participants’ beliefs about their illness, malaria risk, diagnostic testing and treatment were elicited by asking them about the severity of their illness, their confidence in positive test result and a negative test result, and how certain they were that they would recover from malaria after treatment with AL. ‘Perceived prevalence’ was defined as the proportion of fevers that the respondent believed would be due to malaria among 10 people with fever from their village. High perceived prevalence was assigned to those who responded 8–10 out of 10, medium prevalence to those who responded 4–7 out of 10 and low to those who responded 0–3 out of 10. The survey tool can be found in
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Midpoint CHW survey | malaria | MALARIA | As part of the process evaluation, at the midpoint of this study, interviews were conducted with a random sample of 70 CHWs (median of 4 per CU) who were trained to conduct mRDTs (intervention CUs). The primary objective of these interviews was to determine the CHWs’ satisfaction with their role in the malaria project and the feasibility of their continued involvement. Secondary objectives included eliciting the main challenges the CHWs have faced in implementing the study, determining unanticipated burdens on the CHWs’ other activities (including their responsibilities as CHWs outside of the study as well as their non-CHW responsibilities) and identifying changes in the types of services they provide and the recipients of their services.Likert scale questions were also asked, in which the interviewers read a statement aloud and the CHWs were asked to respond how much they agreed with the statement on a 5-point scale (‘strongly agree’, ‘somewhat agree’, ‘neutral’, ‘somewhat disagree’, ‘strongly disagree’). For this analysis, several variables were derived from the survey data. The client score was constructed as a composite score based on four Likert scale questions—whether CHWs agreed that: clients trust the results of a positive mRDT by the CHW, they trust a negative mRDT, they follow the CHW’s advice if the test was positive, they follow advice if the test was negative. A response of strongly agree=2, somewhat agree=1 and neutral/somewhat disagree/strongly disagree=0. If the sum of these four responses was 6 or greater, the score was ‘high’. If less than 6, the score was ‘low’. The survey tool can be found in These same CHWs also performed an mRDT under observation of the study supervision team and were scored on each step using a 20-step checklist that classified steps as relating to safety, accuracy and treatment. The checklist was developed by the study team based on previous research studies to guide training and support supervision. Those who completed at least 17 of 20 steps correctly had a ‘high’ score for mRDT performance and <17 had a ‘low’ score. | PMC10410802 |
Demand and supply | malaria | MALARIA | To investigate factors that might have influenced the success of the intervention, the analysis was divided into demand and supply factors. On the demand side, the analysis investigates factors that might influence the community member’s outcome of having a test, first from any source and then from the CHW. Only respondents with complete data on the variables of interest were included. On the supply side, the analysis investigates the factors associated with the testing output (ie, supply) at the CHW level, measured as the monthly number of tests conducted by each CHW. These factors include: sociodemographic characteristics of the CHW, number of households under the CHW’s care, years of experience of the CHW, the number of other activities the CHW engages in under their role as a CHW (under the assumption that an increasing number of activities may compete for their time, the CHW provided a list of activities and these were summed together), the perception of the intervention by the CHW, the skill of the CHW in conducting mRDTs and the overall prevalence of malaria in their community. | PMC10410802 |
Outcome measures | fevers | SECONDARY | The primary outcome is the uptake of testing in the intervention clusters, defined as the proportion of fevers in the previous 4 weeks that received a diagnostic test from any source. The second primary outcome is the uptake of testing from a CHW among those who received a diagnostic test from any source.The secondary outcome was the testing volume, defined as the mean monthly number of tests performed by each CHW. Monthly number of tests per CHW was available from programme data collected at monthly supervision visits. | PMC10410802 |
Statistical analysis | malaria, fever | REGRESSION, SECONDARY, MALARIA | A mixed-effects logistic regression analysis was used to evaluate the primary outcome measures on the uptake of testing and investigate risk factors that might have contributed to the outcomes of the intervention reported previously.For the primary outcome measures to evaluate the uptake of testing overall and from a CHW, two logistic models were generated. The first model included all individuals who reported fever in the last 4 weeks (ie, all eligible participants enrolled in the survey). The second model includes a subset of those in the first model, specifically those who were tested at any source. For both models, we accounted for clustering within the CU in the univariate analysis and we accounted for clustering, and individual-level covariates like respondent’s age, gender, level of education, occupation, socioeconomic status, geographical proximity to healthcare provider, the time they waited after falling ill before they sought a test, the level of knowledge and opinions about malaria and malaria diagnosis in the multivariate analysis.The logistic regression model is as shown below:
where Fixed effects are measured using an OR and included the 95% CIs. Independent categorical variables were screened for multicollinearity with a Cramér’s V statistic. In case two variables showed signs of correlation (V >0.7), the variable least associated with the response variable was omitted.For the secondary outcome measure of CHW testing, a mixed-effects linear regression model was fitted to account for clustering at the CU. This model investigates the outcome of mean RDTs performed each month by the specific CHW and includes potential CHW-level covariates like CHW age, marital status, education level, number of households for which they were responsible, previous training on malaria case management or mRDTs, years of experience as a CHW and formal employment status.The linear regression model is as shown below:
where All statistical analyses were done in STATA V.15 (StataCorp). | PMC10410802 |
Patient and public involvement | None. | PMC10410802 |
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Results | MAY | A total of 272 CHWs in 16 intervention CUs were trained to perform mRDTs and 36 retail shops were enrolled to redeem vouchers. The intervention was launched on 21 July, 17 August and 22 September 2015 in Bokoli, Kiminini and Ndivisi subcounties, western Kenya, respectively, and continued until 5 May 2017. | PMC10410802 |
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Demand-side factors for use of malaria diagnostic testing | malaria, fever, acute illness | MALARIA, FEBRILE ILLNESS | In total, 3719 households were approached, 1877 had an eligible fever in the last 4 weeks, 56 did not know if there was an eligible fever, 0 refused and 1738 completed the survey with no missing answers (92.6%). The community-based demand analysis relies on 1738 complete surveys from participants in randomly selected households in intervention clusters with an acute illness in the last 4 weeks (Participant characteristics at the 12-month and 18-month surveys and association between participant characteristics and malaria diagnostic testingThis table refers to those who reported getting a test from any source.Adjusted and unadjusted ORs for receiving a malaria diagnostic test, either microscopy or mRDT, from any source for the most recent febrile illness.Bold indicate results significant to p<0.05.CHW, community health worker; ITN, insecticide-treated net; mRDT, malaria rapid diagnostic test.Demand-side factors that were associated with uptake of malaria testing for their most recent illness are examined (The analysis further focused on those who were tested for malaria by a CHW (Association between patient characteristics and having an mRDT from a CHW before taking any treatmentThis table refers to those who reported getting a test from a CHW.In this analysis, awareness of a CHW in the village was not included as a covariate because 100% of individuals who had a test by a CHW were also aware of the CHW in the village. Of note, 73.5% of those tested elsewhere were also aware of a CHW in their village.Bold indicate results significant to p<0.05.CHW, community health worker; ITN, insecticide-treated net; mRDT, malaria rapid diagnostic test.To understand how individual perceptions about malaria testing and treatment, malaria risk, and illness severity affected uptake of testing or testing by a CHW, the analysis focused on the final survey at the 18-month survey (Relationship between participant beliefs and perceptions and uptake of testing from any source or from a CHWModels are adjusted for patient age, gender, household wealth quintile and the education level of the respondent in addition to the variables in the table.Bold indicate results significant to p<0.05.AL, artemether–lumefantrine; CHW, community health worker; mRDT, malaria rapid diagnostic test. | PMC10410802 |
Diagnostic testing by CHWs | malaria | MALARIA | In total, 32 404 mRDTs were conducted by the CHWs over the intervention period, and 33.7% (n=10 870) were positive. Those with a positive test received a voucher for a discounted quality-assured AL. These vouchers were redeemed at a participating outlet by 93.9% of voucher recipients. There were no instances of stock out of mRDTs among our CHWs. To explore factors that may be associated with the CHWs’ ability to conduct mRDTs, we examined the association between testing volume, defined as the mean number of mRDTs conducted per month, and the different CHW demographic characteristics (Association between mean number of tests performed per month and CHW characteristicsTwo hundred seventy-two CHWs were trained, of which 28 were missing one or more of marital status, employment status, previous RDT training or education level. The 244 with complete data are reported here.Bold indicate results significant to p<0.05.*Number of households for which the CHW reported being responsible.†Percentage of mRDTs conducted by the CHWs in that cluster, which turned positive over the study period.CHW, community health worker; mRDT, malaria rapid diagnostic test.In a multivariate analysis, formal employment, previous mRDT training, number of households and mRDT positivity rate at the cluster level were associated with volume of tests done. Sex, age, being married and education level were not significantly associated with testing volume. CHWs who were formally employed in some other capacity alongside their CHW voluntary work performed on average 1.37 more tests per month (adjusted coefficient=1.37, 95% CI: 0.05 to 2.70), but those who reported being trained previously on mRDTs performed 1.4 fewer tests per month (adjusted coefficient=1.4, 95% CI: −2.44 to –0.37). CHWs serving areas with a high proportion of positive tests (proportion of mRDT positive results >25%) tested on average two more clients per month than those in lower prevalence areas (adjusted coefficient=2.14, 95% CI: 1.05 to 3.22). CHWs who were responsible for at least 50 households tested more clients (adjusted coefficient=1.73, 95% CI: 0.70 to 2.74), although this did not increase further when the number of households exceeded 100 (adjusted coefficient=1.49, 95% CI: 0.74 to 2.24).Univariate and multivariate analyses were conducted to test the association between testing volume and CHW perceptions about their role at the midpoint of the intervention period (Association between mean number of tests per month and CHW perceptions about their role at the midpoint surveyMultivariate ORs are adjusted for age, gender, education level and formal employment. The analysis includes a random sample of CHWs selected for midpoint evaluation.Bold indicate results significant to p<0.05.*mRDT score—-CHW scored >17 correct steps on a 20-step checklist for mRDT preparation and interpretation conducted 6 months after training.†Equals 1 if malaria testing was cited as their most important activity or 0 if they cited any other activity as most important.‡Equals 1 if the CHW cited money, or 0 if the CHW only cited non-monetary incentives or desire for recognition as important motivators for their role as a CHW.§Client score was derived from four questions where the CHW reported how confident clients were in the testing they provided.CHW, community health worker; mRDT, malaria rapid diagnostic test. | PMC10410802 |
Discussion | fever, malaria, malarial illness, febrile illness, generalised, febrile | MALARIA, REGRESSION, FEBRILE ILLNESS | This study adds to the evidence that it is feasible for CHWs to offer malaria testing using mRDTs in the community. With the use of CHWs, large-scale malaria testing intervention can reach the underserved population who cannot afford to visit the health facilities for care and those who seek care in the retail sector. The existence of CHWs with the ability to test for malaria using mRDT provides a great opportunity; however, various factors may affect the demand and supply of testing using mRDT by CHWs.Here we examine the outcomes of a community-based malaria testing to understand how to improve intervention design and maximise the impact of such programmes. The analysis was organised around the target group (community members) and their uptake or demand for the diagnostic testing intervention, and the supply of testing by the CHWs responsible for delivering the intervention. We were able to separate the determinants of uptake of malaria diagnostic testing generally from the determinants of uptake of mRDT performed by a CHW. These contrasting but complementary analyses helped us identify bottlenecks to intervention coverage at the community level.Analysis of community survey data revealed that demand for malaria diagnostic testing before treating a fever was lower among adults and is positively associated with being in the highest wealth quintile (relative to the poorest), findings which are consistent with other published studies.From the perspective of CHWs delivering malaria testing, a strong association was not observed between demographic characteristics and testing volume, but we did note that CHWs with concurrent formal employment tested more patients on average than those without, which could indicate greater visibility or mobility in the community. It was also observed that the monthly testing volume increased when the number of households under a CHW’s purview exceeded 50, but we could not detect a significant increase beyond that when households exceeded 100, suggesting a threshold effect whereby more households created more demand for testing but the ability to meet the demand may be undermined by time constraints after some threshold beyond 100 households. Finally, we report that testing rates were higher in clusters with high mRDT positivity rates, possibly reflecting greater awareness of malarial illness or higher demand for malaria services in areas with higher malaria burden. This could also reflect higher confidence in a test among CHWs or community members who have experience with some tests turning positive as has been seen in the healthcare setting.A deeper analysis of CHW perception of the intervention was undertaken in a smaller random sample of participating CHWs. We show that testing volume is not affected by competing CHW-related priorities, but is associated with how they perceive their clients’ confidence in testing and the likelihood of the client accepting the mRDT result and advice. This aligns well with the picture from the demand side where we observe that confidence in an mRDT performed by a CHW is strongly associated with testing with a CHW.This study had several limitations. First, we are not able to estimate the effect of free testing on the uptake of testing. Considering the study used diagnosis-dependent subsidies to test the rational use of AL, a similar study that deploys free testing in the absence of a conditional voucher would be required to resolve this. Similarly, it could be important to compare the effect of an intervention that delivered both the test and the treatment through the CHW rather than using a voucher redeemable in the private sector. Second, although the survey data have provided valuable insight on understanding drivers to demand and supply of malaria testing, seeking provider (CHW) and patient perspectives in a qualitative framework could provide a richer understanding of the facilitating factors and barriers to scaling up such an intervention, particularly the ways in which preferences and changes in behaviour may influence uptake of the intervention. Finally, though our survey design used repeated cross-sectional sampling, it is possible that the same household and/or febrile individual was surveyed at multiple survey time points and any resulting association was not explicitly modelled in our regression analysis. Our results are based on a representative, randomly selected population sample of recent fevers. As a result, our findings could be generalised to other contexts or service delivery programmes working through CHWs in communities where care for febrile illness is provided through a heterogeneous landscape of private, public and retail venues. | PMC10410802 |
Conclusion | In summary, scale-up of health interventions through CHWs is feasible and effective at reaching the poorest households. However, in order to maximise the impact of community-based interventions, it is important to recognise factors that may restrict both delivery and demand for such services. It is critical to not only create awareness of CHW services but foster trust in both the CHW’s ability to deliver services and the health intervention itself. Engendering confidence in the CHW’s proficiency is likely to have a synergistic effect on both demand for services and commitment to delivering services. | PMC10410802 |
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Supplementary Material | PMC10410802 |
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Reviewer comments | PMC10410802 |
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Data availability statement | Data are available upon reasonable request. Trial data are available at | PMC10410802 |
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Ethics statements | PMC10410802 |
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Patient consent for publication | Not required. | PMC10410802 |
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Ethics approval | This study involves human participants and ethical approval was granted by Moi University Institutional Research and Ethics Committee (formal approval no. 0001403) and Duke University Institutional Review Board (Pro00063384). Participants gave informed consent to participate in the study before taking part. | PMC10410802 |
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References | PMC10410802 |
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Trial design: | CHRONIC LOW BACK PAIN | This study investigated the effect of adding abdominal bracing to spinal stability exercise in patients with chronic low back pain (CLBP). This prospective, randomized pilot study included 67 patients and was conducted at the sports medicine center of a single hospital. | PMC10578739 |
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Methods: | Oswestry disability | LORDOSIS | The abdominal bracing group (ABBG) underwent spinal stability exercise with abdominal bracing (N = 33), comprising 50 minutes training twice a week for 24 weeks. The control group performed only spinal stability exercise (N = 34) for 50 minutes twice a week for 24 weeks. The ABBG received abdominal bracing training at each session and applied abdominal bracing during the spinal stability exercise. The lumbar lordosis angle (LLA) and spine extensor muscle strength were measured. Spinal flexion angles were measured every 12° from 0° to 72°. The visual analog scale score and Oswestry disability index were measured before treatment and at 12 and 24 weeks after treatment. | PMC10578739 |
Results: | Pain | The LLA increased over time in both the groups but was not significantly different between the groups. Spine extensor strength was improved over time in both the groups, and an interactive effect was observed at a spinal flexion angle of 60° and 72°. Pain and function were also improved over time in both the groups, but the effect was stronger in the ABBG than in the control group. In patients with CLBP, spinal stability exercise changed the LLA. | PMC10578739 |
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Conclusions: | pain | LORDOSIS | Although adding abdominal bracing to spinal stability exercise did not affect the changes in the LLA, abdominal bracing improved the spinal extensor strength, pain, and function in patients with CLBP. Therefore, it is recommended to add abdominal bracing to spinal stability exercise to maintain the lordosis angle and to improve CLBP symptoms. | PMC10578739 |
1. Introduction | muscle weakness, anxiety, pain, Low back pain, causes disability, depression, LBP | LORDOSIS, MUSCLE WEAKNESS | Low back pain (LBP) is prevalent in modern society; back pain not only causes disability in daily life but also degrades the quality of life and can result in psychological problems, including depression and anxiety.Although various causes of CLBP have been reported, muscle weakness and imbalance around the lumbar spine and changes in the lumbar lordosis angle (LLA) are the main causes of CLBP.It is known that exercise intervention not only improves muscle strength around the lumbar spine but also positively changes the LLA.In addition to SSE, abdominal bracing (ABB) is effective in improving lumbar stability. | PMC10578739 |
2. Methods | In this prospective randomized pilot study, randomization was performed by a therapist who was not involved in the study at the time of the first participant interviews. After baseline measurements, randomization was conducted by distributing blank envelopes with 2 group numbers to the participants, categorized by sex, and subsequently randomly assigning patients to either the abdominal bracing group (ABBG, performed SSE with ABB) or control group (CG, only performed SSE). The blinding method could not be applied to the researcher (S.W.) who conducted the intervention. However, all other researchers were blinded to group allocation and statistical analyses.Before participating, the purpose, methods, and risks of the study were explained to the participants, and written informed consent was obtained. The study procedure was approved by the Institutional Review Board of the Nanoori Hospital (Gangnam-gu, Seoul, Republic of Korea) (NR-IRB 2018-016) and conforms to the guidelines of the Declaration of Helsinki. The trial was registered at the Clinical Research Information Service under code KCT0007777 on 06/10/2022. A CONSORT diagram for this study is shown in Figure Flow diagram showing the progress of the study. | PMC10578739 |
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2.1. Participants | arthritis, scoliosis, pain | ARTHRITIS, SCOLIOSIS | In this study, the sample size was obtained using G* power version 3.1 (University of Dusseldorf, Dusseldorf, Germany), with an effect size (ES) of 0.40, a power of 0.95, and a significance level of.05. Seventy participants were selected considering a drop rate of 30%. Participants diagnosed with CLBP at an orthopedic or neurosurgery outpatient clinic were recruited.The inclusion criteria were participants aged ≥20 years who complained of CLBP for 3 months or longer. The exclusion criteria were an age of ≥65 years, back pain accompanied by neurological symptoms, history of back surgery, visual analog scale score <4, severe scoliosis with Cobb angle exceeding 10º, severe arthritis of the lower extremities (hip, knee, and ankle), and pregnancy. | PMC10578739 |
2.2. Intervention | CONTRACTION, CONTRACTION | Both the groups visited a sports medical center (Nanoori Sports Medical Center, Gangnam-gu, Seoul, Korea) and participated in an SSE program comprising exercise for 50 minutes twice a week for 24 weeks. In each session, the ABBG also underwent ABB, which comprised preparation, relaxation, and contraction phases, before performing the SSE program (Figs. Abdominal bracing training comprised three stages: (A) Preparation phase: a towel is placed underneath the participant torso while in the supine position with their knees bent. (B) Relaxation phase: after the therapist puts his hand on the participant abdomen, the participant pushes his hand while keeping the lower back free from the floor and expanding the rib cage and abdomen as much as possible. (C) Contraction phase: when the therapist pulls the towel, the participant maintains abdominal pressure to prevent the towel from coming out as much as possible. This is repeated 10 times for 10 s each time.The exercise intervention comprised a 10-min warm-up, 30-min of SSE, and 10-min cool-down. SSE programs were divided into an early phase (0–8 weeks), intermediate phase (8–16 weeks), and late phase (16–24 weeks) and included exercises to improve spinal stability and strength.Overview of the spine stabilization exercise program.SSE = spine stabilization exercise. | PMC10578739 |
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2.3. Outcome measurement | Oswestry disability, Pain | LORDOSIS | In this study, the LLA was the primary outcome, and the lateral view was obtained through X-ray imaging (Accury-625R, Dk, Medical system, Seoul, Korea) that included the lumbar spine and pelvis, with the participant in a standing position. To visualize spine alignment, the participant was asked to raise both arms over their head during imaging. After imaging, the LLA was measured according to the Cobb angle measurement method using Picture Archiving and Communication System (PACS, Viewrex, HechEhim, Guro, Korea) by radiologists not involved in the study. The program measured the lordosis angle through the upper endplate of the first lumbar vertebra and lower endplate of the fifth lumbar vertebra using the Cobb angle measuring tool.The Medx extension machine (Medx 96, Ocala, FL) was used to measure the isometric spine extensor strength. The lumbar extensor strength was evaluated at 0°, 12°, 24°, 36°, 48°, 60°, and 72° in the range of spinal flexion. Before the start of the test, the measurement equipment and test method were fully explained to the participant, and a pelvic restraint was applied and fixed using pelvic and head restraints to limit the movement of the lumbar spine. During the measurement, verbal feedback was given to allow the participant to exert maximum muscle strength, and approximately 10 seconds of rest was given between each angle measurement. Each angle was measured twice, and the average value was used.Pain was assessed using a visual analog scale score range of 0 to 10 points, and lumbar function was assessed using the Oswestry disability index, | PMC10578739 |
2.4. Statistical analysis | SPSS program version 23.0 (IBM Corp., Armonk, NY) was used for data analysis. Data normality was verified using the Kolmogorov–Smirnov test and analyzed using the parametric statistical method. An independent | PMC10578739 |
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3. Results | ± | In the ABBG, 2 participants dropped out, and 33 participants (10 male/23 female) were finally analyzed. In the CG, 1 participant dropped out, and 34 participants (10 male/24 female) were finally analyzed (Fig. Baseline characteristics of study participants (n = 67).ABBG = abdominal bracing group, BMI = body mass index, CG = Control group, n.s. = non-significant Data are expressed as mean ± standard deviation. | PMC10578739 |
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3.3. Pain and function | disability, pain | The pain and function results from baseline to week 24 are shown in Table In both the groups, function (disability index) decreased over time. In the post hoc analysis, the function of the ABBG improved over time (baseline vs 12 weeks and 12 vs 24 weeks, | PMC10578739 |
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4. Discussion | Oswestry disability, LBP, pain | LORDOSIS, CONTRACTIONS | According to the results of this pilot study, adding ABB to SSE for patients with nonspecific CLBP was more effective on lumbar extensor strength, pain, and function than SSE alone. However, we were unable to confirm any benefit that the addition of ABB could have on the LLA.Although it is debated whether or not the LLA in the sagittal plane decreases or increases with age, a recent meta-analysis has reported that the LLA is significantly smaller in participants with LBP.To improve this reduced LLA, some researchers applied exercise intervention. In a study of 32 participants divided into an SSE group of 12 who used SSE for 12 sessions and a CG of 16 who used physical therapy alone, Hosseinfar et al reported that LLA recovery was confirmed in the SSE group.Spinal extensor strength also increased at all angles over time in both groups, but the interaction effect between group and time was confirmed at a spinal flexion angle of 60° and 72°. We provide evidence that these results are due to the activation of deep muscles, such as the IO and TrA, and an increase in IAP.Pain was improved over time in both the groups, and it was found that pain in the ABBG was better at 24 weeks. We believe that these results were demonstrated by deep muscle activation and increased IAP through ABB. Aleksiev et al previously performed a 10-year follow-up study designed as a randomized control trial and reported that spinal strength with ABB showed improvement in LBP compared with spinal strength without ABB, spinal flexibility, and spinal flexibility exercises with ABB.Finally, at 24 weeks after treatment, a significant difference was noted in the function, as evaluated by the Oswestry disability index, between the groups; it also showed the largest ES compared to other dependent variables. We believe that deep muscle activation, increased IAP, and concomitant contractions of the trunk muscles by ABB will contribute to stabilization of the spine and to improve pain and function in patients with LBP. Lee et al reported that the thickness of the IO, EB, and TrA increased, and the isometric strength of the lumbar extensor muscles improved as a result of applying straight leg raise with ABB.Based on these findings, the LLA may be improved with SSE, although this does not appear to provide evidence that the LLA is a determinant factor for differences in spine extensor strength, pain, and function. Instead, it can be concluded that these results were caused by the activation of deep spinal muscles and an increase in IAP caused by the addition of ABB to SSE.This study has several limitations. First, the strength of other muscle groups could not be evaluated, as we only measured the spine extension strength. Second, as the functional evaluation relied solely on a questionnaire and lacked physical assessment, making it challenging to evaluate the exact functional capabilities of patients. Finally, although we confirmed muscle strength in this study, we could not confirm morphological changes in the abdominal muscles due to the intervention, as measurements, such as muscle thickness evaluation, were not performed. In some studies, the TrA, IO, and external oblique muscles were examined using ultrasound during exercises such as ABB and abdominal hollowing in patients with CLBP, employing a reliable evaluation methodIn this pilot study, we were unable to confirm the reason behind the changes in the LLA and their effects on pain and function, although it was demonstrated that SSE results in the LLA changes in patients with CLBP.Moreover, adding ABB had no additional effect on changes in the LLA, although it was confirmed that it was more effective in improving spine extensor strength, pain, and function than SSE alone. Therefore, in this study, we recommend adding ABB to SSE to maintain lordosis in the lumbar spine and to improve symptoms in patients with CLBP. | PMC10578739 |
Acknowledgments | We would like to thank Editage for helping with English proofreading. | PMC10578739 |
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Abbreviations: | pain | LORDOSIS, CHRONIC LOW BACK PAIN | abdominal bracingabdominal bracing groupcontrol groupchronic low back paineffect sizeintra-abdominal pressureinternal obliquelow back painlumbar lordosis angleOswestry disability indexspine stabilization exercisetransverse abdominisHSP and SWP contributed equally to this work.All data generated or analyzed during this study are included in this published article [and its supplementary information files].The authors have no funding and conflicts of interest to disclose.How to cite this article: Park HS, Park SW, Oh J-K. Effect of adding abdominal bracing to spinal stabilization exercise on lumbar lordosis angle, extensor strength, pain, and function in patients with non-specific chronic low back pain: A prospective randomized pilot study. Medicine 2023;102:41(e35476). | PMC10578739 |
References | PMC10578739 |
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Background | Binge-eating, eating disorder | PATHOLOGY | Loss of Control Eating (LOC) is the most prevalent form of eating disorder pathology in youth, but research on evidence-based treatment in this group remains scarce. We assessed for the first time the effects and acceptance of a blended treatment program for youth between 14 and 24 years with LOC (Binge-eating Adolescent Treatment, | PMC10683190 |
Methods | Twenty-four youths (mean age 19.1 years) participated in an active treatment of nine-weeks including three face-to-face workshops and six weekly email-guided self-help sessions, followed by four email guided follow-up sessions, one, three, six and 12 months after the active treatment. All patients completed a two-weeks waiting-time period before treatment begin (within-subject waitlist control design). | PMC10683190 |
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Results | The number of weekly LOC episodes substantially decreased during both the waiting-time (effect size | PMC10683190 |
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Conclusions | depressive symptoms | This first blended treatment study BEAT might be well suited to decrease core symptoms of LOC, depressive symptoms and appearance-based rejection sensitivity. More research is needed to establish readily accessible interventions targeted more profoundly at age-salient maintaining factors such as appearance-based rejection sensitivity, while at the same time keeping dropout rates at a low level. | PMC10683190 |
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Trial registration | The trial was registered at the German Clinical Trials Register (ID: DRKS00014580; registration date: 21/06/2018). | PMC10683190 |
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Keywords | PMC10683190 |
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Methods | PMC10683190 |
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Patients | Overall, 24 youths (23 females, one male) were included in the pilot study of whom 16 (all female) completed the posttreatment and 13 the post follow-up assessment of BEAT (see Fig. Patient flow diagram | PMC10683190 |
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Measures | PMC10683190 |
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Statistical analyses | illness, eating disorder, depressive symptoms, ill, Depression, DSM-5 | SECONDARY, PATHOLOGY, DISORDERS | At pretreatment assessment patients were asked to provide age, gender, nationality and occupational status.LOC and further mental disorders were assessed by the Mini-DIPS, a structured interview to assess mental disorders according to the DSM-5 [The following two online self-report questionnaires were assessed weekly during the waiting-time period, before each session of the active treatment, at posttreatment, before each follow-up session, and at post follow-up (total of 17 assessment points).The WBQ consists of six items that assess the regularity of eating and frequency as well as characteristics of LOC and compensatory behavior during the last seven days. In this study only one single item was included in the statistical analyses to assess the frequency of self-reported weekly LOC episodes by asking youth about the number of episodes in which they experienced loss of control over eating a perceived unusual large amount of food during the last seven days (item 5). It is important to note that self-report assessment of objectively large amounts of food has shown to be less reliable than interview-based assessment [The BDI-FS is a short version of the Beck Depression Inventory [The following two online self-report questionnaires were assessed four times (at pre- and posttreatment, 6-month follow-up, and post follow-up).The EDE-Q assesses eating disorder pathology during the last 28 days. It consists of 28 items, of which 22 items can be assigned to four subscales (To assess appearance-based rejection sensitivity, we applied a shortened and adapted version of the German version of the ARS. In the present version of the ARS-D, we chose to present 10 situations, covering topics which are relevant to our age group (the original ARS-D includes 15 situations). For each situation (e. g. “You are trying on clothes in a department store and notice that you have gained some weight in the last week”), patients rated on a 6-point likert scale their appearance-related The CGI assesses the global clinical impression of patients by clinicians before and after treatment, applying three measures: the global severity of illness measure (CGI-S), the global improvement measure (CGI-I) and an efficacy index. The CGI-S, ranging from 1 = not at all ill to 7 = among the most extremely ill patients, was rated at pre- and posttreatment assessment by therapists and additionally by patients. The CGI-I, ranging from 1 = very much improved to 7 = very much worse, was rated at posttreatment assessment by therapists. In the present study, side effects assessed within the efficacy index are reported. Findings regarding the validity of the CGI are inconsistent. While some studies supported the validity of the CGI in clinical trials (e. g. [Patients reported their satisfaction with BEAT at posttreatment assessment applying eight self-developed items based on the Working Alliance Inventory (WAI; [To report descriptive statistics, we used the mean and standard deviation (Abstainer rates, or, the proportion of patients who were abstinent from LOC after active treatment, were calculated based on the total sample of The primary outcome WBQ (weekly LOC) and the secondary outcome BDI-FS (depressive symptoms) were assessed regularly (altogether 17 times), thereby allowing us to analyze their weekly temporal course using a discontinuous multilevel model [To assess the secondary outcome of the change in the CGI-S scale between pre- and posttreatment, we used the Wilcoxon-test (only completers analysed).For the WBQ, the Number Needed to Treat (NNT) for a significant treatment outcome during the active treatment relative to the waiting-time was calculated according to Preti [The WBQ was transformed (ln[x + 1]) prior to analyses and predicted means from the multilevel models were back-transformed for reporting. All other outcomes were left untransformed. For continuous outcomes, the effect size For analyses related to the second study aim (acceptance of BEAT), we used descriptive statistics, i. e. absolute and relative frequencies or means and standard deviations respectively, to report dropout rates and patients’ subjective evaluation of the BEAT program at posttreatment (completers only).All analysis were performed using R for statistical computing, version 3.2 [ | PMC10683190 |
Results | PMC10683190 |
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Preliminary findings on primary and secondary outcomes | PMC10683190 |
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BED diagnoses and the number of patients with LOC | BED diagnoses and the number of patients with LOC at each time point are reported in Table | PMC10683190 |
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Weekly LOC episodes (WBQ) | The WBQ was assessed 17 times during the whole study, which allowed a detailed observation of the temporal course from pretreatment to post follow-up at week 59. Contrary to our hypotheses, the WBQ not only linearly decreased during the active treatment (slope Temporal course of the WBQ from assessment points pretreatment (week 0) to post follow-up (week 59). The line in bold denotes the estimated trendline of the WBQ from the discontinuous multilevel model with turning points set at week 2 and week 11. The values were back-transformed from ln(x + 1). The thin line connects the arithmetic mean of the observed values of the WBQ being present at the different assessment points. These values were first transformed using ln(x + 1), averaged and then back-transformed again to make them comparable to the predicted means form the model-based values. Shaded areas denote ± 1 standard error of the trend lines from the discontinuous multilevel model. Waiting-time: week 0 to week 2, active treatment: week 2 to week 11, follow-up: week 11 to week 59 | PMC10683190 |
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Secondary outcomes | PMC10683190 |
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Depressive symptoms (BDI-FS) | As for the WBQ, the BDI-FS was assessed 17 times during the whole study and thus allowed a detailed observation of the temporal course from pretreatment to post follow-up (see Fig. Temporal course of the BDI-FS from assessment points pretreatment (week 0) to post follow-up (week 59). See Fig. Contrary to our expectations and similar to the WBQ, the BDI-FS declined during both periods, the waiting-time ( | PMC10683190 |
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General eating disorder pathology (EDE-Q global score) and BMI-SDS | As expected, the EDE-Q global score decreased between pretreatment and posttreatment (week 0 to week 11; including the waiting-time and active treatment) by In accordance with our hypothesis, mean BMI-SDS scores did not change between pretreatment, posttreatment, 6-month follow-up and post follow-up ( | PMC10683190 |
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