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3.5. Confidence in Intended Helping Behaviours in Response to the Alicia Vignette | Mean confidence at pre-course was moderate (m = 2.89, SD = 0.89) and increased significantly over time ( | PMC9963380 | ||
3.6. Quality of Intended Helping Behaviours in Response to the Alicia Vignette | PMC9963380 | |||
3.6.1. Recommended Actions | The most frequently endorsed recommended intended action at all time points was “Tell Alicia that there are sources of help and support available”, with over 97% of participants selecting this response. At pre-course, the mean number of intended recommended actions endorsed was 7.19 out of 8 total actions (SD = 1.26; see | PMC9963380 | ||
3.6.2. Non-Recommended Actions | The non-recommended action “Ask Alicia about why she is injuring herself” was incorrectly endorsed by the majority of participants at each time point (73.4% at pre-course, 88.1% at post-course, 77.6% at follow-up; see At pre-course, the mean number of concordant actions (i.e., participants correctly not endorsing actions that are not recommended in the training or guidelines) was 6.89 (SD = 1.92) out of 9 total actions. Participants had a significant mean increase of approximately one action (m = 1.07, 95% CI 0.79, 1.34, | PMC9963380 | ||
3.7. Confidence in Actual Helping Behaviours | Respondents were moderately confident about the help they provided at pre-course, with a mean value of 2.98 (SD = 0.98), which increased to 3.80 (SD = 0.81) at follow-up (see | PMC9963380 | ||
3.8. Quality of Actual Helping Behaviours | NSSI | A total of 85 (57.8%) participants reported having contact with someone who had engaged in NSSI at pre-course and 29 (40.2%) reported having contact with someone at follow-up. Of these, 23 people reported having contact with someone at both pre-course and follow-up. These individuals were most commonly the participant’s client or patient (32.9% at pre-course and 41.4% at follow-up) or a family member (23.5% at pre-course and 34.5% at follow-up). | PMC9963380 | |
3.8.1. Recommended Action | Participants were asked what actions they took to help the person they had the most contact with in the last six months. The most common recommended action taken was “Help them find ways to make their life more manageable or reduce their distress” at pre-course and at follow-up (see The mean number of recommended actions taken at pre-course was 5.27 out of 8 (SD = 2.42), which increased to 5.48 at follow-up (SD = 2.21; see | PMC9963380 | ||
3.8.2. Non-Recommended Actions | injuries | The most common non-recommended action taken at pre-course was “Ask them about why they were injuring themselves” at 48.8%, followed by “Let them know how distressing their injuries were to you” at 17.9% (see The mean number of responses that were concordant with the guidelines (i.e., participants correctly avoided undertaking actions that were not recommended) was 9.51 (SD = 0.83) and increased to 9.83 (SD = 0.47; see | PMC9963380 | |
3.10. Course Satisfaction and Course Feedback | Overall, participant feedback was very positive and all elements of the course were rated very highly (see Areas where the course could be improved included allowing more time to cover course content, better alignment of the different learning materials (i.e., PowerPoint and course handbook), and the use of roleplays that could give participants the opportunity to practice their new skills and knowledge. The most common answers (i.e., those that received endorsement from at least 10% of the sample) are summarised in | PMC9963380 | ||
4. Discussion | NSSI, self-injury | The present uncontrolled trial used a pre-course, post-course, and six-month follow-up survey to evaluate the effects of Mental Health First Aid Australia’s Participant knowledge about NSSI was moderate before the course and showed sustained improvement over time, with mastery being achieved by over three quarters of participants at post-course and follow-up. This was reflected in the participant satisfaction data where participants rated the content as mostly new (see Similar sustained improvements were demonstrated for confidence in intended help and confidence in actual help provided to a person who had engaged in NSSI. Confidence in intended help showed greater mean improvements from pre-course to six-month follow-up than confidence in actual helping situations. This discrepancy may be influenced by additional factors, such as the participant’s relationship to the person they are helping, which are present in real-world interactions and difficult to simulate in roleplay scenarios as taught in the course [The quality of intended helping behaviours significantly increased at post-course and six-month follow-up. Concordance with non-recommended actions showed the greatest improvement, with participants’ reducing the number of non-recommended actions endorsed at the post-course assessment. However, mastery for intended recommended actions was higher at all time points than mastery for non-recommended actions, which may suggest that appropriate actions to take when supporting someone engaging in NSSI are clearer or more memorable than actions to avoid. Furthermore, some non-recommended actions (for example, telling them to stop) may reflect intuitive responses which could be related to participants’ lack of knowledge or confidence. Future iterations of the Interestingly, of the participants who reported that they had provided support to someone who engaged in NSSI after undertaking the course, the proportions for mastery were higher for non-recommended actions than recommended actions. These results may indicate that, although participants knew what actions they should take, there may be barriers present in real-life situations that are not measured in this study that prevent them from taking appropriate action, for example, the participant’s relationship to the person they are supporting or the context in which NSSI was disclosed or discovered [There are several possible explanations for why the non-recommended item “Ask Alicia about why she is injuring herself” was consistently incorrectly endorsed as both an intended and actual behaviour. First, the action may not have been appropriately distinguished from a similarly worded recommended action included in the guidelines that informed the course: “Ask the person questions about their self-injury, but avoid pressuring them to talk about it” [ | PMC9963380 | |
Strengths, Limitations, and Future Directions | The The limitations of the evaluation include low response rates at follow-up and limited data about actual first aid helping actions provided after the course. Additionally, the absence of a control group makes it difficult to discern whether observed effects resulted from the course itself or extraneous factors that were not captured in this evaluation. The largely female, well-educated, English-speaking sample is consistent with participant groups from previous MHFA course evaluations [The results of this study have several implications. First, this evaluation finds that the The findings related to effectiveness and safety may also increase the likelihood that other licensees of MHFA courses, such as the USA, Canada, the UK, and those in other high-income countries, will adopt the | PMC9963380 | ||
5. Conclusions | The present evaluation provides initial evidence to support the effectiveness and acceptability of Mental Health First Aid Australia’s | PMC9963380 | ||
Supplementary Materials | The following supporting information can be downloaded at: Click here for additional data file. | PMC9963380 | ||
Author Contributions | Conceptualisation, K.S.B., F.A.C., C.M.K., N.J.R. and A.F.J.; Data curation, J.N.L., F.A.C., A.R., C.M.K. and A.J.M.; Formal analysis, J.N.L., S.E.B., A.R. and A.J.M.; Investigation, K.S.B.; Methodology, K.S.B., F.A.C., C.M.K., N.J.R. and A.F.J.; Project administration, K.S.B., A.R. and N.J.R.; Resources, L.K.; Supervision, A.J.M.; Writing—original draft, K.S.B., J.N.L., A.V.S., S.E.B., A.R. and A.J.M.; Writing—review and editing, K.S.B., J.N.L., F.A.C., A.V.S., S.E.B., A.R., L.K., C.M.K., N.J.R., A.F.J. and A.J.M. All authors have read and agreed to the published version of the manuscript. | PMC9963380 | ||
Institutional Review Board Statement | The study was conducted in accordance with the Declaration of Helsinki and approved by the Human Research Ethics Committee of the University of Melbourne (Ethics ID 1851649, granted 12 June 2018). | PMC9963380 | ||
Informed Consent Statement | Informed consent was obtained from all subjects involved in the study (see | PMC9963380 | ||
Data Availability Statement | The data presented in this study are available in | PMC9963380 | ||
Conflicts of Interest | K.S.B., J.N.L., F.A.C., A.V.S., S.E.B. and C.M.K. work for Mental Health First Aid Australia. A.R. and L.K. are previous employees of Mental Health First Aid Australia. A.F.J. is the co-founder of Mental Health First Aid Australia and on the board of Mental Health First Aid Australia. A.J.M. and N.J.R. declare no conflict of interest. | PMC9963380 | ||
References | Participant characteristics pre-course (n = 147).Observed means and standard deviations for outcome measures.Note: Mean changes and odds ratio (OR) over time from pre-course to post-course and pre-course to follow-up.Note: Number and percent of participants who intended to undertake recommended actions to support Alicia Note: Number and percent of participants who intended to undertake actions that were not recommended to support Alicia Note: Number and percent of participants who undertook actions to support a person that were recommended by MHFA training.Note: Number and percent of participants who undertook actions to support a person that were not recommended by MHFA training.Note: Results of content analysis for the questions “What were the effects on the person of what you did?” and “What did the person do as a result of your help?”Note: only categories with more than 5% of responses coded to them are reported in this table. Responses were able to be coded into multiple categories. Mean scores for course satisfaction measures (n = 133).Summary of qualitative course satisfaction data and feedback.Note: only responses that received endorsement from at least 10% of the sample (n) population for each question are listed in this table. | PMC9963380 | ||
Introduction | Diabetes | HEART, TYPE 2 DIABETES MELLITUS, DIABETES | Edited by: Sathish Thirunavukkarasu, Emory University, United StatesReviewed by: Tina Cao, La Trobe University, Australia; Quan Huynh, Baker Heart and Diabetes Institute, AustraliaThe aim of this study was to evaluate the effectiveness of a real-life clinical physical activity program (DIAfit) on improving physical fitness, body composition, and cardiometabolic health in an unselected population with type 2 diabetes mellitus, and to compare the effects of two variants a different exercise frequencies on the same outcomes. | PMC10359883 |
Research design and methods | TYPE 2 DIABETES | This was a cluster randomized-controlled assessor-blind trial conducted in 11 clinical centres in Switzerland. All participants in the clinical program with type 2 diabetes were eligible and were randomized to either standard (3 sessions/week for 12 weeks) or alternative (1 session/week for the first four weeks, then 2 sessions/week for the rest of 16 weeks) physical activity program each consisting of 36 sessions of combined aerobic and resistance exercise. Allocation was concealed by a central office unrelated to the study. The primary outcome was aerobic fitness. Secondary outcome measures included: body composition, BMI, HbA | PMC10359883 | |
Results | type 2 diabetes | TYPE 2 DIABETES | All 185 patients with type 2 diabetes (mean age 59.7 +-10.2 years, 48% women) agreed to participate and were randomized in two groups: a standard group (n=88) and an alternative group (n=97)). There was an 11% increase in aerobic fitness after the program (12.5 Watts; 95% CI 6.76 to 18.25; p<0.001). Significant improvements in physical fitness, body composition, and cardiometabolic parameters were observed at the end of the DIAfit program (improvements between 2-29%) except for lean body mass, triglycerides and cholesterol. No differences were observed between both programs, except for a larger weight reduction of -0.97kg (95% CI -0.04 to -1.91; p=0.04) in the standard program. | PMC10359883 |
Conclusions | Both frequency variants of the nation-wide DIAfit program had beneficial effects on physical fitness, HbA | PMC10359883 | ||
Clinical trial registration | PMC10359883 | |||
Introduction | TYPE 2 DIABETES | The global prevalence of type 2 diabetes is high (8.8%) and is projected to increase considerably in the next years (A Cochrane review has stated that the optimal type, frequency, intensity and duration of exercise for achieving therapeutic goals in type 2 diabetes patients are still unknown (This pragmatic randomized trial investigated the feasibility and overall effectiveness of a nationwide PA program in a real-life clinical setting in patients with type 2 diabetes. Firstly, we evaluated the effects of the DIAfit program on aerobic fitness (primary outcome), as well as on strength, flexibility, balance and walking speed, anthropometry, body composition and cardiometabolic parameters independent of the selected frequency variant of the program. Secondly, we compared the effectiveness of the standard DIAfit program (3x/week over 12 weeks) with an alternative program including the same total sessions but differed in frequency (increasing frequency from 1x/week up to 2x/week over 20 weeks) on the same outcomes. | PMC10359883 | |
Materials and methods | PMC10359883 | |||
Design, setting and participants | ischemia, diabetic foot ulceration, type 2 diabetes, autonomic neuropathy | AUTONOMIC NEUROPATHY, ISCHEMIA, PERIPHERAL VASCULAR DISEASE, TYPE 2 DIABETES, PROLIFERATIVE RETINOPATHY | The clinical DIAfit program is a nationwide Swiss lifestyle based real-life clinical group intervention program (Local diabetologist or general practitioners referred their patients to the closest clinical program centre. Inclusion criteria for patient to be enrolled in the clinical DIAfit program were age ≥18 years and a diagnosis of type 2 diabetes for ≥3 months. Exclusion criteria for clinical referrals were active diabetic foot ulceration; ischemia during a cycle ergometry exercise test or state III peripheral vascular disease; untreated proliferative retinopathy and autonomic neuropathy with unstable BP during the exercise test. In order to increase external validity, all patients referred to the clinical program were eligible to participate in the study. All 185 eligible and participating patients that were referred to the clinical program between 2011 and 2012 from the 11 DIAfit treatment centres were invited to participate in the study.All patients underwent the same medical visit by physicians collaborating in the DIAfit program. As part of the clinical routine, patients had a fasting blood analysis and a cycle ergometry according to a standardized protocol at the beginning and the end. For the study, they underwent additional physical fitness tests and filled out questionnaires at both time points. During the centralized clinical training all centres were instructed how to perform all physical fitness tests and medical exams according to standard operating procedures. Baseline data of this study have been previously reported ( | PMC10359883 |
Randomization and blinding | DIAfit was a cluster randomized controlled single-blind trial 1:1. At the start of the clinical program, two different exercise frequency variants were introduced and tested. Patient groups were allocated per cluster (i.e., treatment centre) to randomly start one program variant first and then the other using concealed opaque envelopes. Each centre thus provided both variants. Selection and randomization took place 2 weeks before the start of each program and were performed by a central coordinator (OG) who was not involved in the study. Patients signed informed consent before knowing their group allocation. Health care providers and investigators were blinded to group allocation before the start of the first program. The primary outcome assessors were always blinded to the respective variant. Patients and the clinical staff such as the physical therapists could not be blinded since they knew how many sessions per week were attended. Both program variants were matched by number of sessions (Details of the standard and alternative interventions.HR, heart rate; RM, repetition maximum. | PMC10359883 | ||
Ethics | The study was approved by the ethical committee of Lausanne in 2011 (protocol 252/10) and all participants signed a written informed consent. The trial was registered (clinicaltrials.gov NCT01289587). | PMC10359883 | ||
Outcomes and measures | SECONDARY | All primary and secondary outcomes were reported at the level of the individual. Specially trained researchers and clinicians measured all outcomes. The primary outcome was the change in aerobic fitness. Secondary outcomes included changes in body composition, BMI, HbA | PMC10359883 | |
Physical fitness | LOWER LIMB | Physical fitness was assessed by five parameters: aerobic fitness, lower limb muscle strength, walking speed, balance, and flexibility.Aerobic fitness was evaluated with a maximal graded cycle ergometry test performed by a cardiologist blinded to the other data. Participants started at 20 Watts. Increments of 20 Watts per 2 min were made until exhaustion or until reaching one of the American College of Sports Medicine established criteria for maximal oxygen uptake (Lower limb muscle strength was assessed with the Chair Stand Test. Participants sat with arms folded across the chest and with their back against the chair. The patient was instructed to stand up and sit down five times as quickly as possible and the required time (sec) was recorded ( | PMC10359883 | |
Body composition | CREST | During the medical visits, body weight and height were measure barefoot and clothes off. BMI was calculated based on measured height and weight. Waist circumference was measured midway between the iliac crest and the lowest border of the rib cage. Body composition was assessed by bioelectrical impedance using a 4-polar single frequency device (RJL Systems, Model 101A; Detroit, MI, USA). The fat and lean body mass were predicted using the software Bodygram | PMC10359883 | |
Cardiometabolic measures | Each centre measured HbA | PMC10359883 | ||
Confounder variables | type 2 diabetes | TYPE 2 DIABETES | Along with age and sex, educational level (EL) was included as a covariate since it’s related to physical fitness in patients with type 2 diabetes ( | PMC10359883 |
Statistical analysis | REGRESSION, SECONDARY, COMPLICATIONS | Statistical analyses were conducted using STATA 16 (Stata Corp, College Station, TX, USA). Taking into account a drop-out of 1 centre with an average program size of 10 patients per centre, we assumed that 7 patients per centre would participate in both aerobic fitness tests (due to non-participation, attrition, moving, sickness on the testing day). In case of sickness on the testing day, the stress test (aerobic fitness test) will be repeated on another day. A total number of 10 centres (70 patients per treatment arm) would then provide enough power to detect a true intervention effect of two-thirds of an inter-subject standard deviation at the usual significance level of 0.05 with a probability of 0.8, provided that the standard deviation of the random class effect does not exceed 3% of the inter-subject standard deviation (i.e., corresponding to an intra-class correlation of about 0.03). Therefore, we included 11 treatment centres.Complete-case analyses were performed according to intention to treat. Descriptive statistics were calculated using mean ± SD for continuous variables, or percentage for categorical variables. The analyses of the primary and secondary outcomes were based on a superiority assumption and presented as mean differences with 95% CI and Main baseline characteristic of the participants.The presence of complications and comorbidities are obtained based on the information of the referring physician or the patient.Linear regression analyses were performed to test the difference in outcome at the end of the program between both arms. In the regression models, the dependent variable was represented by baseline to end-of-study change in HbAIn case of significant association between change in outcome and the centre, mixed model analyses were performed. This was the case for aerobic fitness, walking speed, body weight, BMI, lean body mass, fat body mass, HDL, systolic BP. In the mixed models, the centre was the unit of randomization and change in physical fitness, body composition, and cardiometabolic health outcomes as the dependent variables. The predictors were the study arm, age, sex, and educational level. The objective was to check for each outcome if the coefficient related to the program type is significantly different from 0. Statistical level was set at P<0.05 for all analyses.To account for missing values, in a secondary analysis all cases were included in the analysis by using multivariate imputation by chained equation (MICE), with the assumption that the data are missing at random ( | PMC10359883 | |
Results |
Participant flow chart.Baseline characteristics of the study participants are reported in
Physical fitness, body composition, and cardiometabolic outcomes at baseline and at the end of the DIAfit program of all participants and within-group changes.SD, standard deviation; CI, confidence interval; BMI, body mass index; HbA | PMC10359883 | ||
Physical fitness | SECONDARY | Compared to baseline, aerobic fitness increased by 12.5 Watts (95% CI 6.76 to 18.25; p<0.001). This corresponds to a mean improvement of 11%. Also, at the end of the program participants needed 2.95sec (95% CI 2.48 to 3.43; p<0.001) less for the lower limb strength test (=increased strength), increased their flexibility by 3.45cm (95% CI -4.43 to -2.48; p<0.001), could stand on one leg for 1.94sec (95% CI 0.55 to 3.32; p=0.006) longer, and needed 1.27sec (95% CI -1.46 to -1.08; p<0.001) less for the 10m walking speed test. In summary, there was a mean improvement of 10-29% in the secondary physical fitness outcomes. | PMC10359883 | |
Body composition | Body weight decreased by 0.93kg (95% CI -0.43 to -1.42; p<0.001), BMI decreased by 0.34 kg/m | PMC10359883 | ||
Cardiometabolic measures | weight reduction | REGRESSION | Between baseline and the end of the program, HbA
Differences in physical fitness, body composition, and cardiometabolic outcomes in the standard and alternative program and between-group differences.CI, confidence interval; BMI, body mass index; HbADifferences between groups are shown comparing the alternative vs the standard program adjusted for age; sex; and educational level.‡The ANOVA analyses revealed that the centre (cluster) was associated with the outcome; so for these outcomes mixed models were used. For all other outcomes; linear regression analyses were used.Significant differences are shown in bold.Except for body weight, there were no significant differences in all outcomes between the standard and the alternative programs (p>0.05). The difference favoured the standard group, with a more pronounced weight reduction of -0.94kg (95% CI -0.05 to -1.83; p=0.04). For weight metrics, the effects remained the same after adjusting for weight status at baseline (data not shown) when comparing both intervention programs.Throughout the 36 sessions, the average exercise training attendance was 30.6 sessions (85%) for the standard program and 28.9 sessions (80%) for the alterative program (1.7; 95% CI -0.22-3.62, p=0.08). | PMC10359883 |
Discussion | type 2 diabetes, diabetes | TYPE 2 DIABETES, DIABETES | This pragmatic randomized trial demonstrated the effectiveness of a real-life nationwide PA group program (DIAfit) in improving aerobic fitness and other physical fitness outcomes such as strength, flexibility, balance and walking speed by 10-29%. Although to a lesser extent, the program also improved body weight, body composition, HbAThis study showed important findings regarding translating evidence from highly specialized research centres into real-life clinical practice. Indeed, all patients enrolled in the clinical DIAfit program were eligible and agreed to participate in the study. The program took mostly place in small regional hospitals, but also in private practices or university hospitals. The DIAfit program was delivered by regular staff with no specific experience. All of which increased the generalizability of our findings. Furthermore, patients in our study were of similar age or older than those in previous studies. They had a mean baseline HbA1c of 7.3% which is representative of the glycaemic control observed in larger community-based cohorts of patients with diabetes in Switzerland (We evaluated a comprehensive range of physical fitness outcomes. The primary outcome, aerobic fitness, improved by 11%. Similar results were reported in a previous meta-analysis that demonstrated an 11.8% increase in VOThe DIAfit program was associated with a reduction of a 0.19% in HbAThe DIAfit program was effective in improving body composition. The observed mean reduction in weight of 0.93 kg and waist circumference of 1.14 cm are similar to results found in some structured PA programs of similar duration without any dietary intervention and demonstrates the effects that can be achieved with this intensity and volume of PA (In this study, we also compared two program variants and found similar results for physical fitness, body composition, and cardiometabolic parameters in both programs although effect sizes of changes were larger in the standard program regarding anthropometric parameters, body fat mass, HbAStrengths of the current study included the pragmatic nature of a nation-wide PA program which demonstrated the benefits and relevance of structured PA for patients with type 2 diabetes in real-world conditions integrated in routine care. The multicentre design in different settings increased the external validity since the results were observed in different clinical settings. Furthermore, we included a broad range of outcome measures including extensive physical fitness measures relevant for various health outcomes such aerobic fitness, muscular strength, flexibility, balance, and walking speed. And lastly, the comparison of different forms of exercise frequency is not only novel, but also pertinent for clinical practice. Some limitations should be noted. The most important one being the lack of a control group for our first aim. However, participating health care providers and cantonal agencies did not approve the idea of a waiting list which would not let benefit all patients at the time when they are motivated or at least agree to participate in a PA program. All providers were told not to adapt the medical treatment during the testing time period, but we did not control for any potential changes in medication intake. In this real-life trial, small differences between centres were observed in several outcomes such as aerobic fitness, walking speed, anthropometry, body composition, and some cardiometabolic parameters, see | PMC10359883 |
Conclusion | TYPE 2 DIABETES | The national DIAfit PA group program was effective and deliverable in real-world clinical settings for promoting PA and improving important health parameters such as physical fitness, cardiometabolic health, and body composition in patients with type 2 diabetes. The alternative program of one-to-twice weekly supervised combined aerobic and resistance exercise had similar benefits compared to the classical program and can serve as a useful example for implementing a site-tailored PA intervention. | PMC10359883 | |
Data availability statement | Part of the original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author. | PMC10359883 | ||
Ethics statement | The studies involving human participants were reviewed and approved by Lausanne University Hospitals Ethical Committee. The patients/participants provided their written informed consent to participate in this study. | PMC10359883 | ||
Author contributions | JP | JP and OG with the assitance of HD, MC, DD, SB and DS were responsable for the study design and all authors helped data collection. J-BR, AA and JP were responsible for the statistical analysis and AA and NJ helped with data management. AA and JP wrote the manuscript draft. All authors contributed to the article ad approved the submitted version. | PMC10359883 | |
Acknowledgments | We thank DIAfit Switzerland ( | PMC10359883 | ||
Conflict of interest | The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. | PMC10359883 | ||
Publisher’s note | All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. | PMC10359883 | ||
References | PMC10359883 | |||
Background | PIH, hypotension | HYPERTENSION | Certain routine medication could result in post-induction hypotension (PIH), such as angiotensin axis blockades, which are frequently administered as a first-line therapy against hypertension. Remimazolam is reportedly associated with lesser intraoperative hypotension than propofol. This study compared the overall incidence of PIH following remimazolam or propofol administration in patients managed by angiotensin axis blockades. | PMC10286332 |
Methods | PIH | This single-blind, parallel-group, randomized control trial was conducted in a tertiary university hospital in South Korea. Patients undergoing surgery with general anesthesia were considered for enrollment if the inclusion criteria were met: administration of an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, 19 to 65 years old, American Society of Anesthesiologists physical status classification ≤ III, and no involvement in other clinical trials.The primary outcome was the overall incidence of PIH, defined as a mean blood pressure (MBP) < 65 mmHg or decrease by ≥ 30% of the baseline MBP. The time points of measurement were baseline, just before the initial intubation attempt, and 1, 5, 10, and 15 min following intubation. The heart rate, systolic and diastolic blood pressures, and bispectral index were also recorded.Groups P and R included patients administered propofol and remimazolam, respectively, as an induction agent. | PMC10286332 | |
Results | PIH | A total of 81 patients were analyzed, of the 82 randomized patients. PIH was less frequent in group R than group P (62.5% versus 82.9%; t value 4.27, | PMC10286332 | |
Conclusion | PIH | Remimazolam results in less frequent PIH than propofol in patients undergoing routine administration of angiotensin axis blockades. | PMC10286332 | |
Trial registration | This trial was retrospectively registered on Clinical Research Information Service (CRIS), Republic of Korea (KCT0007488). Registration date: 30/06/2022. | PMC10286332 | ||
Keywords | PMC10286332 | |||
Introduction | PIH, hypotension | HYPERTENSION, COMPLICATIONS | General anesthesia induction is frequently followed by hypotension, namely post-induction hypotension (PIH), which is reportedly 18–50% [Propofol is the most commonly administered agent for the induction of general anesthesia [Angiotensin axis blockades are widely administered in the surgical population, owing to their use as first-line treatment for hypertension. Adoption of an appropriate hypnotic agent is warranted to minimize hypotension and prevent potential complications in these patients. Therefore, we conducted a randomized controlled trial to compare the incidence of post-induction hypotension induced by remimazolam versus propofol in patients routinely administered angiotensin axis blockades. | PMC10286332 |
Methods | PMC10286332 | |||
Study setting | This study was designed as a single-blind, parallel-group, randomized controlled trial. The study was reviewed and approved by the Institutional Review Board of Wonju Severance Christian Hospital (CR321057; approval date: 20/07/2021) and registered with the Clinical Research Information Service of Korea (KCT0007488; registration date: 30/06/2022). This study was conducted in a tertiary university hospital in Wonju, Republic of Korea. This study was reported in compliance with the Consolidated Standards of Reporting Trials guidelines [ | PMC10286332 | ||
Variables and assessments | Hypotension, hypotension | BLOOD, SECONDARY, DYSFUNCTION | The primary outcome was the incidence of hypotension following anesthesia induction. Hypotension was defined as a mean blood pressure (MBP) reduced 30% or more from the baseline MBP value or MBP < 65 mmHg, the threshold at which vital organ dysfunction can be initiated [Blood pressure was recorded six times during anesthesia. Time points T0, T1, T2, T3, T4 and T5, were baseline, immediately before the first attempt of intubation, a minute after intubation, 5 min after intubation, 10 min after intubation, and 15 min after intubation, respectively. In case of the arterial cannulation is present, real-time arterial blood pressure values were recorded. Otherwise, blood pressure was monitored using the oscillatory method through a pneumatic cuff at the area of the brachial artery. The MBP measured using this method is widely validated and considered reliable when measured under proper conditions [The secondary outcomes were heart rate, mean, systolic, and diastolic blood pressure (MBP, SBP, and DBP), and bispectral index (BIS). These variables were measured from T0 to T5. An attending anesthesiologist assessed and recorded the primary outcomes and intraoperative variables. These data were verified by the corresponding author upon a reviewing the anesthesia records. | PMC10286332 |
Participants | UNCONTROLLED HYPERTENSION | Patients undergoing surgery with general anesthesia were considered for enrollment if the inclusion criteria were met: routine administration of ACEI or ARB, 19 to 65 years old, American Society of Anesthesiologists physical status classification of III or lower, and no involvement in other prospective clinical trials. The exclusion criteria were as follows: emergency and outpatient surgery, a candidate for transfer to an intensive care unit, body mass index ≥ 35, uncontrolled hypertension (usual SBP > 160 mmHg) [ | PMC10286332 | |
Sample size | hypotension | The incidence of hypotension was considered as 84% in the patients receiving angiotensin axis blockades and propofol as an induction agent based on a previous study [ | PMC10286332 | |
Protocol | postoperative pain, postoperative nausea and vomiting, µg*kgAfter loss of consciousness | Assessment of eligibility and enrollment in the study was performed by the corresponding author. The participants were informed about the study via an informed consent form the day before the surgery, and provided sufficient time to determine their participation and sign the form. The participants were randomly assigned (1:1) to the propofol or remimazolam groups, namely groups P and R, respectively, using a sealed envelope system. A random allocation sequence was generated in advance by one of the authors (SWS) using R software. Paper cards containing the group allocations were sealed in opaque envelopes. Each sealed envelope was opened by another author (SK), and the patient notified the group allocation to an attending anesthesiologist 30 min before surgery. No anesthetic premedication was administered to the participants. The routine administration of ACEI or ARB was continued on the day of surgery.The induction drug was drawn in the anesthesia preparation room and the syringe was placed in a metal tin box. The patient and surgeon were blinded to the bolus drug administered by placing an opaque plastic cardboard, and blinding was maintained until the discharge of the patient from the post-anesthetic care unit.The baseline blood pressure, heart rate, pulse oximetry, and BIS (BIS Complete Monitoring system, Covidien Ireland Limited, Dublin, Ireland) were recorded following the patient identification process. Other standard anesthetic monitoring devices, such as electrocardiograms, were also applied. Remifentanil infusion was initiated at a rate of 0.25 µg*kgAfter loss of consciousness, remimazolam was infused at a rate of 1 mg*kgAn additional bolus of rocuronium 0.15 mg/kg IBW was administered in cases of decreased pulmonary compliance or discretion of the surgeon. Fentanyl 1 µg/kg and ramosetron 0.3 mg were administered for postoperative pain control and postoperative nausea and vomiting prophylaxis. | PMC10286332 | |
Statistical analysis | hypotension | REGRESSION, BLOOD | IBM SPSS 26 Statistics for Windows (IBM Corp., Armonk, NY, USA) was used for statistical analysis, and R Statistics 4.2.2 (R Core Team, Vienna, Austria) was used for visualization. The chi-square test was performed to analyze the primary outcome. The unadjusted and adjusted odds ratio of remimazolam versus propofol for the incidence of hypotension was calculated by logistic regression analysis, and the covariates were the administration of the drugs causing angiotensin axis blockade on the day of surgery and type of surgery.Decrease in the MBP, SBP, and DBP (blood pressure values subtracted from the baseline values) at T1 to T5 were compared using the t-test with Bonferroni correction to correct the multiplicity of the comparisons. The BIS and heart rate at T0 to T5 were compared using the t-test with Bonferroni correction. Other continuous variables were compared using the t-test, and categorical variables were compared using the chi-square test. Statistical significance was set as Blood pressure > 300 mmHg or < 30 mmHg and heart rate > 200 beats per minute were excluded from the analysis. Missing value analysis by SPSS revealed a few missing values (< 5%) in the total remifentanil dose and BIS values; however, they were randomly distributed. The missing values were excluded from the analysis. | PMC10286332 |
Discussion | PIH, supraglottic airway, hypotension | A remarkable proportion of patients (> 70%) in this study developed hypotension. This is higher than the general population and supports the finding that the patients routinely administered angiotensin axis blockades are vulnerable to PIH [In cases of intraoperative hypotension, the amount of reduction in the blood pressure is also critical [Another benefit of remimazolam as an induction agent is that the drug has the antagonist. There are some cases where rapid recovery after loss of consciousness is required. One example is difficult airway management. According to the multiple airway management guidelines, emergence and recovery of spontaneous ventilation are warranted in cases of supraglottic airway or endotracheal tube placement fails, but oxygenation is still possible [A trend of higher BIS was observed in participants administered remimazolam than in those who were administered propofol. Previous studies have reported a discrepancy between the BIS and sedative state in patients administered remimazolam [Our study has certain limitations. First, due to the loading dose of remimazolam in group R, the effect-site concentration after the loss of consciousness could be higher in group R. Further study adopting a target-controlled infusion model is required to overcome this limitation. Second, generalizability is limited due to the exclusion of high-risk surgical populations who require preparation for intensive care units. In addition, long-term postoperative outcomes, such as 30-day mortality, have not been studied. Further well-designed studies addressing the long-term postoperative impact of intraoperative hypotension in patients administered ARB or ACEI are warranted. | PMC10286332 | |
Acknowledgements | Not applicable. | PMC10286332 | ||
Authors’ contributions | Conceptualization: YG Jeon. Data curation: YH Cho, YG Jeon. Formal analysis: SW Song. Investigation: SW Song, S Kim, YH Cho, YG Jeon. Methodology: YG Jeon. Project administration: Jeon YG. Supervision: JH Park. Validation: SW Song, Jeon YG. Visualization: SW Song. Writing – original draft: SW Song, S Kim, JH Park, YH Cho, YG Jeon. Writing – review & editing: SW Song, S Kim, JH Park, YH Cho, YG Jeon. | PMC10286332 | ||
Funding | This research was funded by the departments of the corresponding author. | PMC10286332 | ||
Availability of data and materials | The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request. | PMC10286332 | ||
Declarations | PMC10286332 | |||
Ethics approval and consent to participate | The study was reviewed and approved by the Institutional Review Board of Wonju Severance Christian Hospital (CR321057, approval date: July 20, 2021) and registered with the Clinical Research Information Service of Korea (KCT0007488) on June 30, 2022. Written informed consent was submitted by all subjects when they were enrolled, and all methods were carried out in accordance with relevant guidelines and regulations. | PMC10286332 | ||
Consent for publication | Not applicable. | PMC10286332 | ||
Competing interests | The authors declare no competing interests. | PMC10286332 | ||
References | PMC10286332 | |||
Purpose | breast cancer | BREAST CANCER | The role of neoadjuvant endocrine therapy in the treatment of patients with early-stage, hormone receptor-positive (HR +) breast cancer is not well defined. Tools to better determine which patients may benefit from neoadjuvant endocrine therapy versus chemotherapy or upfront surgery remain an unmet need. | PMC10147793 |
Methods | early-stage HR, ® | RECURRENCE, BREAST, BREAST CANCER | We assessed the rate of clinical and pathologic complete response (cCR, pCR) among a pooled cohort of patients with early-stage HR + breast cancer who had been randomized to neoadjuvant endocrine therapy or neoadjuvant chemotherapy in two earlier studies to understand better how outcomes varied by Oncotype DX Breast Recurrence Score® assay. | PMC10147793 |
Results | RS | We observed that patients with intermediate RS results had no statistically significant differences in pathologic outcomes at the time of surgery based on whether they received neoadjuvant endocrine therapy or neoadjuvant chemotherapy, suggesting that a subgroup of women with a RS 0–25 may omit chemotherapy without compromising outcomes. | PMC10147793 | |
Conclusion | RS | RECURRENCE | These data suggest that Recurrence Score® (RS) results may serve as a useful tool in treatment decision-making in the neoadjuvant setting. | PMC10147793 |
Keywords | PMC10147793 | |||
Introduction | RS, early-stage HR, breast cancer | SECONDARY, BREAST CANCER | Adjuvant endocrine therapy remains the standard of care for patients with early-stage, HR + breast cancer who can safely omit chemotherapy based on RS results; however, the role of neoadjuvant endocrine therapy remains unclear [The use of genomic assays has significantly impacted how physicians approach adjuvant treatment decisions for women with early-stage, HR + breast cancer; however, data for use in the neoadjuvant setting are limited. Tools to better determine which patients may benefit from neoadjuvant endocrine therapy versus neoadjuvant chemotherapy or upfront surgery followed by chemotherapy remain an unmet need. This secondary pooled analysis of randomized phase II prospective studies re-examines the use of neoadjuvant endocrine therapy among a cohort of premenopausal and postmenopausal patients with early-stage HR + , human epidermal growth factor receptor 2-negative (HER2-) breast cancer randomized to neoadjuvant endocrine therapy or neoadjuvant chemotherapy based on Oncotype DX® assay performed on initial core biopsy specimens. Performance of the 21-gene RS assay on biopsy specimens rather than tissue specimens following excision has demonstrated reliable results [ | PMC10147793 |
Patients and methods | tumor, Cancer | TUMOR, INVASIVE BREAST CANCER, CANCER | Data were pooled from two independent randomized phase II prospective studies of early-stage, HR + , HER2- patients with invasive breast cancer in a preoperative setting, performed at Emory University’s Winship Cancer Institute (Emory) and Massey Cancer Center at Virginia Commonwealth University (VCU) from 2010 to 2012; the latter included patients from 6 additional collaborating sites in the US and Canada [The VCU multi-center study included women with HR + (defined as > 10% tumor staining by immunohistochemistry), HER2- invasive breast cancer measuring at least 2 cm and deemed by the surgeon not suitable for breast-conserving surgery unless size reduced by neoadjuvant therapy with ECOG performance status 0–1 [Outcomes evaluated for this analysis include clinical partial and complete response (cPR, cCR) and pathologic complete response (pCR) in the breast and axillary nodes. Pathology reports from surgical specimens were reviewed for determination of pCR, and clinical partial and complete response were determined by review of radiology reports in the medical records using RECIST criteria. Of note, patients in the VCU cohort were deemed not suitable for breast conservation without tumor shrinkage as determined by a multidisciplinary treatment team. | PMC10147793 |
Statistical analysis | RS | REGRESSION, DISSECTION, EVENT | Prior to combining the patients from each study into one analysis cohort, comparisons of the VCU and Emory patients were performed to assess whether the groups were similar enough for pooling. Due to small sample sizes, we were limited to conducting a simple descriptive exploration of study differences. Comparisons of continuous variables (age, RS result, chemotherapy cycles, months of endocrine therapy) were performed using the Wilcoxon Median 2-sample test, and categorical variables (race, ethnicity, menopausal status, nodal stage, HR status, grade, RS group, randomized neoadjuvant treatment group, cCR, cPR, and pCR) were evaluated using the Chi-square test or Fisher’s exact test for cell counts < 5. Comparisons could not be made by overall clinical stage, as this variable was not reported from VCU.No clinically significant differences were identified that would limit pooling of the study data. Although event counts were too low to perform robust regression models predicting study outcomes, associations between RS result, type of neoadjuvant therapy (comparing all RS groups), and pCR in the breast, lymph nodes and breast plus lymph nodes were evaluated using Fisher’s exact test. Of note, one patient who did not receive Sentinel Lymph Node Biopsy (SLNB) or Axillary Lymph Node Dissection (ALND) was excluded from the denominator for pCR Nodes.A sensitivity analysis was performed to assess the impact of the differing RS result cut-points in groups B and C between the studies on the outcomes. In this analysis, Emory patients with RS result = 25 were reassigned from Group D into Group C, since they were treated with neoadjuvant chemotherapy. Analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC).Both studies were designed as pilot studies to assess feasibility and subsequently, there were no pre-planned power and sample size estimates performed in the combined analysis. Post hoc power calculations are controversial and of limited utility. | PMC10147793 |
Results | RS | Our analysis included 109 eligible patients from both institutions (Protocol schema from VCU study [Protocol schema from Emory study [CONSORT diagram for combined Cohort characteristics(a) The Wilcoxon Median 2-sample test was used for (b) No overall clinical stage variable reported for VCU(c) Intermediate RS values of 11–24 (Emory) or 11–25(VCU) | PMC10147793 | |
RS groups | RS, tumors, low RS | RECURRENCE, TUMORS, GROUP B | Patients were pooled and grouped based on RS result: RS < 11 (18.0% Emory and 20.3% VCU), RS 11–24 (Emory) or 25 (VCU) (36.0% Emory and 55.9% VCU), and RS 25 (Emory) or 26 (VCU) or higher (46.0% Emory and 23.7% VCU). Patients in Group A were older (median 64 years vs 59 years in Group D), with a higher percentage of low-grade tumors (47.6% grade 1 vs 5.4% grade 1 among RS > 24/25 in Group D). Patients with high RS result (Group D) had a higher percentage of nodal involvement (48.6%) than those with low RS result (23.8% in Group A). Nodal involvement among randomized patients with intermediate RS results differed somewhat, with 22.2% N + in Group B and 37.5% N + in Group C. Results are summarized in Table Demographic and clinical characteristics by treatment group(a) Nonparametric testing was used for Group A = Recurrence Score < 11, Group B = Recurrence Score 11–24 (Emory study) or 11–25 (VCU study) receiving NHT, Group C = Recurrence score 11–24 (Emory study) or 11–25 (VCU study) receiving NCT, and Group D = Recurrence score > 24 (Emory study) or > 25 (VCU study)Among patients with high RS result in group D, 2 Emory patients (8.7%) achieved cCR versus 4 patients (28.6%) in the VCU group ( | PMC10147793 |
Rates of pCR | RS, breast or breast plus lymph nodes | EVENTS, RECURRENCE, GROUP B | With regard to pCR, there were few events reported among patients with low or intermediate RS results in the pooled data. One patient (4.8%) in Group A was found to have pCR in the breast plus lymph nodes (4.8%), while no patients in either randomized group achieved pCR in the breast or breast plus lymph nodes. While there were different rates of pCR in the lymph nodes in the randomized groups (4.3% in Group B vs 13.6% in Group C), they did not reach statistical significance (pCR according to treatment groups (All Eligible Patients)(a) Fisher’s exact test was used for categorical variables with cell counts < 5Group A = Recurrence Score < 11, Group B = Recurrence Score 11–24 (Emory) or 11–25 (VCU) receiving NET, Group C = Recurrence Score 11–24 (Emory) or 11–25 (VCU) receiving NCT, and Group D = Recurrence Score > 24 (Emory) or > 25 (VCU)Since the one Emory patient with RS result 25 did not experience pCR, sensitivity analyses re-categorizing them to group C only impacted the denominators. Significance for differences did not shift (results not shown). | PMC10147793 |
Discussion | RS, N0), breast cancer, toxicities, early-stage HR, tumors | RECURRENCE, BREAST CANCER, DISEASE, SECONDARY, EVENTS, TUMORS | In this study, we observed that patients with intermediate RS results had no statistically significant differences in pathologic outcomes at the time of surgery based on whether they received neoadjuvant endocrine therapy or neoadjuvant chemotherapy. While our study did not include secondary analyses of pCR based on lymph node involvement or menopausal status among RS groups, the results suggest that a subgroup of women with a RS 0–25 may omit chemotherapy without compromising rates of clinical and pathologic complete response. This aligns with data from the Trial Assigning Individualized Options for Treatments (TAILORx), establishing no benefit of chemotherapy among women over the age of 50 years with HR + node-negative (N0) breast cancer and RS 11–25, as well as RxPONDER, which demonstrated that postmenopausal women with HR + node-positive (1–3 positive nodes) breast cancer and RS ≤ 25 can safely avoid chemotherapy [Our study findings suggest that the RS result may be an impactful tool to help guide treatment decisions in the neoadjuvant setting and reinforces the clinical feasibility of the RS assay using core biopsy specimens. The use of NET, which has been more often used in Europe than in the US, is a reasonable approach to downstaging some HR + tumors to allow de-escalation of surgery, particularly to allow breast conservation that might otherwise not be possible. Currently validated for use in the adjuvant setting, gene expression profiles like the Oncotype DX assay and the 70-gene signature MammaPrint assay have significantly contributed to better understanding of the heterogeneity among early-stage HR + breast cancer and, in doing so, have decreased the number of women exposed to the potential toxicities of chemotherapy [Ongoing trials evaluating the use of neoadjuvant endocrine therapy in combination with cyclin-dependent kinase (CDK) 4/6 inhibitors have shown promising results [Finally, it is important to note the difference in duration of neoadjuvant endocrine therapy between the two institutions. Despite patients in the Emory cohort receiving significantly longer courses of neoadjuvant endocrine therapy (median 10 months versus 5.5), there were no significant differences in pCR across RS result groups between the two institutions, and nearly three quarters of the VCU patients were able to receive breast-conserving treatment despite the pre-treatment assessment that they would require total mastectomies. Duration of neoadjuvant endocrine therapy has historically ranged from 12 to 24 weeks, although adequate duration to optimize outcomes has not been defined [Limitations of this study include the narrow scope in assessing pCR, lack of long-term follow-up and limited number of premenopausal patients. We did not assess the differences in side effects (both immediate or long-term) between treatment groups, nor did we evaluate for differences in disease recurrence. While the difference in RS result groupings (11–24 for Emory, 11–25 for VCU) created an inconsistency between studies, the sensitivity analysis illustrated that it had no impact on the results. Due to the low number of patients as described above and events for each study, we were unable to provide more than a descriptive explanation of the study differences. We explored adjusted analyses accounting for random effects of study and fixed effects for variables including length of endocrine therapy to determine the impact of differences between studies on pooling the data, but were unable to achieve model convergence. Finally, secondary analyses of data from previously designed studies can be subject to bias, even though these two studies had similar objectives. Despite these limitations, this study importantly highlights the potential for the Oncotype DX assay use in the neoadjuvant setting for therapeutic decision-making and the impact this may have on further personalizing treatment plans for a large group of patients with breast cancer. | PMC10147793 |
Authors' contribution | All authors contributed to the study conception and design. The first draft of the manuscript was written by Caitlin Taylor and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. | PMC10147793 | ||
Funding | The authors have not disclosed any funding. | PMC10147793 | ||
Data availability | Enquiries about data availability should be directed to the authors. | PMC10147793 | ||
Declarations | PMC10147793 | |||
Conflicts of interest | Author Russell is an employee of and owns stock in Exact Sciences. Author Foreman is a former employee of Exact Sciences. Author Meisel has conflicts of interest caused by honoraria as follows: AstraZeneca, Clovis, Genentech, Glaxo SmithKline, Novartis, Pfizer, Puma, Sanofi Genzyme, and Seagen. She also has conflicts of interest caused by research grants or other funding from Seagen, Pfizer, and Olema. The remaining authors have no conflicts of interest. | PMC10147793 | ||
References | PMC10147793 | |||
Abstract | PMC10020803 | |||
Background | Iniparib (BSI-201), a novel anticancer agent thought to have poly(ADP-ribose) polymerase (PARP) inhibitory activity and synergy with both gemcitabine and carboplatin (GC) was evaluated in 2 cohorts with GC. | PMC10020803 | ||
Methods | platinum-sensitive, primary peritoneal carcinoma | PRIMARY PERITONEAL CARCINOMA, DISEASE, EPITHELIAL OVARIAN CARCINOMA, FALLOPIAN TUBE CANCER | Parallel multicenter, single-arm, phase II studies using a Simon two-stage design. Eligible patients had a histological diagnosis of epithelial ovarian carcinoma, fallopian tube cancer, or primary peritoneal carcinoma and demonstration of platinum-sensitive (≥6 months [mo]) or -resistant disease (relapse 2-6 mo post-platinum). Carboplatin (AUC 4 IV day 1), gemcitabine (1000 mg/m | PMC10020803 |
Results | DISEASE | The overall response rate (ORR RECIST 1.0) in platinum sensitive disease was 66% (95% CI, 49-80) with a higher response rate in the 15 pts with germline | PMC10020803 | |
Conclusions | ovarian cancer, platinum-sensitive ovarian cancer, platinum-sensitive, -resistant recurrent | BREAST CANCER | Given the subsequent lack of efficacy demonstrated for iniparib in breast cancer, these are studies of GC and demonstrate a higher than traditionally appreciated activity in patients with platinum-sensitive and -resistant recurrent ovarian cancer, especially in patients that harbor a This article evaluates the potential efficacy of iniparib in combination with gemcitabine and carboplatin in platinum-sensitive ovarian cancer. | PMC10020803 |
Implications for Practice | Controlled trials are essential to define standards of care. | PMC10020803 | ||
Background | cancer, Ovarian cancer, PD, Arbeitsgemeinschaft Gynaekologische, platinum-sensitive recurrent ovarian cancer, deaths, tumors | RECURRENCES, GYNECOLOGIC CANCER, CANCER, DISEASE, OVARIAN CANCER, TUMORS | Ovarian cancer is a devastating disease with the highest mortality rate of all gynecologic tumors, with an estimated 22 280 new diagnoses and 14 240 deaths annually in the United States, and is the 8th most common cancer in women worldwide.Approximately one-third of recurrences occur within 6 months of last platinum and are arbitrarily defined as “platinum resistant,” while the majority occur later and are potentially platinum sensitive. The Gynecologic Cancer Inter-Group (GCIG) has helpfully defined 4 categories: platinum refractory (radiologically confirmed progressive disease (PD) on platinum or within one month), resistant (PD in >1-<6 months), partially sensitive (6-12 months), and sensitive (>12 months).Pfisterer et al. conducted the randomized controlled trial (RCT) through the AGO (Arbeitsgemeinschaft Gynaekologische Onkologie) which demonstrated a progression free survival (PFS) advantage for gemcitabine plus carboplatin over single agent carboplatin in patients with platinum-sensitive recurrent ovarian cancer,Iniparib (4-iodo-3-nitrobenzamide) is a novel, highly lipophilic investigational anticancer agent that distributes rapidly and widely into tissues. It is metabolized via a nitro-reduction pathway to a potent nitroso metabolite that binds covalently and irreversibly to PARP1.PARP1 is a critical enzyme in DNA repair and may play a role in resistance to chemotherapy. Inhibiting PARP exploits the synthetic lethality of impaired homologous recombination set up by These 2 studies were designed to evaluate the potential efficacy of this combination in platinum sensitive disease and whether the addition of iniparib and gemcitabine could overcome platinum resistance. | PMC10020803 |
Methods | The studies underwent formal IRB review and were registered at clinicaltrials.gov (Sensitive: NCT01033123; Resistant: NCT01033292). Each study was designed as a multi-center, single-arm phase 2 using a Simon 2-stage design. In both studies, the primary endpoint was objective response rate (ORR), evaluated in all patients who received at least 1 dose of study drug and had 2 post-baseline assessments or progression/death within 60 days of last assessment. Secondary endpoints were progression free survival (PFS) and safety using NCI-CTCAE v3.0. A CA125 response was defined as 50% fall in CA125 initially >2× ULN and maintained for at least 28 days. A prospectively planned exploratory analysis of the relation between | PMC10020803 | ||
Treatment | The regimen (GCI) consisted of gemcitabine given without fixed-dose rate adjustment over 30 min at 1000 mg/m | PMC10020803 | ||
Patient Eligibility | primary peritoneal carcinoma | PRIMARY PERITONEAL CARCINOMA, DISEASE, EPITHELIAL OVARIAN CANCER, FALLOPIAN TUBE CANCER | Key eligibility criteria included having epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal carcinoma, measurable disease per RECIST 1.1 criteria, and ECOG performance status 0-2.Platinum-sensitive disease was defined as radiological relapse >6 months after the last dose of platinum or platinum-based chemotherapy and required that participants had received no prior cytotoxic chemotherapy in the recurrent setting. Platinum-resistant disease was defined as radiologically confirmed relapse within 2-6 months of platinum-based therapy, and patients could have at least 1 but not more than 2 prior therapies. Patients with or without | PMC10020803 |
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