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The physical and emotional burden of relapsed or refractory multiple myeloma (RRMM) has been strongly correlated with declining health-related quality of life (QOL) in the patients it affects. This analysis evaluated patient-reported outcomes (PROs) from B-cell maturation antigen (BCMA)-naive (n = 123) and -exposed (n = 64) patients with RRMM enrolled in the MagnetisMM-3 study (NCT04649359) and treated with the humanized, bispecific BCMA-CD3 antibody elranatamab. Patients received two step-up doses of elranatamab (12 mg on day 1, 32 mg on day 4) before starting the full dose of 76 mg on day 8 (each cycle = 28 days). Global health status, functioning and symptom data were collected electronically using validated and myeloma-specific questionnaires. Improvements in PROs occurred early, with marked reductions in pain and disease symptoms and notable improvements in patients' outlook for their future health. Additionally, 40.2% of BCMA-naive and 52.6% of BCMA-exposed patients perceived their disease as 'a little better' or 'much better' by Cycle 1, Day 15. The results from this analysis demonstrated that elranatamab maintained or improved symptomology and general health status, regardless of prior BCMA-directed therapy. Thus, in addition to its clinical benefits, elranatamab therapy may sustain or improve QOL in heavily pretreated patients with RRMM.
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Mieloma Múltiplo , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Biespecíficos/uso terapêutico , Anticorpos Biespecíficos/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígeno de Maturação de Linfócitos B , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/psicologiaRESUMO
Elranatamab efficacy in the single-arm, registrational MagnetisMM-3 trial (NCT04649359) was compared with that of physician's choice of treatment (PCT) for triple-class refractory multiple myeloma. MagnestisMM-3 eligibility criteria were applied to two USA-based oncology electronic health record databases, COTA and Flatiron Health (FH), to identify cohorts for this study (NCT05932290). Applied statistical techniques accounted for cohort imbalances. MagnetisMM-3 (BCMA-naive; n = 123) outcomes were compared with those from COTA (n = 239) and FH (n = 152). Elranatamab was associated with a significantly higher objective response rate (risk ratios, 1.88-2.25), significantly longer progression-free survival (hazard ratios [HRs], 0.37-0.57), and, across most analyses, significantly longer overall survival (HRs, 0.46-0.66) versus PCT. BCMA-naive patients who were treated with elranatamab exhibited significantly better outcomes than patients treated in real-world clinical practice.
Elranatamab is a new medicine for the treatment of people with multiple myeloma. In the ongoing clinical trial MagnetisMM-3, most people had fewer myeloma cells when treated with elranatamab. However, MagnetisMM-3 only looks at the effects of elranatamab without comparing it to other myeloma treatments. Therefore, a new study was designed to compare the effectiveness of elranatamab in the MagnetisMM-3 study with other treatments used in real-world clinical practice (not in a clinical trial). Data from people in MagnetisMM-3 was compared with data from two US databases (COTA and Flatiron Health) containing health records of patients treated for multiple myeloma in real-life clinical practice. The same criteria used to select patients for the MagnetisMM-3 trial (123 people) were used to identify people with similar characteristics in COTA (239 people) and Flatiron Health (152 people). More people treated with elranatamab had fewer myeloma cells in their bodies after treatment than people who received their doctor's choice of treatment in clinical practice. In fact, six out of ten people treated with elranatamab had fewer myeloma cells versus about three in ten people from each real-world database. People treated with elranatamab versus physician's choice of treatment lived longer without their disease getting worse and lived longer overall. In conclusion, this study found that more people treated with elranatamab responded to treatment and lived longer than similar people from the COTA and Flatiron Health databases who were given treatments available in a real-world clinical setting.Clinical Trial Registration: NCT05932290 (ClinicalTrials.gov).
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Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Intervalo Livre de Progressão , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Idoso de 80 Anos ou mais , AdultoRESUMO
Patient-reported outcomes (PROs), such as symptoms, functioning, and other health-related quality-of-life concepts are gaining a more prominent role in the benefit-risk assessment of cancer therapies. However, varying ways of analysing, presenting, and interpreting PRO data could lead to erroneous and inconsistent decisions on the part of stakeholders, adversely affecting patient care and outcomes. The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints in Cancer Clinical Trials-Innovative Medicines Initiative (SISAQOL-IMI) Consortium builds on the existing SISAQOL work to establish recommendations on design, analysis, presentation, and interpretation for PRO data in cancer clinical trials, with an expanded set of topics, including more in-depth recommendations for randomised controlled trials and single-arm studies, and for defining clinically meaningful change. This Policy Review presents international stakeholder views on the need for SISAQOL-IMI, the agreed on and prioritised set of PRO objectives, and a roadmap to ensure that international consensus recommendations are achieved.
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Neoplasias , Qualidade de Vida , Humanos , Medidas de Resultados Relatados pelo Paciente , Neoplasias/tratamento farmacológico , ConsensoRESUMO
OBJECTIVES: To have confidence in one's interpretation of treatment effects assessed by comparing trial results to external controls, minimizing bias is a critical step. We sought to investigate different methods for causal inference in simulated data sets with measured and unmeasured confounders. METHODS: The simulated data included three types of outcomes (continuous, binary, and time-to-event), treatment assignment, two measured baseline confounders, and one unmeasured confounding factor. Three scenarios were set to create different intensities of confounding effect (e.g., small and blocked confounding paths, medium and blocked confounding paths, and one large unblocked confounding path for scenario 1 to 3, respectively) caused by the unmeasured confounder. The methods of g-computation (GC), inverse probability of treatment weighting (IPTW), overlap weighting (OW), standardized mortality/morbidity ratio (SMR), and targeted maximum likelihood estimation (TMLE) were used to estimate average treatment effects and reduce potential biases. RESULTS: The results with the greatest extent of biases were from the raw model that ignored all the potential confounders. In scenario 2, the unmeasured factor indirectly influenced the treatment assignment through a measured controlling factor and led to medium confounding. The methods of GC, IPTW, OW, SMR, and TMLE removed most of bias observed in average treatment effects for all three types of outcomes from the raw model. Similar results were found in scenario 1, but the results tended to be biased in scenario 3. GC had the best performance followed by OW. CONCLUSIONS: The aforesaid methods can be used for causal inference in externally controlled studies when there is no large, unblockable confounding path for an unmeasured confounder. GC and OW are the preferable approaches.
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Projetos de Pesquisa , Humanos , Pontuação de Propensão , Funções Verossimilhança , Simulação por Computador , ViésRESUMO
OBJECTIVES: The FDA recommends the use of anchor-based methods and empirical cumulative distribution function (eCDF) curves to establish a meaningful within-patient change (MWPC) for a clinical outcome assessment (COA). In practice, the estimates obtained from model-based methods and eCDF curves may not closely align, although an anchor is used with both. To help interpret their results, we investigated and compared these approaches. METHODS: Both repeated measures model (RMM) and eCDF approaches were used to estimate an MWPC on a target COA. We used both real-life (ClinicalTrials.gov: NCT02697773) and simulated data sets that included 688 patients with up to six visits per patient, target COA (range 0 to 10), and an anchor measure on patient global assessment of osteoarthritis from 1 (very good) to 5 (very poor). Ninety-five percent confidence intervals for the MWPC were calculated by the bootstrap method. RESULTS: The distribution of the COA score changes affected the degree of concordance between RMM and eCDF estimates. The COA score changes from simulated normally distributed data led to greater concordance between the two approaches than did COA score changes from the actual clinical data. The confidence intervals of MWPC estimate based on eCDF methods were much wider than that by RMM methods, and the point estimate of eCDF methods varied noticeably across visits. CONCLUSIONS: Our data explored the differences of model-based methods over eCDF approaches, finding that the former integrates more information across a diverse range of COA and anchor scores and provides more precise estimates for the MWPC.
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Animal studies support RCT findings of improved liver function and short-term benefits using repurposed Granulocyte Colonic Stimulating Factor GCSF in adults with decompensated cirrhosis. We describe the protocol for phase 2 RCT of sequential Kasai-GCSF under an FDA-approved IND to test that GCSF improves early bile flow and post-Kasai biliary atresia BA clinical outcome. Immediate post-Kasai neonates, age 15-180 days, with biopsy-confirmed type 3 BA, without access to early liver transplantation, will be randomized 1:1 to standard of care SOC + GCSF at 10 ug/kg in 3 daily doses within 4 days of Kasai vs SOC + NO-GCSF (ClinicalTrials.gov NCT0437391). They will be recruited from children's hospitals in Vietnam, Pakistan and one US center. The primary objective is to demonstrate that GCSF decreases the proportion of subjects with a 3-month post-Kasai serum Total Bilirubin ≥ 34 umol/L by 20%, (for a = 0.05, b = 0.80, i.e., calculated sample size of 218 subjects). The secondary objectives are to demonstrate that the frequency of post-Kasai cholangitis at 6-month and 24-month transplant-free survival are improved. The benefits are that GCSF is an affordable BA adjunct therapy, especially in developing countries, to improve biliary complications, enhance quality of liver and survival while diminishing costly liver transplantation.Clinical trial registration: A phase 1 for GCSF dose and safety determination under ClinicalTrials.gov identifier NCT03395028 was completed in 2019. The current Phase 2 trial was registered under NCT04373941.
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Atresia Biliar , Transplante de Fígado , Atresia Biliar/complicações , Atresia Biliar/tratamento farmacológico , Atresia Biliar/cirurgia , Ensaios Clínicos Fase II como Assunto , Fatores Estimuladores de Colônias/uso terapêutico , Granulócitos , Humanos , Lactente , Recém-Nascido , Estudos Multicêntricos como Assunto , Portoenterostomia Hepática/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: Incident onset and survival outcomes involve multiple risk factors and complex interactions preferably investigated in a single study. A generalized structural equation model (GSEM) was used to build an integrative framework to analyse multiple risk factors for incident rheumatoid arthritis (RA) and factors affecting long-term survival outcome. METHODS: Incident RA cases (n=54) had onsets between 1977 and 1994, after cohort entry in 1974. Four cohort control (CN) subjects (n=216) were matched on entry to each case in the community-based CLUE cohort and 270 subjects were followed from 1995 through 2017. Baseline variables included demographic, RA family history, behavioural factors and z-score levels of serum immunological, cytokine, isotype rheumatoid factors (RFs), adrenal steroids, luteinising hormone, prolactin and sex steroids. Four numerical integration methods of GSEM were performed in Stata 15. RESULTS: Cohort entry factors predicting RA onset included family history of RA, cigarette smoking and IgM RF. Total survival time from cohort entry was associated with incident RA and baseline variables of age, years of completed education, cigarette smoking, immunoreactive proteins and androgenic-anabolic steroids. Mortality of RA was significantly greater than CN subjects for cases having less than good therapy responses in 1995 and only for RA onset before age 60 years. Androgenic-anabolic steroid z-scores significantly correlated with improved survival only in CN subjects with assigned onset before the age of 60. CONCLUSIONS: Successful use of GSEM is feasible in analyses of prospective incident and subsequent survival data and promises to advance understanding of risk factors, survival, and casual pathways.
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Artrite Reumatoide , Fator Reumatoide , Estudos de Casos e Controles , Estudos de Coortes , Humanos , Estudos Prospectivos , Fatores de RiscoRESUMO
Background: Achieving postsurgical pain control after total hip arthroplasty (THA) is a critical factor for successful recovery because inadequately treated pain may lead to a delay in ambulation and hospital discharge and have an adverse impact on a patient's quality of life. Objective: This study compares the effectiveness of immediate-release local anesthetics for pain control in THA vs liposomal bupivacaine (LB) related to patient outcomes and costs of care. Methods: This is a retrospective cohort study of consecutive patients undergoing THA at 3 hospitals from January 2013 to July 2016. The control group received plain bupivacaine or ropivacaine while the study group received LB. Generalized linear models were used controlling for several patient factors. Primary measures included length of stay (LOS), hospitalization costs, pain relief, opioid use, and mobility. Secondary outcomes were discharge disposition and 30-, 60-, and 90-day readmissions. Results: One hundred and ninety-six patients were identified, with 103 as controls, 70 receiving LB, and 23 excluded. The LB group showed a decrease in LOS of 0.5 days (2.5 ± 2.6 vs 3.0 ± 2.1 days, P = .010), increased mobility on the day of surgery (27.6 ± 49.3 vs 12.5 ± 48.5 feet, P = .001) and the first day after surgery (186.8 ± 133.8 vs 155.2 ± 135.6, P = .039), and decreased hospital costs ($10 670 vs $11 351, P = .022). There were no significant differences in pain scores, opioid use, adverse events, discharge disposition, or readmissions. Study limitations include retrospective analysis, unblinded participants, and generalizability of results. Conclusions: LB provides an effective alternative to standard local anesthetics in patients undergoing THA based on improvements of inpatient parameters, LOS, and cost measures.
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BACKGROUND: China's growing population of internal migrants has exceeded 236 million. Driven by rapid development and urbanization, this extreme population mobility creates opportunities for transmission of HIV and sexually-transmitted infections (STI). Large numbers of rural migrants flock to megacities such as Shanghai in search of employment. Although migrants constitute a key population at heightened risk of acquiring HIV or an STI, there is a lack of easily accessible sexual health services available for them. In response, we designed a short, inexpensive sexual health intervention that sought to improve HIV and STI knowledge, while reducing stigma, risky sexual behaviour, and sexual transmission of HIV and STI among migrant construction workers (MCW) situated in Shanghai, China. RESULTS: We implemented a three-armed, community-randomized trial spread across three administrative districts of Shanghai. The low-intensity intervention included educational pamphlets. The medium-intensity intervention included pamphlets, posters, and videos. The high-intensity intervention added group and individual counselling sessions. Across 18 construction sites, 1871 MCW were allocated at baseline to receive one intervention condition. Among baseline participants, 1304 workers were retained at 3-months, and 1013 workers were retained at 6-months, representing a total of 579 person-years of follow-up. All workers, regardless of participation, had access to informational materials even if they did not participate in the evaluation. Overall outputs included: 2284 pamphlets distributed, 720 posters displayed, 672 h of video shown, 376 participants accessed group counselling, and 61 participants attended individual counselling sessions. A multivariable analysis of participation found that men (aOR = 2.2; 95 % CI 1.1, 4.1; p = 0.036), workers situated in Huangpu district (aOR = 5.0; 95 % CI 2.6, 9.5; p < 0.001), and those with a middle school education (aOR = 1.9; 95 % CI 1.2, 3.0; p = 0.01) were more likely to have participated in intervention activities. CONCLUSION: A brief educational intervention that prioritized ease of delivery to a highly mobile workforce was feasible and easily accessed by participants. Routine implementation of sexual health interventions in workplaces that employ migrant labour have the potential to make important contributions toward improving HIV and STI outcomes among migrant workers in China's largest cities.
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BACKGROUND: Female sex workers (FSWs) are at risk for sexually transmitted infections (STIs), including HIV. We implemented an HIV/STI preventive intervention among FSWs in Shanghai that aimed to increase condom use, improve HIV knowledge, and reduce STI and HIV incidence. METHODS: From six districts in Shanghai, 750 randomly selected venue-based FSWs were allocated to either a behavioural intervention or control group. In the intervention and control groups, 221 and 278 participants, respectively, had at least one follow-up at three or six months. In analysis, we randomly selected 57 lost to follow-up cases in the intervention group and imputed baseline values to equalize the arms at n = 278 (74.1% follow-up rate in each group). The impacts of the intervention on condom use, HIV/STI risk perception and knowledge, and STI incidence were assessed using either a logistic or linear model, adjusting for the baseline measure of the outcome and venue type. RESULTS: The intervention improved consistent condom use with any partner type in the previous month (AOR = 2.09, 95% CI, 1.43-3.04, p = 0.0001). Consistent condom use with clients in the three most recent sex acts increased in both arms, and with primary partners in the intervention arm, but there was no difference between groups after adjusting for baseline condom use and venue type. There were no differences in cumulative incidence of any STI (i.e., chlamydia, gonorrhoea, syphilis) between groups. HIV transmission knowledge (p = 0.0001), condom use skill (p = 0.0421), and self-efficacy for using condoms (p = 0.0071) were improved by the intervention. HIV-related stigma declined (p = 0.0119) and HIV and STI risk perception were improved (4.6 to 13.9%, and 9.4 to 20.0%, respectively). The intervention was associated with these improvements after adjusting for the baseline measure and venue type. CONCLUSION: Following a preventive intervention among Shanghai FSWs, our findings demonstrate that a simple, community-based educational intervention improved overall condom use, HIV and STI knowledge, and attitudes in relation to HIV/AIDS. The intervention should be implemented widely after tailoring educational materials regarding condom negotiation with different partner types (i.e., commercial sex clients and primary partners).
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Preservativos/estatística & dados numéricos , Infecções por HIV/prevenção & controle , Educação em Saúde/organização & administração , Conhecimentos, Atitudes e Prática em Saúde , Profissionais do Sexo , Adolescente , Adulto , China , Feminino , Infecções por HIV/epidemiologia , Humanos , Incidência , Perda de Seguimento , Masculino , Assunção de Riscos , Sexo Seguro , Autoeficácia , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/prevenção & controle , Estigma Social , Fatores Socioeconômicos , Adulto JovemRESUMO
BACKGROUND: In most biological experiments, especially infectious disease, the exposure-response relationship is interrelated by a multitude of factors rather than many independent factors. Little is known about the suitability of ordinary, categorical exposures, and logarithmic transformation which have been presented in logistic regression models to assess the likelihood of an infectious disease as a function of a risk or exposure. This study aims to examine and compare the current approaches. METHODS: A simulated human immunodeficiency virus (HIV) population, dynamic infection data for 100,000 individuals with 1% initial prevalence and 2% infectivity, was created. Using the Monte Carlo method (computational algorithm) to repeat random sampling to obtain numerical results, linearity between log odds and exposure, and suitability in practice were examined in the three model approaches. RESULTS: Despite diverse population prevalence, the linearity was not satisfied between log odds and raw exposures. Logarithmic transformation of exposures improved the linearity to a certain extent, and categorical exposures satisfied the linear assumption (which was important for modelling). When the population prevalence was low (assumed < 10%), performances of the three models were significantly different. Comparing to ordinary logistic regression, the logarithmic transformation approach demonstrated better accuracy of estimation except that at the two inflection points: likelihood of infection increased from slowly to sharply, then slowly again. The approach using categorical exposures had better estimations around the real values, but the measurement was coarse due to categorization. CONCLUSIONS: It is not suitable to directly use ordinary logistic regression to explore the exposure-response relationship of HIV as an infectious disease. This study provides some recommendations for practical implementations including: 1) utilize categorical exposure if a large sample size and low population prevalence are provided; 2) utilize a logarithmic transformed exposure if the sample size is insufficient or the population prevalence is too high (such as 30%).
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Infecções por HIV/transmissão , Simulação por Computador , Feminino , Infecções por HIV/epidemiologia , Humanos , Modelos Logísticos , Masculino , Método de Monte Carlo , Análise de Regressão , RiscoRESUMO
A random-effects model is often applied in meta-analysis when considerable heterogeneity among studies is observed due to the differences in patient characteristics, timeframe, treatment regimens, and other study characteristics. Since 2014, the journals Research Synthesis Methods and the Annals of Internal Medicine have published a few noteworthy papers that explained why the most widely used method for pooling heterogeneous studies-the DerSimonian-Laird (DL) estimator-can produce biased estimates with falsely high precision and recommended to use other several alternative methods. Nevertheless, more than half of studies (55.7%) published in top oncology-specific journals during 2015-2022 did not report any detailed method in the random-effects meta-analysis. Of the studies that did report the methodology used, the DL method was still the dominant one reported. Thus, while the authors recommend that Research Synthesis Methods and the Annals of Internal Medicine continue to increase the publication of its articles that report on specific methods for handling heterogeneity and use random-effects estimates that provide more accurate confidence limits than the DL estimator, other journals that publish meta-analyses in oncology (and presumably in other disease areas) are urged to do the same on a much larger scale than currently documented.
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Oncologia , Metanálise como Assunto , Humanos , Projetos de PesquisaRESUMO
BACKGROUND: The appointment-based model (ABM) is a pharmacy service to improve medication-related health outcomes. ABM involves medication synchronization and medication review, plus other services such as medication reconciliation, medication therapy management, vaccine administration, and multimedication packaging. ABM can improve medication adherence, but the economic impact is unknown. OBJECTIVE: To assess the effect of a national pharmacy chain's ABM program for Medicare Advantage beneficiaries on total cost of care (TCOC). METHODS: This study analyzed administrative claims data from April 7, 2017, through February 29, 2020, for Medicare Advantage beneficiaries with Part D using a propensity score-matched cohort design. The national pharmacy chain provided a list of ABM participants. Eligibility criteria for the ABM and control (non-ABM) groups included age 65 years or older on the index date (initial participation, ABM; random fill date, control) and continuous enrollment from at least 6 months pre-index (baseline) date through at least 6 months post-index (follow-up) date. Medical inflation-adjusted (2020) TCOC was calculated as the sum of all health care spending from Medicare Advantage beneficiaries with Part D plan and patient paid amounts, standardized to per patient per month (PPPM), during the follow-up period. Secondary outcomes included medication adherence calculated across prevalent maintenance therapeutic classes using proportion of days covered (PDC). RESULTS: Each group contained 5,225 patients with balanced characteristics after matching: 64% female, 73% White, mean age 75 years, mean Quan-Charlson comorbidity index score 0.9, and hypertension and dyslipidemia, each >65%. Median baseline all-cause PPPM health care costs in the ABM and control groups, respectively, were $517 and $548 ($221 and $234 medical, $135 and $164 pharmacy). Baseline PDC of at least 80% was 83% in the ABM group and, similarly, 84% in the control group. The mean (SD) follow-up was 604 (155) days for the ABM group and 598 (151) days for the control group. During the follow-up period, the median PPPM TCOC for the ABM group was $656 and was $723 for the control group (P = 0.011). Median pharmacy costs were also significantly less in the ABM group ($161 vs $193, P < 0.001), whereas median medical costs were $328 in the ABM group and $358 among controls (P = 0.254). More patients in the ABM group were adherent during follow-up, with 84% achieving PDC of at least 80% vs 82% among controls (P = 0.009). CONCLUSIONS: The ABM program was associated with significantly lower follow-up median total costs (medical and pharmacy), driven primarily by pharmacy costs. More patients were adherent in the ABM program. Payers and pharmacies can use this evidence to assess ABM programs for their members.
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Custos de Cuidados de Saúde , Medicare Part C , Adesão à Medicação , Humanos , Estados Unidos , Idoso , Feminino , Masculino , Medicare Part C/economia , Idoso de 80 Anos ou mais , Custos de Cuidados de Saúde/estatística & dados numéricos , Agendamento de Consultas , Assistência Farmacêutica/economia , Conduta do Tratamento Medicamentoso/economia , Medicare Part D/economia , Estudos de CoortesRESUMO
Objective: Patients with triple-class refractory (TCR) multiple myeloma (MM) have limited treatment options and poor prognoses. This high unmet need has prompted the development of new therapies allowing for improved outcomes for these patients. Recently, new targeted therapies for the treatment of patients with relapsed or refractory MM have been approved based on single-arm clinical trial results. Real-world (RW) data enable a better understanding of the effectiveness of new therapies in clinical practice and provide external controls for single-arm studies. However, using RW data to identify patients with TCR MM is challenging and subject to limitations. Methods: In this retrospective cohort study of an analysis of the COTA electronic health record (EHR) database, we used four algorithms to define refractory status and created four groups of patients with TCR MM initiating post-TCR therapy. Each algorithm relied on slightly different criteria to identify TCR patients, but all were based on the International Myeloma Working Group (IMWG)-derived and/or healthcare provider (HCP)-reported progressions within the database. Results: A total of 3815 patients with newly diagnosed MM met the eligibility criteria for this study. The choice of the algorithm did not impact the characteristics of identified patients with TCR MM (Algorithm 1 [n = 404], Algorithm 2 [n = 123], Algorithm 3 [n = 404], and Algorithm 4 [n = 375]), including their demographic and disease characteristics, MM treatment history, or treatment patterns received after becoming TCR. However, identifying TCR MM using a combination of IMWG-derived and HCP-reported progressions allowed up to a 70% increase in the size of the identified group of patients compared with using only IMWG-derived progressions. Conclusion: In RW settings, progressions from both IMWG-derived data and physician reports may be used to identify patients with TCR MM.
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Algoritmos , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Registros Eletrônicos de Saúde , Resistencia a Medicamentos Antineoplásicos , AdultoRESUMO
OBJECTIVE: The aim of the study is to estimate COVID-19 absenteeism and indirect costs, by care setting. METHODS: A population-based retrospective cohort study using data from the German Statutory Health Insurance (SHI) database to define outpatient (April 2020-December 2021) and hospitalized (April 2020-October 2022) cohorts of employed working-aged individuals. RESULTS: In the outpatient cohort ( N = 369,220), median absenteeism duration and associated cost was 10.0 (Q1, Q3: 5.0, 15.0) days and 1061 (530, 1591), respectively. In the hospitalized cohort ( n = 20,687), median absenteeism and associated cost was 15.0 (7.0, 32.0) days and 1591 (743, 3394), respectively. Stratified analyses showed greater absenteeism in older workers, those at risk, and those with severe disease. CONCLUSIONS: The hospitalized cohort had longer absenteeism resulting in higher productivity loss. Being older, at risk of severe COVID-19 and higher disease severity during hospitalization were important drivers of higher absenteeism duration.
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Absenteísmo , COVID-19 , Eficiência , Hospitalização , Humanos , COVID-19/economia , COVID-19/epidemiologia , Alemanha/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Hospitalização/estatística & dados numéricos , Hospitalização/economia , SARS-CoV-2 , Efeitos Psicossociais da Doença , Adulto Jovem , IdosoRESUMO
BACKGROUND: Long COVID has become a central public health concern. This study characterized the effectiveness of BNT162b2 BA.4/5 bivalent COVID-19 vaccine (bivalent) against long COVID symptoms. METHODS: Symptomatic US adult outpatients testing positive for SARS-CoV-2 were recruited between 2 March and 18 May 2023. Symptoms were assessed longitudinally using a CDC-based symptom questionnaire at Week 4, Month 3, and Month 6 following infection. The odds ratio (OR) of long COVID between vaccination groups was assessed by using mixed-effects logistic models, adjusting for multiple covariates. RESULTS: At Week 4, among 505 participants, 260 (51%) were vaccinated with bivalent and 245 (49%) were unvaccinated. Mean age was 46.3 years, 70.7% were female, 25.1% had ≥1 comorbidity, 43.0% prior infection, 23.0% reported Nirmatrelvir/Ritonavir use. At Month 6, the bivalent cohort had 41% lower risk of long COVID with ≥3 symptoms (OR: 0.59, 95% CI, 0.36-0.96, p = 0.034) and 37% lower risk of ≥2 symptoms (OR: 0.63, 95% CI, 0.41-0.96, p = 0.030). The bivalent cohort reported fewer and less durable symptoms throughout the six-month follow-up, driven by neurologic and general symptoms, especially fatigue. CONCLUSIONS: Compared with unvaccinated participants, participants vaccinated with the bivalent were associated with approximately 40% lower risk of long COVID and less symptom burden over the six-month study duration.
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The appropriate use of regulatory agilities has the potential to accelerate regulatory review, utilize resources more efficiently and deliver medicines and vaccines more rapidly, all without compromising quality, safety and efficacy. This was clearly demonstrated during the COVID-19 pandemic where regulators and industry rapidly adapted to ensure continued supply of existing critical medicines and review and approve new innovative medicines. In this retrospective study, we analyze the impact of regulatory agilities on the review and approval of Pfizer/BioNTech's BNT162b2 mRNA COVID-19 Vaccine globally using regulatory approval data from 73 country/regional approvals. We report on the critical role of reliance and provide evidence that demonstrates reliance approaches and certain regulatory agilities reduced review times for the COVID-19 vaccine. These findings support the case for more widespread implementation of regulatory agilities and demonstrate the important role of such approaches to improve public health outcomes.
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AIM: Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) are common types of non-Hodgkin's lymphoma, and real-world evidence continues to be lacking for healthcare costs and utilization among DLBCL and FL patients. Our study aims to describe medical and pharmacy costs and health resource utilization and to characterize longitudinal treatment patterns among these patients. METHODS: A retrospective observational study was performed among adult patients with DLBCL or FL using the US MarketScan (Truven) administrative claims data from 1 January 2007 to 31 December 2015. Diagnoses of DLBCL and FL were based upon ICD-9 codes. Identifications of treatment lines involved 30 lymphoma-specific anticancer systemic agents. Direct healthcare costs and utilizations were computed in the 1-year postdiagnosis period. Generalized linear models with a gamma link were used to compare healthcare costs between therapies with and without rituximab. RESULTS: A total of 2767 DLBCL and 5989 FL patients received frontline therapy. The majority received treatment within 3 months after initial diagnosis (DLBCL 79.9% and FL 62.4%) and were treated with rituximab or bendamustine either alone or in combination (DLBCL 67.4% and FL 84.7%). The total healthcare costs were US $15,555 and $10,192 per patient per month within 1 year following their initial diagnosis for DLBCL and FL, respectively. The medical costs were nearly twice as much as the drug costs for DLBCL patients. Both DLBCL and FL patients receiving rituximab had higher pharmacy costs but lower medical costs (p < 0.001). During the first year following initial diagnosis, the resource utilization (per patient per month) of DLBCL patients included 0.21 inpatient admissions, 0.26 radiation therapy, 2.63 outpatient or office visits, 0.18 emergency room visits, 0.06 intensive care unit admissions and 0.10 stem cell transplantation. FL patients occupied less health resources than DLBCL patients. CONCLUSION: The healthcare costs and health resources utilized were considerable in non-Hodgkin's lymphoma, especially DLBCL patients.
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Antineoplásicos/uso terapêutico , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/economia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/economia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/economia , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pesquisa Comparativa da Efetividade , Feminino , Gastos em Saúde/estatística & dados numéricos , Recursos em Saúde/economia , Recursos em Saúde/estatística & dados numéricos , Humanos , Linfoma Folicular/terapia , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rituximab/economia , Rituximab/uso terapêutico , Estados Unidos , Adulto JovemRESUMO
Youth gambling is an increasing concern. As a response, the "Don't Gamble Away our Future (DGAOF)" program has been implemented among children in central Illinois. We aim to assess the long-term effectiveness of this school-based youth gambling prevention program in Illinois using the data from 2005 to 2009. The intervention included interactive PowerPoint presentations and prevention materials in parent packets. Students aged 8 to 18 years were eligible to participate in the intervention and the questionnaire pre-post knowledge tests (total score 0-9). Students in 5th grade and above also received a gambling behavior screen test using the Modified South Oaks Gambling Screening for Teens (MSOGST) for identifying probable gamblers. Multivariable generalized mixed models were conducted to detect the effects of a 5-year youth gambling prevention program as controlling potential confounders. A total of 16,262 and 16,421 students completed pre-post tests and MSOGST tests, respectively. Of 16,262, half were female, the majority (76.1%) were from senior high school, and 21.3% received the intervention at least twice. The median gap between interventions was 368 days. Students receiving multiple interventions had higher scores on the pre-test as compared to those receiving a single intervention (P<0.001 for all comparisons among groups), and they demonstrated an increasing trend of awareness about gambling over time (P<0.001 for multiple interventions; P = 0.538 for single intervention). The prevalence of problem gambling had decreased among students receiving the intervention twice as compared to receiving the intervention once (7.9% versus 9.4%; OR = 0.89, 95% CL: 0.82-0.97). However, this effect was not confirmed among students receiving the intervention three or more times. In conclusion, the DGAOF program has demonstrated a positive long-term impact on increasing gambling knowledge and partially reducing pathological gamblers through direct training. It suggests that multiple repeated interventions are important for youth gambling prevention.