Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 11 de 11
Filter
1.
Epidemics ; 41: 100648, 2022 Nov 01.
Article in English | MEDLINE | ID: covidwho-2095324

ABSTRACT

OBJECTIVES: Disease transmission models are used in impact assessment and economic evaluations of infectious disease prevention and treatment strategies, prominently so in the COVID-19 response. These models rarely consider dimensions of equity relating to the differential health burden between individuals and groups. We describe concepts and approaches which are useful when considering equity in the priority setting process, and outline the technical choices concerning model structure, outputs, and data requirements needed to use transmission models in analyses of health equity. METHODS: We reviewed the literature on equity concepts and approaches to their application in economic evaluation and undertook a technical consultation on how equity can be incorporated in priority setting for infectious disease control. The technical consultation brought together health economists with an interest in equity-informative economic evaluation, ethicists specialising in public health, mathematical modellers from various disease backgrounds, and representatives of global health funding and technical assistance organisations, to formulate key areas of consensus and recommendations. RESULTS: We provide a series of recommendations for applying the Reference Case for Economic Evaluation in Global Health to infectious disease interventions, comprising guidance on 1) the specification of equity concepts; 2) choice of evaluation framework; 3) model structure; and 4) data needs. We present available conceptual and analytical choices, for example how correlation between different equity- and disease-relevant strata should be considered dependent on available data, and outline how assumptions and data limitations can be reported transparently by noting key factors for consideration. CONCLUSIONS: Current developments in economic evaluations in global health provide a wide range of methodologies to incorporate equity into economic evaluations. Those employing infectious disease models need to use these frameworks more in priority setting to accurately represent health inequities. We provide guidance on the technical approaches to support this goal and ultimately, to achieve more equitable health policies.

2.
HemaSphere ; 6:2024-2025, 2022.
Article in English | EMBASE | ID: covidwho-2032143

ABSTRACT

Background: MZL is the second most common lymphoma in older pts. Choosing an optimal treatment can be challenging because of patient-or disease-related risk factors and treatment-related toxicities (Curr Opin Oncol. 2019;31(5):386-393). Zanubrutinib is a potent, irreversible next-generation Bruton tyrosine kinase (BTK) inhibitor designed to maximize BTK occupancy and minimize off-target kinase inhibition, which may improve efficacy outcomes and minimize toxicities, such as cardiac arrythmias and bleeding events. Zanubrutinib received accelerated approval from the United States FDA for the treatment of pts with R/R MZL (Haematologica . 2022;107(1):35-43). Aims: We aim to present a subgroup analysis of efficacy and safety of zanubrutinib in pts aged ≥65 years with R/R MZL enrolled in MAGNOLIA (BGB-3111-214;NCT03846427). Methods: MAGNOLIA is a phase 2, multicenter, single-arm study of adults with R/R MZL who had received ≥1 line of therapy including ≥1 CD20-directed regimen. All were treated with zanubrutinib 160 mg twice daily until disease progression or unacceptable toxicity. Use of long-term antiplatelet and anticoagulation agents was permitted. The primary endpoint was overall response rate (ORR;complete response [CR] and partial response [PR]) determined by an independent review committee (IRC) in accordance with the Lugano classification. Secondary endpoints include ORR by investigator assessment (INV), duration of response (DOR), progression-free survival (PFS), and safety. All pts gave informed consent. Results: As of 18 January 2021, a total of 68 pts were enrolled (Table). Forty (61%) pts were ≥65 years old with a median age of 73 (range, 65-85);18 pts were ≥75 years old. Median number of prior therapies was 2 (range, 1-6) and 10 (25%) pts were refractory to last therapy. Most pts received prior rituximab + cyclophosphamide + vincristine + prednisone (48%) or bendamustine + rituximab (30%), while 5 (13%) pts received rituximab monotherapy. MZL subtypes included extranodal (n=17, 43%), nodal (n=14, 35%), and splenic (n=8, 20%). Median duration of treatment was 14.4 months (mo;range, 0.9-19.6). At a median follow-up of 15.8 mo (range, 2.8-21.8), ORR by IRC was 75% (CR 25%, PR 50%;Table). Responses were observed in all subtypes, with an ORR of 71%, 86%, and 75% in extranodal, nodal, and splenic subtypes, respectively (CR 41%, 21%, and 0%, respectively). Median DOR and PFS were not reached;15-month PFS was 87% and 12-month DOR was 93%. Most (63%) pts are continuing zanubrutinib. Treatment discontinuation due to disease progression was 28% by INV. Most common treatmentemergent adverse events (AEs) observed in ≥20% of pts include contusion (28%), diarrhea (25%), and constipation (20%). Grade ≥3 neutropenia occurred in 5% of pts. The most common infection was upper respiratory tract infection (10%). Two (5%) pts discontinued zanubrutinib due to unrelated fatal AEs (COVID-19 pneumonia and myocardial infarction in a patient with pre-existing coronary artery disease). Atrial fibrillation/flutter and hypertension occurred in 2 (5%) pts each and did not lead to treatment discontinuation. No pts required dose reductions, or experienced major or serious hemorrhage. Image: Summary/Conclusion: The safety profile of zanubrutinib observed in older pts was consistent with previously published results (Clin Cancer Res . 2021;27(23):6323-6332). Zanubrutinib was well tolerated and effective, as demonstrated by a high response rate and durable disease control in older pts with R/R MZL.

3.
biorxiv; 2022.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2022.03.28.486152

ABSTRACT

While humoral immune responses to infection or vaccination with ancestral SARS-CoV-2 have been well-characterized, responses elicited by infection with variants are less understood. Here we characterized the repertoire, epitope specificity, and cross-reactivity of antibodies elicited by Beta and Gamma variant infection compared to ancestral virus. We developed a high-throughput approach to obtain single-cell immunoglobulin sequences and isolate monoclonal antibodies for functional assessment. Spike-, RBD- and NTD-specific antibodies elicited by Beta- or Gamma-infection exhibited a remarkably similar hierarchy of epitope immunodominance for RBD and convergent V gene usage when compared to ancestral virus infection. Additionally, similar public B cell clones were elicited regardless of infecting variant. These convergent responses may account for the broad cross-reactivity and continued efficacy of vaccines based on a single ancestral variant.

4.
Science ; 372(6544):815-821, 2021.
Article in English | EMBASE | ID: covidwho-1735994

ABSTRACT

Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.

6.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.12.15.21267805

ABSTRACT

Data obtained on SARS-CoV-2 variant Omicron suggest that Omicron poses an increased risk of symptomatic breakthrough infections in people who receive only 2 doses of mRNA-1273. Administration of a booster mRNA vaccine may substantially reduce this risk.

7.
Journal of the American Society of Nephrology ; 32:88, 2021.
Article in English | EMBASE | ID: covidwho-1489442

ABSTRACT

Background: Vaccination is considered safe in patients with chronic kidney disease. However, given the ability to activate the immune system, immunizations carry a risk of inducing inflammatory disease flares. The mass vaccination for SARS-CoV-2 provides a unique opportunity to investigate potential vaccine-associated glomerular diseases. Methods: Kidney biopsies from patients who presented with acute kidney injury (AKI) and/or nephritic/nephrotic syndrome within three weeks of SARS-CoV-2 vaccination were included in the study (n=16). Kidney biopsies were reviewed at a single center and clinical information was provided from nephrologists for clinicopathologic correlation. Results: Sixteen patients with a new onset of kidney disease or flare within 3 weeks of SARS-CoV-2 vaccination were identified and all had glomerular disease on biopsy. Eleven patients had two vaccine doses prior to symptom onset. The patient cohort included 6 males and 10 females, with a mean age of 58 years. Biopsy diagnoses included IgA nephropathy (n=7), minimal change disease (n=4), ANCA-associated glomerulonephritis (n=3), membranous glomerulopathy (n=1), and diffuse lupus nephritis (n=1). Thirteen patients had co-morbid medical conditions, including hypertension (n=10), diabetes mellitus (n=4), autoimmune disease (n=5), and chronic kidney disease (n=4). The most common clinical presentation was AKI with concurrent nephritic or nephrotic syndrome (n=9), followed by nephritic syndrome with preserved kidney function (n=5), nephrotic syndrome with preserved kidney function (n=1), and isolated hematuria (n=1). Three patients with AKI required dialysis. A majority of patients had an elevated serum creatinine (mean 3.4 mg/dL), 14 had proteinuria (nephrotic range in 4), 11 had hematuria, and 10 had hypoalbuminemia (mean 2.9 g/dL). Six patients had antinuclear antibodies and 4 had a positive ANCA serology at the time of biopsy. Clinical follow-up is ongoing. Conclusions: IgA nephropathy, minimal change disease, ANCA-associated glomerulonephritis, membranous glomerulopathy, and lupus nephritis were identified with temporal association with SARS-CoV-2 vaccination. In the setting of mass vaccination, causality is unclear, but a new onset of glomerular disease should be monitored as a potential adverse event.

8.
HemaSphere ; 5(SUPPL 2):358-359, 2021.
Article in English | EMBASE | ID: covidwho-1393436

ABSTRACT

Background: BCR signaling mediated through Bruton's tyrosine kinase (BTK) plays a critical role in the development and maintenance of marginal zone lymphoma (MZL). BTK inhibitors have established activity in relapsed/refractory (R/R) MZL with the phase 2 study of ibrutinib demonstrating an objective response rate (ORR) of 48% (Noy et al. Blood. 2017;129:2224-2232). Zanubrutinib is a potent and highly specific next-generation BTK inhibitor designed with greater selectivity for BTK vs TEC- and EGFRfamily kinases, which are thought to be related to off-target toxicities. Therapeutic activity of zanubrutinib was established in an early-phase study (BGB-3111-AU-003) of 20 patients (pts) with R/R MZL demonstrating an ORR of 80%, with a complete response (CR) rate of 15%, and partial response (PR) rate of 65% (Tedeschi et al. EHA 2020, abstract 2804). Aims: To present initial efficacy and safety results in pts with R/R MZL enrolled in MAGNOLIA (BGB-3111-214). Methods: MAGNOLIA is a phase 2, multicenter, single-arm study of adults with R/R MZL who had received ≥1 line of therapy including ≥1 CD20-directed regimen. All were treated with zanubrutinib 160 mg twice daily until disease progression or unacceptable toxicity. Use of long-term antiplatelet and anticoagulation agents was permitted. The primary end point was ORR determined by an independent review committee in accordance with the Lugano classification. Secondary end points include ORR by investigator assessment, duration of response (DOR), progression-free survival (PFS), and safety. Results: As of January 11, 2021, 68 pts were enrolled and treated. Median age was 70 years (range, 37-95), with 28% aged ≥75 years. Subtypes included extranodal (mucosa-associated lymphoid tissue;38%), nodal (38%), splenic (18%), and indeterminate (6%) MZL. Median number of prior therapies was 2 (range, 1-6) and 32% of pts had disease that was refractory to last therapy. Median duration of drug exposure was 59.1 weeks (range, 3.7-84.1). Sixty-six pts were evaluable for efficacy. At a median study follow-up of 15.5 months (range, 1.6-21.7), investigator-assessed ORR (CR + PR) was 74% (CR 24%, PR 50%, stable disease 17%). Responses were observed in all subtypes, with an ORR of 68%, 84%, 75%, and 50% in extranodal, nodal, splenic, and indeterminate subtypes, respectively. CR rate was 36% for extranodal MZL, 20% for nodal, 8% for splenic, and 25% for indeterminate subtype. Median DOR and PFS were not reached;15-month PFS was 68% and 12-month DOR was 81%. IRC review is ongoing. Twenty-eight (41%) pts discontinued treatment: 20 due to disease progression, 1 withdrew consent, 3 required prohibited medications, 4 due to adverse events (AEs;2 due to COVID-19 pneumonia, 1 due to pyrexia attributed to disease transformation, and 1 due to myocardial infarction [MI]). The most common (≥10%) treatment-emergent AEs reported were diarrhea (22%), bruising (21%), constipation (15%), pyrexia (13%), abdominal pain (12%), upper respiratory tract infection (12%), back pain (10%), and nausea (10%). Most AEs were grade 1 or 2. Neutropenia was the most common grade ≥3 AE (10%). Two pts died from COVID-19 pneumonia and 1 pt with pre-existing coronary artery disease died from MI. No fatal AEs were considered related to zanubrutinib. All-grade AEs of interest included neutropenia (13%), thrombocytopenia (13%), atrial fibrillation/flutter (3%), and hypertension (3%). No major/serious hemorrhage was reported. No AEs led to dose reductions. Summary/Conclusion: Zanubrutinib demonstrated high response rates and durable disease control with a favorable safety profile in pts with R/R MZL.

9.
Public Health ; 196: 59-61, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1275653

ABSTRACT

OBJECTIVE: The objective of this study was to determine the interaction between psychological factors, belief systems, and engagement around public health initiatives. STUDY DESIGN: We conducted a longitudinal observational study, utilising convenience sampling to examine illness-related perception in the immediate and medium-term stages of the first wave of the SARS-CoV-2 pandemic in the UK. METHODS: Weekly questionnaires assessed our primary measure, illness-related perception, using The Health Anxiety Inventory. Other psychological measures included apathy, loneliness, depersonalisation, state anxiety, trait anxiety as well as personality traits. Multiple regressions were performed to determine which psychological factors predicted the variance of health anxiety every week using the enter method. RESULTS: A combination of psychological variables that varied over time and were modulated by external events predicted the evolution of illness-related perception and associated aversion to perceived threat. CONCLUSION: Our findings highlight how in the face of a public health crisis, psychological factors play a determining role in the synthesis of beliefs as well as guiding human behaviour.


Subject(s)
Behavioral Medicine , COVID-19 , Anxiety , Humans , Pandemics , SARS-CoV-2 , Surveys and Questionnaires
10.
Thorax ; 76(SUPPL 1):A87, 2021.
Article in English | EMBASE | ID: covidwho-1194269

ABSTRACT

Introduction The clinical presentation of Covid-19 varies widely with only a small proportion of those infected requiring hospitalisation. The ability to risk stratify patients upon presentation to the Emergency Department (ED) facilitates early safe discharge, with or without enhanced monitoring, which benefits hospital capacity management and infection control. In other lung parenchymal conditions oxygen desaturation during exercise has been used as an indicator of more severe disease. The exercise modality has typically been a field walking test or a bicycle or treadmill test which are impractical for delivery in ED. We investigated whether an alternative test, the 1-minute sit to stand test (1SST), was deliverable within an ED at the height of the COVID-19 pandemic. Methods During April to June 2020 at two large hospitals we performed 1SST in 201 people presenting with suspected Covid-19 and measured test performance (reps) plus change in pulse and oxygen saturations. Subsequently we identified clinical outcomes for all individuals diagnosed with Covid-19. A positive test was defined as 4% desaturation. Results The test was deliverable with 193/201 (96%) able to complete (2 were too unsteady, 6 failed to complete the minimum 5 reps). 111 (55%) were female, mean age of 49 (SD 16) years and an average of 17 (SD 7) reps completed. Mean fall in saturations was-1.6% and rise in pulse was 22. 34 people were diagnosed with Covid-19 based on a) positive swab or b) negative swab but diagnosed with 'clinical Covid-19' by a senior clinician based on clinical and radiological features. 1 person was unable to complete the 1SST test. The outcomes for people with a positive or negative test are shown in the table 1. In the early part of the study we were only able to swab people admitted to hospital so data from 109 further people is not included in the primary analysis. Conclusion The 1SST is feasible for people presenting acutely with Covid-19. It effectively identifies exercise induced oxygen desaturation and therefore augments the decision making relating to hospital admission.

SELECTION OF CITATIONS
SEARCH DETAIL