Abstract Objectives To describe our experiences with a continuous quality improvement process for the standardization of multicenter urodynamic studies (UDSs) in a multi-institutional network. ...Multicenter UDSs can have considerable variations in testing procedures, training, equipment, and reviewer biases. Methods A quality control process was developed that included protocol development, certification of urodynamic testers, central review to assess compliance with protocol and quality, protocol modifications, standardization of equipment and signal configuration, development of an electronic signal repository, and the development of UDS Interpretation Guidelines. Results We describe our experience and process in the development and implementation of a standardized UDS protocol in a multicenter surgical trial for stress urinary incontinence. The process included our protocol development, quality control measures, standardization processes, electronic signal repository, and the need for UDS Interpretation Guidelines. A urodynamic testing procedures protocol was implemented successfully by 20 urodynamic testers at nine continence treatment centers. The protocol provides explicit and detailed guidelines for equipment, calibration, patient position, specific annotations, lay language bladder sensation parameters, visual leak point pressure techniques, modifications for prolapse, and data recording. A UDS Interpretation Guidelines document provides specific suggestions for validity and plausibility determination, expected ranges of urodynamic variables, and reasonable agreement of measuring systems. Both documents are available to urodynamic investigators on the Urinary Incontinence Treatment Network website ( http://www.uitn.net/resourcesforphysicians.htm ). Conclusions Multicenter UDSs require a continuous quality improvement process and the development of UDS testing procedures and interpretation guidelines.
Functional T-cell responses are essential for virus clearance and long-term protection after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, whereas certain clinical factors, ...such as older age and immunocompromise, are associated with worse outcome.
We sought to study the breadth and magnitude of T-cell responses in patients with coronavirus disease 2019 (COVID-19) and in individuals with inborn errors of immunity (IEIs) who had received COVID-19 mRNA vaccine.
Using high-throughput sequencing and bioinformatics tools to characterize the T-cell receptor β repertoire signatures in 540 individuals after SARS-CoV-2 infection, 31 IEI recipients of COVID-19 mRNA vaccine, and healthy controls, we quantified HLA class I- and class II-restricted SARS-CoV-2-specific responses and also identified several HLA allele-clonotype motif associations in patients with COVID-19, including a subcohort of anti-type 1 interferon (IFN-1)-positive patients.
Our analysis revealed that elderly patients with COVID-19 with critical disease manifested lower SARS-CoV-2 T-cell clonotype diversity as well as T-cell responses with reduced magnitude, whereas the SARS-CoV-2-specific clonotypes targeted a broad range of HLA class I- and class II-restricted epitopes across the viral proteome. The presence of anti-IFN-I antibodies was associated with certain HLA alleles. Finally, COVID-19 mRNA immunization induced an increase in the breadth of SARS-CoV-2-specific clonotypes in patients with IEIs, including those who had failed to seroconvert.
Elderly individuals have impaired capacity to develop broad and sustained T-cell responses after SARS-CoV-2 infection. Genetic factors may play a role in the production of anti-IFN-1 antibodies. COVID-19 mRNA vaccines are effective in inducing T-cell responses in patients with IEIs.
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e20557
Background: Patients with synchronous de novo EGFR sensitising and resistance mutations are rare. Little is known about the response of these patients to EGFR TKIs, especially in ...a Caucasian population. Methods: We identified NSCLC patients found to have EGFR mutations using PCR-based fragment length analysis, mass spectrometry-based genotyping (Sequenom), and Sanger sequencing using a large multi-institutional database. Baseline clinical characteristics, response rate, progression free survival (PFS) and overall survival (OS) were calculated. Results: From 2008-2015, we observed de novo synchronous EGFR sensitising and resistance mutations in 12 patients representing an overall incidence of 3.6% of EGFR mutants and 0.4% of all NSCLC patients tested. Seven patients were treated using EGFR TKI therapy with erlotinib. In all cases, T790M (n = 4,50%) or S768I (n = 4, 50%) occurred concurrently with another sensitising EGFR mutation, either L858R (n = 4, 34%) or exon 19 deletion (n = 8, 66%). Objective responses were seen in two patients (29%). Three further patients had stable disease lasting 6, 23 and 54 months respectively. The median progression-free survival was 24 months and the median overall survival was 34 months. All patients with baseline EGFR S768I mutations (n = 3) had an objective response or stable disease on erlotinib while two of four patients with T790M demonstrated de novo resistance. Conclusions: This is the largest Irish review of synchronous de novo EGFR mutations. The incidence of co-occurring EGFR mutations was 0.4% and erlotinib demonstrated activity in this cohort of patients. Ongoing trials will determine whether next-generation EGFR TKIs such as osimertinib are preferable as first-line therapy in these patients.
Background: Exposure to higher intakes of folic acid (FA) from fortified foods and supplements, although largely considered beneficial, is associated with unmetabolized FA in the circulation, which ...has raised some health concerns.
Objective: The effect of supplemental FA at a dose of 400 μg/d during pregnancy on unmetabolized FA concentrations in maternal plasma and newborn cord blood plasma was investigated.
Methods: A new analysis was performed of blood samples from participants in a randomized trial in pregnancy. Women aged 18–35 y, who had taken 400 μg FA/d as recommended in the first trimester, were recruited at the start of trimester 2 and randomly allocated to receive either 400 μg FA/d (n = 59) or a placebo (n = 67) throughout the second and third trimesters until delivery. Unmetabolized FA concentrations in maternal and cord blood samples were measured by LC–tandem MS analysis.
Results: In response to the intervention from gestational week 14 through delivery, a higher proportion of women in the FA compared with the placebo group had detectable FA (≥0.27 nmol/L) in plasma, but the difference in concentrations was not statistically significant (mean ± SD: 0.44 ± 0.80 compared with 0.13 ± 0.49 nmol/L, P = 0.38). FA treatment throughout pregnancy resulted in higher cord blood plasma total folate (50.6 ± 20.1 compared with 34.5 ± 14.4 nmol/L; P = 0.004) and 5-methyltetrahydrofolate (50.4 ± 20.3 compared with 34.5 ± 14.4 nmol/L; P = 0.005) concentrations, but FA was detected only in 8 of 53 available cord blood samples, and the proportion of samples with detectable FA concentrations was similar in FA-treated and placebo groups.
Conclusions: Plasma concentrations of unmetabolized FA arising from supplemental FA at a dose of 400 μg/d, in addition to FA from fortified foods, were low or undetectable in mothers and newborns. The benefits for mothers and offspring of continuing FA supplementation beyond the first trimester of pregnancy can be achieved without posing any risk of increasing unmetabolized circulating FA, even in those already exposed to FA from fortified foods.
Exposure to higher intakes of folic acid (FA) from fortified foods and supplements, although largely considered beneficial, is associated with unmetabolized FA in the circulation, which has raised ...some health concerns. The effect of supplemental FA at a dose of 400 mg/d during pregnancy on unmetabolized FA concentrations in maternal plasma and newborn cord blood plasma was investigated. A new analysis was performed of blood samples from participants in a randomized trial in pregnancy. Women aged 18-35 y, who had taken 400 mg FA/d as recommended in the first trimester, were recruited at the start of trimester 2 and randomly allocated to receive either 400 μg FA/d (n = 59) or a placebo (n = 67) throughout the second and third trimesters until delivery. Unmetabolized FA concentrations in maternal and cord blood samples were measured by LC-tandem MS analysis. In response to the intervention from gestational week 14 through delivery, a higher proportion of women in the FA compared with the placebo group had detectable FA (≥0.27 nmol/L) in plasma, but the difference in concentrations was not statistically significant (mean ± SD: 0.44 ± 0.80 compared with 0.13 ± 0.49 nmol/L, P = 0.38). FA treatment throughout pregnancy resulted in higher cord blood plasma total folate (50.6 ± 20.1 compared with 34.5 ± 14.4 nmol/L; P = 0.004) and 5-methyltetrahydrofolate (50.4 ± 20.3 compared with 34.5 ± 14.4 nmol/L; P = 0.005) concentrations, but FA was detected only in 8 of 53 available cord blood samples, and the proportion of samples with detectable FA concentrations was similar in FA-treated and placebo groups. Plasma concentrations of unmetabolized FA arising from supplemental FA at a dose of 400 μg/d, in addition to FA from fortified foods, were low or undetectable in mothers and newborns. The benefits for mothers and offspring of continuing FA supplementation beyond the first trimester of pregnancy can be achieved without posing any risk of increasing unmetabolized circulating FA, even in those already exposed to FA from fortified foods.
The association of invasive lobular carcinoma with high rates of compromised margins in breast conservation makes choice of operation for these patients difficult. We sought to identify patients at ...risk of compromised margins following breast conservation surgery.
We reviewed all patients with invasive lobular and invasive ductal carcinoma over a 5-year period (1999–2004). The imaging, pathology and surgical details of patients with invasive lobular carcinoma undergoing breast conservation were analyzed.
A total of 991 patients with invasive ductal carcinoma and 150 patients with invasive lobular carcinoma were identified. Lobular carcinomas had a compromised margin rate of 49% (n = 38/77) in breast conservation compared to 24% (n = 143/588) of ductal carcinomas (
P < .0001). Mammographic size (
P = .017), pathological size (
P = .01), age (
P = .03), multifocality (
P < .0001), and lymphovascular invasion (
P = .015) were significantly associated with compromised margins.
Invasive lobular carcinoma has a 49% rate of compromised margins following breast conservation. Mammographic size greater than 1.5 cm and young age were preoperative factors predictive of compromised margins.
HPV Knowledge Among HPV+ Women Daley, Ellen M.; Perrin, Karen (Kay) M.; Vamos, Cheryl ...
American journal of health behavior,
2008 Sep-Oct, Letnik:
32, Številka:
5
Journal Article
Recenzirano
Objective: To assess knowledge and information seeking among women recently receiving an HPV+ diagnosis.Methods: A 2-phase mixed methods design was used. In both phase I (qualitative) and phase II ...(quantitative), women with scheduled gynecological exams
and Pap smears at clinic sites were approached to participate.Results: Women expressed confusion about HPV, and most could not correctly articulate the meaning of their diagnosis. Women do engage in further information seeking, especially through the Internet.Conclusion:
Identifying gaps in knowledge among HPV+ women who need clear messages to facilitate their comprehension of the diagnosis is an important public health activity.
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