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Background Many breast, cervical, and colorectal cancer screening programmes were disrupted due to the COVID-19 pandemic. This study aimed to estimate the effects of five restart strategies after the disruption on required screening capacity and cancer burden.Methods Microsimulation models simulated five restart strategies for breast, cervical, and colorectal cancer screening. The models estimated required screening capacity, cancer incidence, and cancer-specific mortality after a disruption of 6 months. The restart strategies varied in whether screens were caught up or not and, if so, immediately or delayed, and whether the upper age limit was increased.Results The disruption in screening programmes without catch-up of missed screens led to an increase of 2.0, 0.3, and 2.5 cancer deaths per 100 000 individuals in 10 years in breast, cervical, and colorectal cancer, respectively. Immediately catching-up missed screens minimised the impact of the disruption but required a surge in screening capacity. Delaying screening, but still offering all screening rounds gave the best balance between required capacity, incidence, and mortality.Conclusions Strategies with the smallest loss in health effects were also the most burdensome for the screening organisations. Which strategy is preferred depends on the organisation and available capacity in a country.Subject terms: Health policy, Population screening, Cancer screening, Cancer screening  相似文献   
13.

Objectives

Triazole resistance in Aspergillus spp. is emerging and complicates prophylaxis and treatment of invasive aspergillosis (IA) worldwide. New polymerase chain reaction (PCR) tests on broncho-alveolar lavage (BAL) fluid allow for detection of triazole resistance at a genetic level, which has opened up new possibilities for targeted therapy. In the absence of clinical trials, a modelling study delivers estimates of the added value of resistance detection with PCR, and which empiric therapy would be optimal when local resistance rates are known.

Design

A decision-analytic modelling study was performed based on epidemiological data of IA, extended with estimated dynamics of resistance rates and treatment effectiveness. Six clinical strategies were compared that differ in use of PCR diagnostics (used vs not used) and in empiric therapeutic choice in case of unknown triazole susceptibility: voriconazole, liposomal amphotericin B (LAmB) or both. Outcome measures were proportion of correct treatment, survival and serious adverse events.

Results

Implementing aspergillus PCR tests was projected to result in residual treatment-susceptibility mismatches of <5% for a triazole resistance rate up to 20% (using voriconazole). Empiric LAmB outperformed voriconazole at resistance rates >5–20%, depending on PCR use and estimated survival benefits of voriconazole over LAmB. Combination therapy of voriconazole and LAmB performed best at all resistance rates, but the advantage over the other strategies should be weighed against the expected increased number of drug-related serious adverse events. The advantage of combination therapy over LAmB monotherapy became smaller at higher triazole resistance rates.

Conclusions

Introduction of current aspergillus PCR tests on BAL fluid is an effective way to increase the proportion of patients that receive targeted therapy for IA. The results indicate that close monitoring of background resistance rates and adverse drug events are important to attain the potential benefits of LAmB. The choice of strategy ultimately depends on the probability of triazole resistance, the availability of PCR and individual patient characteristics.  相似文献   
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Objective

To determine frequencies, interlaboratory reproducibility, clinical ratings, and prognostic implications of neural antibodies in a routine laboratory setting in patients with suspected neuropsychiatric autoimmune conditions.

Methods

Earliest available samples from 10,919 patients were tested for a broad panel of neural antibodies. Sera that reacted with leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-2 (CASPR2), or the voltage-gated potassium channel (VGKC) complex were retested for LGI1 and CASPR2 antibodies by another laboratory. Physicians in charge of patients with positive antibody results retrospectively reported on clinical, treatment, and outcome parameters.

Results

Positive results were obtained for 576 patients (5.3%). Median disease duration was 6 months (interquartile range 0.6–46 months). In most patients, antibodies were detected both in CSF and serum. However, in 16 (28%) patients with N-methyl-d-aspartate receptor (NMDAR) antibodies, this diagnosis could be made only in cerebrospinal fluid (CSF). The two laboratories agreed largely on LGI1 and CASPR2 antibody diagnoses (κ = 0.95). The clinicians (413 responses, 71.7%) rated two-thirds of the antibody-positive patients as autoimmune. Antibodies against the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), NMDAR (CSF or high serum titer), γ-aminobutyric acid-B receptor (GABABR), and LGI1 had ≥ 90% positive ratings, whereas antibodies against the glycine receptor, VGKC complex, or otherwise unspecified neuropil had ≤ 40% positive ratings. Of the patients with surface antibodies, 64% improved after ≥ 3 months, mostly with ≥ 1 immunotherapy intervention.

Conclusions

This novel approach starting from routine diagnostics in a dedicated laboratory provides reliable and useful results with therapeutic implications. Counseling should consider clinical presentation, demographic features, and antibody titers of the individual patient.

  相似文献   
15.

Background and aims

Since accelerated atherosclerosis has been reported in systemic lupus erythematosus (SLE), predictive biomarkers of cardiovascular disease (CVD) are needed. Among non-traditional risk factors, bone mineral density (BMD) has been related to CVD. However, its role in SLE remains controversial. This study aims to analyze the associations of subclinical atherosclerosis with traditional and non-traditional CV risk factors.

Methods and results

In a cross-sectional study, atherosclerosis burden was compared between 112 female SLE patients and 31 controls. Plaque number and carotid intima-media wall thickness (cIMT) were assessed by ultrasonography. In a retrospective study, BMD determinations obtained 5-years before the ultrasonography assessment were analyzed in a subgroup of 62 patients. Plaque frequency was increased in SLE, even in patients without CV events or carotid wall thickening. cIMT was increased in patients with CVD, positively correlated with body mass index (BMI). Interestingly, a paradoxical effect of BMI on carotid parameters was observed. Whereas underweight patients (BMI < 20) showed increased prevalence of carotid plaques with low cIMT, those with BMI > 30 showed higher cIMT and plaque burden. Overweight patients (25 < BMI<30) exhibited both elevated cIMT and plaque number. BMI was an independent predictor of BMD. In our retrospective study, patients with either clinical or subclinical CVD exhibited lower BMD levels than their CV-free counterparts. A low lumbar spine BMD independently predicted CVD development after adjusting for confounders.

Conclusion

SLE was associated with a higher subclinical atherosclerosis burden, a bimodal effect being observed for BMI. Decreased BMD can be a CV risk biomarker in SLE.  相似文献   
16.

Aims

Delaying progression, ameliorating symptoms and maintaining quality of life (QoL) are primary aims of treatment for metastatic castrate-resistant prostate cancer (mCRPC). Real-world rather than clinical trial data about symptoms and side-effects are sparse. In EXTREQOL, patients' QoL, pain and information needs were recorded during treatment.

Material and methods

Men with mCRPC from 20 UK cancer centres starting various systemic mCRPC treatments completed QoL, pain and information needs questionnaires at baseline, 3 and 6 months.

Results

In total, 132 patients were recruited. Overall QoL declined significantly by 6 months (Functional Assessment of Cancer Therapy-Prostate [FACT-P] mean = –3.89, 95% confidence interval –6.7 to –1.05, P = 0.007; Trial Outcome Index [TOI] analysis mean = –3.10, 95% confidence interval –5.34 to –0.83, P = 0.007). Those who came off novel therapy and remained on luteinising hormone-releasing hormone agonist therapy alone had worse scores than patients receiving concomitant chemotherapy (Prostate Concerns Subscale mean difference = –4.45, 95% confidence interval –7.06 to –1.83, P = 0.001; TOI mean difference = –5.62, 95% confidence interval –10.97 to –0.26, P = 0.040). At 3 and 6 months, men who reported pain at baseline improved (43%, 40%), but for others pain levels remained the same (45%, 42%) or worsened (13%, 18%). Information regarding supportive care was lacking throughout the period of time on the study.

Conclusion

Most mCRPC treated patients experience reduced QoL and inadequate pain control. More help with pain management and better information provision regarding supportive care is warranted.  相似文献   
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