Differential Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Profiles After Allergic Reactions to Messenger RNA Coronavirus Disease 2019 Vaccine.

Allergic symptoms after messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccines occur in up to 2% of recipients. Compared to nonallergic controls (n = 18), individuals with immediate allergic reactions to mRNA COVID-19 vaccines (n = 8) mounted lower immunoglobulin G1 (IgG1) to multiple antigenic targets in severe acute respiratory syndrome coronavirus 2 spike following vaccination, with significantly lower IgG1 to full-length spike (P = .04). Individuals with immediate allergic reactions to mRNA COVID-19 vaccines bound Fcγ receptors similarly to nonallergic controls. Although there was a trend toward an overall reduction in opsonophagocytic function in individuals with immediate allergic reactions compared to nonallergic controls, allergic patients produced functional antibodies exhibiting a high ratio of opsonophagocytic function to IgG1 titer.

Infection Phenotypes Among Patients with Primary Antibody Deficiency Mined from a US Patient Registry.

PURPOSE: Primary immunodeficiency disorders (PIDs) affect immune system development and/or function, increase infection susceptibility, and cause dysregulation or both. Recognition of PID requires assessment about the normal state of infection frequency and microbiology. To help clarify infection characteristics, we use data mined from the US Immunodeficiency Network (USIDNET) registry among primary antibody deficiency (PAD) patients before diagnosis. METHODS: We analyzed PAD patient data from the USIDNET registry prior to ultimate diagnosis. Our analysis included basic descriptive statistics for 8 major infection subtypes and significance testing for comparing infection rate by specific organisms across 7 distinct PAD subtypes. RESULTS: Of 2038 patients reviewed, 1259 (61.8%) had infections reported prior to diagnosis. Most (77.4%) had four or less reported infections prior to diagnosis; however, some suffered up to 16 infections. Infection patterns differed across the PAD subtypes. Patients with agammaglobulinemia differed significantly from patients with all other forms of PAD studied in at least one infection category, whereas patients with CVID differed from 3 other PAD categories in at least one infection category. Patterns of infections in patients with hypogammaglobulinemia, specific antibody deficiency, and transient hypogammaglobulinemia were less unique. For each of the infection types, bacteria were the most prevalent cause of disease. CONCLUSIONS: Our data shows that distinct subtypes of PAD display unique infection patterns. We also show that patients with agammaglobulinemia suffer more invasive infections and differ most significantly from all other forms of PAD studied. Our analysis has broad implications about infection surveillance, progression, and vulnerability by PAD subtype.

Hereditary angioedema: Special considerations in women.

There are several challenges that arise in caring for women with hereditary angioedema (HAE). Most notably, the disease course during pregnancy is unpredictable, but studies show that plasma-derived C1-inhibitor is effective and safe for treatment of attacks as well as long-term prophylaxis (LTP) in select patients. Vaginal deliveries are preferred to caesarean sections, and epidural anesthesia is preferred to general anesthesia in lowering the risk of an acute attack. Lactation postpartum may increase HAE attacks. With regard to contraception, combined oral contraceptive pills that contain estrogen exacerbate symptoms. Similarly, estrogen-replacement therapy in menopause may increase attacks and is contraindicated. Fertility is not impacted by HAE itself or by HAE medications. The risk of breast cancer and female reproductive cancer in women with HAE is comparable with that of the general population, but, in patients with HAE and breast cancer, LTP with androgens is contraindicated. Estrogen modulators, e.g., tamoxifen, should be used with caution. Here, we reviewed these special considerations and others that are vital to providers in caring for women with HAE.

Responsiveness of the testing morbidities index in colonoscopy.

OBJECTIVES: The Testing Morbidities Index (TMI) was developed to measure the effects of any diagnostic or screening procedure on health-related quality of life (HRQOL); it includes seven domains incorporating mental and physical aspects before, during, and after testing. To add to prior work on the validity of the TMI classification, responsiveness of a summated scale version was evaluated in 71 colonoscopy patients. Further data on construct validity were also obtained. METHODS: Patients enrolled in the study when scheduling colonoscopy days to weeks beforehand. The baseline survey included the EuroQol five-dimensional (EQ-5D) questionnaire with five levels in each attribute (EQ-5D-5L questionnaire) and its visual analogue scale (VAS) assessment (EQ-VAS), the Short Form 12 version 2 (SF-12v2) component summary scores and six-dimensional health state short-form (derived from the short-form 12v2 health survey [SF-6D] utilities), and an original construct-specific VAS (CS-VAS) for usual HRQOL using utility scale anchors. The TMI's highest possible summated score (all best levels) served as its baseline. Survey data were generally obtained by telephone interview. A postprocedure survey was given to patients after colonoscopy and interviews conducted as soon as possible after the day of the procedure. The postprocedure survey included the SF-12v2/SF-6D, EQ-5D questionnaire instruments, TMI items, and a CS-VAS incorporating the overall HRQOL effects of colonoscopy. RESULTS: Standardized response means showed greatest responsiveness by the TMI (-1.52) followed by the CS-VAS instruments (-0.42). The EQ-5D-5L questionnaire, the EQ-VAS, and the SF-12 component summaries were unresponsive, and the SF-6D was minimally responsive (-0.05). Correlation of the post-CS-VAS with the TMI was substantial (r = -0.52), suggesting TMI construct validity. Moderate to strong correlation of the baseline CS-VAS with standard indexes was observed (r = 0.54-0.81). CONCLUSION: The TMI appears responsive and exhibits further evidence of construct validity.

PI Prob: A risk prediction and clinical guidance system for evaluating patients with recurrent infections.

BACKGROUND: Primary immunodeficiency diseases represent an expanding set of heterogeneous conditions which are difficult to recognize clinically. Diagnostic rates outside of the newborn period have not changed appreciably. This concern underscores a need for novel methods of disease detection. OBJECTIVE: We built a Bayesian network to provide real-time risk assessment about primary immunodeficiency and to facilitate prescriptive analytics for initiating the most appropriate diagnostic work up. Our goal is to improve diagnostic rates for primary immunodeficiency and shorten time to diagnosis. We aimed to use readily available health record data and a small training dataset to prove utility in diagnosing patients with relatively rare features. METHODS: We extracted data from the Texas Children's Hospital electronic health record on a large population of primary immunodeficiency patients (n = 1762) and appropriately-matched set of controls (n = 1698). From the cohorts, clinically relevant prior probabilities were calculated enabling construction of a Bayesian network probabilistic model(PI Prob). Our model was constructed with clinical-immunology domain expertise, trained on a balanced cohort of 100 cases-controls and validated on an unseen balanced cohort of 150 cases-controls. Performance was measured by area under the receiver operator characteristic curve (AUROC). We also compared our network performance to classic machine learning model performance on the same dataset. RESULTS: PI Prob was accurate in classifying immunodeficiency patients from controls (AUROC = 0.945; p<0.0001) at a risk threshold of ≥6%. Additionally, the model was 89% accurate for categorizing validation cohort members into appropriate International Union of Immunological Societies diagnostic categories. Our network outperformed 3 other machine learning models and provides superior transparency with a prescriptive output element. CONCLUSION: Artificial intelligence methods can classify risk for primary immunodeficiency and guide management. PI Prob enables accurate, objective decision making about risk and guides the user towards the appropriate diagnostic evaluation for patients with recurrent infections. Probabilistic models can be trained with small datasets underscoring their utility for rare disease detection given appropriate domain expertise for feature selection and network construction.

Breast cancer risk, worry, and anxiety: Effect on patient perceptions of false-positive screening results.

OBJECTIVE: The impact of mammography screening recall on quality-of-life (QOL) has been studied in women at average risk for breast cancer, but it is unknown whether these effects differ by breast cancer risk level. We used a vignette-based survey to evaluate how women across the spectrum of breast cancer risk perceive the experience of screening recall. METHODS: Women participating in mammography or breast MRI screening were recruited to complete a vignette-based survey. Using a numerical rating scale (0-100), women rated QOL for hypothetical scenarios of screening recall, both before and after benign results were known. Lifetime breast cancer risk was calculated using Gail and BRCAPRO risk models. Risk perception, trait anxiety, and breast cancer worry were assessed using validated instruments. RESULTS: The final study cohort included 162 women at low (n = 43, 26%), intermediate (n = 66, 41%), and high-risk (n = 53, 33%). Actual breast cancer risk was not a predictor of QOL for any of the presented scenarios. Across all risk levels, QOL ratings were significantly lower for the period during diagnostic uncertainty compared to after benign results were known (p < 0.05). In multivariable regression analyses, breast cancer worry was a significant predictor of decreased QoL for all screening scenarios while awaiting results, including scenarios with non-invasive imaging alone or with biopsy. High trait anxiety and family history predicted lower QOL scores after receipt of benign test results (p < 0.05). CONCLUSIONS: Women with high trait anxiety and family history may particularly benefit from discussions about the risk of recall when choosing a screening regimen.

Hemodialysis patient with finger ulcerations.

The patient reported pain and paresthesias of his left ring finger, and his left hand was cooler than his right. An angiogram helped us recognize the cause of his symptoms.

Comparing morbidities of testing with a new index: screening colonoscopy versus core-needle breast biopsy.

PURPOSE: Focusing on outcomes of care alone may be too restrictive. Patients can experience morbidity that is important to them from health care processes themselves. However, many processes, such as testing and screening, have been little evaluated. This study's purpose was to assess the construct validity of a new preference-based index, the Testing Morbidities Index (TMI), by comparing two common cancer-related procedures in prior publications: screening colonoscopy and core-needle breast biopsy. METHODS: Women evaluating their breast biopsies (n = 100) were compared with men and women who had undergone screening colonoscopy (n = 109) after both groups completed the TMI. The TMI addresses physical and mental or emotional quality of life affected by test-specific aspects occurring before, during, or after any test. It has 7 domains and survey items. TMI scores can be scaled in various ways, including multi-attribute value theory-based patient or societal preferences, where 0 = dead and 1.0 = full health, as used here. RESULTS: There was significantly greater morbidity from breast biopsy (mean, 0.84) than from screening colonoscopy (mean, 0.88) comparing overall TMI preference scores (P < .0001). Breast biopsy showed significantly worse morbidity (P = .005 to P < .0001) in most domains. Pain or discomfort before testing was worse for colonoscopy because of bowel preparation. The TMI showed no floor effect and an acceptable ceiling effect. CONCLUSIONS: The TMI provides the first objective evidence comparing the morbidity of one cancer-related testing procedure with another. The TMI may be useful in assessments of medical care processes informative to institutions and imaging departments, shared decision-making scenarios, and economic analyses.

Auditing a breast MRI practice: performance measures for screening and diagnostic breast MRI.

PURPOSE: Breast MRI is increasingly used for both screening and diagnostic purposes. Although performance benchmarks for screening and diagnostic mammography have been published, performance benchmarks for breast MRI have yet to be established. The purpose of this study was to comprehensively evaluate breast MRI performance measures, stratified by screening and diagnostic indications, from a single academic institution. METHODS: Institutional review board approval was acquired for this HIPAA-compliant study. Informed consent was not required. Retrospective review of the institutional database identified all breast MRI examinations performed from April 1, 2007, to March 31, 2008. After application of exclusion criteria, the following performance measures for screening and diagnostic indications were calculated: cancer detection rate, positive predictive value (PPV), and abnormal interpretation rates. RESULTS: The study included 2,444 examinations, 1,313 for screening and 1,131 for diagnostic indications. The cancer detection rates were 14 per 1,000 screening breast MRI examinations and 47 per 1,000 diagnostic examinations (P < .00001). The abnormal interpretation rate was 12% (152 of 1,313) for screening and 17% (194 of 1,131) for diagnostic indications (P = .00008). The PPVs of MRI were lower for screening [PPV1 (abnormal findings) = 12%, PPV2 (biopsy recommended) = 24%, PPV3 (biopsy performed) = 27%] compared with diagnostic indications (PPV1 (abnormal findings) = 28%, PPV2 (biopsy recommended) = 36%, PPV3 (biopsy performed) = 38%]. CONCLUSIONS: Breast MRI performance measures differ significantly between screening and diagnostic MRI indications. Medical audits for breast MRI should calculate performance measures for screening and diagnostic breast MRI separately, as recommended for mammography.