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Careful characterization of the phenotype and genotype of Huntington disease (HD) can foster better understanding of the condition.We conducted a cohort study in the United States, Canada, and Australia of members of families affected by HD. We collected demographic and clinical data, conducted the Unified Huntington's Disease Rating Scale and Mini-Mental State Examination, and determined Huntingtin trinucleotide CAG repeat length. We report primarily on cross-sectional baseline data from this recently completed prospective, longitudinal, observational study.As of December 31, 2009, 2,318 individuals enrolled; of these, 1,985 (85.6%) were classified into six analysis groups. Three groups had expanded CAG alleles (36 repeats or more): individuals with clinically diagnosed HD [n = 930], and clinically unaffected first-degree relatives who had previously pursued [n = 248] or not pursued [n = 112] predictive DNA testing. Three groups lacked expanded alleles: first-degree relatives who had previously pursued [n = 41] or not pursued [n = 224] genetic testing, and spouses and caregivers [n = 430]. Baseline mean performance differed across groups in all motor, behavioral, cognitive, and functional measures (p

Abstract Background The UK Collaborative HIV Cohort (UK CHIC) is an observational study that collates data on HIV-positive adults accessing HIV clinical care at (currently) 13 large clinics in the UK but does not collect pregnancy specific data. The National Study of HIV in Pregnancy and Childhood (NSHPC) collates data on HIV-positive women receiving antenatal care from every maternity unit in the UK and Ireland. Both studies collate pseudonymised data and neither dataset contains unique patient identifiers. A methodology was developed to find and match records for women reported to both studies thereby obtaining clinical and treatment data on pregnant HIV-positive women not available from either dataset alone. Results Women in UK CHIC receiving HIV-clinical care in 1996–2009, were found in the NSHPC dataset by initially ‘linking’ records with identical date-of-birth, linked records were then accepted as a genuine ‘match’, if they had further matching fields including CD4 test date. In total, 2063 women were found in both datasets, representing 23.1% of HIV-positive women with a pregnancy in the UK (n = 8932). Clinical data was available in UK CHIC following most pregnancies (92.0%, 2471/2685 pregnancies starting before 2009). There was bias towards matching women with repeat pregnancies (35.9% (741/2063) of women found in both datasets had a repeat pregnancy compared to 21.9% (1502/6869) of women in NSHPC only) and matching women HIV diagnosed before their first reported pregnancy (54.8% (1131/2063) compared to 47.7% (3278/6869), respectively). Conclusions Through the use of demographic data and clinical dates, records from two independent studies were successfully matched, providing data not available from either study alone.

Cervical cancer screening programs reduce the number of cervical cancer cases and deaths, but the success of any screening program is dependent on high participant uptake and coverage and many European countries are observing declining cervical cancer screening coverage to below national targets. Self-collection of vaginal samples for human papillomavirus testing, also termed self-sampling, is one strategy which is being introduced to try to increase screening coverage by removing barriers to participation and it has attracted growing interest and support globally. Informed by peer-reviewed and gray literature, this narrative review starts with a case study from the Netherlands and outlines the self-collection landscape in Europe within the themes of program implementation and relative test performance. It highlights some of the current evidence gaps needed to inform policy decisions on the use of self-collection within screening programs.

Background: T-cell lymphomas are a heterogeneous group of lymphoid malignancies with poor outcomes. Frontline multiagent chemotherapy options include CHOP (prednisone, vincristine, cyclophosphamide, and doxorubicin), brentuximab-CHP, CHOEP, and EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin)., Patients and Methods: We report our single institution data for safety and efficacy of EPOCH in 38 patients with aggressive T-cell lymphoma including both peripheral T cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL)., Results: Eighteen patients received EPOCH as first-line and 21 in the relapsed/refractory (R/R) setting. In 36 evaluable patients, the overall response rate (ORR) was 77% (95% CI, 61%-89%) with 19 (53%) patients achieving complete response (CR) (95% CI, 36%-69%). The ORR in first line and R/R settings were 80% (95% CI, 46%-94%) and 75% (95% CI, 52%-90%), respectively. Response rate was similar in African American versus Caucasian patients but was higher in CD30 negative versus positive patients. Most common grade 3/4 adverse events included cytopenias., Conclusions: Overall, EPOCH was well tolerated with high response rates in first line and R/R setting., Competing Interests: Disclosure Dr Francine Foss is on the speakers bureau for Pfizer. No other relevant disclosures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: To assess the costs and benefits of two algorithms for cervical cancer screening in Belgium (1) high-risk human papillomavirus (HR-HPV) primary screening and (2) HR-HPV and liquid-based cytology (LBC) co-testing., Methods: A decision tree was adapted from published work and parameterised using HORIZON study data and Belgian cost and population data. The theoretical model represents two different screening algorithms for a cohort of 577 846 women aged 25-64 attending routine cervical screening. Scenario analyses were used to explore the impact of including vaccinated women and alternative pricing approaches. Uncertainty analyses were conducted., Results: The cost per woman screened was €113.50 for HR-HPV primary screening and €101.70 for co-testing, representing a total cost of €65 588 573 and €58 775 083, respectively, for the cohort; a 10% difference. For one screening cycle, compared to HR-HPV primary, co-testing resulted in 13 173 more colposcopies, 67 731 more HR-HPV tests and 477 020 more LBC tests. Co-testing identified 2351 more CIN2+ cases per year (27% more than HR-HPV primary) and 1602 more CIN3+ cases (24% more than HR-HPV primary) than HR-HPV primary., Conclusion: In Belgium, a co-testing algorithm could increase cervical pre-cancer detection rates compared to HR-HPV primary. Co-testing would cost less than HR-HPV primary if the cost of the HPV test and LBC were cost-neutral compared to the current cost of LBC screening but would cost more if the cost per HPV test and LBC were the same in both co-testing and HR-HPV primary strategies., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Immunotherapy has been shown to improve cancer survival, but there are no consensus guidelines to inform use in patients with both cancer and autoimmune disease (AD). We sought to examine immunotherapy utilization patterns between cancer patients with and without AD., Patients and Methods: This retrospective cohort study utilized data from a de-identified nationwide oncology database. Patients diagnosed with advanced melanoma, non-small cell lung cancer, and renal cell carcinoma were included. Outcomes of interest included first-line immunotherapy, overall immunotherapy, and number of immunotherapy cycles. We used logistic and Poisson regression models to examine associations between AD and immunotherapy utilization patterns., Results: A total of 25,076 patients were included (796 with AD). Patients with AD were more likely to be female, White, receive care at academic centers, and have ECOG ≥ 3. Controlling for demographic and clinical variables, AD was associated with lower odds of receiving first-line (odds ratio [OR] = 0.68, 95% confidence interval [CI] 0.56-0.82) and overall (OR = 0.80, 95% CI 0.67-0.94) immunotherapy. Among patients who received at least one cycle of immunotherapy, there was no difference in mean number of cycles received between patients with and without AD (11.3 and 10.5 cycles respectively). The incident rate of immunotherapy cycles received for patients with AD was 1.03 times that of patients without AD (95% CI 1.01-1.06)., Discussion: Patients with AD were less likely to receive immunotherapy as first-line and overall therapy for treatment of their advanced cancer. However, among those who did receive at least one cycle of immunotherapy, patients with AD received a similar number of cycles compared to patients without AD. This not only indicates that AD is not an absolute contraindication for immunotherapy in clinical practice but may also demonstrate overall treatment tolerability and net benefit in patients with AD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cluster EA4 Guetzie and SirVictor are lytic siphoviral bacteriophages that were isolated from soil in Waverly, Iowa, using Microbacterium foliorum NRRL B-24224 as the host. The Guetzie and SirVictor genomes are both 39,758 bp each, and both contain 58 predicted protein-coding genes with one tRNA gene each., Competing Interests: The authors declare no conflict of interest.

Introduction: Accurate, patient-centred evaluation of physical function in patients with cancer can provide important information on the functional impacts experienced by patients both from the disease and its treatment. Increasingly, digital health technology is facilitating and providing new ways to measure symptoms and function. There is a need to characterise the longitudinal measurement characteristics of physical function assessments, including clinician-reported outcome, patient-reported ported outcome (PRO), performance outcome tests and wearable data, to inform regulatory and clinical decision-making in cancer clinical trials and oncology practice., Methods and Analysis: In this prospective study, we are enrolling 200 English-speaking and/or Spanish-speaking patients with breast cancer or lymphoma seen at Mayo Clinic or Yale University who will receive intravenous cytotoxic chemotherapy. Physical function assessments will be obtained longitudinally using multiple assessment modalities. Participants will be followed for 9 months using a patient-centred health data aggregating platform that consolidates study questionnaires, electronic health record data, and activity and sleep data from a wearable sensor. Data analysis will focus on understanding variability, sensitivity and meaningful changes across the included physical function assessments and evaluating their relationship to key clinical outcomes. Additionally, the feasibility of multimodal physical function data collection in real-world patients with breast cancer or lymphoma will be assessed, as will patient impressions of the usability and acceptability of the wearable sensor, data aggregation platform and PROs., Ethics and Dissemination: This study has received approval from IRBs at Mayo Clinic, Yale University and the US Food and Drug Administration. Results will be made available to participants, funders, the research community and the public., Trial Registration Number: NCT05214144; Pre-results., Competing Interests: Competing interests: GT has received research funding from the from the Food and Drug Administration for the Yale-Mayo Clinic Center of Excellence in Regulatory Science and Innovation (CERSI) (U01FD005938) that directly supports this work. She also receives grant funding from the US National Cancer Institute (NCI) U01 Tolerability Consortium (U01CA 2330463), and the Mayo Clinic Center for Clinical and Translational Research (CTSA) (KL2TR 023794). CG has received research funding from the NCCN Foundation (Astra-Zeneca) and Genentech, as well as funding from Johnson and Johnson to help devise and implement new approaches to sharing clinical trial data. Over the past three years, MMJ reports grant funding from the US Food and Drug Administration, National Institutes on Drug Abuse, Centers for Disease Control and Prevention, Agency for Healthcare Research and Quality, American Cancer Society, and the National Center for Advancing Translational Sciences. JSR currently receives research support through Yale University from Johnson and Johnson to develop methods of clinical trial data sharing, from the Food and Drug Administration for the Yale-Mayo Clinic Center of Excellence in Regulatory Science and Innovation (CERSI) (U01FD005938), from the Medical Devices Innovation Consortium as part of the National Evaluation System for Health Technology (NEST), from the Agency for Healthcare Research and Quality (R01HS022882), from the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH) (R01HS025164, R01HL144644), and from Arnold Ventures for the Collaboration for Regulatory Rigor, Integrity, and Transparency (CRRIT); in addition, Ross is an expert witness at the request of Relator's attorneys, the Greene Law Firm, in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen. JDR currently receives research support through Yale University from Johnson & Johnson to develop methods of clinical trial data sharing and from the US Food and Drug Administration for the Yale-Mayo Clinic Center of Excellence in Regulatory Science and Innovation (CERSI) (U01FD005938). SH has received consulting fees outside of this work from Janssen, Genentech, AbbVie, Flatiron Health, BeiGene, AstraZeneca, ADC Therapeutics, Epizyme, Merck, Seattle Genetics, TG Therapeutics, Tyme, Pharmacyclics, SeaGen, and Arvinas. Over the past three years, KR reports grant funding from the US Food and Drug Administration, National Institutes of Health, United States Department of Defense, and American Cancer Society. SS has received consulting fees from Eisai, Celgene, SeaGen, and Cardinal Health. She has previously received research funding to her institution from Genetech and Pfizer. All other authors have no relevant conflicts of interest to disclose., (© Where applicable, author(s) (or their employer(s)) 2024. Re-use permitted under [CC BY]. Published by BMJ.)

Detecting hypermethylation of tumour suppressor genes could provide an alternative to liquid-based cytology (LBC) triage within HPV primary cervical screening. The impact of using the QIAsure ® FAM19A4/mir124-2 DNA Methylation Test (QIAGEN, N.V, Hilden, Germany) on CIN3+ diagnoses, retention, unnecessary colposcopies, and programme costs is unknown. A decision-tree model was developed to compare LBC with the QIAsure Methylation testing to guide colposcopy referral. Incorporating clinician- and self-sampling pathways the model was informed by the Dutch cervical cancer screening programme, published studies, and manufacturer data. Clinical and cost outcomes were assessed using two scenarios for DNA methylation testing and LBC relative performance. Sensitivity analyses (deterministic and probabilistic) were performed to assess model and parameter uncertainty. A range of self-sampling uptake was assessed in scenario analyses. For the screening cohort ( n = 807,269) where 22.1% self-sampled, the number of unnecessary colposcopies and CIN3+ diagnoses varied according to the relative performance of methylation testing and LBC. Irrespective of relative performance, the cost per complete screen was lower and fewer people were lost to follow-up when using DNA methylation testing. The results indicate that, within an HPV primary screening programme that incorporates self-sampling, using the QIAsure Methylation Test for triage reduces the cost per screen compared to LBC.

BACKGROUND: Hairy cell leukemia (HCL) is characterized by the underlying genetic lesion of BRAFV600E and responsiveness to BRAF inhibitors. We assessed the safety and activity of the BRAF inhibitor vemurafenib combined with obinutuzumab in patients with previously untreated HCL. METHODS: We conducted a single-arm, multicenter clinical study of vemurafenib plus obinutuzumab. Vemurafenib 960 mg twice daily was administered for four cycles, and obinutuzumab was administered in cycles 2 to 4. The primary end point was complete remission (CR). Secondary end points included assessment of safety, minimal residual disease (MRD), and BRAF allele burden according to digital droplet polymerase chain reaction (ddPCR). RESULTS: Thirty patients were enrolled in the study, and 27 patients completed all four cycles of treatments and achieved CR (90%; 95% confidence interval [CI], 73 to 98). Three patients discontinued the study early because of adverse events and were not evaluable for response. Of the 27 patients who achieved CR, 26 patients (96%; 95% CI, 81 to 99) achieved MRD negativity. BRAFV600E allele was undetectable by ddPCR in all 21 evaluable patients. At a median follow-up of 34.9 months (95% CI, 29.6 to 36.9), no patient experienced disease relapse. The most common vemurafenib-related adverse events were rash and arthralgia. Febrile neutropenia occurred in two patients, and blood or platelet transfusions were required in two patients. CONCLUSIONS: Combined time-limited vemurafenib and obinutuzumab achieved CR in more than 90% of patients with previously untreated HCL. In this small study, acquired vemurafenib resistance or dose-limiting toxicity was not observed. Patients were not observed long enough to reveal secondary malignancies. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT03410875.)

Background: On admission to hospital, patients with community-acquired pneumonia (CAP), undergo extensive diagnostic testing. Two high-throughput laboratory-based PCR panels which return a result in 5.5 hours (h) have been developed to test for pathogens commonly associated with upper (Respiratory 1 Panel) and lower (Respiratory 3 Panel) respiratory tract infections (GeneFirst, Oxford). These could replace multiple diagnostic tests currently used., Methods: An online survey, completed by senior clinicians in the UK, France and Spain, was used to collect data on the diagnostic testing of immunocompetent and immunocompromised adults admitted to hospital with CAP, including the cost of diagnostics. Data were used to inform a cost-comparison model. For each country, the average cost of diagnostic testing per patient was calculated separately for immunocompetent and immunocompromised patients. The model compared three testing strategies with standard of care (SoC). In the Panel 1 strategy, the Respiratory 1 Panel was used for patients that would otherwise have tests which could be replaced by Respiratory 1 Panel, equivalent strategies for Respiratory 3 Panel and for both panels combined were assessed., Results: In total, 48 surveys were completed (UK = 17; France = 15; Spain = 16). Compared with SoC, the Panel 1 + 3 strategy was most favourable, resulting in cost savings for immunocompetent and immunocompromised patients respectively, of €22.09 (£18.50) and €26.12 (£21.88) in the UK, €99.60 and €108.77 in France and €27.07 and €51.87 in Spain., Conclusion: In all three countries, the use of these respiratory panels could reduce the average cost of diagnostics used for patients admitted to hospital with CAP., (© 2023. The Author(s).)

Objective: To compare the costs and effects of three sampling strategies for human papillomavirus (HPV) primary screening., Design: Cost-consequence analysis from a health system perspective using a deterministic decision tree model., Setting: England., Participants: A cohort of 10 000 women aged 25-65 years eligible for the National Health Service Cervical Screening Programme (NHSCSP)., Methods: The model was based on the NHSCSP HPV primary screening pathway and adapted for self-sampling. It used a 3-year cycle: routine screening (year 1) and recall screening (years 2/3). Parameter inputs were informed using published studies, NHSCSP reports and input from experts and manufacturers. Costs were from 2020/2021, British pound sterling (£)., Interventions: Three sampling strategies were implemented: (1) routine clinician-collected cervical sample, (2) self-collected first-void (FV) urine, (3) self-collected vaginal swab. The hypothetical self-sampling strategies involved mailing women a sampling kit., Main Outcome Measures: Primary outcomes: overall costs (for all screening steps to colposcopy), number of complete screens and cost per complete screen., Secondary Outcomes: number of women screened, number of women lost to follow-up, cost per colposcopy and total screening costs for a plausible range of uptake scenarios., Results: In the base case, the average cost per complete screen was £56.81 for clinician-collected cervical sampling, £38.57 for FV urine self-sampling and £40.37 for vaginal self-sampling. In deterministic sensitivity analysis, the variables most affecting the average cost per screen were the cost of sample collection for clinician-collected sampling and the cost of laboratory HPV testing for the self-sampling strategies. Scaled to consider routine screening in England, if uptake in non-attenders increased by 15% and 50% of current screeners converted to self-sampling, the NHSCSP would save £19.2 million (FV urine) or £16.5 million (vaginal) per year., Conclusion: Self-sampling could provide a less costly alternative to clinician-collected sampling for routine HPV primary screening and offers opportunities to expand the reach of cervical screening to under-screened women., Competing Interests: Competing interests: SH, KPS, VS, KT and EJA are employed by Aquarius Population Health, which received funding for this study. Aquarius Population Health works on projects related to diagnostics for different commercial and academic clients and as part of grant-funded projects. EJC is a National Institute for Health Research (NIHR) Advanced Fellow (NIHR300650), and her work is funded by the NIHR Manchester Biomedical Research Centre (IS-BRC-1215-20007). AS is a clinical scientist employed by the NHS working within the NHSCSP in the capacity of HPV lead scientist and pathway manager., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Peripheral T-Cell Lymphomas (PTCL) are a rare subgroup of lymphomas with a poor outcome.Traditional prognostic measures rely heavily on disease stage, and with the advent of targeted treatment, further stratificationcriteria are needed to guide treatment. To date, the impact of blood involvement at diagnosis on outcomes has not been assessed., Materials and Methods: We retrospectively reviewed blood involvement by flow cytometry at diagnosis in 102 consecutivelytreated patients who had flow cytometry data available at diagnosis. Of these, 78 patients with nodal subtypes were identified andstudied in this analysis., Results: Of 78 patients with nodal subtypes of PTCL who had flow data available at the time ofdiagnosis, circulating populations of malignant T cells matching those in the biopsied lymph nodes were found in 21 patients bymultiparameter flow cytometry. A positive flow cytometry was highly correlated with bone marrow involvement. The patientswith a negative flow cytometry had a trend toward a longer median PFS compared to those with a positive flow but there was noimpact on overall survival., Conclusions: Circulating malignant tumor cells can be found in the peripheral blood in a subset ofpatients with aggressive nodal T-cell lymphomas, including peripheral t-cell lymphoma not otherwise specified andangioimmunoblastic T-cell lymphomas, and blood involvement is correlated with bone marrow involvement., (Copyright © 2022. Published by Elsevier Inc.)

Objectives: To assess clinical metrics and resource use of a 30-minute point-of-care test (POCT) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) compared to laboratory-based testing., Methods: Three English sexual health services (SHSs) were recruited as part of a study. Existing processes for CT/NG testing and treatment were assessed, and adaptions to incorporate the CT/NG POCT were developed during semi-structured interviews. Staff time and consumables data were collected by clinic staff prior to and following introduction of the POCT., Results: SHSs selected patient groups for whom the CT/NG POCT would be used. Testing and treatment process data were collected for 225 patients (n = 118 POC; n = 107 standard). The percentage of patients receiving unnecessary CT treatment was 5% (5/95) and 13% (12/93) for POC and standard care respectively. The average CT/NG pathway cost varied and was on average £61.55 for POC and £50.88 for standard care. For the two SHSs where the POCT was used during a patient's visit, for standard and POC respectively, the average time to CT treatment was 10.0 and 0.0 days and to NG treatment, 0.3 and 0.0 days., Conclusion: Use of a 30-minute POCT at three SHSs yielded clinical benefits by reducing time to treatment and unnecessary CT treatment., Competing Interests: Conflict of interest statement: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SH, GW, and EA work at Aquarius Population Health and have received consultancy fees from the following organisations on projects related to STIs: Abbott, Cepheid, binx health, Hologic, Public Health England, and St. Georges University of London. SHSs participating in the wider project received free CT/NG POCT cartridges for use during the project with some surplus for use after the project plus a fridge in which to store the cartridges., (© The Author(s), 2021.)

Purpose: Intravenous immune globulin (IVIG) therapy is used in patients with hypogammaglobulinemia to lower the risk of infections. IVIG and subcutaneous IVIG (SCIG) therapy have been to shown to be safe and effective when administered as clinic-based infusions. Concern from both patients and providers for increased transmission of the coronavirus disease 2019 (COVID-19) virus to immunosuppressed patients with scheduled medical visits and procedures made it necessary for us to reassess our process of how we manage patient care in general and chronic clinic infusions in particular. Here we describe our experience of transitioning patients from clinic-based to home based IVIG and/or SCIG infusions to decrease the risk of COVID-19 exposure., Methods: Criteria were developed to identify high-risk immunosuppressed patients who would be appropriate candidates for potential conversion to home based IVIG infusions. Data were collected via chart review, and cost analysis was performed using Medicare Part B reimbursement data. A patient outcome questionnaire was developed for administration through follow-up phone calls., Results: From March to May 2020, 45 patients met criteria for home-based infusion, with 27 patients (60%) agreeing to home-based infusion. Posttransition patient outcomes assessment, conducted in 26 patients (96%), demonstrated good patient understanding of the home-based infusion process. No infusion-related complications were reported, and 24 patients (92%) had no concerns about receiving future IVIG and/or SCIG doses at home. No patient tested positive for COVID-19 during the study period. Clinic infusion visits decreased by 26.6 visits per month, resulting in a total of 106 hours of additional available infusion chair time per month and associated cost savings of $12,877., Conclusion: Transition of clinic based to home based IVIG/SCIG infusion can be successfully done to decrease potential exposure during a pandemic in a high-risk immunosuppressed population, with no impact on patient satisfaction, adherence, or efficacy. The home-based infusion initiative was associated with a reduction in costs to patients and an increase in available chair time in the infusion clinic., (© American Society of Health-System Pharmacists 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Single-use detergent sacs (SUDSs) represent a relatively new household hazard to children. Brand differences and packaging changes may contribute to differential risks with accidental exposure. We sought to identify high-risk features from SUDS exposures in children and to assess whether product packaging changed trends in SUDS exposures reported to poison centers., Methods: In this institutional review board-approved, retrospective chart review of SUDS exposures from January 2013 to August 2015, deidentified case records of a large statewide poison control system were extracted and analyzed for clinical associations and trends. Clinical and demographic data were gathered, and outcomes were analyzed for differences by brand type, presenting complaints, and occurrence in relation to SUDS packaging changes., Results: There were 3502 SUDS exposures, with 3343 (95%) in children 5 years or younger. Metabolic, central nervous system, and pulmonary effects were significantly associated with moderate or severe outcome (P < 0.05). Forty patients received invasive procedures such as endoscopy, bronchoscopy, and/or endotracheal intubation, and more than half had mucosal lesions discovered by the diagnostic procedure. The presence of stridor, wheezing, drooling, lethargy, and exposure to the brand All Mighty Pacs were all significant predictors of moderate or severe outcome (P < 0.05). After the implementation of packaging changes, there was a transient decline in the number of exposures to the Tide Pods product., Conclusion: Central nervous system and respiratory effects as well as certain brand types predict serious outcomes from SUDS exposures. Manufacturing changes had a brief beneficial effect on the volume of SUDS exposures reported between 2013 and 2015.

A recent phase II trial showed that use of polatuzumab vedotin in combination with bendamustine plus rituximab (Pola-BR) in transplant-ineligible patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) resulted in longer progression-free survival and overall survival compared to bendamustine plus rituximab (BR) alone. In this study, we constructed a Markov model to assess the cost-effectiveness of Pola-BR versus BR in transplant-ineligible R/R DLBCL. We calculated the incremental cost-effectiveness ratio (ICER) of each treatment strategy from a US payer perspective, using a lifetime horizon and a willingness-to-pay threshold of $100,000 per quality-adjusted life-year (QALY). Use of Pola-BR was associated with an incremental cost of $92,641 compared to BR alone ($200,905 vs $108,265, respectively), an incremental effectiveness of 1.76 QALYs (2.35 vs 0.59 QALYs, respectively), and an ICER of $52,519/QALY. These data suggest that use of Pola-BR for R/R DLBCL is likely to be cost-effective compared to BR alone.

Objectives: To assess the cost-effectiveness of universal repeat screening for syphilis in late pregnancy, compared with the current strategy of single screening in early pregnancy with repeat screening offered only to high-risk women., Design: A decision tree model was developed to assess the incremental costs and health benefits of the two screening strategies. The base case analysis considered short-term costs during the pregnancy and the initial weeks after delivery. Deterministic and probabilistic sensitivity analyses and scenario analyses were conducted to assess the robustness of the results., Setting: UK antenatal screening programme., Population: Hypothetical cohort of pregnant women who access antenatal care and receive a syphilis screen in 1 year., Primary and Secondary Outcome Measures: The primary outcome was the cost to avoid one case of congenital syphilis (CS). Secondary outcomes were the cost to avoid one case of intrauterine fetal demise (IUFD) or neonatal death and the number of women needing to be screened/treated to avoid one case of CS, IUFD or neonatal death. The cost per quality-adjusted life year gained was assessed in scenario analyses., Results: Base case results indicated that for pregnant women in the UK (n=725 891), the repeat screening strategy would result in 5.5 fewer cases of CS (from 8.8 to 3.3), 0.1 fewer cases of neonatal death and 0.3 fewer cases of IUFD annually compared with the single screening strategy. This equates to an additional £1.8 million per case of CS prevented. When lifetime horizon was considered, the incremental cost-effectiveness ratio for the repeat screening strategy was £120 494., Conclusions: Universal repeat screening for syphilis in pregnancy is unlikely to be cost-effective in the current UK setting where syphilis prevalence is low. Repeat screening may be cost-effective in countries with a higher syphilis incidence in pregnancy, particularly if the cost per screen is low., Competing Interests: Competing interests: SH, GW and EA work at Aquarius Population Health and have received consultancy fees from the following companies on projects related to STIs: Abbott, Cepheid, Binx Health, Hologic and St. Georges University of London. IA, KT and MT were funded as consultants on the project through Aquarius Population Health. MT has received support from Cepheid for conference attendance. KT is in receipt of funding to University of Bristol from GlaxoSmithKline for work unrelated to this work., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Community-based screening may be one solution to increase testing and treatment of sexually transmitted infections in sexually active teenagers, but there are few data on the practicalities and cost of running such a service. We estimate the cost of running a 'Test n Treat' service providing rapid chlamydia (CT) and gonorrhoea (NG) testing and same day on-site CT treatment in technical colleges., Methods: Process data from a 2016/17 cluster randomised feasibility trial were used to estimate total costs and service uptake. Pathway mapping was used to model different uptake scenarios. Participants, from six London colleges, provided self-taken genitourinary samples in the nearest toilet. Included in the study were 509 sexually active students (mean 85/college): median age 17.9 years, 49% male, 50% black ethnicity, with a baseline CT and NG prevalence of 6 and 0.5%, respectively. All participants received information about CT and NG infections at recruitment. When the Test n Treat team visited, participants were texted/emailed invitations to attend for confidential testing. Three colleges were randomly allocated the intervention, to host (non-incentivised) Test n Treat one and four months after baseline. All six colleges hosted follow-up Test n Treat seven months after baseline when students received a £10 incentive (to participate)., Results: The mean non-incentivised daily uptake per college was 5 students (range 1 to 17), which cost £237 (range £1082 to £88) per student screened, and £4657 (range £21,281 to £1723) per CT infection detected, or £13,970 (range £63,842 to £5169) per NG infection detected. The mean incentivised daily uptake was 19 students which cost £91 per student screened, and £1408/CT infection or £7042/NG infection detected. If daily capacity for screening were achieved (49 students/day), costs including incentives would be £47 per person screened and £925/CT infection or £2774/NG infection detected., Conclusions: Delivering non-incentivised Test n Treat in technical colleges is more expensive per person screened than CT and NG screening in clinics. Targeting areas with high infection rates, combined with high, incentivised uptake could make costs comparable., Trial Registration: ISRCTN58038795, Assigned August 2016, registered prospectively.

Objective: To test the hypotheses that insufficient duration, high fragmentation, and poor sleep quality are temporally associated with migraine onset on the day immediately following the sleep period (day 0) and the following day (day 1)., Methods: In this prospective cohort study of 98 adults with episodic migraine, participants completed twice-daily electronic diaries on sleep, headaches, and other health habits, and wore wrist actigraphs for 6 weeks. We estimated the incidence of migraine following nights with short sleep duration, high fragmentation, or low quality compared to nights with adequate sleep with conditional logistic regression models stratified by participant and adjusted for caffeine intake, alcohol intake, physical activity, stress, and day of week., Results: Participants were a mean age of 35.1 ± 12.1 years. We collected 4,406 days of data, with 870 headaches reported. Sleep duration ≤6.5 hours and poor sleep quality were not associated with migraine on day 0 or day 1. Diary-reported low efficiency was associated with 39% higher odds of headache on day 1 (odds ratio [OR] 1.39, 95% confidence interval [CI] 1.06-1.81). Actigraphic-assessed high fragmentation was associated with lower odds of migraine on day 0 (wake after sleep onset >53 minutes, OR 0.64, 95% CI 0.48-0.86; efficiency ≤88%, OR 0.74, 95% CI 0.56-0.99)., Conclusion: Short sleep duration and low sleep quality were not temporally associated with migraine. Sleep fragmentation, defined by low sleep efficiency, was associated with higher odds of migraine on day 1. Further research is needed to understand the clinical and neurobiologic implications of sleep fragmentation and risk of migraine., (© 2019 American Academy of Neurology.)

Migraine-type photophobia, most commonly described as exacerbation of headache by light, affects nearly 90% of the patients. It is the most bothersome symptom accompanying an attack. Using subjective psychophysical assessments, we showed that migraine patients are more sensitive to all colors of light during ictal than during interictal phase and that control subjects do not experience pain when exposed to different colors of light. Based on these findings, we suggested that color preference is unique to migraineurs (as it was not found in control subjects) rather than migraine phase (as it was found in both phases). To identify the origin of this photophobia in migraineurs, we compared the electrical waveforms that were generated in the retina and visual cortex of 46 interictal migraineurs to those generated in 42 healthy controls using color-based electroretinography and visual-evoked potential paradigms. Unexpectedly, it was the amplitude of the retinal rod-driven b wave, which was consistently larger (by 14%-19% in the light-adapted and 18%-34% in the dark-adapted flash ERG) in the migraineurs than in the controls, rather than the retinal cone-driven a wave or the visual-evoked potentials that differs most strikingly between the 2 groups. Mechanistically, these findings suggest that the inherent hypersensitivity to light among migraine patients may originate in the retinal rods rather than retinal cones or the visual cortex. Clinically, the findings may explain why migraineurs complain that the light is too bright even when it is dim to the extent that nonmigraineurs feel as if they are in a cave.

While health care costs can be considerable in individuals with diffuse large B-cell lymphoma (DLBCL), the degree to which health care expenditures vary following first-line treatment for non-relapsed versus relapsed DLBCL is unknown. Using 100% Medicare claims, we identified beneficiaries with DLBCL treated with first-line therapy between 1 January 2010 and 30 June 2014. We then compared health care expenditures of patients who received a second-line immunochemotherapy (relapse cohort) to those who did not begin a second-line therapy during follow-up (non-relapse cohort). After propensity score matching, the relapsed cohort incurred significantly higher health care costs ($6998 vs $3314 per month; p < .001), driven by inpatient ($2548 vs $1943 per month; p < .001) and outpatient office visit costs ($3581 vs $753 per month; p < .001). Our analysis confirms older adults with relapsed DLBCL incur higher medical costs and suggests improved first-line treatment would not only reduce the likelihood of relapse, but also contain health care costs.

Aversion to light is common among migraineurs undergoing acute attacks. Using psychophysical assessments in patients with episodic migraine, we reported that white, blue, amber, and red lights exacerbate migraine headache in a significantly larger percentage of patients and to a greater extent compared with green light. This study aimed at determining whether these findings are phase-dependent-namely, manifested exclusively during migraine (ictally) but not in its absence (interictally), or condition-dependent-ie, expressed uniquely in migraineurs but not in healthy controls. To determine whether the color preference of migraine-type photophobia is phase- or condition-dependent, we compared the effects of each color of light in each intensity between migraineurs during and in-between attacks and healthy controls. During the ictal and interictal phases, the proportion of migraineurs reporting changes in headache severity when exposed to the different colors of light increased in accordance with elevated light intensities. During the ictal phase, white, blue, amber, and red lights exacerbated headaches in ∼80% of the patients; however, during the interictal phase, light initiated headache in only 16% to 19%. Notably, green light exacerbated headaches in 40% and triggered headaches in 3% of the patients studied during the ictal and interictal phases, respectively. With one exception (highest red light intensity), no control subject reported headache in response to the light stimuli. These findings suggest that color preference is unique to migraineurs-as it was not found in control subjects-and that it is independent of whether or not the patients are in their ictal or interictal phase.

Introduction: Topical benzocaine is a local anesthetic commonly used to relieve pain caused by teething, periodontal irritation, burns, wounds, and insect bites. Oral preparations may contain benzocaine concentrations ranging from 7.5% to 20%. Pediatric exposure to such large concentrations may result in methemoglobinemia and secondarily cause anemia, cyanosis, and hypoxia., Methods: This is a retrospective study of exposures reported to a statewide poison control system. The electronic health records were queried for pediatric exposures to topical benzocaine treated at a healthcare facility from 2004 to 2014. Cases of benzocaine exposure were reviewed for demographic and clinical information, and descriptive statistical analysis was performed., Results: The query resulted in 157 cases; 58 were excluded due to co-ingestants, or miscoding of non-benzocaine exposures. Children four years of age and younger represented the majority of cases (93%) with a median age of 1 year. There were 88 cases of accidental/ exploratory exposure, while 6 cases resulted from therapeutic application or error, 4 cases from adverse reactions, and 1 case from an unknown cause. Asymptomatic children accounted for 75.5% of cases, but major clinical effects were observed in 5 patients. Those with serious effects were exposed to a range of benzocaine concentrations (7.5-20%), with 4 cases reporting methemoglobin levels between 20.2%-55%. Methylene blue was administered in 4 of the cases exhibiting major effects., Conclusion: The majority of exposures were accidental ingestions by young children. Most exposures resulted in minor to no effects. However, some patients required treatment with methylene blue and admission to a critical care unit. Therapeutic application by parents or caregivers may lead to adverse effects from these commonly available products., Competing Interests: Conflicts of Interest: By the WestJEM article submission agreement, all authors are required to disclose all affiliations, funding sources and financial or management relationships that could be perceived as potential sources of bias. No author has professional or financial relationships with any companies that are relevant to this study. There are no conflicts of interest or sources of funding to declare.