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Goals: To examine the prevalence of chemotherapy-or radiotherapy-associated side effects and related treatment burden, and correlates of fatigue and missed work days among cancer patients.Materials and Methods: A cross-sectional survey was conducted using a dual sampling frame of 63,949 cancer patients (35,751 from an online panel and 28,198 from telephone listings) > or = 18 years receiving chemotherapy and/or radiotherapy at the time of the survey or during the previous 12 months. Data were collected on cancer type, time since diagnosis, treatment side effects, visits, caregiver burden, missed work days, and sociodemographic characteristics. Data are presented only for patients receiving cancer treatment at the time of the survey.Main Results: Of the 15,532 patients (24%) who responded to the screening questionnaire, 1,572 met the eligibility criteria and 1,569 completed the survey; 814 received chemotherapy and/or radiotherapy at the time of the survey. The most common side effects were fatigue (80%), pain (48%), and nausea/vomiting (48%). Patients spent 4.5 h, on average, per visit to treat side effects. Approximately 43% of the patients were employed; of these, 78% were actively working. Employed patients missed, on average, 18 work days annually for side effect treatment. Females, younger and unemployed patients, and those with higher levels of anxiety and depression experienced more fatigue; patients with a greater number of side effects endured more missed work days.Conclusions: In addition to the symptomatic experience of side effects, patients reported a considerable time burden for treatment. It is important to consider supportive care strategies that may effectively reduce side effects and their associated treatment burden. [ABSTRACT FROM AUTHOR]

Objective: Metformin was approved by the Food and Drug Administration in 1995 subject to the conduct of a randomized trial to evaluate the risk of lactic acidosis or other serious adverse events (SAEs) with this agent, under usual care conditions.Research Design and Methods: The Comparative Outcomes Study of Metformin Intervention versus Conventional (COSMIC) Approach Study was a randomized, open-label, active-comparator, parallel-group, 1-year trial in type 2 diabetic patients suboptimally controlled on diet or sulfonylurea. Patients received metformin (n = 7,227) or other usual care treatments (n = 1,505). The primary end point was the incidence of SAEs, death, and hospitalization.Results: SAEs occurred in 10.3% (95% CI 9.6-11.1%) of the metformin group and in 11.0% (9.5-12.7%) of the usual care group (P = 0.431). Lactic acidosis did not occur. All-cause mortality (1.1% [0.9-1.4%] vs. 1.3% [0.8-2.0%], P = 0.596) and hospitalization (9.4% [8.8-10.1%] vs. 10.4% [8.9-12.1%], P = 0.229) were similar between groups.Conclusions: The incidence of SAEs was similar between groups. Lactic acidosis was not observed. Metformin may be safely prescribed for type 2 diabetes if contraindications and warnings are respected. This study demonstrates the utility of large, simple trials for risk evaluation of treatments for common diseases. [ABSTRACT FROM AUTHOR]

Background: The incidence of systemic non-Hodgkin's lymphoma (NHL) is higher in the population infected with human immunodeficiency virus (HIV) than in the uninfected population. Standard treatment for this cancer involves the administration of systemic chemotherapy.Purpose: Our objective was to determine the relative risk (RR) of opportunistic infection and the relative change in immunologic function in a cohort of patients who had HIV-associated NHL and who were treated with combination chemotherapy and to compare them with those in a matched cohort of control subjects who had advanced HIV infection but no signs of NHL.Methods: We performed a case-control study in which the clinical course of each patient with HIV-associated NHL (n = 43; case subjects) treated with infusional cyclophosphamide, doxorubicin, and etoposide was compared with that of two patients with HIV infection but without lymphoma who were matched for CD4 lymphocyte count and prior opportunistic infection (n = 86; control subjects). The patients' medical records were reviewed for all information related to acquired immunodeficiency syndrome (AIDS)-defining opportunistic infections, survival, cause of death, and lymphocyte subset analyses. Univariate and multivariate analyses were performed to determine whether any of a number of confounding factors (e.g., age, sex, CD4 count, prior opportunistic infection, and prior antiretroviral therapy) could have influenced the risk of developing a first infectious event (defined as opportunistic infection or nonlymphoma death). All P values resulted from two-sided statistical tests.Results: In the univariate analysis, a significantly greater risk for a first event was associated with being a case subject (RR = 1.8; 95% confidence intervals [CI] = 1.1-3.0; P < .05), having a low CD4 count (< 100/microL) (RR = 3.1; 95% CI = 1.8-5.4; P < .0001), being female (RR = 1.7; 95% CI = 1.1-3.3; P < .05), having prior Pneumocystis carinii pneumonia (RR = 3.5; 95% CI = 1.9-6.3; P < .0001), having any prior opportunistic infection (RR = 3.6; 95% CI = 2.1-6.4; P < .0001), and having prior antiretroviral therapy (RR = 1.9; 95% CI = 1.1-3.3; P < .05). In the multivariate analysis, however, being a case subject (RR = 2.1; 95% CI = 1.2-3.6; P < .01), having a low CD4 count (RR = 2.1; 95% CI = 1.2-3.9; P < .05), and being female (RR = 3.0; 95% CI = 1.8-5.6; P < .001) were the only characteristics associated with an increased risk of a first event. When the mean CD4 lymphocyte count at approximately 1 year was compared with that at baseline, there was a significantly greater decrease in the CD4 count among case subjects than among control subjects (mean decrease +/- standard deviation [SD] = 99/microL +/- 138/microL versus 29/microL +/- 100/microL; P = .03).Conclusions: Treatment of patients who have HIV-associated NHL with a non-steroid-containing chemotherapy regimen was associated with a significant and sustained reduction in the CD4 lymphocyte count and a twofold increase in the risk of developing opportunistic infection.Implications: Oncologists and other physicians who treat patients with HIV-associated NHL should be familiar with the prophylaxis, recognition, and management of opportunistic infection. In addition, there is a need to identify effective strategies for the amelioration of chemotherapy-induced immunosuppression in this population. [ABSTRACT FROM AUTHOR]

Background and Objectives: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a subtype of CAA with distinct clinical and radiologic features. Existing diagnostic criteria require the presence of characteristic asymmetrical white matter hyperintensity (WMH), together with classical hemorrhagic neuroimaging markers of CAA. There are limited data for other diagnostic neuroimaging markers of CAA-ri., Methods: This is a case series from a specialist hospital intracerebral hemorrhage service., Results: We describe 4 patients with CAA-ri who had regions of sulcal hyperintensity, with or without gyral swelling at clinical presentation, but did not fulfill current diagnostic criteria because of the absence of typical asymmetric WMH on brain MRI. All 4 patients were subsequently diagnosed with CAA-ri; three later developed asymmetric WMHs with disease relapse, and 2 had pathologically proven CAA-ri; 1 patient had both., Discussion: Regions of sulcal hyperintensity, sometimes with associated gyral swelling, can be an early imaging finding in CAA-ri. These neuroimaging markers could potentially improve the accuracy of existing diagnostic criteria for CAA-ri to allow earlier diagnosis and treatment without biopsy in patients with atypical presentations.

Background: Steatotic liver disease (SLD) prevalence is rising worldwide, linked to insulin resistance and obesity. SLD prevalence can surpass 10% even among those with normal weight. In Lao People's Democratic Republic (Lao PDR), where Opisthorchis viverrini (OV) trematode infection and type 2 diabetes mellitus (T2DM) are common, infection related liver morbidity such as cholangiocarcinoma (CCA) is high, but data on SLD prevalence is lacking. The objective of this study was to estimate the prevalence and explore determinants of SLD in rural southern Lao PDR for lean and non-lean populations., Method: A cross-sectional community-based study assessed SLD prevalence using abdominal ultrasonography (US). Factors investigated for association with SLD were identified by interview, serological tests (Hepatitis B surface antigen (HBsAg); lipids and HbA1c), anthropometrical measurements, and parasitological assessments (OV infection). Uni- and multivariable logistic regression analyses with SLD as endpoint were conducted separately for lean (body mass index (BMI) <23.0 kg/m 2 ) and non-lean (BMI ≥ 23.0 kg/m 2 ) participants., Result: 2,826 participants were included. SLD prevalence was 27.1% (95% confidence interval (95% CI) 24.0%-30.4%), higher among non-lean (39.8%) than lean individuals (17.4%). Lean individuals with OV infection had a statistically significant association with lower odds of SLD (adjusted odds ratio (aOR) 0.49, 95% CI 0.33 - 0.73). T2DM showed a significant positive association with SLD in both lean (aOR 3.58, 95% CI 2.28 - 5.63) and non-lean individuals (aOR 3.31, 95% CI 2.31 - 4.74) while dyslipidemia was significantly associated only in the non-lean group (aOR 1.83, 95% CI 1.09 - 3.07). Females participants exhibited elevated odds of SLD in both lean (aOR 1.43, 95% CI 1.02 - 2.01) and non-lean SLD (aOR 1.50, 95% CI 1.12 - 2.01)., Conclusion: SLD prevalence is notably high among Laotian adults in rural areas, particularly in females and in non-lean individuals. Lean individuals with OV infection exhibited lower SLD prevalence. SLD was more prevalent in individuals with T2DM, independent of BMI. SLD adds to the burden of infection-related liver morbidity in Lao PDR.

Introduction: Cholangiocarcinoma (CCA) is a major contributor to hepatobiliary mortality in the Lao People's Democratic Republic (Lao PDR). Infection with the carcinogenic trematode Opisthorchis viverrini (OV), acquired through consumption of insufficiently-cooked river fish, is a known risk factor for the development of CCA. Together with OV, other risk factors contribute to the pathogenesis of CCA. We conducted this study to identify the burden of CCA and identify risk factors in high-risk communities in Lao PDR., Method: A cross-sectional study was performed in Champasack and Savannakhet provinces, southern Lao PDR, where OV infection is highly endemic. We assessed hepatobiliary morbidity with abdominal ultrasound (US). In addition, multiple risk factors known or suspected to be associated with CCA were assessed such as OV infection (examined by Kato-Katz technique for stool examination), lifestyle risks (e.g. smoking and alcohol consumption by face-to-face questionnaire), co-morbidity (e.g. diabetes mellitus) and hepatitis B infection status, both serologically tested., Results: In 3,400 participants, the overall prevalence of suspected CCA was 7.2% (95% confidence interval [95% CI] 5.4-9.6). The suspected CCA prevalence increased with age, and was higher in men at all ages. Almost all participants (88.3%) were infected with OV. In the multivariate regression analysis, suspected CCA was positively associated with OV infection (adjusted odds ratio [aOR] 3.4, 95% CI 1.7-6.5), and a history of cholecystectomy (aOR 2.7, 95% CI 1.5-4.9)., Conclusion: Our CCA screening in high OV prevalence rural areas of Lao PDR uncovers a high public health burden, primarily driven by elevated OV infection rates. Urgent interventions are needed to curb OV infection in these communities. Age and gender disparities in suspected CCA prevalence highlight the need for targeted efforts. Beyond OV, notable factors like a history of cholecystectomy offer valuable insights for preventive strategies. This research enhances our understanding of hepatobiliary morbidity and informs public health initiatives in Lao PDR., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Homsana 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.)

Schistosomiasis mekongi is endemic in a restricted area in Northern Cambodia and the Southern Lao People's Democratic Republic. Severe hepatobiliary morbidity is associated with chronic untreated S. mekongi infection. Since the 1980s extensive control efforts have been employed in endemic areas, resulting in substantial reduction of infection rates and disease burden. We report on a patient with a fatal course of clinically-assessed chronic schistosomiasis. This report underscores that patients with severe chronic Mekong schistosomiasis may still exist and may need treatment support., (Copyright © 2024. Published by Elsevier B.V.)

In patients with lower-risk myelodysplastic syndromes/neoplasms (MDS), response to first-line therapy is limited and transient. The MATTERHORN randomized, double-blind, phase 3 trial evaluated roxadustat versus placebo for patients with transfusion-dependent, lower-risk MDS. Eligible patients had very low-, low-, or intermediate-risk MDS with or without prior erythropoiesis-stimulating agent treatment, and a transfusion burden of 1-4 packed red blood cell (pRBC) units every 8 weeks (Q8W). Patients were randomized (3:2) to oral roxadustat (2.5 mg/kg) or placebo, both three times weekly, with best supportive care. Primary efficacy endpoint was transfusion independence (TI) for ≥56 days within 28 weeks (TI responders). MATTERHORN was terminated due to interim analysis outcomes not meeting statistical significance. In total, 272 patients were screened, and 140 patients were enrolled (82, roxadustat, and 58, placebo). At final analysis, 38/80 (47.5%) patients and 19/57 (33.3%) in the roxadustat and placebo arms, respectively, were TI responders (p = .217). A greater percentage of patients in the roxadustat arm with a transfusion burden of ≥2 pRBC units Q4W were TI responders (36.1%; 13/36) compared with the placebo arm (11.5%; 3/26; p-nominal = .047). The seven on-study deaths (4, roxadustat, and 3, placebo) were considered unrelated to treatment. Three roxadustat patients progressed to acute myeloid leukemia. Despite MATTERHORN not meeting its primary endpoint, a numerically higher TI rate was achieved with roxadustat treatment compared with placebo. Further analyses are needed to confirm the MDS patient subgroups deriving clinical benefit from this novel treatment., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)

Objective: To explore the trends and changes in the transport of children to paediatric intensive care units (PICUs) between 2013 and 2022., Design: Retrospective analysis of routinely collected data., Patients: Children transported for care in a PICU in the UK and Ireland aged<16 years., Interventions: None., Measurements and Main Results: There were 43 058 transports to a PICU involving 36 438 children from 2013 to 2022 with the majority of children requiring only one transport. The number of transports increased from 4131 (2013) to 4792 (2022). Over the study period the percentage of children aged under 1 year who were transported decreased from 50.2% to 45.2% and similarly, the percentage who were invasively ventilated also decreased from 81.1% to 70.2%. Conversely, the use of non-invasive ventilation during transports increased slightly from 4.0% to 7.0%. The percentage of transports where a parent was able to accompany the child increased over time (2013: 66.2% to 2019: 74.9%), although there were reductions due to the COVID-19 pandemic and requirements for social distancing (2020: 52.4%)., Conclusions: We have demonstrated an increased use of specialist paediatric transport services and changes in the PICU population over time. Routine data collection from the transport services provide a means to measure improvements and changes over time in the service provided to critically ill children and young people who need transport to the PICU., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Coxiella burnetii, the causative agent of Q fever, and Rift Valley fever virus are two under-researched zoonotic pathogens in Ethiopia. Potential outbreaks of these diseases, in light of the high dependency of nomadic pastoralists on their livestock, poses a risk to both human and animal health in addition to risking the pastoralists livelihoods. Our study aimed to determine the seroprevalence and associated risk factors for Q fever and Rift Valley fever in pastoral communities in the Afar region of north-eastern Ethiopia., Methodology/principal Findings: This cross-sectional study screened pastoralists (n = 323) and their livestock (n = 1377) for IgG antibodies to Coxiella burnetii and Rift Valley fever virus. A seroprevalence for Q fever of 25.0% (95%CI 18.6-32.6) was found in pastoralists and 34.3% (95%CI 27.9-41.3) in livestock overall; with 51.9% in goats (95%CI 44.9-58.8), 39.9% in sheep (95%CI 24.6-51.2), 16.3% in camels (95%CI 10.4-24.6) and 8.8% in cattle (95%CI 5.0-15.0). For Rift Valley fever the seroprevalence in pastoralists was 6.1% (95%CI 3.3-11.0) and 3.9% (95%CI 2.6-5.7) in livestock overall; cattle had the highest seroprevalence (8.3%, 95%CI 3.3-19.2), followed by goats (2.7%; 95%CI 1.4-5.1), sheep (2.5%; 95%CI 1.0-5.9) and camels (1.8%; 95%CI 0.4-6.9). Human Q fever seropositivity was found to be associated with goat abortions (OR = 2.11, 95%CI 1.18-3.78, p = 0.011), while Rift Valley fever seropositivity in livestock was found to be associated with cattle abortions (OR = 2.52, 95%CI 1.05-6.08, p = 0.039)., Conclusions/significance: This study provides evidence for a notable exposure to both Q fever and Rift Valley fever in pastoralists and livestock in Afar. The outbreak potential of these pathogens warrants ongoing integrated human and animal surveillance requiring close collaboration of the human and animal health sectors with community representatives following a One Health approach., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Oakley 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.)

Objective: To demonstrate nanoscale motion tracing of spermatozoa and present analysis of the motion traces to characterize the consistency of motion of spermatozoa as a complement to progressive motility analysis., Design: Anonymized sperm samples were videographed under a quantitative phase microscope, followed by generating and analyzing superresolution motion traces of individual spermatozoa., Setting: Not applicable., Patient(s): Centrifuged human sperm samples., Intervention(s): Not applicable., Main Outcome Measure(s): Precision of motion trace of individual sperms, presence of a helical pattern in the motion trace, mean and standard deviations of helical periods and radii of sperm motion traces, speed of progression., Result(s): Spatially sensitive quantitative phase imaging with a superresolution computational technique MUltiple SIgnal Classification ALgorithm allowed achieving motion precision of 340 nm using ×10, 0.25 numerical aperture lens whereas the diffraction-limited resolution at this setting was 1,320 nm. The motion traces thus derived facilitated new kinematic features of sperm, namely the statistics of helix period and radii per sperm. Through the analysis, 47 sperms with a speed >25 μm/s were randomly selected from the same healthy donor semen sample, it is seen that the kinematic features did not correlate with the speed of the sperms. In addition, it is noted that spermatozoa may experience changes in the periodicity and radius of the helical path over time. Further, some very fast sperms (e.g., >70 μm/s) may demonstrate irregular motion and need further investigation. Presented computational analysis can be used directly for sperm samples from both fertility patients with normal and abnormal sperm cell conditions. We note that MUltiple SIgnal Classification ALgorithm is an image analysis technique that may vaguely fall under the machine learning category, but the conventional metrics for reporting found in Enhancing the QUAlity and Transparency Of health Research network do not apply. Alternative suitable metrics are reported, and bias is avoided through random selection of regions for analysis. Detailed methods are included for reproducibility., Conclusion(s): Kinematic features derived from nanoscale motion traces of spermatozoa contain information complementary to the speed of the sperms, allowing further distinction among the progressively motile sperms. Some highly progressive spermatozoa may have irregular motion patterns, and whether irregularity of motion indicates poor quality regarding artificial insemination needs further investigation. The presented technique can be generalized for sperm analysis for a variety of fertility conditions., Competing Interests: Declaration of Interests S.B. has nothing to disclose. A patent application containing the idea and application of this work as a subset of the claims has been submitted, where A.B. and K.A. are coinventors. They have not received any monetary gains pertaining this. They have received funding from European Research Council and Forskningsradet for commercialization of the patented technology; University hospital of North Norway UNN’s fertility clinic provided anonymized and centrifuged sperm samples. S.A. has nothing to disclose. D.H.H. has nothing to disclose. J.-C.T. has nothing to disclose. M.N. has nothing to disclose. D.S.M. has nothing to disclose. K.A. reports European Research Council Starting grant 804233 and European Research Council PoC 101123485 that funded the study., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Targeting cell surface molecules using radioligand and antibody-based therapies has yielded considerable success across cancers. However, it remains unclear how the expression of putative lineage markers, particularly cell surface molecules, varies in the process of lineage plasticity, wherein tumor cells alter their identity and acquire new oncogenic properties. A notable example of lineage plasticity is the transformation of prostate adenocarcinoma (PRAD) to neuroendocrine prostate cancer (NEPC)-a growing resistance mechanism that results in the loss of responsiveness to androgen blockade and portends dismal patient survival. To understand how lineage markers vary across the evolution of lineage plasticity in prostate cancer, we applied single-cell analyses to 21 human prostate tumor biopsies and two genetically engineered mouse models, together with tissue microarray analysis on 131 tumor samples. Not only did we observe a higher degree of phenotypic heterogeneity in castrate-resistant PRAD and NEPC than previously anticipated but also found that the expression of molecules targeted therapeutically, namely PSMA , STEAP1 , STEAP2 , TROP2, CEACAM5 , and DLL3 , varied within a subset of gene-regulatory networks (GRNs). We also noted that NEPC and small cell lung cancer subtypes shared a set of GRNs, indicative of conserved biologic pathways that may be exploited therapeutically across tumor types. While this extreme level of transcriptional heterogeneity, particularly in cell surface marker expression, may mitigate the durability of clinical responses to current and future antigen-directed therapies, its delineation may yield signatures for patient selection in clinical trials, potentially across distinct cancer types., Competing Interests: Competing interests statement:P.S.N. has received consulting fees from Janssen, Merck and Bristol Myers Squibb and research support from Janssen for work unrelated to the present studies. S.Z. has received consulting fees from Guidepoint and GLG consulting. J.L.Z. is a current employee of AstraZeneca. M.C.H served as a paid consultant/received honoraria from Pfizer and has received research funding from Merck, Novartis, Genentech, Promicell and Bristol Myers Squibb. C.L.S is on the board of directors of Novartis, is a co-founder of ORIC Pharmaceuticals, and is a co-inventor of the prostate cancer drugs enzalutamide and apalutamide, covered by U.S. patents 7,709,517, 8,183,274, 9,126,941, 8,445,507, 8,802,689, and 9,388,159 filed by the University of California. C.L.S. is on the scientific advisory boards of the following biotechnology companies: Beigene, Blueprint, Cellcarta, Column Group, Foghorn, Housey Pharma, Nextech, PMV.

Testing for dispersal of fluorescent gel from sink drains was sensitive for detection of sinks that dispersed gram-negative bacilli outside the bowl. Reducing the flow rate of sinks with rapid water inflow and/or elimination of obstruction leading to slow outflow was effective in preventing dispersal of fluorescence and gram-negative bacilli., Competing Interests: Potential conflicts of interest. C. J. D. has received research funding from Clorox, Ecolab, and Pfizer. All other authors report no potential conflicts., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Objectives: This study aims to compare obstetric outcomes between Eritrean and Swiss women in Switzerland, focusing on instrumental or surgical interventions and analgesia use. Methods: The study included data from 45,412 Swiss and 1,132 Eritrean women who gave birth in Swiss hospitals (2019-2022). Mixed-effects logistic regression was used to assess the effect of nationality on mode of delivery and analgesia use and multinomial mixed-effects logistic regression to assess the effect of nationality on mode of delivery in women intended for spontaneous vaginal delivery. Results: Compared with Swiss, Eritrean women had a lower rate of primary C-section (Adj. OR 0.73, 95% CI [0.60, 0.89]) but a higher risk of initially planned vaginal deliveries ending in emergency C-section (RRR 1.31, 95% CI [1.05, 1.63]). Eritrean women were less likely to receive epidural analgesia (Adj. OR 0.53, 95% CI [0.45, 0.62]) and more likely to not receive any analgesia (Adj. OR 1.73, 95% CI [1.52, 1.96]). Conclusion: This study reveals disparities in obstetric care, notably in higher emergency C-section rates and lower analgesia use among Eritrean women. For promoting equitable healthcare practices deeper understanding of obstetrics decision-making is needed., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2024 Erhardt, Jafflin, Zepro, Abongomera, Chernet, Paris and Merten.)

This study aimed to review the considerations for choosing a suitable sealer according to various endodontic scenarios. An electronic search of PubMed, Scopus, and the Web of Science was undertaken for the keywords of 'sealer choosing', 'appropriate sealer', 'suitable sealer', 'sealer for clinical scenario', and 'sealer for clinical situations'. However, the literature review revealed a lack of studies with practical clinical recommendations regarding the choice of appropriate endodontic root canal sealers for particular clinical situations of root canal treatment. Therefore, a narrative review was undertaken under the basis of the characteristics of an epoxy resin-based sealer (ERS) versus a calcium silicate-based sealer (CSS). Based on the evidence found through the review, the choice of an appropriate sealer in a variety of clinical scenarios was proposed. An ERS is recommended for one-visit non-vital cases, teeth with periodontal involvement, cracked teeth, and internal root resorption without root perforation. A CSS is recommended for vital or non-vital cases in multiple visits, teeth with internal root resorption with perforation or internal approach for external cervical resorption, teeth with open apices, and teeth with iatrogenic aberrations.

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating chronic disease of significant public health and clinical importance. It affects multiple systems in the body and has neuro-immunological characteristics. The disease is characterized by a prominent symptom called post-exertional malaise (PEM), as well as abnormalities in the immune-inflammatory pathways, mitochondrial dysfunctions and disturbances in neuroendocrine pathways. The purpose of this study was to evaluate the impact of ME/CFS on the mental health and secondary psychosocial manifestations of patients, as well as their coping mechanisms., Method: In 2021, a descriptive cross-sectional study was conducted in Switzerland. A self-administered paper questionnaire survey was used to gather data from 169 individuals diagnosed with ME/CFS., Results: The majority of the patients (90.5%) reported a lack of understanding of their disease, resulting in patients avoiding talking about the disease due to disbelief, trivialization and avoidance of negative reactions. They felt most supported by close family members (67.1%). Two thirds of the patients (68.5%) experienced stigmatization. ME/CFS had a negative impact on mental health in most patients (88.2%), leading to sadness (71%), hopelessness for relief (66.9%), suicidal thoughts (39.3%) and secondary depression (14.8%). Half of the male patients experienced at least one suicidal thought since clinical onset. Factors significantly associated with depression were the lack of cure, disabilities associated with ME/CFS, social isolation and the fact that life was not worth anymore with ME/CFS. The three main factors contributing to suicidal thoughts were (i) being told the disease was only psychosomatic (89.5%), (ii) being at the end of one's strength (80.7%) and (iii) not feeling being understood by others (80.7%)., Conclusion: This study provided first time significant insights into the mental and psychological well-being of ME/CFS patients in Switzerland. The findings highlight the substantial experiences of stigmatization, secondary depression and suicidal thoughts compared to other chronic diseases, calling for an urgent need in Switzerland to improve ME/CFS patient's medical, psychological and social support, in order to alleviate the severe mental health burden associated with this overlooked somatic disease., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Systemic therapy (ST) is a psychotherapeutic intervention in complex human systems (both psychological and interpersonal). Cognitive behavioural therapy (CBT) is an established treatment for children and adolescents with mental disorders. As methodologically rigorous systematic reviews on ST in this population are lacking, we conducted a systematic review and meta-analysis to compare the benefit and harm of ST (and ST as an add-on to CBT) with CBT in children and adolescents with mental disorders., Methods: We searched MEDLINE, Embase, PsycINFO and other sources for randomised controlled trials in 14 mental disorder classes for the above comparisons in respect of effects on patient-relevant outcomes (search date: 7/2022). Where possible, meta-analyses were performed and results were graded into 3 different evidence categories: "proof", "indication", or "hint" (or none of these categories). PRISMA standards were followed., Results: Fifteen studies in 5 mental disorder classes with usable data were identified. 2079 patients (mean age: 10 to 19 years) were analysed. 12/15 studies and 29/30 outcomes showed a high risk of bias. In 2 classes, statistically significant and clinically relevant effects in favour of ST were found, supporting the conclusion of a hint of greater benefit of ST for mental and behavioural disorders due to psychoactive substance use and of ST as an add-on to CBT for obsessive-compulsive disorders. In 2 other classes (eating disorders; hyperkinetic disorders), there was no evidence of greater benefit or harm of ST. For affective disorders, a statistically significant effect to the disadvantage of ST was found for 1 outcome, supporting the conclusion of a hint of lesser benefit of ST., Conclusions: Our results show a hint of greater benefit of ST (or ST as an add-on to CBT) compared with CBT for 2 mental disorder classes in children and adolescents (mental and behavioural disorders due to psychoactive substance use, obsessive compulsive disorders). Given the importance of CBT as a control intervention, ST can therefore be considered a beneficial treatment option for children and adolescents with certain mental disorders. Limitations include an overall high risk of bias of studies and outcomes and a lack of data for several disorders., (© 2024. The Author(s).)

Mitigating heat is a vital ecosystem service of trees, particularly with climate change. Land surface temperature measures captured at a single time of day (in the morning) dominate the urban heat island literature. Less is known about how local tree canopy and impervious surface regulate air temperature throughout the day, and/or across many days with varied weather conditions, including cloud cover. We use bike-mounted air temperature sensors throughout the day in New Haven, Connecticut, USA, from 2019 to 2021 and generalized additive mixed models across 156 rides to estimate the daily variation in cooling benefits associated with tree canopy cover, and warming from impervious surface cover in 90 m buffers surrounding bike observations. Cooling is inferred by subtracting the bicycle-observed temperature from a reference station. The cooling benefits from tree canopy cover were strongest in the midday (11:00-14:00, -1.62 °C), afternoon (14:00-17:00, -1.19 °C), and morning (8:00-11:00, -1.15 °C) on clear days. The cooling effect was comparatively smaller on cloudy mornings -0.92 °C and afternoons -0.51 °C. Warming from impervious surfaces was most pronounced in the evening (17:00-20:00, 1.11 °C) irrespective of clouds, and during cloudy nights (20:00-23:00) and cloudy mornings 1.03 °C 95 % CI [1.03, 1.04]. Among the hottest observed days (top 25th percentile of reference station daily maxima), tree canopy was associated with lower temperatures on clear afternoons -1.78 °C [-1.78, -1.78], cloudy midday -1.17 °C [-1.19, -1.15], clear midday -1.12 °C [-1.12, -1.11]. We add a broader spectrum of weather conditions by explicitly including clouds, and greater temporal resolution by measuring throughout the day to bike-based urban heat research. Future mobile sampling campaigns may broaden the spatial extent with more environmental variation, representing an opportunity for public science and engagement., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

In the Northern Great Plains, cattle may be exposed to water with an elevated sulfate concentration resulting in ruminal hydrogen sulfide (H2S) production and risk of copper deficiency. There are currently few strategies available to help mitigate effects arising from high-sulfate water (HS). The objective of this study was to evaluate the effects of feeding a moderate-forage diet with or without bismuth subsalicylate (BSS; 0.0% vs. 0.4% DM basis) when provided water with a low- (LS; 346 ± 13) or HS (4,778 ± 263 mg/L) concentration on feed and water intake, ruminal H2S concentration, and liver and serum trace-mineral concentrations. Twenty-four Limousin × Simmental cross beef heifers (221 ± 41 kg) were stratified based on initial liver Cu into a completely randomized block design with a 2 × 2 factorial treatment arrangement. Feed and water intake (measured weekly), ruminal H2S concentration (measured on days 42 and 91), liver (measured on days -13 and 91), and serum trace-mineral concentrations (measured on days 1, 28, 56, and 91) were evaluated. Initial liver trace-mineral concentrations were used as a covariate in the statistical model. Water intake tended to be reduced with the inclusion of BSS (P = 0.095) but was not affected by water sulfate (P = 0.40). Water sulfate and BSS did not affect dry matter intake (DMI; P ≥ 0.89). Heifers consuming HS had a ruminal H2S concentration that was 1.58 mg/L more (P < 0.001) than LS. The inclusion of BSS reduced (P = 0.035) ruminal H2S concentration by more than 44% (1.35 vs. 0.75 mg/L). Regardless of the water sulfate concentration, heifers fed BSS had lesser liver Cu concentration (average of 4.08 mg/kg) than heifers not provided BSS, and when not provided BSS, HS had lesser Cu than LS (42.2 vs. 58.3; sulfate × BSS, P = 0.019). The serum concentration of Cu did not differ over time for heifers not provided BSS; whereas, heifers provided BSS had lesser serum Cu concentration on day 91 than on days 28 and 55 (BSS × time, P < 0.001). The liver concentration of selenium was reduced (P < 0.001) with BSS inclusion but the selenium concentration in serum was not affected by sulfate, BSS, or time (P ≥ 0.16). BSS reduced ruminal H2S concentration, but depleted liver Cu and Se. Moreover, sulfate concentration in water did not appear to affect DMI, water intake, or growth, but increased ruminal H2S and reduced liver Cu concentration., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: There is a risk for transmission of severe acute respiratory syndrome 2 (SARS-CoV-2) and other respiratory viruses in motor vehicles, particularly if ventilation is inadequate., Methods: We used carbon dioxide monitoring to examine the quality of ventilation in several public transportation buses and in university student shuttle vans in the Cleveland metro area during peak and non-peak travel times. Carbon dioxide levels above 800 parts per million (ppm) were considered an indicator of suboptimal ventilation for the number of people present. In the shuttle vans, we evaluated the impact of an intervention to improve ventilation., Results: In large articulated buses with 2 ventilation systems, carbon dioxide concentrations never exceeded 800 ppm, whereas in standard buses with 1 ventilation system concentrations rose above 800 ppm during peak travel times and on some trips during non-peak travel times. In shuttle vans, the ventilation system was not turned on during routine operation, and carbon dioxide levels rose above 800 ppm on all trips during peak and non-peak travel times. In the shuttle vans, an intervention involving operation of the existing ventilation system resulted in a significant reduction in carbon dioxide levels (mean concentration, 1,042 no intervention versus 785 with intervention; P < 0.001)., Conclusions: Our findings demonstrate substantial variability in the quality of ventilation in public transportation buses and university shuttle vans. There is a need for efforts to assess and optimize ventilation in motor vehicles used for public transportation to reduce the risk for aerosol-mediated transmission of respiratory viruses. Carbon dioxide monitoring may provide a useful tool to assess and improve ventilation., Competing Interests: C.J.D has received research grants from Clorox, Pfizer, and Ecolab. All other authors report no conflicts of interest relevant to this article., (Copyright © 2023 Pathogens and Immunity.)

Importance: Engineering of biological pathways in various microorganisms is a promising direction for biotechnology. Since the existing microbial cells have evolved over a long period of time, any artificial engineering may cause some unexpected and harmful effects on them. Systematically studying and evaluating these engineered strains are very important and necessary. In order to produce therapeutic proteins with human-like N-glycan structures, much progress has been achieved toward the humanization of N-glycosylation pathways in yeasts. The properties of a P. pastoris strain with humanized N-glycosylation machinery were carefully evaluated in this study. Our work has identified a key glycoprotein (PpSpi1) responsible for the poor growth and morphological defects of this glycoengineered strain. Overexpression of PpSpi1 could significantly rescue the growth defect of the glycoengineered P. pastoris and facilitate its future industrial applications., Competing Interests: The authors declare no conflict of interest.

Background: Brentuximab vedotin in combination with doxorubicin, vinblastine, and dacarbazine (AVD) is approved in the upfront setting for advanced stage classical Hodgkin lymphoma (cHL). People living with HIV have been excluded from these studies. We aimed to understand the activity and safety of brentuximab vedotin-AVD in people living with HIV diagnosed with Hodgkin lymphoma, while focusing on HIV disease parameters and antiretroviral therapy (ART) interactions., Methods: We present the phase 2 portion of a multicentre phase 1/2 study. Eligible patients were 18 years or older, had untreated stage II-IV HIV-associated cHL (HIV-cHL), a Karnofsky performance status of more than 30%, a CD4 + T-cell count of 50 cells per μL or more, were required to take ART, and were not on strong CYP3A4 or P-glycoprotein inhibitors. Patients were treated intravenously with 1·2 mg/kg of brentuximab vedotin (recommended phase 2 dose) with standard doses of AVD for six cycles on days 1 and 15 of a 28-day cycle. The primary endpoint of the phase 2 portion was 2-year progression-free survival (PFS), assessed in all eligible participants who began treatment. Accrual has been completed. This trial is registered at ClinicalTrials.gov, NCT01771107., Findings: Between March 8, 2013, and March 7, 2019, 41 patients received study therapy with a median follow up of 29 months (IQR 16-38). 34 (83%) of 41 patients presented with stage III-IV and seven (17%) with stage II unfavourable HIV-cHL. 37 (90%) of 41 patients completed therapy, all 37 of whom achieved complete response. The 2-year PFS was 87% (95% CI 71-94) and the overall survival was 92% (78-97). The most common grade 3 or worse adverse events were peripheral sensory neuropathy (four [10%] of 41 patients), neutropenia (18 [44%]), and febrile neutropenia (five [12%]). One treatment-related death was reported, due to infection., Interpretation: Brentuximab vedotin-AVD was highly active and had a tolerable adverse event rate in HIV-cHL and is an important therapeutic option for people with HIV-cHL. The complete reponse rate is encouraging and is possibly related to a unique aspect of HIV-cHL biology. Upcoming 5-year data will evaluate the sustainability of the outcomes obtained., Funding: National Institutes of Health and National Cancer Institute., Competing Interests: Declaration of interests AN has an MSK core grant National Institutes of Health (NIH) P30 CA008748 and NIH grant PO1 1568 G TA390. MAR is supported by the Johns Hopkins University Core Grant P30CA006973, contracts with Cullinan Apollo and RenovoRx, and is a founder and serves on the Board of Directors of Geminus Therapeutics. EGR is the co-chair of the National Comprehensive Cancer Network panel of Cancer in Persons With HIV and Kaposi Sarcoma, an unpaid position. PCM is supported by an MSK core grant (P30CA008748). PGR, AN, EGR, PCM, MB, JYL, RM, DHH, JCR, RFA, CD, MAR, AC, LR, and EC are supported in part by National Cancer Institute-sponsored AIDS Malignancy Consortium grant UM1CA121947 and UM1CA181255. RFA is supported by John Hopkins Cancer Center (5P30CA006973). CB and NM are supported in part by Lymphoma Study Association, and DC and YT are supported in part by the French Agency for Research on AIDS and Viral Hepatitis. DC also has contracts with Jansen and speaker bureau funding from Gilead and Pfizer. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: The implementation of Nationwide Water Fluoridation in Israel in 2002 led to a significant reduction in caries among children. However, this practice was discontinued in 2014 due to a change in legislation. In 2010, as part of the Israeli National Health Insurance Law, free dental care for children under 10 years of age was legislated. This policy was gradually extended to include adolescents under 18 years of age in 2018. We examined the association between these efforts and changes in the caries-related treatment needs of young adults over the course of two decades., Methods: This cross-sectional study analyzed data on the need for dental restorations, root canal therapy, and extractions that were retrieved from dental records of 34,450 soldiers recruited into military service between 2012 and 2021. These data were cross-matched with the subjects' year of birth to determine whether the implementation of water fluoridation, dental care legislation, or both were associated with changes in the need for and provision of dental care. Sociodemographic data, including sex, age, socioeconomic cluster (SEC), intellectual capability score (ICS), body mass index, and place of birth, were also extracted., Results: A multivariate generalized linear model (GLM) revealed that male sex, older age, low ICS, and low SEC were significant predictors for greater caries-related treatment needs (P < 0.001). Our findings indicated that subjects exposed to fluoridated water during their childhood had significantly lower rates of caries-related treatment, regardless of access to free dental care., Conclusion: Mandatory water fluoridation was associated with significantly lower caries-related treatment needs while national dental health legislation providing free dental care to children and adolescents was not. Therefore, we suggest that water fluoridation should be continued to maintain the observed reduction in treatment needs., Clinical Significance: Our findings provide support for the effectiveness of water fluoridation in preventing caries, whereas the impact of free dental care programs focused on clinical intervention remains to be determined., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Adolescents have special sexual and reproductive health (ASRH) needs and are susceptible to poor health outcomes. The global burden of ill sexual health includes a significant proportion of Adolescents. The existing ASRH services in Ethiopia and particularly in the Afar region are currently not well suited to meet the needs of pastoralist adolescents. This study assesses the level of ASRH service utilization among pastoralists in Afar regional state, Ethiopia., Method: A community based cross-sectional study was conducted from January to March 2021 in four randomly chosen pastoralist villages or kebeles of Afar, Ethiopia. A multistage cluster sampling procedure was used to select 766 volunteer adolescents aged 10-19. SRH services uptake was measured asking whether they had used any SRH service components during the last year. Data was collected through face-to-face interviews with a structured questionnaire; data entry was done with Epi info 3.5.1. Logistic regression analyses was used to assess associations with SRH service uptake. SPSS version 23 statistical software package was used for advanced logistic regression analyses to assess the associations between dependent and predictor variables., Results: The study revealed that two-thirds or 513 (67%) of the respondents are aware of ASRH services. However, only one-fourth (24.5%) of the enrolled adolescents used at least one ASRH service in the past twelve months. ASRH services utilization was significantly associated with gender (being female [AOR = 1.87 (CI 1.29-2.70)], being in school [AOR = 2.38(CI: 1.05-5.41), better family income [AOR = 10.92 (CI; 7.10-16.80)], prior discussions of ASRH issues [AOR = 4.53(CI: 2.52, 8.16)], prior sexual exposure [AOR = 4.75(CI: 1.35-16.70)], and being aware of ASRH services [AOR = 1.96 (CI: 1.02-3.822)]. Being pastoralist, religious and cultural restrictions, fear of it becoming known by parents, services not being available, income, and lack of knowledge were found to deter ASRH service uptake., Conclusion: Addressing ASRH needs of pastoralist adolescents is more urgent than ever, sexual health problems are increasing where these groups face broad hurdles to SRH service uptake. Although Ethiopian national policy has created an enabling environment for ASRH, multiple implementation issues require special attention to such neglected groups. "Gender-culture-context-appropriate" interventions are favorable to identify and meet the diverse needs of Afar pastoralist adolescents. Afar regional education bureau and concerned stakeholders need to improve adolescent education to overcome social barriers (e.g. humiliation, disgrace, and deterring gender norms) against ASRH services through community outreach programs. In addition, economic empowerment, peer education, adolescent counseling, and parent-youth communication will help address sensitive ASRH issues., (© 2023. The Author(s).)

Introduction: The role of a community pharmacist is well recognized in the literature as the most accessible health care provider that promotes health wellness and disease prevention. Evidence supports their role in cancer health promotion though this is not seen yet in practice. The aim of the study was to assess community pharmacists' preparedness in terms of knowledge, role perception and barriers for providing cancer health promotion in North Cyprus., Methods: A cross-sectional face-to-face questionnaire-based study was carried among a randomly selected representative sample of community pharmacists in North Cyprus between June 2020 and August 2020. A pre-validated 31-item questionnaire tool was revised by an expert panel and adopted for purpose of this study., Results: 200 (64.5%) out of 310 approached community pharmacists' have accepted and responded to the questionnaire of which 183 were fully answered. The community pharmacists' awareness of cancer was moderate, as 70% answered correctly. Most respondents (93.4%) agree that pharmacists should be involved in cancer health promotion. Most respondents (> 90%) agree that pharmacist's lack of interest in oncology, lack of educational material and pharmacist's hesitancy about their knowledge of cancer are respectively the most important barriers for cancer health promotion., Conclusion: The study shows that community pharmacist well perceives their role in cancer health promotion despite moderate awareness of cancer related facts and hesitancy of their knowledge necessary for assuming their role. Lack of interest, motivation and cancer educational materials availability are also major barrier to address.

Anemia is a common side effect of myelosuppressive chemotherapy; however, chemotherapy-induced anemia (CIA) management options are suboptimal. We evaluated the efficacy and safety of roxadustat in this setting. This open-label Phase 2 study included patients with non-myeloid malignancies and CIA (hemoglobin [Hb] ≤10 g/dL) who had planned concurrent myelosuppressive chemotherapy for ≥8 additional weeks. Oral roxadustat was administered for ≤16 weeks (starting dose 2.0 or 2.5 mg/kg, then titrated every 4 weeks). The primary efficacy endpoint was mean maximum change in Hb within 16 weeks of baseline without red blood cell (RBC) transfusion. Patients were assigned to roxadustat 2.0 (n = 31) or 2.5 mg/kg (n = 61) starting doses, and 89 were assessed for efficacy. The mean (standard deviation) maximum Hb change from baseline without RBC transfusion was 2.4 (1.5) and 2.5 (1.5) g/dL in the roxadustat 2.0 and 2.5 mg/kg groups, respectively. Median (range) time to Hb increase of ≥2 g/dL was 71 (57-92) days. Twelve patients (14.5%) had RBC transfusions (Week 5 to the end of treatment). Roxadustat was efficacious regardless of tumor type and chemotherapy regimen. Deep vein thrombosis (DVT) and pulmonary embolism (PE) occurred in 14 (15.2%) and nine (9.8%) patients, respectively, and three had serious adverse events attributed to roxadustat in the opinion of the investigators (PE: n = 2 [2.2%]; DVT: n = 1 [1.1%]). Roxadustat increased Hb in patients with CIA regardless of tumor type and chemotherapy regimen. Adverse events were consistent with observations in patients with advanced-stage malignancies., (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Introduction: over one third of total Disability-Adjusted-Life-Years lost in Kenya are due to non-communicable diseases (NCD). In response, the Government declared significant commitment towards improving NCD care. The COVID-19 pandemic increased the burden on the already overstretched health systems in Kenya. The aims of this study are to assess whether health care providers perceived NCD care to be optimal during the pandemic and explore how to improve responses to future emergencies., Methods: this cross-sectional online survey included healthcare personnel with non-clinical roles (public health workers and policy-makers) and those delivering health care (doctors and nurses). Respondents were recruited between May and September 2021 by random sampling, completed by snowball sampling., Results: among 236 participants (42% in clinical, 58% in non-clinical roles) there was an overall consensus between respondents on NCD care being disrupted and compromised during the pandemic in Kenya. Detracted supplies, funding, and technical resources affected the continuity of NCDs' response, despite government efforts. Respondents agreed that the enhanced personnel capacity and competencies to manage COVID-19 patients were positive, but noted a lack of guidance for redirecting care for chronic diseases, and advocated for digital innovation as a solution., Conclusion: this paper explores the perceptions of key stakeholders involved in the management of NCDs in Kenya to improve planning for future emergency responses. Gaps were identified in health system response and preparedness capacity during the pandemic including the perceived need to strengthen NCD services, with solutions offered to guide resilience efforts to protect the health system from disruption., Competing Interests: The authors declare no competing interests., (Copyright: Sugitha Sureshkumar et al.)

Structured illumination microscopy suffers from the need of sophisticated instrumentation and precise calibration. This makes structured illumination microscopes costly and skill-dependent. We present a novel approach to realize super-resolution structured illumination microscopy using an alignment non-critical illumination system and a reconstruction algorithm that does not need illumination information. The optical system is designed to encode higher order frequency components of the specimen by projecting PSF-modulated binary patterns for illuminating the sample plane, which do not have clean Fourier peaks conventionally used in structured illumination microscopy. These patterns fold high frequency content of sample into the measurements in an obfuscated manner, which are de-obfuscated using multiple signal classification algorithm. This algorithm eliminates the need of clean peaks in illumination and the knowledge of illumination patterns, which makes instrumentation simple and flexible for use with a variety of microscope objective lenses. We present a variety of experimental results on beads and cell samples to demonstrate resolution enhancement by a factor of 2.6 to 3.4 times, which is better than the enhancement supported by the conventional linear structure illumination microscopy where the same objective lens is used for structured illumination as well as collection of light. We show that the same system can be used in SIM configuration with different collection objective lenses without any careful re-calibration or realignment, thereby supporting a range of resolutions with the same system.

Background: Individuals with a history of tuberculosis (TB) disease are at higher risk of developing a subsequent episode than those without. Considering the role of social and environmental factors in tuberculosis, we assessed neighbourhood-level risk factors associated with recurrent tuberculosis in Cape Town, South Africa., Methods: This cohort consisted of patients who completed treatment for their first drug-sensitive TB episode between 2003 and 2015. Addresses were geocoded at neighbourhood level. Data on neighbourhood-level factors were obtained from the Census 2011 (household size, population density) and the City of Cape Town (Socio-Economic Index). Neighbourhood-level TB burden was calculated annually by dividing the number of notified TB episodes by the population in that neighbourhood. Multilevel survival analysis was performed with the outcome recurrent TB, defined as a second episode of TB, and controlling for individual-level risk factors (age, gender and time since first episode in years). Follow-up ended at the second episode, or on 31 December 2015, whichever came first., Results: The study included 173 421 patients from 700 neighbourhoods. Higher Socio-Economic Index was associated with a lower risk of recurrence compared with average Socio-Economic Index. An increased risk was found for higher household size and TB burden, with an increase of 20% for every additional person in mean household size and 10% for every additional TB episode/100 inhabitants. No association was found with population density., Conclusion: Recurrent TB was associated with increased household size and TB burden at neighbourhood level. These findings could be used to target TB screening activities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

During the past 4 decades, oral vancomycin has been a mainstay of Clostridioides difficile infection (CDI) therapy with no reports of treatment failure due to emergence of vancomycin resistance. However, C. difficile isolates with high-level phenotypic resistance to vancomycin have recently been reported in 3 distinct geographic regions. There is an urgent need for surveillance to determine if strains with reduced vancomycin susceptibility are circulating in other areas. In a Cleveland-area hospital, screening of 176 CDI stool specimens yielded no C. difficile isolates with reduced vancomycin susceptibility and highlighted the potential for false-positive results due to contamination with vancomycin-resistant enterococci. Additional studies are needed to clarify whether reduced vancomycin susceptibility is an emerging problem that will alter clinical practice. Clinicians should alert their health department if they observe a substantial increase in the frequency of vancomycin treatment failure in patients diagnosed with CDI with no alternative explanation for diarrhea., Competing Interests: Potential conflicts of interest. C. J. D. has received research funding from Clorox, PDI, and Pfizer. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2022.)

Purpose: To assess the efficacy and safety of cabozantinib plus nivolumab in a phase II trial in patients with non-clear-cell renal cell carcinoma (RCC)., Patients and Methods: Patients had advanced non-clear-cell renal carcinoma who underwent 0-1 prior systemic therapies excluding prior immune checkpoint inhibitors. Patients received cabozantinib 40 mg once daily plus nivolumab 240 mg once every 2 weeks or 480 mg once every 4 weeks. Cohort 1 enrolled patients with papillary, unclassified, or translocation-associated RCC; cohort 2 enrolled patients with chromophobe RCC. The primary end point was objective response rate (ORR) by RECIST 1.1; secondary end points included progression-free survival, overall survival, and safety. Next-generation sequencing results were correlated with response., Results: A total of 47 patients were treated with a median follow-up of 13.1 months. Objective response rate for cohort 1 (n = 40) was 47.5% (95% CI, 31.5 to 63.9), with median progression-free survival of 12.5 months (95% CI, 6.3 to 16.4) and median overall survival of 28 months (95% CI, 16.3 to not evaluable). In cohort 2 (n = 7), no responses were observed; one patient had stable disease > 1 year. Grade 3/4 treatment-related adverse events were observed in 32% treated patients. Cabozantinib and nivolumab were discontinued because of toxicity in 13% and 17% of patients, respectively. Common mutations included NF2 and FH in cohort 1 and TP53 and PTEN in cohort 2. Objective responses were seen in 10/12 patients with either NF2 or FH mutations., Conclusion: Cabozantinib plus nivolumab showed promising efficacy in most non-clear-cell RCC variants tested in this trial, particularly those with prominent papillary features, whereas treatment effects were limited in chromophobe RCC. Genomic findings in non-clear-cell RCC variants warrant further study as predictors of response.

The use of polytetrafluoroethylene (PTFE) tape as the base layer of temporary restorations had gained popularity mainly due to the ease of manipulation. The aim of this study was to assess whether this method changes the potential for bacterial growth and leakage of temporary restorations. The direct contact test and live/dead fluorescent staining were used for comparing Enterococcus faecalis growth and biofilm formation on PTFE, composite, intermediate restorative material (IRM) and Coltosol F. Confocal laser scanning microscopy was employed to evaluate E. faecalis penetration through 2 mm of PTFE, IRM or Coltosol F placed on the bottom of the pulp chamber and into radicular dentinal tubules in extracted maxillary third molars. The results demonstrated that E. faecalis grows on and penetrates through PTFE significantly more than it does with IRM and Coltosol F, revealing its comparably reduced overall antimicrobial sealing ability when placed as the base part of temporary restorations., (© 2022 Australian Society of Endodontology Inc.)

Background: Clinical practice guidelines recommend the use of bone-targeting agents for preventing skeletal-related events (SREs) among patients with bone metastases from solid tumors. The anti-RANKL monoclonal antibody denosumab is approved for the prevention of SREs in patients with bone metastases from solid tumors. However, real-world data are lacking on the impact of individual risk factors for SREs, specifically in the context of denosumab discontinuation., Purpose: We aim to identify risk factors associated with SRE incidence following denosumab discontinuation using a machine learning approach to help profile patients at a higher risk of developing SREs following discontinuation of denosumab treatment., Methods: Using the Optum PanTher Electronic Health Record repository, patients diagnosed with incident bone metastases from primary solid tumors between January 1, 2007, and September 1, 2019, were evaluated for inclusion in the study. Eligible patients received ≥ 2 consecutive 120 mg denosumab doses on a 4-week (± 14 days) schedule with a minimum follow-up of ≥ 1 year after the last denosumab dose, or an SRE occurring between days 84 and 365 after denosumab discontinuation. Extreme gradient boosting was used to develop an SRE risk prediction model evaluated on a test dataset. Multiple variables associated with patient demographics, comorbidities, laboratory values, treatments, and denosumab exposures were examined as potential factors for SRE risk using Shapley Additive Explanations (SHAP). Univariate analyses on risk factors with the highest importance from pooled and tumor-specific models were also conducted., Results: A total of 1,414 adult cancer patients (breast: 40%, prostate: 30%, lung: 13%, other: 17%) were eligible, of whom 1,133 (80%) were assigned to model training and 281 (20%) to model evaluation. The median age at inclusion was 67 (range, 19-89) years with a median duration of denosumab treatment of 253 (range, 88-2,726) days; 490 (35%) patients experienced ≥ 1 SRE 83 days after denosumab discontinuation. Meaningful model performance was evaluated by an area under the receiver operating curve score of 77% and an F1 score of 62%; model precision was 60%, with 63% sensitivity and 78% specificity. SHAP identified several significant factors for the tumor-agnostic and tumor-specific models that predicted an increased SRE risk following denosumab discontinuation, including prior SREs, shorter denosumab treatment duration, ≥ 4 clinic visits per month with at least one hospitalization (all-cause) event from the baseline period up to discontinuation of denosumab, younger age at bone metastasis, shorter time to denosumab initiation from bone metastasis, and prostate cancer., Conclusion: This analysis showed a higher cumulative number of SREs, prior SREs relative to denosumab initiation, a higher number of hospital visits, and a shorter denosumab treatment duration as significant factors that are associated with an increased SRE risk after discontinuation of denosumab, in both the tumor-agnostic and tumor-specific models. Our machine learning approach to SRE risk factor identification reinforces treatment guidance on the persistent use of denosumab and has the potential to help clinicians better assess a patient's need to continue denosumab treatment and improve patient outcomes., Competing Interests: Dionna Jacobson, Benoit Cadieux, and Basia A. Bachmann, were employees of Amgen. Marko Rehn and Hossam Saad are employees and stockholders of Amgen. Celestia S. Higano – consulting fees: Bayer, Ferring, Clovis Oncology, Blue Earth Diagnostics, Janssen, Hinova, Pfizer, AstraZeneca, Carrick Therapeutics, Novartis, Merck Sharp & Dohme, Astellas Pharma, Myovant Sciences, Genentech, Menarini; contracted research support: Aragon Pharmaceuticals, AstraZeneca, Medivation, Emergent BioSolutions, Bayer, Roche, Astellas Pharma, Clovis Oncology, Ferring Pharmaceuticals, eFFECTOR Therapeutics; ownership interest: CTI BioPharma CORP; honoraria: Astellas Pharma. David H. Henry has nothing to disclose. Alison T. Stopeck – consulting fees: Amgen, AstraZeneca, Athenex, BeiGene, Exact Sciences; contracted research support: Amgen, Genomic Health, AstraZeneca, Seattle Genetics; speaker’s bureau: Genomic Health; honoraria: Amgen., (© 2022 The Authors.)

Anemia is the predominant cytopenia in myelodysplastic syndromes (MDS) and treatment options are limited. Roxadustat is a hypoxia-inducible factor prolyl hydroxylase inhibitor approved for the treatment of anemia of chronic kidney disease in the UK, EU, China, Japan, South Korea, and Chile. MATTERHORN is a phase 3, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of roxadustat in anemia of lower risk-MDS. Eligible patients had baseline serum erythropoietin ≤ 400 mIU/mL, and a low packed RBC transfusion burden. In this open-label (OL), dose-selection, lead-in phase, enrolled patients were assigned to 1 of 3 roxadustat starting doses (n = 8 each): 1.5, 2.0, and 2.5 mg/kg. The primary efficacy endpoint of the OL phase was the proportion of patients with transfusion independence (TI) for ≥ 8 consecutive weeks in the first 28 treatment weeks. A secondary efficacy endpoint was the proportion of patients with a ≥ 50% reduction in RBC transfusions over an 8-week period compared with baseline. Adverse events were monitored. Patients were followed for 52 weeks. Of the 24 treated patients, TI was achieved in 9 patients (37.5%) at 28 and 52 weeks; 7 of these patients were receiving 2.5 mg/kg dose when TI was achieved. A ≥ 50% reduction in RBC transfusions was achieved in 54.2% and 58.3% of patients at 28 and 52 weeks, respectively. Oral roxadustat dosed thrice weekly was well tolerated. There were no fatalities or progression to acute myeloid leukemia. Based on these outcomes, 2.5 mg/kg was the chosen starting roxadustat dose for the ongoing double-blind study phase., (© 2021 Wiley Periodicals LLC.)

Background: Nearly half of HIV-related deaths occur in East and Southern Africa, yet data on causes of death (COD) are scarce. We determined COD and associated factors among people living with HIV (PLHIV) in rural Tanzania., Methods: PLHIV attending the Chronic Diseases Clinic of Ifakara, Morogoro are invited to enrol in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO). Among adults (≥ 15 years) enrolled in 2005-2018, with follow-up through April 2019, we classified COD in comprehensive classes and as HIV- or non-HIV-related. In the subset of participants enrolled in 2013-2018 (when data were more complete), we assessed cause-specific mortality using cumulative incidences, and associated factors using proportional hazards models., Results: Among 9871 adults (65% female, 26% CD4 count < 100 cells/mm 3 ), 926 (9%) died, among whom COD were available for 474 (51%), with missing COD mainly in earlier years. The most common COD were tuberculosis (N = 127, 27%), non-AIDS-related infections (N = 72, 15%), and other AIDS-related infections (N = 59, 12%). Cardiovascular and renal deaths emerged as important COD in later calendar years, with 27% of deaths in 2018 attributable to cardiovascular causes. Most deaths (51%) occurred within the first six months following enrolment. Among 3956 participants enrolled in 2013-2018 (N = 203 deaths, 200 with COD ascertained), tuberculosis persisted as the most common COD (25%), but substantial proportions of deaths from six months after enrolment onwards were attributable to renal (14%), non-AIDS-related infections (13%), other AIDS-related infections (10%) and cardiovascular (10%) causes. Factors associated with higher HIV-related mortality were sex, younger age, living in Ifakara town, HIV status disclosure, hospitalisation, not being underweight, lower CD4 count, advanced WHO stage, and gaps in care. Factors associated with higher non-HIV-related mortality included not having an HIV-positive partner, lower CD4 count, advanced WHO stage, and gaps in care., Conclusion: Incidence of HIV-related mortality was higher than that of non-HIV-related mortality, even in more recent years, likely due to late presentation. Tuberculosis was the leading specific COD identified, particularly soon after enrolment, while in later calendar years cardiovascular and renal causes emerged as important, emphasising the need for improved screening and management., (© 2022. The Author(s).)

Objective: Ritonavir-boosted protease inhibitors (bPI) in people living with HIV (PLWH) have been associated with renal impairment. Limited data are available from rural sub-Saharan Africa., Methods: Using data from the Kilombero and Ulanga Antiretroviral Cohort Study (KIULARCO) in rural Tanzania from 2005-01/2020, we assessed the prevalence of renal impairment (estimated glomerular filtration rate <60 mL/min/1.73m2) at the time of switch from first-line antiretroviral treatment (ART) to bPI-regimen and the incidence of renal impairment on bPI. We assessed risk factors for renal impairment using logistic and Cox regression models., Results: Renal impairment was present in 52/687 PLWH (7.6%) at the switch to bPI. Among 556 participants with normal kidney function at switch, 41 (7.4%) developed renal impairment after a median time of 3.5 (IQR 1.6-5.1) years (incidence 22/1,000 person-years (95%CI 16.1-29.8)). Factors associated with renal impairment at switch were older age (adjusted odds ratio (aOR) 1.55 per 10 years; 95%CI 1.15-2.11), body mass index (BMI) <18.5 kg/m2 (aOR 2.80 versus ≥18kg/m2; 95%CI 1.28-6.14) and arterial hypertension (aOR 2.33; 95%CI 1.03-5.28). The risk of renal impairment was lower with increased duration of ART use (aOR 0.78 per one-year increase; 95%CI 0.67-0.91). The renal impairment incidence under bPI was associated with older age (adjusted hazard ratio 2.01 per 10 years; 95%CI 1.46-2.78)., Conclusions: In PLWH in rural sub-Saharan Africa, prevalence and incidence of renal impairment among those who were switched from first-line to bPI-regimens were high. We found associations between renal impairment and older age, arterial hypertension, low BMI and time on ART., Competing Interests: The authors have declared that no competing interests exist.

Objective: Non-human teeth have been commonly used in research as replacements for human teeth, and potential dissimilarities between the dental tissues should be considered when interpreting the outcomes. To compare the proteolytic activity and degradation rate of bovine and human dentin matrices., Methodology: Dentin beam specimens were obtained from human molars (n=30) and bovine incisors (n=30). The beams were weighed hydrated and after complete dehydration to obtain the mineralized wet and dry masses. Then, the beams were demineralized in 10 wt% phosphoric acid. Next, 15 beams from each substrate were randomly selected and again dehydrated and weighed to obtain the initial demineralized dry mass (DM). Then, the beams were stored in saliva-like buffer solution (SLBS) for 7, 14 and 21 days. SLBS was used to evaluate hydroxyproline (HYP) release after each storage period. The remaining beams of each substrate (n=15) were tested for initial MMP activity using a colorimetric assay and then also stored in SLBS. DM and MMP activity were reassessed after 7, 14 and 21 days of incubation. The data were subjected to two-way ANOVA tests with repeated measures complemented by Bonferroni's tests. Unpaired two-tailed t-tests were also used (p<0.05)., Results: Similar water and inorganic fractions were found in human and bovine dentin, while human dentin had a higher protein content. The most intense proteolytic activity and matrix deterioration occurred short after dentin was demineralized. Both substrates exhibited a sharp reduction in MMP activity after seven days of incubation. Although human dentin had higher MMP activity levels, greater HYP release and DM loss after seven days than bovine dentin, after 14 and 21 days, the outcomes were not statistically different., Conclusion: Bovine dentin is a suitable substrate for long-term studies involving the degradation of dentin matrices.

Erythropoiesis-stimulating agents (ESA) are effective for chemotherapy-induced anemia (CIA) but associated with serious adverse events. Safer alternatives would be beneficial in this population. The efficacy and safety of ferric carboxymaltose (FCM) as monotherapy for CIA was evaluated. This Phase 3, 18-week, double-blind, placebo-controlled study randomized adults with ≥ 4 weeks of chemotherapy remaining for treatment of nonmyeloid malignancies with CIA to FCM (two 15 mg/kg infusions 7 days apart; maximum dose, 750 mg single/1500 mg total) or placebo. The primary efficacy endpoint was percentage of patients with decreases in hemoglobin (Hb) ≥ 0.5 g/dL from weeks 3 to 18; the key secondary efficacy endpoint was change in Hb from baseline to week 18. Inclusion criteria included: (Hb) 8-11 g/dL, ferritin 100-800 ng/mL, and transferrin saturation (TSAT) ≤35%. In 244 patients (n = 122, both groups), the percent of patients who maintained Hb within 0.5 g/dL of baseline from weeks 3 to 18 was significantly higher with FCM versus placebo (50.8% vs. 35.3%; p = 0.01). Mean change in Hb from baseline to week 18 was similar between FCM and placebo (1.04 vs. 0.87 g/dL) but significantly greater with FCM with baseline Hb ≤ 9.9 g/dL (1.08 vs. 0.42 g/dL; p = 0.01). The percent with ≥ 1 g/dL increase from baseline was significantly higher with FCM versus placebo (71% vs. 54%; p = 0.01), occurring in a median 43 versus 85 days (p = 0.001). Common adverse events in the FCM arm included neutropenia (17%), hypophosphatemia (16%), and fatigue (15%). FCM monotherapy effectively maintained Hb and was well tolerated in CIA., (© 2021 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Previous research has established an impact of acute exercise on cognitive performance, which has inspired investigations into neurobiological mechanisms that may underlie the observed benefits. Pupillary responses have been posited to reflect activation of such underlying neurobiological mechanisms. The current study recruited healthy young adults to investigate the effects of a single bout of moderate-to-vigorous intensity aerobic exercise on subsequent performance and pupillary responses during an inhibitory control task. Results showed that an acute bout of exercise was related to shorter reaction times and increased tonic pupil dilation during an inhibitory control task. Although pupillary responses did not mediate the acute exercise effect on inhibitory control, higher cardiorespiratory fitness was associated with greater phasic pupil dilation following exercise relative to seated rest. The current study supported the plausibility of the pupillary response as a marker of LC-NE system activation that is sensitive to acute exercise. Whether pupillary responses could account for transient benefits of acute exercise on brain and cognition remains unclear., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aim: To investigate macrophage function in the presence of sustained infection with Enterococcus faecalis, a prevalent root canal resident in asymptomatic apical periodontitis., Methodology: The human monocyte cell line (THP-1) was differentiated into macrophages by exposure to phorbol myristate acetate (PMA), and the cultures were inoculated with E. faecalis for up to 48 h. At three time-points 90 min, 24 and 48 h after inoculation, the macrophages and their supernatants were examined. Assays included macrophage phagocytosis rate and vitality, bacterial survival, reactive oxygen species (ROS) production, mitochondrial activity, cytokine production and the expression of pro/anti-inflammatory M1/M2 markers. Also, periapical tissue from apicectomy samples of human endodontically treated teeth were collected for histological and immunofluorescent analysis. Statistical differences were analysed with RM ANOVA., Results: E. faecalis were phagocytized, and subsequently, most of the macrophages underwent apoptosis and necrosis. The small population of macrophages that remained vital after 48 h post-inoculation harboured surviving bacteria. Despite a reduction in the number of macrophages over time, the mitochondrial activity of the surviving macrophages remained constant and external ROS decreased, whereas internal ROS increased. During the infection, a shift to a M2 macrophage population at 48 h post-infection was observed; the results were similar to those obtained in periapical human tissue biopsies (p < .05)., Conclusions: The study portrays a continuous non-resolved infection with E. faecalis and activation of macrophages that are polarized to the M2 pro-resolution phenotype., (© 2021 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Background: The risk factors for scrub typhus in Vietnam remain unknown. Scrub typhus caused by Orientia tsutsugamushi often presents as an undifferentiated febrile illness and remains under appreciated due to the limited availability of diagnostic tests. This tropical rickettsial illness is increasingly recognized as an important cause of non-malaria acute undifferentiated fever in Asia. This study aimed to investigate behavioural and ecological related risk factors of scrub typhus to prevent this potentially life-threatening disease in Vietnam., Methods: We conducted a clinical hospital-based active surveillance study, and a retrospective residence-enrolment date-age-matched case-control study in Khanh Hoa province, Vietnam, from August 2018 to March 2020. Clinical examinations, polymerase chain reaction and enzyme-linked immunosorbent assay IgM tests were applied to define cases and controls. All enrolled participants filled out a questionnaire including demographic socio-economic status, personal behaviors/protective equipment, habitat connections, land use, and possible exposure to the vector. Multivariable conditional logistic regression was used to define the scrub typhus associated risk factors., Results: We identified 44 confirmed cases and matched them with 152 controls. Among cases and controls, the largest age group was the 41-50 years old and males accounted for 61.4% and 42.8%, respectively. There were similarities in demographic characteristics between the two groups, with the exception of occupation. Several factors were significantly associated with acquisition of scrub typhus, including sitting/laying directly on household floor [adjusted OR (aOR) = 4.9, 95% CI: 1.6-15.1, P = 0.006], household with poor sanitation/conditions (aOR = 7.9, 95% CI: 1.9-32.9, P = 0.005), workplace environment with risk (aOR = 3.0, 95% CI: 1.2-7.6, P = 0.020), always observing mice around home (aOR = 3.7, 95% CI: 1.4-9.9, P = 0.008), and use of personal protective equipment in the field (aOR = 0.4, 95% CI: 0.1-1.1, P = 0.076)., Conclusions: Ecological and household hygiene-related factors were more associated with scrub typhus infection, than individual-level exposure activities in the hyper-endemic area. These findings support local education and allow people to protect themselves from scrub typhus, especially in areas with limitations in diagnostic capacity., (© 2021. The Author(s).)

Nasopalatine duct cysts (NPDCs) and other nonodontogenic lesions of the oral cavity may mimic odontogenic pathoses. We present a case of a 22-year-old man with a history of dental trauma and a lesion displaying the typical clinical and radiographic signs of a chronic apical abscess- a buccal sinus tract that was traced to a radiolucent area in the periapex of a maxillary central incisor. A comprehensive diagnostic process that included a cone-beam computed tomographic scan and a histopathologic examination of the lesion after complete enucleation led to the final diagnosis of an infected NPDC. The adjacent tooth was vital at the 1-year posttreatment follow-up, and a radiograph demonstrated complete healing of the periradicular structures. This case demonstrates the ability of NPDCs to present clinical and radiographic signs similar to apical inflammatory lesions and the need for a meticulous diagnostic process in order to avoid unnecessary endodontic intervention. The article also discusses the differential diagnoses of nonodontogenic lesions in the premaxillary area., (Copyright © 2021 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Purpose: The primary aims of this investigation were to describe the magnitude of asymmetries of common variables during running among healthy athletes and to determine if sex and speed influence magnitudes of asymmetry., Methods: This study analyzed routinely collected running gait data on healthy Division I collegiate athletes. All athletes had no history of lower extremity surgery, no lower extremity injuries for 3 months before testing, and running data available at 2.68, 2.95, 3.35, 3.80, and 4.47 m·s-1. Asymmetries were calculated for ground reaction forces, spatiotemporal metrics, joint kinematics, and joint kinetics. Separate linear mixed-effects models assessed the influence of sex, speed, and the interaction on asymmetries of interest. z Scores were calculated for significant effects to further assess the magnitude of differences., Results: Results from 204 athletes were included. The magnitude of asymmetry varied depending on the variable of interest, with asymmetries ≤3° observed for joint kinematics and greater asymmetries observed among joint work asymmetries ranging from 10% to 40%. No significant interactions between sex and speed were observed. Differences in sex and speed were noted; however, the effect sizes were very small based on z score comparison (-0.17 ≤ z ≤ 0.36) and were unlikely to be meaningful., Conclusions: The magnitude of asymmetry varies considerably depending on the running gait variable. Interpretation of between-limb asymmetry in running mechanics needs to be specific to the variable of interest, whereas sex or running speed seem to be minor factors., (Copyright © 2020 by the American College of Sports Medicine.)

Four cycles of rituximab plus CHOP chemotherapy is as effective as 6 cycles in low-risk diffuse large B-cell lymphoma (DLBCL). Here we report a post-hoc analysis of a prospective clinical trial in patients with HIV-associated DLBCL and high-grade lymphoma treated with 4-6 cycles of EPOCH plus rituximab based a response-adapted treatment strategy. 106 evaluable patients with HIV-associated DLBCL or high-grade CD20-positive non-Hodgkin's lymphoma were randomized to receive rituximab (375 mg/m2) given either concurrently prior to each infusional EPOCH cycle, or sequentially (weekly for 6 weeks) following completion of EPOCH. EPOCH consisted of a 96-hour IV infusion of etoposide, doxorubicin, and vincristine plus oral prednisone followed by IV bolus cyclophosphamide every 21 days for 4 to 6 cycles. Patients received 2 additional cycles of therapy after documentation of a complete response (CR) by computerized tomography after cycles 2 and 4. 64 of 106 evaluable patients (60%, 95% CI 50%, 70%) had a CR in both treatment arms. The 2-year event-free survival (EFS) rates were similar in the 24 patients with CR who received 4 or fewer EPOCH cycles (78%, 95% confidence intervals [55%, 90%]) due to achieving a CR after 2 cycles, compared with those who received 5-6 cycles of EPOCH (85%, 95% CI 70%, 93%) because a CR was first documented after cycle 4. A response-adapted strategy may permit a shorter treatment duration without compromising therapeutic efficacy in patients with HIV-associated lymphoma treated with EPOCH plus rituximab, which merits further evaluation in additional prospective trials. Clinical Trials.gov identifier NCT00049036.