Laboratory practice is central to earlier myeloma diagnosis: Utilizing a primary care diagnostic tool and laboratory guidelines integrated into haematology services.

Treatment advances have greatly improved survival, but myeloma is among the worst of all cancers for delayed diagnosis, causing serious morbidities and early deaths. This delay is largely because the symptom profile of myeloma has very low specificity, and in primary care, myeloma is rare. However, initiating the journey to diagnosis simply requires considering myeloma and sending blood to test for monoclonal immunoglobulin. Laboratory tests reliably detect monoclonal immunoglobulin, which is present in 99% of myeloma cases, so why do health care systems have such a problem with delayed diagnosis? The Myeloma UK early diagnosis programme has brought together diverse expertise to investigate this problem, and this article was prepared by the programme's working group for laboratory best practice. It reviews evidence for test requesting, analysis and reporting, for which there is large variation in practice across the United Kingdom. It presents a 'GP Myeloma diagnostic tool' and how it can be integrated into laboratory practice alongside a laboratory best practice tool. It proposes improved requesting and integration with haematology services for reporting and interpretation. Here the laboratory has a central role in creating efficient and cost-effective pathways for appropriate and timely bone marrow examination for myeloma diagnosis.

Investigating the Current Harmonization Status of Tumor Markers Using Global External Quality Assessment Programs: A Feasibility Study.

BACKGROUND: The harmonization status of most tumor markers (TMs) is unknown. We report a feasibility study performed to determine whether external quality assessment (EQA) programs can be used to obtain insights into the current harmonization status of the tumor markers α-fetoprotein (AFP), prostate specific antigen (PSA), carcinoembryonic antigen (CEA), cancer antigen (CA)125, CA15-3 and CA19-9. METHODS: EQA sample results provided by 6 EQA providers (INSTAND [Germany], Korean Association of External Quality Assessment Service [KEQAS, South Korea], National Center for Clinical Laboratories [NCCL, China], United Kingdom National External Quality Assessment Service [UK NEQAS, United Kingdom], Stichting Kwaliteitsbewaking Medische Laboratoriumdiagnostiek [SKML, the Netherlands], and the Royal College of Pathologists of Australasia Quality Assurance Programs [RCPAQAP, Australia]) between 2020 and 2021 were used. The consensus means, calculated from the measurement procedures present in all EQA programs (Abbott Alinity, Beckman Coulter DxI, Roche Cobas, and Siemens Atellica), was used as reference values. Per measurement procedure, the relative difference between consensus mean for each EQA sample and the mean of all patient-pool-based EQA samples were calculated and compared to minimum, desirable, and optimal allowable bias criteria based on biological variation. RESULTS: Between 19040 (CA15-3) and 25398 (PSA) individual results and 56 (PSA) to 76 (AFP) unique EQA samples were included in the final analysis. The mean differences with the consensus mean of patient-pool-based EQA samples for all measurement procedures were within the optimum bias criterion for AFP, the desirable bias for PSA, and the minimum bias criterion for CEA. However, CEA results <8 µg/L exceeded the minimum bias criterion. For CA125, CA15-3, and CA19-9, the harmonization status was outside the minimum bias criterion, with systematic differences identified. CONCLUSIONS: This study provides relevant information about the current harmonization status of 6 tumor markers. A pilot harmonization investigation for CEA, CA125, CA15-3, and CA19-9 would be desirable.

Detection of antinuclear antibodies: recommendations from EFLM, EASI and ICAP.

OBJECTIVES: Antinuclear antibodies (ANA) are important for the diagnosis of various autoimmune diseases. ANA are usually detected by indirect immunofluorescence assay (IFA) using HEp-2 cells (HEp-2 IFA). There are many variables influencing HEp-2 IFA results, such as subjective visual reading, serum screening dilution, substrate manufacturing, microscope components and conjugate. Newer developments on ANA testing that offer novel features adopted by some clinical laboratories include automated computer-assisted diagnosis (CAD) systems and solid phase assays (SPA). METHODS: A group of experts reviewed current literature and established recommendations on methodological aspects of ANA testing. This process was supported by a two round Delphi exercise. International expert groups that participated in this initiative included (i) the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group "Autoimmunity Testing"; (ii) the European Autoimmune Standardization Initiative (EASI); and (iii) the International Consensus on ANA Patterns (ICAP). RESULTS: In total, 35 recommendations/statements related to (i) ANA testing and reporting by HEp-2 IFA; (ii) HEp-2 IFA methodological aspects including substrate/conjugate selection and the application of CAD systems; (iii) quality assurance; (iv) HEp-2 IFA validation/verification approaches and (v) SPA were formulated. Globally, 95% of all submitted scores in the final Delphi round were above 6 (moderately agree, agree or strongly agree) and 85% above 7 (agree and strongly agree), indicating strong international support for the proposed recommendations. CONCLUSIONS: These recommendations are an important step to achieve high quality ANA testing.

Pharmacotherapy Prescriptions for Relapse Prevention of Psychotic Depression After Electroconvulsive Therapy.

PURPOSE/BACKGROUND: Electroconvulsive therapy (ECT) is effective in the treatment of acute episodes of psychotic depression. However, no adequately powered studies have directly investigated the efficacy of antipsychotic pharmacotherapy in relapse prevention of psychotic depression after ECT. In the absence of such literature, we reviewed the clinical practice of 4 academic medical centers that have made research contributions in the treatment of psychotic depression over the past 20 years. METHODS/PROCEDURES: We reviewed medical records of patients with a diagnosis of psychotic depression who received 1 or more acute courses of ECT over the span of 3 years. Chi-square tests were used to compare pharmacotherapy prescribed at the time of completion of ECT. FINDINGS/RESULTS: A total of 163 patients received 176 courses of ECT for separate episodes of psychotic depression. The combination of an antidepressant plus an antipsychotic was the most common regimen, ranging from 61.9% to 85.5% of all prescriptions. One center added lithium in 45.5% of cases treated with the combination of an antidepressant plus an antipsychotic. An antipsychotic alone was prescribed in less than 10% of cases. An antidepressant alone or other drug combinations were rare. IMPLICATIONS/CONCLUSIONS: The combination of an antidepressant plus an antipsychotic was the most commonly prescribed regimen at the completion of ECT for relapse prevention in patients with psychotic depression acutely treated with ECT. Although this report offers a view of the clinical practice of 4 academic medical centers, it also points to the need of randomized controlled trials on continuation pharmacotherapy after treatment of psychotic depression with ECT.

Hepatitis B infection and risk factors among pregnant women and their male partners in the Baby Shower Programme in Nigeria: a cross-sectional study.

OBJECTIVES: To determine the population prevalence and determinants of hepatitis B (Hep B) status, and status discordance, among pregnant women and their male partners in Nigeria. METHODS: Cross-sectional study assessing the seroprevalence of Hep B virus in a cohort of 16 920 pregnant women and their male partners in northcentral Nigeria. Rapid HBsAg antibody test was used for Hep B diagnosis. Demographic, socio-economic and behavioural information was collected through interviewer-administered questionnaires and evaluated as determinants of Hep B status and couple status discordance using logistic regression. RESULTS: Of 16 920 participants who had a Hep B test result, 6750 couples and 1316 discordant couples were identified. The prevalence of Hep B among all participants was 10.9%, with lower prevalence among pregnant women (10.2%) than their male partners (11.9%), P < 0.001. The prevalence of Hep B sero-discordance among couples was 19.5% (1316/6750). Younger age, prior Hep B testing and a prior positive Hep B test increased the odds of Hep B infection while being a woman decreased the odds of Hep B among all participants, and among couples. Furthermore, polygamy (adjusted odds ratio [AOR]: 1.49, 95% confidence interval [CI]: 1.19-1.87), prior Hep B testing (AOR: 2.38, 95% CI: 1.14-4.97) and a prior positive Hep B test result were significant determinants of status discordance among the participating couples. CONCLUSION: The prevalence of Hep B among pregnant women and their male partners in northcentral Nigeria is high. A large-scale intervention is required to reduce Hep B prevalence in this setting.

OBJECTIFS: Déterminer la prévalence dans la population et les déterminants du statut de l'hépatite B (Hep B) et de la discordance de statut chez les femmes enceintes et leurs partenaires masculins au Nigéria. MÉTHODES: Etude transversale évaluant la séroprévalence du virus Hep B dans une cohorte de 16.920 femmes enceintes et leurs partenaires masculins dans le centre-nord du Nigéria. Un test rapide des anticorps anti-HBsAg a été utilisé pour le diagnostic de l'Hep B. Des informations démographiques, socio-économiques et comportementales ont été recueillies au moyen de questionnaires administrés par les intervieweurs et évaluées en tant que déterminants du statut Hep B et de la discordance du statut de couple à l'aide de la régression logistique. RÉSULTATS: Sur 16.920 participants qui avaient un résultat de dépistage de l'Hep B, 6.750 couples et 1.316 couples discordants ont été identifiés. La prévalence de l'Hep B chez tous les participants était de 10,9%, avec une prévalence plus faible chez les femmes enceintes (10,2%) que chez leurs partenaires masculins (11,9%), p <0,001. La prévalence de la séro-discordance de l'Hep B chez les couples était de 19,5% (1.316/6.750). Un âge plus jeune, un dépistage antérieur de l'Hep B et un test Hep B positif antérieur augmentaient les risques d'infection à l'Hep B alors que le sexe féminin diminuait les risques d'Hep B chez tous les participants et parmi les couples. De plus, la polygamie (rapport de cotes ajusté [AOR]: 1,49, intervalle de confiance [IC] à 95%: 1,19-1,87), un dépistage antérieur de l'Hep B (AOR: 2,38 ; IC95%: 1,14-4,97) et un test hépatique B positif antérieur résultat étaient des déterminants significatifs de la discordance de statut parmi les couples participants. CONCLUSION: La prévalence de l'Hep B chez les femmes enceintes et leurs partenaires masculins dans le centre-nord du Nigéria est élevée. Une intervention à grande échelle est nécessaire pour réduire la prévalence de l'Hep B dans cette région.

Opportunities and challenges to integrating mental health into HIV programs in a low- and middle-income country: insights from the Nigeria implementation science Alliance.

BACKGROUND: In Nigeria, there is an estimated 1.9 million people living with HIV (PLHIV), 53% of whom utilize HIV care and services. With decreasing HIV-related deaths and increasing new infections, HIV with its associated comorbidities continue to be a key public health challenge in Nigeria. Untreated, comorbid mental disorders are a critical but potentially modifiable determinant of optimal HIV treatment outcomes. This study aimed to identify the challenges and opportunities related to integrating mental health care into existing HIV programs in Nigeria. METHOD: Attendees at the Nigeria Implementation Science Alliance (NISA)'s 2019 conference participated in nominal group technique (NGT) exercise informed by the "Exploration, Preparation, Implementation, and Sustainment (EPIS)" framework. The NGT process was conducted among the nominal groups in two major sessions of 30-min phases followed by a 30-min plenary session. Data analysis proceeded in four steps: transcription, collation, theming and content analysis. RESULTS: The two major theoretical themes from the study were - opportunities and challenges of integrating mental health treatment into HIV services. Three sub-themes emerged on opportunities: building on health care facilities for HIV services (screening, counseling, task-sharing monitoring and evaluation frameworks), utilizing existing human resources or workforce in HIV programs (in-service training and including mental health in education curriculum) and the role of social and cultural structures (leveraging existing community, traditional and faith-based infrastructures). Four sub-themes emerged for challenges: double burden of stigma and the problems of early detection (HIV and mental health stigma, lack of awareness), existing policy gaps and structural challenges (fragmented health system), limited human resources for mental health care in Nigeria (knowledge gap and burnout) and dearth of data/evidence for planning and action (research gaps). CONCLUSIONS: Potential for integrating treatments for mental disorders into HIV programs and services exist in Nigeria. These include opportunities for clinicians' training and capacity building as well as community partnerships. Multiple barriers and challenges such as stigma, policy and research gaps would need to be addressed to leverage these opportunities. Our findings serve as a useful guide for government agencies, policy makers and research organizations to address co-morbid mental disorders among PLHIV in Nigeria.

Developing a Theoretical Framework for a Complex Maternal-Child Health Intervention: Health Beginning Initiative.

A theoretical framework serves as a roadmap for the implementation and application of a complex, health promotion intervention; is used to test hypotheses; and guides analysis and evaluation of the intervention. The purpose of this article is to demonstrate how a theoretical framework was developed and used to guide the implementation of Healthy Beginning Initiative (HBI) to promote uptake of HIV services in a low-income country. We used the guide for developing a theoretical framework published in Health Promotion Practice. Developing the theoretical framework included seven steps: (1) identifying the essential elements of the intervention; (2) identifying the variables and the context; (3) listing the postulated mechanisms, mediating variables, and postulated outcomes; (4) identifying existing theoretical models supporting the theoretical framework underdevelopment; (5) scripting the theoretical framework into either a figure or sets of statements; (6) conducting content and face validation of the theoretical framework; and (7) revising the theoretical framework. The theoretical framework was developed and used to evaluate HBI's impact on HIV testing, linkage to care and retention in care for pregnant women, their male partners, and newborns. The theoretical framework will also be adapted for other screenings and other settings while remaining true to the essential elements of HBI.

"PSYCH-PASS": the Development, Adaptation, and Implementation of a Psychiatric Handoff.

OBJECTIVE: The primary purpose of the study was to develop and implement a psychiatry mnemonic PSYCH-PASS for transitions of care in residency training programs. METHODS: The authors examined areas of improvement in the handoff system with residency training administration, service directors, and psychiatry residents to create PSYCH-PASS, a novel mnemonic that could be integrated in the electronic medical record (EMR). The components of PSYCH-PASS are Patient summary, Situational awareness, "whY" is the patient here, Comorbidities, Hemodynamics, Pharmacology/PRNs, Action list, Specifics, and Synthesis. The authors developed a 14 question pre- and post-survey with a 4-point Likert scale measuring five categories. RESULTS: Pre-survey and post-surveys completed by post-graduate year 2 and 3 residents at Montefiore Medical Center (n = 24) noted increased satisfaction, handoff efficiency, handoff efficiency, accessibility, accuracy, communication, awareness, and adherence to PSYCH-PASS, along with a decrease in frequency of errors. CONCLUSIONS: With promising results across a range of metrics indicating resident-reported positive impacts on patient care, further research on the implementation of PSYCH-PASS and its integration into EMR systems is merited. Future directions include gathering objective data from Epic and expansion of the initiative to other psychiatric services and institutions.

A Patient-Held Smartcard With a Unique Identifier and an mHealth Platform to Improve the Availability of Prenatal Test Results in Rural Nigeria: Demonstration Study.

BACKGROUND: Community-based strategies to test for HIV, hepatitis B virus (HBV), and sickle cell disease (SCD) have expanded opportunities to increase the proportion of pregnant women who are aware of their diagnosis. In order to use this information to implement evidence-based interventions, these results have to be available to skilled health providers at the point of delivery. Most electronic health platforms are dependent on the availability of reliable Internet connectivity and, thus, have limited use in many rural and resource-limited settings. OBJECTIVE: Here we describe our work on the development and deployment of an integrated mHealth platform that is able to capture medical information, including test results, and encrypt it into a patient-held smartcard that can be read at the point of delivery without the need for an Internet connection. METHODS: We engaged a team of implementation scientists, public health experts, and information technology specialists in a requirement-gathering process to inform the design of a prototype for a platform that uses smartcard technology, database deployment, and mobile phone app development. Key design decisions focused on usability, scalability, and security. RESULTS: We successfully designed an integrated mHealth platform and deployed it in 4 health facilities across Benue State, Nigeria. We developed the Vitira Health platform to store test results of HIV, HBV, and SCD in a database, and securely encrypt the results on a Quick Response code embedded on a smartcard. We used a mobile app to read the contents on the smartcard without the need for Internet connectivity. CONCLUSIONS: Our findings indicate that it is possible to develop a patient-held smartcard and an mHealth platform that contains vital health information that can be read at the point of delivery using a mobile phone-based app without an Internet connection. TRIAL REGISTRATION: ClinicalTrials.gov NCT03027258; https://clinicaltrials.gov/ct2/show/NCT03027258 (Archived by WebCite at http://www.webcitation.org/6owR2D0kE).

Gaps and strategies in developing health research capacity: experience from the Nigeria Implementation Science Alliance.

BACKGROUND: Despite being disproportionately burdened by preventable diseases than more advanced countries, low- and middle-income countries (LMICs) continue to trail behind other parts of the world in the number, quality and impact of scholarly activities by their health researchers. Our strategy at the Nigerian Implementation Science Alliance (NISA) is to utilise innovative platforms that catalyse collaboration, enhance communication between different stakeholders, and promote the uptake of evidence-based interventions in improving healthcare delivery. This article reports on findings from a structured group exercise conducted at the 2016 NISA Conference to identify (1) gaps in developing research capacity and (2) potential strategies to address these gaps. METHODS: A 1-hour structured group exercise was conducted with 15 groups of 2-9 individuals (n = 94) to brainstorm gaps for implementation, strategies to address gaps and to rank their top 3 in each category. Qualitative thematic analysis was used. First, duplicate responses were merged and analyses identified emerging themes. Each of the gaps and strategies identified were categorised as falling into the purview of policy-makers, researchers, implementing partners or multiple groups. RESULTS: Participating stakeholders identified 98 gaps and 91 strategies related to increasing research capacity in Nigeria. A total of 45 gaps and an equal number of strategies were ranked; 39 gaps and 43 strategies were then analysed, from which 8 recurring themes emerged for gaps (lack of sufficient funding, poor research focus in education, inadequate mentorship and training, inadequate research infrastructure, lack of collaboration between researchers, research-policy dissonance, lack of motivation for research, lack of leadership buy-in for research) and 7 themes emerged for strategies (increased funding for research, improved research education, improved mentorship and training, improved infrastructure for research, increased collaboration between academic/research institutions, greater engagement between researchers and policy-makers, greater leadership buy-in for research). CONCLUSIONS: The gaps and strategies identified in this study represent pathways judged to be important in increasing research and implementation science capacity in Nigeria. The inclusion of perspectives and involvement of stakeholders who play different roles in policy, research and implementation activities makes these findings comprehensive, relevant and actionable, not only in Nigeria but in other similar LMICs.

What do You Need to Get Male Partners of Pregnant Women Tested for HIV in Resource Limited Settings? The Baby Shower Cluster Randomized Trial.

Male partner involvement has the potential to increase uptake of interventions to prevent mother-to-child transmission of HIV (PMTCT). Finding cultural appropriate strategies to promote male partner involvement in PMTCT programs remains an abiding public health challenge. We assessed whether a congregation-based intervention, the Healthy Beginning Initiative (HBI), would lead to increased uptake of HIV testing among male partners of pregnant women during pregnancy. A cluster-randomized controlled trial of forty churches in Southeastern Nigeria randomly assigned to either the HBI (intervention group; IG) or standard of care referral to a health facility (control group; CG) was conducted. Participants in the IG received education and were offered onsite HIV testing. Overall, 2498 male partners enrolled and participated, a participation rate of 88.9%. Results showed that male partners in the IG were 12 times more likely to have had an HIV test compared to male partners of pregnant women in the CG (CG = 37.71% vs. IG = 84.00%; adjusted odds ratio = 11.9; p < .01). Culturally appropriate and community-based interventions can be effective in increasing HIV testing and counseling among male partners of pregnant women.

Timely reminder interventions to improve annual Papanicolaou (Pap) smear rates among HIV-infected women in an outpatient center of southern Nevada: a short report.

Current guidelines recommend annual Papanicolaou (Pap) smears for human immunodeficiency virus (HIV)-infected women for cervical cancer screening. Rates for such screening in Nevada are below the national rate. Our cohort includes 485 eligible HIV-infected adult women from an outpatient center in Southern Nevada of which only 12 women had obtained a Pap smear in the past year. An intervention was conducted from June 2015 to September 2015, in which reminders to schedule a Pap smear were sent to the remaining cohort of 473 women via sequential text messaging, followed by phone call attempts. Of all subjects, 94% contacted by text messages and 41% contacted by phone calls were successfully reached. There was an increase in the rate of completed Pap smears from 2.5% (12/485) at baseline to 11.8% (56/473) after interventions (p < 0.0001) in a period of three months. Out of the 68 Pap smear results, 20 (29.4%) were abnormal. Our intervention, utilizing methods of communication such as text messaging and phone calls, markedly increased the rate of completed Pap smear screening in our population.

Using a Cultural Framework to Understand Factors Influencing HIV Testing in Nigeria.

With support from the U.S. President's Emergency Plan for AIDS Relief and the global fund for HIV, tuberculosis, and malaria, Nigeria offers free services for prevention of mother-to-child transmission of HIV. However, uptake of these services is low, and pediatric transmission of HIV remains a significant public health challenge. Using the PEN-3 cultural model as the theoretical framework, we examined social, cultural, and contextual factors that influenced uptake of HIV counseling and testing among pregnant women and their male partners. This was a qualitative study of participants in the Healthy Beginning Initiative (HBI), a congregation-based program to prevent mother-to-child transmission of HIV in Enugu, southeast Nigeria. We conducted eight focus group discussion sessions with 83 pregnant women and their male partners. Participants' perspectives on why they did or did not test for HIV were obtained. The most cited reasons for getting tested for HIV included the following: "the need to know one's status", "the role of prenatal testing" (positive perceptions); "the role of the church", "personal rapport with healthcare worker" (positive enablers); and the "influence of marriage" (positive nurturer). The most cited reason for not testing were: "fear of HIV test", "shame associated with HIV+ test results", "conspiratorial beliefs about HIV testing" (negative perceptions); "lack of confidentiality with HIV testing", (negative enabler); and "HIV-related stigma from family and community systems" (negative nurturer). Overall, numerous facilitators and barriers influence uptake of HIV testing in the study setting. Public health practitioners and policymakers need to consider how sociocultural and religious factors unique to specific local contexts may promote or hinder uptake of available HIV/AIDS prevention and care interventions.

Impact of male partner's awareness and support for contraceptives on female intent to use contraceptives in southeast Nigeria.

BACKGROUND: Despite the growing body of evidence on use of modern contraceptives among women in sub-Saharan African countries, little is known about the broader context in which female decision-making concerning contraceptive use occurs, particularly the role of their male partners' awareness and support of modern contraceptives. METHODS: We conducted a cross-sectional survey of 2468 pregnant women and their male partners enrolled in the Healthy Beginning Initiative (HBI), an intervention to increase HIV testing among pregnant women in Enugu, southeast Nigeria. The aims of this study were to determine: 1) male partners' awareness of, and support for, female contraceptive methods, and 2) influence of male partners' contraceptive awareness and support on pregnant women's expressed desire to use contraception. We used logistic regression models to examine the association between male partners' awareness and support of modern contraceptives on their spouses' desire to use contraceptives. RESULTS: Men's awareness of, and support for, use of modern contraceptives were significantly associated with their female partners' desire to use contraception. A majority of the men who were aware of modern contraceptives (66.5 %) and those who supported their spouses' use of contraception (72.5 %) had partners who expressed a desire to use contraception. Men who were aware of female contraception were 3 times more likely to have spouses who desired to use contraception (AOR = 3.17, 95 % C.I: 2.70-3.75). In addition, men who showed support for their spouses' use of contraception were over 5 times more likely to have spouses who indicated a desire to use contraception (AOR = 5.76, 95 % C.I: 4.82-6.88). Living in a household of 5 or more people (AOR = 1.45, 95 % C.I: 1.23-1.72) and residing in an urban area (AOR = 0.81, 95 % C.I: 0.67-0.97) were also significantly associated with women's expressed desire to use modern contraception. CONCLUSION: Men's awareness of, and support for, use of modern contraceptives were markedly associated with their spouses' desire to use contraception. This underscores the need for men's involvement in programs that seek to address women's uptake of contraception in low and middle income countries.

Floxuridine hepatic arterial infusion associated biliary toxicity is increased by concurrent administration of systemic bevacizumab.

PURPOSE: Systemic bevacizumab (Bev) was added to hepatic arterial infusion (HAI) floxuridine (FUDR)-based chemotherapy in three studies in an attempt to improve outcomes. A specific review of biliary toxicity was carried out. METHODS: This analysis included 203 patients from three prospective studies. The first (study A) was an adjuvant study after liver resection of colorectal metastases in which patients received HAI and systemic chemotherapy (Sys) with or without Bev. Study B comprised unresectable colorectal patients who received HAI and Sys plus Bev. Study C included patients with unresectable cholangiocarcinoma or hepatocellular carcinoma who received HAI plus systematic Bev. The outcome and toxicity of patients in studies B and C were compared with historical controls. RESULTS: In all three studies, the incidence of hyperbilirubinemia and biliary stent placement within 1 year of treatment was increased with the addition of Bev. In the no-Bev versus Bev groups, the placement of biliary stents was as follows: study A, 0 of 38 versus 4 of 35 patients (p = 0.05); study B, 0 of 49 versus 3 of 24 (p = 0.06); and study C, 0 of 34 versus 3 of 22 (p = 0.15). Elevation in bilirubin was noted in the no-Bev versus Bev groups: study A, 0 of 38 versus 5 of 35 patients (p = 0.02); study B, 1 of 49 versus 7 of 24 (p = 0.005); and study C, 2 of 34 versus 5 of 22 (p = 0.10). The addition of Bev did not seem to be associated with improved progression-free or overall survival. CONCLUSIONS: The addition of Bev to HAI FUDR resulted in increased biliary toxicity in three separate studies. Although the sample sizes were small, there was no evidence of improved PFS or OS with the addition of Bev. Bev should not be combined with HAI FUDR.

The 3rd International Standard for serum IgE: international collaborative study to evaluate a candidate preparation.

BACKGROUND: The measurement of serum IgE aids in the diagnosis and management of atopic allergic disease and hyper-IgE immunodeficiency syndromes. The 2nd World Health Organization (WHO) International Reference Reagent (IRR) for serum IgE (75/502; 5000 IU/ampoule), is widely used to calibrate assays for serum IgE. Exhaustion of stocks of the 2nd IRR necessitated the production of a replacement preparation and its evaluation in an international collaborative study to determine its suitability to serve as the 3rd International Standard (IS) for serum IgE. METHODS: Sera and defibrinated plasma with elevated IgE levels were pooled and lyophilised in ampoules. This preparation, coded 11/234, was assayed by 18 laboratories in 11 countries using commercial assay methodology for IgE, along with the 2nd IRR, 75/502, and two lyophilised serum samples. RESULTS: Overall, there were no consistent differences in the way that the candidate IS (11/234), the IRR (75/502), and the two serum samples behaved in the assays with respect to linearity and parallelism. The mean IgE value of the candidate IS, 11/234, relative to the IRR, 75/502, was 13,411 IU/mL based on parallel line analysis of raw assay data at NIBSC, and 13,551 IU/mL based on the laboratories' own estimates after correcting for the values obtained for 75/502. CONCLUSIONS: The use of 11/234 will ensure that assays for serum IgE continue to be well standardised. The preparation was established by the WHO Expert Committee on Biological Standardization as the 3rd IS for serum IgE with an assigned value of 13,500 IU/mL, corresponding to 6750 IU/ampoule.

Evaluation of cryoprotein investigation using a digital external quality assurance scheme.

Background: Robust preanalytical and analytical processes are critical for the detection of cryoproteins. There is significant variation in practice in the detection, analysis and reporting. Results: A survey in 2018 of 137 laboratories participating in the UK National External Quality Assessment Service (UK NEQAS) (6) quality control program showed significant variation in the laboratory processes which highlighted the need for standardisation of the detection, analysis and reporting of cryoglobulins.Conclusion: The first available EQA scheme aiming to harmonise practice for cryoprotein testing has been developed by UK NEQAS and laboratories should participate in an appropriate EQA scheme to fulfil requirements for ISO accreditation.

Hepatic arterial infusion and systemic chemotherapy for breast cancer liver metastases.

Hepatic failure from breast cancer liver metastases (BCLM) is a major cause of morbidity and mortality. We reviewed the treatment histories and outcomes of nine patients with heavily treated BCLM, who received hepatic arterial infusion (HAI) of floxuridine (FUDR)/dexamethasone (Dex) and systemic chemotherapy at our institution. Patients received a median of five (range 1-15) HAI treatments. There were seven (78%) objective responses. Four patients had grade 3 elevations in liver enzymes attributable to HAI. There were no treatment-related deaths. Median hepatic and extrahepatic time to progression on HAI were both 6 months. Median survival after starting HAI was 17 months (range 1-115). Median overall survival from the original breast cancer diagnosis was 110 months (range 52-248). One patient is alive with stable disease on systemic therapy alone. HAI and systemic chemotherapy is feasible and can benefit selected patients with BCLM, who have progressed on prior therapies. Patients require close monitoring for treatment-limiting toxicities.

Clients in Uganda accessing preferred differentiated antiretroviral therapy models achieve higher viral suppression and are less likely to miss appointments: a cross-sectional analysis.

INTRODUCTION: The Uganda Ministry of Health recommends facility- and community-based differentiated antiretroviral therapy (DART) models to support person-centred care for eligible clients receiving antiretroviral therapy (ART). Healthcare workers assess client eligibility for one of six DART models upon initial enrolment; however, client circumstances evolve, and their preferences are not routinely adjusted. We developed a tool to understand the proportion of clients accessing preferred DART models and compared the outcomes of clients accessing preferred DART models to the outcomes of clients not receiving preferred DART models. METHODS: We conducted a cross-sectional study. A sample of 6376 clients was selected from 113 referrals, general hospitals and health centres purposely selected from 74 districts. Clients receiving ART accessing care from the sampled sites were eligible for inclusion. Healthcare workers interviewed clients (caretakers of clients under 18), over a 2-week period between January and February 2022 using a client preference tool to elicit whether clients were receiving DART services through their preferred model. Treatment outcomes of viral load test, viral load suppression and missed appointment date were extracted from clients' medical files before or immediately after the interview and de-identified. The descriptive analysis determined the interaction between client preferences and predefined treatment outcomes by comparing outcomes of clients whose care aligned with their preferences to outcomes of clients whose care misaligned with their preferences. RESULTS: Of 25% (1573/6376) of clients not accessing their preferred DART model, 56% were on facility-based individual management and 35% preferred fast-track drug refills model. Viral load coverage was 87% for clients accessing preferred DART models compared to 68% among clients not accessing their preferred model. Viral load suppression was higher among clients who accessed the preferred DART model (85%) compared to (68%) clients who did not access their preferred DART model. Missed appointments were lower at 29% for clients who accessed preferred DART models compared to 40% among clients not enrolled in the DART model of their choice. CONCLUSIONS: Clients who accessed their preferred DART model have better clinical outcomes. Preferences should be integrated throughout health systems, improvement interventions, policies and research efforts to ensure client-centred care and client autonomy.