Primary cutaneous, epidermotropic mycosis fungoides-like presentation: critical appraisal and description of two novel cases, broadening the spectrum of ALK+ T-cell lymphoma.

Leading from a two-case series, including two patients receiving a diagnosis of epidermotropic T-cell lymphoma, featuring a mycosis fungoides (MF)-like clinical pattern and ALK expression and molecular alteration, we performed a critical appraisal of ALK+ primary cutaneous T-cell lymphomas (pcTCL). Considering our patients and the literature, 32 cases were retrieved, 7 of which featured an MF-like clinical picture over a 4-to-20-year period. MF-like cases show distinctive histology, comprising a predominantly epidermotropic infiltration of small-to-large, atypical-to-pleomorphic, with few anaplastic cells, negligible-to-intense CD30-expression, and a CD4+/cytotoxic granule+ phenotype. These features should prompt a search for ALK expression captured by the ALK D5F3 clone. Bona fide ALK+ pcTCL is very rare, and existent data suggest the presence of a broader pattern of disease, including instances mimicking MF and/or primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma. The major challenges in dealing with this subset include prodromal phases, misinterpreted as inflammatory dermatosis or parapsoriasis/early phase MF both clinically and histologically, while recognition of its ALK-driven biology is hampered both by the unusual clinic-pathologic pattern of the disease, which stands apart from the classical (i.e., nodal) picture of ALK+ anaplastic large cell lymphoma and by the low sensitivity of ALK1 clone. Data on its optimal management are far from being conclusive: An MF-like approach is currently chosen, but depending on CD30 and, most notably, ALK expression, a targeted therapy could be envisaged in advanced stages, as clinical response to ALK inhibition was documented in one patient.

Evaluating the real-world implementation of the Family Nurse Partnership in England: a data linkage study.

Background/objectives: The Family Nurse Partnership is an intensive home visiting programme for adolescent mothers. We aimed to evaluate the effectiveness of the Family Nurse Partnership on outcomes up to age 7 using national administrative data. Design: We created a linked cohort of all mothers aged 13-19 using data from health, educational and children's social care and defined mothers enrolled in the Family Nurse Partnership or not using Family Nurse Partnership system data. Propensity scores were used to create matched groups for analysis. Setting: One hundred and thirty-six local authorities in England with active Family Nurse Partnership sites between 2010 and 2017. Participants: Mothers aged 13-19 at last menstrual period with live births between April 2010 and March 2019, living in a Family Nurse Partnership catchment area and their firstborn child(ren). Interventions: The Family Nurse Partnership includes up to 64 home visits by a family nurse from early pregnancy until the child's second birthday and is combined with usual health and social care. Controls received usual health and social care. Main outcome measures: Indicators of child maltreatment (hospital admissions for injury/maltreatment, referral to social care services); child health and development (hospital utilisation and education) outcomes and maternal hospital utilisation and educational outcomes up to 7 years following birth. Data sources: Family Nurse Partnership Information System, Hospital Episode Statistics, National Pupil Database. Results: Of 110,520 eligible mothers, 25,680 (23.2%) were enrolled in the Family Nurse Partnership. Enrolment rates varied across 122 sites (range: 11-68%). Areas with more eligible mothers had lower enrolment rates. Enrolment was higher among mothers aged 13-15 (52%), than 18-19 year-olds (21%). Indicators of child maltreatment: we found no evidence of an association between the Family Nurse Partnership and indicators of child maltreatment, except for an increased rate of unplanned admissions for maltreatment/injury-related diagnoses up to age 2 for children born to Family Nurse Partnership mothers (6.6% vs. 5.7%, relative risk 1.15; 95% confidence interval 1.07 to 1.24). Child health and developmental outcomes: there was weak evidence that children born to Family Nurse Partnership mothers were more likely to achieve a Good Level of Development at age 5 (57.5% vs. 55.4%, relative risk 1.05; 95% confidence interval 1.00 to 1.09). Maternal outcomes: There was some evidence that Family Nurse Partnership mothers were less likely to have a subsequent delivery within 18 months of the index birth (8.4% vs. 9.3%, relative risk 0.92; 95% confidence interval 0.88 to 0.97). Younger and more vulnerable mothers received higher numbers of visits and were more likely to achieve fidelity targets. Meeting the fidelity targets was associated with some outcomes. Limitations: Bias by indication and variation in the intervention and usual care over time and between areas may have limited our ability to detect effects. Multiple testing may have led to spurious, significant results. Conclusions: This study supports findings from evaluations of the Family Nurse Partnership showing no evidence of benefit for maltreatment outcomes measured in administrative data. Amongst all the outcomes measured, we found weak evidence that the Family Nurse Partnership was associated with improvements in child development at school entry, a reduction in rapid repeat pregnancies and evidence of increased healthcare-seeking in the mother and child. Future work: Future evaluations should capture better measures of Family Nurse Partnership interventions and usual care, more information on maternal risk factors and additional outcomes relating to maternal well-being. Study registration: The study is registered as NIHR CRN Portfolio (42900). Funding: This award was funded by the National Institute of Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 17/99/19) and is published in full in Health and Social Care Delivery Research; Vol. 12, No. 11. See the NIHR Funding and Awards website for further award information.

The Family Nurse Partnership is an intensive home visiting service that offers first-time young mothers up to 64 visits with a family nurse from pregnancy to their child's second birthday. The Family Nurse Partnership aims to improve birth outcomes, child health and development and promote economic self-sufficiency among young mothers. Previous research in England found no differences in birthweight, maternal smoking, repeat pregnancies or accident and emergency attendances between mothers who did or did not take part in the Family Nurse Partnership. However, children in the Family Nurse Partnership group had better measures of development at school age. We aimed to add to the evidence from earlier studies, by using electronic records that are routinely collected as part of health, education and social care services, to compare outcomes for around 26,000 mothers enrolled in the Family Nurse Partnership between 2010 and 2019 with similar mothers who were not enrolled. This study showed that around one in four mothers who were eligible for the programme were enrolled in the Family Nurse Partnership, and family nurses gave priority to mothers who were younger, more deprived or who had other markers of vulnerability (e.g. a history of substance misuse violence, self-harm or mental health conditions). We found no evidence of a difference in indicators of child maltreatment between mothers who were enrolled in the Family Nurse Partnership and those who were not enrolled, but we found weak evidence to suggest that children born to mothers enrolled in the Family Nurse Partnership were more likely to achieve a Good Level of Development at school entry (age 5). We also saw that mothers enrolled in the Family Nurse Partnership were less likely than those who were not enrolled to have their next child within 18 months of their first child. More research is needed to understand which elements of intensive home visiting services work best, for whom and when. This will help inform decisions about whether it is better to offer highly intensive services for a small portion of the target population or to extend and enhance existing universal health visiting services to better support all adolescent mothers.

Antibody based therapeutics for autoimmune hemolytic anemia.

INTRODUCTION: Autoimmune hemolytic anemia (AIHA) treatment has been revolutionized by the introduction of target therapies, mainly monoclonal antibodies (MoAbs). AREAS COVERED: The anti-CD20 rituximab, which targets Ab production by B-cells, induces 80% of response in warm-type AIHA (wAIHA) and 50-60% in cold agglutinin disease (CAD). Other B-cell targeting MoAbs including ianalumab, povetacicept, and obexelimab are under active study. The anti-CD38 MoAb daratumumab has been used in several reports to target long-lived plasma-cells responsible for AIHA relapse, being effective even in multi-refractory cases. Anti-complement MoAbs will soon change the treatment paradigm in CAD; the anti-C1s sutimlimab rapidly increased Hb in more than 80% of the cases. Finally, MoAbs inhibiting the neonatal Fc receptor (FcRn), such as nipocalimab, can reduce the half-life of the pathogenic autoAbs, representing a promising treatment for wAIHA. EXPERT OPINION: MoAbs offer the potential to improve efficacy by reducing toxicity. However, there is a huge need for clinical trials exploring response duration rather than short-term efficacy. Complement inhibitors and anti-FcRns do not abrogate autoAb production and are being developed as long-term therapies. Thus, the combination of B-cell/plasma cell targeting drugs deserves to be explored. On the other hand, their rapid efficacy should be exploited for the acute AIHA phase.

Lessons learned from using linked administrative data to evaluate the Family Nurse Partnership in England and Scotland.

Introduction: "Big data" - including linked administrative data - can be exploited to evaluate interventions for maternal and child health, providing time- and cost-effective alternatives to randomised controlled trials. However, using these data to evaluate population-level interventions can be challenging. Objectives: We aimed to inform future evaluations of complex interventions by describing sources of bias, lessons learned, and suggestions for improvements, based on two observational studies using linked administrative data from health, education and social care sectors to evaluate the Family Nurse Partnership (FNP) in England and Scotland. Methods: We first considered how different sources of potential bias within the administrative data could affect results of the evaluations. We explored how each study design addressed these sources of bias using maternal confounders captured in the data. We then determined what additional information could be captured at each step of the complex intervention to enable analysts to minimise bias and maximise comparability between intervention and usual care groups, so that any observed differences can be attributed to the intervention. Results: Lessons learned include the need for i) detailed data on intervention activity (dates/geography) and usual care; ii) improved information on data linkage quality to accurately characterise control groups; iii) more efficient provision of linked data to ensure timeliness of results; iv) better measurement of confounding characteristics affecting who is eligible, approached and enrolled. Conclusions: Linked administrative data are a valuable resource for evaluations of the FNP national programme and other complex population-level interventions. However, information on local programme delivery and usual care are required to account for biases that characterise those who receive the intervention, and to inform understanding of mechanisms of effect. National, ongoing, robust evaluations of complex public health evaluations would be more achievable if programme implementation was integrated with improved national and local data collection, and robust quasi-experimental designs.

Real-life monocentric experience of venetoclax-based regimens for acute myeloid leukemia.

Introduction: Combination of venetoclax and hypomethylating agents (HMAs) has become a standard of care in acute myeloid leukemia (AML) aged >75 years or who have comorbidities that preclude intensive induction chemotherapy. Methods: We conducted a monocentric retrospective analysis on adult patients affected by treatment-naïve AML not eligible for standard induction therapy or refractory/relapsed (R/R) AML treated with venetoclax combinations outside clinical trials. Venetoclax was administered at the dose of 400 mg/daily after a short ramp-up and reduced in case of concomitant CYP3A4 inhibitors. Results: Sixty consecutive AML were identified. Twenty-three patients (38%) were affected by treatment-naïve AML and 37 (62%) by R/R AML. Median age was 70 years. Among R/R AML 30% had received a prior allogeneic stem cell transplantation (allo-HSCT). In combination with venetoclax, 50 patients (83%) received azacitidine. Antifungal prophylaxis was performed in 33 patients (55%).Overall response rate was 60%, with 53% of complete remission (CR; 78% for treatment-naïve and 49% for R/R, p 0.017). Median overall survival was 130 days for R/R patients and 269 days for treatment-naïve patients; median event free survival was 145 days for R/R cohort and 199 days for treatment-naïve AML.Measurable residual disease was negative in 26% of evaluable patients in CR/CR with incomplete hematologic recovery after 2 cycles and in 50% after 4 cycles, with no significant association with survival.Eleven patients (18%) received an allo-HSCT after venetoclax combinations. Most common grade 3/4 adverse events were infectious (51% of the patients), or hematological without infections (25% of the patients). Use of CYP3A4 inhibitors was associated with a trend to shorter cytopenias and with a lower rate of infections. Invasive fungal infections were less frequent among patients receiving azole prophylaxis (6% vs 26%; p 0.0659). Discussion: Venetoclax-based regimens are a viable option for AML considered not eligible for standard induction therapy and a valid rescue therapy in the R/R setting.Azole prophylaxis did not significantly affect response and it was associated with a lower rate of invasive fungal infections. Despite a limited number of patients, the association of venetoclax and HMAs proved to be also a feasible bridging therapy to transplantation.

Study protocol: evaluation of the 0-5 public health investment in England - a mixed-methods study integrating analyses of national linked administrative data with in-depth case studies.

INTRODUCTION: Health visiting is a long-established, nationally implemented programme that works with other services at a local level to improve the health and well-being of children and families. To maximise the impact and efficiency of the health visiting programme, policy-makers and commissioners need robust evidence on the costs and benefits of different levels and types of health visiting, for different families, in different local contexts. METHODS AND ANALYSIS: This mixed-methods study will analyse individual-level health visiting data for 2018/2019 and 2019/2020 linked with longitudinal data from children's social care, hospitals and schools to estimate the association of number and type of health visiting contacts with a range of children and maternal outcomes. We will also use aggregate local authority data to estimate the association between local models of health visiting and area-level outcomes. Outcomes will include hospitalisations, breast feeding, vaccination, childhood obesity and maternal mental health. Where possible, outcomes will be valued in monetary terms, and we will compare total costs to total benefits of different health visiting service delivery models. Qualitative case studies and extensive stakeholder input will help explain the quantitative analyses and interpret the results in the context of local policy, practice and circumstance. ETHICS AND DISSEMINATION: The University College London Research Ethics Committee approved this study (ref 20561/002). Results will be submitted for publication in a peer-reviewed journal and findings will be shared and debated with national policy-makers, commissioners and managers of health visiting services, health visitors and parents.

Characteristics of enrolment in an intensive home-visiting programme among eligible first-time adolescent mothers in England: a linked administrative data cohort study.

BACKGROUND: Intensive home visiting for adolescent mothers may help reduce health disparities. Given limited resources, such interventions need to be effectively targeted. We evaluated which mothers were enrolled in the Family Nurse Partnership (FNP), an intensive home-visiting service for first-time young mothers commissioned in >130 local authorities in England since 2007. METHODS: We created a population-based cohort of first-time mothers aged 13-19 years giving birth in English National Health Service hospitals between 1 April 2010 and 31 March 2017, using administrative hospital data linked with FNP programme, educational and social care data. Mothers living in a local authority with an active FNP site were eligible. We described variation in enrolment rates across sites, and identified maternal and FNP site characteristics associated with enrolment. RESULTS: Of 110 520 eligible mothers, 25 680 (23.2% (95% CI: 23.0% to 23.5%)) were enrolled. Enrolment rates varied substantially across 122 sites (range: 11%-68%), and areas with greater numbers of first-time adolescent mothers achieved lower enrolment rates. Mothers aged 13-15 years were most likely to be enrolled (52%). However, only 26% of adolescent mothers with markers of vulnerability (including living in the most deprived areas and ever having been looked after as a child) were enrolled. CONCLUSION: A substantial proportion of first-time adolescent mothers with vulnerability markers were not enrolled in FNP. Variation in enrolment across sites indicates insufficient commissioning of places that is not proportional to level of need, with mothers in areas with large numbers of other adolescent mothers least likely to receive support.

Does hospital variation in intrapartum-related perinatal mortality among caesarean births reflect differences in quality of care? Cross-sectional study in 21 hospitals in Burkina Faso.

OBJECTIVES: To examine hospital variation in crude and risk-adjusted rates of intrapartum-related perinatal mortality among caesarean births. DESIGN: Secondary analysis of data from the DECIDE (DECIsion for caesarean DElivery) cluster randomised trial postintervention phase. SETTING: 21 district and regional hospitals in Burkina Faso. PARTICIPANTS: All 5134 women giving birth by caesarean section in a 6-month period in 2016. PRIMARY OUTCOME MEASURE: Intrapartum-related perinatal mortality (fresh stillbirth or neonatal death within 24 hours of birth). RESULTS: Almost 1 in 10 of 5134 women giving birth by caesarean experienced an intrapartum-related perinatal death. Crude mortality rates varied substantially from 21 to 189 per 1000 between hospitals. Variation was markedly reduced after adjusting for case mix differences (the median OR decreased from 1.9 (95% CI 1.5 to 2.5) to 1.3 (95% CI 1.2 to 1.7)). However, higher and more variable adjusted mortality persisted among hospitals performing fewer caesareans per month. Additionally, adjusting for caesarean care components did not further reduce variation (median OR=1.4 (95% CI 1.2 to 1.8)). CONCLUSIONS: There is a high burden of intrapartum-related perinatal deaths among caesarean births in Burkina Faso and sub-Saharan Africa more widely. Variation in adjusted mortality rates indicates likely differences in quality of caesarean care between hospitals, particularly lower volume hospitals. Improving access to and quality of emergency obstetric and newborn care is an important priority for improving survival of babies at birth. TRIAL REGISTRATION NUMBER: ISRCTN48510263.

Determinants of care-seeking behaviour for fever, acute respiratory infection and diarrhoea among children under five in Nigeria.

BACKGROUND: Despite available, inexpensive and effective treatments, malaria, diarrhoea, and pneumonia still contribute the majority of the global burden of childhood morbidity and mortality. Nigeria has the highest absolute numbers of child deaths worldwide. Appropriate care-seeking is important for prompt diagnosis, appropriate and timely treatment, and prevention of complications. The objective of this cross-sectional study was to examine the prevalence of and factors associated with appropriate care-seeking for childhood illnesses. METHODS: We used the most recent Nigeria Demographic and Health Survey (2018) to assess the prevalence of appropriate care-seeking among mothers of children under five with symptoms of common childhood illnesses. For diarrhoea, we defined appropriate care-seeking as seeking care from a formal health provider. For fever and acute respiratory infection (ARI), appropriate care-seeking was defined as seeking care from a formal provider the day of or after symptom onset. Multivariate logistic regression was carried out to assess factors associated with optimal care-seeking for each illness. RESULTS: At least 25% of parents did not seek any care for children with fever or ARI; this figure was over one third for diarrhoea. Only 15% and 13% of caregivers showed appropriate care-seeking for their children with fever and ARI respectively, and 27% of mothers sought care from a formal provider for diarrhoea. Predictors of appropriate care-seeking varied according to childhood illness. Previous facility delivery was the only risk factor associated with increased odds of appropriate care-seeking for all three illnesses; other risk factors varied between illnesses. CONCLUSION: Overall, care-seeking for childhood illnesses was suboptimal among caregivers in Nigeria. Interventions to increase caregivers' awareness of the importance of appropriate care-seeking are needed alongside quality of care interventions that reinforce people's trust in formal health facilities, to improve timely care-seeking and ultimately reduce the high burden of child deaths in Nigeria.

Pyruvate Kinase Deficiency: Current Challenges and Future Prospects.

Pyruvate kinase deficiency (PKD) is a rare autosomal recessive disease marked by chronic hemolytic anemia of various severity and frequent complications including gallstones, splenomegaly, iron overload, and others. Disease phenotype is highly heterogeneous and changes over time with children, adolescents and adult patients displaying different transfusion requirement and rates of complications. The diagnosis relies on the initial clinical suspicion in a patient with chronic hemolysis and exclusion of other more common congenital forms of hemolytic anemias; it is supported by the demonstration of reduced PK enzyme activity, and further confirmed by the detection of (homozygous or compound heterozygous) mutations of PKLR gene. Therapy is mainly supportive, with vitamin supplementation and transfusions (based on symptoms and patient growth rather than on fixed Hb thresholds). Splenectomy is widely performed, although it is less effective than in membrane defects and carries thrombotic and infectious risk. In the last decade, the allosteric PK enzyme activator mitapivat showed dramatic clinical benefit in clinical trials and gene therapy is also being studied to substitute the defective enzyme. In this review, we provide an insight in the current challenges of PKD diagnosis and management and discuss the future application of novel drugs and gene therapy, including a focus on quality of life.

Managing Fatigue in Patients with Paroxysmal Nocturnal Hemoglobinuria: A Patient-Focused Perspective.

The most frequently reported symptom in patients with paroxysmal nocturnal hemoglobinuria (PNH), a disease characterized by complement mediated hemolysis and chronic anemia, is "fatigue". The latter seems the best word to communicate patient' perception of personal health status and disease impact on daily living, namely quality of life (QoL). Objectivating QoL and grading patient's fatigue is one of the most difficult medical tasks given the highly heterogeneous communication skills of patients and caregivers and the multitude of meanings that might be attributed to this term. Along with anemia, QoL in PNH is also affected by the emotional burden of a chronic life-long disease with heterogeneous treatment requirement, risk of hemolytic exacerbations (breakthrough hemolysis) and of thrombosis. In the last decade, structured surveys and scores have been adapted from cancer settings to evaluate fatigue and QoL in patients with PNH, and to assess the benefit of complement inhibitors in this setting. Eculizumab was the first drug utilized and was shown to improve QoL scores in the registrative trials. However, the intravenous fortnightly administration, the presence of residual anemia, and the risk of extravascular hemolysis are some of the unmet needs impacting QoL under eculizumab. Several novel drugs have been designed to improve patients' convenience and alleviate anemia and fatigue. In this review, we focus on available studies that evaluated fatigue and QoL in PNH patients, and the effect of old and new therapeutic strategies.

Seroconversion to mRNA SARS-CoV-2 Vaccines in Hematologic Patients.

Hematologic patients show lower responses to SARS-CoV-2 vaccines, but predictors of seroconversion are lacking. In this prospective cohort study, hematologic patients undergoing SARS-CoV-2 mRNA vaccination at a single center in Milan, Italy, were sampled for anti-Spike and anti-Nucleocapsid IgG titer at 5 ± 1 weeks and at 3 months from the second vaccine dose. Patients (N = 393) received either BNT162b2 (Pfizer-BioNTech, 48%) or MRNA-1273 (Moderna, 52%), and 284 (72%) seroconverted and 100% persisted at 3 months. Non-response was higher in chronic lymphocytic leukemia (CLL) and lymphoma patients, and in those treated with small molecules and monoclonal antibodies. In myeloid neoplasms, lower responses were detected in patients with acute myeloid leukemia treated with venetoclax plus hypomethylating agents and in patients with myelofibrosis receiving ruxolitinib. Multivariable analysis showed that seroconversion was favorably associated with a diagnosis other than indolent lymphoma/CLL [OR 8.5 (95% CI 4.1-17.6)], lack of B-cell-depleting therapy [OR 3.15 (1.7-5.9)], and IgG levels within the normal range [OR 2.2 (1.2-4.2)]. We developed a simple algorithm according to these 3 risk factors [(A) diagnosis of indolent lymphoma/CLL, (B) B-cell-depleting treatment, and (C) low IgG] to predict non-response. IgG levels and treatment may be modifiable risk factors and should be considered for timing of vaccine administration.

Safety of outpatient stem cell mobilization with low- or intermediate-dose cyclophosphamide in newly diagnosed multiple myeloma patients.

OBJECTIVES: Autologous stem cell transplantation is the gold standard for eligible newly diagnosed multiple myeloma patients. Patients are usually hospitalized for administration of mobilization chemotherapy. We aimed to assess safety and efficacy of mobilization therapy with low-dose (2 g/m2 ) and intermediate-dose (3-4 g/m2 ) cyclophosphamide administered as outpatient. METHODS: A total of 176 consecutive newly diagnosed transplant-eligible myeloma patients receiving outpatient mobilization were retrospectively evaluated. Induction therapy was mainly performed with new drugs (91%). RESULTS: Chemotherapy was very well tolerated with 16.6% of patients having all-grade adverse events (AEs) and only 1.2% having severe AEs. The most frequently reported AEs were nausea and vomiting grade 1-2 (6.8%). Only 5.7% of patients required hospitalization for AEs. Stem cell collection was successful in 93.1% of patients, with a median CD34+ harvest of 8.7 × 106 /kg. Target for 2 autologous stem cell transplantation (at least 6 CD34+  × 106 /kg) was reached by 76.3% of patients. Administration of plerixafor on demand was necessary in 12.1% of patients. CONCLUSIONS: Outpatient mobilization with low- and intermediate-dose cyclophosphamide appears an efficient and safe procedure, with minimal and manageable AEs and low rate of hospitalization.

Recent insights into the role of the microbiome in malignant and benign hematologic diseases.

Growing evidence suggests the impact of microbiome alteration, named dysbiosis, on the development of neoplasms, infections, inflammatory diseases, and immuno-mediated disorders. Regarding hematologic diseases, most data regard hematopoietic stem cell transplant (HSCT). In this review, we systematically evaluate the studies concerning microbiome in malignant and benign hematologic disorders beyond HSCT. A permissive microbiota is associated to the development of hematologic malignancies (including acute leukemia, lymphoma, and multiple myeloma), as well as of iron deficiency anemia, autoimmune cytopenias, and aplastic anemia. This happens through various mechanisms; chronic inflammatory triggering, epithelial barrier alteration, antigen dissequestration, and molecular mimicry. Hematologic therapies (chemo and immunosuppression) may induce/worsen dysbiosis and favour disease progression and infectious complications. Antibiotics may also induce dysbiosis with possible long-term consequences. Finally, novel target therapies are likely to alter microbiome, inducing gut inflammation (i.e. small molecules such as tyrosine-kinase-inhibitors) or enhancing host's immune system (as observed with CAR-T cells and checkpoint inhibitors).

Changes over time in HIV testing and counselling uptake and associated factors among youth in Zambia: a cross-sectional analysis of demographic and health surveys from 2007 to 2018.

INTRODUCTION: Zambia is among the countries with the highest HIV burden and where youth remain disproportionally affected. Access to HIV testing and counselling (HTC) is a crucial step to ensure the reduction of HIV transmission. This study examines the changes that occurred between 2007 and 2018 in access to HTC, inequities in testing uptake, and determinants of HTC uptake among youth. METHODS: We carried out repeated cross-sectional analyses using three Zambian Demographic and Health Surveys (2007, 2013-14, and 2018). We calculated the percentage of women and men ages 15-24 years old who were tested for HIV in the last 12 months. We analysed inequity in HTC coverage using indicators of absolute inequality. We performed bivariate and multivariate logistic regression analyses to identify predictors of HTC uptake in the last 12 months. RESULTS: HIV testing uptake increased between 2007 and 2018, from 45 to 92% among pregnant women, 10 to 58% among non-pregnant women, and from 10 to 49% among men. By 2018 roughly 60% of youth tested in the past 12 months used a government health centre. Mobile clinics were the second most common source reaching up to 32% among adolescent boys by 2018. Multivariate analysis conducted among men and non-pregnant women showed higher odds of testing among 20-24 year-olds than adolescents (aOR = 1.55 [95%CI:1.30-1.84], among men; and aOR = 1.74 [1.40-2.15] among women). Among men, being circumcised (aOR = 1.57 [1.32-1.88]) and in a union (aOR = 2.44 [1.83-3.25]) were associated with increased odds of testing. For women greater odds of testing were associated with higher levels of education (aOR = 6.97 [2.82-17.19]). Education-based inequity was considerably widened among women than men by 2018. CONCLUSION: HTC uptake among Zambian youth improved considerably by 2018 and reached 65 and 49% tested in the last 12 months for women and men, respectively. However, achieving the goal of 95% envisioned by 2020 will require sustaining the success gained through government health centres, and scaling up the community-led approaches that have proven acceptable and effective in reaching young men and adolescent girls who are less easy to reach through the government facilities.

Infectious Complications in Autoimmune Hemolytic Anemia.

Autoimmune hemolytic anemia (AIHA) may be frequently challenged by infectious complications, mainly as a result of immunosuppressive treatments administered. Furthermore, infectious agents are known triggers of AIHA onset and relapse. Although being risk factors for mortality, infections are an underestimated issue in AIHA. This review will collect the available evidence on the frequency and type of infectious complications in AIHA, detailing the risk related to each treatment (i.e., steroids, rituximab, splenectomy, classic immunosuppressive agents, and new target drugs). Moreover, we will briefly discuss the infectious complications in AIHA secondary to other diseases that harbor an intrinsic infectious risk (e.g., primary immunodeficiencies, systemic autoimmune diseases, lymphoproliferative disorders, solid organ and hematopoietic stem cell transplants). Finally, viral and bacterial reactivations during immune suppressive therapies will be discussed, along with suggested screening and prophylactic strategies.