Treatment of attention-deficit-hyperactivity disorder.

New England Journal of Medicine

Absolute iron deficiency, defined as low iron stores with or without anemia, affects approximately 2 billion people worldwide and 14% of adults in the US. Iron-deficiency anemia, defined as low hemoglobin due to low iron stores, affects approximately 1.2 billion people worldwide, including 10 million in the US.

Absolute iron deficiency progresses from low iron stores to iron-deficiency anemia. Individuals with nonanemic iron deficiency or iron-deficiency anemia may be asymptomatic or experience fatigue, irritability, depression, difficulty concentrating, restless legs syndrome (32%-40%), pica (40%-50%), dyspnea, lightheadedness, exercise intolerance, and worsening heart failure (HF). Symptom prevalences vary depending on age, comorbidities (eg, chronic kidney disease [CKD], HF), and severity and rate of development of iron deficiency. The most common causes of iron deficiency are bleeding (menstrual, gastrointestinal), impaired iron absorption (atrophic gastritis, celiac disease, bariatric surgical procedures), inadequate dietary iron intake, and pregnancy. In high-income countries, approximately 38% of nonpregnant, reproductive-age women have iron deficiency without anemia and about 13% have iron-deficiency anemia. During the third trimester of pregnancy, iron deficiency affects up to 84% of pregnant women, based on data from high-income countries. Additional risk factors include use of nonsteroidal anti-inflammatory drugs, inflammatory bowel disease (IBD [13%-90%]), and other chronic inflammatory conditions, such as CKD (24%-85%), HF (37%-61%), and cancer (18%-82%). Testing for iron deficiency is indicated for patients with anemia and/or symptoms of iron deficiency (fatigue, pica, or restless legs syndrome) and should be considered for those with risk factors such as heavy menstrual bleeding, pregnancy, or IBD. Iron deficiency is diagnosed by low serum ferritin (typically &lt;30 ng/mL) in individuals without inflammatory conditions or by transferrin saturation (iron/total iron binding capacity&#x2009;&#xd7;&#x2009;100) less than 20%. Causes of iron deficiency should be identified and treated. Oral iron (ferrous sulfate 325 mg/d or on alternate days) is typically first-line therapy. Intravenous iron is indicated for patients with oral iron intolerance, poor absorption (celiac disease, post-bariatric surgical procedure), chronic inflammatory conditions (CKD, HF, IBD, cancer), ongoing blood loss, and during the second and third trimesters of pregnancy.

Iron deficiency and iron-deficiency anemia are common conditions that may cause symptoms such as fatigue, exercise intolerance, and difficulty concentrating. Ferritin and/or transferrin saturation are required for diagnosis and screening. Oral iron is first-line therapy for most patients. Intravenous iron is used for individuals who do not tolerate or have impaired absorption of oral iron, those with ongoing blood loss, certain chronic inflammatory conditions (IBD, CKD, HF, cancer), and during the second and third trimesters of pregnancy.

Iron Deficiency in Adults: A Review.

JAMA

At the 10th European Conference on Infections in Leukaemia (ECIL), the guidelines for antifungal prophylaxis in pediatric and adult patients with hematological malignancies (HM) were updated and some changes introduced. Regarding acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) patients undergoing remission induction chemotherapy, a B-II grading has been assigned to isavuconazole, micafungin, and caspofungin, based on non-randomized studies that have shown efficacy in preventing invasive fungal diseases (IFD). Regarding high-risk MDS patients treated with azacytidine, prophylaxis with posaconazole during the first four cycles of treatment is supported in the literature. Prophylaxis is not indicated in patients treated for myeloproliferative neoplasms (NPM), acute lymphoid leukemia (ALL), and Hodgkin lymphoma (HL). For patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), prophylaxis is not generally indicated. For patients with multiple myeloma (MM), prophylaxis is not indicated and the limited epidemiological data available do not support the use of prophylaxis in subjects treated with bispecific antibodies. For patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT), no substantial changes were made, apart from the addition of isavuconazole with grading B-II in the post-engraftment period. In patients undergoing auto-HSCT, antifungal prophylaxis is not indicated. Previous ECIL guidelines did not include CAR-T cells. The expert panel proposes to endorse the use of anti-mold prophylaxis in high-risk patients during pre-infusion and post-infusion, while in low-risk patients, anti-yeast prophylaxis can be recommended (B-II). For pediatric hematology patients, based on newly published data, caspofungin received a B-I grading as mold-active prophylaxis. Moreover, patients with ALL with insufficient treatment response during induction therapy, and children older than 12&#x2009;y.o are now considered at high risk for IFD and are recommended to receive antifungal prophylaxis.

Primary antifungal prophylaxis in hematological malignancies. Updated clinical practice guidelines by the European Conference on Infections in Leukemia (ECIL).

Leukemia

Background : Antiphospholipid syndrome (APS) is a rare systemic autoimmune disease characterized by persistent antiphospholipid antibodies (aPL) in combination with recurrent thrombosis in the veins and/or arteries, obstetric morbidity, and various non-thrombotic associated complications. APS can be primary, as an isolated condition, or secondary in the context of another autoimmune disease, especially systemic lupus erythematosus. This comprehensive clinical review aims to summarize the current understanding of APS pathogenesis, diagnostic approaches, and treatment strategies for this unique clinical entity. Methods : A comprehensive review of the existing literature on APS was conducted, focusing on pathophysiological mechanisms, current diagnostic criteria, and therapeutic approaches. Results : APS pathogenesis involves complex interactions between aPL, phospholipid-binding proteins, and the coagulation cascade. Apart from the cardinal features of thrombosis and APS-related obstetric morbidity, APS is associated with a wide spectrum of clinical manifestations. Diagnosis remains challenging due to overlapping symptoms with other conditions, and clinicians should maintain a high index of suspicion in order to set the diagnosis. The recently published 2023 ACR/EULAR criteria although not definitive for clinical decision-making, these criteria offer clinicians a valuable tool to aid in determining whether further investigation for APS is warranted. Continued refinement of these criteria through ongoing feedback and updates is anticipated. Treatment strategies center on anticoagulation, but individualized approaches are necessary. Conclusions : Early diagnosis and multidisciplinary management of APS are critical to reducing morbidity and improving outcomes. Moreover, familiarization with the 2023 ACR/EULAR criteria is encouraged, recognizing that ongoing feedback and updates will contribute to their ongoing refinement and improvement. While VKAs remain the mainstay of treatment for most APS patients further research is needed to optimize treatment strategies and deepen our understanding of APS's underlying disease mechanisms.

Antiphospholipid Syndrome: A Comprehensive Clinical Review.

Journal of Clinical Medicine

Pancreatic cancer is frequently a lethal disease with an aggressive tumour biology often presenting with non-specific symptoms. Median survival is approximately 4 months with a 5-year survival of 13%. Surveillance is recommended in individuals with familial pancreatic cancer, specific mutations, and high-risk intraductal papillary mucinous neoplasm, as they are at high risk of developing pancreatic cancer. Chemotherapy combined with surgical resection remains the cornerstone of treatment. However, only a small subset of patients are candidates for surgery. Multi-agent chemotherapy has improved survival in the palliative setting for patients with metastatic disease, as (neo)adjuvant and induction therapy have in patients with borderline resectable and locally advanced pancreatic. Given that pancreatic cancer is predicted to become the second leading cause of cancer-related death by 2030, novel therapies are urgently needed.

Pancreatic cancer.

Lancet

As more lupus nephritis (LN) medications become available, identifying treatments that are disease-modifying is critical in making treatment decisions. Based on our 2022 published working definition of LN disease modification as 'minimizing disease activity with the fewest treatment-associated toxicities and slowing progression to end-stage kidney disease' (ESKD), the objective of this review was to classify current LN treatments according to the proposed kidney disease modification criteria, excluding toxicities. Based upon a selection of LN clinical trial (n&#x2009;=&#x2009;27) and observational study (n&#x2009;=&#x2009;20) publications, as well as the authors' clinical experiences, we evaluated the disease modification potential for 16 LN treatments (inclusive of antimalarials, glucocorticoids, immunosuppressants, calcineurin inhibitors and biologics) according to the proposed kidney disease activity and organ damage criteria at year 1, years 2-5, and&#x2009;&gt;&#x2009;5-year time points. Fulfilling criteria at year 1 and years 2-5 was considered evidence for disease modification potential. Satisfying criteria at&#x2009;&gt;&#x2009;5 years (slowing or preventing progression in SLICC/ACR Damage Index [SDI] and ESKD, and/or doubling of serum creatinine) was used to confirm disease modification. Each treatment was designated as one of the following at each time point: (a) criterion met; (b) inconclusive; (c) no available supportive data. This review excluded an assessment of potential toxicities. All LN treatments met at least one of the potential kidney disease-modification criteria at any time point, but limited relevant data in the literature meant disease modification&#x2009;&gt;&#x2009;5 years could only be confirmed for cyclophosphamide. Belimumab met more criteria across the three time points than any other biologic treatment but lacked&#x2009;&gt;&#x2009;5-year data to confirm disease modification. Further research is needed to support the classification of LN treatments as disease modifiers, particularly for&#x2009;&gt;&#x2009;5 years. We discuss considerations for future studies, challenges to the classification, and possible updates to published criteria.

Disease-Modifying Therapies in Lupus Nephritis: A Narrative Review Evaluating Currently Used Pharmacologic Agents.

Rheumatology and Therapy

Transcatheter tricuspid valve repair (TTVr) is a treatment option for tricuspid regurgitation (TR) in patients with high surgical risk. Given the heterogeneity in clinical benefit, there is a need for markers to assess mortality risk in patients undergoing TTVr. The C-reactive protein (CRP)/albumin ratio (CAR) is a marker of systemic inflammation and reduced nutritional status, which can both occur in TR.

Consecutive patients undergoing TTVr at a tertiary care center were retrospectively analyzed. Serum CRP and albumin were collected at baseline. Intraprocedural success (IS) was defined according to TVARC criteria. The primary outcome of all-cause mortality was assessed up to 2&#xa0;years after TTVr.

A total of 215 patients (69% females, median age 80&#xa0;years) were identified. IS was achieved in 61% of patients. AUC of CAR for 2-year mortality was 0.695, with an optimal threshold of 1.2945 (Youden index) dividing patients in high CAR (n&#x2009;=&#x2009;93) and low CAR (n&#x2009;=&#x2009;122) groups. In the high CAR group, the primary endpoint occurred more frequently (43% vs 15%, p&#x2009;&lt;&#x2009;0.001) and significantly higher right atrial pressure, worse renal function, and less IS during TTVr were observed. High CAR was independently associated with an increased mortality risk even when adjusted for renal and liver function, right-ventricular function, and procedural failure (HR 2.188; 95%CI 1.2-3.9; p&#x2009;=&#x2009;0.011).

Higher CAR reflects patients with advanced right-heart failure and extracardiac organ damage and is associated with mortality after TTVr. CAR is derived from readily available parameters and may be useful additive to established risk scores.

C-reactive protein-to-albumin ratio is associated with mortality after transcatheter tricuspid valve repair.

Clinical Research in Cardiology : Official Journal of the German Cardiac Society

Urinary and sexual symptoms are common following neurological disease, and we aimed to develop multidisciplinary inter-society evidence-based management guidelines.

The ADAPTE framework was used, and a systematic search of guidelines published in different languages was performed. Guidelines, consensus statements, and systematic reviews were included, and guideline quality was appraised using AGREE II. Patient representatives reviewed the relevance and suitability of recommendations. A modified Delphi process integrating the Evidence to Decision framework adapted from GRADE and the Oxford Centre for Evidence Based Medicine system was used to reach consensus on recommendation wording and strength.

Recommendations were drafted, using guidelines/consensus statements (59 urinary, 50 sexual), systematic reviews (8 urinary, 2 sexual) and others (7 urinary,13 sexual), and wordings/strengths achieved at least 80% consensus through 2 Delphi rounds. Eleven evidence-based recommendations, 19 good practice statements, and 8 consensus-based recommendations were made. Individuals with neurological diseases should be asked about urogenital symptoms and undergo targeted physical examination when appropriate. Urinary symptom assessments include urinalysis, bladder diary completion, and post-void residual volume measurement. Treatments include fluid intake optimization, pelvic physiotherapy, tibial nerve stimulation, and oral medications. Urinary retention is managed by intermittent catheterization. Antibiotics should not be recommended to treat asymptomatic bacteriuria. Suprapubic catheterization is preferred for long-term catheterization. A comprehensive sexual history should be taken, focusing on multidimensional factors affecting sexual health. Treatments include lubricants, vibrators, and phosphodiesterase-5 inhibitors. Red flag symptoms warrant a shared-care approach with specialist colleagues.

The 38 NEUROGED recommendations will guide neurologists to comprehensively manage urogenital symptoms reported by individuals with neurological diseases.

European Academy of Neurology (EAN)/European Federation of Autonomic Societies (EFAS)/International Neuro-Urology Society (INUS) Guidelines for Practising Neurologists on the Assessment and Treatment of Neurogenic Urinary and Sexual Symptoms (NEUROGED Guidelines).

European Journal of Neurology

Influenza is a significant cause of morbidity and mortality, particularly in critically ill patients. The availability of effective antiviral therapies is pivotal in mitigating the severity and complications associated with influenza.

This review evaluates the antivirals available for the treatment of severe influenza in critically ill patients, focusing on the strength of recommendations and levels of evidence derived from clinical trials, observational studies, and guidelines. The aim is to provide clinicians with evidence-based insights to optimise antiviral strategies in the ICU setting.

A comprehensive literature search was conducted using PubMed, Embase, and Cochrane Library databases for studies published up to January 2025. Keywords included "antiviral therapy," "influenza," "critically ill patients," "oseltamivir," "peramivir," "zanamivir," "lanimavir," "baloxavir," and "favipiravir." Additional references were identified from the bibliographies of relevant articles.

The following topics are covered: antivirals available for treating influenza and evidence supporting their use in critically ill patients, pharmacokinetic issues of enteral oseltamivir administration in critically ill patients, and neuraminidase inhibitors resistance.

Neuraminidase inhibitors constitute the vast majority of antivirals currently prescribed for influenza. The most commonly prescribed NAI to date is oseltamivir. While its efficacy in non-severe cases of influenza is well established, the evidence for its efficacy in critically ill patients is based on less robust studies, as no randomised controlled trials have been conducted in this population. Limited data on oseltamivir pharmacokinetics is available in critically ill patients. The selection of A(H1N1)pdm09 resistant variants to oseltamivir is particularly problematic in critically-ill patients hospitalised in intensive care units. Data on other antivirals, including NAIs (i.e., zanamivir, peramivir and laninamivir) or baloxavir marboxil in critically ill patients are scarce. Further research is needed to develop new drugs and assess their efficacy in critically ill patients and to better assess the effect of oseltamivir in this population.

Treatment of attention-deficit-hyperactivity disorder.

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