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Many individuals with autism spectrum disorder (ASD) experience various degrees of impairment in social interaction and communication, restricted, repetitive behaviours, interests/activities. These impairments make a significant contribution to poorer everyday adaptive functioning. Yet, there are no pharmacological therapies to effectively treat the core symptoms of ASD. Since symptoms of ASD likely emerge from a complex interplay of vulnerabilities, environmental factors and compensatory mechanisms during the early developmental period, pharmacological interventions arguably would have the greatest impact to improve long-term outcomes when implemented at a young age. It is essential therefore, that clinical development programmes of investigational drugs in ASD include the paediatric population early on in clinical trials. Such trials need to offer the prospect of direct benefit (PDB) for participants. In most cases in drug development this prospect is supported by evidence of efficacy in adults. However, the effectiveness of treatment approaches may be age-dependent, so that clinical trials in adults may not provide sufficient evidence for a PDB in children. In this white paper, we consolidate recommendations from regulatory guidelines, as well as advice from the Food and Drug Administration, USA (FDA) and the Committee for Human Medicinal Products (CHMP) consultations on various development programmes on: 1) elements to support a PDB to participants in early paediatric clinical trials in ASD, including single-gene neurodevelopment disorders, 2) aspects of study design to allow for a PDB. This white paper is intended to be complementary to existing regulatory guidelines in guiding industry and academic sponsors in their conduct of early paediatric clinical trials in ASD. [ABSTRACT FROM AUTHOR]

The Heart Failure Association of the European Society of Cardiology has published a previous position paper and various guidelines over the past decade recognizing the value of palliative care for those affected by this burdensome condition. Integrating palliative care into evidence‐based heart failure management remains challenging for many professionals, as it includes the identification of palliative care needs, symptom control, adjustment of drug and device therapy, advance care planning, family and informal caregiver support, and trying to ensure a 'good death'. This new position paper aims to provide day‐to‐day practical clinical guidance on these topics, supporting the coordinated provision of palliation strategies as goals of care fluctuate along the heart failure disease trajectory. The specific components of palliative care for symptom alleviation, spiritual and psychosocial support, and the appropriate modification of guideline‐directed treatment protocols, including drug deprescription and device deactivation, are described for the chronic, crisis and terminal phases of heart failure. [ABSTRACT FROM AUTHOR]

Purpose UNC Medical Center converted to an electronic health record (EHR) in 2014. This conversion allowed for the transition of paper chemotherapy orders to be managed electronically. This article describes the process for converting inpatient paper chemotherapy orders into the new EHR in a safe and effective manner. Summary A collaborative interdisciplinary approach to the EHR transition enabled our organization to move from using paper chemotherapy orders to fully electronic chemotherapy treatment plans in both ambulatory and acute care areas. Active chemotherapy orders for acute care inpatients were reviewed and transcribed by two oncology pharmacists in the cancer hospital prior to being signed by an attending physician. The newly input orders were independently verified by two pharmacists in the cancer hospital inpatient pharmacy. Nurse review of the signed and verified treatment plans, along with reconciliation of the medication administration record ensured a safe transition to the new EHR workflow. Providers benefit from the ability to review treatment plans remotely, track changes, and include supportive medications in one consolidated location. The coordinated team effort allowed for a smooth transition with minimal interruptions to patient care. Conclusion The pharmacist-led, multidisciplinary conversion to electronic chemotherapy orders was safe, accurate, and occurred ahead of schedule for the EHR go-live. Advance communication and planning around scheduled inpatient admissions helped to minimize the impact of the transition from paper to electronic treatment plans. Both pharmacist and physician engagement were necessary to ensure a smooth transition for active inpatient treatment plans. [ABSTRACT FROM AUTHOR]

Chronic airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), together with their comorbidities, bear a significant burden on public health. Increased appreciation of molecular networks underlying inflammatory airway disease needs to be translated into new therapies for distinct phenotypes not controlled by current treatment regimens. On the other hand, development of new safe and effective therapies for such respiratory diseases is an arduous and expensive process. Antibody‐based (biological) therapies are successful in treating certain respiratory conditions not controlled by standard therapies such as severe allergic and refractory eosinophilic severe asthma, while in other inflammatory respiratory diseases, such as COPD, biologicals are having a more limited impact. Small molecule drug (SMD)‐based therapies represent an active field in pharmaceutical research and development. SMDs expand biologicals' therapeutic targets by reaching the intracellular compartment by delivery as either an oral or topically based formulation, offering both convenience and lower costs. Aim of this review was to compare and contrast the distinct pharmacological properties and clinical applications of SMDs‐ and antibody‐based treatment strategies, their limitations and challenges, in order to highlight how they should be integrated for their optimal utilization and to fill the critical gaps in current treatment for these chronic inflammatory respiratory diseases. [ABSTRACT FROM AUTHOR]

Over the last 70 years, pharmacotherapy in gout with urate-lowering drugs has consisted of four drugs only: In 1952, a mild uricosuric probenecid became available, the xanthine oxidase inhibitor Allopurinol in 1964, and the latter became the most frequently used urate-lowering drug worldwide; in the Eurozone, the uricosuric benzbromarone was welcomed in 1977. Only in 2002, the potent non-purine xanthine oxidase inhibitor febuxostat was introduced. In many countries, uricosurics such as probenecid and benzbromarone have not been available up to now, and these days, the new uricosuric lesinurad is the first uricosuric that may be introduced in these countries, which is the reason for describing the position this novel uricosuric deserves in treating gout. Recent literature will be shortly reviewed, and the current proposed position for lesinurad will be given as an aid for clinicians. [ABSTRACT FROM AUTHOR]

Winnicott's unique contributions to a psychoanalytic theory of depression are not as familiar as Freud and Klein's writings. I concentrate on six areas: depression as a developmental achievement which denotes unit status; the role of destruction which arises from love (as opposed to hate which for Winnicott is a more mature affect); the importance of contributing‐in and the response of the (m)other in recovery from depression; the startling idea that the patient seeks out the analyst's depression; some thoughts on the differences between Winnicott and Freud and Klein; and lastly, the effect of depression on the development of self, creativity and the capacity to play. Winnicott does not shirk the darker side of being human, but at the same time he offers us a hopeful picture. [ABSTRACT FROM AUTHOR]

In 1958, Apley and Naish authored a groundbreaking paper in Archives of Disease in Childhood, elucidating the epidemiology and risk factors of recurrent abdominal pain in children—a subject that had confounded clinicians of their time. Surprisingly, even after 65 years, there are several unanswered questions regarding the etiology, pathophysiology, and management of pediatric abdominal pain. Contrary to the prevailing notion that children naturally outgrow functional abdominal pain, compelling evidence suggests it's possible these children develop a number of clinically significant psychological issues that could profoundly impact their quality of life and, consequently, future health and educational outcomes. In this light, we aimed to comprehensively review the current literature to update the knowledge of practicing clinicians on functional abdominal pain, summarizing the evidence from the last 65 years. Conclusion: The enduring unanswered questions surrounding childhood abdominal pain continue to challenge clinicians, resulting in unnecessary investigations, thereby contributing to substantial healthcare expenditures. It is also evident that children with long-standing symptoms would progress to adulthood with the potential to develop irritable bowel syndrome and many psychological disturbances. Several key interventions using pharmacological agents, such as amitriptyline, showed that some of these drugs are no more effective than the placebo in clinical trials. Several research during the recent past suggest that psychological interventions such as gut-directed hypnotherapy alleviate symptoms and ensure better prognosis in the long run. Therefore, clinicians and researchers must join hands to explore the pathophysiological mechanisms underpinning functional abdominal pain and novel therapeutic strategies to ensure the well-being of these children. What is Known: • Functional abdominal pain disorders are common among children, with a worldwide prevalence of 13.5% of children suffering from at least one of these disorders • These disorders contribute to a significant reduction in the quality of life of affected children and their families and lead to an array of psychological problems What is New: • The biological basis of functional abdominal pain is becoming more explicit, including complex interactions between altered microbiome, deranged motility, and psychological dysfunction with gut-brain interactions • Novel approaches giving minimal emphasis on pharmacological interventions and exploring psychological interventions are showing promising results [ABSTRACT FROM AUTHOR]

Aclarubicin (aclacinomycin A) is one of the anthracycline antineoplastic antibiotics with a multifaceted mechanism of antitumor activity. As a second-generation drug, it offers several advantages compared to standard anthracycline drugs such as doxorubicin or daunorubicin, which could position it as a potential blockbuster drug in antitumor therapy. Key mechanisms of action for aclarubicin include the inhibition of both types of topoisomerases, suppression of tumor invasion processes, generation of reactive oxygen species, inhibition of chymotrypsin-like activity, influence on cisplatin degradation, and inhibition of angiogenesis. Therefore, aclarubicin appears to be an ideal candidate for antitumor therapy. However, despite initial interest in its clinical applications, only a limited number of high-quality trials have been conducted thus far. Aclarubicin has primarily been evaluated as an induction therapy in acute myeloid and lymphoblastic leukemia. Studies have indicated that aclarubicin may hold significant promise for combination therapies with other anticancer drugs, although further research is needed to confirm its potential. This paper provides an in-depth exploration of aclarubicin's diverse mechanisms of action, its pharmacokinetics, potential toxicity, and the clinical trials in which it has been investigated. [ABSTRACT FROM AUTHOR]

Oral candidiasis is an opportunistic infection caused by fungi of the genus Candida. Nystatin, fluconazole, and miconazole are the most widely used antifungal drugs in dentistry, but in recent years, they have been shown to be less effective due to the increase in the resistance to antifungal drugs. The growing challenge of antifungal resistance emphasizes the importance of exploring not only alternative strategies in the fight against Candida spp. infections but also supportive treatment for pharmacological treatment for oral candidiasis. This review aims to evaluate and compare the in vitro reports on antifungal efficacy against Candida spp. exhibited by mouthwashes distributed on the European market. The research question was elaborated through the PEO framework recommended by PRISMA 2020. A bibliographic search strategy was developed for the scientific online databases Pubmed and ScienceDirect. According to the eligibility criteria, 21 papers were included in this study over a 27-year period. Mouthwashes containing chlorhexidine digluconate, cetylpyridinium chloride, hexetidine, and fluorine compounds among others, and natural antimicrobials, such as menthol, thymol, eucalyptol, and Glycyrrhiza glabra extracts, have demonstrated antifungal effectiveness. Nonetheless, the methodological variance introduces ambiguity concerning the comparative efficacy of distinct molecules or mouthwash formulations and complicates the evaluation and the comparison of results between studies. Some mouthwashes commercially available in Europe have the potential to be used in anti-Candida therapy and prevention since they have shown antifungal effect. [ABSTRACT FROM AUTHOR]

As Faculty of the British Association for Psychopharmacology course on child and adolescent psychopharmacology, we present here what we deem are the most common pitfalls, and how to avoid them, in child and adolescent psychopharmacology. In this paper, we specifically addressed common pitfalls in the pharmacological treatment of autism and intellectual disability, eating disorders, neuropsychiatric correlates of epilepsy, and psychosis. Pitfalls in relation to the treatment of other disorders are addressed in a separate paper (Part I). [ABSTRACT FROM AUTHOR]

Background and objectives: Treatment of spasticity poses a major challenge given the complex clinical presentation and variable efficacy and safety profiles of available drugs. We present a systematic review of the pharmacological treatment of spasticity in multiple sclerosis (MS) patients. Methods: Controlled trials and observational studies were identified. Scientific evidence was evaluated according to pre-specified levels of certainty. Results: The evidence supports the use of baclofen, tizanidine and gabapentin as first-line options. Diazepam or dantrolene could be considered if no clinical improvement is seen with the previous drugs. Nabiximols has a positive effect when used as add-on therapy in patients with poor response and/or tolerance to first-line oral treatments. Despite limited evidence, intrathecal baclofen and intrathecal phenol show a positive effect in severe spasticity and suboptimal response to oral drugs. Conclusion: The available studies on spasticity treatment offer some insight to guide clinical practice but are of variable methodological quality. Large, well-designed trials are needed to confirm the effectiveness of antispasticity agents and to produce evidence-based treatment algorithms. [ABSTRACT FROM AUTHOR]

Purpose: For individuals with atopic dermatitis (AD), interpreting scientific papers that present clinical outcomes including the Eczema Area and Severity Index (EASI) and Investigators Global Assessment may be difficult. When compared to tabulated data and graphs, images from before and after treatment are often far more meaningful to these patients that ultimately will be candidates for the treatment. This systematic review focused on determining the frequency of clinical image sharing in AD research. Materials and methods: Conducted in accordance with PRISMA guidelines, the review concentrated on randomized controlled trials that investigated predefined and available systemic treatments for AD. The search was performed in the MEDLINE database for studies published from the inception until 21 December 2023. Results: The review included 60 studies, encompassing 17,799 randomized patients. Across these studies, 16 images representing 6 patients were shared in the manuscripts, leading to a sharing rate of 0.3‰. Conclusions: The almost missing inclusion of patient images in clinical trial publications hinders patient understanding. Adding images to scientific manuscripts could significantly improve patients’ comprehension of potential treatment outcomes. This review highlights the need for authors, the pharmaceutical industry, study sponsors, and publishers to enhance and promote patient information through increased use of visual data. [ABSTRACT FROM AUTHOR]

Introduction: Idiopathic granulomatous mastitis (IGM) is an inflammatory breast disorder of unknown etiology. This benign condition can mimic the clinical presentation of breast cancer and is characterized by symptoms such as breast pain, erythema, and swelling. Over the past few years, Disease-Modifying Antirheumatic Drugs (DMARDs) have been increasingly used to manage this condition. However, strong evidence to support their use is lacking. Objectives: This systematic review aimed to summarize the evidence and evaluate the efficacy of DMARDs in the management of IGM. Methods: A systematic literature review, adhering to PRISMA guidelines, was conducted across electronic databases, including PubMed, EMBASE, SCOPUS, directory of open access journals (DOAJ) and Cochrane Library from their inception until May 2024. We included retrospective and prospective studies while excluding case reports and case series of less than 10 patients. Results: Eighteen studies met our eligibility criteria. Fifteen studies were retrospective, while 2 were prospective. No randomized controlled trials were identified. Of these, 16 papers examined the effect of methotrexate on IGM, revealing significant disease improvement in most cases. Several of the studies indicated that patients treated with azathioprine and mycophenolate mofetil also achieved favorable responses. Conclusion: Given the rarity of IGM, only a limited number of studies have explored the use of DMARDs as a pharmacological treatment option. A significant barrier to advancing our understanding is the substantial heterogeneity in the quality and volume of data provided by these studies. Therefore, there is a need for well-designed, randomized, placebo-controlled trials to rigorously assess the efficacy of DMARDs in the treatment of IGM. [ABSTRACT FROM AUTHOR]

The article offers information on catalyzing Neglected Tropical Diseases (NTD) gender and equity research. Topics discussed include significance of the NTD program predicated opportunity to treat disease, prevent morbidity and disability, and interrupt infection transmission among large populations; addresses the issue of gender equity, organizational, policy, and practice activities; and sex and gender roles can profound effect on healthcare access and health outcomes.

Treatment of motor symptoms of degenerative cerebellar ataxia remains difficult. Yet there are recent developments that are likely to lead to significant improvements in the future. Most desirable would be a causative treatment of the underlying cerebellar disease. This is currently available only for a very small subset of cerebellar ataxias with known metabolic dysfunction. However, increasing knowledge of the pathophysiology of hereditary ataxia should lead to an increasing number of medically sensible drug trials. In this paper, data from recent drug trials in patients with recessive and dominant cerebellar ataxias will be summarized. There is consensus that up to date, no medication has been proven effective. Aminopyridines and acetazolamide are the only exception, which are beneficial in patients with episodic ataxia type 2. Aminopyridines are also effective in a subset of patients presenting with downbeat nystagmus. As such, all authors agreed that the mainstays of treatment of degenerative cerebellar ataxia are currently physiotherapy, occupational therapy, and speech therapy. For many years, well-controlled rehabilitation studies in patients with cerebellar ataxia were lacking. Data of recently published studies show that coordinative training improves motor function in both adult and juvenile patients with cerebellar degeneration. Given the well-known contribution of the cerebellum to motor learning, possible mechanisms underlying improvement will be outlined. There is consensus that evidence-based guidelines for the physiotherapy of degenerative cerebellar ataxia need to be developed. Future developments in physiotherapeutical interventions will be discussed including application of non-invasive brain stimulation. [ABSTRACT FROM AUTHOR]

The article reports on the importance of electronic systems in improving safety in chemotherapy ordering and management. Topics discussed include the move of oncology practices from paper-based chemotherapy ordering to computerized provider order entry, advantages of electronic chemotherapy orders, their effect on patient safety and safety features. Also explored is the oncology nurse's role in electronic chemotherapy ordering systems. INSETS: NEW ONS/ONCC CHEMOTHERAPY BIOTHERAPY CERTIFICATE COURSE OFFERS...;NIOSH ALERT GUIDES PREVENTION OF HAZARDOUS DRUG EXPOSURE IN....

Stargardt disease (STGD) is the most common form of inherited juvenile macular dystrophy and is caused by sequence variants in the ABCA4 gene. Due to its genetic complexity and phenotypic variability, STGD poses significant therapeutic challenges. In the past decade, a lot of progress has been made regarding our understanding of the molecular and clinical aspects of STGD, along with its mechanisms. This has led to the development of new therapies, and there are human clinical trials currently ongoing. This paper evaluates the emergence of pharmacological approaches targeting the visual cycle to mitigate retinal damage, the role of gene therapy in correcting specific genetic defects, and the use of stem cell therapies aimed at retinal regeneration by showcasing the latest clinical trials and precision medicine approaches. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) constitutes a multifactorial neurodegenerative pathology characterized by cognitive deterioration, personality alterations, and behavioral shifts. The ongoing brain impairment process poses significant challenges for therapeutic interventions due to activating multiple neurotoxic pathways. Current pharmacological interventions have shown limited efficacy and are associated with significant side effects. Approaches focusing on the early interference with disease pathways, before activation of broad neurotoxic processes, could be promising to slow down symptomatic progression of the disease. Curcumin—an integral component of traditional medicine in numerous cultures worldwide—has garnered interest as a promising AD treatment. Current research indicates that curcumin may exhibit therapeutic potential in neurodegenerative pathologies, attributed to its potent anti‐inflammatory and antioxidant properties. Additionally, curcumin and its derivatives have demonstrated an ability to modulate cellular pathways via epigenetic mechanisms. This article aims to raise awareness of the neuroprotective properties of curcuminoids that could provide therapeutic benefits in AD. The paper provides a comprehensive overview of the neuroprotective efficacy of curcumin against signaling pathways that could be involved in AD and summarizes recent evidence of the biological efficiency of curcumins in vivo. [ABSTRACT FROM AUTHOR]

The article explores the field of therapeutic drug monitoring (TDM) and its role in tailoring drug therapy to individual patients. TDM is a multidisciplinary branch of clinical medicine that provides valuable information for managing pharmacotherapy. The article emphasizes the importance of TDM-guided treatments for vulnerable patient populations, such as those with cancer, critical illness, or unique biological characteristics. It also presents research articles and review papers on various drugs, including antibiotics, antifungals, antivirals, immunosuppressants, and antidiabetics, and their pharmacokinetic processing. The goal is to showcase the usefulness of TDM in optimizing drug treatments for specific patient groups. The authors conclude that TDM is a dynamic and important field that will continue to be relevant in the future, despite ongoing challenges and unanswered scientific questions. [Extracted from the article]

In children and adolescents, autism spectrum disorders (ASD) and obsessive–compulsive disorders (OCD) may share similar features, such as deficits in social communication, repetitive behaviours and presence of obsession and compulsion. Studies have shown that children with OCD may exhibit the presence of ASD traits. Up to date research shows that selective serotonin reuptake inhibitors are commonly used to treat OCD, while treatment options for ASD are limited. A literature search was performed using the PubMed database and retrieving relevant papers up to December 2022. This review includes 9 case reports and 8 randomized controlled trials. The main psychopharmacological drugs used include antidepressants and antipsychotics. This review shows that the management of OCD behaviours in individuals with ASD and related conditions is of complex nature and pharmacological interventions may not be an effective method in managing this group of patients. Hence, more comprehensive research and deeper knowledge is important in optimizing pharmacological management for patients with OCD behaviours with underlying ASD. [ABSTRACT FROM AUTHOR]

Coumarins, a subgroup of colorless and crystalline oxygenated heterocyclic compounds originally discovered in the plant Dipteryx odorata, were the subject of a recent study investigating their quantitative structure–activity relationship (QSAR) in cancer pharmacotherapy. This study utilized graph theoretical molecular descriptors, also known as topological indices, as a numerical representation method for the chemical structures embedded in molecular graphs. These descriptors, derived from molecular graphs, play a pivotal role in quantitative structure–property relationship (QSPR) analysis. In this paper, intercorrelation between the Balban index, connective eccentric index, eccentricity connectivity index, harmonic index, hyper Zagreb index, first path Zagreb index, second path Zagreb index, Randic index, sum connectivity index, graph energy and Laplacian energy is studied on the set of molecular graphs of coumarins. It is found that the pairs of degree-based indices are highly intercorrelated. The use of these molecular descriptors in structure–boiling point modeling was analyzed. Finally, the curve-linear regression between considered molecular descriptors with physicochemical properties of coumarins and coumarin-related compounds is obtained. Some of the coumarin-related anti-cancer compounds considered in this study [ABSTRACT FROM AUTHOR]

Aim: In this paper we review the current literature on the clinical problem that some patients do not achieve response after adequately conducted psychotherapy. We explicate our understanding of nonresponse and treatment resistance including the operational definitions, summarize the theoretical explanations and empirical studies and put forward possible study designs and treatment options. Methods: Literature search using PubMed and Web of Science. Results: For the domain of psychotherapy, the term treatment resistance does not seem appropriate; instead, we use the more descriptive terms nonresponse and recurrent nonresponse. Generally, this topic is far less represented in psychotherapy than in pharmacotherapy. Controlled switching studies with a switch from pharmacotherapy to psychotherapy are rare and those switching from one psychotherapeutic approach to another are nearly nonexistent. Building on clinical considerations, we propose a flow-chart for clinical decision making after nonresponse in psychotherapy. Discussion: Learning from errors is highly beneficial. This principle should be more consistently followed up in psychotherapy research as well as in supervision and training. Guidelines should include consensual and evidence-based advice on how to deal with nonresponse and recurring nonresponse. [ABSTRACT FROM AUTHOR]

Background: Appetite suppression and weight loss are established potential side effects of most medications for attention deficit/hyperactivity disorder (ADHD). These side effects may be especially problematic when using stimulants to treat ADHD in the context of a restrictive eating disorder, such as avoidant restrictive food intake disorder (ARFID), although these diagnoses are often comorbid in children. This paper presents a combined approach to treating ADHD comorbid with ARFID using stimulant medication and behavior management within a partial hospitalization program (PHP) and intensive outpatient program (IOP)for eating disorders. The aim of this paper is to determine if the continued or new use of stimulant medication allows for adequate weight restoration by reviewing a series of cases receiving the combined treatment. Case presentations: Consecutive patients with a historical or new diagnosis of ADHD when presenting for treatment for ARFID were included in this case series. This series included 10 patients (8 male, 2 female) who received pharmacotherapy using stimulants and behavior management interventions involving structured mealtimes and contingency management. All treatment occurred within the context of a PHP/IOP for childhood eating disorders. All youth were able to effectively continue on stimulant medication, show clinical benefit in core ADHD symptoms, and able to gradually restore weight. In all cases, stimulant medications were not discontinued, but in some cases, doses were optimized (increased or decreased), switched to a different stimulant, or augmented with non-ADHD medication, such as mirtazapine, to support the management of ADHD while concurrently assisting in weight gain as necessary for the treatment of ARFID. Only one patient was newly started on a stimulant medication; as this was near the end of her treatment stay, limited conclusions can be drawn from this case. Conclusions: These findings support the use of pharmacotherapy, including continuing stimulant medication, when combined with behavior management strategies as a potentially effective treatment approach for ADHD in youth with ARFID in the PHP/IOP setting. Future studies using more rigorous methodology, longer follow-up times, and within other treatment settings are needed. [ABSTRACT FROM AUTHOR]

Heart failure ( HF) care takes place in multiple settings, with a variety of providers, and generally involves patients who have multiple comorbidities. This situation is a 'perfect storm' of factors that predispose patients to medication errors. The goals of this paper are to outline potential roles for clinical pharmacists in a multidisciplinary HF team, to document outcomes associated with interventions by clinical pharmacists, to recommend minimum training for clinical pharmacists engaged in HF care, and to suggest financial strategies to support clinical pharmacy services within a multidisciplinary team. As patients transition from inpatient to outpatient settings and between multiple caregivers, pharmacists can positively affect medication reconciliation and education, assure consistency in management that results in improvements in patient satisfaction and medication adherence, and reduce medication errors. For mechanical circulatory support and heart transplant teams, the Centers for Medicare and Medicaid Services considers the participation of a transplant pharmacology expert (e.g., clinical pharmacist) to be a requirement for accreditation, given the highly specialized and complex drug regimens used. Although reports of outcomes from pharmacist interventions have been mixed owing to differences in study design, benefits such as increased use of evidence-based therapies, decreases in HF hospitalizations and emergency department visits, and decreases in all-cause readmissions have been demonstrated. Clinical pharmacists participating in HF or heart transplant teams should have completed specialized postdoctoral training in the form of residencies and/or fellowships in cardiovascular and/or transplant pharmacotherapy, and board certification is recommended. Financial mechanisms to support pharmacist participation in the HF teams are variable. Positive outcomes associated with clinical pharmacist activities support the value of making this resource available to HF teams. [ABSTRACT FROM AUTHOR]

Although the use of oral anticoagulants (vitamin K antagonists) has been abandoned in primary cardiovascular prevention due to lack of a favorable benefit-to-risk ratio, the indications for aspirin use in this setting continue to be a source of major debate, with major international guidelines providing conflicting recommendations. Here, we review the evidence in favor and against aspirin therapy in primary prevention based on the evidence accumulated so far, including recent data linking aspirin with cancer protection. While awaiting the results of several ongoing studies, we argue for a pragmatic approach to using low-dose aspirin in primary cardiovascular prevention and suggest its use in patients at high cardiovascular risk, defined as ≥2 major cardiovascular events (death, myocardial infarction, or stroke) projected per 100 person-years, who are not at increased risk of bleeding. [ABSTRACT FROM AUTHOR]

Abstract: Treatments currently recommended for metastatic renal cell cancer (mRCC) have not been evaluated specifically in elderly patients. Here we consider what may be learned by analysing according to age the efficacy and toxicity data from key phase III trials of the targeted agents sorafenib (Nexavar), sunitinib (Sutent), temsirolimus (Torisel), and bevacizumab (Avastin), and from a study of expanded access to sunitinib and sorafenib. This paper represents the first systematic review of the role of targeted agents specifically in the elderly population. Retrospective subgroup analyses of clinical trial data cannot be considered definitive. However, they suggest in general that the progression-free and overall survival benefits seen in mRCC patients aged 65 years and over are similar to those in the younger age group. The frequency of major toxicities in elderly patients treated with targeted agents is no greater than in younger patients, although such toxicities may have greater impact on the quality of life. That said, no meaningful data are available for patients over 85 years. To confirm and extend these conclusions, prospective studies should be undertaken in the elderly to determine whether recommendations made for the wider mRCC population apply equally to this group of patients in whom comorbidities, comedication and the greater impact of low-grade toxicity may influence the efficacy and tolerability of treatment. Such studies are increasingly needed, given the growing number of elderly people and their rising life expectancy. Meanwhile, when considering the most appropriate drug to use in a particular patient, the toxicity profiles of the individual targeted agents – and any implications for specific comorbid conditions – should be taken into account. [Copyright &y& Elsevier]

In competition sports, a diuretic is a substance widely prohibited by the World Anti-Doping Agency (WADA). In this paper, a sensitive, rapid and convenient analytical method for the determination of acidic [furosemide (FUROS) and bumetanide (BUMET)] and basic [triamterene (TRIAM)] diuretics in human urine was developed by hollow fiber-based liquid–liquid–liquid microextraction (LLLME) coupled with HPLC-UV. The LLLME conditions, such as the organic extraction solvent, the acidity and basicity of the donor- and acceptor-phases, stirring speed, extraction time and ionic strength, were studied in detail. Under the optimum conditions, the linear ranges of furosemide, bumetanide and triamterene were 1.2–250, 5.0–250 and 5.0–500 ng mL−1, respectively. The detection limits were 0.5 ng mL−1for furosemide, 1.2 ng mL−1for bumetanide and 2.0 ng mL−1for triamterene. The LLLME obtained a great improvement of the detection limits for all the analytes considered here, to the ng mL−1level, which almost reaches the level of the LC–MS method. This new LLLME method provided very high enrichments: 117-fold for furosemide, 175-fold for bumetanide and 68-fold for triamterene. Since the hollow fiber membrane was sealed, it could be used for extracting the diuretics directly from ‘dirty’ human urine samples without any clean-up procedures. With LLLME–HPLC, the corresponding recoveries ranged from 79.2 to 109% with the RSDs not exceeding 5.5% for the three diuretics in the spiked urine samples. The method was successfully applied to analyse the amounts of the three diuretics in real urine samples of volunteers after oral drug-taking. This new method proves to be sensitive and reliable and thus renders a very suitable means for the determination of trace diuretics in human urine based on the common HPLC instrument. [ABSTRACT FROM AUTHOR]

The article presents the summaries of papers related to photodermatology. Patients with systemic psoralen sensitization need to wear adequate eye protection for the day of ingestion of psoralen. A comparative assessment of the ultraviolet radiation transmission of sunglasses for patients receiving photochemotherapy. A simplified method for checking patient eyewear for suitability for systemic psoralen ultraviolet A (PUVA) uses a suitably filtered detector to measure the transmission of UVA from a hand/foot PUVA unit. However, not all units have the equipment or expertise to be able to treat patientsown glasses routinely for suitability for use after PUVA therapy.

The article reports on several research papers related to cancer and its treatment. It informs that loss of the apoptotic response has been implicated in carcinogenesis as a consequence of increased survival of DNA-damage bearing cells. Many cancer cells have an inherent resistance to chemotherapy due to the abnormal expression of anti-apoptosis genes. The increased risk of cancer in immunosuppressed patients after organ transplantation, and in patients with inherited defects in immune function, such as severe combined immune deficiency, was thought to support the immune surveillance hypothesis.

Chronic pain is one of the main leading causes of disability in the world at present. A variety in the symptomatology, intensity and duration of this phenomenon has led to an ever-increasing demand of pharmacological treatment and relief. This demand for medication, ranging from well-known groups, such as antidepressants and benzodiazepines, to more novel drugs, was followed by a rise in safety concerns of such treatment options. The validity, frequency, and diversity of such concerns are discussed in this paper, as well as their possible effect on future prescription practices. A specific caution is provided towards the psychological safety and toll of these medications, regarding suicidality and suicidal ideation. Most significantly, this paper highlights the importance of pharmacovigilance and underscores the necessity of surveillance programs when considering chronic pain medication. [ABSTRACT FROM AUTHOR]

Objective: To characterize global research on the effectiveness of drug use prevention policies, plans, programs and projects, based on the analysis of research articles published and indexed in scientific databases. Material and methods: Articles on this topic contained in the Web of Science Core Collection database were downloaded and transferred to a Microsoft Access database using a broad search profile that has already been successfully applied in other works. To characterize the scientific production, methods and indicators from the field of bibliometrics were used, as well as social network analysis. Results: The number of published articles (1266) increased, only diminished in the first years of the epidemic by Covid-19. The subject areas with the highest number of papers were Substance Abuse (435), Public Environmental & Occupational Health (394), Psychiatry (163) and Psychology Clinical (157). Articles published by institutions in the United States, United Kingdom, Australia and Canada predominated. The most studied topics were those related to alcohol abuse, smoking, opioids and cannabis. Conclusions: A progressive increase in the number of articles on the analyzed topic and institutional collaboration has been confirmed, which is indicative of its health and scientific interest. Alcoholism and smoking are the two most studied addictions in these papers, and the most frequent and most cited topics deal with prevention in adolescence, therapeutic compliance, the effectiveness of harm reduction programs and prevention from primary care. [ABSTRACT FROM AUTHOR]

Post-traumatic stress disorder (PTSD) is a psychopathological condition with a heterogeneous clinical picture that is complex and challenging to treat. Its multifaceted pathophysiology still remains an unresolved question and certainly contributes to this issue. The pharmacological treatment of PTSD is mainly empirical and centered on the serotonergic system. Since the therapeutic response to prescribed drugs targeting single symptoms is generally inconsistent, there is an urgent need for novel pathogenetic hypotheses, including different mediators and pathways. This paper was conceived as a narrative review with the aim of debating the current pharmacological treatment of PTSD and further highlighting prospective targets for future drugs. The authors accessed some of the main databases of scientific literature available and selected all the papers that fulfilled the purpose of the present work. The results showed that most of the current pharmacological treatments for PTSD are symptom-based and show only partial benefits; this largely reflects the limited knowledge of its neurobiology. Growing, albeit limited, data suggests that the hypothalamic-pituitary-adrenal axis, opioids, glutamate, cannabinoids, oxytocin, neuropeptide Y, and microRNA may play a role in the development of PTSD and could be targeted for novel treatments. Indeed, recent research indicates that examining different pathways might result in the development of novel and more efficient drugs. [ABSTRACT FROM AUTHOR]

Aim. This article discusses the clinical implications of adverse health outcomes derived during heatwaves for people with mental health disorders, substance misuse and those taking prescribed medications such as lithium, various neuroleptic and anticholinergic drugs. Background. With climate change it is predicted that the incidence of prolonged periods of extreme heat will increase. Specific adverse health outcomes associated with high environmental temperatures include heat stroke and heat exhaustion. Those at increased risk for heat-related mortality are those with chronic health conditions, including those with mental health disorders and substance misuse. Data sources. Sources of evidence included and 'grey' literature published between 1985 and 2010, such as key texts, empirical research, public policies, training manuals and community information sheets on heat waves. Discussion. Current clinical practice and clinical impact of heatwaves on those people with comorbidity is explored. This includes the physiological components of heat stress, heat regulation, and the impact of alcohol and other drugs; and, ramifications and professional practice issues for those with mental health conditions and those requiring mental health medications. Implications for nursing. Client education covering modification of the environment and the use of client heat safety action plans. Secure, accessible stores of prescribed medication are recommended and emergency substance withdrawal kits could be made available. Conclusion. All nurses have a responsibility to increase the capability and resilience of their clients to manage their chronic health needs during a heatwave. At these times nurses need to give extra monitoring and assistance when clients lack the capacity or resources to protect themselves. [ABSTRACT FROM AUTHOR]

The article presents research summaries related to dermatopathology in Great Britain. In one of the studies, it aims to increase the awareness of prototheca wickerhamii which causes neutropenic sepsis after a chemotherapy. Another study reports a case of histiocyctic sarcoma having secondary skin involvement and a presumed primary in the lung. Furthermore, a case report on symplastic haemangioma which is developing on a background of chronic leg ulcer is given.

External comparator (EC) studies are increasingly being used to generate evidence that supports the evaluation of emerging pharmacological treatments for regulatory and health technology assessment (HTA) purposes. However, the reliability of evidence generated from EC studies can vary. In this paper, we outline how an existing framework for causal inference, the target trial emulation (TTE) framework, can be appropriately applied to improve the design and analysis of EC studies. Applying the TTE framework involves specifying the protocol of an ideal target trial which would answer the causal question of interest, then emulating its key elements under real-world (RW) settings. We describe each component of the original TTE framework and explain how it can be applied to EC studies, supplemented with practical recommendations. We also highlight special considerations and limitations in applying the TTE framework to EC studies. We describe how the TTE framework can be applied to improve the clarity, transparency, and reliability of evidence generated from EC studies. [ABSTRACT FROM AUTHOR]

Background: This paper investigates whether age of onset of depression, duration of the last episode, number of episodes, and residual symptoms of depression and anxiety are associated with depression relapse in primary care patients who have been on long–term maintenance antidepressant treatment and no longer meet ICD10 criteria for depression. Methods: An observational cohort using data from ANTLER (N = 478), a double-blind placebo-controlled trial. The primary outcome was time to relapse using the retrospective CIS-R. Participants were followed for 12 months. Results: Primary outcome was available for 468 participants. Time to relapse in those with more than five previous episodes of depression was shorter, hazard ratio (HR) 1.84 (95% confidence interval [CI] 1.23–2.75) compared to people with two episodes; HR 1.57 (95% CI 1.01–2.43) after adjustment. The residual symptoms of depression at baseline were also associated with increased relapse: HR 1.05 (95% CI 1.01–1.09) and HR 1.06 (95% CI 1.01–1.12) in the adjusted model. There was evidence of reduced rate of relapse in older age of onset group: HR 0.86 (95% CI 0.78–0.95); HR attenuated after adjustment HR 0.91 (95% CI 0.81–1.02). There was no evidence of an association between duration of the current episode and residual anxiety symptoms with relapse. Conclusions: The number of previous episodes and residual symptoms of depression were associated with increased likelihood of relapse. These factors could inform joint decision making when patients are considering tapering off maintenance antidepressant treatment or considering other treatments to prevent relapse. [ABSTRACT FROM AUTHOR]

Background: Epidemiological studies often rely on self-reported health problems and validation greatly improves study quality. In a study of late effects after childhood cancer, we validated self-reported cardiovascular problems by contacting general practitioners (GPs). This paper describes: (a) the feasibility of this approach; and (b) the agreement between survivor-reports and reports from their GP. Methods: The Swiss Childhood Cancer Survivor Study (SCCSS) contacts all childhood cancer survivors registered in the Swiss Childhood Cancer Registry since 1976 who survived at least 5 years from cancer diagnosis. We validated answers of all survivors who reported a cardiovascular problem in the questionnaire. Reported cardiovascular problems were hypertension, arrhythmia, congestive heart failure, myocardial infarction, angina pectoris, stroke, thrombosis, and valvular problems. In the questionnaire, we further asked survivors to provide a valid address of their GP and a consent for contact. We sent case-report forms to survivors' GPs and requested information on cardiovascular diagnoses of their patients. To determine agreement between information reported by survivors and GPs, we calculated Cohen's kappa (κ) coefficients for each category of cardiovascular problems. Results: We used questionnaires from 2172 respondents of the SCCSS. Of 290 survivors (13% of 2172) who reported cardiovascular problems, 166 gave consent to contact their GP and provided a valid address. Of those, 135 GPs (81%) replied, and 128 returned the completed case-report form. Survivor-reports were confirmed by 54/128 GPs (42%). Of the 54 GPs, 36 (28% of 128) confirmed the problems as reported by the survivors; 11 (9% of 128) confirmed the reported problem(s) and gave additional information on more cardiovascular outcomes; and seven GPs (5% of 128) confirmed some, but not all cardiovascular problems. Agreement between GPs and survivors was good for stroke (κ = 0.79), moderate for hypertension (κ = 0.51), arrhythmias (κ = 0.41), valvular problems (κ = 0.41) and thrombosis (κ = 0.56), and poor for coronary heart disease (κ = 0.15) and heart failure (κ = 0.32). Conclusions: Despite excellent GP compliance, it was found unfeasible to validate self-reported cardiovascular problems via GPs because they do not serve as gatekeepers in the Swiss health care system. It is thus necessary to develop other validation methods to improve the quality of patient-reported outcomes. [ABSTRACT FROM AUTHOR]

With the acceleration of the aging process and change in social lifestyle, the prevalence rate of late-life depression (LLD) in the elderly is increasing year by year. As the most common mental disorder in the elderly, LLD seriously affects the quality of life of patients, and thus brings a heavy burden to the family and society. It may even become life-threatening for the elderly patients. The pathogenesis of LLD is still unclear, which may be caused by a combination effects of biological, social and psychological factor. Given the declined body functions and more comorbid physical diseases in the elderly population, the diagnosis and treatment of LLD patients would be different from that of younger adult patients with depression. This paper reviews the epidemiological characteristics, clinical evaluation, diagnosis, comorbidity, treatment and intervention of LLD, and focuses on the selection of therapeutic drugs and adverse reactions, in order to provide references for better diagnosis and treatment of LLD and improve the prognosis of patients. [ABSTRACT FROM AUTHOR]

Human glioblastoma is probably the most malignant and aggressive among cerebral tumors, of which it represents approximately 80% of the reported cases, with an overall survival rate that is quite low. Current therapies include surgery, chemotherapy, and radiotherapy, with associated consistent side effects and low efficacy. The hardness in reaching the site of action, and overcoming the blood–brain barrier, is a major limitation of pharmacological treatments. In this paper, we report the synthesis and characterization of ZIF-90 (ZIF, Zeolitic Imidazolate Framework) nanoparticles as putative carriers of anticancer drugs to the brain. In particular, we successfully evaluated the biocompatibility of these nanoparticles, their stability in body fluids, and their ability to uptake in U251 human glioblastoma cell lines. Furthermore, we managed to synthesize ZIF-90 particles loaded with berberine, an alkaloid reported as a possible effective adjuvant in the treatment of glioblastoma. These findings could suggest ZIF-90 as a possible new strategy for brain cancer therapy and to study the physiological processes present in the central nervous system. [ABSTRACT FROM AUTHOR]

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a persistent pattern of inattention, hyperactivity, and impulsivity. It is the most common neurodevelopmental disorder presenting to pediatric services, and pediatricians are often involved in the early assessment, diagnosis, and treatment of children with ADHD. The treatment of ADHD typically involves a multimodal approach that encompasses a combination of psychoeducation, parent/teacher training, psychosocial/psychotherapeutic interventions, and pharmacotherapy. Concerning pharmacotherapy, guidelines vary in drug choice and sequencing, with psychostimulants, such as methylphenidate and (lis)dexamfetamine, generally being the favored initial treatment. Alternatives include atomoxetine and guanfacine. Pharmacotherapy has been proven effective, but close follow-up focusing on physical growth, cardiovascular monitoring, and the surveillance of potential side effects including tics, mood fluctuations, and psychotic symptoms, is essential. This paper presents an overview of current pharmacological treatment options for ADHD and explores disparities in treatment guidelines across different European countries. Conclusion: Pharmacological treatment options for ADHD in children and adolescents are effective and generally well-tolerated. Pharmacotherapy for ADHD is always part of a multimodal approach. While there is a considerable consensus among European guidelines on pharmacotherapy for ADHD, notable differences exist, particularly concerning the selection and sequencing of various medications. What is Known: • There is a significant base of evidence for pharmacological treatment for ADHD in children and adolescents. • Pediatricians are often involved in assessment, diagnosis and management of children with ADHD. What is New: • Our overview of different European guidelines reveals significant agreement in the context of pharmacotherapy for ADHD in children and adolescents. • Discrepancies exist primarily in terms of selection and sequencing of different medications. [ABSTRACT FROM AUTHOR]

Introduction: Post-stroke mania is a complex neuropsychiatric phenomenon that poses challenges in both diagnosis and management. This paper presents a detailed analysis of three distinct cases, comprising two females and one male, each exhibiting post-stroke mania following cerebrovascular events. Our study aims to provide insights into the varied clinical presentations, contributing factors, and therapeutic interventions in this unique subset of stroke survivors. Case 1: A 71-year-old female experienced a left hemispheric stroke, subsequently displaying manic symptoms characterized by elevated mood, impulsivity, and increased energy. Neuroimaging revealed damage to the parieto-occipital lobe, prompting further exploration into the neural correlates of post-stroke mania. Case 2: A 51-year-old female presented with right hemiparesis. Shortly after the stroke, she manifested manic features, including decreased need for sleep and heightened irritability. Psychosocial factors and pharmacological interventions were investigated to better understand the interplay of biological and environmental influences. Case 3: A 55-year-old male suffered a left hemispheric stroke. Poststroke, she exhibited manic symptoms such as distractibility and excessive goal-directed activity. The impact of lesion location on the manifestation of post-stroke mania was explored in this case. Conclusion:Through a comprehensive analysis of these cases, we aim to contribute to the growing body of literature on post-stroke mania, shedding light on its clinical heterogeneity and paving the way for tailored treatment approaches. Recognizing the nuanced nature of post-stroke mania is crucial for healthcare providers to optimize care strategies and improve the quality of life for stroke survivors grappling with this challenging neuropsychiatric condition. [ABSTRACT FROM AUTHOR]

In this paper, a metal–organic skeleton material MIL‐101‐NH2‐AL was prepared for loading the chemotherapeutic drug Oridonin (Ori) and photosensitizer Chlorin e6 (Ce6). A drug delivery system for synergistic chemotherapy and photodynamic therapy was constructed. At the same time, we evaluated MIL‐101‐NH2‐AL as a drug therapy carrier, including drug loading, cytotoxicity, and safety, verified the photodynamic efficiency of MIL‐101‐NH2‐AL@Ori@Ce6 in vitro, and studied the ability of MIL‐101‐NH2‐AL@Ori@Ce6 cancer cells to produce reactive oxygen species, cell uptake, cytotoxicity, and so on. Experiments have confirmed that MIL‐101‐NH2‐AL, as a nano‐carrier, encapsulated Oridonin and Ce6, the combination of PDT and chemotherapy showed enhanced tumor inhibition and high biosafety. The killing effect on cells was caused by reactive oxygen species produced by photosensitizers and apoptosis of tumor cells induced by Oridonin. The drug delivery system demonstrates enormous potential for synergistic anti‐tumor effects of photodynamic and chemotherapy. [ABSTRACT FROM AUTHOR]

Objectives: Blue rubber bleb nevus syndrome (BRBNS) is a rare challenging cause of gastrointestinal bleeding. We performed a systematic review of case reports and case series on BRBNS to gather information on the treatment options currently available. Methods: All studies reporting a case of BRBNS in humans were evaluated. Papers were ruled out if CARE criteria and explanations on patient's selection, ascertainment, causality, and reporting were not respected or identified. PROSPERO 2021 CRD 42021286982. Results: Blue rubber bleb nevus syndrome was treated in 106 cases from 76 reports. 57.5% of the population was under 18 years old, and up to 50% of the cases reported a previous treatment. Clinical success was achieved in 98 patients (92.4%). Three main types of interventions were identified: systemic drug therapy, endoscopy, and surgery. After BRBNS recurrence or previous therapy failure, systemic drug therapy emerged as a preferred second‐line treatment over endoscopy (P = 0.01), but with a higher rate of reported adverse events when compared with surgery and endoscopy (P < 0.001). Endoscopic treatment was associated with a higher number of required sessions to achieve complete eradication when compared with surgery (P < 0.001). No differences between the three main areas were found in the overall follow‐up time (P = 0.19) or in the recurrence rate (P = 0.45). Conclusion: Endoscopy, surgery, and systemic drug therapy are feasible treatment options for BRBNS. Systemic drug therapy was the favorite second‐line treatment after endoscopic failure or recurrence of BRBNS, but adverse events were more frequently reported. [ABSTRACT FROM AUTHOR]

The article presents abstract of medical research. They include "Tamoxifen treatment after adjuvant chemotherapy has opposite effects on bone mineral density in premenopausal patients depending on menstrual status", "Hypertension, menopause, and coronary artery disease risk in the Women's Ischemia Syndrome Evaluation (WISE) Study" and "Neoadjuvant chemotherapy in vulvar cancer: Avoiding primary exenteration".

A combination of methods is used for diagnosis of bladder cancer because no single procedure detects all malignancies. Urine tests are frequently part of an evaluation, but have either been nonspecific for cancer or required specialized analysis at a laboratory. Adjuvant chemotherapy improves survival for patients with local-regional breast cancer, but healthy older patients at high risk of recurrence are frequently not offered adjuvant chemotherapy, and the benefit of adjuvant chemotherapy in older patients is uncertain. The current report is a long-term evaluation of breast carcinoma recurrence, factors predicting recurrence, and postrecurrence prognosis in relation to patients’ use of service screening, which has been provided in Turku, Finland, since 1987 for women ages 40-74 years.

The article presents several studies related to cancer research. Certain alkylating agents because of their toxic properties, are also used for cancer chemotherapy. These affect very different target cell populations. Results on its study demonstrate that global cellular responses to alkylation damage are far more complex than first thought. It also discusses about replicating adenoviruses that target colon cancer. Adenoviruses that were developed, selectively replicate in cells with activated Wnt signaling by inserting binding sites for the Tcf family of transcription factors in the early promoters of human adenovirus 5.

Sixty-five patients who were primary or secondary refractory to melphalan/prednisone or other type of chemotherapy, or relapsed within 6 months after high dose chemotherapy with stem cell support, were given thalidomide at a dose of 200 mg/d escalating to 800 mg. The patients were followed for a median of 2 years and 22 weeks. Response was evaluated according to M-protein reduction combined with improvement of haemoglobin (Hb) concentration, renal function and pain. Altogether, 14% of patients had a minor response, 14% partial response and 6% complete response. Median survival was 12 months and 29% were alive at last contact. Decline of M protein started early and a minimum 25% reduction of M protein was detected in 14 of 20 responders (70%) after 3 weeks, and in 20 of 22 responders (91%) after 5 weeks of treatment. Reduction of M protein continued for 3 months and further decline was observed in only four patients. The Hb concentration showed a different time course, with a significant increase after 3 months and further increases continued for up to 12 months. Blood concentration levels of thalidomide from 40 patients were used to evaluate the pharmacokinetics of the drug. Rate of absorption, rate of elimination, volume of distribution, clearance and elimination half-life were calculated to be 0·200/h, 0·140/h, 0·886 l/kg, 0·126 l/h/kg and 4·98 h respectively. We found no relationship between thalidomide concentration and effect after 12 weeks. [ABSTRACT FROM AUTHOR]

Whether the response to chemotherapy is a prognosticator in multiple myeloma (MM) is still not known. Therefore, the relationship between survival and the rate of monoclonal protein (M-protein) decrement during the first cycles of therapy was prospectively assessed in 262 patients with newly diagnosed MM that were included in a phase III trial (HOVON-16). M-proteins were collected monthly during melphalan–prednisone therapy (MP: melphalan 0·25 mg/kg, prednisone 1·0 mg/kg orally for 5 d every 4 weeks). Patients with light chain disease ( n = 18), immunoglobulin M (IgM)-MM ( n = 1) and no immunotyping ( n = 1) were excluded. Of the 242 patients studied, 75% had IgG M-protein and 25% IgA; MM stages: I: 1%, II: 35% and III: 64%. The median M-protein decrease after the first cycle of MP was 21% for IgG and 27% for IgA, and declined to < 5% after four cycles. An obvious survival advantage was seen for patients who had an M-protein decrease of at least 30% after the first MP cycle, which became significant when an M-protein decrease of 40% or more was reached. As established prognostic parameters (Salmon & Durie stage, serum creatinine, and haemoglobin) also remained prognostically significant, we concluded that early response to MP predicts for survival in MM. [ABSTRACT FROM AUTHOR]

Both single and tandem cycles of high dose therapy and autologous peripheral blood stem cell transplantation (ASCT) have been shown to improve survival in multiple myeloma (MM) patients. We report outcomes in 104 MM patients undergoing a single transplant after conditioning with a conventional myeloablative regimen, busulphan and cyclophosphamide. The patients were either in a first (71%), or subsequent remission (29%). Peripheral blood stem cells were mobilized using cyclophosphamide and granulocyte colony stimulating factor. The conditioning regimen consisted of busulphan 0·85 mg/kg given orally every 6 h (16 doses) and cyclophosphamide 60 mg/kg/d given intravenously for 2 d. The entire conditioning, transplant and post-transplant course were in the outpatient setting for 45% patients. At a median follow-up of 26 months (range 2–98 months), the median overall and progression-free survival were 57 months [95% confidence interval (CI) 47–68] and 26 months (95% CI 20–32) respectively. Younger age and higher CD34+ cell dose infused were independently predictive of improved overall and progression-free survival. Busulphan and cyclophosphamide is an effective and well-tolerated preparative regimen for ASCT that can be given to MM patients in the outpatient setting. [ABSTRACT FROM AUTHOR]

Summarizes several clinically relevant articles addressing topics in benign and malignant breast disease published in the U.S. in 2002. "Revision of the American Joint Committee on Cancer Staging System for Breast Cancer," by S. Singletary et al; "Twenty-Five Year Follow-up of a Randomized Trial Comparing Radical Mastectomy and Total Mastectomy Followed by Irradiation," by B. Fisher et al; "Does Aggressive Local Therapy Improve Survival in Metastatic Breast Cancer?," by B. Khan et al; "A Prospective Trial of Preoperative Chemotherapy in Resectable Breast Cancer: Predictors of Breast-Conservation Therapy Feasibility," L.A. Newman.