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Abstract: The treatment of common nodal peripheral T-cell lymphomas (PTCLs), including PTCL, not otherwise specified (PTCL, NOS), anaplastic large-cell lymphomas, and T-follicular helper lymphomas, is evolving. These entities are currently treated similarly with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP) for CD30-negative diseases, or brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (CHP) for CD30-positive diseases, followed by consolidation with autologous stem cell transplantation in the first remission. Ongoing improvements in PTCL classification, identification of predictive biomarkers, and development of new targeted agents will lead to more specific therapies that address the unique biologic and clinical properties of each entity. For example, widespread efforts focused on molecular profiling of PTCL, NOS is likely to identify distinct subtypes that warrant different treatment approaches. New agents, such as EZH1/2 and JAK/STAT pathway inhibitors, have broadened treatment options for relapsed or refractory diseases. Furthermore, promising strategies for optimizing immune therapy for PTCL are currently under investigation and have the potential to significantly alter the therapeutic landscape. Ongoing frontline study designs incorporate an understanding of disease biology and drug sensitivities and are poised to evaluate whether newer-targeted agents should be incorporated into frontline settings for various disease entities. Although current treatment strategies lump most disease entities together, future treatments will include distinct strategies for each disease subtype that optimize therapy for individuals. This movement toward individualized therapy will ultimately lead to dramatic improvements in the prognosis of patients with PTCL., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

An introduction to the 10th edition of the annual Pharmacy Forecast published within the issue is presented.

The article discusses the strategic planning advice and forecast from the American Society of Health-System Pharmacists (ASHP) for pharmacy departments in health systems and hospitals. Other topics include the factors affecting the pharmacy sector like personal privacy issues, big data, and trend toward globalization, the industry's global supply chain, and the international drug market.

The article presents the 2020 annual Pharmacy Forecast, published by the ASHP Research and Education Foundation. Topics covered include the challenges facing health-system pharmacy leaders, the importance of strategic planning to deal with the unexpected and unpredictable events known as black swans, and the ability of states to make progress in healthcare reform.

The article reports on the launch of the seventh edition of the annual Pharmacy Forecast by the ASHP Research and Education Foundation. The Pharmacy Forecast is considered a vital component of the Foundation's efforts to advance pharmacy practice leadership. It has offered insight into emerging trends that have influenced the practice of pharmacy. It is intended to be a stimulant for the discussion and planning that must take place in every hospital and health system.

Diabetes is associated with several diabetic-related abnormalities which increase the risk of onset or worsening of heart failure. Recent studies showed that the majority of diabetic patients present with heart failure with preserved ejection fraction (HFpEF), and the prevalence of HFpEF in diabetics is alarming. Moreover, outcomes in HFpEF are poor and could be compared to those of heart failure with reduced ejection fraction (HFrEF), with 1-year mortality ranging between 10 and 30%. In contrast to HFrEF, there is very limited evidence for pharmacologic therapy in symptomatic patients with preserved ejection fraction, and therefore, the optimal selection of treatment for diabetic HFpEF remains challenging. This narrative review article summarizes the currently available data on the pharmacological treatment of HFpEF in patients with diabetes., Competing Interests: Jakub Benko, Matej Samoš, Tomáš Bolek, Dana Prídavková, Jakub Jurica, Martin Jozef Péč, Peter Galajda, and Marián Mokáň have no conflicts of interest to declare, (Copyright © 2022 Jakub Benko et al.)

Biological drugs or biopharmaceuticals off patent open a large market for biosimilars and biobetters, follow-on biologics. Biobetters, in particular, are new drugs designed from existing ones with improved properties such as higher selectivity, stability, half-life and/or lower toxicity/immunogenicity. Glycosylation is one of the most used strategies to improve biological drugs, nonetheless bioconjugation is an additional alternative and refers to the covalent attachment of polymers to biological drugs. Extensive research on novel polymers is underway, nonetheless PEGylation is still the best alternative with the longest clinical track record. Innovative trends based on genetic engineering techniques such as fusion proteins and PASylation are also promising. In this review, all these alternatives wereexplored as well as current market trends, legislation and future perspectives., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Competing Interests: Conflict of interest J. Bridgewater declares consulting or advisory roles for Merck Serono, SERVIER, Roche, Bayer, AstraZeneca, Incyte and Basilea; travel support from MSD Oncology, Merck Serono, Servier and BMS. Please refer to the accompanying ICMJE disclosure forms for further details.

In 2020, the US Food and Drug Administration approved 53 novel drugs. Thirty-six of the 53 (68%) drugs were reviewed and approved through an expedited review pathway, and 31 of the 53 (58%) were approved for treatment of a rare disease. This review includes a summary of the novel drugs approved by the US Food and Drug Administration in 2020., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Physical fitness levels and the amount of accumulated adipose tissue (fatness) relate to current and future individuals' heath status. Nevertheless, the interrelationships of their combined patterns with polypharmacy and the types of medications consumed have not been sufficiently investigated., Methods: This cross-sectional study was carried out in six Spanish regions between 2008 and 2009 with a sample of older community-dwelling adults (≥65 years old) without dementia or cancer. Fitness was measured with one-leg balance and senior fitness tests, as well as by measuring weight and fat mass with a bioelectrical impedance analyzer. Polypharmacy was defined as the use of five or more medications. An analysis of variance was performed for comparisons between the physical fitness and fatness patterns and the medication consumed., Results: A total of 1709 elders were included in the study (72.1 ± 5.2 years). The two unfit patterns were those with the highest drug consumption. The High-Fat-Unfit pattern was the one that had the most significant consumption and had the highest percentage of polymedicated subjects. The Low-Fat-Fit pattern had a significantly lower percentage of people that did not consume any medications. The highest percentages of drug consumption in 7 of the 10 groups that were included were concentrated in the two unfit patterns., Conclusions: This study highlights the importance of fitness in older adults, as it is at least as important as the avoidance of accumulation of excess fat with respect to the consumption of a smaller number of medicines.

Patients with decompensated cirrhosis are currently managed through targeted strategies aimed at preventing or treating specific complications. In contrast, a disease-modifying agent should, by definition, be aimed at globally addressing 'decompensated cirrhosis'. To be defined as a disease-modifying agent in decompensated cirrhosis, interventions need to demonstrate an unequivocal benefit on the course of disease in well-designed and adequately powered randomised clinical trials with hard endpoints (i.e. patient survival). These trials also need to define the target population, dosage and timing of administration, factors guiding treatment, temporary or permanent stopping rules, transferability to daily clinical practice, cost-effectiveness, and global treatment access. By eliminating the underlying cause of cirrhosis, aetiologic treatments can still influence the course of decompensated disease by halting or slowing down disease progression or even inducing reversion to the compensated state. In contrast, there remains an unmet clinical need for disease-modifying agents which can antagonise key pathophysiological mechanisms of decompensated cirrhosis, such as portal hypertension, gut translocation, circulatory dysfunction, systemic inflammation, and immunological dysfunction. However, in the last few years, the repurposing of "old drugs" that have already been prescribed for more limited indications in hepatology or for other diseases has provided a few candidates, including human albumin, statins, and poorly absorbable oral antibiotics, which are under further evaluation in large-scale randomised clinical trials. New disease-modifying agents are also expected to be identified in the next decade through the systematic repurposing of existing drugs and the development of novel molecules which are currently undergoing pre-clinical or early clinical testing., Competing Interests: Conflict of interest Dr. Caraceni reports personal fees from Grifols SA, grants and personal fees from Octapharma SA, personal fees from Kedrion Biopharma SpA, personal fees from Mallinkrodt SA, personal fees from Gilead SA, personal fees from Takeda Sa, outside the submitted work. Dr. Ginès reports grants and personal fees from Grifols, grants and personal fees from Gilead, grants and personal fees from Mallinckrodt, personal fees from Martin pharmaceuticals, personal fees from Novartis, personal fees from Intercept, from null, outside the submitted work. Dr. Abraldes, Dr. Newsome and Dr. Sarin have nothing to disclose., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Purpose: To describe trends in the pharmacological treatment of BPH in the United Kingdom (UK) from 1998 to 2016., Methods: We created a cohort of men with a diagnosis of BPH between 1998 and 2016 using the Clinical Practice Research Datalink. Using Poisson regression, we estimated annual prescription rates of 5αRIs, α-blockers, and combination therapy (5αRIs + α-blockers). Adherence was defined by a proportion of days covered > 80%., Results: Our cohort included 192,640 men with BPH who generated 1,176,264 person-years (PYs) of follow-up. The mean age was 68.0 (standard deviation: 10.7) years. The prescription rate of all BPH medications during the study period was 347.6 per 100 PYs (95% CI 347.2-347.9). α-Blockers had the highest prescription rate (222.9 per 100 PYs, 95% CI 222.7-223.2); prescription rates of 5αRIs and combination therapy were 69.1 per 100 PYs (95% CI 69.0-69.3) and 55.5 per 100 PYs (95% CI 55.4-55.7), respectively. The prescription rate for combination therapy was 19 times greater in 2013-2016 than in 1998-2000 (rate ratio: 19.2, 95% CI 18.6-19.7), while the prescription rates for 5αRIs and α-blockers each doubled during this period (rate ratio: 1.86, 95% CI 1.84-1.88 and rate ratio: 2.02, 95% CI 2.01-2.04, respectively). The proportion of patients who were adherent at 1 year to 5αRIs (32.3%), α-blockers (44.0%), and combination therapy (45.6%) was low., Conclusion: The prescription rate of BPH medications increased substantially between 1998 and 2016 in the UK, with the greatest relative increase observed with combination therapy. Adherence to BPH medications was low in this population-based study.

Drug-related problems (DRP) cause preventable negative health outcomes, especially during hospital admissions. The aim of our study was to examine the prevalence and characteristics of DRP in regular clinical pharmacy, as well as to determine those factors associated with a higher risk of DRP in the hospital setting. We analyzed data from a standardized registry database of regular pharmacy practice (2015- 2016). DRP were classified according to the Pharmaceutical Care Network Europe v6.2 classification. Cross-sectional data were obtained from 1602 adults admitted to medical wards. Crude and adjusted binary logistic regressions were performed to identify associations between potential risk factors and DRP. Overall DRP prevalence was high across medical specialties (45,1%), in a population characterized by advanced age, polypharmacy and multimorbidity. Problems leading to DRP were mainly classified into two domains (effectiveness and adverse reactions), being drug and dose selection the most frequent causes. Interventions were accepted and DRP were totally or partially solved in 74.1% and 4.81% of cases, respectively. In the adjusted model polypharmacy, allergies, BMI > 25 kg/m2 and clearance < 30 mL/min were associated with a higher risk of DRP. The participation of clinical pharmacists into multidisciplinary teams promotes the detection and solution of DRP. Polypharmacy, obesity, renal impairment and allergy are associated with a higher risk of DRP during admission.

ARDS, first described in 1967, is the commonest form of acute severe hypoxemic respiratory failure. Despite considerable advances in our knowledge regarding the pathophysiology of ARDS, insights into the biologic mechanisms of lung injury and repair, and advances in supportive care, particularly ventilatory management, there remains no effective pharmacological therapy for this syndrome. Hospital mortality at 40% remains unacceptably high underlining the need to continue to develop and test therapies for this devastating clinical condition. The purpose of the review is to critically appraise the current status of promising emerging pharmacological therapies for patients with ARDS and potential impact of these and other emerging therapies for COVID-19-induced ARDS. We focus on drugs that: (1) modulate the immune response, both via pleiotropic mechanisms and via specific pathway blockade effects, (2) modify epithelial and channel function, (3) target endothelial and vascular dysfunction, (4) have anticoagulant effects, and (5) enhance ARDS resolution. We also critically assess drugs that demonstrate potential in emerging reports from clinical studies in patients with COVID-19-induced ARDS. Several therapies show promise in earlier and later phase clinical testing, while a growing pipeline of therapies is in preclinical testing. The history of unsuccessful clinical trials of promising therapies underlines the challenges to successful translation. Given this, attention has been focused on the potential to identify biologically homogenous subtypes within ARDS, to enable us to target more specific therapies 'precision medicines.' It is hoped that the substantial number of studies globally investigating potential therapies for COVID-19 will lead to the rapid identification of effective therapies to reduce the mortality and morbidity of this devastating form of ARDS.

Background: Rational medication use for treatment is mandatory, particularly in children as they are vulnerable to possible hazards of drugs. Understanding the medication use pattern is of importance to identify the problems of drug therapy and to improve the appropriate use of medication among this population., Methods: A post-hoc study of the RV3-BB Phase IIb trial to children aged 0-18 months which was conducted in Indonesia during January 2013 to July 2016. Any concomitant medication use and health events among 1621 trial participants during the 18 months of follow-up were documented. Information on medication use included the frequency, formulation, indication, duration of usage, number of regimens, medication types, and therapeutic classes., Results: The majority of participants (N = 1333/1621; 82.2%) used at least one non-antibiotic medication for treatment during the 18-month observation period. A total of 7586 medication uses were recorded, mostly in oral formulation (90.5%). Of all illnesses recorded, 24.7% were treated with a single drug regimen of non-antibiotic medication. The most common therapeutic classes used were analgesics/antipyretics (30.1%), antihistamines for systemic use (17.4%), cough and cold preparations (13.5%), vitamins (8.6%), and antidiarrheals (6.6%). The main medication types used were paracetamol (29.9%), chlorpheniramine (16.8%), guaifenesin (8.9%), zinc (4.6%), and ambroxol (4.1%). Respiratory system disorder was the most common reason for medication use (51.9%), followed by gastrointestinal disorders (19.2%), pyrexia (16.9%), and skin disorders (7.0%)., Conclusion: A large number of children were exposed to at least one medication during their early life, including those where evidence of efficacy and safety in a pediatric population is lacking. This supports the need for further research on pediatric drug therapy to improve the appropriate use of medication in this population., Competing Interests: The authors have the following interests: NSB is a paid employee of PT Biofarma. PT Biofarma is a state-owned company (owned by Indonesia government) that provides all vaccines for Indonesia National Immunization Program. Additionally, PT Biofarma was one of the non-commercial funders for the RV3-BB Phase IIB trial. No consultation was done to the funder relating to the trial. The trial was a phase IIB trial and while the RV3-BB rotavirus vaccine is not yet marketed, this vaccine is being developed with the intention for eventual usage in the national immunization program. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Proteasome is vital for intracellular protein homeostasis as it eliminates misfolded and damaged protein. Inhibition of proteasome has been validated as a powerful strategy for anti-cancer therapy, and several drugs have been approved for treatment of multiple myeloma. Recent studies indicate that proteasome has potent therapeutic effects on a variety of diseases besides cancer, including parasite infectious diseases, bacterial/fungal infections diseases, neurodegenerative diseases and autoimmune diseases. In this review, recent developments of proteasome inhibitors for various diseases and related structure activity relationships are going to be summarized., Competing Interests: The authors confirm that this article content has no conflicts of interest., (© 2020 Cao et al.)

Objectives: This study aimed to review the degree of personalization of benefit and harm in the reporting of recent high-profile randomized controlled trials (RCTs) involving pharmacological interventions., Study Design and Setting: This study is a systematic review of RCTs published between 2012 and 2017 with at least one intervention evaluating drug therapy and meeting the "high-profile" threshold in a premier academic literature abstraction service. Our primary outcome was the proportion of trials reporting subgroup analyses of a combined benefit-harm outcome. Secondary outcomes included the proportion of trials reporting subgroup analyses or clinical prediction guide for benefits or harms. We assessed the quality of the subgroup analyses using a modified version of previously published credibility criteria., Results: Of 296 eligible RCTs, nine studies (3%) reported a combined benefit-harm endpoint. We found subgroup analyses of a combined benefit-harm endpoint in three studies (1%), a benefit endpoint in 167 studies (56.4%), and a harm endpoint in 18 studies (6.1%). The overall quality of the subgroup analyses was poor. Only one study reported a clinical prediction guide for an outcome., Conclusion: Despite great interest in the personalization of therapies, it is rarely reported in high-profile trials. Lack of rigorous and widely accepted methods may be the major barrier., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Over the last two decades, developments in nanomedicine have resulted in technical advances with application to clinical science. Both organic and inorganic nanoparticles (NPs) have shown tolerability, pharmacologic specificity and biodegradability. A subclass of NPs, protein NPs, have garnered recent attention due to the inherent biocompatibility of protein substrates. Protein NPs are currently being employed widely in pharmaceuticals development with applications in nasal, pulmonary, intravenous, ocular and oral delivery. Despite the distinct advantages of orally administered pharmaceuticals, the development of oral delivery systems has been comparatively limited. Therefore, this review attempts to discuss the most recent experimental and pre-clinical findings in the development of protein NPs for oral delivery, while envisioning upcoming challenges., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Geriatric patients are the main users of medicinal products, although this patient group is most commonly excluded from clinical trials. Several guidelines from the International Conference on Harmonisation (ICH) and the European Medicines Agency (EMA) have tried to ensure the development and the safe use of medicines for geriatric patients., Objective: This article aims to evaluate geriatric information provided by the summary of product characteristics (SmPC) to prescribers using relevant medicinal products in Germany for patients older than 65 years., Material and Methods: Based on the annually published drug prescription report (Arzneiverordnungsreport), medication which was prescribed mainly (above 80%) or at a high defined daily dose (DDD [doses per day] > 400) to patients older than 65 years in 2016 was reviewed regarding relevant geriatric information., Results: The average compliance for the investigated drugs regarding geriatric information according to EMA guidelines is 27%. At least older patients are mentioned in the SmPC most frequently (68%). Information about doses or dose adjustments for patients with certain stages of frailty was not provided by the pharmaceutical companies., Conclusion: Current information in the SmPC for a safe and effective use of medicines for older patients is insufficient and does not conform to EMA guidelines. Compared to drug authorization in pediatrics where the industry is obliged to submit a special pediatric investigation plan (PIP) to cover the needs of this certain patient group, a mandatory geriatric investigation plan (GIP) similar to the PIP would be an appropriate measure to provide safe and effective medicines for older patients.

European guidelines for heart failure (HF) have continuously incorporated new evidence since the first publication in 1995. We aimed to explore time trends in utilisation of pharmacological treatment for HF and dispensing of recommended dosages among patients with a first-time diagnosis of HF. We performed a historical cohort study of patients with a first-time HF diagnosis from 1997 to 2015, identified in the Danish National Patient Registry. Dispensed pharmacological treatment included angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), beta-blockers, mineralocorticoid receptor blockers (MRAs), digoxin and diuretics. Furthermore, we estimated the proportion of patients receiving the recommended target dosages 1 year after the diagnosis. The utilisation increased and correlated with publication of landmark studies, and among patients diagnosed in 2015, approximately two of three received ACEI/ARB and beta-blocker, respectively. Less than half of the patients redeeming prescriptions for ACEIs, ARBs, beta-blockers or MRAs received the recommended target dosages. The utilisation of pharmacological therapy for HF appears to be correlated with the publications of landmark Phase III clinical trials. However, a high proportion of patients do not receive the recommended target dosages. Despite improvements over time, a substantial gap appears to remain between guideline recommendations and pharmacological therapy in routine care., (© 2020 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Recently, combination therapy has received much attention because of its highly therapeutic effect in various types of cancers. In particular, chemo-photodynamic combination therapy has been considered as an outstanding strategy. However, an abnormal increase in tumor angiogenesis caused by reactive oxygen species (ROS) generated during photodynamic therapy (PDT) has been reported. In this study, the complex of doxorubicin (DOX)-encapsulating anti-angiogenic small interfering RNA (siRNA) nanoparticle and chlorin e6 (Ce6)-encapsulating microbubble has been developed to suppress tumor angiogenesis. The first compartment, doxorubicin-encapsulating siRNA nanoparticle, was electrostatically coated using two biocompatible polymers to prevent the damage of genetic materials. The other part, Ce6-encapsulating microbubble, serves as an ultrasound-triggered local delivery system as well as a drug carrier. Both the in vitro and in vivo experimental results demonstrate successful inhibition of angiogenesis with a minimized damage of siRNAs caused by ROS as well as improved therapeutic effect by chemo-photodynamic-gene triple combination therapy using ultrasound-triggered local delivery., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Sex-based medicine, which can be defined as the process of understanding the inherent differences in disease pathophysiology and response to medications that exist between the sexes, seems like a necessary step in the movement towards personalized medicine. While there are strict guidelines for weight-based dosage of pediatric medications, similar guidelines do not exist for the treatment of adults, despite prominent biologic differences between the sexes. The lack of individualization is of particular importance in the treatment of adult patients in the emergency department (ED), because it can determine the trajectory of a patient's stay at the hospital., Objectives: This review was conducted to better understand the need for and possible benefits of altering drug dosing guidelines for different categories of medications in the ED. PubMed, SCOPUS, and Google Scholar were queried using a combination of the keywords "gender differences," "sex differences," "treatment," and "emergency". Abstracts, unpublished data, and duplicate articles were excluded., Discussion: In considering some of the most common causes of ED visits, the majority of diseases demonstrate differences in morbidity and mortality between female and male patients, despite similar treatment regimens. These differences can be attributed to variations in drug pharmacodynamics and pharmacokinetics, which may be affected by sex-based biologic variations in body mass index and body composition, and physiologic variations such as hormonal changes, menstruation, pregnancy, and lactation. Regardless of the mechanism of these differences, there is overwhelming evidence that universal drug dosing results in suboptimal outcomes for both male and female patients., Conclusions: Female sex is a risk factor for clinically significant adverse drug reactions, which range from cutaneous reactions to major bleeding, and can have long-standing implications on patient outcomes. However, future studies are needed to understand the exact pathophysiology of these sex differences, after controlling for potential confounding factors such as demographic differences and provider bias in treatment., Competing Interests: Declaration of competing interest The authors do not have a financial interest or relationship to disclose regarding this research project., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The COVID-19 pandemic has focused attention on issues of epidemiology, public health, and vaccine design. I submit that attention to COVID-19 pharmacologic therapy needs similar emphasis, including identifying any existing medications that can be repurposed to treat COVID-19 patients.

Background: Research investigating trends in the general prescription medicine use of older people in New Zealand is limited., Aim: To examine trends in the use of outpatient medicines by older adults and assess changing patterns in use from 2010 to 2015., Methods: A retrospective cohort study including all New Zealand primary care patients over 65 years of age utilising data from the national pharmaceutical claims database. We calculated the prevalence of use within three age groups and by sex in each year by anatomical therapeutic class, therapeutic group and individual medicine. Rate ratios were calculated to compare the prevalence of use in 2010 and 2015., Results: The study included 829,026 patients with a mean of 4.4 years of potential drug exposure. Overall prevalence of medicine use was 92% in 2010 and 93% in 2015. The mean number of prescriptions per patient-year for patients >=85 years of age (39.2) was almost double that of patients 65-74 years (21.8). Prevalence of use was similar between females (94%) and males (92%). Antibacterials, analgesics, cardiovascular drugs and proton pump inhibitors were the most widely used medicines. The use of systemic antibiotics increased by 2% between 2010 and 2015, but there were significant decreases in use of antithrombotics (6%), beta blockers (6%), diuretics (19%), nitrates (19%) and antiarrhythmics (24%)., Conclusion: Our findings indicate both positive changes in response to guidance on safe and appropriate medicine use and several areas of concern. Continued monitoring of changing patterns in the medicine use of older people will be important, particularly with regard to the use of combinations of medicines that increase their risk of adverse events., Competing Interests: Nil.

Recent years have seen important changes in pharmacology. New techniques have been developed which are increasingly aimed at smaller groups of patients or even individual patients. In the past, thousands of chemical molecules were tested on a potential molecular target and the most effective molecules were selected. Nowadays a growing number of drugs are designed to aim at a specific molecular target, an example being monoclonal antibodies. There are developments that go fundamentally further and enable patients to be treated in an increasingly targeted and individual manner. These new therapies (i.e., Advanced Therapy Medicinal Products) are based on different principles than those of classical pharmacotherapy, and require different risk assessments as well as a different regulatory system. In this paper we discuss a selection of the developments in pharmacotherapy that have taken place during the past decade. In addition, we look into what sort of developments can be expected in the future.

Background: Prostate cancer is a common tumour type in Australian men., Objective: The aim of this article is to review important changes in prostate cancer diagnosis and management over the past five years, particularly as they pertain to general practice., Discussion: The management of prostate cancer has changed significantly in recent years, particularly the use of imaging, with the introduction of prostate magnetic resonance imaging as routine in the diagnostic pathway, and the increasing use of prostate-specific membrane antigen positron emission tomography for early stratification in the salvage setting for failure of primary treatment in localised disease. In addition, upfront combinations of androgen deprivation therapy with other systemic treatments have yielded significant gains in overall survival for patients with metastatic disease. There has also been an increasing recognition of the association between germline DNA repair defects and progressive disease, and interest in the potential to identify patients for therapies that target these defects. There have been significant changes in how prostate cancer is diagnosed and managed in the past five years, with the introduction of new clinical pathways that were unprecedented just a decade previously.

Background: German S3 guidelines are subject to the highest methodological standards. This includes that they are only valid for a certain time period. Following the first edition in 2012 the first update of the S3 guidelines on bipolar disorder has now been published (2019)., Objective: What has changed in the field of pharmacological recommendations comparing the first edition with the update in 2019?, Material and Methods: Comparison of the 1st edition from 2012 with the update from 2019 of the S3 guidelines for the diagnostics and treatment of bipolar disorders., Results: The three principle treatment targets of acute treatment of bipolar depression, acute treatment of mania and phase prophylaxis (maintenance treatment) can be distinguished. For acute treatment of bipolar depression, for the first time a medication has received a level A recommendation: quetiapine. For the acute treatment of mania, several drugs are still recommended with the same level of recommendation (B). Asenapine has been added as the tenth substance. Lithium is still the only drug with a level A recommendation for maintenance and prophylactic treatment and is also the only drug approved for this indication without restrictions. A new recommendation is that in the absence of contraindications, phase prophylaxis with a serum level of at least 0.6 mmol/l should be carried out. With a B recommendation, quetiapine has been added to the drugs for phase prophylactic treatment., Conclusion: The S3 guidelines make recommendations at the highest scientific level. In view of these findings, lithium is clearly underutilized for maintenance therapy. In the absence of clear contraindications (advanced renal insufficiency), every patient with bipolar disease should be given the chance of lithium prophylaxis for an adequately long period.

This article provides background information, descriptions, and evidential support for the more recent treatments for adolescents with anorexia nervosa, including family-based treatment, adolescent focused therapy, cognitive behavioral therapy, systemic family therapy, and psychopharmacologic treatments. At this time, family-based treatment has the best evidence of efficacy and cost-effectiveness. Future directions in treatment research for adolescent anorexia nervosa are discussed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: To describe the trends in pharmacologic treatment for patients newly diagnosed with chronic obstructive pulmonary disease (COPD) in Alberta, Canada., Methods: We linked Alberta health databases to identify patients aged ≥35 years with incident COPD between April 2010 and March 2017. Incident cases were defined as those who did not have a hospitalization or outpatient visit with COPD in the previous 2 years. Patients were categorized into two groups: 1) incident cases at a hospital and 2) incident cases at an outpatient clinic, and both were followed until death or being censored by 31 March 2018. Utilization of COPD medication for 30 days following incident event and adherence in maintenance therapy over time were reported., Results: The study included 33,169 patients with incident COPD (hospital: 9,089; outpatient: 24,080). In 18,666 (56.3%) patients starting medication within 30 days of the incident event (2010: 52.7%; 2016: 56.6%; p=0.002), SABA (60.5%) and LABA/ICS (41.6%) were most commonly used. ICS (without LABA) was used in 14.2% and was used as monotherapy in 4.5% of patients. The proportion of patients who initiated any ICS was similar (hospital: 56.7%; outpatient: 55.7%; p=0.194) and decreased in both settings over time (p<0.001). Drug adherence during the first year after the incident event was 54.3%, higher among hospital patients (66.5% vs 48.9%; p<0.001), and improved over time (2010: 53.4%; 2016: 57.4%; p<0.001)., Conclusion: The initiation of and adherence to pharmacologic therapy for patients with COPD is low but improves over time. While SABA and LABA/ICS are most commonly used, ICS utilization decreases over time., Competing Interests: The Lung Association - Ontario funded the research for this study with an unrestricted grant to the Institute of Health Economics (IHE). Dat T Tran and Ilke Akpinar are IHE employees. Dr Dat T Tran reports grants from Lung Association- Ontario, during the conduct of the study. Dr Ilke Akpinar reports grants from Lung Association - Ontario, during the conduct of the study. Dr Philip Jacobs reports grants from Lung Association - Ontario, during the conduct of the study; and grant from Boehringer Ingelheim to study COPD market. The authors report no other conflicts of interest to this work., (© 2019 Tran et al.)

An aging worldwide population demands that anesthesiologists consider geriatrics a unique subset of patients requiring customization of practice. This article reviews the current literature investigating physiologic changes of the elderly that affect pharmacokinetics and pharmacodynamics. Changes in drug absorption, distribution, metabolism, and excretion are discussed as well as the ultimate effects of medications. Implications for practice regarding specific anesthetic and analgesic drugs are addressed. Despite the immense body of research that contributes to understanding of geriatric pharmacology, elderly patients often are excluded from rigorous research trials, and further scientific investigation to inform best practices for this group of patients is needed., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction : ADHD is characterized by a developmentally inappropriate level of inattentiveness, impulsivity and/or hyperactivity. In adults, the disorder is frequently accompanied by Emotional Dysregulation (ED), associated to a variety of related psychiatric comorbidities, complicating its recognition and treatment management. Areas covered : This paper reviews randomized active comparator-controlled or placebo-controlled trials evaluating the use of pharmacotherapy in adults with ADHD and ED, other neurodevelopmental disorders, Bipolar Disorder (BD) and Anxiety Disorders (ADs). When controlled data are unavailable, the authors have included open-label and observational studies. Expert opinion : ED in adult patients with ADHD is a very common and impairing problem that can be treated with stimulants or atomoxetine. ADHD studies in adults with other neurodevelopment disorders are scarce; stimulants seem to be the most effective and safe drugs in treating ADHD symptoms, without worsening the core features of other neurodevelopmental disorders. In patients with ADHD and comorbid BD, the treatment of BD alone may result in residual symptoms of ADHD. Patients should be treated hierarchically: BD should be treated first, while ADHD should be treated combining ADHD medications and mood stabilizers after mood stabilization. The available evidence for treating patients with ADHD and comorbid ADs in adults supports the idea of an anti-anxiety/ADHD-specific treatment association.

Introduction : Nosocomial pneumonia is the second most common infection in hospital settings, resulting in substantial increases in morbidity, mortality, and length of hospital stay. The rapid increase in resistance of nosocomial pathogens to many antibiotics and the high dissemination of resistance genes highlight the need for innovative approaches to combat difficult-to-treat nosocomial respiratory infections. Areas covered : This review summarizes the synthetic antimicrobials that are currently in development for the treatment of nosocomial pneumonia, focusing on antibiotics in the final phases of clinical development and on the strategies employed by novel synthetic antimicrobial peptides. Expert opinion : Several novel synthetic antimicrobials are currently in the pipeline, and it appears that new antimicrobial peptides or mimetics will soon be made available, expanding the opportunities to treat nosocomial pneumonia. However, the approval process for use in the treatment of nosocomial pneumonia is arduous. Given that significant investments by pharmaceutical companies have ended in failure to obtain the approval of regulatory agencies, novel platforms for antimicrobial discovery are needed. The identification of new and fully synthetic chemical structures with activity against nosocomial pathogens needs to be followed by preclinical studies in large animals and by pharmacokinetic and pharmacodynamic studies in specific critically ill populations to assess lung penetration.

Objective: During medical emergencies, underweight and obese children are at a higher risk of weight-estimation errors than 'average' children, which may lead to poorer outcomes. In obese children, optimum drug dosing requires a measure of both total body weight (TBW) and ideal body weight (IBW) for appropriate scaling. We evaluated the ability of the Broselow tape, the Mercy method and the PAWPER XL tape to estimate TBW and IBW in obese and underweight children., Participants and Methods: Data for children aged 0-18 years were extracted and pooled from three previous weight-estimation studies. The accuracy of estimation of TBW and IBW by each method was evaluated using percentage of estimations within 10% of target weight (PW10) as the primary outcome measure., Results: The Broselow tape estimated TBW poorly in obese and underweight children (PW10: 3.9 and 41.4%), but estimated IBW extremely accurately (PW10: 90.6%). The Mercy method estimated TBW accurately in both obese and underweight children (PW10: 74.3 and 76.3%) but did not predict IBW accurately (PW10: 14.3%). The PAWPER XL tape predicted TBW well (PW10: 73.0% in obese children and 74.9% in underweight children) and predicted IBW extremely accurately (PW10: 100%)., Conclusion: The Broselow tape predicted IBW, but not TBW, accurately. The Mercy method estimated TBW very accurately, but not IBW. The PAWPER XL tape estimated both TBW and IBW accurately. The PAWPER XL tape should be considered when choosing a weight-estimation strategy for obese and underweight children.

Research suggests that women may have poorer tobacco cessation outcomes than men; however, the literature is somewhat mixed. Less is known about gender differences in cessation within quitline settings. This study examined gender differences in the utilization of services (i.e., coaching sessions, pharmacotherapy) and tobacco cessation among callers to the Arizona Smokers' Helpline (ASHLine). The study sample included callers enrolled in ASHLine between January 2011 and June 2016. We tracked number of completed coaching sessions. At the 7-month follow-up, callers retrospectively reported use of cessation pharmacotherapy (gum, patch, or lozenge), as well as current tobacco use. Associations between gender and tobacco cessation were tested using logistic regression models. At month 7, 36.4% of women (3,277/9,004) and 40.3% of men (2,960/7,341) self-reported 30-day point prevalence abstinence. Compared to men, fewer women reported using pharmacotherapy (women: 71.4% vs. men: 73.6%, p = .01) and completed at least five coaching sessions (women: 35.1% vs. men: 38.5%, p < .01). After adjusting for baseline characteristics, women had significantly lower odds of reporting tobacco cessation than men (OR = 0.91, 95% CI: 0.84 to 0.99). However, after further adjustment for use of pharmacotherapy and coaching, there was no longer a significant relationship between gender and tobacco cessation (OR: 0.96, 95% CI: 0.87 to 1.06). Fewer women than men reported tobacco cessation. Women also had lower utilization of quitline cessation services. Although the magnitude of these differences were small, future research on improving the utilization of quitline services among women may be worth pursuing given the large-scale effects of tobacco., (© Society of Behavioral Medicine 2018. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: We analyzed the demographics and disease characteristics of patients prescribed treatment for chronic hepatitis C virus (HCV) infection from 2013 through 2017, a time frame that encompasses the expansion of available direct-acting antiviral inhibitors., Study Design: Retrospective analysis., Methods: Using a proprietary disease-management program, data for 19,944 patients receiving HCV treatment were collected from providers and specialty pharmacies. Six-month time periods accounting for introductions of novel treatments were established as follows: December 2013 to May 2014 (n = 1438), simeprevir and sofosbuvir; October 2014 to March 2015 (n = 2242), ledipasvir/sofosbuvir and ombitasvir/paritaprevir/ritonavir plus dasabuvir; October 2015 to March 2016 (n = 5514), daclatasvir; July 2016 to December 2016 (n = 5562), elbasvir/grazoprevir and sofosbuvir/velpatasvir; and July 2017 to December 2017 (n = 5188), sofosbuvir/velpatasvir/voxilaprevir and glecaprevir/pibrentasvir. Changes over time were evaluated for statistical significance., Results: In the 2013-2014 time period, 44% of patients receiving prescriptions for HCV treatment were treatment-experienced and 45% had cirrhosis. By 2017, only 14% were treatment-experienced (P <.001) and 21% had cirrhosis (P <.001). The percentage of patients with HCV genotype 1 increased from 69% to 87% from 2013-2014 to 2014-2015 (P <.001) but subsequently decreased to 74% in 2017 (P <.001). The percentage of patients receiving HCV prescriptions in an academic setting declined from 61% in 2013-2014 to 13% in 2017 (P <.001)., Conclusions: In the United States, since the introduction of interferon-free HCV regimens, the patient population prescribed treatment has changed, becoming predominantly treatment-naïve, without cirrhosis, and treated in nonacademic centers.

Treatment options for hematologic malignancies have been rapidly expanding in the past decade, resulting in better survival outcomes for many patients. Infection is an important cause of morbidity and mortality in this patient population. Cytotoxic chemotherapy has well-studied infectious risks related to the degree and duration of myelosuppression. Targeted therapies and immunotherapies have less clearly predictable infectious risk and diverse effects on immune function. This review discusses contemporary management of hematologic malignancies, followed by special discussion of novel agents, including signaling/small molecule inhibitors, monoclonal antibodies, immunomodulators, and immunotherapies, for treatment of hematologic malignancies with focus on infectious risk., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background and Purpose: Emergent evaluation of inpatients with suspected acute ischemic stroke faces difficulty of symptoms recognition, false alarms, and high rate of contraindications to reperfusion therapies. We aim to assess the clinical characteristics and therapeutic interventions implemented in patients evaluated though the in-hospital Stroke Alert Protocol., Methods: We analyzed 4 years-worth of Stroke Alert cases at a university hospital. Demographics, clinical presentation, final diagnosis, and acute interventions were compared between inpatients and those presenting to the emergency department., Findings: A total of 1965 Stroke Alert cases were included: 959 (48.8%) were acute cerebrovascular events and 1006 (51.2%) were noncerebrovascular. Hospitalized patients accounted for 489 (24.9%) of Stroke Alerts and patients in the emergency department for 1476 (75.1%). Inpatients were more likely to present with nonfocal neurological deficits (46.2% versus 32.4%, P < .0001) and be diagnosed with noncerebrovascular disorders (62.4% versus 47.5%, P < .0001). Acute interventions other than thrombolysis were delivered in 77.1% of in-hospital cases. Compared to the emergency department, inpatients were more commonly managed with rectification of metabolic abnormalities (21.5% versus 13.7%, P < .001), suspension or pharmacological reversal of drugs (11% versus 3.7%, P < .001), and initiation of respiratory support (13.5% versus 9.3%, P = .01). Inpatients with acute ischemic stroke received intravenous thrombolysis less frequently (4.9% versus 23.9%, P < .001), but the endovascular treatment rate was comparable (9.8% versus 10.3%) to the emergency department., Conclusion: Nonfocal neurological deficits and noncerebrovascular disorders are commonly encountered during in-hospital Stroke Alerts. In the inpatient setting, intravenous thrombolysis is rarely delivered while other time-sensitive therapeutic interventions are frequently implemented., (Copyright © 2019 Elsevier Inc. All rights reserved.)

About half a million adverse drug reactions are reported in the US each year that result in disability, hospitalization or death. The efficacy or toxicity of a drug in a patient can be strongly influenced by their genetics as well as environment. Application of genomics to clinical pharmacology, "pharmacogenomics," promises to transform patient care and health resource utilization in the coming decade.