Effect of Transcutaneous Spinal Direct Current Stimulation in Patients with Painful Polyneuropathy and Influence of Possible Predictors of Efficacy including BDNF Polymorphism: A Randomized, Sham-Controlled Crossover Study.

Introduction: The neuromodulating effects of transcutaneous-spinal Direct Current Stimulation (tsDCS) have been reported to block pain signaling. For patients with chronic pain, tsDCS could be a potential treatment option. To approach this, we studied the effect of anodal tsDCS on patients with neuropathic pain approaching an optimal paradigm including the investigation of different outcome predictors. Methods: In this randomized, double-blinded, sham-controlled crossover study we recruited twenty patients with neurophysiologically evaluated neuropathic pain due to polyneuropathy (PNP). Variables (VAS; pain and sleep quality) were reported daily, one week prior to, and one week after the stimulation/sham period. Anodal tsDCS (2.5 mA, 20 min) was given once daily for three days during one week. BDNF-polymorphism, pharmacological treatment, and body mass index (BMI) of all the patients were investigated. Results: Comparing the effects of sham and real stimulation at the group level, there was a tendency towards reduced pain, but no significant effects were found. However, for sleep quality a significant improvement was seen. At the individual level, 30 and 35% of the subjects had a clinically significant improvement of pain level and sleep quality, respectively, the first day after the stimulation. Both effects were reduced over the coming week and these changes were negatively correlated. The BDNF polymorphism Val66Met was carried by 35% of the patients and this group was found to have a lower general level of pain but there was no significant difference in the tsDCS response effect. Neither pharmacologic treatment or BMI influenced the treatment effect. Conclusions: Short-term and sparse anodal thoracic tsDCS reduces pain and improves sleep with large inter-individual differences. Roughly 30% will benefit in a clinically meaningful way. The BDNF genotype seems to influence the level of pain that PNP produces. Individualized and intensified tsDCS may be a treatment option for neuropathic pain due to PNP.

Correction: Tagger-A Swiss army knife for multiomics to dissect cell type-specific mechanisms of gene expression in mice.

[This corrects the article DOI: 10.1371/journal.pbio.3000374.].

Tagger-A Swiss army knife for multiomics to dissect cell type-specific mechanisms of gene expression in mice.

A deep understanding of how regulation of the multiple levels of gene expression in mammalian tissues give rise to complex phenotypes has been impeded by cellular diversity. A handful of techniques were developed to tag-select nucleic acids of interest in specific cell types, thereby enabling their capture. We expanded this strategy by developing the Tagger knock-in mouse line bearing a quad-cistronic transgene combining enrichment tools for nuclei, nascent RNA, translating mRNA, and mature microRNA (miRNA). We demonstrate that Tagger can capture the desired nucleic acids, enabling multiple omics approaches to be applied to specific cell types in vivo using a single transgenic mouse line.

New Medications in the Treatment of Acute Migraine.

Migraine is a common disorder affecting 12% of the US population. Use of triptans results in migraine pain relief within 2 hours in 16% to 51% of patients. However, due to their vasoconstrictive properties, triptans are contraindicated in patients with cardiovascular disease, peripheral vascular disease, cerebrovascular disease, and uncontrolled hypertension because of the potential for ischemia. This article will review 2 new classes of drugs being developed for the treatment of acute migraine without vasoconstrictive effects.

New Medications in the Treatment of Peanut Allergy.

In the general population, the prevalence of peanut allergy has remained stable at 1.3%. However, in children, the prevalence appears to be increasing. There are no approved treatments for peanut allergy so current treatment involves educating the patient on avoiding products that contain peanut protein. Two drugs that allow controlled desensitization with controlled amounts of peanut protein have reached late stages of development.

New Medications in the Treatment of Nonalcoholic Steatohepatitis.

Nonalcoholic fatty liver disease, an accumulation of fat in the liver, is estimated to occur in almost 1 in 5 adults. With 2 of the most common risk factors being obesity and diabetes, its prevalence is growing. Nonalcoholic steatohepatitis is a more severe form of nonalcoholic fatty liver disease. There are currently no approved drugs to treat nonalcoholic steatohepatitis, but several drugs are being developed to treat this disease.

New Medications in the Treatment of Hereditary Transthyretin Amyloidosis.

Hereditary transthyretin amyloidosis is an inherited disorder that results in the gradual progressive deposit of abnormal protein called amyloid in the body's organs and tissues. There are currently no approved drugs to treat transthyretin amyloidosis, and patients may require liver transplantation for survival. There are a few drugs in development to treat hereditary transthyretin amyloidosis either by stabilizing the abnormal protein or by decreasing production of transthyretin. Both methods are being developed to slow progression of the disease.

New Medications in the Treatment of Acute Decompensated Heart Failure.

Acute decompensated heart failure is a sudden worsening of heart failure symptoms, typically resulting in peripheral edema and dyspnea as a result of pulmonary congestion. Acute decompensated heart failure is responsible for over 1 million hospitalizations every year. Current pharmacologic therapy is limited in its options. Despite an improved survival rate, statistic still suggests that about 50% of patients die within 5 years of diagnosis. New pharmacologic agents aim to improve efficacy by targeting previously unexplored physiological pathways.

Antibiotics in Development for the Treatment of Resistant Bacterial Disease.

Many bacterial infections can be treated with the use of antibiotics. These medications continue to reduce morbidity and mortality; unfortunately, their use has brought about drug-resistant pathogens that produce difficult-to-treat infections, which require more extreme treatments. New antibiotics are needed to combat this ever-evolving resistance pathogenesis.

Providing Comprehensive Medication Management in Telehealth.

The goal of this white paper is to provide direction for clinical pharmacists providing telehealth. Telehealth care is rapidly emerging to improve patient access to health care and optimize patient health outcomes. With the increasing ability to access electronic health record portals, as many as 75 million telehealth encounters are expected in North America annually. Although electronic "point of access" undoubtedly increases the use of medical and pharmacy services, the real value of telehealth lies in improved access to patients in remote areas lacking adequate medical and pharmacy services and to high-risk patients requiring frequent monitoring. This document is intended to serve as a guide for those interested in or already using telehealth to provide direct patient care. Specifically, it focuses on general concepts of telehealth and demonstrates how the delivery of comprehensive medication management (CMM) by telehealth aligns with the Standards of Practice for Clinical Pharmacists set forth by the American College of Clinical Pharmacy. Although clinical pharmacists must be appropriately credentialed and privileged to provide CMM, their process of care must also be adapted to suit the remote patient. Patient assessment, evaluation of medication therapy, development and implementation of a plan of care, follow-up, monitoring, and documentation of all processes of care are influenced by the technology available, the collaborations established, and the applicable regulations and requirements for telehealth practice.

Janus Kinase Inhibitors for the Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a disease where the immune system attacks the linings of the joints, resulting in joint pain, stiffness, swelling, and destruction. Although many products are available for the treatment of RA, limitations such as adverse reactions and tolerance greatly affect adherence. Many of the current biologic disease-modifying antirheumatic drugs on the market are injectables, leaving a void to be filled for a product that can be taken orally. The most advanced of these approaches, the Janus kinase (JAK) inhibitors, are oral drugs that have not only made a breakthrough in RA, but also other skin conditions.

BACE Inhibitors and Tau Protein Targeting Drugs in Prevention of Alzheimer's Disease.

Alzheimer's disease (AD) is a common disease in the United States with almost 10% of people older than 65 suffering from the disease. A few drugs provide some improvement in mental function in mild-to-moderate disease, but no treatments are available to prevent the development of AD. Two new classes of drugs being investigated for the treatment or prevention of AD include drugs to decrease beta amyloid accumulation and Tau protein aggregation inhibitors. After disappointing results for treatment of AD, both classes are being tested in prevention trials.

Calcitonin Gene-Related Peptide Receptor Antagonists for Migraine Prophylaxis.

Migraine is a common disorder affecting 12% of the U.S. POPULATION: Prophylaxis is recommended for patients who experience frequent migraines. Because current drugs used for prophylaxis are not 100% effective and cause adverse effects that affect compliance, new strategies have been studied to prevent headaches. One new pharmacologic strategy is to use an inhibitor of the calcitonin gene-related peptide (CGRP). As a class, the CGRP receptor inhibitors have reduced monthly migraine days and are well tolerated. This article will briefly review CGRP inhibitors in development.

Chimeric Antigen Receptor T-Cell Therapy for Lymphomas.

It is estimated that 2.1% of the population of the United States will develop non-Hodgkin lymphoma (NHL) in a lifetime. With treatment, 71% of patients with NHL live to 5 years. Because current drugs used for treatment do not cure all patients and cause serious adverse effects, new strategies have been studied to treat lymphoma. One new pharmacologic strategy is to use chimeric antigen receptor T-cell (CAR T-cell) therapy. CAR T-cell therapies are very potent. As a class, the CAR T-cell therapies have induced complete remission in 50% to 80% of patients. Most patients using CAR T-cell therapies develop cytokine release syndrome, with about 1 in 3 having a severe form of the syndrome. This article will briefly review CAR T-cell therapies in development.

Cholesterol Ester Transfer Protein Inhibitor Review.

Treatment of blood cholesterol is part of a strategy to lower atherosclerotic cardiovascular (ASCVD) risk. While use of HMG-CoA reductase inhibitors to modify cholesterol levels is the primary means of lowering the risk of an ASCVD event, residual risk remains. A new strategy being investigated is the use of cholesterol ester transfer protein (CETP) inhibitors to raise the levels of high-density lipoprotein cholesterol (HDL-C) and lower low-density lipoprotein cholesterol (LDL-C). While initial large-scale studies demonstrated no reduction of cardiovascular events, one CETP inhibitor, anacetrapib, has demonstrated a reduction in cardiovascular events in the REVEAL trial.

White Paper on Natural Products.

The American College of Clinical Pharmacy (ACCP) published an initial white paper on herbal products in 2000. Since then, the global market for natural products has continued to expand, with tens of millions of consumers using such products on an annual basis in the United States alone. However, despite this expansion, natural products remain largely unregulated compared with prescription medications, have moderate- to low-level clinical evidence for efficacy, and continue to have safety concerns, including adulteration and misbranding. As comprehensive medication management experts, clinical pharmacists are uniquely qualified to navigate these concerns and advise patients appropriately. To develop and recommend a suitable care plan involving natural products, clinical pharmacists must establish a strong pharmacist-patient relationship, assess the appropriateness of therapy, educate the patient regarding key issues, and continuously monitor and follow up on the effectiveness of the care plan. This process should not only occur in an individual community or hospital setting, but also whenever a patient transitions from one care setting to another in cooperation with other clinicians.

Collaborative drug therapy management and comprehensive medication management-2015.

The American College of Clinical Pharmacy (ACCP) previously published position statements on collaborative drug therapy management (CDTM) in 1997 and 2003. Since 2003, significant federal and state legislation addressing CDTM has evolved and expanded throughout the United States. CDTM is well suited to facilitate the delivery of comprehensive medication management (CMM) by clinical pharmacists. CMM, defined by ACCP as a core component of the standards of practice for clinical pharmacists, is designed to optimize medication-related outcomes in collaborative practice environments. New models of care delivery emphasize patient-centered, team-based care and increasingly link payment to the achievement of positive economic, clinical, and humanistic outcomes. Hence clinical pharmacists practicing under CDTM agreements or through other privileging processes are well positioned to provide CMM. The economic value of clinical pharmacists in team-based settings is well documented. However, patient access to CMM remains limited due to lack of payer recognition of the value of clinical pharmacists in collaborative care settings and current health care payment policy. Therefore, the clinical pharmacy discipline must continue to establish and expand its use of CDTM agreements and other collaborative privileging mechanisms to provide CMM. Continued growth in the provision of CMM by appropriately qualified clinical pharmacists in collaborative practice settings will enhance recognition of their positive impact on medication-related outcomes.