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Concept: Classification of Pharmaco-Therapeutic Referrals


The way hemodynamic therapies are delivered today in anesthesia and critical care is suboptimal. Hemodynamic variables are not always understood correctly and used properly. The adoption of hemodynamic goal-directed strategies, known to be clinically useful, is poor. Ensuring therapies are delivered effectively is the goal of decision support tools and closed loop systems. Graphical displays (metaphor screens) may help clinicians to better capture and integrate the multivariable hemodynamic information. This may result in faster and more accurate diagnosis and therapeutic decisions. Graphical displays (target screens) have the potential to increase adherence to goal-directed strategies and ultimately improve patients' outcomes, but this remains to be confirmed by prospective studies. Closed loop systems are the ultimate solution to ensure therapies are delivered. However, most therapeutic decisions cannot be based on a limited number of output variables. Therefore, one should focus on the development of systems designed to relieve clinicians from very simple and repetitive tasks. Whether intraoperative goal-directed fluid therapy may be one of these tasks remains to be evaluated.

Concepts: Medicine, Therapy, Classification of Pharmaco-Therapeutic Referrals, Decision theory, Control theory, Decision support system, Graphic design, Medical error


The obesity pandemic presents a significant burden, both in terms of healthcare and economic outcomes, and current medical therapies are inadequate to deal with this challenge. Bariatric surgery is currently the only therapy available for obesity which results in long-term, sustained weight loss. The favourable effects of this surgery are thought, at least in part, to be mediated via the changes of gut hormones such as GLP-1, PYY, PP and oxyntomodulin seen following the procedure. These hormones have subsequently become attractive novel targets for the development of obesity therapies. Here, we review the development of these gut peptides as current and emerging therapies in the treatment of obesity.

Concepts: Medicine, Obesity, Surgery, Therapy, Classification of Pharmaco-Therapeutic Referrals, Weight loss, Bariatric surgery, Gastric bypass surgery


Manufacturing methods for cell-based therapies differ markedly from those established for noncellular pharmaceuticals and biologics. Attempts to ‘shoehorn’ these into existing frameworks have yielded poor outcomes. Some excellent clinical results have been realized, yet emergence of a ‘blockbuster’ cell-based therapy has so far proved elusive.

Concepts: Medicine, Therapy, Classification of Pharmaco-Therapeutic Referrals, Therapy?, Lean manufacturing


Hepatocarcinogenesis is a multistep process, heralded by abnormalities in cell differentiation and proliferation and sustained by an aberrant neoangiogenesis. Understanding the underlying molecular pathogenesis leading to hepatocellular carcinoma is a prerequisite to develop new drugs that will hamper or block the steps of these pathways. As hepatocellular carcinoma has higher arterial vascularization than normal liver, this could be a good target for novel molecular therapies. Introduction of the antiangiogenic drug sorafenib into clinical practice since 2008 has led to new perspectives in the management of this tumor. The importance of this drug lies not only in the modest gain of patients' survival, but in having opened a roadmap towards the development of new molecules and targets. Unfortunately, after the introduction of sorafenib, during the last years, a wide number of clinical trials on antiangiogenic therapies failed in achieving significant results. However, many of these trials are still ongoing and promise to improve overall survival and progression-free survival. A recent clinical trial has proven regorafenib effective in patients showing tumor progression under sorafenib, thus opening new interesting therapeutic perspectives. Many other expectations have been borne from the discovery of the immune checkpoint blockade, already known in other solid malignancies. Furthermore, a potential role in hepatocellular carcinoma therapy may derive from the use of branched-chain amino acids and of nutritional support. This review analyses the biomolecular pathways of hepatocellular carcinoma and the ongoing studies, the actual evidence and the future perspectives concerning drug therapy in this open field.

Concepts: Immune system, Pharmacology, Clinical trial, Cancer, The Canon of Medicine, Therapy, Classification of Pharmaco-Therapeutic Referrals, Clinical trial protocol


Current therapeutic approaches to depression fail for millions of patients due to lag in clinical response and non-adherence. Here we provide new support for the antidepressant effect of an anesthetic drug, ketamine, by Inverse-Frequency Analysis of eight million reports from the FDA Adverse Effect Reporting System. The results of the examination of population scale data revealed that patients who received ketamine had significantly lower frequency of reports of depression than patients who took any other combination of drugs for pain. The analysis also revealed that patients who took ketamine had significantly lower frequency of reports of pain and opioid induced side effects, implying ketamine’s potential to act as a beneficial adjunct agent in pain management pharmacotherapy. Further, the Inverse-Frequency Analysis methodology provides robust statistical support for the antidepressant action of other currently approved therapeutics including diclofenac and minocycline.

Concepts: Therapeutic effect, Pharmacology, Therapy, Classification of Pharmaco-Therapeutic Referrals, Opioid, Morphine, Ketamine, Recreational drug use


STUDY DESIGN.: A retrospective cohort. OBJECTIVE.: To describe physical therapy utilization following primary care consultation for low back pain (LBP) and evaluate associations between the timing and content of physical therapy and subsequent health care utilization and costs. SUMMARY OF BACKGROUND DATA.: Primary care management of LBP is highly variable and the implications for subsequent costs are not well understood. The importance of referring patients from primary care to physical therapy has been debated, and information on how the timing and content of physical therapy impact subsequent costs and utilization is needed. METHODS.: Data were extracted from a national database of employer-sponsored health plans. A total of 32,070 patients with a new primary care LBP consultation were identified and categorized on the basis of the use of physical therapy within 90 days. Patients utilizing physical therapy were further categorized based on timing (early [within 14 d] or delayed)] and content (guideline adherent or nonadherent). LBP-related health care costs and utilization in the 18-months following primary care consultation were examined. RESULTS.: Physical therapy utilization was 7.0% with significant geographic variability. Early physical therapy timing was associated with decreased risk of advanced imaging (odds ratio [OR] = 0.34, 95% confidence interval [CI]: 0.29, 0.41), additional physician visits (OR = 0.26, 95% CI: 0.21, 0.32), surgery (OR = 0.45, 95% CI: 0.32, 0.64), injections (OR = 0.42, 95% CI: 0.32, 0.64), and opioid medications (OR = 0.78, 95% CI: 0.66, 0.93) compared with delayed physical therapy. Total medical costs for LBP were $2736.23 lower (95% CI: 1810.67, 3661.78) for patients receiving early physical therapy. Physical therapy content showed weaker associations with subsequent care. CONCLUSION.: Early physical therapy following a new primary care consultation was associated with reduced risk of subsequent health care compared with delayed physical therapy. Further research is needed to clarify exactly which patients with LBP should be referred to physical therapy; however, if referral is to be made, delaying the initiation of physical therapy may increase risk for additional health care consumption and costs.

Concepts: Health care, Health care provider, Medicine, Spinal disc herniation, Classification of Pharmaco-Therapeutic Referrals, Illness, Opioid, Massage


Treatment of multidrug-resistant Mycobacterium tuberculosis is a challenge. This letter describes the emergence of resistance to new therapies, bedaquiline and delamanid.

Concepts: Therapy, Classification of Pharmaco-Therapeutic Referrals, Tuberculosis, Mycobacterium, Mycobacterium tuberculosis, Therapy?


OBJECTIVES To explore student pharmacists' attitudes toward complementary and alternative medicine (CAM) and examine factors shaping students' attitudes. DESIGN Descriptive, exploratory, nonexperimental study. SETTING Electronic survey of student pharmacists between March and October 2011. PARTICIPANTS 887 student pharmacists in 10 U.S. colleges/schools of pharmacy. INTERVENTION Cross-sectional survey. MAIN OUTCOME MEASURES Student pharmacists' attitudes regarding CAM using the attitudes toward CAM scale (15 items), attitudes toward specific CAM therapies (13 items), influence of factors (e.g., coursework, personal experience) on attitudes (18 items), and demographic characteristics (15 items). RESULTS Mean (±SD) score on the attitudes toward CAM scale was 52.57 ± 7.65 (of a possible 75; higher score indicated more favorable attitudes). Students agreed that a patient’s health beliefs should be integrated in the patient care process (4.39 ± 0.70 [of 5]) and that knowledge about CAM would be required in future pharmacy practice (4.05 ± 0.83). Scores on the attitudes toward CAM scale varied by gender (women higher than men, P = 0.001), race/ethnicity (nonwhite higher than white, P < 0.001), type of institution (private higher than public, P < 0.001), previous CAM coursework ( P < 0.001), and previous CAM use ( P < 0.001). Personal experience, pharmacy education (e.g., coursework and faculty attitudes), and family background were important factors shaping students' attitudes. CONCLUSION Student pharmacists hold generally favorable views of CAM, and both personal and educational factors shape their views. These results provide insight into factors shaping future pharmacists' perceptions of CAM. Additional research is needed to examine how attitudes influence future pharmacists' confidence and willingness to talk to patients about CAM.

Concepts: Medicine, Patient, Hospital, Ayurveda, Education, Classification of Pharmaco-Therapeutic Referrals, Alternative medicine, Pharmacy


We performed a systematic review of the literature to compare the efficacy of different drug therapies for the termination of stable, monomorphic ventricular tachycardia (VT).

Concepts: Medicine, Therapy, Pharmacotherapy, Classification of Pharmaco-Therapeutic Referrals, Ventricular tachycardia, Supraventricular tachycardia, Tachycardia, Therapy?


BACKGROUND: Glaucoma comprises age-related neurodegenerative diseases of retinal ganglion cells, the worldwide prevalence of which is increasing. Local pharmacotherapy is the primary treatment option, especially in the elderly. But this therapeutic approach may include risks for adverse drug effects and drug-drug interactions, of particular importance in frail nursing home resident populations. OBJECTIVE: The aim of the present study was to investigate anti-glaucoma pharmacotherapy in nursing home residents in the context of multi-morbidity and related systemic co-medication. METHODS: Data for 8,685 nursing home residents with 88,695 drug prescriptions were analysed according to diagnosis and local or systemic pharmacotherapy. Data were provided in anonymous form by a German public health insurance company. RESULTS: The study cohort was characterized by a mean age of 83.6 ± 7.3 years (range: 65-106 years), 21 % of nursing home residents were at least 90 years old and 83.7 % were women. For each nursing home resident, an average of 6.0 ± 3.3 different drugs were registered. A diagnosis of glaucoma was recorded in 520 (6.0 %) nursing home residents; all subjects had co-existing medical conditions. Dementia was a frequent co-morbidity, diagnosed in 51.7 % of nursing home residents with glaucoma. Anti-glaucoma drugs contributed to 0.5 % of all prescriptions and were prescribed to 341 nursing home residents. The most frequently used anti-glaucoma ophthalmics were β-blockers (n = 219), followed by prostaglandin analogues (n = 101) and carbonic anhydrase inhibitors (n = 86). Local anti-glaucoma therapy was co-prescribed with a systemic pharmacotherapy in 338 nursing home residents. An ophthalmic agent was, on average, combined with 6.5 ± 3.2 prescriptions for systemic agents. Thus, 71.9 % of nursing home residents were prescribed ophthalmic β-blockers and a concomitant antihypertensive medication; local and systemic β-blockers were combined in 20.2 % of these patients. Co-treatment with cardiac glycosides or calcium antagonists was found in 13 % of nursing home residents prescribed ophthalmic parasympathomimetics, and in 14 % of those prescribed ophthalmic β-blockers, with the potential for drug-drug interactions to influence cardiac function. CONCLUSIONS: Anti-glaucoma pharmacotherapy in nursing home residents is frequently prescribed in the context of polypharmacy. This may modify the efficacy and safety of local and systemic therapies. Therefore, individualized pharmacotherapy that integrates anti-glaucoma drug therapy into the overall treatment rationale in nursing home residents is necessary. However, to realize this concept, further clinical research in nursing home residents is warranted.

Concepts: Pharmacology, Drug, Therapy, Classification of Pharmaco-Therapeutic Referrals, Drug addiction, Adverse drug reaction, Prostaglandin analogue, Retinal ganglion cell