Optimization of drug therapy in elderly individuals admitted to a geriatric unit.

Clin Interv Aging. 2017;12:1691-1696

Authors: Piau A, Huet Y, Gallini A, Andre L, Vellas B, Nourhashemi F

Abstract
BACKGROUND: A substantial share of adverse drug events involves inappropriate prescribing (IP). Specialized geriatric units are supposed to pay particular attention to prescribing appropriateness and to promoting a higher prescribing quality.
OBJECTIVE: The objective of this study was to evaluate the reality of such assessment and optimization in real life (usual care) in a population of elderly individuals admitted to a geriatric unit.
METHOD: This is an observational study including all older patients admitted to an acute geriatric unit over a 6-month period. As part of usual care, the geriatrician is supposed to detect potentially inappropriate medication and potential prescribing omission using validated tools. The primary outcome was the prevalence rate of therapeutic modifications motivated by treatment optimization (stop, switch, or introduction). Multivariate logistic regression analyses were performed to identify the factors associated with therapeutic discontinuation.
RESULTS: A total of 216 patients were included. The mean age was 85.7 years. Included patients had an average of 7.2±3.3 drugs at admission and 5.8±2.7 at discharge. IP was highly prevalent in our study where about 63% of the patients had experienced at least one modification because of overuse. The most commonly discontinued medications were drugs used to treat gastroesophageal reflux disease and peptic ulcer disease and serotonin reuptake inhibitor antidepressants. The most commonly introduced medications were analgesics and warfarin. By using multivariate analysis, we found that patient age and number of drugs on admission were significantly associated with medication discontinuation during hospital stay.
CONCLUSION: In this real-life study of all patients admitted to a Geriatric Post Emergency Unit, 83% of the patients had a treatment modification during hospital stay. The most original result of our study is the clear reduction in polypharmacy during hospitalization.

PMID: 29066874 [PubMed - indexed for MEDLINE]

Effect of Herbal Medicines During Surgery.

Plast Surg Nurs. 2017 Jul/Sep;37(3):99

Authors: Powell A

PMID: 28858165 [PubMed - indexed for MEDLINE]

Target Safety Assessment: Strategies and Resources.

Methods Mol Biol. 2017;1641:213-228

Authors: Brennan RJ

Abstract
An in-depth evaluation of target safety is an invaluable resource throughout drug discovery and development. The goal of a target safety evaluation is to identify potential unintended adverse consequences of target modulation, and to propose a risk evaluation and mitigation strategy to shepherd compounds through the discovery and development pipeline, to confirm and characterize unavoidable on-target toxicities in a timely manner to assist in early program advancement decisions, and to anticipate, monitor, and manage potential clinical adverse events. The role of an experienced discovery toxicologist in synthesizing the available information into an actionable set of recommendations for a safety evaluation strategy is critical to its successful application in early discovery programs. This chapter presents a summary of some of the information types and sources that should be investigated, and approaches that can be taken to generate an early assessment of potential safety liabilities.

PMID: 28748467 [PubMed - indexed for MEDLINE]

Adverse drug reactions after intravenous rituximab infusion are more common in hematologic malignancies than in autoimmune disorders and can be predicted by the combination of few clinical and laboratory parameters: results from a retrospective, multicenter study of 374 patients.

Leuk Lymphoma. 2017 Nov;58(11):2633-2641

Authors: D'Arena G, Simeon V, Laurenti L, Cimminiello M, Innocenti I, Gilio M, Padula A, Vigliotti ML, De Lorenzo S, Loseto G, Passarelli A, Di Minno MND, Tucci M, De Feo V, D'Auria F, Silvestris F, Di Minno G, Musto P

Abstract
Rituximab is an effective treatment for CD20 + B-cell malignancies and autoimmune disorders. However, adverse drug reactions (ADRs) may occur after rituximab infusion, causing, in rare cases, its discontinuation. In this multicenter, retrospective study, among 374 patients treated with rituximab i.v., 23.5% experienced ADRs. Mean follow-up was 20.6 months (range 8-135). Overall, ADRs were significantly more frequent in non-Hodgkin lymphomas (NHL) and chronic lymphocytic leukemias (25-35.9%), than in autoimmune diseases (9.4-17.5%) (p < .0001). Grade 3-4 toxicity was observed in eight patients (2.1%), and in four of them (1% of all patients) definitive drug discontinuation was necessary. Interestingly, three groups of patients with different risk of developing ADR were identified, according to a predictive heat-map developed combining four parameters (splenomegaly, history of allergy, hemoglobin levels and gender) selected by multivariate analysis. This model may be useful in identifying patients at higher risk of ADRs, needing appropriate preventing therapies.

PMID: 28367662 [PubMed - indexed for MEDLINE]

Adverse drug reactions.

Dis Mon. 2017 Feb;63(2):49-53

Authors: Seagrave Z, Bamba S

PMID: 28034457 [PubMed - indexed for MEDLINE]

First-in human, phase 1, dose-escalation pharmacokinetic and pharmacodynamic study of the oral dual PI3K and mTORC1/2 inhibitor PQR309 in patients with advanced solid tumors (SAKK 67/13).

Eur J Cancer. 2018 Apr 13;96:6-16

Authors: Wicki A, Brown N, Xyrafas A, Bize V, Hawle H, Berardi S, Cmiljanović N, Cmiljanović V, Stumm M, Dimitrijević S, Herrmann R, Prêtre V, Ritschard R, Tzankov A, Hess V, Childs A, Hierro C, Rodon J, Hess D, Joerger M, von Moos R, Sessa C, Kristeleit R

Abstract
BACKGROUND: PQR309 is an orally bioavailable, balanced pan-phosphatidylinositol-3-kinase (PI3K), mammalian target of rapamycin (mTOR) C1 and mTORC2 inhibitor.
PATIENTS AND METHODS: This is an accelerated titration, 3 + 3 dose-escalation, open-label phase I trial of continuous once-daily (OD) PQR309 administration to evaluate the safety, pharmacokinetics (PK) and pharmacodynamics in patients with advanced solid tumours. Primary objectives were to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D).
RESULTS: Twenty-eight patients were included in six dosing cohorts and treated at a daily PQR309 dose ranging from 10 to 150 mg. Common adverse events (AEs; ≥30% patients) included fatigue, hyperglycaemia, nausea, diarrhoea, constipation, rash, anorexia and vomiting. Grade (G) 3 or 4 drug-related AEs were seen in 13 (46%) and three (11%) patients, respectively. Dose-limiting toxicity (DLT) was observed in two patients at 100 mg OD (>14-d interruption in PQR309 due to G3 rash, G2 hyperbilirubinaemia, G4 suicide attempt; dose reduction due to G3 fatigue, G2 diarrhoea, G4 transaminitis) and one patient at 80 mg (G3 hyperglycaemia >7 d). PK shows fast absorption (Tmax 1-2 h) and dose proportionality for Cmax and area under the curve. A partial response in a patient with metastatic thymus cancer, 24% disease volume reduction in a patient with sinonasal cancer and stable disease for more than 16 weeks in a patient with clear cell Bartholin's gland cancer were observed.
CONCLUSION: The MTD and RP2D of PQR309 is 80 mg of orally OD. PK is dose-proportional. PD shows PI3K pathway phosphoprotein downregulation in paired tumour biopsies. Clinical activity was observed in patients with and without PI3K pathway dysregulation.
CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov # NCT01940133.

PMID: 29660598 [PubMed - as supplied by publisher]

[Recurrent atypical hemolytic uremic syndrome after renal transplantation: treatment with eculizumab].

Medicina (B Aires). 2018;78(2):119-122

Authors: Latzke AB, Fernández P, Chiurchiu C, Sarmantano D, De Arteaga J, Douthat W, De la Fuente J

Abstract
Atypical hemolytic uremic syndrome (aHUS) is a rare entity. It is characterized by a thrombotic microangiopathy (nonimmune hemolytic anemia, thrombocytopenia, and acute renal failure), with a typical histopathology of thickening of capillary and arteriolar walls and an obstructive thrombosis of the vascular lumen. The syndrome is produced by a genetic or acquired deregulation of the alternative pathway of the complement system, with high rates of end stage renal disease, post-transplant recurrence, and high mortality. Mutations associated with factor H, factor B and complement C3 show the worst prognosis. Even though plasma therapy is occasionally useful, eculizumab is effective both for treatment and prevention of post-transplant recurrence. We describe here an adult case of congenital aHUS (C3 mutation) under preventive treatment with eculizumab after renal transplantation, with neither disease recurrence nor drug-related adverse events after a 36-months follow-up.

PMID: 29659362 [PubMed - in process]

Longterm Safety and Efficacy of Adalimumab and Infliximab for Uveitis Associated with Juvenile Idiopathic Arthritis.

J Rheumatol. 2018 Apr 15;:

Authors: Cecchin V, Zannin ME, Ferrari D, Pontikaki I, Miserocchi E, Paroli MP, Bracaglia C, Marafon DP, Pastore S, Parentin F, Simonini G, De Libero C, Falcini F, Petaccia A, Filocamo G, De Marco R, La Torre F, Guerriero S, Martino S, Comacchio F, Muratore V, Martini G, Vittadello F, Zulian F

Abstract
OBJECTIVE: Anti-TNF-α agents have significantly changed the management of juvenile idiopathic arthritis (JIA). We evaluated the safety and efficacy of adalimumab (ADA) and infliximab (IFX) for the treatment of JIA-associated uveitis in patients treated for ≥ 2 years.
METHODS: Patients with JIA-associated uveitis treated with IFX and ADA were managed by a standardized protocol and data were entered in the ORCHIDEA registry. At baseline, all patients were refractory to standard immunosuppressive treatment or were corticosteroid-dependent. Data recorded every 3 months were uveitis course, number/type of ocular flares and complications, drug-related adverse events (AE), and treatment switch or withdrawal. Data of patients treated for ≥ 2 years were analyzed by descriptive statistics.
RESULTS: Up to December 2014, 154 patients with ≥ 24 months followup were included in the study. Fifty-nine patients were treated with IFX and 95 with ADA. Clinical remission, defined as the absence of flares for > 6 months on treatment, was achieved in 69 patients (44.8%), with a better remission rate for ADA (60.0%) as compared to IFX (20.3%; p < 0.001). A significant reduction of flares was observed in all patients without difference between the 2 treatment modalities. The number of new ocular complications decreased in both groups but was lower for ADA (p = 0.015). No serious AE were recorded; 16.4% of patients experienced 35 minor AE and the incidence rate was lower with ADA than with IFX.
CONCLUSION: At the 2-year followup, ADA showed a better efficacy and safety profile than IFX for the treatment of refractory JIA-associated uveitis.

PMID: 29657140 [PubMed - as supplied by publisher]

Exploring the effect of end-binding proteins and microtubule targeting chemotherapy drugs on microtubule dynamic instability.

J Theor Biol. 2017 Sep 21;429:18-34

Authors: White D, Honoré S, Hubert F

Abstract
Microtubules (MTs) play a key role in normal cell development and are a primary target for many cancer chemotherapy MT targeting agents (MTAs). As such, understanding MT dynamics in the presence of such agents, as well as other proteins that alter MT dynamics, is extremely important. In general, MTs grow relatively slowly and shorten very fast (almost instantaneously), an event referred to as a catastrophe. These dynamics, referred to as dynamic instability, have been studied in both experimental and theoretical settings. In the presence of MTAs, it is well known that such agents work by suppressing MT dynamics, either by promoting MT polymerization or promoting MT depolymerization. However, recent in vitro experiments show that in the presence of end-binding proteins (EBs), low doses of MTAs can increase MT dynamic instability, rather than suppress it. Here, we develop a novel mathematical model, to describe MT and EB dynamics, something which has not been done in a theoretical setting. Our MT model is based on previous modeling efforts, and consists of a pair of partial differential equations to describe length distributions for growing and shortening MT populations, and an ordinary differential equation (ODE) system to describe the time evolution for concentrations of GTP- and GDP-bound tubulin. A new extension of our approach is the use of an integral term, rather than an advection term, to describe very fast MT shortening events. Further, we introduce an ODE system to describe the binding and unbinding of EBs with MTs. To compare simulation results with experiment, we define novel mathematical expressions for time- and distance-based catastrophe frequencies. These quantities help to define MT dynamics in in vivo and in vitro settings. Simulation results show that increasing concentrations of EBs work to increase time-based catastrophe while distance-based catastrophe is less affected by changes in EB concentration, a result that is consistent with experiment. We further describe how EBs and MTAs alter MT dynamics. In the context of this modeling framework, we show that it is likely that MTAs and EBs do not work independently from one another. Thus, we propose a mechanism for how EBs can work synergistically with MTAs to promote MT dynamic instability at low MTA dose.

PMID: 28645857 [PubMed - indexed for MEDLINE]

Evaluation of prescription along three health-care periods in the elderly.

Geriatr Psychol Neuropsychiatr Vieil. 2017 Jun 01;15(2):153-162

Authors: Santoni F, Antoine V, di Castri A, Viala M, Geronimi-Robelin L, LeGuillou C, de Taddeo C, Bastide S, Jeandel C, de Wazieres B

Abstract
Polypharmacy, potentially inappropriate prescriptions and inadequate coordination between prescribers are among main factors explaining the occurrence of adverse drug events in elderly patients. Prospective and descriptive study of medication prescriptions for elderly patients during a continuous period of health-care: entry in an acute geriatric unit (T1), at discharge (T2) and two months after hospitalization (T3). A global iatrogenic risk was defined: presence of poly-pharmacy and/or PPI (Laroche criteria) and/or absence of quality indicators for prescription according to the French health authority. For the 79 patients (mean age 87), mean number of medication decreased from 7.33 (T1) to 6 (T2) (p=0.0018) and 6 (T3). Number of quality indicators for prescription improved from 6.67 (T1) to 6.92 (T2) (p=0.001) then decreased to 6.84 (T3). Number of PPI decreased from 1.16 to 0.42 between T1 and T2 (p=0.001) then increased to 0.59 at T3. The global iatrogenic risk indicator fluctuated from 80% (T1) to 64% (T2) and 75% (T3). Selected interventions were developed to prevent adverse drug events during hospitalization and ambulatory follow-up. If geriatric intervention can enhance quality of prescription, iatrogenic risk remains frequent all along health-care follow-up. A local study of prescriptions can be a first step to develop an adequate program for adverse drug events prevention.

PMID: 28625935 [PubMed - indexed for MEDLINE]

Letters to the Editor.

AACN Adv Crit Care. 2017;28(2):133-134

Authors: Gosselin S, Lavergne V, Stork C, Hoffman RS

PMID: 28592470 [PubMed - indexed for MEDLINE]

Overview of systematic reviews of therapeutic ranges: methodologies and recommendations for practice.

BMC Med Res Methodol. 2017 Jun 02;17(1):84

Authors: Cooney L, Loke YK, Golder S, Kirkham J, Jorgensen A, Sinha I, Hawcutt D

Abstract
BACKGROUND: Many medicines are dosed to achieve a particular therapeutic range, and monitored using therapeutic drug monitoring (TDM). The evidence base for a therapeutic range can be evaluated using systematic reviews, to ensure it continues to reflect current indications, doses, routes and formulations, as well as updated adverse effect data. There is no consensus on the optimal methodology for systematic reviews of therapeutic ranges.
METHODS: An overview of systematic reviews of therapeutic ranges was undertaken. The following databases were used: Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts and Reviews of Effects (DARE) and MEDLINE. The published methodologies used when systematically reviewing the therapeutic range of a drug were analyzed. Step by step recommendations to optimize such systematic reviews are proposed.
RESULTS: Ten systematic reviews that investigated the correlation between serum concentrations and clinical outcomes encompassing a variety of medicines and indications were assessed. There were significant variations in the methodologies used (including the search terms used, data extraction methods, assessment of bias, and statistical analyses undertaken). Therapeutic ranges should be population and indication specific and based on clinically relevant outcomes. Recommendations for future systematic reviews based on these findings have been developed.
CONCLUSION: Evidence based therapeutic ranges have the potential to improve TDM practice. Current systematic reviews investigating therapeutic ranges have highly variable methodologies and there is no consensus of best practice when undertaking systematic reviews in this field. These recommendations meet a need not addressed by standard protocols.

PMID: 28577540 [PubMed - indexed for MEDLINE]

Efficacy and Safety of Panobinostat in Relapsed or/and Refractory Multiple Myeloma: Meta Analyses of Clinical Trials and Systematic Review.

Sci Rep. 2016 06 07;6:27361

Authors: Liu JD, Sun CY, Tang L, Wu YY, Wang QY, Hu B, Hu Y

Abstract
During the past decades, many novel agents have improved response and survival of patients with multiple myeloma. Nevertheless, it remains challenging when they suffer relapsing. Thus, novel therapeutic agents are needed. We aimed to assess the efficacy and safety of a novel agent panobinostat for patients with relapsed or/and refractory MM. A systematic literature review identified studies for clinical trials about panobinostat in patients with relapsed or/and refractory MM. We searched studies published between January 2000 and December 2015 in Pubmed, Ovid, EBSCO and the Cochrane library. Random-effect pooled estimates were calculated for overall response rate and rates of common adverse effects. The results showed 11 clinical trials including 700 patients with relapsed or/and refractory MM treated with panobinostat were identified. The ORR varied between 0.08 and 0.67. Pooled analyses showed the results that the ORR was 0.45 (95% CI: 0.31-0.59, I(2) = 90.5%, P = 0.000) for panobinostat combined with any other kind of drugs. The most common Grade3/4 adverse effects were thrombocytopenia, neutropenia, lymphopenia, anemia, diarrhea, fatigue, nausea and so on. In conclusion, based on our analyses, the regimen of panobinostat combining with other agents seems to be well tolerated and efficacious in patients with relapsed or/and refractory MM.

PMID: 27270478 [PubMed - indexed for MEDLINE]

Pharmacokinetic and pharmacodynamic profile of the sodium-glucose co-transporter-2 inhibitor empagliflozin in young people with Type 2 diabetes: a randomized trial.

Diabet Med. 2018 Apr 14;:

Authors: Laffel LMB, Tamborlane WV, Yver A, Simons G, Wu J, Nock V, Hobson D, Hughan KS, Kaspers S, Marquard J

Abstract
AIMS: To assess the pharmacokinetic and pharmacodynamic profile of a single dose of empagliflozin in young people with Type 2 diabetes to identify the appropriate doses for further paediatric development.
METHODS: We conducted a single-dose, open-label, randomized, parallel-group study with empagliflozin 5 mg, 10 mg and 25 mg in young people with Type 2 diabetes aged 10-17 years.
RESULTS: Of 39 participants screened, 27 were randomized and completed the study; their mean (± sd) age was 14.1±2.0 years and body weight was 96.7±23.5 kg. Compared with similar studies in adults with Type 2 diabetes, the maximum observed plasma concentrations were slightly lower with the 10-mg and 25-mg doses, and the area under the plasma concentration-time curve was slightly lower with the 10-mg but slightly higher with the 25-mg dose. The adjusted mean increases in urinary glucose excretion were 53 g/24 h (95% CI 32,74), 73 g/24 h (95% CI 52,94) and 87 g/24 h (95% CI 68,107), and the adjusted mean decreases in fasting plasma glucose were 0.9 mmol/l (95% CI -1.6,-0.1), 0.9 mmol/l (95% CI -1.7,-0.2) and 1.1 mmol/l (95% CI -1.8,-0.5) for the 5- 10- and 25-mg doses, respectively. There were no serious adverse events and one investigator-reported drug-related event (dehydration).
CONCLUSIONS: After a single oral dose of empagliflozin, adults and young people with Type 2 diabetes had similar exposure-response relationships after adjusting for significant covariates. These data support testing 10-mg and/or 25-mg doses of empagliflozin in an upcoming paediatric phase III Type 2 diabetes trial. This article is protected by copyright. All rights reserved.

PMID: 29655290 [PubMed - as supplied by publisher]

Cardiovascular safety signals with dipeptidyl peptidase-4 inhibitors: A disproportionality analysis among high-risk patients.

Pharmacoepidemiol Drug Saf. 2018 Apr 14;:

Authors: Baksh SN, McAdams-DeMarco M, Segal JB, Alexander GC

Abstract
PURPOSE: In 2008, the US Food and Drug Administration (FDA) issued Draft Guidance on investigating cardiovascular risk with oral diabetic drugs, including dipeptidyl peptidase-4 inhibitors (DPP-4i). In 2014, underpowered, post hoc analyses of clinical trials suggested an increased risk of heart failure with the use of these products. As such, we assessed disproportionate reporting of major adverse cardiac events (MACE) among reports for DPP-4i submitted to the FDA Adverse Event Reporting System (FAERS) from 2006 to 2015.
METHODS: We assessed the empirical Bayes geometric mean (EBGM) and its lower bound (EB05) of the relative reporting ratio for MACE among DPP-4i reports in the full FAERS database and in a subset of reports limited to cardiovascular and diabetic drugs. We then compared the EB05 in these 2 analyses and calculated the percent positive agreement for signals of disproportional reporting (SDRs) involving MACE.
RESULTS: Of 180.3 million adverse event reports, 13.4 million were for diabetic and cardiovascular drugs. In the cardiovascular subset, there was an SDR for heart failure with linagliptin (EB05 = 2782.47) and saxagliptin (EB05 = 2.40), myocardial infarction with alogliptin (EB05 = 290.11), and cerebral infarction with sitagliptin (EB05 = 2.80). Of the 14 MACE, 8 had a percent positive agreement ≥50% for an SDR in both analyses. Overall, the cardiovascular subset elicited 11 more SDRs for DPP-4i than the full dataset.
CONCLUSIONS: Postmarketing surveillance of DPP-4i through FAERS suggest increased reporting of MACE, supporting the current FDA warning of heart failure risk. This suggests the need for additional longitudinal, observational research into the association of DPP-4i and other MACE.

PMID: 29655237 [PubMed - as supplied by publisher]

Factors affecting adherence to antiretroviral therapy among pregnant women in the Eastern Cape, South Africa.

BMC Infect Dis. 2018 Apr 13;18(1):175

Authors: Adeniyi OV, Ajayi AI, Ter Goon D, Owolabi EO, Eboh A, Lambert J

Abstract
BACKGROUND: Context-specific factors influence adherence to antiretroviral therapy (ART) among pregnant women living with HIV. Gaps exist in the understanding of the reasons for the variable outcomes of the prevention of mother-to-child transmission (PMTCT) programme at the health facility level in South Africa. This study examined adherence levels and reasons for non-adherence during pregnancy in a cohort of parturient women enrolled in the PMTCT programme in the Eastern Cape, South Africa.
METHODS: This was a mixed-methods study involving 1709 parturient women in the Eastern Cape, South Africa. We conducted a multi-centre retrospective analysis of the mother-infant pair in the PMTCT electronic database in 2016. Semi-structured interviews of purposively selected parturient women with self-reported poor adherence (n = 177) were conducted to gain understanding of the main barriers to adherence. Binary logistic regression was used to determine the independent predictors of ART non-adherence.
RESULTS: A high proportion (69.0%) of women reported perfect adherence. In the logistic regression analysis, after adjusting for confounding factors, marital status, cigarette smoking, alcohol use and non-disclosure to a family member were the independent predictors of non-adherence. Analysis of the qualitative data revealed that drug-related side-effects, being away from home, forgetfulness, non-disclosure, stigma and work-related demand were among the main reasons for non-adherence to ART.
CONCLUSIONS: Non-adherence to the antiretroviral therapy among pregnant women in this setting is associated with lifestyle behaviours, HIV-related stigma and ART side-effects. In order to eliminate mother-to-child transmission of HIV, clinicians need to screen for these factors at every antenatal clinic visit.

PMID: 29653510 [PubMed - in process]

Nanomedicine formulations for the delivery of antiviral drugs: a promising solution for the treatment of viral infections.

Expert Opin Drug Deliv. 2018 Jan;15(1):93-114

Authors: Lembo D, Donalisio M, Civra A, Argenziano M, Cavalli R

Abstract
INTRODUCTION: Viral infections represent a public health problem and one of the leading causes of global mortality. Nanomedicine strategies can be considered a powerful tool to enhance the effectiveness of antiviral drugs, often associated with solubility and bioavailability issues. Consequently, high doses and frequent administrations are required, resulting in adverse side effects. To overcome these limitations, various nanomedicine platforms have been designed. Areas covered: This review focuses on the state of the art of organic-based nanoparticles for the delivery of approved antivirals. A brief description of the main characteristics of nanocarriers is followed by an overview of the most promising research addressing the treatment of most important viral infections. Expert opinion: The activity of antiviral drugs could be improved with nanomedicine formulations. Indeed, nanoparticles can affect the fate of the encapsulated drugs, allowing controlled release kinetics, enhanced bioavailability, modified pharmacokinetics, and reduced side effects. In addition, the physicochemical properties of nanocarriers can enable their capability to target specific sites and to interact with virus structures. In this regard, nanomedicines can be considered an opportunity to enhance the therapeutic index of antivirals. Efficacy, safety, and manufacturing issues need to be carefully assessed to bring this promising approach to the clinic.

PMID: 28749739 [PubMed - indexed for MEDLINE]

Implementing exercise in cancer care: study protocol to evaluate a community-based exercise program for people with cancer.

BMC Cancer. 2017 Feb 06;17(1):103

Authors: Cormie P, Lamb S, Newton RU, Valentine L, McKiernan S, Spry N, Joseph D, Taaffe DR, Doran CM, Galvão DA

Abstract
BACKGROUND: Clinical research has established the efficacy of exercise in reducing treatment-related side-effects and increasing wellbeing in people with cancer. Major oncology organisations have identified the importance of incorporating exercise in comprehensive cancer care but information regarding effective approaches to translating evidence into practice is lacking. This paper describes the implementation of a community-based exercise program for people with cancer and the protocol for program evaluation.
METHODS/DESIGN: The Life Now Exercise program is a community-based exercise intervention designed to mitigate and rehabilitate the adverse effects of cancer and its treatment and improve physical and psychosocial wellbeing in people with cancer. Involvement in the program is open to people with any diagnosis of cancer who are currently receiving treatment or within 2 years of completing treatment. The 3-month intervention consists of twice weekly group-based exercise sessions administered in community exercise clinics under the supervision of exercise physiologists trained to deliver the program. Evaluation of the program involves measures of uptake, safety, adherence and effectiveness (including cost effectiveness) as assessed at the completion of the program and 6 months follow-up.
DISCUSSION: To bridge the gap between research and practice, the Life Now Exercise program was designed and implemented to provide people with cancer access to evidence-based exercise medicine. The framework for program implementation and evaluation offers insight into the development of feasible, generalizable and sustainable supportive care services involving exercise. Community-based exercise programs specifically designed for people with cancer are necessary to facilitate adherence to international guidelines advising patients to participate in high-quality exercise.
TRIAL REGISTRATION: ACTRN12616001669482 (retrospectively registered 5 Dec 2016).

PMID: 28166766 [PubMed - indexed for MEDLINE]

Slow infusion of low{\hyphen}dose ketamine reduces bothersome side effects compared to IV push: a double{\hyphen}blind, double dummy, randomized controlled trial.

Acad Emerg Med. 2018 Apr 12;:

Authors: Clattenburg EJ, Hailozian C, Haro D, Yoo T, Flores S, Louie D, Herring AA

Abstract
STUDY OBJECTIVE: We compared the analgesic efficacy and incidence of side effects when low{\hyphen}dose (0.3 mg{\sol}kg) ketamine (LDK) is administered as a slow infusion (SI) over 15 minutes versus an intravenous push (IVP) over one minute.
METHODS: This was a prospective, randomized, double blind, double dummy, placebo{\hyphen}controlled trial of adult ED patients presenting with moderate to severe pain (numerical rating score ≥ 5). Patients received ketamine 0.3mg{\sol}kg administered either as a SI or IVP. Our primary outcome was the proportion of patients experiencing any psychoperceptual side effect over 60 minutes. A secondary outcome was incidence of moderate or greater psychoperceptual side effects. Additional outcomes included reduction in pain NRS scores at 60 minutes and percent maximum summed pain intensity difference ({\percnt}SPID).
RESULTS: Fifty{\hyphen}nine participants completed the study. 86.2{\percnt} of the IVP arm and 70.0{\percnt} of the SI arm experienced any side effect (difference 16.2{\percnt}, 95{\percnt}CI {\hyphen}5.4 - 37.8). We found a large reduction in moderate or greater psychoperceptual side effects with SI administration-75.9{\percnt} reported moderate or greater side effects versus 43.4{\percnt} in the SI arm (difference 32.5{\percnt}, 95{\percnt}CI 7.9 - 57.1). Additionally, the IVP arm experienced more hallucinations (n{\equal}8, 27.6{\percnt}) than the SI arm (SI n{\equal}2, 6.7{\percnt}; difference 20.9{\percnt}, 95{\percnt}CI 1.8 - 43.4). We found no significant differences in analgesic efficacy. At 60 minutes, the mean {\percnt}SPID in the IVP and SI arms was 39.9{\percnt} and 33.5{\percnt}, respectively, with a difference of 6.5{\percnt} (95{\percnt}CI {\hyphen}5.8 - 18.7).
CONCLUSION: Most patients who are administered LDK experience a psychoperceptual side effect regardless of administration via SI or IVP. However, patients receiving LDK as a SI reported significantly fewer moderate or greater psychoperceptual side effects and hallucinations with equivalent analgesia. This article is protected by copyright. All rights reserved.

PMID: 29645317 [PubMed - as supplied by publisher]

[Pharmacological treatment of osteoarthritis-related pain].

Schmerz. 2018 Apr 11;:

Authors: Nees TA, Schiltenwolf M

Abstract
Joint pain due to osteoarthritis (OA) is often severe and disabling and affects a large proportion of the aging population impairing daily living and quality of life. Numerous pharmacological treatment approaches are available. Including major OA guidelines this review presents the current evidence of pharmacological therapies in OA-related pain and covers topical, oral and intraarticular treatment approaches. In patients with mild OA topical nonsteroidal antiinflammatory drugs (NSAIDs) can be recommended. Topical capsaicin can be used when other treatments are ineffective or contraindicated. In patients with moderate to severe OA oral NSAIDs are suggested at the lowest effective dose for the shortest possible duration to control symptoms. Importantly, drug-related side effects and gastrointestinal, cardiovascular and renal comorbidities need to be taken into account. In patients with multiple-joint OA and high risk of NSAID-induced adverse events duloxetine can be considered. The evidence of metamizole, symptomatic slow-acting drugs in osteoarthritis and other nutritional supplements in the treatment of OA pain is uncertain and the use of opioids is not routinely recommended. In patients suffering from severe OA-related pain intraarticular injections with glucocorticoids can be suggested to achieve short-term pain relief. Evidence for interventional approaches using hyaluronic acid or platelet-rich plasma is uncertain. Yet, the efficacy of pharmacological therapies in OA-related pain is often inconsistent and severe adverse events might occur. Thus, critical use of the different treatment options considering patient-related comorbidities and nonpharmacological therapies is of major importance.

PMID: 29644468 [PubMed - as supplied by publisher]