The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

Frailty Consensus: A Call to Action

Potentially inappropriate medications (PIMs) continue to be prescribed and used as first-line treatment for the most vulnerable of older adults, despite evidence of poor outcomes from the use of PIMs in older adults. PIMs now form an integral part of policy and practice and are incorporated into several quality measures. The specific aim of this project was to update the previous Beers Criteria using a comprehensive, systematic review and grading of the evidence on drug-related problems and adverse drug events (ADEs) in older adults. This was accomplished through the support of The American Geriatrics Society (AGS) and the work of an interdisciplinary panel of 11 experts in geriatric care and pharmacotherapy who applied a modified Delphi method to the systematic review and grading to reach consensus on the updated 2012 AGS Beers Criteria. Fifty-three medications or medication classes encompass the final updated Criteria, which are divided into three categories: potentially inappropriate medications and classes to avoid in older adults, potentially inappropriate medications and classes to avoid in older adults with certain diseases and syndromes that the drugs listed can exacerbate, and finally medications to be used with caution in older adults. This update has much strength, including the use of an evidence-based approach using the Institute of Medicine standards and the development of a partnership to regularly update the Criteria. Thoughtful application of the Criteria will allow for (a) closer monitoring of drug use, (b) application of real-time e-prescribing and interventions to decrease ADEs in older adults, and (c) better patient outcomes.

/pdf/american-geriatrics-society-updated-beers-criteria-for-2xwgw2dsk5.pdf

American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults

The purpose of this paper is to provide a brief review of the current state of our knowledge regarding pesticides and oxidative stress. To this end, we performed a search of the literature using Medline/Index Medicus, EMBASE/Excerpta Medica, and Chemical Abstracts; most of the relevant citations were studied and summarized. In order to better understand the nature of oxidative stress, the principles of free radical production and the body's normal defense system are discussed. The pesticides are categorized and discussed according to their ability to produce lipid peroxidation or alter body antioxidant status. It is concluded that stimulation of free radical production, induction of lipid peroxidation, and disturbance of the total antioxidant capability of the body are mechanisms of toxicity in most pesticides, including organophosphates, bipyridyl herbicides and organochlorines.

Pesticides and oxidative stress: a review.

Appropriate prescribing in elderly people: how well can it be measured and optimised?

To evaluate drug-related problems in the elderly, various lists of potentially inappropriate medications have been published in North America. Unfortunately, these lists are hardly applicable in France. The purpose of this study was to establish a list of inappropriate medications for French elderly using the Delphi method. A two-round Delphi method was used to converge to an agreement between a pool of 15 experts from various parts of France and from different backgrounds (five geriatricians, five pharmacologists, two pharmacists, two general practitioners, one pharmacoepidemiologist). In round one, they were sent a questionnaire based on a literature review listing medications and clinical situations. They were asked to comment on the potential inappropriateness of the criteria proposed using a 5-point Likert scale (from strong agreement to strong disagreement) and to suggest therapeutic alternatives and new criteria. In round two, the experts confirmed or cancelled their previous answers from the synthesis of the responses of round one. After round two, a final list of potentially inappropriate drugs was established. The final list proposed 36 criteria applicable to people ≥75 years of age. Twenty-nine medications or medication classes applied to all patients, and five criteria involved medications that should be avoided in specific medical conditions. Twenty-five medications or medication classes were considered with an unfavourable benefit/risk ratio, one with a questionable efficacy and eight with both unfavourable benefit/risk ratio and questionable efficacy. This expert consensus should provide prescribers with an epidemiological tool, a guideline and a list of alternative therapies.

Potentially inappropriate medications in the elderly: a French consensus panel list

Two thousand and eighteen patients were included. The number of drugs taken was 7.3 3.0 in the patients with ADRs and 6.0 3.0 in those without ADRs (P < 0.0001). Sixty-six percent of the patients were given at least one IM prior to admission. ADR prevalence was 20.4% among the 1331 patients using IMs and 16.4% among those using only appropriate drugs (P < 0.03). In only 79 of the 1331 IM users (5.9%) were ADRs directly attributable to IMs. The IMs most often involved in patients with ADRs were: anticholinergic antidepressants, cerebral vasodilators, long-acting benzodiazepines and concomitant use of two or more psychotropic drugs from the same therapeutic class. Using multivariate analysis, after adjusting for confounding factors, IM use was not associated with a significant increased risk of ADRs (odds ratio 1.0, 95% confidence interval 0.8, 1.3).

/pdf/is-inappropriate-medication-use-a-major-cause-of-adverse-35vx9kanrx.pdf

Is inappropriate medication use a major cause of adverse drug reactions in the elderly

Paraoxonase is an esterase that hydrolyzes organo- phosphate compounds. The enzyme is associated with HDL and could protect LDL against peroxidation, which suggests a possible involvement of paraoxonase in the antiatherogenic properties of HDL. Paraoxonase activity has been shown to be low in patients with myocardial infarction, diabetes mellitus, or familial hypercholesterobemia. Because cardiovascular disease is the main cause of death in chronic renal failure, serum paraoxonase activity was measured by spectrophotometry us- ing three synthetic substrates (phenyl acetate, paraoxon, and 4-nitrophenyl acetate) in 305 patients with kidney disease, including 47 patients with non-end-stage chronic renal failure, 104 patients treated with hemodialysis, 22 patients treated with peritoneab dialysis, and 132 renal transplant patients. Patients were compared with two groups of aged-matched control sub- jects (total number = 195). Especially with 4-nitrophenyl acetate, paraoxonase activity was lower in patients with some degree of renal insufficiency (chronic renal failure (P < 0.05), chronic hemodialysis (P < b0�1, chronic peritoneab dialysis (P < l0�)) than in control subjects. In transplant patients, paraoxonase activity was not found to be different from that in control subjects. The decrease of paraoxonase activity and thus the reduction of its antiatherogenic properties in renal failure could be an essential factor of premature vascular aging, es- peciably when dialysis is used. Renal transplantation seems to restore paraoxonase activity. Cardiovascular disease is the main cause of death in chronic renal failure (CRF) patients (accounting for approximately 50% of cases; references 1 and 2). The relative risk of myocardial infarc- tion is five times greater in patients on renal replacement therapy than in the general population (3). No clear explanation of this "accelerated" atherosclerosis has been found. Several factors, including increased prevalence of hypertension, diabetes melbitus, and lipid abnormalities, may contribute (4,5). After renal trans- plantation, atherosclerosis remains a major cause of mortality, and dyslipidemias are also frequently observed (6). Recently, several studies have shown a higher susceptibility of LDL to oxidation in CRF patients, suggesting that the protection of lipoproteins against oxidation might be impaired (7-9). Because the oxidation hypothesis of atherosclerosis seems to be currently established (oxidized LDL promoting a number of processes leading to the formation of atherosclerotic plaques in the arterial wall: enhancement of macrophage uptake, cytotox- icity toward endothelial cells, immunogenicity, and production of oxysterols, cytokines, and growth factors) (10,1 1), several

Decrease of serum paraoxonase activity in chronic renal failure.

The size of the elderly population has been increasing steadily for several years. Individuals in this age group often have several concomitant diseases that require treatment with multiple medications. These drugs, for various reasons and especially as a consequence of potential accumulation, may be associated with adverse reactions. Of the numerous factors that can favour the occurrence of these adverse drug reactions, the most important are the pathophysiological consequences of aging, particularly as these apply to the very old. Although absorption of drugs is not usually reduced in the elderly, diffusion, distribution and particularly elimination decline with age. Furthermore, while hepatic metabolic function is fairly normal, renal function is usually markedly depressed in very old individuals, and this can translate into clinical consequences if it is not taken into account. This is why, before administration of any drug in the elderly, evaluation of glomerular filtration rate is essential. Validated estimations such as those obtained from the classical Cockcroft-Gault formula or from more recent methodologies are required. In addition to reductions in various organ functions, factors connected with very old age such as frailty, falls, abnormal sensitivity to medications and polypathology, all of which tend to be more common in the last years of life, all directly impact on adverse drug reaction occurrence. Given these characteristics of the elderly population, the best way to reduce the prevalence of adverse drug reactions in this group is to limit drug prescription to essential medications, make sure that use of prescribed agents is clearly explained to the patient, give drugs for as short a period as possible, and periodically re-evaluate all use of drugs in the elderly.

Predicting and preventing adverse drug reactions in the very old.

Drug induced adverse effects are frequently encountered in geriatrics. Their occurrence can be limited by an adapted prescription. Potentially inappropriate medications are drugs with an unfavourable benefit to risk ratio when other safer or more efficient therapeutic alternatives are available. An expert consensus allowed us to establish a new list of potentially inappropriate medications for people aged 75 or over, taking into account French prescribing habits. The drugs or the drug-classes proposed in this list are, generally speaking, and when possible, to be avoided in the elderly, but can be prescribed at times, under special clinical conditions, provided that the benefit to risk ratio is assessed. The French list proposed here could be considered as (i) an epidemiological tool for evaluating the quality of drug prescription in geriatrics and as (ii) a prescription guide suggesting an alternative treatment whenever a therapeutic alarm is raised. This guide could be used both as a base for the education of prescribers and as a way of increasing patients awareness. This French list should be kept up-to-date so as to remain adapted to the evolution of the knowledge on the effect of drugs in the elderly and of the pharmaceutical market.

Louis Merle

Papers

Potentially inappropriate medications in the elderly: a French consensus panel list

Is inappropriate medication use a major cause of adverse drug reactions in the elderly

Decrease of serum paraoxonase activity in chronic renal failure.

Predicting and preventing adverse drug reactions in the very old.

Médicaments potentiellement inappropriés aux personnes âgées : intérêt d’une liste adaptée à la pratique médicale française