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Socio-economic disadvantage may make family life more difficult and impact on the adjustment of children cefuroxime 250mg mastercard treatment. Schooling calls for separation from mother (usually) and may trigger/reveal separation anxiety cefuroxime 500 mg online medications requiring central line. The overactive or poorly socialized child may be punished or ostracized cheap cefuroxime 250mg on line medicine on airplanes. Child abuse (physical purchase cefuroxime toronto treatment xerostomia, emotional and sexual) is not infrequent, and can have long-term deleterious effects on mental health. Mental illness or criminality of parents may lead to emotional neglect or periods of parental absence. While divorce is common and frequently leads to emotional trauma for the child, the experience of parental divorce is childhood is not an indicator of adult psychiatric or somatic disorder (Linberg & Wadsby, 2010). Bullying behaviors are distinct from other forms of aggressive behaviors. They are characterized by repeated hurtful actions between peers where a power imbalance exists, and being bullied is considered a significant stressful life experience. Bullying appears to be common, and is reported by 13% of children and adolescents during a school year world wide (Craig et al, 2009). Direct bullying (physical acts) is more common among boys and indirect bullying (exclusion and ostracism) is more common among girls. Genetic factors Genetic factors have been identified in many childhood psychiatric disorders. Separation anxiety, which is known to be influenced by environmental factors (including paternal absence), has significantly heritable components in large twin studies (Eley et al, 2003; Cronk et al, 2004). Attention Deficit/Hyperactivity Disorder is familial and highly heritable, and the disorder is being refined to identify phenotypes for use in the search for susceptibility genes (Thapar et al, 2006). Associations have been reported with variations in genes for the dopamine receptors 4 (DRD4) and 5 (DRD5) and a dopamine transporter (DAT1) (Collier et al, 2000). The most robust of these is the association between ADHD and a repeat within the coding region of DRD4 (Faraone et al, 2001). Twin studies report MZ concordance rates of 60-90% compared with DZ concordance of 5%, giving an estimated heritability of over 90% (Rutter et al, 1999). There is some evidence for a locus on chromosome 7 and another on chromosome 2, but multiple genes of small effect is the probable mechanism (Klauck, 2006). For the latest on the genetics of autism and Tourette syndrome, see State (2010). DNA is wrapped around histone proteins to form chromatin. The state (condensation) of the histones causes the DNA to be more tightly or loosely packed – resulting in regulation of access to particular genes, thereby influencing gene expression. Histones condensation is achieved by methylation, acetylation and other chemical changes, and may remain life-long [and in some circumstances, may be inherited]. Hoffmann and Spengler (2012) summarize, “(e)arly social life experiences become embedded in the circuitry of the developing brain and are associated with lifelong consequences”. A study (Wang et al, 2012) of the first two years of life found a range of individual variation in genome-wide methylation. It is also suggested that maltreatment of children may produce epigenetic changes which result in mental health and physical disorders later in life (Yang et al, 2013). These children may have significantly different methylation marks. Separation anxiety disorder In DSM-5, Separation anxiety disorders is listed under “Anxiety Disorders”. Separation anxiety in characterized by inappropriate or excessive anxiety which occurs when the child is separated from the people or home to which he/she has developed strong emotional attachment. It may be seen when children first begin to attend school, but may occur at other stages. There may be recurring distress at the anticipation of separation, or worry about losing the subject of attachment. There may be fear about being alone, refusal to sleep separate from the attachment figure, or nightmares about separation. There may be complaints of physical symptoms when separation is imminent. Separation anxiety is often managed by advice on parenting skills. Separation anxiety is difficult to distinguish from generalized anxiety in children (some regard these as synonymous terms). In the epidemiology study of Silva and Stanton (1997) separation anxiety was reported at 3. In a recent report (Keeton et al, 2009) generalized anxiety was reported at 10%, with a mean age of onset at 8. A combination of CBT and SSRI is recommended, with the continuation of medication for 1 year following remission of symptoms. A persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with function, as characterized by (1) and/or (2) 1) Inattention - six (or more) of the following symptoms of inattention have persisted for at least 6 months to a degree that is maladaptive and inconsistent with developmental level: a) often fails to give close attention to details or makes careless mistakes in schoolwork, work, or other activities b) often has difficulty sustaining attention in task or play activities c) often does not seem to listen when spoken to directly d) Often does not follow through on instructions and fails to finish schoolwork, chores or duties in the workplace e) often has difficulty organizing tasks and activities f) often avoid, dislikes, or is reluctant to engage in tasks that require sustained mental effort g) often loses things necessary for tasks or activities h) often easily distracted by extraneous stimuli i) often forgetful in daily activities 2) Hyperactivity and impulsivity - six (or more) of the following symptoms have persisted for at least 6 months to a degree that is maladaptive and inconsistent with developmental levels: a) often fidgets with hands or feet or squirms in seat b) often leaves seat in classroom or in other situations in which remaining seated is expected c) often runs about or climbs excessively in situations in which it is inappropriate d) often has difficulty playing or engaging in leisure activities quietly e) is often “on the go” or often acts as if “driven by a motor” f) often talks excessively g) often blurts out answer before questions have been completed h) often has difficulty awaiting turn i) often interrupts or intrudes on others B. Some hyperactive-impulsive or inattentive symptoms that caused impairment were present before age 7 years. Some impairment from the symptoms is present in two or more settings (school, work, home) D. There must be clear evidence of clinically significant impairment in social, academic or occupational functioning. These diagnostic criteria look simple but are actually difficult to use properly, and special training may be necessary. This diagnosis is frequently made incorrectly, often by teachers, parents or patients themselves. Cardinal features include inattention, hyperactivity, and impulsivity. The differential diagnosis includes age appropriate behaviour and a mismatch between parents and child (e. ADHD has recently been associated with obesity (Ptacek et al, 2010). This is somewhat counterintuitive as increased activity might be expected to cause weight loss. The explanation is unclear, but may involve impulsivity and eating habits. The prevalence is around 4% of primary school children, boys being three times more commonly affected than girls. An association between early attachment problems and ADHD is probable. A neuroimaging study (Adisetivo et al, 2013) which was careful to exclude children with co-morbid disorders reports that in pure ADHD (compared to healthy controls) showed abnormal grey and white matter changes in bilateral frontal and parietal lobes, insula, corpus callosum , and right external and internal capsules. Parents and teachers need to be educated about the disorder and involved in the designing and provision of management strategies. Where symptoms interfere with learning or social integration and family life, psychostimulants (methylphenidate and dexamphetamine) may be useful, as they enable children to participate in other aspects of management.
Genuine multiplex families are rare; ate narcolepsy in animal models cefuroxime 250 mg with mastercard medicine questions. Only Following up on this discovery buy cheapest cefuroxime and cefuroxime the treatment 2014, hypocretin 1-peptide 1% to 2% of first-degree relatives of narcolepsy patients (Orexin A) levels were measured in the cerebrospinal fluid ever develop narcolepsy-cataplexy (20 discount 250 mg cefuroxime with mastercard symptoms quitting tobacco,44 buy cheap cefuroxime on line medicine 93,78). Autosomal recessive occurrence better understanding and control of the disorder by the of narcolepsy in doberman pinschers and Labrador retrievers patient is achieved. In a recent survey by a patient group was subsequently discovered, and a colony of genetically organization (8), 94% of all patients reported using pharma- narcoleptic Dobermans and Labradors was established at cologic therapies, mostly stimulant medications. Polygraphic studies in narcoleptic dogs to the amphetamines (Table 131. The most important pharmacologic property gogic hallucinations may also exist in narcoleptic dogs, but of amphetamine-like stimulants is to release catecholamines, are impossible to document owing to their subjective nature. Linkage analysis with various genetic mark- macologic effects varies from one amphetamine derivative ers, including minisatellite probes and functional candidate to another (73). After 10 years of chromosome walking in dogs, modafinil (103). The widespread misuse of methamphetamine had led to severe legal restriction on its manufacture, sale; and prescription in many countries (112). Note that the molecular weight of this compound is about half that of d- and l-amphetamine; thus, methamphetamine contains twice as much active molecules as d- or l-amphetamine per mg dose. Of importance is the report that in animals, amphetamine- amine, and methamphetamine) are then used if needed. Some patients prefer to use high doses of dards of Practice publication (9). Typically, the patient is long-acting, slow-release preparations to stay awake all day started at a low dose, which is then increased progressively long, whereas others combine lower doses and short half-life to obtain satisfactory results (Table 131. Minor jectively, but that sleep variables are never completely nor- side effects such as headaches, irritability, nervousness, malized by stimulant treatment (92). Low efficacy com- tremors, anorexia, palpitations, sweating, and gastric dis- pounds/milder stimulants (e. Cardiovascular impact pemoline) are usually tried first. More effective amphet- such as increased blood pressure is possible considering es- amine-like stimulants (i. The simple Surprisingly, tolerance rarely occurs in this patient popula- chlorate to sulfate formulation difference largely explains tion and 'drug holidays' are not recommended by the the higher potency of methamphetamine. Rather, a slight Yoss and Daly introduced methylphenidate for the treat- increase in dosage is preferable. Exceptionally, psychotic ment of narcolepsy almost 50 years ago (160). It is now complications are observed, most often when the medica- the most commonly prescribed stimulant medication in the tions are used at high doses and chronically disrupt noctur- United States, with 46% of narcoleptic patients using the nal sleep. Part of its popularity is Amphetamine was first used to treat narcolepsy in 1935 owing to its relatively short duration of action (approxi- (120), only 8 years after Alles initially synthesized it (5). This property allows narcoleptic pa- Both the l- and d-isomers have been used for the treatment tients to use the compound on an as-needed basis while of narcolepsy, either in isolation or as a racemic mixture keeping open the possibility of napping. The d-isomer is a slightly also reported to produce fewer psychotic complications at more potent stimulant (113,115) and is most generally high doses (116). L-Amphetamine is occasionally used in some Euro- less frequently used. D-Amphet- Pemoline is generally better tolerated than methamphet- amine is the second most frequently prescribed narcolepsy amine or d-amphetamine but it is also less efficacious and treatment after methylphenidate (8). It is well absorbed by less potent, and occasionally produces liver toxicity. After the gastrointestinal tract and partially metabolized in the taking a therapeutic dose of pemoline (40 mg), peak levels liver using aromatic and aliphatic hydroxylation. The half-life is cess yields parahydroxyamphetamine and norephedrine, re- 16 to 18 hours. Pemoline is partially metabolized by the spectively, both of which are biologically active (158). Metabolites include pemoline conjugates, pemoline phetamine is metabolized into benzoic acid (23%), which dine, and mandelic acid. After oral administration of 40 is subsequently converted to hippuric acid or parahydroxy- mg of pemoline, 35% to 50% of the dose is excreted in the amphetamine (2%). This in turn is converted to parahy- urine within 32 hours, and only a minor fraction is present droxynorephedrine (. Thirty-three percent of the oral as metabolites (41). The long duration of action of pemoline dose is excreted unchanged in the urine. Importantly, uri- may be associated with a better compliance in narcoleptic nary excretion of amphetamine and many amphetamine- patients (130). Pemoline most selectively blocks dopamine like stimulants is greatly influenced by urinary pH. Amphet- reuptake and only weakly stimulates dopamine release. Pemoline should not be prescribed to patients sorbed in the renal tubules. Acidifying the urine thus favors with impaired hepatic function, and hepatic function the excretion of the charged form of the amine (16), in- should be carefully monitored during chronic drug adminis- creases urinary excretion versus liver catabolism, and reduces tration. The recent introduction of modafinil, a novel wake- the half-life. Finally, dextroamphetamine is available as a sulfate-base mine, but it also blocks dopamine and norepinephrine reup- derivative or as spansule (slow-release) capsules. Mazindol is effective for both Methamphetamine is the most efficacious and most po- excessive daytime sleepiness and cataplexy (58). This compound is is absorbed quantitatively at a medium rate from the gastro- extremely useful in subjects with severe sleepiness who need intestinal tract, and the peak blood concentration is reached high doses. The addition of a methyl group makes this deriv- after 2 to 4hours. The wide- spread misuse of methamphetamine has led to severe legal Modafinil and Other Wake-Promoting restriction on its manufacture, sale, and prescription in Agents many countries (112), but it is available in the United States. It should also be noted that the molecular weight Modafinil, a compound structurally distinct from ampheta- of the most commonly used form of methamphetamine mines, has recently been approved in the United States for (hydrochloride) is about half that of d- and l-amphetamine the treatment of narcolepsy and essential hypersomnia. Methamphetamine preparations thus contain compound is also increasingly explored to treat other condi- twice as many active amphetamine molecules when com- tions, such as residual sleepiness in treated obstructive sleep 1912 Neuropsychopharmacology: The Fifth Generation of Progress apnea or fatigue in multiple sclerosis. Third, data obtained to date available in France since 1986, and long-term follow-up suggest that tolerance and dependence are limited with this suggests no remarkable side-effect profile and low abuse compound (15), although a recent animal study reports a potential.
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Legal system involvement health services reform on clinical practice in the United Kingdom buy cefuroxime australia medicines. How transfer payments are treated in the state hospital in the care and treatment of older adults: state cost-effectiveness and cost-benefit analyses generic cefuroxime 250mg otc treatment 1860 neurological. Balancing the interests of the state and the local commu- for mental health order cefuroxime 250 mg with amex symptoms ulcerative colitis. Administration and Policy in Mental Health 1995;23: 36 buy 500mg cefuroxime with mastercard medications in mothers milk. Managed behavioral health care: Current realities analysis approach. Int J Psychiatry Clinical Pract 1998;2: and future potential. Quality of care in mental health: the case of schizo- 14. Cost-effectiveness in search Triangle Park, NC: Research Triangle Institute, 1981. Cost-effectiveness of clo- Research Triangle Park, NC: Research Triangle Institute, 1984. The economic costs of alcohol Gen Psychiatry 1999;56:565–572. Rockville, MD: National Institute of Mental Health, clozapine compared to conventional antipsychotic medication for 1990. J Clin Psychiatry improve treatment of depression in primary care. Cost-effectiveness of related to treatment with clozapine. Hosp Community Psychiatry treatments for major depression in primary care practice. Alternative projections of mortality and effectiveness (letter). Am ethics and validity of disability adjusted life years. Weighing disability when measuring tiveness for patients in state hospitals: results from a randomized health and ruling on 'compassionate' murder. Suicidal behavior in ity among state hospital patients. A comparison of clozapine Psychiatry 1999;156:1590–1595. Clinical trials in psychiatry: should protocol devia- 50. The CE plane: a graphic representation of cost-effec- tion censor patient data? Psychopharmacol Bull 1998;34: of statistical analysis. Strangers in the night: research and managed mental 71. Health status and health and functioning as a cost-effectiveness measure for olanzapine care costs for publicly funded patients with schizophrenia started versus haloperidol treatment of schizophrenia. Olanzapine compared of clozapine therapy for severe psychosis. Psychiatr Serv 1998;49: with chlorpromazine in treatment-resistant schizophrenia. Acta Psychiatr Scand 1995; clinical decision analysis model for schizophrenia. Olanzapine: a pharmacoeconomic review of ine treatment in the outpatient clinic: service utilization and cost its use in schizophrenia. Cost effectiveness of clozapine patient outcomes with use of risperidone in a public mental health in neuroleptic-resistant schizophrenia. Savings in hospital bed-days timore: Johns Hopkins University Press, 1992. MELTZER ATYPICAL ANTIPSYCHOTIC DRUGS: kinsonism, and akathisia, and, after chronic use, tardive dys- WHAT IS TO BE EXPLAINED kinesia or dystonia (see Chapter 56) as a direct or indirect result of blockade of D2 receptors in the dorsal striatum, in vulnerable individuals. The immediate cause of acute and The designation of chlorpromazine, and subsequently halo- subacute EPSs is considered to be blockade of the dopami- peridol, thioridazine, loxapine, thiothixene, molindone, pi- nergic inhibition of striatal cholinergic neurons, leading to mozide, and related compounds as antipsychotic drugs (1) increased cholinergic activity in the basal ganglia (2). Subse- reflects their predominant action in humans, namely the quently, clozapine was found to achieve an antipsychotic suppression of auditory hallucinations and delusions, in effect without causing EPSs, whereas loxapine, a clozapine some, but not all, individuals with diagnoses of schizophre- congener, was equipotent in producing its antipsychotic ac- nia as well as other psychoses. These drugs are also called tion and EPS in humans and laboratory animals (10). This neuroleptics because they caused catalepsy in rodents and led Hippius and Angst to describe clozapine as an atypical extrapyramidal side effects (EPSs) in humans (2). Preclinical scientists almost invaria- ity to diminish psychotic symptoms was convincingly bly refer to clozapine and other drugs that have antipsy- shown to be initiated by blockade of dopamine (DA) D2 chotic properties and low EPSs as atypical antipsychotics receptors in mesolimbic nuclei, especially the nucleus ac- but, as will be discussed, clinical investigators do not univer- cumbens, stria terminalis, and the extended amygdala sally accept this designation. The subsequent evidence that clozapine, compared (6). This so-called depolarization block was suggested to be to neuroleptic drugs such as haloperidol, had at least six the reason for the slow onset of antipsychotic action, which advantages in addition to producing significantly less EPS is observed in some, but not all, psychotic patients. The and tardive dyskinesia, has attracted enormous interest to development of depolarization block following subchronic clozapine and other subsequently developed atypical anti- haloperidol treatment has been challenged by Melis et al. These six effects of clozapine, not all of (7) on the basis of microdialysis studies of DA release in which are fully shared with other atypical antipsychotic the nigrostriatal system, but those findings have been sug- drugs, are (a) absence of tardive dyskinesia; (b) lack of serum gested by Moore et al. Meltzer: Bixler Professor of Psychiatry and Pharmacology, ophrenia who fail to respond to typical neuroleptic drug; Vanderbilt University School of Medicine, Nashville, Tennessee. Thus, in patients with schizophrenia, especially secondary memory this chapter continues to use the term atypical to designate and semantic memory (verbal fluency) (9,11,13). These collective advantages of clozapine led to the ing some of the other highly valued advantages of these search for the mechanism(s) involved in these effects and agents, as well as their unique side effects. This chapter reviews the classified as atypical, by consensus, are, in order of their major hypotheses, which are based on the pharmacologic introduction, risperidone, olanzapine, sertindole, quetia- profiles of the numerous classes of agents with atypical prop- pine, and ziprasidone. Melperone, a butyrophenone, intro- erties as well as current theories of the action of drugs effec- duced at about the same time as clozapine, has also been tive in animal models of psychosis, but not yet adequately suggested to be an atypical antipsychotic drug because of tested in humans, e. Zotepine and amisulpride, both of which are for the D1, D2, D3, D4, 5-HT , 5-HT , 5-HT ,5- 1A 1D 2A widely used antipsychotic drugs in Europe, are also some- HT , 5-HT , 5-HT , , ,H, and muscarinic M1 2C 6 7 1 2 1 times grouped with the atypical antipsychotic drugs (9,10). Of these, the greatest interest is in the role of With the exception of aripiprazole, a partial DA agonist D2, D4, 5-HT , 5-HT , 5-HT , , and receptors. There are a very large number of drugs in development as antipsychotics that have the property of being active in ROLE OF D2 RECEPTORS various animal models that predict antipsychotic action, e.
A further criticism of the existing classification of CKD has been the suggestion that loss of GFR is a feature of ageing and that many people classified as stage 3 CKD are merely exhibiting a normal ageing process 500mg cefuroxime with amex medications ok for dogs. The effects of normal ageing on renal function are controversial order cefuroxime us lb 95 medications. Data from some studies suggest that the decline in GFR with increasing age may be largely attributable to comorbidities such as hypertension and heart failure order cefuroxime 500 mg treatment diffusion. Loss of renal function may not generic 250 mg cefuroxime with mastercard symptoms irritable bowel syndrome, therefore, be an inevitable consequence of ageing. However, controversy over what constitutes normality in the group with the highest prevalence of CKD makes defining what constitutes progression even more difficult. Consideration must also be given to the inherent biological and analytical variation associated with estimation of GFR from serum creatinine measurements. The power of this study was undermined by a high drop-out rate in the macro- albuminuria, impaired renal function, and haematuria groups, although the authors noted that the baseline characteristics of those who were lost to follow-up were NS different from subjects who completed follow-up. GFR was measured by iothalamate clearance in 365 potential living kidney donors163 or by inulin clearance in 141 healthy subjects who had a nephrectomy. This was evident in the lower GFR values in apparently healthy people (mean GFR=111 ml/min/1. As this was a retrospective analysis of medical records, there was no detail on how often GFR was measured. The cross-sectional Biomedical Nijmegen Study measured eGFR (MDRD) in apparently healthy men and women (N=3732) and in men and women with comorbid conditions (N=2365). Limitations of this study included: q a questionnaire, rather than a clinical examination, was used to assess the health of participants q GFR was estimated with the MDRD equation and creatinine was measured only once q the GFR decline was inferred from cross-sectional data, rather than from a longitudinal follow-up. The younger and older healthy subjects were matched for body weight. This study was limited by the small sample size and it did not address rate of GFR decline. In the first study,166 the decline in creatinine clearance with increasing age was assessed in healthy males (N=548). In a follow-up study,158 the decline in creatinine clearance over time in healthy males (N=254) was compared with creatinine clearance decline in men with renal/urinary tract disease (N=118) or 74 6 Defining progression of CKD with hypertensive/oedematous disorders (N = 74). The effect of increasing blood pressure on creatinine clearance was also examined. An observational study (N=10,184, mean age 76 years, 2 years follow-up) examined GFR decline over time in older (>66 years old) males and females stratified by GFR. The decline in GFR in diabetics was compared with non-diabetics. Regression analysis of GFR normalised to body surface area was significant for age (p<0. After age 60, creatinine clearance declined steeply. This data suggests that macroalbuminuria is a better predictor of GFR decline than low baseline GFR. Renal function decreased more rapidly as mean arterial pressure (MAP) increased. Mean GFR was NS different between older healthy and older hypertensive people. Few participants in this older cohort experienced a rapid progression of CKD (decline in GFR >15 ml/min/1. Mean GFR (inulin clearance) was significantly lower in older people with heart failure (92 ml/min/1. The longitudinal studies contained mixed populations in that not all participants were followed up for the full duration of the study. The lower kidney function described in one study of older people may be due to unrecognised kidney disease. Nevertheless it was recommended that the interpretation of GFR measurements should not normally be affected by the age of the person and that a low value should prompt the same response regardless of age. The GDG agreed that a decline in GFR of more than 2 ml/min/1. The GDG recommended that, when interpreting the rate of decline of eGFR, it was also necessary to consider the baseline level of kidney function and the likelihood that kidney function would reach a level where renal replacement therapy would be needed if the rate of decline was maintained. When assessing the rate of decline in eGFR, the GDG agreed that a minimum of 3 measurements in not less than 90 days was required (depending on the initial level of eGFR). If a large and unexplained fall in GFR was observed, more frequent monitoring would be needed. Changes in GFR must be interpreted in light of the evidence on biological and assay variability in serum creatinine measurements, which is estimated at 5%. A calculation based on this would suggest that a decline in eGFR of 10 ml/min/1. However, given that a decline in eGFR of more than 2 ml/min/1. The list of possible factors associated with progression does not consider how differences in access to healthcare and poverty may influence the initiation and progression of CKD. Specifically, neither early life influences governing foetal development and low birth weight nor childhood factors contributing to the emergence of hypertension and diabetes are considered here. In those that do progress, the subsequent mortality and morbidity risks rise exponentially, as do the associated healthcare costs. A reduced GFR is also associated with a wide range of complications such as hypertension, anaemia, renal bone disease, malnutrition, neuropathy and reduced quality of life. It is therefore important to clarify exactly what factors are associated with CKD progression, and which are remediable or potentially modifiable, in order to intervene at the earliest possible stage and improve the associated adverse outcomes. The literature was reviewed to examine additional promoters of renal disease progression: cardiovascular disease, acute kidney injury, obesity, smoking, urinary tract obstruction, ethnicity, and chronic use of non-steroidal anti-inflammatory drugs (NSAIDs). There were no studies examining acute kidney injury or urinary tract obstruction on progression of CKD. In a pooled analysis of the ARIC Study and Cardiovascular Health Studies (CHS), kidney function decline (serum creatinine increase ≥0. A diabetic cohort of smokers (N=44, mean age 47 years, 86% had baseline proteinuria >0. Progression to ESRD was compared between males who smoked for 0–5 pack-years (N=73), 5–15 pack years (N=28), or >15 pack years (N=43). It was difficult to determine whether these participants had CKD at baseline. One small, open-label RCT compared changes in creatinine clearance and adverse events with chronic use of ibuprofen, piroxicam, or sulindac in adults aged over 65 years with (CrCl <70 ml/min, N=15) or without renal insufficiency (CrCl >70 ml/min, N=14) 177. In two Spanish case control studies, cases (people who had progressed to ESRD, N=520) were age-, sex- and hospital-matched with controls (hospital patients who had not progressed to ESRD, N=982) and the effects of chronic use of salicylates, pyrazolones and non-aspirin NSAIDs on progression to ESRD were analysed. This relationship persisted after adjustment for diabetes type or control, retinopathy, age, BMI, ACEI use, BP, proteinuria. Proteinuria increased in both smokers and non-smokers, but there were NS differences between the two groups. When ACEI use was taken into account, the association between smoking and progression to ESRD was NS.