Publications

BACKGROUND

Agitation affects up to 70% of older people with dementia. Valproic acid derivatives have been used for the past 10 years to control agitation in dementia, but no systematic review of the effectiveness of this treatment has been published to date. A systematic review of 2004 examined three randomised, placebo-controlled trials of the effect of valproate therapy on older people with dementia who were agitated. The review was updated (October 2008) to include two additional studies.

OBJECTIVES

To determine whether evidence supports the use of valproate preparations in the treatment of agitation of people with dementia.

SEARCH STRATEGY

The Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (CDCIG), The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL and LILACS were searched on 7 February 2008 using the terms: valproic OR valproate OR divalproex* . The CDCIG Specialized Register contains records from all major health care databases (The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS) as well as from many trials databases and grey literature sources.

SELECTION CRITERIA

Randomized, placebo-controlled trials with concealed allocation where agitation and dementia of participants were assessed

DATA COLLECTION AND ANALYSIS

1. Two reviewers extracted data from published trials 2. Odds ratios of average differences were calculated 3. Only "intention to treat" analyses were included 4. Analysis compared participants treated with valproic acid with controls

MAIN RESULTS

Meta-analysis in 2004 of the pooled results was limited because of the following problems.In Porsteinsson 2001, although the physicians having direct responsibility for patient care were blinded, a non-blinded physician, who had no direct contact with these physicians, adjusted divalproex sodium dosage on the basis of reports from blinded raters and from confidential laboratory reports. Therefore, because the physician who controlled therapy knew which patients were receiving divalproex, the trial did not satisfy the criterion of concealed allocation.In Tariot 2001, 54% of the treated patients dropped out compared with 29% of control patients. Of all treated patients, 22% dropped out because of adverse effects, and the study had to be discontinued prematurely.The third trial (Sival 2002) had a cross-over design. No results from the first phase of the study were available, and although the statistical section stated, "the t-test for independent samples is used to analyse the two-period cross-over trial", because the samples were not independent - they are the same patients in the treatment and placebo groups - a question must be raised about the correctness of the analyses.The valproate preparation used in the trials varied - one used short-acting sodium valproate, one long-acting divalproex sodium, and the third early-onset acting divalproex sodium. Average doses differed (480 mg/d - 1000 mg/d), as did duration of therapy (3 weeks - 6 weeks), and ways of evaluating patients and their response to therapy.A limited meta-analysis, pooling the results concerning adverse effects (Porsteinsson 2001, Tariot 2001) revealed the following: sedation occurred more frequently in patients treated with valproic acid than in controls. Urinary tract infection was more common among patients treated with valproic acid than controls.An updated systematic review (October 2008) of two new studies (Tariot 2005, Herrmann 2007) applied meta-analysis to the effect of valproate on agitation in demented patients and also combined these studies with the earlier reports to examine adverse effects among valproate treated patients. Because the study of Herrmann et al involved a cross-over design, only those results from the first part of this study were included in the updated review.The new meta-analysis of pooled results showed no improvement of agitation among valproate treated patients, compared with controls, and showed an increase in adverse events (falls, infection, gastrointestinal disorders) among valproate treated patients.

AUTHORS' CONCLUSIONS

The updated review corroborates the earlier findings that valproate preparations are ineffective in treating agitation among demented patients, and that valproate therapy is associated with an unacceptable rate of adverse effects. More research on the use of valproate preparations for agitation of people with dementia is needed. On the basis of current evidence, valproate therapy cannot be recommended for management of agitation in dementia.

BACKGROUND

Delirium occurs in 30% of hospitalised patients and is associated with prolonged hospital stay and increased morbidity and mortality. The results of uncontrolled studies have been unclear, with some suggesting that benzodiazepines may be useful in controlling non-alcohol related delirium.

OBJECTIVES

To determine the effectiveness and incidence of adverse effects of benzodiazapines in the treatment of non-alcohol withdrawal related delirium.

SEARCH STRATEGY

The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 26 February 2008 using the search terms: (deliri* or confusion) and (benzo* or lorazepam," or "alprazolam" or "ativan" or diazepam or valium or chlordiazepam).The CDCIG Specialized Register contains records from major health databases (including MEDLINE, EMBASE, CINAHL, PsycINFO, CENTRAL, LILACS) as well as many ongoing trial databases and grey literature sources.

SELECTION CRITERIA

Trials had to be unconfounded, randomized and with concealed allocation of subjects. Additionally, selected trials had to have assessed patients pre- and post-treatment. Where crossover design was present, only data from the first part of the trial were to be examined.

DATA COLLECTION AND ANALYSIS

Two reviewers extracted data from included trials. Data were pooled where possible, and were to be analysed using appropriate statistical methods. Odd ratios or average differences were to be calculated. Only "intention to treat" data were to be included.

MAIN RESULTS

Only one trial satisfying the selection criteria could be identified. In this trial, comparing the effect of the benzodiazepine, lorazepam, with dexmedetomidine, a selective alpha-2-adrenergic receptor agonist, on delirium among mechanically ventilated intensive care unit patients, dexmedetomidine treatment was associated with an increased number of delirium- and coma-free days compared with lorazepam treated patients (dexmedetomidine patients, average seven days; lorazepam patients, average three days; P = 0.01). One partially controlled study showed no advantage of a benzodiazepine (alprazolam) compared with neuroleptics in treating agitation associated with delirium, and another partially controlled study showed decreased effectiveness of a benzodiazepine (lorazepam), and increased adverse effects, compared with neuroleptics (haloperidol, chlorpromazine) for the treatment of acute confusion.

AUTHORS' CONCLUSIONS

No adequately controlled trials could be found to support the use of benzodiazepines in the treatment of non-alcohol withdrawal related delirium among hospitalised patients, and at this time benzodiazepines cannot be recommended for the control of this condition. Because of the scarcity of trials with randomization of patients, placebo control, and adequate concealment of allocation of subjects, it is clear that further research is required to determine the role of benzodiazepines in the treatment of non-alcohol withdrawal related delirium.

BACKGROUND

Deathbed wills by their nature are susceptible to challenge. Clinicians are frequently invited to give expert opinion about a dying testator's testamentary capacity and/or vulnerability to undue influence either contemporaneously, when the will is made, or retrospectively upon a subsequent challenge, yet there is minimal discourse in this area to assist practice.

METHODS

The IPA Capacity Taskforce explored the issue of deathbed wills to provide clinicians with an approach to the assessment of testamentary capacity at the end of life. A systematic review searching PubMed and Medline using the terms: "deathbed and wills," "deathbed and testamentary capacity," and "dying and testamentary capacity" yielded one English-language paper. A search of the individual terms "testamentary capacity" and "deathbed" yielded one additional relevant paper. A focused selective review was conducted using these papers and related terms such as "delirium and palliative care." We present two cases to illustrate the key issues here.

RESULTS

Dying testators are vulnerable to delirium and other physical and psychological comorbidities. Delirium, highly prevalent amongst terminal patients and manifesting as either a hyperactive or hypoactive state, is commonly missed and poorly documented. Whether the person has testamentary capacity depends on whether they satisfy the Banks v Goodfellow legal criteria and whether they are free from undue influence. Regardless of the clinical diagnosis, the ultimate question is can the testator execute a specific will with due consideration to its complexity and the person's circumstances?

CONCLUSIONS

Dual ethical principles of promoting autonomy of older people with mental disorders whilst protecting them against abuse and exploitation are at stake here. To date, there has been scant discourse in the scientific literature regarding this issue.

BACKGROUND

As part of a broader effort aimed at improving hospital safety, a large coalition of employers, the Leapfrog Group, will soon require hospitals caring for their employees to meet volume standards for 5 high-risk surgical procedures. We estimated the potential benefits of full nationwide implementation of these volume standards. METHODS. Using data from Nationwide Inpatient Sample and other sources, we first estimated the total number of each of the 5 procedures-coronary-artery bypass graft, abdominal aortic aneurysm repair, coronary angioplasty, esophagectomy, and carotid endarterectomy-performed each year in hospitals in US metropolitan areas. (Leapfrog exempts hospitals in rural areas to avoid access issues.) We then projected the effectiveness of volume standards (in terms of relative risks of mortality) for each procedure using data from a published structured literature review.

RESULTS

With full implementation nationwide, the Leapfrog volume standards would save 2581 lives. Of the procedures, volume standards would save the most lives with coronary-artery bypass graft (1486), followed by abdominal aortic-aneurysm repair (464), coronary angioplasty (345), esophagectomy (168), and carotid endarterectomy (118). In our estimates of the number of lives saved, we considered assumptions about how many patients would be affected and the effectiveness of volume standards (ie, strength of underlying volume-outcome relationships with each procedure).

CONCLUSIONS

If the Leapfrog volume standards are successfully implemented, employers and health-care purchasers could prevent many surgical deaths by requiring hospital volume standards for high-risk procedures.

Background. Studies of medical admissions have questioned the validity of using claims data to adjust for preexisting medical conditions (comorbidities), but the impact of using comorbidities from claims data to risk-adjust mortality rates for high-risk surgery is not well characterized. The purpose of this study was to evaluate the relationship between comorbidities and mortality in administrative data in surgical populations and identify better risk-adjustment methods. Methods. Using the national Medicare database (1994-1997), we identified admissions for elective abdominal aortic aneurysm repair (140,577) and pancreaticoduodenectomy (10,530). We calculated the relative risk of mortality (adjusted for age, sex, race, and admission acuity) for 5 chronic conditions that are known (from clinical series) to increase the risk of postoperative mortality and are commonly used in claims-based risk-adjustment models. To explore the potential value of alternative risk-adjustment strategies, we examined relationships between surgical mortality and comorbidities using diagnosis codes identified from previous admissions. Results. Overall, in-hospital mortality for elective abdominal aortic aneurysm (AAA) repair and pancreaticoduodenectomy were 5.1% and 10.4%, respectively. For both procedures, 3 of the 5 comorbidities were associated with decreased risk of mortality: prior myocardial infarction (MI) [RR = 0.38; 95% confidence interval (CI), 0.33-0.43 for AAA; RR = 0.38; 95% CI, 0.21-0.69 for pancreaticoduodenectomy), malignancy (RR = 0.67; 95% CI, 0.59-0.76 for AAA; RR = 0.74; 95% CI, 0.45-1.21 for pancreaticoduodenectomy], and diabetes (RR = 0.76; 95% CI, 0.64-0.84 for AAA; RR = 0.59; 95% CI, 0.49-0.69 for pancreaticoduodenectomy). Using comorbidities identified from prior admissions increased the mortality risk estimates for prior MI (RR = 1.22; 95% CI, 1.08-1.38 for AAA; RR = 0.80; 95% CI, 0.49-1.30 for pancreaticoduodenectomy) and diabetes (RR = 1.41; 95% CI, 1.25-1.59 for AAA; RR = 0.94; 95% CI, 0.78-1.14 for pancreaticoduodenectomy). Conclusions. Because comorbidities coded on the index admission appear protective, incorporating them in risk-adjustment models for studies comparing surgical performance may penalize providers for taking care of sicker patients. When available, comorbidity information from prior hospitalizations may be more useful for risk adjustment.