Cardiorespiratory patterns in severe delirium tremens

To define the hemodynamic and oxygen metabolism patterns associated with severe delirium tremens, we examined cardiorespiratory variables in five patients over the 24 hours before (control), at the time of (delirium tremens), and during the 24 hours after resolution of (postresolution) delirium tremens. In comparing the delirium tremens period with the control period, significant increases were found in mean +/- SD cardiac index (4.9 +/- 1.7 L/min X sq m vs 3.6 +/- 0.7 L/min X sq m), left cardiac work index (6.4 +/- 2.4 kg X m/sq m vs 5.0 +/- 1.7 kg X m/sq m), oxygen delivery (681 +/- 204 mL/min X sq m vs 546 +/- 176 mL/min X sq m), and oxygen consumption (204 +/- 38 mL/min X sq m vs 165 +/- 16 mL/min X sq m). Values for the control and postresolution periods were not significantly different. These results demonstrate that a hyperdynamic cardiorespiratory state is present during delirium tremens; this increased cardiac output may be a compensatory hemodynamic response to increased oxidative metabolism that requires additional therapeutic support.     

Risk factors for delirium tremens development

OBJECTIVE: To identify clinical characteristics associated with inpatient development of delirium tremens so that future treatment efforts can focus on patients most likely to benefit from aggressive therapy. DESIGN: Retrospective cohort study among patients discharged with diagnoses related to alcohol abuse. SETTING: University-affiliated inner-city hospital. PATIENTS/PARTICIPANTS: Two hundred consecutive patients discharged between June 1991 and August 1992 who underwent evaluation and treatment for alcohol withdrawal or detoxification. MEASUREMENTS AND MAIN RESULTS: Mean age was 41.9 years, 85% were male, 57% were white and 84% were unmarried. Forty-eight (24%) of the patients developed delirium tremens during hospitalization. Bivariate analysis indicated that those who developed delirium tremens were more likely to be African-American, unemployed, and homeless, and were more likely to have gone more days since their last drink, and to have concurrent acute medical illness, high admission blood urea nitrogen level and respiratory rate, and low admission albumin level and systolic blood pressure. In multiple logistic regression analyses, patients who developed delirium tremens were more likely to have gone more days since their last drink (odds ratio [OR] 1.3; 95% confidence interval [CI] 1.09, 1.61) and to have concurrent acute medical illness (OR 5.1; 95% CI 2.07, 12.55). These risk factors were combined for assessment of their ability to predict the occurrence of delirium tremens. If no factors were present, 9% developed delirium tremens; if one factor was present, 25% developed delirium tremens; and if two factors were present, 54% developed delirium tremens. CONCLUSIONS: Inpatient development of delirium tremens was common among patients treated for alcohol detoxification or withdrawal and correlated with several readily available clinical variables.     

Delirium severity and psychomotor types: their relationship with outcomes after hip fracture repair

OBJECTIVES: To validate the Memorial Delirium Assessment Scale (MDAS) as a measure of delirium severity in a cohort of patients aged 65 and older; to examine the association between severity of delirium and patient outcomes; and to examine the association between psychomotor variants of delirium and each of those outcomes. DESIGN: Prospective assessment of sample. SETTING: Hospital. PARTICIPANTS: One hundred twenty-two older patients (mean age +/- standard deviation = 79 +/- 8) who had undergone acute hip fracture surgery. MEASUREMENTS: We used standardized instruments to assess prefracture activities of daily living (ADLs), ambulatory status, cognition, and living situation. Postoperatively, each patient was interviewed daily. Delirium was diagnosed using the Confusion Assessment Method (CAM), and delirium severity was measured using the MDAS. The MDAS was also used to categorize the psychomotor types of delirium into "purely hypoactive" or "any hyperactivity." Telephone or face-to-face interviews were conducted at 1 and 6 months to assess survival, ADL function, ambulatory status, and living situation. RESULTS: Of 122 patients, 40% developed CAM-defined delirium. Delirious patients had higher average MDAS scores than nondelirious patients (11.7 vs 2.4, P <.0001). We used the median of the average MDAS score to classify patients into mild or severe delirium. Severe delirium was generally associated with worse outcomes than was mild delirium, and the associations reached statistical significance for nursing home placement or death at 6 months (52% vs 17%, P =.009). Additionally, patients who did not meet full CAM criteria for delirium experienced worse outcomes if they had some symptoms of delirium than if they had no or few symptoms (nursing home placement or death at 6 months: 27% vs 0%, P =.001). Surprisingly, these patients with subsyndromal delirium who did not fulfill CAM criteria for delirium but demonstrated significant delirium symptoms, had outcomes similar to or worse than those with mild CAM-defined delirium. Pure hypoactive delirium accounted for 71% (34/48) of cases and was less severe than was delirium with any hyperactivity (average MDAS score 10.6 vs 14.8, P =.007). In our cohort, patients with pure hypoactive delirium had better outcomes than did those with any hyperactivity (nursing home placement or death at 1 month: 32% vs 79%, P =.003); this difference persisted after adjusting for severity. CONCLUSION: In this study of delirium in older hip fracture patients, the MDAS, a continuous severity measure, was a useful adjunct to the CAM, a dichotomous diagnostic measure. In patients with CAM-defined delirium, severe delirium was generally associated with worse outcomes than was mild delirium. In patients who did not fulfill CAM criteria, subsyndromal delirium was associated with worse outcomes than having few or no symptoms of delirium. Patients with subsyndromal delirium had outcomes similar to patients with mild delirium, suggesting that a dichotomous approach to diagnosis and management may be inappropriate. Pure hypoactive delirium was more common than delirium with any hyperactive features, tended to be milder, and was associated with better outcomes even after adjusting for severity. Future studies should confirm our preliminary associations and examine whether treatment to reduce the severity of delirium symptoms can improve outcomes after hip fracture repair.     

The Acute Alcohol Withdrawal Syndrome: Findings and Problems

The acute alcohol withdrawal syndrome includes a whole serifs of gastrointestinal, cardiovascular, autonomic, neurological and psychic symptoms. In this study delirium tremens is regarded as the most severe stage of the withdrawal syndrome. In a study of 184 alcoholics (112 with delirium tremens) in which 14 symptoms of the types mentioned above were considered, a general syndrome was identified which could be divided into somatic and psychic subsyndromes. There were significant differences in the percentages of patients with and without delirium tremens who developed particular symptoms. No significant differences were found, however, between those patients in which delirium tremens occurred following alcohol withdrawal and those in which it occurred without prior withdrawal. These findings are in agreement with clinical and experimental observations of the symptoms within the acute alcohol withdrawal syndrome while alcohol intake was still being increased. It is therefore assumed that the syndromes discussed are not dependent solely on alcohol withdrawal but rather are based on a general impairment in the mechanism for adaptation to alcohol.     

Delirium is a Strong Predictor of Mortality in Patients Receiving Non-invasive Positive Pressure Ventilation

Purpose

Non-invasive positive pressure ventilation (NIPPV) has gained popularity over the years in the treatment of acute respiratory failure (ARF). Preliminary evidence suggests that delirium is an important factor contributing to NIPPV failure and death. This study was conducted to evaluate delirium and other associated factors of deaths in patients with ARF requiring the use of NIPPV.

Methods

A prospective observational study was conducted in a specialised NIPPV unit. Consecutive patients admitted for ARF requiring NIPPV were assessed by a psychiatrist for presence of delirium using the Diagnostic and Statistical Manual Version IV (DSM-IV). APACHE II score, co-morbidities-, and lung function were also assessed. Patients were followed until their deaths for a minimum of 1 year. Univariate and multivariate Cox’s regression analyses were performed to explore predictive factors for death.

Results

A total of 153 subjects were recruited, 49 (32.0 %) of whom had delirium. On univariate analysis, higher APACHE II score, lower BMI, presence of delirium, higher Charlson’s co-morbidity index but not FEV₁ were associated with earlier death. On multivariate analysis, delirium (HR 4.4; 95 % CI 2.6–7.4; p < 0.001) and lower BMI (HR 0.92; 95 % CI 0.86–0.98; p = 0.013) were independently associated with earlier death within 1 year.

Conclusions

There is a high prevalence of delirium in patients requiring NIPPV. The presence of delirium is a strong predictor of mortality. There is strong need to identify and manage these high-risk patients to improve their mortality. The collaboration between psychiatrists and physicians should be strengthened.

     

Reducing delirium after hip fracture: a randomized trial

OBJECTIVES: Delirium (or acute confusional state) affects 35% to 65% of patients after hip-fracture repair, and has been independently associated with poor functional recovery. We performed a randomized trial in an orthopedic surgery service at an academic hospital to determine whether proactive geriatrics consultation can reduce delirium after hip fracture. DESIGN: Prospective, randomized, blinded. SETTING: Inpatient academic tertiary medical center. PARTICIPANTS: 126 consenting patients 65 and older (mean age 79 +/- 8 years, 79% women) admitted emergently for surgical repair of hip fracture. MEASUREMENTS: Detailed assessment through interviews with patients and designated proxies and review of medical records was performed at enrollment to ascertain prefracture status. Subjects were then randomized to proactive geriatrics consultation, which began preoperatively or within 24 hours of surgery, or "usual care." A geriatrician made daily visits for the duration of the hospitalization and made targeted recommendations based on a structured protocol. To ascertain study outcomes, all subjects underwent daily, blinded interviews for the duration of their hospitalization, including the Mini-Mental State Examination (MMSE), the Delirium Symptom Interview (DSI), and the Memorial Delirium Assessment Scale (MDAS). Delirium was diagnosed using the Confusion Assessment Method (CAM) algorithm. RESULTS: The 62 patients randomized to geriatrics consultation were not significantly different (P>.1) from the 64 usual-care patients in terms of age, gender, prefracture dementia, comorbidity, type of hip fracture, or type of surgical repair. Sixty-one percent of geriatrics consultation patients were seen preoperatively and all were seen within 24 hours postoperatively. A mean of 10 recommendations were made throughout the duration of the hospitalization, with 77% adherence by the orthopedics team. Delirium occurred in 20 /62 (32%) intervention patients, versus 32 / 64 (50%) usual-care patients (P =.04), representing a relative risk of 0.64 (95% confidence interval (CI) = 0.37-0.98) for the consultation group. One case of delirium was prevented for every 5.6 patients in the geriatrics consultation group. There was an even greater reduction in cases of severe delirium, occurring in 7/ 60 (12%) of intervention patients and 18 / 62 (29%) of usual-care patients, with a relative risk of 0.40 (95% CI = 0.18-0.89). Despite this reduction in delirium, length of stay did not significantly differ between intervention and usual-care groups (median +/- interquartile range = 5 +/- 2 days in both groups), likely because protocols and pathways predetermined length of stay. In subgroup analyses, geriatrics consultation was most effective in reducing delirium in patients without prefracture dementia or activities of daily living (ADL) functional impairment. CONCLUSIONS: Proactive geriatrics consultation was successfully implemented with good adherence after hip-fracture repair. Geriatrics consultation reduced delirium by over one-third, and reduced severe delirium by over one-half. Our trial provides strong preliminary evidence that proactive geriatrics consultation may play an important role in the acute hospital management of hip-fracture patients.     

A pilot exercise intervention to improve lower extremity functioning in peripheral arterial disease unaccompanied by intermittent claudication

PURPOSE: A pilot study was conducted to test the feasibility of supervised treadmill exercise training to improve functioning in study participants with peripheral arterial disease who did not have classical symptoms of intermittent claudication. METHODS: For this study, 32 men and women with peripheral arterial disease but no symptoms of claudication were randomized to exercise training or usual care. The intervention was a 12-week supervised treadmill walking program. Outcomes included 6-minute walk distance, maximum treadmill walking distance, and 4-meter walking velocity. Participant-reported community walking ability was measured with the Walking Impairment Questionnaire (WIQ). Inflammatory blood factor levels also were measured. RESULTS: Altogether, 25 participants who completed follow-up testing were included in intention-to-treat analyses. Of 24 participants (58%) randomized to exercise, 14 completed the entire exercise training program. The participants randomized to the intervention showed greater improvement in their WIQ walking speed score than the control subjects (P =.05). The participants randomized to the intervention showed improvements in their 6-minute walk distance (1134 +/- 347 vs 1266 +/- 295 feet; P =.03), maximal treadmill walking distance (389 +/- 248 vs 585 +/- 293 feet; P <.001), WIQ distance score (52.3 +/- 29.1 vs 63.1 +/- 25.1; P =.002), and WIQ speed score (48.7 +/- 26.8 vs 59.7 +/- 22.7; P =.008). The participants randomized to the control condition showed improvements in maximal treadmill walking distance (362 +/- 180 vs 513 +/- 237 feet; P =.014). There were no significant changes in the inflammatory blood factors after exercise. CONCLUSIONS: This pilot study demonstrated that a supervised treadmill walking program may be feasible and may improve functioning for individuals with peripheral arterial disease who do not have classical symptoms of intermittent claudication. Further study is needed with a larger sample to identify optimal exercise methods that improve lower extremity functioning in men and women with peripheral arterial disease who do not have intermittent claudication.     

Anticholinergic drug exposure at intensive care unit admission affects the occurrence of delirium. A prospective cohort study

BackgroundAnticholinergic drugs may increase the risk of delirium in non-critically ill patients, but it is unclear whether exposure to these drugs is also a risk factor for Intensive Care Unit (ICU) delirium. In this study the hypothesis was tested that anticholinergic drug exposure at ICU admission increases the risk to develop delirium during ICU stay, particularly in patients with advanced age and severe sepsis.MethodsA prospective cohort study was performed in the mixed 32-bed medical-surgical ICU of the University Medical Center Utrecht, the Netherlands in the period from January 2011 till June 2013. Included were nonneurological patients that were consecutively admitted for more than 24 hours. The presence of delirium was evaluated each day using a validated algorithm based on the Confusion Assessment Method for the ICU (CAM-ICU), the initiation of delirium treatment as well as chart review by researchers. Anticholinergic drug exposure at ICU admission was assessed using the Anticholinergic Drug Scale (ADS). To evaluate the association between anticholinergic drug exposure at ICU admission and the risk of developing delirium, we performed multivariable competing risk Cox proportional hazard analysis corrected for confounding factors.ResultsApproximately half (47%, n=513) of the 1090 included patients developed delirium during ICU admission. The absolute risk for delirium development increased with more anticholinergic drug exposure: 42% in patients with ADS score=0, 49% in patients with ADS score=1, and 53% in patients with ADS higher than 1. Taking competing events (death and discharge) and potential confounding factors into account, the subdistribution hazard ratio (SHR) was 1.13 (95% CI: 0.91-1.40) for ADS score=1 point and 1.35 (95% CI: 1.09-1.68) for ADS ≥2 compared with an ADS score=0 (no anticholinergic drug exposure). The effect was strongest during the first days of ICU admittance and was strongest in patients above 65 year without severe sepsis and/or septic shock (SHR 2.15, 95% CI 1.43-3.25).ConclusionsAnticholinergic drug exposure at ICU admission increases the risk of delirium in critically ill patients. This effect was most pronounced in patients older than 65 years without severe sepsis and/or septic shock, and declining over time.     

Genetic Association Between Alcohol Withdrawal Symptoms and Polymorphism of CCK Gene Promoter

In the central nervous system, cholecystokinin (CCK) is an important neurotransmitter that gives the influences on firings, anxiety, notiception, and dopamine-related behavior. CCK co-exists in the dopaminergic neurons, interacting with dopamine. In this study, we examined the genetic variant −45 C to T substitution of the CCK gene promoter region among 195 healthy Japanese and 174 patients with alcohol withdrawal syndrome (52 delirium tremens, 39 hallucinosis, 20 seizures, and 92 lack of these symptoms) by using polymerase chain reaction-based single-strand conformational polymorphism analysis. Patients with delirium tremens showed a significantly higher frequency of the variant, compared with the controls (X²= 4.91, p < 0.03), but patients with other symptoms showed no difference. These data suggested that the individuals possessing allelic mutation (−45T) in the promoter region of the CCK gene might be susceptible to delirium tremens caused by alcohol abuse.     

Qigong for hypertension: a systematic review of randomized clinical trials

OBJECTIVES: To assess systematically the clinical evidence of qigong for hypertension. METHODS: Databases were searched up to August 2006. All randomized clinical trials (RCTs) testing qigong in patients with hypertension of any origin and assessing clinically relevant outcomes were considered. Trials using any type of control intervention were included. The selection of studies, data extraction and quality assessment were performed independently by at least two reviewers. Methodological quality was evaluated using the Jadad score. RESULTS: A total of 121 potentially relevant articles were identified and 12 RCTs were included. Seven RCTs tested qigong in combination with antihypertensive drugs compared with antihypertensive drugs alone. The meta-analysis of two trials reporting adequate data suggested beneficial effects in favour of qigong [weighted mean difference, systolic blood pressure (SBP) -12.1 mmHg, 95% confidence interval (CI) -17.1 to -7.0; diastolic blood pressure -8.5 mmHg, 95% CI -12.6 to -4.4]. Qigong was compared with waiting list control in two RCTs and was found to reduce SBP significantly (weighted mean difference -18.5 mmHg, 95% CI -23.1 to -13.9). In three further RCTs the comparisons made were: qigong combined with conventional therapy versus muscle relaxation combined with conventional therapy; qigong as a sole treatment versus exercise. All reported positive results in at least some of the relevant outcome measures. The methodological quality of the studies was low. CONCLUSION: There is some encouraging evidence of qigong for lowering SBP, but the conclusiveness of these findings is limited. Rigorously designed trials are warranted to confirm these results.     

Successful Use of Propofol in Refractory Delirium Tremens

Alcohol withdrawal is a common problem encountered by emergency physicians, with delirium tremens (DT) as the extreme manifestation. DT is a true medical emergency. Although benzodiazepines are the mainstay of therapy, some patients require massive amounts to control their symptoms. We report the successful use of propofol for DT refractory to benzodiazepines in a 42-year-old alcoholic man. We briefly discuss alcohol withdrawal, as well as the pharmacokinetics and adverse affects of propofol. The use of propofol in treating DT refractory to benzodiazepines has previously not been reported. [Coomes TR, Smith SW: Successful use of propofol in refractory delirium tremens. Ann Emerg Med December 1997;30:825-828.]     

Do observational studies using propensity score methods agree with randomized trials? A systematic comparison of studies on acute coronary syndromes

Aims Randomized controlled trials (RCTs) are the gold standard for assessing the efficacy of therapeutic interventions because randomization protects from biases inherent in observational studies. Propensity score (PS) methods, proposed as a potential solution to confounding of the treatment-outcome association, are widely used in observational studies of therapeutic interventions for acute coronary syndromes (ACS). We aimed to systematically assess agreement between observational studies using PS methods and RCTs on therapeutic interventions for ACS. Methods and results We searched for observational studies of interventions for ACS that used PS methods to estimate treatment effects on short- or long-term mortality. Using a standardized algorithm, we matched observational studies to RCTs based on patients' characteristics, interventions, and outcomes ('topics'), and we compared estimates of treatment effect between the two designs. When multiple observational studies or RCTs were identified for the same topic, we performed a meta-analysis and used the summary relative risk for comparisons. We matched 21 observational studies investigating 17 distinct clinical topics to 63 RCTs (median = 3 RCTs per observational study) for short-term (7 topics) and long-term (10 topics) mortality. Estimates from PS analyses differed statistically significantly from randomized evidence in two instances; however, observational studies reported more extreme beneficial treatment effects compared with RCTs in 13 of 17 instances (P = 0.049). Sensitivity analyses limited to large RCTs, and using alternative meta-analysis models yielded similar results. Conclusion For the treatment of ACS, observational studies using PS methods produce treatment effect estimates that are of more extreme magnitude compared with those from RCTs, although the differences are rarely statistically significant.     

Why have meta‐analyses of randomized controlled trials of the association between non‐white‐blood‐cell‐reduced allogeneic blood transfusion and postoperative infection produced discordant results?

Intention-to-treat analyses of randomized controlled trials (RCTs) of the association between non-white-blood-cell (WBC)-reduced allogeneic blood transfusion (ABT) and postoperative infection were reported as the reason why meta-analyses of RCTs of this association have produced discordant results. We examined three possible reasons for disagreements between meta-analyses: (i) sources of medical heterogeneity and integration of RCTs despite extreme heterogeneity; (ii) reliance on as-treated (vs. intention-to-treat) comparisons; and (iii) inclusion (or not) of the three most recent RCTs. When nine RCTs reported up to 2002 were combined despite extreme heterogeneity, both intention-to-treat and as-treated comparisons found an association between non-WBC-reduced ABT and postoperative infection [summary odds ratio (OR) = 1.38, 95% confidence interval (CI) 1.03-1.85, P < 0.05; and summary OR = 1.56, 95% CI 1.06-2.31, P < 0.05, respectively]. When 12 RCTs reported up to 2005 were integrated despite extreme heterogeneity, both intention-to-treat and as-treated comparisons found no association of non-WBC-reduced ABT with postoperative infection (summary OR = 1.24, 95% CI 0.98-1.56, P > 0.05; and summary OR = 1.31, 95% CI 0.98-1.75, P > 0.05, respectively). In both analyses, the separate integration of four RCTs transfusing red blood cells (RBCs) or whole blood filtered after storage showed an association between non-WBC-reduced ABT and postoperative infection, whereas the separate integration of six (or nine) RCTs, reported through 2002 or 2005, and transfusing prestorage-filtered RBCs showed no association, whether intention-to-treat or as-treated comparisons were used. Thus, the published meta-analyses have produced discordant results because they did (or did not) investigate medical sources of heterogeneity and did (or did not) include the most recent RCTs. Intention-to-treat and as-treated comparisons produced concordant results.     

Viewing videotape of themselves while experiencing delirium tremens could reduce the relapse rate in alcohol-dependent patients

AIMS: The aim of this prospective randomized controlled study was to determine whether viewing videotape of themselves while experiencing delirium tremens (DT) reduces the relapse rate in alcohol-dependent patients. Our hypothesis about the efficacy of videotapes exposure to DT is consistent with a cognitive behavior model. DESIGN: Sixty patients with DT and a minimum of 3 years of severe alcohol dependence [Diagnostic and Statistical Manual version IV (DSM-IV criteria] were included in this study. Patients were videotaped during the acute phase of DT and randomized into two groups: group A patients received individual exposure to their videotape and an explanation of the symptoms by a psychiatrist; and control group B patients, who were without videotape experience. Both groups received the same treatment during the acute and the maintenance phases, without aversive therapy or psychotherapy. The two groups did not differ significantly in number of drinks per day prior to admission, age, marital status, social environment, education, professional and financial status or family psychiatric history. SETTING: An in-patient crisis unit for patients with alcohol dependence. MEASUREMENTS: All patients were observed for 6 months during monthly visits. Outcomes included relapse, drinking days per week and number of drinks per drinking day. All patients and their families signed informed consent. FINDINGS: The patients with videotape experience had a significantly lower relapse rate after the first month (0% versus 20%), 2 months (13.33% versus 46.67%) and 3 months (26.67% versus 53.33%). Patients with videotape experience had less severe relapses and consumed fewer units of alcohol than controls. CONCLUSIONS: Videotape exposure in delirium tremens is an original therapeutic method which seems to be effective in reducing relapse risk in patients with alcohol dependence.     

Quantifying the Severity of a Delirium Episode Throughout Hospitalization: the Combined Importance of Intensity and Duration

Background

The ability to determine which episodes of delirium are likely to lead to poor clinical outcomes has remained a major area of challenge.

Objective

To quantify delirium severity and course over an entire hospitalization using several measures, and to evaluate their predictive validity for 30- and 90-day outcomes post-discharge.

Design

Two prospective cohort studies.

Participants

Analysis was conducted in two independent cohorts of adult patients aged ≥70.

Main Measures

Nine delirium episode severity measures were examined: (1) measures reflecting delirium intensity (peak Confusion Assessment Method-Severity [CAM-S] and mean CAM-S score), (2) a measure reflecting delirium intensity and duration (sum of all CAM-S scores, sum of all CAM-S scores on delirium days only, peak CAM-S score x days with delirium), (3) measures requiring information on delirium duration and delirium at discharge (total number of delirium days, percentage of delirium days, delirium at discharge), and (4) a measure of cognitive change. Associations of the delirium episode severity measures with 30- and 90-day post-hospital outcomes (death, nursing home placement, and readmission) relevant to delirium were examined.

Key Results

The delirium episode severity measure that required information on both delirium intensity and duration (sum of all CAM-S scores) was the most strongly associated with 30- and 90-day post-hospital outcomes. Using this measure, the relative risk [95 % confidence interval] for death at 30-days increased across levels of sum of all CAM-S scores from 1.0 (referent) to 2.1 [0.8, 5.4] for ‘low,’ to 2.9 [1.2, 7.1] for ‘moderate,’ to 6.4 [2.9, 14.0] for ‘high’ (p for trend <.01).

Conclusions

The delirium episode severity measure that included both intensity and duration had the strongest association with important post-hospital outcomes.

     

Investigation of Quantitative Trait Loci in the CCKAR Gene With Susceptibility to Alcoholism

Background Cholecystokinin (CCK) plays an important role in the function of the central nervous system by interacting with dopamine and other neurotransmitters. We previously reported genetic variations in the promoter and coding regions of the CCKA receptor (CCKAR), CCKBR, and CCK genes and a possible association between polymorphisms of the CCKAR gene and alcoholism. In this study, association analyses were re-examined between the polymorphisms of the promoter region of the CCKAR gene and patients with alcohol withdrawal symptoms, in addition to patients with alcoholic liver injury.
Methods A total of 131 Japanese male patients with alcohol withdrawal symptoms, 70 Japanese patients with alcoholic liver injury, and 98 age-matched Japanese male controls (nonhabitual drinkers) were examined using polymerase chain reaction-based single strand conformational polymorphism and sequencing analyses.
Results Significant differences between patients with hallucination and controls were found in the allele frequencies at the −388 and −85 loci of the CCKAR gene ( p = 0.0095, p = 0.0087, respectively), but these differences were not significant after Bonferroni correction for multiple testing. In contrast, the frequency of the homozygous genotype −85 CC was significantly higher in hallucination-positive patients than in controls ( p = 0.0031) and in patients with hallucination accompanying delirium tremens than in controls ( p = 0.0022), and these differences were significant after Bonferroni correction.
Conclusions The data from the case control suggest that polymorphisms of the promoter region of the CCKAR gene do not play a major role in the pathogenesis of alcohol withdrawal symptoms or alcoholic liver injury. However, a significant association was found between polymorphism at the −85 locus of the CCKAR gene and patients with hallucination, and especially patients with hallucination accompanying delirium tremens.     

Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis

Heparin-induced thrombocytopenia (HIT) is an uncommon but potentially devastating complication of anticoagulation with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). Our objective was to determine and compare the incidences of HIT in surgical and medical patients receiving thromboprophylaxis with either UFH or LMWH. All relevant studies identified in the MEDLINE database (1984-2004), not limited by language, and from reference lists of key articles were evaluated. Randomized and nonrandomized controlled trials comparing prophylaxis with UFH and LMWH and measuring HIT or thrombocytopenia as outcomes were included. Two reviewers independently extracted data on thromboprophylaxis (type, dose, frequency, and duration), definition of thrombocytopenia, HIT assay, and rates of the following outcomes: HIT, thrombocytopenia, and thromboembolic events. HIT was defined as a decrease in platelets to less than 50% or to less than 100 x 10(9)/L and positive laboratory HIT assay. Fifteen studies (7287 patients) were eligible: 2 randomized controlled trials (RCTs) measuring HIT (1014 patients), 3 prospective studies (1464 patients) with nonrandomized comparison groups in which HIT was appropriately measured in both groups, and 10 RCTs (4809 patients) measuring thrombocytopenia but not HIT. Three analyses were performed using a random effects model and favored the use of LMWH: (1) RCTs measuring HIT showed an odds ratio (OR) of 0.10 (95% confidence interval [CI], 0.01-0.2; P = .03); (2) prospective studies measuring HIT showed an OR of 0.10 (95% CI, 0.03-0.33; P < .001); (3) all 15 studies measured thrombocytopenia. The OR was 0.47 (95% CI, 0.22-1.02; P = .06). The inverse variance-weighted average that determined the absolute risk for HIT with LMWH was 0.2%, and with UFH the risk was 2.6%. Most studies were of patients after orthopedic surgery.     

Effects of hypogonadism and testosterone administration on depression indices in HIV-infected men

Hypogonadism is prevalent among human immunodeficiency virus-infected men, in whom significantly reduced quality of life and mood disturbances have been reported. Previous studies have not investigated the relationship between depression score and gonadal function among such patients. We first compared depression scores in hypogonadal (n = 52) and eugonadal (n = 10) patients with acquired immunodeficiency syndrome (AIDS) wasting, matched for weight and disease status, and then investigated the effects of testosterone administration on depression score in a randomized, double-blind, placebo-controlled study among the group of hypogonadal men with AIDS wasting. The primary end point in all comparisons was the Beck Depression Inventory. Hypogonadal patients demonstrated significantly increased scores on the Beck inventory compared with eugonadal-, age-, weight-, and disease status-matched subjects (15.5+/-1.1 vs. 10.6+/-1.4 mean +/- SEM, P = 0.02). Among the combined hypogonadal and eugonadal subjects, a significant inverse correlation was seen between the Beck score and both free (r = 0.41, P<0.01) and total serum testosterone levels (r = -0.43, P<0.001). The relationship between the Beck score and testosterone levels remained highly significant, controlling for weight, viral load, CD4 count, and antidepressant use (P<0.01 for free testosterone, P<0.001 for total testosterone). Furthermore, when subjects were divided into two groups, based on a Beck score greater than 18 or less than or equal to 18, serum total and free testosterone levels were significantly lower in the subjects with a Beck score greater than 18, whereas there were no differences in weight, viral load, CD4 count, or Karnofsky status. End of study data were available in 39 patients who completed the randomized, placebo-controlled study. Beck score decreased significantly only in the subjects receiving testosterone (-5.8+/-1.3, P< 0.001), but not in subjects randomized to placebo (-2.7+/-1.3, P> 0.05). In a regression analysis, the change in Beck score was related significantly to change in weight (P<0.01). These data demonstrate increased depression score in association with hypogonadism in men with AIDS wasting, independent of weight, virologic status, and other disease factors. In such patients, administration of testosterone results in a significant improvement in depression inventory score. This effect may be a direct effect of testosterone or related to positive effects of testosterone on weight and/or other anthropometric indices. Additional studies are needed to assess the effects of testosterone on clinical depression indices in human immunodeficiency virus-infected patients.     

Compilation and meta-analysis of randomized placebo-controlled clinical trials on the prevention of respiratory tract infections in children using immunostimulants.

BACKGROUND: Several immunostimulants presume to prevent respiratory tract infections (RTIs) in children, but their efficacy is controversial. OBJECTIVES: To compile the findings of the randomized, placebo-controlled trials (RCTs) on the prevention of acute respiratory tract infections (ARTIs) in children using immunostimulants, and to perform a meta-analysis. DATA SOURCES: Medline, EMBASE databases, and register of Cochrane Acute Respiratory Infection Group. REVIEW METHODS: We searched all the references of immunostimulants and selected papers referring to RCTs on the prevention of ARTIs in children. Papers were rated according to Jadad's instrument. We abstracted the number of ARTIs, and a one-tailed probability value (p) was abstracted for each trial. Effect of medication was determined as weighted mean +/- SE of percent reduction of ARTIs regarding ARTIs of placebo groups as 100%. RESULTS: Four of five RCTs with Jadad's score > 3 showed significant reduction of ARTIs in immunostimulant groups. When only the trials reporting mean +/- SD and/or dispersion were considered (n = 16), the global weighted percent effect of immunostimulants showed a change of -42.64%, with 95% confidence intervals from -45.19% to -40.08%; i. e., the treated group presented about 60% of the mean number of ARTIs in the placebo group. CONCLUSIONS: According to this meta-analysis and RCTs with Jadad's score > 3, immunostimulants are an effective treatment for the prevention of ARTI. Further high-quality RCTs are required to demonstrate the effect and the size of the effect of each individual immunostimulant.     

Radioiodine therapy (RAI) for Graves' disease (GD) and the effect on ophthalmopathy: a systematic review

Background An association between radioiodine therapy (RAI) for Graves’ disease (GD) and the development or worsening of Graves’ ophthalmopathy (GO) is widely quoted but there has been no systematic review of the evidence. Aims We undertook a systematic review of randomized controlled trials (RCTs) to assess whether RAI for GD is associated with increased risk of ophthalmopathy compared with antithyroid drugs (ATDs) or surgery. We also assessed the efficacy of glucocorticoid prophylaxis in the prevention of occurrence or progression of ophthalmopathy, when used with RAI. Methods We identified RCTs regardless of language or publication status by searching six databases and trial registries. Dual, blinded data abstraction and quality assessment were undertaken. Random effects meta‐analyses were used to combine the study data. Ten RCTs involving 1136 patients permitted 13 comparisons. Two RCTs compared RAI with ATD. Two RCTs compared RAI with thyroidectomy. Four RCTs compared the use of adjunctive ATD with RAI vs. RAI. Five RCTs examined the use of glucocorticoid prophylaxis with RAI. Results RAI was associated with an increased risk of ophthalmopathy compared with ATD [relative risk (RR) 4·23; 95% confidence interval (CI): 2·04–8·77] but compared with thyroidectomy, there was no statistically significant increased risk (RR 1·59, 95% CI 0·89–2·81). The risk of severe GO was also increased with RAI compared with ATD (RR 4·35; 95% CI 1·28–14·73). Prednisolone prophylaxis for RAI was highly effective in preventing the progression of GO in patients with pre‐existing GO (RR 0·03; 95% CI 0·00–0·24). The use of adjunctive ATD with RAI was not associated with any significant benefit on the course of GO. Conclusion RAI for GD is associated with a small but definite increased risk of development or worsening of Graves’ ophthalmopathy compared with ATDs. Steroid prophylaxis is beneficial for patients with pre‐existing GO.