Efficacy of Non-Pharmacological Interventions to Prevent and Treat Delirium in Older Patients: A Systematic Overview. The SENATOR project ONTOP Series

Background

Non-pharmacological intervention (e.g. multidisciplinary interventions, music therapy, bright light therapy, educational interventions etc.) are alternative interventions that can be used in older subjects. There are plenty reviews of non-pharmacological interventions for the prevention and treatment of delirium in older patients and clinicians need a synthesized, methodologically sound document for their decision making.

Methods and Findings

We performed a systematic overview of systematic reviews (SRs) of comparative studies concerning non-pharmacological intervention to treat or prevent delirium in older patients. The PubMed, Cochrane Database of Systematic Reviews, EMBASE, CINHAL, and PsychINFO (April 28th, 2014) were searched for relevant articles. AMSTAR was used to assess the quality of the SRs. The GRADE approach was used to assess the quality of primary studies. The elements of the multicomponent interventions were identified and compared among different studies to explore the possibility of performing a meta-analysis. Risk ratios were estimated using a random-effects model. Twenty-four SRs with 31 primary studies satisfied the inclusion criteria. Based on the AMSTAR criteria twelve reviews resulted of moderate quality and three resulted of high quality. Overall, multicomponent non-pharmacological interventions significantly reduced the incidence of delirium in surgical wards [2 randomized trials (RCTs): relative risk (RR) 0.71, 95% Confidence Interval (CI) 0.59 to 0.86, I²=0%; (GRADE evidence: moderate)] and in medical wards [2 CCTs: RR 0.65, 95%CI 0.49 to 0.86, I²=0%; (GRADE evidence: moderate)]. There is no evidence supporting the efficacy of non-pharmacological interventions to prevent delirium in low risk populations (i.e. low rate of delirium in the control group)[1 RCT: RR 1.75, 95%CI 0.50 to 6.10 (GRADE evidence: very low)]. For patients who have developed delirium, the available evidence does not support the efficacy of multicomponent non-pharmacological interventions to treat delirium. Among single component interventions only staff education, reorientation protocol (GRADE evidence: very low)] and Geriatric Risk Assessment MedGuide software [hazard ratio 0.42, 95%CI 0.35 to 0.52, (GRADE evidence: moderate)] resulted effective in preventing delirium.

Conclusions

In older patients multi-component non-pharmacological interventions as well as some single-components intervention were effective in preventing delirium but not to treat delirium.     

Effectiveness of intrapartum penicillin prophylaxis in preventing early-onset group B streptococcal infection: results of a meta-analysis.

OBJECTIVE: To determine the effectiveness of intrapartum penicillin prophylaxis in preventing early-onset group B streptococcal (GBS) infection in neonates of women whose birth canals are colonized by group B streptococci. DATA SOURCES: Articles published between 1966 and 1992 identified from MEDLINE, EMBASE, the Science Citation Index and the Oxford Perinatal Database; the bibliographies of primary studies, textbooks and review articles and published abstracts from major conferences and symposia. DATA SELECTION: Studies were selected if four criteria were met: (a) the target population was intrapartum women and neonates, (b) the intervention was penicillin prophylaxis, (c) invasive early-onset GBS infection was an outcome measure, and (d) the studies were controlled trials or cohort studies. Seven primary studies were identified, four of which were randomized controlled trials. DATA EXTRACTION: Explicit methodologic criteria were used by two of the authors to assess independently the study quality; one of the reviewers was blind as to author, institution and journal. The baseline characteristics of the population, intervention and outcome were summarized twice and checked for accuracy by two of the authors. DATA SYNTHESIS: Five of the studies showed a trend toward a beneficial effect of penicillin prophylaxis, and two showed a statistically significant effect. The pooled odds ratio indicated a 30-fold reduction (95% confidence interval 0.0013 to 0.17) in the incidence of early-onset GBS infection with intrapartum penicillin prophylaxis. Subgroup analyses did not change these results. The magnitude of improvement observed did not differ between women with prenatal risk factors (premature rupture of the membranes and premature labour) and those without these risk factors. CONCLUSIONS: There is accumulative evidence that intrapartum penicillin prophylaxis is effective in preventing early-onset GBS infection. Such therapy is beneficial to women whose birth canals are colonized with group B streptococci. Further studies are needed to determine the optimum timing and method of detecting vaginal colonization during pregnancy.     

Outcomes of a Geriatric Liaison Intervention to Prevent the Development of Postoperative Delirium in Frail Elderly Cancer Patients: Report on a Multicentre,Randomized, Controlled Trial

Background

Delirium is a serious and common postoperative complication, especially in frail elderly patients. The aim of this study was to evaluate the effect of a geriatric liaison intervention in comparison with standard care on the incidence of postoperative delirium in frail elderly cancer patients treated with an elective surgical procedure for a solid tumour.

Methods

Patients over 65 years of age who were undergoing elective surgery for a solid tumour were recruited to a multicentre, prospective, randomized, controlled trial. The patients were randomized to standard treatment versus a geriatric liaison intervention. The intervention consisted of a preoperative geriatric consultation, an individual treatment plan targeted at risk factors for delirium, daily visits by a geriatric nurse during the hospital stay and advice on managing any problems encountered. The primary outcome was the incidence of postoperative delirium. The secondary outcome measures were the severity of delirium, length of hospital stay, complications, mortality, care dependency, quality of life, return to an independent preoperative living situation and additional care at home.

Results

In total, the data of 260 patients were analysed. Delirium occurred in 31 patients (11.9%), and there was no significant difference between the incidence of delirium in the intervention group and the usual-care group (9.4% vs. 14.3%, OR: 0.63, 95% CI: 0.29–1.35).

Conclusions

Within this study, a geriatric liaison intervention based on frailty for the prevention of postoperative delirium in frail elderly cancer patients undergoing elective surgery for a solid tumour has not proven to be effective.

Trial Registration

Nederlands Trial Register Trial ID NTR 823     

Tuberculosis Vaccines and Prevention of Infection

SUMMARY

Tuberculosis (TB) is a leading cause of death worldwide despite the availability of effective chemotherapy for over 60 years. Although Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination protects against active TB disease in some populations, its efficacy is suboptimal. Development of an effective TB vaccine is a top global priority that has been hampered by an incomplete understanding of protective immunity to TB. Thus far, preventing TB disease, rather than infection, has been the primary target for vaccine development. Several areas of research highlight the importance of including preinfection vaccines in the development pipeline. First, epidemiology and mathematical modeling studies indicate that a preinfection vaccine would have a high population-level impact for control of TB disease. Second, immunology studies support the rationale for targeting prevention of infection, with evidence that host responses may be more effective during acute infection than during chronic infection. Third, natural history studies indicate that resistance to TB infection occurs in a small percentage of the population. Fourth, case-control studies of BCG indicate that it may provide protection from infection. Fifth, prevention-of-infection trials would have smaller sample sizes and a shorter duration than disease prevention trials and would enable opportunities to search for correlates of immunity as well as serve as a criterion for selecting a vaccine product for testing in a larger TB disease prevention trial. Together, these points support expanding the focus of TB vaccine development efforts to include prevention of infection as a primary goal along with vaccines or other interventions that reduce the rate of transmission and reactivation.     

Hospital costs associated with delirium in older medical patients

Introduction

Delirium is a common and serious complication in older patients, associated with increased, potentially preventable, morbidity and mortality. The aim of this study was to evaluate the associated costs of delirium during hospitalization in a university affiliated hospital in Chile.

Materials and methods

Prospective cohort study of consecutive patients 65 years and older, admitted to a medical ward. A psychogeriatric team assessed patients during the first and every 48 h until discharge using the Confusion Assessment Method (CAM-S), length of hospital stay, pharmacy and total hospitalization costs were analyzed. Statistical analysis was performed using bivariate and multivariate analysis according to delirium diagnosis.

Results

Data from 454 patients was analyzed, 160 of them in a delirium cohort (35.2%) and 294 in a non-delirium cohort (64.8%). The delirium cohort had a longer hospital stay (DATA) and higher mortality (7.0% versus 1.7%). The median of total costs of delirium during hospital stay was 38.7% higher than the non-delirium cohort (P < .001). Total costs were significantly higher in the delirium cohort after adjustment of covariables (P = .01).

Conclusions

This study confirms that delirium is associated with significantly greater costs. Considering that effective delirium prevention is possible, the knowledge of associated costs can help health care providers to justify prevention strategies and finally give better care for older patients.     

Opvattingen van artsen en verpleegkundigen over de preventie, diagnose en behandeling van delirium

To assess the current opinions of physicians and nurses regarding the prevention, diagnosis and management of delirium, survey administration was conducted to 2256 nurses and 982 physicians within the University Hospitals of Leuven (Belgium). Response rate was 26% with 819 respondents (600 nurses; 219 physicians) completing the questionnaire. 72% of the respondents considered delirium as a minor problem or no problem at all. Yet over half of respondents working on a palliative care unit (87%, n=15), traumatological ward (67%, n=18), cardio-thoracic surgery ward (58%, n=20), intensive care unit (55%, n=120) and geriatric ward (55%, n=42) reported it as a serious problem. Delirium was considered as an underdiagnosed (85%) but preventable (75%) syndrome. Yet patients at risk are rarely (34%) or never (52%) screened for delirium. In case of screening (48%), only 4% used a specific validated assessment tool. 97% of all respondents were convinced that delirium requires an active and immediate intervention of nurse and physician. 82% of the physicians preferred haldol to treat delirium, in case of alcohol withdrawal 69% chose tranxene. Physical restraints were considered important in the management of delirium by a greater proportion of nurses (49%) than physicians (28%). The severity of the problem is underestimated. While opinions regarding the treatment were quite correct, prevention and early detection of delirium deserve more attention.     

Interventions to prevent or treat obesity in preschool children: a review of evaluated programs

Objective: To identify effective programs to prevent or treat overweight among 2‐ to <6‐year‐old children. Research Methods and Procedures: We searched six databases to identify evaluated intervention programs assessing changes in weight status or body fat and systematically summarized study attributes and outcomes. Results: Four of the seven studies (two intervention, two prevention) documented significant reductions in weight status or body fat. Among these, three sustained reductions at 1 or 2 years after program initiation, three incorporated a framework/theory, two actively and one passively involved parents, three included multicomponent strategies, and all four monitored behavioral changes. Of the three (prevention) studies that did not show reduction in weight or fat status, all performed assessments between 4 and 9 months after program initiation, and one used a multicomponent strategy. Other significant changes reported were reductions in television viewing, cholesterol, and parental restriction of child feeding. Discussion: The paucity of studies limits our ability to generalize findings. Among the available studies, multicomponent programs with 1‐ to 2‐year follow‐up in clinics or child care settings were successful in their impact on weight; they were likely enhanced by parental involvement. Both treatment programs and two of five prevention programs reduced weight/fat status. Our review highlights the need to evaluate more programs, advocate for use of a framework/behavioral theory and objective behavioral measures, further examine the impact of involving parents and the impact of intervention duration and follow‐up time, strengthen prevention programs, and further evaluate successful programs in other settings and among other racial/ethnic groups.     

Long Term Outcomes of a Geriatric Liaison Intervention in Frail Elderly Cancer Patients

Background

The aim of this study was to evaluate the long term effects after discharge of a hospital-based geriatric liaison intervention to prevent postoperative delirium in frail elderly cancer patients treated with an elective surgical procedure for a solid tumour. In addition, the effect of a postoperative delirium on long term outcomes was examined.

Methods

A three month follow-up was performed in participants of the Liaison Intervention in Frail Elderly study, a multicentre, prospective, randomized, controlled trial. Patients were randomized to standard treatment or a geriatric liaison intervention. The intervention consisted of a preoperative geriatric consultation, an individual treatment plan targeted at risk factors for delirium and daily visits by a geriatric nurse during the hospital stay. The long term outcomes included: mortality, rehospitalisation, Activities of Daily Living (ADL) functioning, return to the independent pre-operative living situation, use of supportive care, cognitive functioning and health related quality of life.

Results

Data of 260 patients (intervention n = 127, Control n = 133) were analysed. There were no differences between the intervention group and usual-care group for any of the outcomes three months after discharge. The presence of postoperative delirium was associated with: an increased risk of decline in ADL functioning (OR: 2.65, 95% CI: 1.02–6.88), an increased use of supportive assistance (OR: 2.45, 95% CI: 1.02–5.87) and a decreased chance to return to the independent preoperative living situation (OR: 0.18, 95% CI: 0.07–0.49).

Conclusions

A hospital-based geriatric liaison intervention for the prevention of postoperative delirium in frail elderly cancer patients undergoing elective surgery for a solid tumour did not improve outcomes 3 months after discharge from hospital. The negative effect of a postoperative delirium on late outcome was confirmed.

Trial Registration

Nederlands Trial Register, Trial ID NTR 823.     

School-Based Internet Obesity Prevention Programs for Adolescents: A Systematic Literature Review

In response to the childhood obesity epidemic, numerous studies on school-based Internet obesity prevention interventions have been conducted. The purpose of this systematic review is to describe, synthesize, and evaluate the research on school-based Internet obesity prevention programs for adolescents. Medline, CINAHL, and PsycInfo were searched from January 1995 to August 2012 to locate relevant studies. Ninety-one reports were initially identified, with 12 meeting the inclusion criteria. Studies had variable control groups, program content, and sample characteristics. Though few authors reported on implementation processes or body mass index (BMI) outcomes, the majority of studies were effective in improving health behaviors in the short term. Most studies were judged to have a high or unclear risk of bias in at least two domains, thus the quality of evidence for this body of literature is moderate. Further research is needed to examine programs of longer duration, optimal dose and timing of programs, cost-effectiveness, and mediators and moderators of intervention outcomes.     

Clinical trials of antioxidants as cancer prevention agents: past, present, and future

The purpose of this review is to summarize the most important human clinical trials of antioxidants as cancer prevention agents conducted to date, provide an overview of currently ongoing studies, and discuss future steps needed to advance research in this field. To date there have been several large (at least 7000 participants) trials testing the efficacy of antioxidant supplements in preventing cancer. The specific agents (diet-derived direct antioxidants and essential components of antioxidant enzymes) tested in those trials included β-carotene, vitamin E, vitamin C, selenium, retinol, zinc, riboflavin, and molybdenum. None of the completed trials produced convincing evidence to justify the use of traditional antioxidant-related vitamins or minerals for cancer prevention. Our search of ongoing trials identified six projects at various stages of completion. Five of those six trials use selenium as the intervention of interest delivered either alone or in combination with other agents. The lack of success to date can be explained by a variety of factors that need to be considered in the next generation research. These factors include lack of good biological rationale for selecting specific agents of interest; limited number of agents tested to date; use of pharmacological, rather than dietary, doses; and insufficient duration of intervention and follow-up. The latter consideration underscores the need for alternative endpoints that are associated with increased risk of neoplasia (i.e., biomarkers of risk), but are detectable prior to tumor occurrence. Although dietary antioxidants are a large and diverse group of compounds, only a small proportion of candidate agents have been tested. In summary, the strategy of focusing on large high-budget studies using cancer incidence as the endpoint and testing a relatively limited number of antioxidant agents has been largely unsuccessful. This lack of success in previous trials should not preclude us from seeking novel ways of preventing cancer by modulating oxidative balance. On the contrary, the well demonstrated mechanistic link between excessive oxidative stress and carcinogenesis underscores the need for new studies. It appears that future large-scale projects should be preceded by smaller, shorter, less expensive biomarker-based studies that can serve as a link from mechanistic and observational research to human cancer prevention trials. These relatively inexpensive studies would provide human experimental evidence for the likely efficacy, optimum dose, and long-term safety of the intervention of interest that would then guide the design of safe, more definitive large-scale trials.     

Understanding the Potential Impact of a Combination HIV Prevention Intervention in a Hyper-Endemic Community

Objectives

Despite demonstrating only partial efficacy in preventing new infections, available HIV prevention interventions could offer a powerful strategy when combined. In anticipation of combination HIV prevention programs and research studies we estimated the population-level impact of combining effective scalable interventions at high population coverage, determined the factors that influence this impact, and estimated the synergy between the components.

Methods

We used a mathematical model to investigate the effect on HIV incidence of a combination HIV prevention intervention comprised of high coverage of HIV testing and counselling, risk reduction following HIV diagnosis, male circumcision for HIV-uninfected men, and antiretroviral therapy (ART) for HIV-infected persons. The model was calibrated to data for KwaZulu-Natal, South Africa, where adult HIV prevalence is approximately 23%.

Results

Compared to current levels of HIV testing, circumcision, and ART, the combined intervention with ART initiation according to current guidelines could reduce HIV incidence by 47%, from 2.3 new infections per 100 person-years (pyar) to 1.2 per 100 pyar within 4 years and by almost 60%, to 1 per 100 pyar, after 25 years. Short-term impact is driven primarily by uptake of testing and reductions in risk behaviour following testing while long-term effects are driven by periodic HIV testing and retention in ART programs. If the combination prevention program incorporated HIV treatment upon diagnosis, incidence could be reduced by 63% after 4 years and by 76% (to about 0.5 per 100 pyar) after 15 years. The full impact of the combination interventions accrues over 10–15 years. Synergy is demonstrated between the intervention components.

Conclusion

High coverage combination of evidence-based strategies could generate substantial reductions in population HIV incidence in an African generalized HIV epidemic setting. The full impact could be underestimated by the short assessment duration of typical evaluations.     

非药物干预治疗物质使用障碍

物质使用障碍（substance use disorder,SUD）是一个全球性的卫生和社会问题。针对大多数成瘾性物质，目前还没有有效的治疗药物，普遍还是采用心理治疗和行为矫治。近年来，针刺、深部脑刺激（DBS）、重复经颅磁刺激（rTMS）、经颅直流电刺激（tDCS）和运动等非药物干预手段在治疗神经系统疾病的有效性逐渐得到重视。越来越多的研究也开始关注非药物干预手段在治疗SUD中的应用。本综述在文献检索（如PubMed、Google Scholar等）的基础上总结了针刺、DBS、rTMS、tDCS和运动等非药物干预手段对阿片类药物、精神活性物质、尼古丁、酒精等不同成瘾性物质的心理渴求、戒断时间、使用剂量和成瘾伴随的情绪、认知功能障碍等的影响。研究表明，针刺、DBS、rTMS、tDCS和运动等非药物干预手段可以有效降低成瘾性物质引起的心理渴求、降低物质摄入量、增加戒断时间，同时改善长期使用成瘾性物质引起的认知障碍、焦虑和抑郁样行为等。如果非药物干预手段结合药物、心理等治疗方式，效果更佳。尽管非药物干预方法在现阶段主要作为辅助性治疗手段，未来的研究应注重明确非药物干预手段的神经生物学机制，...     

Cost Analysis of an Intervention to Prevent Methicillin-Resistant Staphylococcus Aureus (MRSA) Transmission

Introduction

Our objective was to assess the cost implications of a vertical MRSA prevention program that led to a reduction in MRSA bacteremia.

Methods

We performed a matched historical cohort study and cost analysis in a single hospital in Israel for the years 2005-2011. The cost of MRSA bacteremia was calculated as total hospital cost for patients admitted with bacteremia and for patients with hospital-acquired bacteremia, the difference in cost compared to matched controls. The cost of prevention was calculated as the sum of the cost of microbiology tests, single-use equipment used for patients in isolation, and infection control personnel.

Results

An average of 20,000 patients were screened yearly. The cost of prevention was $208,100 per year, with the major contributor being laboratory cost. We calculated that our intervention averted 34 cases of bacteremia yearly: 17 presenting on admission and 17 acquired in the hospital. The average cost of a case admitted with bacteremia was $14,500, and the net cost attributable to nosocomial bacteremia was $9,400. Antibiotics contributed only 0.4% of the total disease management cost. When the annual cost of averted cases of bacteremia and that of prevention were compared, the intervention resulted in annual cost savings of $199,600.

Conclusions

A vertical MRSA prevention program targeted at high-risk patients, which was highly effective in preventing bacteremia, is cost saving. These results suggest that allocating resources to targeted prevention efforts might be beneficial even in a single institution in a high incidence country.     

The European acamprosate trials: Conclusions for research and therapy

In an excellent methodological approach, the European acamprosate study project showed that acamprosate increases sobriety times. In one randomized prospective study (n = 260) comparing acamprosate and placebo, with a 1-year treatment phase and 1-year follow-up phase, the authors found that acamprosate is effective only in Lesch type I and type II patients. To investigate the possible influence of diagnostic subgrouping, we applied the Lesch typology in a co-work with the main researchers of the UK study. The UK results concerning acamprosate's effects in the types do not mirror the Vienna results, but the numbers of type I and type II patients, retrospectively found as included in the UK centers, were too small for any conclusions. The distribution of the types points to the fact that too many type III and IV patients had been included to give acamprosate the chance to be effective. Following our typology and also these studies, we developed special treatment approaches. For relapse prevention studies, the cumulative abstinence duration together with the Lesch typology seems to be promising.     

Preoperative circadian physical activity rhythm and postoperative delirium in cardiovascular surgery patients

ABSTRACT

Postoperative delirium, a common perioperative complication, is frequently observed in elderly surgical patients. Few studies have investigated the life rhythm of preoperative patients, and whether or not the preoperative life rhythm is associated with the development of postoperative delirium. The purpose of this study was to investigate the relationship between the preoperative circadian physical activity rhythm and postoperative delirium in cardiovascular surgery patients. A total of 43 patients who underwent cardiovascular surgery were included in this prospective study between July 2016 and September 2017 at Kobe University Hospital. All subjects used a “Life Microscope” wristband (a wristwatch-type terminal incorporating a 3-axis accelerometer monitoring) for 3–7 days at home before the planned surgery. Hourly mean values were calculated for the metabolic equivalents from the obtained activity amounts, and subsequently evaluated using cosine periodic regression analysis. The circadian rhythm parameters of mesor (24 h time series mean), amplitude (half the peak-trough variation), and acrophase (peak time) for the metabolic equivalents were obtained. The intensive care delirium screening checklist was used to assess for postoperative delirium. The acrophase significantly advanced in the postoperative delirium group (median, 11:55 h [interquartile range, 11:06–12:27 h]) compared to the group without postoperative delirium (median, 13:25 h [interquartile range, 12:52–14:13 h]) (p < .001). Furthermore, binary logistic regression analysis showed that advances in the physical activity phase remained independently associated with postoperative delirium (odds ratio, 0.003 [95% confidence interval, 0–0.63]). These results suggest that misalignment between advanced life rhythm before hospitalization and life rhythm after hospitalization might be associated with risk for developing postoperative delirium. Our results led us to speculate that adequate consideration of the patient’s life rhythm before hospitalization is needed to prevent postoperative delirium.     

Improving quality of care: focus on liaison old age psychiatry

Introduction Elderly patients occupy up to 65% of acute hospital beds and a significant proportion of them present with a comorbid psychiatric condition such as depression, delirium or dementia. Liaison old age psychiatry (LOAP) services have been developed to provide psychiatric consultation in medical and surgical settings, improving at the same time the knowledge and expertise of general ward staff.Objective The aim of this study is to evaluate clinical characteristics across different psychiatric disorders among elderly patients in medical wards.Method A prospective observational study was developed between October 2011 and January 2013, which involved 107 subjects aged 65 years or older that were hospitalised in the Department of Internal Medicine and referred to the LOAP service. Psychiatric diagnostic was assessed using the Confusion Assessment Method, the Geriatric Depression Scale, the Mini-Mental State Examination and the Clinical Global Impression Scale.Results Delirium (40.6%), depression (22.4%) and dementia (20.4%) were the most common psychiatric diagnoses. Patients with delirium were significantly older, had more severe psychiatric symptomatology (mean CGI = 5.35) and presented infectious processes as acute medical conditions more frequently than the other patients.Conclusion Psychiatric disturbances occurring in elderly inpatients in medical wards are highly prevalent and complex. A LOAP service may play an important role in effectively reducing the overutilisation and consumption of health resources through early recognition of these conditions, effective management and prevention of adverse outcomes, and effective communication with out-patient clinics, community mental health teams and day-care centres.     

Protein restriction and cancer

Protein restriction without malnutrition is currently an effective nutritional intervention known to prevent diseases and promote health span from yeast to human. Recently, low protein diets are reported to be associated with lowered cancer incidence and mortality risk of cancers in human. In murine models, protein restriction inhibits tumor growth via mTOR signaling pathway. IGF-1, amino acid metabolic programing, FGF21, and autophagy may also serve as potential mechanisms of protein restriction mediated cancer prevention. Together, dietary intervention aimed at reducing protein intake can be beneficial and has the potential to be widely adopted and effective in preventing and treating cancers.     

Evaluating temporal factors in combined interventions of workforce shift and school closure for mitigating the spread of influenza

Background

It is believed that combined interventions may be more effective than individual interventions in mitigating epidemic. However there is a lack of quantitative studies on performance of the combination of individual interventions under different temporal settings.

Methodology/Principal Findings

To better understand the problem, we develop an individual-based simulation model running on top of contact networks based on real-life contact data in Singapore. We model and evaluate the spread of influenza epidemic with intervention strategies of workforce shift and its combination with school closure, and examine the impacts of temporal factors, namely the trigger threshold and the duration of an intervention. By comparing simulation results for intervention scenarios with different temporal factors, we find that combined interventions do not always outperform individual interventions and are more effective only when the duration is longer than 6 weeks or school closure is triggered at the 5% threshold; combined interventions may be more effective if school closure starts first when the duration is less than 4 weeks or workforce shift starts first when the duration is longer than 4 weeks.

Conclusions/Significance

We therefore conclude that identifying the appropriate timing configuration is crucial for achieving optimal or near optimal performance in mitigating the spread of influenza epidemic. The results of this study are useful to policy makers in deliberating and planning individual and combined interventions.     

A pilot study of rivastigmine in the treatment of delirium after stroke: A safe alternative

Background

Delirium is a common disorder in the early phase of stroke. Given the presumed cholinergic deficiency in delirium, we tested treatment with the acetylcholinesterase inhibitor rivastigmine.

Methods

This pilot study was performed within an epidemiological study. In 527 consecutive stroke patients presence of delirium was assessed during the first week with the confusion assessment method. Severity was scored with the delirium rating scale (DRS). Sixty-two patients developed a delirium in the acute phase of stroke. Only patients with a severe and persistent delirium (defined as a DRS of 12 or more for more than 24 hours) were enrolled in the present study. In total 26 fulfilled these criteria of whom 17 were treated with orally administered rivastigmine with a total dose between 3 and 12 mg a day. Eight patients could not be treated because of dysphagia and one because of early discharge.

Results

No major side effects were recorded. In 16 patients there was a considerable decrease in severity of delirium. The mean DRS declined from 14.8 on day one to 8.5 after therapy and 5.6 after tapering. The mean duration of delirium was 6.7 days (range; 2–17).

Conclusion

Rivastigmine is safe in stroke patients with delirium even after rapid titration. In the majority of patients the delirium improved after treatment. A randomized controlled trial is needed to establish the usefulness of rivastigmine in delirium after stroke.

Trial registration

Nederlands Trial Register NTR1395