Stability of a formalin-inactivated Rift Valley fever vaccine: evaluation of a vaccination campaign for cattle in Mozambique.

In Africa and the Arabian Peninsula, outbreaks of Rift Valley fever (RVF) are characterized by abortions in gestating animals and high mortality rates among domestic ruminants. An immunization program using a formalin-inactivated vaccine was initiated in Mozambique in 2002 to control RVF in cattle. In this intervention, the vaccine must be transported for more than a week within the country before it can be administered to the animals, and it is practically impossible to maintain low storage temperatures during that time. Here, we evaluated the influence of transportation conditions on the efficacy of the vaccine. Sixty-three previously unvaccinated and RVF virus seronegative cattle were divided into four groups, which were given vaccine that had been stored for 1 week at 4°C (n=9, group A), at 25°C (n=8, group B), or alternating between 4 and 25°C (n=8, group C), or under the temperature conditions ordinarily occurring during transportation within Mozambique (n=38, group D). The antibody responses induced were monitored for 6-9 months and in some animals up to 21 months. Two immunizations (3 weeks apart) with the formalin-inactivated vaccine induced a long-lasting neutralizing antibody response that was still detectable up to 21 months later. The antibody titers in the animals did not differ significantly between the temperature-assigned vaccine groups A, B, and C, whereas they were significantly higher in group D. These results show that the formalin-inactivated RVF virus vaccine is stable, and, importantly, it is not adversely affected by the variation in temperature that ordinarily occurs during transport within Mozambique.

A virtual reality test battery for assessment and screening of spatial neglect.

BACKGROUND: There is a need for improved screening methods for spatial neglect. AIM: To construct a VR-test battery and evaluate its accuracy and usability in patients with acute stroke. METHOD: VR-DiSTRO consists of a standard desktop computer, a CRT monitor and eye shutter stereoscopic glasses, a force feedback interface, and software, developed to create an interactive and immersive 3D experience. VR-tests were developed and validated to the conventional Star Cancellation test, Line bisection, Baking Tray Task (BTT), and Visual Extinction test. A construct validation to The Rivermead Behavioral Inattention Test, used as criterion of visuospatial neglect, was made. Usability was assessed according to ISO 9241-11. RESULTS: Thirty-one patients with stroke were included, 9/31 patients had neglect. The sensitivity was 100% and the specificity 82% for the VR-DiSTRO to correctly identify neglect. VR-BTT and VR-Extinction had the highest correlation (r² = 0.64 and 0.78), as well as high sensitivity and specificity. The kappa values describing the agreement between traditional neglect tests and the corresponding virtual reality test were between 0.47-0.85. Usability was assessed by a questionnaire; 77% reported that the VR-DiSTRO was 'easy' to use. Eighty-eight percent reported that they felt 'focused', 'pleased' or 'alert'. No patient had adverse symptoms. The test session took 15 min. CONCLUSIONS: The VR-DiSTRO quickly and with a high accuracy identified visuospatial neglect in patients with stroke in this construct validation. The usability among elderly patients with stroke was high. This VR-test battery has the potential to become an important screening instrument for neglect and a valuable adjunct to the neuropsychological assessment.

Physical activity in middle-aged women and hip fracture risk: the UFO study.

UNLABELLED: In a population-based case-control study, we demonstrate that middle-aged women who were active with walking or in different physical spare time activities were at lower risk of later sustaining a hip fracture compared to more sedentary women. INTRODUCTION: In middle-aged women participating in the Umeå Fracture and Osteoporosis (UFO) study, we investigated whether physical activity is associated with a subsequent decreased risk of sustaining a hip fracture. METHODS: The UFO study is a nested case-control study investigating associations between bone markers, lifestyle, and osteoporotic fractures. We identified 81 female hip fracture cases that had reported lifestyle data before they sustained their fracture. Each case was compared with two female controls who were identified from the same cohort and matched for age and week of reporting data, yielding a total cohort of 237 subjects. Mean age at baseline was 57.2 ± 5.0 years, and mean age at fracture was 65.4 ± 6.4 years. RESULTS: Conditional logistic regression analysis with adjustments for height, weight, smoking, and menopausal status showed that subjects who were regularly active with walking or had a moderate or high frequency of physical spare time activities (i.e. berry/mushroom picking and snow shovelling) were at reduced risk of sustaining a hip fracture (OR 0.14; 95% CI; 0.05-0.53 for walking and OR 0.19; 95% CI; 0.08-0.46, OR 0.17, 95% CI; 0.05-0.64 for moderate and high frequency of spare time activities, respectively) compared to more sedentary women. CONCLUSION: An active lifestyle in middle age seems to reduce the risk of future hip fracture. Possible mechanisms may include improved muscle strength, coordination, and balance resulting in a decreased risk of falling and perhaps also direct skeletal benefits.

The beneficial effects of exercise on BMD are lost after cessation: a 5-year follow-up in older post-menopausal women.

This study investigates whether the positive effects on bone mineral density (BMD, g/cm(2)) and neuromuscular function following a combined weight-bearing program are sustained in older women, a longer period after cessation of training. Thirty-four women (18 exercisers and 16 controls) aged 73-88 years, who completed a 12-month randomized-controlled trial, were invited to a 5-year follow-up assessment of BMD and neuromuscular function. Both groups sustained significant losses in BMD of the femoral neck, trochanter, and Ward's triangle during the follow-up period. Significant losses were also seen in all neuromuscular function tests. The inter-group change was, however, significant only for maximal walking speed where the exercise group had a significantly greater loss. In conclusion, this study suggests that gains in bone density and neuromuscular functions achieved by training are lost after cessation of training. Continuous high-intensity weight-loading physical activity is probably necessary to preserve bone density and neuromuscular function in older women.

PCR-generated linear DNA fragments utilized as a hantavirus DNA vaccine.

The field of DNA vaccines has grown rapidly, and since most such vaccines involve the inoculation of large circular DNA molecules previously propagated in bacteria, several inconveniences (e.g. the presence of antibiotic resistance genes, impurities from bacterial cultures or inefficient uptake of the large and bulky plasmid DNA molecules to the nucleus) are debated. In this study, we have explored the possibility of using smaller and more flexible PCR-generated linear DNA fragments instead. Phosphorothioate (PTO)-modified primers were used successfully to protect the PCR-generated DNA fragments from exonuclease degradation, and by using a nuclear localization signal-peptide to target the linear DNA to the nucleus the immune response against the encoded antigen was further improved. This approach was tested in cell culture using a sensitive reporter system and in vivo with DNA encoding the amino-terminus of the Puumala hantavirus nucleocapsid protein. Our results indicate that linear DNA fragments have a great potential as a genetic vaccine and phosphorothioate modification in combination with a nuclear localization signal peptide increase the stability and targets the linear DNA molecules to the nucleus resulting in an improved biological response examined both in vitro and in vivo.

Nasal continuous positive airway pressure in stroke patients with sleep apnoea: a randomized treatment study.

The authors have investigated whether treatment of sleep apnoea with nasal continuous positive airway pressure (nCPAP) improves depressive symptoms, personal activities of daily living (ADL), cognitive functioning and delirium in patients that have suffered a stroke. Sixty-three patients consecutively admitted to a stroke rehabilitation unit 2-4 weeks after a stroke, with an apnoea/hypopnoea index > or =15, were randomized to either nCPAP treatment (n=33) or a control group (n=30). Four patients dropped out after randomization. Both groups were assessed at baseline and after 7 and 28 nights using the Montgomery-Asberg Depression Rating Scale (MADRS), Barthel-ADL index, and the Mini-Mental State Examination (MMSE) scale. Compared to the control group, depressive symptoms (MADRS total score) improved in patients randomized to nCPAP treatment (p=0.004). No significant treatment effect was found with regard to delirium, MMSE or Barthel-ADL index. Delirium and low cognitive level (MMSE score) explained poor compliance with nCPAP. Depressive symptoms are reduced through nasal continuous positive airway pressure treatment in patients with severe stroke and sleep apnoea. Compliance with nasal continuous positive airway pressure treatment is a problem in stroke patients, especially when delirium and severe cognitive impairment occur.

Modifying the cellular transport of DNA-based vaccines alters the immune response to hantavirus nucleocapsid protein.

Puumala virus is a member of the hantavirus genus (family Bunyaviridae) and is one of the causative agents of hemorrhagic fever with renal syndrome (HFRS) in Europe. A genetic vaccination approach was conducted to investigate if the immune response could be modulated using different cellular secretion and/or localisation signals, and the immune responses were analysed in BALB/c mice and in a bank vole infectious model. Rodents vaccinated with DNA constructs encoding the antigen fused to an amino-terminal secretion signal raised significantly higher antibody levels when compared to using constructs lacking secretion signals. Furthermore, the ratios of the IgG subclasses (IgG2a/IgG1) were raised by the use of cellular localisation signals, indicating a more pronounced Th1-type of immune response. The majority of the mice, or bank voles, immunised with DNA encoding a secreted form of the antigen showed a positive lymphoproliferative response and were protected against challenge with Puumala virus (strain Kazan-wt).

Sleep apnea, delirium, depressed mood, cognition, and ADL ability after stroke.

OBJECTIVES: The incidence of sleep apnea and stroke increases with age. The aim of this study was to investigate the presence of sleep apnea after stroke and its relationship to delirium, depressed mood, cognitive functioning, ability to perform activities of daily living (ADLs), and psychiatric and behavior symptoms. DESIGN: Cross-sectional study. SETTING: Geriatric stroke rehabilitation unit. PARTICIPANTS: 133 patients (78 women and 55 men, mean age 77.1 +/- 7.7 years) consecutively admitted to a geriatric stroke rehabilitation unit. MEASUREMENTS: All patients underwent overnight respiratory sleep recordings at 23 +/- 7 days (range 11 to 41 days) after suffering a stroke. The patients were assessed using the Organic Brain Syndrome Scale, Montgomery-Asberg-Depression-Rating Scale, Mini-Mental State Examination (MMSE), and Barthel-ADL Index. Sleep apnea was defined as an apnea-hypopnea index (AHI) of 10 or more. RESULTS: The median of the AHI for the studied sample (N = 133) was 13 (range 0-79; interquartile range 6-28). Fifty-nine percent fulfilled the criteria for sleep apnea; 52% with first-ever stroke had sleep apnea. More patients with sleep apnea than without were delirious, depressed, or more ADL-dependent. Sleep apnea patients also had a higher frequency of ischemic heart disease and had more often suffered from an earlier cerebral infarction. Multivariate analysis showed that obesity, low ADL scores, ischemic heart disease, and depressed mood were independently associated with sleep apnea. Low ADL scores, apnea-related hypoxemia, body mass index < or = 27, and impaired vision were independently associated with delirium. The presence of sleep apnea was not associated with any specific type of stroke or location of the brain lesion. CONCLUSIONS: Sleep apnea is common in stroke patients and is associated with delirium, depressed mood, latency in reaction and in response to verbal stimuli, and impaired ADL ability. We suggest a trial investigating whether delirium, depressed mood, and ADL ability improve with nasal continuous positive airway pressure treatment of sleep apnea in stroke patients.

Delirium before and after operation for femoral neck fracture.

OBJECTIVES: The aim of this study was to investigate the differences between preoperative and postoperative delirium regarding predisposing, precipitating factors and outcome in older patients admitted to hospital with femoral neck fractures. DESIGN: A prospective clinical assessment of patients treated for femoral neck fractures. SETTING: Department of orthopedic surgery at Umeå University Hospital, Sweden. PARTICIPANTS: One hundred one patients, age 65 and older admitted to the hospital for treatment of femoral neck fractures. MEASUREMENTS: The Organic Brain Syndrome (OBS) Scale. RESULTS: Thirty patients (29.7%) were delirious before surgery and another 19 (18.8%) developed delirium postoperatively. Of those who were delirious preoperatively, all but one remained delirious postoperatively. The majority of those delirious before surgery were demented, had been treated with drugs with anticholinergic properties (mainly neuroleptics), had had previous episodes of delirium, and had fallen indoors. Patients who developed postoperative delirium had perioperative falls in blood pressure and had more postoperative complications such as infections. Male patients were more often delirious both preoperatively and postoperatively. Patients with preoperative delirium were more often discharged to institutional care and had poorer walking ability both on discharge and after 6 months than did patients with postoperative delirium only. CONCLUSIONS: Because preoperative and postoperative delirium are associated with different risk factors it is necessary to devise different strategies for their prevention.

Factors relating to the use of physical restraints in geriatric care settings.

Physical restraints are commonly used on older persons living in geriatric care settings. The aim of this study was to investigate the influence of environmental and organizational variations and resident and staff characteristics on restraint prevalence. In this cross-sectional study of 33 nursing home wards and 12 group living units for old persons with dementia in two municipalities in northern Sweden, 540 residents (mean age 82) and 529 staff members were evaluated for resident and staff characteristics and organizational and environmental variables. The proportion of residents with impaired mobility function, the number of behavioral disturbances, and nursing staff's attitudes towards use of restraints were the strongest discriminators between restraint-free wards and wards that used restraints. A classification function analysis showed that these three variables could correctly classify the wards as restraint-free, low-use, and high-use wards in 63.6% of the cases, with the highest figures for restraint-free wards (91%). This study has shown that the use of physical restraints is strongly connected with residents' functional status and nursing staffs' attitudes toward their use.

Geriatric-based versus general wards for older acute medical patients: a randomized comparison of outcomes and use of resources.

BACKGROUND: The effects of residence in an acute geriatrics-based ward (AGW) with emphasis on early rehabilitation and discharge planning for older patients with acute medical illnesses were assessed. Outcome and use of resources were compared with those of patients treated in general medical wards (MWs). A per-protocol rather than intention-to-treat analysis was performed. METHODS: A randomized trial with 3-months follow-up. A total of 190 patients aged 70 years and older were randomized to an acute geriatrics-based ward, and 223 patients were randomized to general medical wards. RESULTS: The two groups were comparable at inclusion. However, after care in the AGW, 71% of patients could be discharged directly home compared with 64% of those treated in MWs (relative risk 1.17; 95% CI, 0.93-1.49). The length of stay was shorter in the AGW (mean 5.9 vs 7.3 days; P = .002). The proportion of patients in geriatric or other hospital wards or in nursing homes did not differ, but the proportion of AGW patients in sheltered living tended to be lower (P = .085). At the follow-up, case fatality, ADL function, psychological well-being, need for daily personal assistance, drug consumption, need for readmission to hospital, and total health care costs after discharge did not differ between the two groups. Poor global outcome was observed in 37% of AGW and 34% of MW patients. CONCLUSIONS: A geriatric approach with greater emphasis on early rehabilitation and discharge planning in the AGW shortened the length of hospital stay and may have reduced the need for long-term institutional living. This occurred despite patients in an acute geriatric ward not having better medical or functional outcome than older acute patients treated in general medical wards.

Inpatient care quality: analyzing Swedish hospitals with stroke as a tracer.

Mortality statistics are an important source of information concerning variations in time and place, identification of risk factors and the evaluation of treatment programs. In this study, a new death certificate was completed "blind" on the basis of hospital records from the last episode of care, across a random sample of 1,376 cases. The results showed that the overlap between the official register's underlying cause of death and that of a panel was 72 per cent at the three-digit level. The official underlying cause of death from cerebrovascular diseases (CVD) was 72 cases in this sample, while 93 were deemed to have CVD by a panel. Additionally, of the 1,233 cases originally reported as non-CVD, the panel deemed non-CVD to be the true underlying cause in 1,176 cases. The paper concludes that CVD was most often correctly reported as the underlying cause of death in the investigated ages up to 75 years but plain differences were found between specialities and in different hospital size.

Clinical profile of delirium in older patients.

OBJECTIVE: To examine the prevalence, psychiatric and behavior symptoms, differing symptom profiles, and diurnal variations of delirium in older patients. DESIGN: A descriptive, point prevalence study with a cross-sectional design. SETTING: One ordinary county hospital (n = 148), three nursing homes (n = 202), five old people's homes (n = 196), and home medical care patients (n = 171) in parts of a hospital catchment area in Mid-Sweden. PARTICIPANTS: A total of 717 patients 75 years of age and older were observed and assessed for the prevalence of delirium. Women accounted for 66.4% of the studied population, and the mean age for both sexes was 83.7 years. MEASUREMENTS: All patients were examined using the OBS (Organic Brain Syndrome) scale, and delirium was diagnosed according to DSM-III-R. RESULTS: Delirium was diagnosed in 315 of 717 (43.9%) patients, and 135 of 315 (42.9%) of the delirious patients had dementia. Thirty-seven percent of the patients with delirium were delirious in the afternoon, evening, or at night, and 47% of the delirious patients had morning delirium. The delirious patients presented a wide variety of psychiatric symptoms. More than half the patients exhibiting anxiety, psychomotor slowing, depressed mood, and irritability. Nearly 26% were classified as having hypoactive, 22% as having hyperactive, and 42% as having mixed delirium, whereas 11% had neither hypo- nor hyperactive delirium. Seventy-seven percent were classified as having delirium with pronounced emotional and 43% with pronounced psychotic symptoms. CONCLUSIONS: This study shows that patients with delirium have very different clinical profiles. This might indicate a need for different treatment strategies for patients with different types of delirium.

Epidemiology of delirium.

Delirium is one of the most frequent symptoms of disease in the elderly. A large variation of incidence and prevalence data is reported probably due to different patient populations and inconsistent diagnostic criteria. In medical and surgical elderly inpatients recent studies report a prevalence rate of approximately 15% and in postoperative patients the incidence and prevalence rates vary greatly, 7-52%, depending on patient population and clinical setting. In nursing homes the prevalence is even higher and delirium is often combined with dementia. Data supports the statement that delirium is most often found in hospitalized somatically ill elderly patients. As a consequence of the rising number of elderly in hospitals we have to expect an increase in the prevalence and incidence of delirium.

Optimising the signal peptide for glycosyl phosphatidylinositol modification of human acetylcholinesterase using mutational analysis and peptide-quantitative structure-activity relationships.

Glycosyl phosphatidylinositol (GPI)-modified proteins have a C-terminal signal peptide (GPIsp) that mediates the addition of a GPI-anchor to an amino acid residue at the cleavage and modification site (omega-site). Within the GPIsp, a stretch of hydrophilic amino acid residues are found which constitutes the spacer region that separates the omega-site residue from a hydrophobic C-terminus. Deletions and insertions into the spacer region of human acetylcholinesterase (AChE) show that the length of this spacer region is very important for efficient GPI-modification. Surprisingly, the natural length of the spacer region in human AChE was not optimal for the highest degree of GPI modification. The importance of the two adjacent residues downstream of the omega-site, the omega+1 and omega+2 residues, was investigated by peptide-quantitative structure-activity relationships (Peptide-QSAR). A model was made that predicts the efficiency of the GPI modification when these residues are substituted with others, and suggests important features for these residues. The most preferred omega+1 and omega+2 residues, predicted by the model, in combination with an ideal spacer length resulted in an optimised GPIsp. This mutant protein is more efficiently GPI-modified than any mutant AChE tested thus far.

Physical restraints in geriatric care. Knowledge, attitudes and use.

The aim of the present study was to investigate the use of physical restraints in institutional elder care and staff knowledge about and attitudes toward the use of these restraints. Poor knowledge and negative attitudes toward the use of restraints were found among staff. Significant differences between various staff categories were found concerning knowledge about the use of restraints; nurse aids had the lowest and physicians the highest scores on the knowledge test. Nurse aids demonstrated the least negative attitudes (were most prone to use restraints) and physicians the most negative. Furthermore, there was a significant relation between attitudes and knowledge, i.e. staff with poor knowledge also demonstrated the least negative attitudes toward the use of restraints. Despite these negative attitudes among staff, we found a large proportion of restrained patients in the institutions investigated. Twenty-nine percent of the patients at the investigated clinics were physically restrained. The most common reason given was that restraints were used to prevent falls. No documentation of the observed use of restraints was found in any of the restrained patients' hospital records.

Prevalence of dementia, delirium and psychiatric symptoms in various care settings for the elderly.

A prevalence study of psychiatric symptoms was performed in parts of a hospital catchment area in Mid-Sweden. In total 717 patients, aged 75 years and above, who were receiving care in an emergency hospital, three nursing homes, five old people's homes and two home medical care districts were included. All patients were examined using the OBS-scale (Organic Brain Syndrome Scale). Anxiety (51%), psychomotor slowing (45%), delirium (44%), depressed mood (41%), irritability (40%) and dementia (33%) were the most prevalent psychiatric symptoms or diagnoses in the sample but there were wide differences between the four care settings. The present study shows that the prevalence of dementia, delirium and psychiatric symptoms is high in all types of care settings for the elderly. It also demonstrates the need for psychiatric medical and nursing competence in all types of care for the elderly.

Physical restraints in geriatric care in Sweden: prevalence and patient characteristics.

OBJECTIVE: Physical restraints are used frequently in geriatric care to promote the safety of frail older patients. This study investigated the prevalence of the use of physical restraints in geriatric care and the way in which patient characteristics are related to the use of physical restraints. DESIGN: A point prevalence study of patients cared for in various types of geriatric settings. SETTING: Eight nursing homes, 15 old people's homes, a somatic geriatric clinic, and a psychogeriatric clinic in a health care district in northern Sweden. PARTICIPANTS: A total of 1325 patients, mean age 82 years, 64% of whom were women. MEASUREMENTS: The Multi-Dimensional Dementia Assessment Scale (MDDAS) was used to measure motor function, vision, hearing, speech, ADLs, behavioral symptoms, psychiatric symptoms, use of psychoactive drugs, and the physical and psychological workload of the staff. In addition, questions concerning the use of physical restraints were added to the instrument. RESULTS: Twenty-four percent of the patients were physically restrained. The highest prevalence was found in nursing homes and psychogeriatric care. Physical restraints were found to relate most strongly to cognitive impairment, impaired ADLs, and speech and walking ability. Ninety-four percent of the restrained patients were cognitively impaired. Other variables relating to the use of physical restraints were psychiatric symptoms and behavioral disturbances. CONCLUSIONS: This study has shown that physical restraints are used frequently in geriatric care in Sweden and that cognitive and physical impairments relate very closely to the use of physical restraints.

Incidence and clinical characterization of unprovoked seizures in adults: a prospective population-based study.

In a population-based prospective study of epileptic seizures in adult s aged > 17 years, we identified 563 patients with possible seizures in a period of 34 months. Seizures were unprovoked in 160 patients, an incidence of 56 in 100,000 person-years. There was no difference in incidence between sexes. Age-specific incidences of unprovoked seizures increased sharply in men from age 60 years and in women from age 70 years. The incidence of unprovoked seizures in those aged > 65 years was 139 (men 166, women 116). The cumulative incidence of unprovoked seizures between the ages of 17 and 84 years was 4.6%. The proportion with an identified presumptive cause for unprovoked seizures increased with advancing age. A presumed etiology was identified in 77% of persons aged > 60 years. Stroke was the most common etiology, detected in 30% (incidence 16) and in 45% at ages > 60 years. Tumors were detected in 11% (incidence 6) and Alzheimer's disease was detected in 7% (incidence 4). Eighteen percent of patients were demented. Unprovoked seizures were partial in 68% of cases (incidence 38), and generalized in 16% (incidence 9). Another 13% of patients had generalized seizures, but seizure onset was not witnessed (incidence 7). In 16%, there was a delay of > 1 year from the first unprovoked seizure to initial diagnosis.

Residues in Torpedo californica acetylcholinesterase necessary for processing to a glycosyl phosphatidylinositol-anchored form.

Acetylcholinesterase from Torpedo californica (TcAChE) can be found as a glycosyl phosphatidylinositol (GPI)-anchored, membrane associated form. The C-terminal amino-acid sequence of the precursor protein resembles the signal peptide sequence found in proteins and enzymes destined for GPI-modification. Characteristics of such a signal peptide are a relatively polar stretch of amino acids, separating a cleavage- and modification-site (omega-site) residue from a hydrophobic C-terminus. We have introduced mutations, both at putative omega-sites and in the hydrophobic region, and analysed their effects on GPI-anchoring of TcAChE. Our results show that substitution of all three Ser residues in the region Ser542-Ser544 prevents GPI-modification and membrane anchoring. Individual substitution of each of these residues resulted in no or only a minor effect on the modification. We therefore conclude that more than one residue within this sequence can be utilised as the omega-site. Our analyses of double substitutions indicated that Ser543 and Ser544 are the preferred residues for GPI-modification. Moreover, the hydrophobic region is shown to be essential for GPI-anchoring of TcAChE.