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1.  Association of Day Length and Weather Conditions with Physical Activity Levels in Older Community Dwelling People 
PLoS ONE  2014;9(1):e85331.
Background
Weather is a potentially important determinant of physical activity. Little work has been done examining the relationship between weather and physical activity, and potential modifiers of any relationship in older people. We therefore examined the relationship between weather and physical activity in a cohort of older community-dwelling people.
Methods
We analysed prospectively collected cross-sectional activity data from community-dwelling people aged 65 and over in the Physical Activity Cohort Scotland. We correlated seven day triaxial accelerometry data with daily weather data (temperature, day length, sunshine, snow, rain), and a series of potential effect modifiers were tested in mixed models: environmental variables (urban vs rural dwelling, percentage of green space), psychological variables (anxiety, depression, perceived behavioural control), social variables (number of close contacts) and health status measured using the SF-36 questionnaire.
Results
547 participants, mean age 78.5 years, were included in this analysis. Higher minimum daily temperature and longer day length were associated with higher activity levels; these associations remained robust to adjustment for other significant associates of activity: age, perceived behavioural control, number of social contacts and physical function. Of the potential effect modifier variables, only urban vs rural dwelling and the SF-36 measure of social functioning enhanced the association between day length and activity; no variable modified the association between minimum temperature and activity.
Conclusions
In older community dwelling people, minimum temperature and day length were associated with objectively measured activity. There was little evidence for moderation of these associations through potentially modifiable health, environmental, social or psychological variables.
doi:10.1371/journal.pone.0085331
PMCID: PMC3907400  PMID: 24497925
2.  External validation of the CURSI criteria (confusion, urea, respiratory rate and shock index) in adults hospitalised for community-acquired pneumonia 
Background
For patients hospitalised due to community-acquired pneumonia (CAP), mortality risk is usually estimated with prognostic scores such as CRB-65 or CURB-65. For elderly patients, a new score referred to as CURSI has been proposed which uses shock index (SI) instead of the blood pressure (B) and age (65) criteria. The new score has not been externally validated to date.
Methods
We used data from a hospital-based CAP registry to compare the ability of CURSI, CURB-65 and CRB-65 to predict mortality at day 30 after hospital admission. Patients were stratified by score points as well as score-point-based risk categories, and mortality for each group was assessed. To compare test performance, receiver-operating characteristic (ROC) curves were constructed, and the areas under the curve (AUROC) were calculated with 95% confidence intervals (CI).
Results
We analysed 553 inpatients (45% females, median age 78 years) hospitalised between 2005 and 2009 for CAP. Overall, mortality at day 30 was 11% (59/553). The study sample was characterised by advanced comorbidity (chronic heart failure: 22%, chronic kidney failure: 27%) and functional impairment (nursing home residency: 26%, dementia: 31%). All risk scores were significantly associated with 30-day mortality. The AUROC values with 95% CI using score points for risk prediction were as follows: 0.63 [0.56-0.71] for CRB-65, 0.68 [0.61-0.75] for CURB-65 and 0.68 [0.61-0.75] for CURSI. The CURSI-defined low-risk group (0 or 1 score point) had a higher mortality (8%) than the low-risk groups defined by CURB-65 and CRB-65 (4% and 3%, respectively). Lowering the cut-off for the CURSI-defined low-risk group (0 point only) would lower the mortality to 4%, making it comparable to the CURB-65-defined low-risk group.
Conclusions
In our study, the CURSI-defined low-risk group had a higher 30-day mortality than the low-risk groups defined by CURB-65 and CRB-65. Lowering the cut-off value for the CURSI low-risk group would result in a mortality comparable to the CURB-65-defined low risk group. Even then, however, CURSI does not perform better than the established risk scores.
doi:10.1186/1471-2334-14-39
PMCID: PMC3901892  PMID: 24447823
Community-acquired pneumonia; Pneumonia severity; CURB-65; CRB-65; CURSI; Risk assessment; Mortality; Elderly; Inpatients
3.  Falls and EQ-5D rated quality of life in community-dwelling seniors with concurrent chronic diseases: a cross-sectional study 
Background
Although recommended for use in studies investigating falls in the elderly, the European Quality of Life Group instrument, EQ-5D, has not been widely used to assess the impact of falls on quality of life. The aim of this study was to investigate the association of single and frequent falls with EQ-5D rated quality of life in a sample of German community-dwelling seniors in primary care suffering a variety of concurrent chronic diseases and conditions.
Methods
In a cross-sectional study, a sample of community-dwelling seniors aged ≥ 72 years was interviewed by means of a standardised telephone interview. According to the number of self-reported falls within twelve months prior to interview, participants were categorised into one of three fall categories: no fall vs. one fall vs. two or more falls within twelve months. EQ-5D values as well as other characteristics were compared across the fall categories. Adjustments for a variety of concurrent chronic diseases and conditions and further variables were made by using multiple linear regression analysis, with EQ-5D being the target variable.
Results
In total, 1,792 participants (median age 77 years; 53% female) were analysed. The EQ-5D differed between fall categories. Participants reporting no fall had a mean EQ-5D score of 81.1 (standard deviation [s.d.]: 15.4, median: 78.3), while participants reporting one fall (n = 265; 14.8%) and participants with two or more falls (n = 117; 6.5%) had mean total scores of 77.0 (s.d.: 15.8, median: 78.3; mean difference to participants without a fall: -4.1, p < 0.05) and 72.1 (s.d.: 17.6, median: 72.5; mean difference: -9.0, p < 0.05), respectively. The mean difference between participants with one fall and participants with two or more falls was -4.9 (p < 0.05). Under adjustment for a variety of chronic diseases and conditions, the mean decrease in the total EQ-5D score was about -1.0 score point for one fall and about -2.5 points for two or more falls within twelve months. In quantity, this decrease is comparable to other chronic diseases adjusted for. Among the variables with the greatest negative association with EQ-5D ratings in multivariate analysis were depression and fear of falling.
Conclusions
The findings suggest that falls are negatively associated with EQ-5D rated quality of life independent of a variety of chronic diseases and conditions.
doi:10.1186/1477-7525-12-2
PMCID: PMC3895701  PMID: 24400663
Falls; Accidental falls; Fear of falling; Multiple chronic diseases; Quality of life; EQ-5D; Elderly; Cross-sectional study
4.  A Qualitative Assessment of the Content Validity of the ICECAP-A and EQ-5D-5L and Their Appropriateness for Use in Health Research 
PLoS ONE  2013;8(12):e85287.
Purpose
The ICECAP-A and EQ-5D-5L are two index measures appropriate for use in health research. Assessment of content validity allows understanding of whether a measure captures the most relevant and important aspects of a concept. This paper reports a qualitative assessment of the content validity and appropriateness for use of the eq-5D-5L and ICECAP-A measures, using novel methodology.
Methods
In-depth semi-structured interviews were conducted with research professionals in the UK and Australia. Informants were purposively sampled based on their professional role. Data were analysed in an iterative, thematic and constant comparative manner. A two stage investigation - the comparative direct approach - was developed to address the methodological challenges of the content validity research and allow rigorous assessment.
Results
Informants viewed the ICECAP-A as an assessment of the broader determinants of quality of life, but lacking in assessment of health-related determinants. The eq-5D-5L was viewed as offering good coverage of health determinants, but as lacking in assessment of these broader determinants. Informants held some concerns about the content or wording of the Self-care, Pain/Discomfort and Anxiety/Depression items (EQ-5D-5L) and the Enjoyment, Achievement and attachment items (ICECAP-A).
Conclusion
Using rigorous qualitative methodology the results suggest that the ICECAP-A and EQ-5D-5L hold acceptable levels of content validity and are appropriate for use in health research. This work adds expert opinion to the emerging body of research using patients and public to validate these measures.
doi:10.1371/journal.pone.0085287
PMCID: PMC3868594  PMID: 24367708
5.  Does Social Isolation and Low Societal Participation Predict Disability Pension? A Population Based Study 
PLoS ONE  2013;8(11):e80655.
Purpose
The aim was to examine the potential influence of social isolation and low societal participation on the future risk of receiving disability pension among individuals in Sweden. A specific aim was to describe differences depending on disability pension diagnoses, and how the results were modified by sex and age.
Method
The study comprised representative samples of Swedish women and men, who had been interviewed in any of the annual Swedish Surveys of Living Conditions between 1990 and 2007. Information on disability pension and diagnoses was added from the Swedish Social Insurance Agency’s database (1991-2011). The mean number of years of follow-up for the 53920 women and men was twelve years (SD 5.5), and the study base was restricted to the ages 20 to 64 years of age. The predictors were related to disability pension by Cox’s proportional hazards regression.
Results
Social isolation and low societal participation were associated with future disability pension also after control for age, year of interview, socio demographic conditions and self reported longstanding illness. Lone individuals were at increased risk of disability pension, and the effect of living without children was modified by sex and age. An increase in risk was particularly noticeable among younger women who reported that they had sparse contacts with others, and no close friend. Both women and men who reported that they did not participate in political discussions and who could not appeal on a decision by a public authority were also at increased risk. The effects of social isolation were mainly attributed to disability pension with mental diagnoses, and to younger individuals.
Conclusions
The study suggests that social isolation and low societal participation are predictors of future disability pension. Social isolation and low societal participation increased particularly the risk of future disability pension in mental diagnoses among younger individuals.
doi:10.1371/journal.pone.0080655
PMCID: PMC3819288  PMID: 24223229
6.  Cemented versus Uncemented Hemiarthroplasty for Femoral Neck Fractures in Elderly Patients: A Meta-Analysis 
PLoS ONE  2013;8(7):e68903.
Objective
Controversy still exists regarding using cemented or uncemented hemiarthroplasty for femoral neck fractures in elderly patients. The aim of this study is to compare the effectiveness and safety of the two surgical techniques in femoral neck fracture patients over 70 years old.
Methods
We searched PUBMED, EMBASE, Cochrane Library, CNKI and VIP Database from inception to December 2012 for relevant randomized controlled trials (RCTs). Outcomes of interest include postoperative hip function, residue pain, complication rates, mortality, reoperation rate, operation time and intraoperative blood loss. Odds ratios (OR) and weighted mean differences (WMD) from each trial were pooled using random-effects model or fixed-effects model given on the heterogeneity of the included studies.
Results
7 RCTs involving 1,125 patients (1,125 hips) were eligible for meta-analysis. Our results demonstrate that cemented hemiarthroplasty is associated with better postoperative hip function (OR = 0.48, 95% CI, 0.31–0.76; P = 0.002), lower residual pain (OR = 0.43, 95%CI, 0.29–0.64; P<0.0001), less implant-related complications (OR = 0.15, 95%CI, 0.09–0.26; P<0.00001) and longer operation time (WMD = 7.43 min, 95% CI, 5.37–9.49 min; P<0.00001). No significant difference was observed between the two groups in mortality, cardiovascular and cerebrovascular complications, local complications, general complications, reoperation rate and intraoperative blood loss.
Conclusions
Compared with uncemented hemiarthroplasty, the existing evidence indicates that cemented hemiarthroplasty can achieve better hip function, lower residual pain and less implant-related complications with no increased risk of mortality, cardiovascular and cerebrovascular complications, general complications, local complications and reoperation rate in treating elderly patients with femoral neck fractures.
doi:10.1371/journal.pone.0068903
PMCID: PMC3720851  PMID: 23935902
7.  Serum Metalloproteinases 2 and 9 as Predictors of Gait Status, Pressure Ulcer and Mortality after Hip Fracture 
PLoS ONE  2013;8(2):e57424.
Introduction
The aim of this study is to evaluate the serum activity of metalloproteinases (MMPs) -2 and -9 as predictors of pressure ulcer (PU), gait status and mortality 6 months after hip fracture.
Methods
Eighty-seven patients over the age of 65 admitted to the orthopedic unit from January to December 2010 with hip fracture were prospectively evaluated. Upon admission, patient demographic information, including age, gender and concomitant diseases, was recorded. Blood samples were taken for analysis of MMP -2 and -9 activity by gel zymography and for biochemical examination within the first 72 hours of the patient’s admission, after clinical stabilization. The fracture pattern (neck, trochanteric or subtrochanteric), time from admission to surgery, surgery duration and length of hospital stay were also recorded.
Results
Two patients were excluded due to the presence of pathological fractures (related to cancer), and three patients were excluded due to the presence of PU before admission. Eighty-two patients, with a mean age of 80.4 ± 7.3 years, were included in the analysis. Among these patients, 75.6% were female, 59.8% had PU, and 13.4% died 6 months after hip fracture. All patients underwent hip fracture repair. In a univariate analysis, there were no differences in serum MMP activity between hip fracture patients with or without PU. In addition, the multiple logistic regression analysis models, which were adjusted by age, gender, length of hospital stay and C-reactive protein, showed that the pro-MMP-9 complexed with neutrophil gelatinase-associated lipocalin form (130 kDa) was associated with gait status recovery 6 months after hip fracture.
Conclusions
In conclusion, serum pro-MMP-9 is a predictor of gait status recovery 6 months after hip fracture.
doi:10.1371/journal.pone.0057424
PMCID: PMC3577718  PMID: 23437384
8.  Cause-Specific Cardiovascular Risk Associated with Nonsteroidal Anti-Inflammatory Drugs among Myocardial Infarction Patients - A Nationwide Study 
PLoS ONE  2013;8(1):e54309.
Background
Non steroidal anti-inflammatory drugs (NSAIDs) increase mortality and morbidity after myocardial infarction (MI). We examined cause-specific mortality and morbidity associated with NSAIDs in a nationwide cohort of MI patients.
Methods and Results
By individual-level linkage of nationwide registries of hospitalization and drug dispensing from pharmacies in Denmark, patients aged >30 years admitted with first-time MI during 1997–2009 and their subsequent NSAID use were identified. The risk of three cardiovascular specific endpoints: cardiovascular death, the composite of coronary death and nonfatal MI, and the composite of fatal and nonfatal stroke, associated with NSAID use was analyzed by Cox proportional hazard analyses. Of 97,698 patients included 44.0% received NSAIDs during follow-up. Overall use of NSAIDs was associated with an increased risk of cardiovascular death (hazard ratio [HR] 1.42, 95% confidence interval [CI] 1.36–1.49). In particular use of the nonselective NSAID diclofenac and the selective cyclooxygenase-2 inhibitor rofecoxib was associated with increased risk of cardiovascular death (HR 1.96 [1.79–2.15] and HR1.66 [1.44–1.91], respectively) with a dose dependent increase in risk. Use of ibuprofen was associated with increased risk of cardiovascular death (HR 1.34[1.26–1.44]), whereas naproxen was associated with the lowest risk of (e.g., HR 1.27[1.01–1.59].
Conclusion
Use of individual NSAIDs is associated with different cause-specific cardiovascular risk and in particular rofecoxib and diclofenac were associated with increased cardiovascular morbidity and mortality. These results support caution with use of all NSAIDs in patients with prior MI.
doi:10.1371/journal.pone.0054309
PMCID: PMC3559685  PMID: 23382889
9.  Associations and Impact Factors between Living Arrangements and Functional Disability among Older Chinese Adults 
PLoS ONE  2013;8(1):e53879.
Objectives
To examine the association of living arrangements with functional disability among older persons and explore the mediation of impact factors on the relationship.
Design
Cross-sectional analysis using data from Healthy Aging study in Zhejiang Province.
Participants
Analyzed sample was drawn from a representative rural population of older persons in Wuyi County, Zhejiang Province, including 1542 participants aged 60 and over in the second wave of the study.
Measurements
Living arrangements, background, functional disability, self-rated health, number of diseases, along with contemporaneous circumstances including income, social support (physical assistance and emotional support). Instrument was Activities of Daily Living (ADL) scale, including Basic Activities Daily Living (BADL) and Instrumental Activities of Daily Living (IADL).
Results
Living arrangements were significantly associated with BADL, IADL and ADL disability. Married persons living with or without children were more advantaged on all three dimensions of functional disability. Unmarried older adults living with children only had the worst functional status, even after controlling for background, social support, income and health status variables (compared with the unmarried living alone, ß for BADL: −1.262, ß for IADL: −2.112, ß for ADL: −3.388; compared with the married living with children only, ß for BADL: −1.166, ß for IADL: −2.723, ß for ADL: −3.902). In addition, older adults without difficulty in receiving emotional support, in excellent health and with advanced age had significantly better BADL, IADL and ADL function. However, a statistically significant association between physical assistance and functional disability was not found.
Conclusion
Functional disabilities vary by living arrangements with different patterns and other factors. Our results highlight the association of unmarried elders living with children only and functioning decline comparing with other types. Our study implies policy makers should pay closer attention to unmarried elders living with children in community. Community service especially emotional support such as psychological counseling is important social support and should be improved.
doi:10.1371/journal.pone.0053879
PMCID: PMC3544765  PMID: 23342030
10.  Attitudes of the German General Population toward Early Diagnosis of Dementia – Results of a Representative Telephone Survey 
PLoS ONE  2012;7(11):e50792.
Background
Early detection of dementia has clearly improved. Even though none of the currently available treatments for the most common form of dementia, Alzheimer’s dementia, promises a cure, early diagnosis provides several benefits for patients, caregivers, and health care systems. This study aimed to describe attitudes toward early diagnosis of dementia in the German general population.
Methods
A representative telephone survey of the German population aged 18+ years (n = 1,002) was conducted in 2011.
Results
The majority of respondents (69%) would be willing to be examined for early diagnosis of dementia. Almost two thirds reported that they would prefer their general practitioner (GP) as the first source of professional help. More than half of the respondents (55%) stated their belief that dementia could be prevented. Respondents mostly indicated psychosocial prevention options.
Conclusions
Our findings suggest that the general population in Germany is very open to early diagnosis of dementia; however, this seems connected with large expectations on the effectiveness of prevention options. Dementia awareness campaigns may be employed to carefully inform the public about the prevention options currently available and their efficacy. To exploit GPs’ potential as a gatekeeper for early detection of dementia, their ability to identify patients with antecedent and mild stages of the disease must be improved.
doi:10.1371/journal.pone.0050792
PMCID: PMC3507733  PMID: 23209827
11.  Impact of Health Literacy in Patients with Chronic Musculoskeletal Disease–Systematic Review 
PLoS ONE  2012;7(7):e40210.
Objectives
To estimate the prevalence of low health literacy, and evaluate the impact of low health literacy on outcomes in patients with chronic musculoskeletal conditions.
Data Sources
We searched Embase, Pubmed, PsycInfo, and CINAHL in January 2011 for relevant studies, restricted to English-language articles.
Study Selection and Data Extraction
Studies were included if they measured health literacy and/or reported on the link between outcomes and health literacy levels in patients with osteoporosis, osteoarthritis, or rheumatoid arthritis. We assessed risk of bias from participant selection, methods of measuring health literacy and functional outcomes, missing data, and potential for confounding.
Data Synthesis
We reviewed 1863 citations and judged 8 studies to be relevant. Most were cross-sectional in nature, and five were based in the United States. Diversity in measurements, participant characteristics, and settings meant that results had to be synthesized narratively. Prevalence of low health literacy varied from 7% to 42%. Of the five studies that reported on musculoskeletal outcomes, only one showed an association (unadjusted) between low health literacy and greater pain and limitations in physical functioning. However, other studies, including those with multivariate analyses, found no significant relationship between health literacy and measures of pain or disease specific questionnaires. One clinical trial found short-term improvements in the mental health of patients with musculoskeletal conditions after an intervention to improve health literacy.
Limitations
Most of the studies were cross-sectional in nature, which precludes interpretation of a causal relationship. The sample sizes may not have been sufficiently large to enable detection of significant associations.
Conclusions
The current evidence does not show a consistent association between low health literacy and poorer functional outcomes in patients with chronic musculoskeletal conditions. In the absence of a definite link, efforts to develop interventions to improve health literacy would not necessarily improve health service or patient-related outcomes.
doi:10.1371/journal.pone.0040210
PMCID: PMC3391211  PMID: 22792242
12.  Temporomandibular Joint Disorder Complaints in Tinnitus: Further Hints for a Putative Tinnitus Subtype 
PLoS ONE  2012;7(6):e38887.
Objective
Tinnitus is considered to be highly heterogeneous with respect to its etiology, its comorbidities and the response to specific interventions. Subtyping is recommended, but it remains to be determined which criteria are useful, since it has not yet been clearly demonstrated whether and to which extent etiologic factors, comorbid states and interventional response are related to each other and are thus applicable for subtyping tinnitus. Analyzing the Tinnitus Research Initiative Database we differentiated patients according to presence or absence of comorbid temporomandibular joint (TMJ) disorder complaints and compared the two groups with respect to etiologic factors.
Methods
1204 Tinnitus patients from the Tinnitus Research Initiative (TRI) Database with and without subjective TMJ complaints were compared with respect to demographic, tinnitus and audiological characteristics, questionnaires, and numeric ratings. Data were analysed according to a predefined statistical analysis plan.
Results
Tinnitus patients with TMJ complaints (22% of the whole group) were significantly younger, had a lower age at tinnitus onset, and were more frequently female. They could modulate or mask their tinnitus more frequently by somatic maneuvers and by music or sound stimulation. Groups did not significantly differ for tinnitus duration, type of onset (gradual/abrupt), onset related events (whiplash etc.), character (pulsatile or not), hyperacusis, hearing impairment, tinnitus distress, depression, quality of life and subjective ratings (loudness etc.).
Conclusion
Replicating previous work in tinnitus patients with TMJ complaints, classical risk factors for tinnitus like older age and male gender are less relevant in tinnitus patients with TMJ complaints. By demonstrating group differences for modulation of tinnitus by movements and sounds our data further support the notion that tinnitus with TMJ complaints represents a subgroup of tinnitus with clinical features that are highly relevant for specific therapeutic management.
doi:10.1371/journal.pone.0038887
PMCID: PMC3378537  PMID: 22723902
13.  Reliability of accelerometric measurement of physical activity in older adults-the benefit of using the trimmed sum 
There is general consensus that physical activity is important for preserving functional capacities of older adults and positively influencing quality of life. While accelerometry is widely accepted and applied to assess physical activity in studies, several problems with this method remain (e.g., low retest reliability, measurement errors). The aim of this study was to test the intra-instrumental retest reliability of a wrist-worn accelerometer in a 3-day measurement of physical activity in older adults and to compare different estimators. A sample of 123 older adults (76.5 ± 5.1 years, 59 % female) wore a uniaxial accelerometer continuously for 1 week. The data were split into two repeated measurement values (week set) of 3 days each. The sum, the 80–99th quantiles and the 80–99th trimmed sums were built for each week set. Retest reliability was assessed for each estimator and graphically demonstrated by Bland–Altman plots. The intraclass correlation of the retest reliability ranged from 0.22 to 0.91. Retest reliability increases when a more robust estimator than the overall sum is used. Therefore, the trimmed sum can be recommended as a conservative estimate of the physical activity level of older adults.
doi:10.1007/s11556-012-0100-x
PMCID: PMC3459084  PMID: 23144665
Aged; Reproducibility of results; Activities of daily living; Bias (epidemiology)
14.  Losing the Ability in Activities of Daily Living in the Oldest Old: A Hierarchic Disability Scale from the Newcastle 85+ Study 
PLoS ONE  2012;7(2):e31665.
Objectives
To investigate the order in which 85 year olds develop difficulty in performing a wide range of daily activities covering basic personal care, household care and mobility.
Design
Cross-sectional analysis of baseline data from a cohort study.
Setting
Newcastle upon Tyne and North Tyneside, UK.
Participants
Individuals born in 1921, registered with participating general practices.
Measurements
Detailed health assessment including 17 activities of daily living related to basic personal care, household care and mobility. Questions were of the form ‘Can you …’ rather than ‘Do you…’ Principal Component Analysis (PCA) was used to confirm a single underlying dimension for the items and Mokken Scaling was used to determine a subsequent hierarchy. Validity of the hierarchical scale was assessed by its associations with known predictors of disability.
Results
839 people within the Newcastle 85+ study for whom complete information was available on self-reported Activities of Daily Living (ADL). PCA confirmed a single underlying dimension; Mokken scaling confirmed a hierarchic scale where ‘Cutting toenails’ was the first item with which participants had difficulty and ‘feeding’ the last. The ordering of loss differed between men and women. Difficulty with ‘shopping’ and ‘heavy housework’ were reported earlier by women whilst men reported ‘walking 400 yards’ earlier. Items formed clusters corresponding to strength, balance, lower and upper body involvement and domains specifically required for balance and upper/lower limb functional integrity.
Conclusion
This comprehensive investigation of ordering of ability in activities in 85 year olds will inform researchers and practitioners assessing older people for onset of disability and subsequent care needs.
doi:10.1371/journal.pone.0031665
PMCID: PMC3280316  PMID: 22355385
15.  Massage Therapy for Osteoarthritis of the Knee: A Randomized Dose-Finding Trial 
PLoS ONE  2012;7(2):e30248.
Background
In a previous trial of massage for osteoarthritis (OA) of the knee, we demonstrated feasibility, safety and possible efficacy, with benefits that persisted at least 8 weeks beyond treatment termination.
Methods
We performed a RCT to identify the optimal dose of massage within an 8-week treatment regimen and to further examine durability of response. Participants were 125 adults with OA of the knee, randomized to one of four 8-week regimens of a standardized Swedish massage regimen (30 or 60 min weekly or biweekly) or to a Usual Care control. Outcomes included the Western Ontario and McMaster Universities Arthritis Index (WOMAC), visual analog pain scale, range of motion, and time to walk 50 feet, assessed at baseline, 8-, 16-, and 24-weeks.
Results
WOMAC Global scores improved significantly (24.0 points, 95% CI ranged from 15.3–32.7) in the 60-minute massage groups compared to Usual Care (6.3 points, 95% CI 0.1–12.8) at the primary endpoint of 8-weeks. WOMAC subscales of pain and functionality, as well as the visual analog pain scale also demonstrated significant improvements in the 60-minute doses compared to usual care. No significant differences were seen in range of motion at 8-weeks, and no significant effects were seen in any outcome measure at 24-weeks compared to usual care. A dose-response curve based on WOMAC Global scores shows increasing effect with greater total time of massage, but with a plateau at the 60-minute/week dose.
Conclusion
Given the superior convenience of a once-weekly protocol, cost savings, and consistency with a typical real-world massage protocol, the 60-minute once weekly dose was determined to be optimal, establishing a standard for future trials.
Trial Registration
ClinicalTrials.gov NCT00970008
doi:10.1371/journal.pone.0030248
PMCID: PMC3275589  PMID: 22347369
16.  Patterns of Multimorbidity in the Aged Population. Results from the KORA-Age Study 
PLoS ONE  2012;7(1):e30556.
Multimorbidity is a common problem in aged populations with a wide range of individual and societal consequences. The objective of the study was to explore patterns of comorbidity and multimorbidity in an elderly population using different analytical approaches. Data were gathered from the population-based KORA-Age project, which included 4,127 persons aged 65–94 years living in the city of Augsburg and its two surrounding counties in Southern Germany. Information on the presence of 13 chronic conditions was collected in a standardized telephone interview and a self-administered questionnaire. Patterns of comorbidity and multimorbidity were analyzed using prevalence figures, logistic regression models and exploratory tetrachoric factor analysis. The prevalence of multimorbidity (≥2 diseases) was 58.6% in the total sample. Hypertension and diabetes (Odds Ratio [OR] 2.95, 99.58% confidence interval [CI] [2.19–3.96]), as well as hypertension and stroke (OR 2.00, 99.58% CI [1.26–3.16]) most often occurred in combination. This association was independent of age, sex and the presence of other conditions. Using factor analysis, we identified four patterns of multimorbidity: the first pattern includes cardiovascular and metabolic diseases, the second includes joint, liver, lung and eye diseases, the third covers mental and neurologic diseases and the fourth pattern includes gastrointestinal diseases and cancer. 44% of the persons were assigned to at least one of the four multimorbidity patterns; 14% could be assigned to both the cardiovascular/metabolic and the joint/liver/lung/eye pattern. Further common pairs were the mental/neurologic pattern combined with the cardiovascular/metabolic pattern (7.2%) or the joint/liver/lung/eye pattern (5.3%), respectively. Our results confirmed the existence of co-occurrence of certain diseases in elderly persons, which is not caused by chance. Some of the identified patterns of multimorbidity and their overlap may indicate common underlying pathological mechanisms.
doi:10.1371/journal.pone.0030556
PMCID: PMC3264590  PMID: 22291986
17.  Clinical Characteristics and Outcomes of Hospitalized Older Patients with Distinct Risk Profiles for Functional Decline: A Prospective Cohort Study 
PLoS ONE  2012;7(1):e29621.
Background
The aim of this research was to study the clinical characteristics and mortality and disability outcomes of patients who present distinct risk profiles for functional decline at admission.
Methods
Multicenter, prospective cohort study conducted between 2006 and 2009 in three hospitals in the Netherlands in consecutive patients of ≥65 years, acutely admitted and hospitalized for at least 48 hours. Nineteen geriatric conditions were assessed at hospital admission, and mortality and functional decline were assessed until twelve months after admission. Patients were divided into risk categories for functional decline (low, intermediate or high risk) according to the Identification of Seniors at Risk-Hospitalized Patients.
Results
A total of 639 patients were included, with a mean age of 78 years. Overall, 27%, 33% and 40% of the patients were at low, intermediate or high risk, respectively, for functional decline. Low-risk patients had fewer geriatric conditions (mean 2.2 [standard deviation [SD] 1.3]) compared with those at intermediate (mean 3.8 [SD 2.1]) or high risk (mean 5.1 [SD 1.8]) (p<0.001). Twelve months after admission, 39% of the low-risk group had an adverse outcome, compared with 50% in the intermediate risk group and 69% in the high risk group (p<0.001).
Conclusion
By using a simple risk assessment instrument at hospital admission, patients at low, intermediate or high risk for functional decline could be identified, with distinct clinical characteristics and outcomes. This approach should be tested in clinical practice and research and might help appropriately tailor patient care.
doi:10.1371/journal.pone.0029621
PMCID: PMC3251572  PMID: 22238628
18.  Predictors of Health-Related Quality of Life in Patients at Risk for Cardiovascular Disease in European Primary Care 
PLoS ONE  2011;6(12):e29334.
Background
Cardiovascular risk management plays an important role in primary care. In patients at high risk for cardiovascular diseases (CVD) lifestyle and, where appropriate, medical interventions are recommended in guidelines. Health-related quality of life (HRQoL) is an important outcome in clinical practice. This study aimed to assess the HRQoL of this patient group and to investigate the impact of both patients' characteristics and practice quality scores on their assessments of HRQoL.
Methods and Findings
An observational study in 218 general practices from 8 European countries was conducted. 2142 patients at risk for CVD (33.5% female) with a mean age of 66.3 (SD 9.1) years completed a questionnaire including the EQ-5D instrument and provided data from medical record. Validated quality indicators of general practices were assessed using practice questionnaires and face-to-face interviews. A hierarchical multilevel analysis was performed to identify predictors of EQ-5D scores at patient and practice level. The mean EQ-5D score was 0.78 (SD 0.19). Female gender (r = −0.03, p<0.0016), age (r = −0.01, p = 0.0387) and lower educational level (r = −0.03, p<0.0001) were correlated negatively with EQ-5D scores. Clinically more important was the correlation of HRQoL with the frequency of practice contacts (r = −0.12, p<0.0001) and the number of uncontrolled risk factors (r = −0.01, p<0.0039). Medication adherence (r = 0.032, p<0.0001), and physical activity (r = 0.02, p<0.0001) were identified as positive predictors of HRQoL. The EUPROPEP-score category ‘organization’ (r = 0.02, p<0.0001) was positively related to EQ-5D scores, whereas other practice scores were not correlated to EQ-5D-scores.
Conclusions
In patients at risk for CVD, good medication adherence, regular physical activity, controlling of biomedical risk factor levels and patient-centered practice organization have been shown to be positively correlated to HRQoL and should therefore be targeted in interventions not only to reduce morbidity but also to sustain or even to ameliorate HRQoL.
doi:10.1371/journal.pone.0029334
PMCID: PMC3245263  PMID: 22216250
19.  Assessing Quality of Care of Elderly Patients Using the ACOVE Quality Indicator Set: A Systematic Review 
PLoS ONE  2011;6(12):e28631.
Background
Care of the elderly is recognized as an increasingly important segment of health care. The Assessing Care Of Vulnerable Elderly (ACOVE) quality indicators (QIs) were developed to assess and improve the care of elderly patients.
Objectives
The purpose of this review is to summarize studies that assess the quality of care using QIs from or based on ACOVE, in order to evaluate the state of quality of care for the reported conditions.
Methods
We systematically searched MEDLINE, EMBASE and CINAHL for English-language studies indexed by February 2010. Articles were included if they used any ACOVE QIs, or adaptations thereof, for assessing the quality of care. Included studies were analyzed and relevant information was extracted. We summarized the results of these studies, and when possible generated an overall conclusion about the quality of care as measured by ACOVE for each condition, in various settings, and for each QI.
Results
Seventeen studies were included with 278 QIs (original, adapted or newly developed). The quality scores showed large variation between and within conditions. Only a few conditions showed a stable pass rate range over multiple studies. Overall, pass rates for dementia (interquartile range (IQR): 11%–35%), depression (IQR: 27%–41%), osteoporosis (IQR: 34%–43%) and osteoarthritis (IQR: 29–41%) were notably low. Medication management and use (range: 81%–90%), hearing loss (77%–79%) and continuity of care (76%–80%) scored higher than other conditions. Out of the 278 QIs, 141 (50%) had mean pass rates below 50% and 121 QIs (44%) had pass rates above 50%. Twenty-three percent of the QIs scored above 75%, and 16% scored below 25%.
Conclusions
Quality of care per condition varies markedly across studies. Although there has been much effort in improving the care for elderly patients in the last years, the reported quality of care according to the ACOVE indicators is still relatively low.
doi:10.1371/journal.pone.0028631
PMCID: PMC3241679  PMID: 22194872
20.  MRI Findings for Frozen Shoulder Evaluation: Is the Thickness of the Coracohumeral Ligament a Valuable Diagnostic Tool? 
PLoS ONE  2011;6(12):e28704.
Background
Recent studies have demonstrated that the coracohumeral ligament (CHL) is shortened and thickened in a frozen shoulder. We analyzed the rate in CHL visualization between patients with frozen shoulder and normal volunteers using Magnetic Resonance Imaging (MRI) to determine the CHL thickness in the patients with a frozen shoulder.
Methods and Findings
There were 72 shoulder joints in 72 patients (50 femles and 22 males with a mean age of 53.5 years) with clinical evidence and MR imaging evidence of frozen shoulder. These were prospectively analyzed to identify and measure the maximum thickness of the CHL. The control group, which included 120 shoulder joints in 60 normal volunteer individuals (30 females and 30 males with a mean age of 50.5 years) was also referred for MR imaging. A chi-square test was used to analyze the data of the rate of CHL visualization between the patients with frozen shoulder and the control group. A two-way ANOVA was used to analyze the mean maximal thickness of CHL. The CHL was visualized in 110 out of 120 shoulders in the control group (91.7%), and in 57 out of 72 shoulders for the frozen shoulder group (79.2%), there was significant difference, using a chi-square test (P<0.05). The CHL was not visualized in 10 out of 120 shoulders in the control group (8.3%), and 15 out of 72 shoulders in the frozen shoulder group (20.8%), there was a significant difference (P<0.05). The CHL thickness (3.99±1.68 mm) in the patients with frozen shoulder was significantly greater than that thickness (3.08±1.32 mm) in the control group, using a two-way ANOVA (P<0.001). The CHL thickness (3.52±1.52 mm, n = 97) in the female shoulders was no significantly greater than that thickness (3.22±1.49 mm, n = 70) in the male shoulders, using a two-way ANOVA (P>0.05).
Conclusions
MR Imaging is a satisfactory method for CHL depiction, and a thickened CHL is highly suggestive of frozen shoulder.
doi:10.1371/journal.pone.0028704
PMCID: PMC3233594  PMID: 22163326
21.  Recognition of Morphometric Vertebral Fractures by Artificial Neural Networks: Analysis from GISMO Lombardia Database 
PLoS ONE  2011;6(11):e27277.
Background
It is known that bone mineral density (BMD) predicts the fracture's risk only partially and the severity and number of vertebral fractures are predictive of subsequent osteoporotic fractures (OF). Spinal deformity index (SDI) integrates the severity and number of morphometric vertebral fractures. Nowadays, there is interest in developing algorithms that use traditional statistics for predicting OF. Some studies suggest their poor sensitivity. Artificial Neural Networks (ANNs) could represent an alternative. So far, no study investigated ANNs ability in predicting OF and SDI. The aim of the present study is to compare ANNs and Logistic Regression (LR) in recognising, on the basis of osteoporotic risk-factors and other clinical information, patients with SDI≥1 and SDI≥5 from those with SDI = 0.
Methodology
We compared ANNs prognostic performance with that of LR in identifying SDI≥1/SDI≥5 in 372 women with postmenopausal-osteoporosis (SDI≥1, n = 176; SDI = 0, n = 196; SDI≥5, n = 51), using 45 variables (44 clinical parameters plus BMD). ANNs were allowed to choose relevant input data automatically (TWIST-system-Semeion). Among 45 variables, 17 and 25 were selected by TWIST-system-Semeion, in SDI≥1 vs SDI = 0 (first) and SDI≥5 vs SDI = 0 (second) analysis. In the first analysis sensitivity of LR and ANNs was 35.8% and 72.5%, specificity 76.5% and 78.5% and accuracy 56.2% and 75.5%, respectively. In the second analysis, sensitivity of LR and ANNs was 37.3% and 74.8%, specificity 90.3% and 87.8%, and accuracy 63.8% and 81.3%, respectively.
Conclusions
ANNs showed a better performance in identifying both SDI≥1 and SDI≥5, with a higher sensitivity, suggesting its promising role in the development of algorithm for predicting OF.
doi:10.1371/journal.pone.0027277
PMCID: PMC3208634  PMID: 22076144
22.  Adherence of Pharmaceutical Advertisements in Medical Journals to FDA Guidelines and Content for Safe Prescribing 
PLoS ONE  2011;6(8):e23336.
Background
Physician-directed pharmaceutical advertising is regulated in the United States by the Food and Drug Administration (FDA); adherence to current FDA guidelines is unknown. Our objective was to determine adherence rates of physician-directed print advertisements in biomedical journals to FDA guidelines and describe content important for safe prescribing.
Methods and Findings
Cross-sectional analysis of November 2008 pharmaceutical advertisements within top U.S.-based biomedical journals publishing original research. We excluded advertisements for devices, over the counter medications, and disease awareness. We utilized FDA guideline items identifying unique forms of advertisement bias to categorize advertisements as adherent to FDA guidelines, possibly non-adherent to at least 1 item, or non-adherent to at least 1 item. We also evaluated advertisement content important for safe prescribing, including benefit quantification, risk information and verifiable references. All advertisements were evaluated by 2 or more investigators, with differences resolved by discussion. Twelve journals met inclusion criteria. Nine contained pharmaceutical advertisements, including 192 advertisements for 82 unique products; median 2 per product (range 1–14). Six “teaser” advertisements presented only drug names, leaving 83 full unique advertisements. Fifteen advertisements (18.1%) adhered to all FDA guidelines, 41 (49.4%) were non-adherent with at least one form of FDA-described bias, and 27 (32.5%) were possibly non-adherent due to incomplete information. Content important for safe prescribing was often incomplete; 57.8% of advertisements did not quantify serious risks, 48.2% lacked verifiable references and 28.9% failed to present adequate efficacy quantification. Study limitations included its focus on advertisements from a single month, the subjectivity of FDA guidelines themselves, and the necessary subjectivity of determinations of adherence.
Conclusions
Few physician-directed print pharmaceutical advertisements adhere to all FDA guidelines; over half fail to quantify serious risks. The FDA could better protect public health by creating new more objective advertisement guidelines requiring transparent presentation of basic safety and efficacy information.
doi:10.1371/journal.pone.0023336
PMCID: PMC3157354  PMID: 21858076
23.  Large Scale Replication Study of the Association between HLA Class II/BTNL2 Variants and Osteoarthritis of the Knee in European-Descent Populations 
PLoS ONE  2011;6(8):e23371.
Osteoarthritis (OA) is the most common form of arthritis and a major cause of disability. This study evaluates the association in Caucasian populations of two single nucleotide polymorphisms (SNPs) mapping to the Human Leukocyte Antigen (HLA) region and deriving from a genome wide association scan (GWAS) of knee OA in Japanese populations. The frequencies for rs10947262 were compared in 36,408 controls and 5,749 knee OA cases from European-descent populations. rs7775228 was tested in 32,823 controls and 1,837 knee OA cases of European descent. The risk (major) allele at rs10947262 in Caucasian samples was not significantly associated with an odds ratio (OR)  = 1.07 (95%CI 0.94 -1.21; p = 0.28). For rs7775228 the meta-analysis resulted in OR = 0.94 (95%CI 0.81-1.09; p = 0.42) for the allele associated with risk in the Japanese GWAS. In Japanese individuals these two SNPs are in strong linkage disequilibrium (LD) (r2 = 0.86) with the HLA class II haplotype DRB1*1502 DQA1*0103 DQB1*0601 (frequency 8%). In Caucasian and Chinese samples, using imputed data, these SNPs appear not to be in LD with that haplotype (r2<0.07). The rs10947262 and rs7775228 variants are not associated with risk of knee OA in European descent populations and they do not appear tag the same HLA class II haplotype as they do in Japanese individuals.
doi:10.1371/journal.pone.0023371
PMCID: PMC3154440  PMID: 21853121
24.  Reduced Health-Related Quality of Life in Elders with Frailty: A Cross-Sectional Study of Community-Dwelling Elders in Taiwan 
PLoS ONE  2011;6(7):e21841.
Purpose
Exploring the domains and degrees of health-related quality of life (HRQOL) that are affected by the frailty of elders will help clinicians understand the impact of frailty. This association has not been investigated in community-dwelling elders. Therefore, we examined the domains and degree of HRQOL of elders with frailty in the community in Taiwan.
Methods
A total of 933 subjects aged 65 years and over were recruited in 2009 from a metropolitan city in Taiwan. Using an adoption of the Fried criteria, frailty was defined by five components: shrinking, weakness, poor endurance and energy, slowness, and low physical activity level. HRQOL was assessed by the short form 36 (SF-36). The multiple linear regression model was used to test the independent effects of frailty on HRQOL.
Results
After multivariate adjustment, elders without frailty reported significantly better health than did the pre-frail and frail elders on all scales, and the pre-frail elders reported better health than did the frail elders for all scales except the scales of role limitation due to physical and emotional problems and the Mental Component Summary (MCS). The significantly negative differences between frail and robust elders ranged from 3.58 points for the MCS to 22.92 points for the physical functioning scale. The magnitude of the effects of frail components was largest for poor endurance and energy, and next was for slowness. The percentages of the variations of these 10 scales explained by all factors in the models ranged from 11.1% (scale of role limitation due to emotional problems) to 49.1% (scale of bodily pain).
Conclusions
Our study demonstrates that the disabilities in physical health inherent in frailty are linked to a reduction in HRQOL. Such an association between clinical measures and a generic measure of the HRQOL may offer clinicians new information to understand frailty and to conceptualize it within the broader context of disability.
doi:10.1371/journal.pone.0021841
PMCID: PMC3128625  PMID: 21747961
25.  Validation of Case-Finding Algorithms Derived from Administrative Data for Identifying Adults Living with Human Immunodeficiency Virus Infection 
PLoS ONE  2011;6(6):e21748.
Objective
We sought to validate a case-finding algorithm for human immunodeficiency virus (HIV) infection using administrative health databases in Ontario, Canada.
Methods
We constructed 48 case-finding algorithms using combinations of physician billing claims, hospital and emergency room separations and prescription drug claims. We determined the test characteristics of each algorithm over various time frames for identifying HIV infection, using data abstracted from the charts of 2,040 randomly selected patients receiving care at two medical practices in Toronto, Ontario as the reference standard.
Results
With the exception of algorithms using only a single physician claim, the specificity of all algorithms exceeded 99%. An algorithm consisting of three physician claims over a three year period had a sensitivity and specificity of 96.2% (95% CI 95.2%–97.9%) and 99.6% (95% CI 99.1%–99.8%), respectively. Application of the algorithm to the province of Ontario identified 12,179 HIV-infected patients in care for the period spanning April 1, 2007 to March 31, 2009.
Conclusions
Case-finding algorithms generated from administrative data can accurately identify adults living with HIV. A relatively simple “3 claims in 3 years” definition can be used for assembling a population-based cohort and facilitating future research examining trends in health service use and outcomes among HIV-infected adults in Ontario.
doi:10.1371/journal.pone.0021748
PMCID: PMC3128093  PMID: 21738786

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