Development of a shape-based algorithm for identification of asymptomatic vertebral compression fractures: A proof-of-principle study.

Objectives: Vertebral fracture is both common and serious among adults, yet it often goes undiagnosed. This study aimed to develop a shape-based algorithm (SBA) for the automatic identification of vertebral fractures. Methods: The study included 144 participants (50 individuals with a fracture and 94 without a fracture) whose plain thoracolumbar spine X-rays were taken. Clinical diagnosis of vertebral fracture (grade 0 to 3) was made by rheumatologists using Genant's semiquantitative method. The SBA algorithm was developed to determine the ratio of vertebral body height loss. Based on the ratio, SBA classifies a vertebra into 4 classes: 0 = normal, 1 = mild fracture, 2 = moderate fracture, 3 = severe fracture). The concordance between clinical diagnosis and SBA-based classification was assessed at both person and vertebra levels. Results: At the person level, the SBA achieved a sensitivity of 100% and specificity of 62% (95% CI, 51%-72%). At the vertebra level, the SBA achieved a sensitivity of 84% (95% CI, 72%-93%), and a specificity of 88% (95% CI, 85%-90%). On average, the SBA took 0.3 s to assess each X-ray. Conclusions: The SBA developed here is a fast and efficient tool that can be used to systematically screen for asymptomatic vertebral fractures and reduce the workload of healthcare professionals.

Health Perceptions, Multimorbidity, and New Fractures and Mortality Among Patients With a Fracture.

Importance: A high proportion of patients who sustain a fracture have multimorbidity. However, the association of multimorbidity with postfracture adverse outcomes, such as subsequent fractures and premature mortality, has not been widely explored. Objective: To examine the association of multimorbidity and self-rated health with subsequent fractures and mortality after fracture. Design, Setting, and Participants: This prospective cohort study included participants from New South Wales, Australia, in the Sax Institute's 45 and Up Study (n = 267 357). Participants were recruited from July 2005 to December 2009 and followed up from the date of the incident fracture until subsequent fracture, death, or the end of the study (April 2017), whichever occurred first, with questionnaire data linked to hospital admission and medication records. Data analysis was reported between March and September 2023. Exposures: Charlson Comorbidity Index (CCI) score and self-rated health (SRH). Main Outcomes and Measures: The main outcomes were subsequent fracture or mortality after an incident fracture. Associations between SRH measures and subsequent fracture and mortality were also assessed. All analyses were stratified by sex given the different fracture and mortality risk profiles of females and males. Results: Of 25 280 adults who sustained incident fractures, 16 191 (64%) were female (mean [SD] age, 74 [12] years) and 9089 (36%) were male (mean [SD] age, 74 [13] years). During a median follow-up time of 2.8 years (IQR, 1.1-5.2 years), 2540 females (16%) and 1135 males (12%) sustained a subsequent fracture and 2281 females (14%) and 2140 males (24%) died without a subsequent fracture. Compared with a CCI score of less than 2, those with a CCI score of 2 to 3 had an increased risk of subsequent fracture (females: hazard ratio [HR], 1.16 [95% CI, 1.05-1.27]; males: HR, 1.25 [95% CI, 1.09-1.43]) and mortality (females: HR, 2.19 [95% CI, 1.99-2.40]; males: HR, 1.89 [95% CI, 1.71-2.09]). Those with a CCI score of 4 or greater had greater risks of subsequent fracture (females: HR, 1.33 [95% CI, 1.12-1.58]; males: HR, 1.48 [95% CI, 1.21-1.81]) and mortality (females: HR, 4.48 [95% CI, 3.97-5.06]; males: HR, 3.82 [95% CI 3.41-4.29]). Self-rated health was also significantly associated with subsequent fracture and mortality. Those reporting the poorest health and quality of life had the highest subsequent fracture risks, and their mortality risks were even higher. Conclusions and Relevance: In this cohort study, both CCI and SRH measures were associated with increased risk of subsequent fractures and mortality after fracture, underscoring the importance of managing the care of patients with comorbidities who sustain a fracture.

Association between Fat Mass and Obesity-Related Transcript Polymorphisms and Osteoporosis Phenotypes.

BACKGROUND: Common variants in the fat mass and obesity-related transcript (FTO) gene are related to body mass index and obesity, suggesting its potential association with bone mineral density (BMD) and fracture risk. This study sought to define the association between FTO gene variants and the following phenotypes: (1) BMD; (2) bone loss; and (3) fracture risk. METHODS: This analysis was based on the Dubbo Osteoporosis Epidemiology Study that included 1,277 postmenopausal women aged ≥60 years living in Dubbo, Australia. BMD at the femoral neck and lumbar spine was measured biennially by dual energy X-ray absorptiometry (GE Lunar). Fractures were radiologically ascertained. Six single nucleotide polymorphisms (SNPs; rs1421085, rs1558902, rs1121980, rs17817449, rs9939609, and rs9930506) of the FTO gene were genotyped using TaqMan assay. RESULTS: Women homozygous for the minor allele (GG) of rs9930506 had a significantly higher risk of hip fracture (adjusted hazard ratio, 1.93; 95% confidence interval, 1.15-3.23) than those homozygous for the major allele (AA) after adjusting for potential confounding effects. Similar associations were also observed for the minor allele of rs1121980. However, there was no significant association between the FTO SNPs and BMD or the rate of bone loss. CONCLUSIONS: Common variations in the FTO gene are associated with a hip fracture risk in women, and the association is not mediated through BMD or bone loss.

Prevalence, incidence of and risk factors for vertebral fracture in the community: the Vietnam Osteoporosis Study.

The epidemiology of vertebral fractures (VF) in underrepresented populations is not well-documented. This cohort study was part of a longitudinal osteoporosis research project with the aim of determining the prevalence, incidence, and risk factors for VF. 401 individuals (155 men) aged 50 years and older without a clinical diagnosis of VF were took radiographs at baseline and 2 years later. VF were ascertained using the Genant's semi-quantitative method. Bone mineral density (BMD) of femoral neck and lumbar spine were measured by dual-energy X-ray absorptiometry (Hologic Inc). The association between VF and risk factors was analyzed by the multiple logistic regression. The 95% confidence interval for prevalence and incidence was estimated by exact Poisson test. At baseline, the prevalence of VF was 12.2% (n = 49, 95% CI 9.0-16.2%) and increased with advancing age with one-fifth of those aged 70 and older having a VF. During the follow-up period, we observed 6 new VF, making the incidence of 6.6/1000 person-years (n = 6, 95% CI 2.4-14.3). The risk of prevalent VF was associated with male gender (OR: 2.67; 95% CI 1.28-5.87) and T-score at the femoral neck (OR per one SD decrease: 1.1; 1.03-1.17). These data indicate that VF is common among adults, and that lower femoral neck BMD was a risk factor for VF.

Machine learning to detect the SINEs of cancer.

We previously described an approach called RealSeqS to evaluate aneuploidy in plasma cell-free DNA through the amplification of ~350,000 repeated elements with a single primer. We hypothesized that an unbiased evaluation of the large amount of sequencing data obtained with RealSeqS might reveal other differences between plasma samples from patients with and without cancer. This hypothesis was tested through the development of a machine learning approach called Alu Profile Learning Using Sequencing (A-PLUS) and its application to 7615 samples from 5178 individuals, 2073 with solid cancer and the remainder without cancer. Samples from patients with cancer and controls were prespecified into four cohorts used for model training, analyte integration, and threshold determination, validation, and reproducibility. A-PLUS alone provided a sensitivity of 40.5% across 11 different cancer types in the validation cohort, at a specificity of 98.5%. Combining A-PLUS with aneuploidy and eight common protein biomarkers detected 51% of the cancers at 98.9% specificity. We found that part of the power of A-PLUS could be ascribed to a single feature-the global reduction of AluS subfamily elements in the circulating DNA of patients with solid cancer. We confirmed this reduction through the analysis of another independent dataset obtained with a different approach (whole-genome sequencing). The evaluation of Alu elements may therefore have the potential to enhance the performance of several methods designed for the earlier detection of cancer.

BONEcheck: A digital tool for personalized bone health assessment.

Objectives: Osteoporotic fracture is a significant public health burden associated with increased mortality risk and substantial healthcare costs. Accurate and early identification of high-risk individuals and mitigation of their risks is a core part of the treatment and prevention of fractures. Here we introduce a digital tool called 'BONEcheck' for personalized assessment of bone health. Methods: The development of BONEcheck primarily utilized data from the prospective population-based Dubbo Osteoporosis Epidemiology Study and the Danish Nationwide Registry. BONEcheck has 3 modules: input data, risk estimates, and risk context. Input variables include age, gender, prior fracture, fall incidence, bone mineral density (BMD), comorbidities, and genetic variants associated with BMD. Results: Based on the input variables, BONEcheck estimates the probability of any fragility fracture and hip fracture within 5 years, subsequent fracture risk, skeletal age, and time to reach osteoporosis. The probability of fracture is shown in both numeric and human icon array formats. The risk is also contextualized within the framework of treatment and management options on Australian guidelines, with consideration given to the potential fracture risk reduction and survival benefits. Skeletal age was estimated as the sum of chronological age and years of life lost due to a fracture or exposure to risk factors that elevate mortality risk. Conclusions: BONEcheck is an innovative tool that empowers doctors and patients to engage in well-informed discussions and make decisions based on the patient's risk profile. Public access to BONEcheck is available via https://bonecheck.org and in Apple Store (iOS) and Google Play (Android).

Prevention of Hip Fractures: Trade-off between Minor Benefits to Individuals and Large Benefits to the Community.

Goeffrey Rose postulated that a population-based measure bringing a small benefit to each individual can yield large benefits to the community. We aimed to test this axiom by quantifying the relationship between change in bone mineral density (BMD) and hip fracture incidence between two prospective cohorts separated by ~10 years. In this prospective population-based Dubbo Osteoporosis Epidemiology Study (DOES), the participants aged 60+ were recruited in two waves: the initial cohort (1311 women, 842 men) in 1989 to 1992 and the second cohort (974 women, 544 men) in 1999 to 2001. The incident hip fracture was radiologically ascertained. Femoral neck BMD was measured biannually. Multivariable-adjusted Cox's proportional hazards models were adjusted for the predefined covariates such as age, BMI, lifestyle factors, falls, and prior fracture. Compared with the initial cohort, the second cohort had a higher femoral neck BMD by ~0.04 g/cm2 in women and 0.03 g/cm2 in men. However, the prevalence of osteoporosis in the second cohort was halved (prevalence ratio 0.51, 95% CI 0.36 to 0.73 in women; 0.45, 0.24 to 0.84 in men), and its hip fracture incidence was significantly reduced (hazard ratio 0.54, 95% CI, 0.38 to 0.78 in women; 0.39, 0.19 to 0.80 in men). Sensitivity analyses indicated that the "effect" was unlikely due to unmeasured confounders. These findings suggest that a population-wide strategy aimed at enhancing BMD across the entire population could lead to a substantial decrease in the incidence of hip fractures. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Genetic Prediction of Lifetime Risk of Fracture.

CONTEXT: Fragility fracture is a significant public health problem because it is associated with increased mortality. We want to find out whether the risk of fracture can be predicted from the time of birth. OBJECTIVE: To examine the association between a polygenic risk score (PRS) and lifetime fracture risk. METHODS: This population-based prospective study involved 3515 community-dwelling individuals aged 60+ years who have been followed for up to 20 years. Femoral neck bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry. A PRS was created by summing the weighted number of risk alleles for each single nucleotide polymorphism using BMD-associated coefficients. Fragility fractures were radiologically ascertained, whereas mortality was ascertained through a state registry. Residual lifetime risk of fracture (RLRF) was estimated by survival analysis. RESULTS: The mortality-adjusted RLRF for women and men was 36% (95% CI, 34%-39%) and 21% (18%-24%), respectively. Individuals with PRS > 4.24 (median) had a greater risk (1.2-fold in women and 1.1-fold in men) than the population average risk. For hip fracture, the average RLRF was 10% (95% CI, 8%-12%) for women and ∼5% (3%-7%) for men; however, the risk was significantly increased by 1.5-fold and 1.3-fold for women and men with high PRS, respectively. CONCLUSION: A genetic profiling of BMD-associated genetic variants is associated with the residual lifetime risk of fracture, suggesting the potential for incorporating the polygenic risk score in personalized fracture risk assessment.

Longitudinal changes in bone mineral density during perimenopausal transition: the Vietnam Osteoporosis Study.

Based on the prospective cohort of the Vietnam Osteoporosis Study, we show that bone loss occurred before menopause, and that the loss accelerated in the first 5 years post-menopause. PURPOSE: To define the change in bone mineral density (BMD) among women during the menopausal transition. METHODS: The study involved 1062 women aged 40-59 who were participants of the population-based prospective Vietnam Osteoporosis Study. BMD at the femoral neck (FN), lumbar spine (LS), and whole body scan was measured by DXA. Each woman has had two BMD measurements separated by approximately 2 years, and the rate of BMD change was calculated for each woman. Multivariable linear regression models were used to quantify the association between body composition parameters and the rate of BMD change. RESULTS: At FN, there were 3 phases of BMD change: a slight decline before the age of 45-49 (average loss of 0.51%/year); a substantial decline between the ages of 49 and 54 (average loss of 1.39%/year); and then slowed down between the ages of 54 and 59 (average loss of 0.31%/year). The same trend was also observed at LS: a slight decline (- 0.56%/year) among women aged 45-49; then a significant decline between the ages of 50 and 54 (- 1.33%/year); but then slowed down at - 0.31%/year after the age of 55. Changes in BMD were not significantly associated with changes in lean mass or fat mass. CONCLUSIONS: Although bone loss occurred before menopause, the loss accelerated in the early perimenopausal transition (45-50 years of age). This finding suggests that screening for osteoporosis in women should be considered at the age of 45.

Muscle strength and physical performance contribute to and improve fracture risk prediction in older people: A narrative review.

Osteoporotic fractures present a major health problem with an increasing prevalence in older people. Fractures are associated with premature mortality, reduced quality of life, subsequent fracture, and increased costs. Hence, it is crucial to identify those at higher risk of fracture. Fracture risk assessment tools incorporated clinical risk factors to improve fracture predictive power over BMD alone. However, fracture risk prediction using these algorithms remains suboptimal, warranting further improvement. Muscle strength and physical performance measurements have been associated with fracture risk. In contrast, the contribution of sarcopenia, the composite condition of low muscle mass, muscle strength and/or physical performance, to fracture risk is unclear. It is uncertain whether this is due to the problematic definition of sarcopenia per se or limitations of the diagnostic tools and cut-off points of the muscle mass component. The recent position statement from the Sarcopenia Definition and Outcomes Consortium confirmed the inclusion of muscle strength and performance in the definition of sarcopenia but not DXA-assessed lean mass. Therefore, clinicians should focus on functional assessment (muscle strength and performance) rather than muscle mass, at least as assessed by DXA, as predictors of fractures. Muscle strength and performance are modifiable risk factors. Resistance exercise improves muscle parameters in the elderly, potentially leading to reduced risk of falls and fractures in the general population and in those who sustained a fracture. Therapists may consider exercise intervention to improve muscle parameters and potentially reduce the risk of fractures. The aim of this review was to explore 1) the contribution of muscle parameters (i.e., muscle mass, strength, and physical performance) to fracture risk in older adults, and 2) the added predictive accuracy of these parameters beyond the existing fracture assessment tools. These topics provide the rationale for investigating strength and physical performance interventions to reduce fracture risk. Most of the included publications showed that muscle mass is not a good predictor of fracture risk, while poor muscle strength and performance are associated with an increased risk of fracture, particularly in men, independent of age, BMD, and other risk factors for fractures. Muscle strength and performance can potentially improve the predictive accuracy in men beyond that obtained by the fracture risk assessment tools, Garvan FRC and FRAX.

Detection of rare mutations, copy number alterations, and methylation in the same template DNA molecules.

The analysis of cell-free DNA (cfDNA) from plasma offers great promise for the earlier detection of cancer. At present, changes in DNA sequence, methylation, or copy number are the most sensitive ways to detect the presence of cancer. To further increase the sensitivity of such assays with limited amounts of sample, it would be useful to be able to evaluate the same template molecules for all these changes. Here, we report an approach, called MethylSaferSeqS, that achieves this goal, and can be applied to any standard library preparation method suitable for massively parallel sequencing. The innovative step was to copy both strands of each DNA-barcoded molecule with a primer that allows the subsequent separation of the original strands (retaining their 5-methylcytosine residues) from the copied strands (in which the 5-methylcytosine residues are replaced with unmodified cytosine residues). The epigenetic and genetic alterations present in the DNA molecules can then be obtained from the original and copied strands, respectively. We applied this approach to plasma from 265 individuals, including 198 with cancers of the pancreas, ovary, lung, and colon, and found the expected patterns of mutations, copy number alterations, and methylation. Furthermore, we could determine which original template DNA molecules were methylated and/or mutated. MethylSaferSeqS should be useful for addressing a variety of questions relating genetics and epigenetics.

Muscle Strength and Physical Performance Are Associated With Risk of Postfracture Mortality But Not Subsequent Fracture in Men.

Muscle strength and physical performance are associated with incident fractures and mortality. However, their role in the risk of subsequent fracture and postfracture mortality is not clear. We assessed the association between muscle strength (grip strength) and performance (gait speed and chair stands time) and the risk of subsequent fracture and mortality in 830 men with low-trauma index fracture, who participated in the Osteoporotic Fractures in Men (MrOS) USA Study and had their index measurements assessed within 5 years prior to the index fracture. The annual decline in muscle strength and performance following index fracture, estimated using linear mixed-effects regression, was also examined in relation to mortality. The associations were assessed using Cox proportional hazards models adjusted for age, femoral neck bone mineral density (FN BMD), prior fractures, falls, body mass index (BMI), index fracture site, lifestyle factors, and comorbidities. Over a median follow-up of 3.7 (interquartile range [IQR], 1.3-8.1) years from index fracture to subsequent fracture, 201 (24%) men had a subsequent fracture and over 5.1 (IQR, 1.8-9.6) years to death, and 536 (65%) men died. Index measurements were not associated with subsequent fracture (hazard ratios [HRs] ranging from 0.97 to 1.07). However, they were associated with postfracture mortality. HR (95% confidence interval [CI]) per 1 standard deviation (1-SD) decrement in grip strength: HR 1.12 (95% CI, 1.01-1.25) and gait speed: HR 1.14 (95% CI, 1.02-1.27), and 1-SD increment in chair stands time: HR 1.08 (95% CI, 0.97-1.21). Greater annual declines in these measurements were associated with higher mortality risk, independent of the index values and other covariates. HR (95% CI) per 1-SD annual decrement in change in grip strength: HR 1.15 (95% CI, 1.01-1.33) and in gait speed: HR 1.38 (95% CI, 1.13-1.68), and 1-SD annual increment in chair stands time: HR 1.28 (95% CI, 1.07-1.54). Men who were unable to complete one or multiple tests had greater risk of postfracture mortality (24%-109%) compared to those performed all tests. It remains to be seen whether improvement in these modifiable factors can reduce postfracture mortality. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Trends in colorectal cancer incidence in Ho Chi Minh City, Vietnam (1996-2015): Joinpoint regression and age-period-cohort analyses.

BACKGROUND: Little is known about the trends in colorectal cancer (CRC) in Vietnam. We aimed to investigate the trends in epidemiology and anatomical subsites of CRC in Ho Chi Minh City, Vietnam. METHODS: Based on the Ho Chi Minh City Cancer Registry data during 1996-2015, we calculated the average annual percent changes (AAPCs) of the age-standardized incidence rates (ASRs) by sex, age groups, and anatomical subsites, using joinpoint regressions analysis. We further performed age-period-cohort (APC) analysis using the United States National Cancer Institute's web-based statistical tool to explore the underlying reason for the incidence trend. RESULTS: Over 20 years the overall ASR of CRC increased from 10.5 to 17.9 per 100,000, a 1.7-fold increase. CRC incidence elevated more rapidly in men (AAPC 4.7, 95%CI 2.2-7.3) than in women (AAPC 2.6, 95%CI 0.6-4.8). The highest and lowest increasing rates of ASRs were observed in the 50-64-year-old age group (AAPC 5.3, 95%CI 2.8-7.9) and < 50-year-old age group (AAPC 1.1, 95%CI -0.7 to 2.9), respectively. Regarding subsites, rectal cancer had the highest rate of increase (AAPC 3.3, 95%CI 1.0-5.7). Furthermore, the APC analysis indicated significant increases in CRC incidence in birth cohorts after 1975 in both genders. CONCLUSIONS: The CRC incidence in Ho Chi Minh City increased, with the more prominent rates being among men and older populations, in rectal subsites, and in people born after 1975. The upward trend of CRC incidence in Ho Chi Minh City may be due to the adoption of a westernized lifestyle.

Trends in incidence and histological pattern of thyroid cancer in Ho Chi Minh City, Vietnam (1996-2015): a population-based study.

BACKGROUND: The burden and trend of thyroid cancer in Vietnam have not been well documented. This study aimed to investigate the trends in incidence and histological pattern of thyroid cancer in Ho Chi Minh City from 1996 to 2015. METHODS: A population-based study retrieved data from the Ho Chi Minh City Cancer Registry during 1996-2015. Trends in the incidence of thyroid cancer were investigated based on age, gender, and histology for each 5-year period. Annual percentage change (APC) in incidence rates was estimated using Joinpoint regression analysis. RESULTS: In the study period, there were 5953 thyroid cancer cases (men-to-women ratio 1:4.5) newly diagnosed in Ho Chi Minh City with the mean age of 42.9 years (±14.9 years). The age-standardized incidence rate of thyroid cancer increased from 2.4 per 100,000 during 1996-2000 (95% confidence interval [95% CI]: 2.2-2.6) to 7.5 per 100,000 during 2011-2015 (95% CI: 7.3-7.9), corresponded to an overall APC of 8.7 (95% CI 7.6-9.9). The APC in men and women was 6.2 (95% CI: 4.2-8.2) and 9.2 (95% CI: 8.0-10.4), respectively. The incidence rate in the < 45 years age group was the highest diagnosed overall and increased significantly in both men (APC 11.0) and women (APC 10.1). Both genders shared similar distribution of subtype incidences, with papillary thyroid cancer constituted the most diagnosed (73.3% in men and 85.2% in women). The papillary thyroid cancer observed a markedly increase overall (APC of 10.7 (95% CI 9.3-12.0)). CONCLUSIONS: There were appreciable increases in the age-standardized incidence rate of thyroid cancer in both genders, mainly contributed by the papillary subtype. The age of patients at diagnosis decreased gradually. The widespread utilization of advanced diagnostic techniques and healthcare accessibility improvement might play a potential role in these trends. Further investigations are needed to comprehend the risk factors and trends fully.

Epidemiological transition to mortality and refracture following an initial fracture.

This study sought to redefine the concept of fracture risk that includes refracture and mortality, and to transform the risk into "skeletal age". We analysed data obtained from 3521 women and men aged 60 years and older, whose fracture incidence, mortality, and bone mineral density (BMD) have been monitored since 1989. During the 20-year follow-up period, among 632 women and 184 men with a first incident fracture, the risk of sustaining a second fracture was higher in women (36%) than in men (22%), but mortality risk was higher in men (41%) than in women (25%). The increased risk of mortality was not only present with an initial fracture, but was accelerated with refractures. Key predictors of post-fracture mortality were male gender (hazard ratio [HR] 2.4; 95% CI, 1.79-3.21), advancing age (HR 1.67; 1.53-1.83), and lower femoral neck BMD (HR 1.16; 1.01-1.33). A 70-year-old man with a fracture is predicted to have a skeletal age of 75. These results were incorporated into a prediction model to aid patient-doctor discussion about fracture vulnerability and treatment decisions.

Predictors of Unlikely Bacterial Pneumonia and Adverse Pneumonia Outcome in Children Admitted to a Hospital in Central Vietnam.

BACKGROUND: Pneumonia is the leading cause of antibiotic use and hospitalization in Vietnam. There is a need for better prediction of unlikely bacterial pneumonia and adverse pneumonia outcome in order to guide hospital admission and improve rational antibiotic use. METHODS: All children under 5 admitted with pneumonia (per clinician assessment) to the Da Nang Hospital for Women and Children were prospectively enrolled. Children were classified as having likely or unlikely bacterial pneumonia and followed for outcome assessment. A Bayesian model averaging approach was used to identify predictors of unlikely bacterial pneumonia and adverse pneumonia outcome, which guided the development of a pragmatic management algorithm. RESULTS: Of 3817 patients assessed, 2199 (57.6%) met World Health Organization (WHO) pneumonia criteria. In total, 1594 (41.7%) children were classified as having unlikely and 129 (3.4%) as having likely bacterial pneumonia. The remainder (2399; 62.9%) were considered to have disease of uncertain etiology. Factors predictive of unlikely bacterial pneumonia were no fever, no consolidation on chest radiograph, and absolute neutrophil count <5 × 109/L at presentation, which had a negative predictive value (NPV) for likely bacterial pneumonia of 99.0%. Among those who met WHO pneumonia criteria, 8.6% (189/2199) experienced an adverse outcome. Not having any WHO danger sign or consolidation on chest radiograph had an NPV of 96.8% for adverse pneumonia outcome. CONCLUSIONS: An algorithm that screens for predictors of likely bacterial pneumonia and adverse pneumonia outcome could reduce unnecessary antibiotic use and hospital admission, but its clinical utility requires validation in a prospective study.

Characterisation of children hospitalised with pneumonia in central Vietnam: a prospective study.

Pneumonia is the most common reason for paediatric hospital admission in Vietnam. The potential value of using the World Health Organization (WHO) case management approach in Vietnam has not been documented.We performed a prospective descriptive study of all children (2-59 months) admitted with "pneumonia" (as assessed by the admitting clinician) to the Da Nang Hospital for Women and Children to characterise their disease profiles and assess risk factors for an adverse outcome. The disease profile was classified using WHO pneumonia criteria, with tachypnoea or chest indrawing as defining clinical signs. Adverse outcome was defined as death, intensive care unit admission, tertiary care transfer or hospital stay >10 days.Of 4206 admissions, 1758 (41.8%) were classified as "no pneumonia" using WHO criteria and only 252 (6.0%) met revised criteria for "severe pneumonia". The inpatient death rate was low (0.4% of admissions) with most deaths (11 out of 16; 68.8%) occurring in the "severe pneumonia" group. An adverse outcome was recorded in 18.7% of all admissions and 60.7% of the "severe pneumonia" group. Children were hospitalised for a median of 7 days at an average cost of 253 USD per admission. Risk factors for adverse outcome included WHO-classified "severe pneumonia", age <1 year, low birth weight, previous recent admission with an acute respiratory infection and recent tuberculosis exposure. Breastfeeding, day-care attendance and pre-admission antibiotic use were associated with reduced risk.Few hospital admissions met WHO criteria for "severe pneumonia", suggesting potential unnecessary hospitalisation and use of intravenous antibiotics. Better characterisation of the underlying diagnosis requires careful consideration.

Two-Thirds of All Fractures Are Not Attributable to Osteoporosis and Advancing Age: Implications for Fracture Prevention.

CONTEXT: Although bone mineral density (BMD) is strongly associated with fracture and postfracture mortality, the burden of fractures attributable to low BMD has not been investigated. OBJECTIVES: We sought to estimate the population attributable fraction of fractures and fracture-related mortality that can be attributed to low BMD. DESIGN AND SETTING: This study is a part of an ongoing population-based prospective cohort study, the Dubbo Osteoporosis Epidemiology study. In total, 3700 participants aged ≥50 years participated in the study. Low-trauma fracture was ascertained by X-ray reports, and mortality was ascertained from the Birth, Death and Marriage Registry. RESULTS: Overall, 21% of women and 11% of men had osteoporotic BMD. In univariable analysis, 21% and 16% of total fractures in women and men, respectively, were attributable to osteoporosis. Osteoporosis combined with advancing age (>70 years) accounted for 34% and 35% of fractures in women and men, respectively. However, these two factors accounted for ∼60% of hip fractures. About 99% and 66% of postfracture mortality in women and men, respectively, were attributable to advancing age, osteoporosis, and fracture; however, most of the attributable proportion was accounted for by advancing age. CONCLUSIONS: A substantial health care burden of fracture is on people aged <70 years or nonosteoporosis, suggesting that treatment of people with osteoporosis is unlikely to reduce a large number of fractures in the general population.