Estimated epidemiologic parameters and morbidity associated with pandemic H1N1 influenza

Background

In the face of an influenza pandemic, accurate estimates of epidemiologic parameters are required to help guide decision-making. We sought to estimate epidemiologic parameters for pandemic H1N1 influenza using data from initial reports of laboratory-confirmed cases.

Methods

We obtained data on laboratory-confirmed cases of pandemic H1N1 influenza reported in the province of Ontario, Canada, with dates of symptom onset between Apr. 13 and June 20, 2009. Incubation periods and duration of symptoms were estimated and fit to parametric distributions. We used competing-risk models to estimate risk of hospital admission and case-fatality rates. We used a Markov Chain Monte Carlo model to simulate disease transmission.

Results

The median incubation period was 4 days and the duration of symptoms was 7 days. Recovery was faster among patients less than 18 years old than among older patients (hazard ratio 1.23, 95% confidence interval 1.06–1.44). The risk of hospital admission was 4.5% (95% CI 3.8%–5.2%) and the case-fatality rate was 0.3% (95% CI 0.1%–0.5%). The risk of hospital admission was highest among patients less than 1 year old and those 65 years or older. Adults more than 50 years old comprised 7% of cases but accounted for 7 of 10 initial deaths (odds ratio 28.6, 95% confidence interval 7.3–111.2). From the simulation models, we estimated the following values (and 95% credible intervals): a mean basic reproductive number (R₀, the number of new cases created by a single primary case in a susceptible population) of 1.31 (1.25–1.38), a mean latent period of 2.62 (2.28–3.12) days and a mean duration of infectiousness of 3.38 (2.06–4.69) days. From these values we estimated a serial interval (the average time from onset of infectiousness in a case to the onset of infectiousness in a person infected by that case) of 4–5 days.

Interpretation

The low estimates for R₀ indicate that effective mitigation strategies may reduce the final epidemic impact of pandemic H1N1 influenza.The emergence and global spread of pandemic H1N1 influenza led the World Health Organization to declare a pandemic on June 11, 2009. As the pandemic spreads, countries will need to make decisions about strategies to mitigate and control disease in the face of uncertainty.For novel infectious diseases, accurate estimates of epidemiologic parameters can help guide decision-making. A key parameter for any new disease is the basic reproductive number (R₀), defined as the average number of new cases created by a single primary case in a susceptible population. R₀ affects the growth rate of an epidemic and the final number of infected people. It also informs the optimal choice of control strategies. Other key parameters that affect use of resources, disease burden and societal costs during a pandemic are duration of illness, rate of hospital admission and case-fatality rate. Early in an epidemic, the case-fatality rate may be underestimated because of the temporal lag between onset of infection and death; the delay between initial identification of a new case and death may lead to an apparent increase in deaths several weeks into an epidemic that is an artifact of the natural history of the disease.We used data from initial reports of laboratory-confirmed pandemic H1N1 influenza to estimate epidemiologic parameters for pandemic H1N1 influenza. The parameters included R₀, incubation period and duration of illness. We also estimated risk of hospital admission and case-fatality rates, which can be used to estimate the burden of illness likely to be associated with this disease.     

Effectiveness of A(H1N1)pdm09 Influenza Vaccine in Adults Recommended for Annual Influenza Vaccination

Introduction

Because of variability in published A(H1N1)pdm09 influenza vaccine effectiveness estimates, we conducted a study in the adults belonging to the risk groups to assess the A(H1N1)pdm09 MF59-adjuvanted influenza vaccine effectiveness.

Methods

VE against influenza and/or pneumonia was assessed in the cohort study (n>25000), and vaccine effectiveness against laboratory-confirmed A(H1N1)pdm09 influenza was assessed in a matched case-control study (16 pairs). Odds ratios (OR) and their 95% confidence intervals (95% CI) were calculated by using multivariate logistic regression; vaccine effectiveness was estimated as (1-odds ratio)*100%.

Results

Vaccine effectiveness against laboratory-confirmed A(H1N1)pdm09 influenza and influenza and/or pneumonia was 98% (84–100%) and 33% (2–54%) respectively. The vaccine did not prevent influenza and/or pneumonia in 18–59 years old subjects, and was 49% (16–69%) effective in 60 years and older subjects.

Conclusions

Even though we cannot entirely rule out that selection bias, residual confounding and/or cross-protection has played a role, the present results indicate that the MF59-adjuvanted A(H1N1)pdm09 influenza vaccine has been effective in preventing laboratory-confirmed A(H1N1)pdm09 influenza and influenza and/or pneumonia, the latter notably in 60 years and older subjects.     

Household Transmission of Influenza A(H1N1)pdm09 in the Pandemic and Post-Pandemic Seasons

Background

The transmission of influenza viruses occurs person to person and is facilitated by contacts within enclosed environments such as households. The aim of this study was to evaluate secondary attack rates and factors associated with household transmission of laboratory-confirmed influenza A(H1N1)pdm09 in the pandemic and post-pandemic seasons.

Methods

During the 2009–2010 and 2010–2011 influenza seasons, 76 sentinel physicians in Navarra, Spain, took nasopharyngeal and pharyngeal swabs from patients diagnosed with influenza-like illness. A trained nurse telephoned households of those patients who were laboratory-confirmed for influenza A(H1N1)pdm09 to ask about the symptoms, risk factors and vaccination status of each household member.

Results

In the 405 households with a patient laboratory-confirmed for influenza A(H1N1)pdm09, 977 susceptible contacts were identified; 16% of them (95% CI 14–19%) presented influenza-like illness and were considered as secondary cases. The secondary attack rate was 14% in 2009–2010 and 19% in the 2010–2011 season (p = 0.049), an increase that mainly affected persons with major chronic conditions. In the multivariate logistic regression analysis, the risk of being a secondary case was higher in the 2010–2011 season than in the 2009–2010 season (adjusted odds ratio: 1.72; 95% CI 1.17–2.54), and in children under 5 years, with a decreasing risk in older contacts. Influenza vaccination was associated with lesser incidence of influenza-like illness near to statistical significance (adjusted odds ratio: 0.29; 95% CI 0.08–1.03).

Conclusion

The secondary attack rate in households was higher in the second season than in the first pandemic season. Children had a greater risk of infection. Preventive measures should be maintained in the second pandemic season, especially in high-risk persons.     

Early outbreak of 2009 influenza A (H1N1) in Mexico prior to identification of pH1N1 virus

Background

In the aftermath of the global spread of 2009 influenza A (pH1N1) virus, still very little is known of the early stages of the outbreak in Mexico during the early months of the year, before the virus was identified.

Methodology/Main Findings

We fit a simple mathematical model, the Richards model, to the number of excess laboratory-confirmed influenza cases in Mexico and Mexico City during the first 15 weeks in 2009 over the average influenza case number of the previous five baseline years of 2004-2008 during the same period to ascertain the turning point (or the peak incidence) of a wave of early influenza infections, and to estimate the transmissibility of the virus during these early months in terms of its basic reproduction number. The results indicate that there may have been an early epidemic in Mexico City as well as in all of Mexico during February/March. Based on excess influenza cases, the estimated basic reproduction number R₀ for the early outbreak was 1.59 (0.55 to 2.62) for Mexico City during weeks 5–9, and 1.25 (0.76, 1.74) for all of Mexico during weeks 5–14.

Conclusions

We established the existence of an early epidemic in Mexico City and in all of Mexico during February/March utilizing the routine influenza surveillance data, although the location of seeding is unknown. Moreover, estimates of R₀ as well as the time of peak incidence (the turning point) for Mexico City and all of Mexico indicate that the early epidemic in Mexico City in February/March had been more transmissible (larger R₀) and peaked earlier than the rest of the country. Our conclusion lends support to the possibility that the virus could have already spread to other continents prior to the identification of the virus and the reporting of lab-confirmed pH1N1 cases in North America in April.     

Estimated cumulative incidence of pandemic (H1N1) influenza among pregnant women during the first wave of the 2009 pandemic

Background

Hospitalization and lab confirmed cases of H1N1 have been reported during the first wave of the 2009 pandemic but these are not accurate measures of influenza incidence in the population. We estimated the cumulative incidence of pandemic (H1N1) influenza among pregnant women in the province of Manitoba during the first wave of the 2009 pandemic.

Methods

Two panels of stored frozen serum specimens collected for routine prenatal screening were randomly selected for testing before (March 2009, n = 252) and after (August 2009, n = 296) the first wave of the pandemic. A standard hemagglutination inhibition assay was used to detect the presence of IgG antibodies against the pandemic (H1N1) 2009 virus. The cumulative incidence of pandemic (H1N1) influenza was calculated as the difference between the point prevalence rates in the first and second panels.

Results

Of the specimens collected in March, 7.1% were positive for the IgG antibodies (serum antibody titre ≥ 1:40). The corresponding prevalence was 15.7% among the specimens collected in August. The difference indicated a cumulative incidence of 8.6% (95% confidence interval [CI] 3.2%–13.7%). The rate differed geographically, the highest being in the northern regions (20.8%, 95% CI 7.9%–31.8%), as compared with 4.0% (95% CI 0.0%–11.9%) in Winnipeg and 8.9% (95% CI 0.0%–18.8%) in the rest of the province.

Interpretation

We estimated that the cumulative incidence of pandemic (H1N1) influenza among pregnant women in Manitoba during the first wave of the 2009 pandemic was 8.6%. It was 20.8% in the northern regions of the province.During the first wave of the pandemic (H1N1) 2009, the province of Manitoba was more severely affected than almost any other Canadian province.¹ Pregnant women in particular had higher rates of laboratory-confirmed infection and of severe illness.² However, the number of laboratory-confirmed cases is not an accurate measure of the incidence of influenza in the population. The number and geographic distribution of confirmed cases are influenced by differences in access to medical care, physicians’ practices and other factors.³We estimated the cumulative incidence of pandemic (H1N1) influenza among pregnant women in the province of Manitoba during the first wave of the 2009 pandemic. We did this by measuring the point seroprevalence in random samples of pregnant women presenting for routine prenatal screening before and after the first wave.     

Association between the 2008–09 Seasonal Influenza Vaccine and Pandemic H1N1 Illness during Spring–Summer 2009: Four Observational Studies from Canada

Background

In late spring 2009, concern was raised in Canada that prior vaccination with the 2008–09 trivalent inactivated influenza vaccine (TIV) was associated with increased risk of pandemic influenza A (H1N1) (pH1N1) illness. Several epidemiologic investigations were conducted through the summer to assess this putative association.

Methods and Findings

Studies included: (1) test-negative case-control design based on Canada''s sentinel vaccine effectiveness monitoring system in British Columbia, Alberta, Ontario, and Quebec; (2) conventional case-control design using population controls in Quebec; (3) test-negative case-control design in Ontario; and (4) prospective household transmission (cohort) study in Quebec. Logistic regression was used to estimate odds ratios for TIV effect on community- or hospital-based laboratory-confirmed seasonal or pH1N1 influenza cases compared to controls with restriction, stratification, and adjustment for covariates including combinations of age, sex, comorbidity, timeliness of medical visit, prior physician visits, and/or health care worker (HCW) status. For the prospective study risk ratios were computed. Based on the sentinel study of 672 cases and 857 controls, 2008–09 TIV was associated with statistically significant protection against seasonal influenza (odds ratio 0.44, 95% CI 0.33–0.59). In contrast, estimates from the sentinel and three other observational studies, involving a total of 1,226 laboratory-confirmed pH1N1 cases and 1,505 controls, indicated that prior receipt of 2008–09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring–summer 2009, with estimated risk or odds ratios ranging from 1.4 to 2.5. Risk of pH1N1 hospitalization was not further increased among vaccinated people when comparing hospitalized to community cases.

Conclusions

Prior receipt of 2008–09 TIV was associated with increased risk of medically attended pH1N1 illness during the spring–summer 2009 in Canada. The occurrence of bias (selection, information) or confounding cannot be ruled out. Further experimental and epidemiological assessment is warranted. Possible biological mechanisms and immunoepidemiologic implications are considered. Please see later in the article for the Editors'' Summary     

Significantly Lower Anti-Leishmania IgG Responses in Sudanese versus Indian Visceral Leishmaniasis

Background

Visceral leishmaniasis (VL), a widely distributed systemic disease caused by infection with the Leishmania donovani complex (L. donovani and L. infantum), is almost always fatal if symptomatic and untreated. A rapid point-of-care diagnostic test for anti-Leishmania antibodies, the rK39-immunochromatographic test (rK39-ICT), has high sensitivity and specificity in South Asia but is less sensitive in East Africa. One of the underlying reasons may be continent-specific molecular diversity in the rK39 antigen within the L. donovani complex. However, a second reason may be differences in specific IgG anti-Leishmania levels in patients from different geographical regions, either due to variable antigenicity or immunological response.

Methodology/Principal Findings

We determined IgG titres of Indian and Sudanese VL patients against whole cell lysates of Indian and Sudanese L. donovani strains. Indian VL patients had significantly higher IgG titres against both L. donovani strains compared to Sudanese VL patients (p<0.0001). Mean reciprocal log₁₀ 50% end-point titres (1/log₁₀t₅₀) were i) 3.80 and 3.88 for Indian plasma and ii) 2.13 and 2.09 for Sudanese plasma against Indian and Sudanese antigen respectively (p<0.0001). Overall, the Indian VL patients therefore showed a 46.8–61.7 -fold higher mean ELISA titre than the Sudanese VL patients. The higher IgG titres occurred in children (<16 years old) and adults of either sex from India (mean 1/log₁₀t₅₀: 3.60–4.15) versus Sudan (mean 1/log₁₀t₅₀: 1.88–2.54). The greatest difference in IgG responses was between male Indian and Sudanese VL patients of ≥ 16 years old (mean 1/log₁₀t₅₀: 4.15 versus 1.99 = 144-fold (p<0.0001).

Conclusions/Significance

Anti-Leishmania IgG responses among VL patients in Sudan were significantly lower than in India; this may be due to chronic malnutrition with Zn²⁺ deficiency, or variable antigenicity and capacity to generate IgG responses to Leishmania antigens. Such differential anti-Leishmania IgG levels may contribute to lower sensitivity of the rK39-ICT in East Africa.     

Measles Outbreak in South Africa: Epidemiology of Laboratory-Confirmed Measles Cases and Assessment of Intervention, 2009–2011

Background

Since 1995, measles vaccination at nine and 18 months has been routine in South Africa; however, coverage seldom reached >95%. We describe the epidemiology of laboratory-confirmed measles case-patients and assess the impact of the nationwide mass vaccination campaign during the 2009 to 2011 measles outbreak in South Africa.

Methods

Serum specimens collected from patients with suspected-measles were tested for measles-specific IgM antibodies using an enzyme-linked immunosorbent assay and genotypes of a subset were determined. To estimate the impact of the nationwide mass vaccination campaign, we compared incidence in the seven months pre- (1 September 2009–11 April 2010) and seven months post-vaccination campaign (24 May 2010–31 December 2010) periods in seven provinces of South Africa.

Results

A total of 18,431 laboratory-confirmed measles case-patients were reported from all nine provinces of South Africa (cumulative incidence 37 per 100,000 population). The highest cumulative incidence per 100,000 population was in children aged <1 year (603), distributed as follows: <6 months (302/100,000), 6 to 8 months (1083/100,000) and 9 to 11 months (724/100,000). Forty eight percent of case-patients were ≥5 years (cumulative incidence 54/100,000). Cumulative incidence decreased with increasing age to 2/100,000 in persons ≥40 years. A single strain of measles virus (genotype B3) circulated throughout the outbreak. Prior to the vaccination campaign, cumulative incidence in the targeted vs. non-targeted age group was 5.9-fold higher, decreasing to 1.7 fold following the campaign (P<0.001) and an estimated 1,380 laboratory-confirmed measles case-patients were prevented.

Conclusion

We observed a reduction in measles incidence following the nationwide mass vaccination campaign even though it was conducted approximately one year after the outbreak started. A booster dose at school entry may be of value given the high incidence in persons >5 years.     

Genetic Variants of MICB and PLCE1 and Associations with Non-Severe Dengue

Background

A recent genome-wide association study (GWAS) identified susceptibility loci for dengue shock syndrome (DSS) at MICB rs3132468 and PLCE1 rs3740360. The aim of this study was to define the extent to which MICB (rs3132468) and PLCE1 (rs3740360) were associated with less severe clinical phenotypes of pediatric and adult dengue.

Methods

3961 laboratory-confirmed dengue cases and 5968 controls were genotyped at MICB rs3132468 and PLCE1 rs3740360. Per-allele odds ratios (OR) with 95% confidence intervals (CI) were calculated for each patient cohort. Pooled analyses were performed for adults and paediatrics respectively using a fixed effects model.

Results

Pooled analysis of the paediatric and adult cohorts indicated a significant association between MICB rs3132468 and dengue cases without shock (OR  =  1.15; 95%CI: 1.07 – 1.24; P  =  0.0012). Similarly, pooled analysis of pediatric and adult cohorts indicated a significant association between dengue cases without shock and PLCE1 rs3740360 (OR  =  0.92; 95%CI: 0.85 – 0.99; P  =  0.018). We also note significant association between both SNPs (OR  =  1.48; P  =  0.0075 for MICB rs3132468 and OR  =  0.75, P  =  0.041 for PLCE1 rs3740360) and dengue in infants.

Discussion

This study confirms that the MICB rs3132468 and PLCE1 rs3740360 risk genotypes are not only associated with DSS, but are also associated with less severe clinical phenotypes of dengue, as well as with dengue in infants. These findings have implications for our understanding of dengue pathogenesis.     

Copy Number Variation of GSTT1 and GSTM1 and the Risk of Prostate Cancer in a Caribbean Population of African Descent

Background

Deletions of the glutathione S-transferase genes M1 and T1 (GSTM1 and GSTT1) have been studied as potential risk factors for prostate cancer. Conflicting results have been obtained. Moreover, most such studies could not discriminate heterozygous from homozygous carriers of the non-deleted alleles.

Objective

We investigated whether copy number variation (CNV) of the GSTM1 and/or GSTT1 genes contribute to the risk of prostate cancer in the Caribbean population of African descent of Guadeloupe.

Methods

In a population-based case-control study, we compared 629 prostate cancer patients and 622 control subjects. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Exact copy numbers of GSTM1 and GSTT1 were determined by real-time PCR.

Results

A higher copy number of GSTM1 was marginally associated with prostate cancer risk. Men with 2 and 3 or more GSTT1 genes were at higher risk of prostate cancer (OR: 1.55, 95% CI: 1.11–2.16 and OR: 4.89, 95% CI: 1.71–13.99, respectively; P_trend<0.001). Men with 3, 4 and 5 or more copies of both GSTM1 and GSTT1 genes were at higher risk of prostate cancer (OR: 2.18, 95% CI: 1.21–3.91, OR: 3.24, 95% CI: 1.63–6.46, and OR: 5.77, 95% CI: 1.40–23.84, respectively; P_trend<0.001).

Conclusions

Copy number of GSTT1 and combined GSTM1/GSTT1 appear to be associated with prostate cancer risk in our population study with gene dose relationship. Our results support the hypothesis that variations in copy number of GSTT1 modulate the risk of prostate cancer.     

Magnetic Resonance Imaging Diagnosis of Metastatic Lymph Nodes in a Rabbit Model: Efficacy of PJY10, a New Ultrasmall Superparamagnetic Iron Oxide Agent,with Monodisperse Iron Oxide Core and Multiple-Interaction Ligands

Background

Accurate diagnosis of lymph node metastasis is crucial in treatment planning for cancer patients. Despite the use of various parameters, making correct diagnosis of a small metastatic or a hyperplastic benign node is still a challenge. In this study, we evaluated the feasibility of detecting lymph node metastasis using a new ultrasmall superparamagnetic iron oxide particle, PJY10, in a rabbit model.

Methods

To make metastatic and benign lymph nodes, either VX2 carcinoma or fecal material suspension was inoculated into thighs of 56 rabbits three weeks or three days before magnetic resonance (MR) imaging, respectively. T2*-weighted 3T MR imaging was performed before and 24 hours after PJY10 injection (5.2 [n = 15], 7.8 [n = 17], and 10.4 [n = 24] mg Fe/kg). MR images were correlated with pathologic results to calculate sensitivity and specificity. Quantitative analysis of the signal intensity (SI) – number of voxels_[low] (the fraction of the number of voxels with the normalized SI on the postcontrast image lower than that on the precontrast image) and mean SI ratio – was also performed for each lymph node.

Results

Sensitivities were 100% at all three dosages, whereas specificity increased with increasing dosage (89% at 10.4 mg Fe/kg). The benign nodes had a significantly higher number of voxels_[low] and a lower mean SI ratio than the metastatic nodes at the dosage of 10.4 mg Fe/kg (P<.001). Az values were 0.905 for the number of voxels_[low] and 0.952 for the mean SI ratio. The number of voxels_[low] (P = .019) and the mean SI ratio (P = .034) had significant correlations with the histopathologic area ratio of metastatic foci in the metastatic nodes at 10.4 mg Fe/kg.

Conclusions

PJY10 enabled clear demonstration of lymph node metastasis with high sensitivity and specificity at its optimal dosage of 10.4 mg Fe/kg.     

Nutritional Status of Children Hospitalized for Parapneumonic Effusion

Background & Aims

Among children hospitalized for pneumonia, those with parapneumonic effusion (PPE) are at particular risk for nutritional deterioration. This study aimed to 1) investigate the evolution of the nutritional status during hospitalization and at outpatient follow-up; 2) determine clinical risk factors for weight loss during hospitalization; 3) describe the nutritional interventions for these children.

Methods

Retrospective chart review (January ‘07 - September ‘12) of 56 children with pneumonia, complicated by PPE in two Belgian hospitals for data on body weight and height at admission (t₀) and discharge (t₁), and two weeks (t₂) and one month (t₃) after discharge. Length of hospitalization (LoS), length of stay in paediatric intensive care (LoS_PICU) and maximal in-hospital weight loss (t_max) were calculated and nutritional interventions were recorded.

Results

The median (range) age was 3.5 (1.0–14.8) years. Weight or height was lacking in five (8.9%) children at t₀ and in 28 (50%) at t₁; 21.4% was weighed only once during hospitalization. At t_max, respectively 17/44 and 5/44 children lost ≥5% and ≥10% of their weight. Median (range) LoS and LoS_PICU were 18.0 (10–41) and 4.0 (0–23) days. One-fourth received a nutritional intervention. Weight for height at admission (WFH(t₀)) significantly predicted maximal weight loss (β (95% CI) = −0.34 (−2.0–−0.1); p = 0.03). At t₂ and t₃, 13/32 and 5/22 of the children with available follow-up data did not reach WFH(t₀), whilst in 4/35 and 5/26 body weight remained ≥5% under the weight(t₀).

Conclusions

One-third of children with pneumonia complicated by PPE and monitored for weight and height, lost ≥5% of their body weight during hospitalization. One-fourth did not reach initial WFH one month after discharge. Those with a higher WFH at admission were at higher risk of weight loss. More attention for monitoring of weight loss and the nutritional policy during and after hospitalization is warranted.     

In Silico Identification of a Candidate Synthetic Peptide (Tsgf118–43) to Monitor Human Exposure to Tsetse Flies in West Africa

Background

The analysis of humoral responses directed against the saliva of blood-sucking arthropods was shown to provide epidemiological biomarkers of human exposure to vector-borne diseases. However, the use of whole saliva as antigen presents several limitations such as problems of mass production, reproducibility and specificity. The aim of this study was to design a specific biomarker of exposure to tsetse flies based on the in silico analysis of three Glossina salivary proteins (Ada, Ag5 and Tsgf1) previously shown to be specifically recognized by plasma from exposed individuals.

Methodology/Principal Findings

Synthetic peptides were designed by combining several linear epitope prediction methods and Blast analysis. The most specific peptides were then tested by indirect ELISA on a bank of 160 plasma samples from tsetse infested areas and tsetse free areas. Anti-Tsgf1_18–43 specific IgG levels were low in all three control populations (from rural Africa, urban Africa and Europe) and were significantly higher (p<0.0001) in the two populations exposed to tsetse flies (Guinean HAT foci, and South West Burkina Faso). A positive correlation was also found between Anti-Tsgf1_18–43 IgG levels and the risk of being infected by Trypanosoma brucei gambiense in the sleeping sickness foci of Guinea.

Conclusion/Significance

The Tsgf1_18–43 peptide is a suitable and promising candidate to develop a standardize immunoassay allowing large scale monitoring of human exposure to tsetse flies in West Africa. This could provide a new surveillance indicator for tsetse control interventions by HAT control programs.     

Relationship between HbA1c and Continuous Glucose Monitoring in Chinese Population: A Multicenter Study

Objective

Since there is a paucity of reference data in the literature to indicate the relationship between HbA1c, and 24 h mean blood glucose (MBG) from continuous glucose monitoring (CGM) in Chinese populations, we described the above relationship in adult Chinese subjects with different glucose tolerance status.

Methods

Seven-hundred-and-forty-two individuals without history of diabetes were included to the study at 11 hospitals in urban areas across China from 2007–2009 and data of 673 subjects were included into the final analysis. Oral glucose tolerance test (OGTT) classified the participants as nondiabetic subjects, including those with normal glucose regulation (NGR; n = 121) and impaired glucose regulation (IGR; n = 209), or newly diagnosed type 2 diabetes (n = 343). All participants completed testing for HbA1c levels and wore a CGM system for three consecutive days. The 24 h MBG levels were calculated. Spearman correlations and linear regression analyses were applied to quantify the relationship between glucose markers.

Results

The levels of HbA1c and 24 h MBG significantly increased with presence of glucose intolerance (NGR<IGR<type 2 diabetes; both, P<0.001). Analysis of the total population indicated that HbA1c was strongly correlated with 24 h MBG (r = 0.735). The correlation was also found to be significant for the subgroup of participants with newly diagnosed type 2 diabetes (r = 0.694, P<0.001). Linear regression analysis of the total study population yielded the following equation: 24 h MBG _mmol/L = 1.198×HbA1c–0.582 (24 h MBG _mg/dL = 21.564×HbA1c–10.476) (R² = 0.670, P<0.001). The model fit was not improved by application of exponential or quadratic modeling. When HbA1c was 6.5%, the calculated 24 h MBG was 7.2 (6.4–8.1) mmol/L (130 (115–146) mg/dL); and when HbA1c was 7.0%, the 24 h MBG was 7.8 (6.9–8.7) mmol/L (140 (124–157) mg/dL).

Conclusions

Our study provided the reference data of the relationship between HbA1c and CGM in Chinese subjects.     

Association between Depressive Symptoms and Bone Stiffness Index in Young Adults: The Kangwha Study

Objective

Young adulthood is an important period for both bone and mental health. This study investigated the association between depressive symptoms and bone density in apparently healthy Korean men and women aged 29−32 years.

Methods

This study is a cross-sectional analysis of data from 123 men and 133 women who completed follow-up examinations of the Kangwha study in 2010−2011. Bone stiffness index (SI) was measured at the os calcis using a quantitative ultrasound device. Depressive symptoms were evaluated using the Korean version of the Beck Depression Inventory (K-BDI) and classified as normal (K-BDI <10), mild (K-BDI 10–15), and moderate to severe (K-BDI ≥16).

Results

Moderate to severe depressive symptoms were prevalent among 11.4% of men and 19.6% of women. Higher K-BDI scores were significantly correlated to SI in men, before (ρ = –0.286, p = 0.001) and after (ρ = –0.228, p = 0.013) adjustment for covariates. Men with depressive symptoms tended to have a lower SI; multivariate-adjusted mean SI in men with normal, mild, and moderate to severe depressive symptoms was 104.1±3.1, 100.9±5.9, and 94.1±7.8, respectively (p for trend = 0.021). In contrast, no significant correlations were identified in women.

Conclusions

Depressive symptoms were significantly associated with lower SI in men, but not in women. Further studies are necessary to evaluate the impact of depression on developing osteoporosis or osteoporotic fractures later in life.     

Insulin-Like Growth Factor 1 Receptor and Response to Anti-IGF1R Antibody Therapy in Osteosarcoma

Background

Survival outcomes for patients with osteosarcoma (OS) have remained stagnant over the past three decades. Insulin-like growth factor 1 receptor (IGF1R) is over-expressed in a number of malignancies, and anti-IGF1R antibodies have and are currently being studied in clinical trials. Understanding the molecular aberrations which result in increased tumor response to anti-IGF1R therapy could allow for the selection of patients most likely to benefit from IGF1R targeted therapy.

Methods

IGF1R mRNA expression was assessed by RT PCR in OS patient primary tumors, cell lines, and xenograft tumors. IGF1R copy number was assessed by 3 approaches: PCR, FISH, and dot blot analysis. Exons 1–20 of IGF1R were sequenced in xenograft tumors and 87 primary OS tumors, and surface expression of IGF1R was assessed by flow cytometry. Levels of mRNA and protein expression, copy number, and mutation status were compared with tumor response to anti-IGF1R antibody therapy in 4 OS xenograft models.

Results

IGF1R mRNA is expressed in OS. Primary patient samples and xenograft samples had higher mRNA expression and copy number compared with corresponding cell lines. IGF1R mRNA expression, cell surface expression, copy number, and mutation status were not associated with tumor responsiveness to anti-IGF1R antibody therapy.

Conclusions

IGF1R is expressed in OS, however, no clear molecular markers predict response to IGF1R antibody-mediated therapy. Additional pre-clinical studies assessing potential predictive biomarkers and investigating targetable molecular pathways critical to the proliferation of OS cells are needed.