Using bedside ultrasound in diagnosing acute cholecystitis in the emergency department (ED) can save time, help the decision making process and allocate resources wisely. This study aimed to evaluate the diagnostic accuracy of bedside right upper quadrant (RUQ) ultrasonography in detection of acute cholecystitis.In this diagnostic accuracy study, patients presenting to ED, suffering from RUQ pain in favor of acute cholecystitis underwent RUQ ultrasonography in emergency and radiology departments and interrater agreement between reports was calculated. 342 patients with the mean age of 53.92 ± 11.18 (20 – 83) years were studied . The number of patients with at least one sonographic finding of acute cholecystitis were 53 (15.50%) and 48 (14.00%) based on ED and radiology reports (Kappa = 0.826). Sensitivity, specificity, positive and negative predictive values, as well as positive and negative likelihood ratios of bedside sonography were 89.58 (95%CI: 76.55 – 96.10), 96.59 (95%CI: 93.63 – 98.29), 81.13 (95%CI: 67.58 – 90.11), 98.26 (95%CI: 95.77 – 99.36), 4.30 (95%CI: 2.42 – 7.62) and 0.017 (95%CI: 0.007 – 0.041), respectively. There was a very good agreement between ED and radiology departments’ sonography reports regarding the presence or absence of acute cholecystitis. Sensitivity and specificity of bedside RUQ sonography were 89.58 and 96.59, respectively.  Around 10 to 20 percent of the normal population in the US have biliary stone but only 1 to 2 percent of them get symptomatic . These fst century visual stethoscopes”  ultrasonography in emergency settings for diagnosis of acute cholecystitis . KendallThere was a recent massive improvement in point of care ultrasound science and technology, which made it useful for daily practice; however, there is still the question of accuracy. Therefore, the present study aimed to evaluate the diagnostic accuracy of bedside RUQ ultrasonography by trained emergency medicine residents or attending emergency physicians in detection of acute cholecystitis.Study design and settingIn this diagnostic accuracy study, patients presenting to emergency department of Firouzgar  and Besat Hospitals, Tehran, Iran, from 2015 to 2017, suffering from RUQ pain in favor of acute cholecystitis underwent bedside ultrasonography. Then, the accuracy of bedside ultrasonography performed by trained emergency residents or attending emergency physician was calculated, considering the radiology department reports as a standard. The study protocol was approved by ethics committee of AJA University of Medical Sciences and researchers adhered to all aspects of ethical practice and confidentiality of patients’ information. Informed consent was obtained before patients’ enrollment.ParticipantsPatients with RUQ or epigastric pain suspected to acute cholecystitis who were brought to the mentioned emergency departments were enrolled using non-probability sampling techniques. Patients with history of biliary disease, jaundice, and cholecystectomy as well as intubated, pregnant and cases < 18 years old were excluded. InvestigationFollowing physical examination and history taking, each case was examined via bedside RUQ abdominal ultrasonography in the emergency department. All exams were either done by attending emergency physicians, expert in point of care ultrasound, or under their direct supervision by trained emergency residents. Ultrasonographies were done by a 2-5 MHZ curve transducer by an HM-70 Samsung device or an M-turbo Sonosite device. The examinations were started from the subcostal area. In case of no view from subcostal or intercostal window, the patient was asked to sit upright or rotate to the left lateral decubitus position. After examination, the sonographer filled out an online form consisting of 5 yes-no questions regarding the presence or absence of sonographic findings of acute cholecystitis as follows:Was there any stone in gallbladder? Was there gallbladder wall thickening > 3 millimeters? Was there any fluid around the gallbladder?Was there any wall edema in the gallbladder? Are the ultrasound findings in favor of acute cholecystitis? DICOM) system reports. Then, patients were transferred to the radiology department to be examined  and the answer of mentioned questions were extracted from radiology department digital imaging and communications in medicine  as well as sonographic findings of emergency and radiology departments regarding presence or absence of acute cholecystitis sonographic findings were collected using a predesigned checklist by a trained medical doctor.Statistical analysisData were analyzed using Statistical package for social sciences (SPSS) software version 20. All quantitative data were reported as mean ± standard deviation and qualitative data as frequency and percentage. For measuring inter-rater agreement between radiology and emergency departments’ reports Cohen's kappa coefficient was calculated. In this study kappa coefficient < 0.20 was considered as poor, 0.21 - 0.40 as fair, 0.41 - 0.60 as moderate, 0.61 - 0.80 as good, and 0.81 - 1.00 as very good strength of agreement.Screening performance characteristics of emergency department’s RUQ sonography in diagnosis of acute cholecystitis were calculated using VassarStats medical software, considering radiology ward reports as standard test. rd year emergency medicine residents. 342 patients with the mean age of 53.92 ± 11.18 (20 – 83) years were studied . 179 (52.3%) ED sonographies were done by emergency physicians and 163 (47.7%) by trained 353 (15.50%) patients had at least one sonographic finding of acute cholecystitis based on ED reports, while radiology department reported the presence of these findings for 48 (14.00%) cases (Kappa = 0.826). Frequency of each sonographic finding in ED and radiology department reports is shown in Sensitivity, specificity, positive and negative predictive values, as well as positive and negative likelihood ratios of ED sonography for screening of cholecystitis were 89.58 (95%CI: 76.55 – 96.10), 96.59 (95%CI: 93.63 – 98.29), 81.13 (95%CI: 67.58 – 90.11), 98.26 (95%CI: 95.77 – 99.36), 4.30 (95%CI: 2.42 – 7.62) and 0.017 (95%CI: 0.007 – 0.041), respectively. Based on the findings of the present study, there was a very good agreement between ED and radiology departments’ sonography reports regarding the presence or absence of acute cholecystitis. Sensitivity and specificity of ED RUQ sonography were 89.58 and 96.59, respectively. Zenobi et al. in 2016 had their emphasis on murphy sign value in sonographic diagnosis of acute cholecystitis . KendallHowever, lower agreement in detecting some sonographic findings of cholecystitis such as gallbladder wall edema shows the necessity of continuous training in this regard. In point of care sonography the goal is finding an easy to do and easy to learn method without sacrificing the reliability. In 2009 Gaspari et al., in an attempt to specify a learning curve for bedside RUQ ultrasonography, concluded that after seven cases one will reach adequate image acquisition quality and technique and it will take around 25 cases to interpret the images reliably with a significant level of agreement with experts . HoweverLimitationsThe first limitation of this study was lack of a systematic image storing system; we had to export our data manually from our devices and it made the process more time-consuming. Lack of a gold standard as a scale for comparison was another problem. We don’t use HIDA scan in our centers, surgery is mostly done after passing the acute inflammatory phase, and computed tomography scan is used only in cases of suspected complications.Based on the findings of the present study, there was a very good agreement between ED and radiology departments’ sonography reports regarding the presence or absence of acute cholecystitis. Sensitivity and specificity of bedside RUQ sonography were 89.58 and 96.59, respectively. Yet, lower agreement in detecting some sonographic findings of acute cholecystitis such as gallbladder wall edema shows the necessity of continuous training in this regard.


Teens who give birth at age 15–17 years are at increased risk for adverse medical and social outcomes of teen pregnancy.To examine trends in the rate and proportion of births to teens aged 15–19 years that were to teens aged 15–17 years, CDC analyzed 1991–2012 National Vital Statistics System data. National Survey of Family Growth (NSFG) data from 2006–2010 were used to examine sexual experience, contraceptive use, and receipt of prevention opportunities among female teens aged 15–17 years.During 1991–2012, the rate of births per 1,000 teens declined from 17.9 to 5.4 for teens aged 15 years, 36.9 to 12.9 for those aged 16 years, and 60.6 to 23.7 for those aged 17 years. In 2012, the birth rate per 1,000 teens aged 15–17 years was higher for Hispanics (25.5), non-Hispanic blacks (21.9), and American Indians/Alaska Natives (17.0) compared with non-Hispanic whites (8.4) and Asians/Pacific Islanders (4.1). The rate also varied by state, ranging from 6.2 per 1,000 teens aged 15–17 years in New Hampshire to 29.0 in the District of Columbia. In 2012, there were 86,423 births to teens aged 15–17 years, accounting for 28% of all births to teens aged 15–19 years. This percentage declined from 36% in 1991 to 28% in 2012 (p<0.001). NSFG data for 2006–2010 indicate that although 91% of female teens aged 15–17 years received formal sex education on birth control or how to say no to sex, 24% had not spoken with parents about either topic; among sexually experienced female teens, 83% reported no formal sex education before first sex. Among currently sexually active female teens (those who had sex within 3 months of the survey) aged 15–17 years, 58% used clinical birth control services in the past 12 months, and 92% used contraception at last sex; however, only 1% used the most effective reversible contraceptive methods.Births to teens aged 15–17 years have declined but still account for approximately one quarter of births to teens aged 15–19 years.These data highlight opportunities to increase younger teens exposure to interventions that delay initiation of sex and provide contraceptive services for those who are sexually active; these strategies include support for evidence-based programs that reach youths before they initiate sex, resources for parents in talking to teens about sex and contraception, and access to reproductive health-care services. The U.S. teen birth rate has continued to decline, from 84.1 births per 1,000 teens aged 15–19 years in 1991 to an all-time low of 29.4 in 2012 . Teens iGiven the demonstrated impact of early teen childbearing, CDC analyzed data from the natality files of the National Vital Statistics System to better understand patterns of childbearing among this age group, and from the National Survey of Family Growth (NSFG) to describe sexual experience, contraceptive use, and receipt of prevention opportunities among female teens aged 15–17 years.U.S. natality files are compiled annually by CDC’s National Center for Health Statistics and include demographic information, such as maternal age, race, and Hispanic ethnicity for all births in all 50 states and the District of Columbia. This report includes national data from 1991–2012 and state-specific data for 2012 .NSFG is an in-person, household survey that uses a stratified, multistage probability sample of females and males aged 15–44 years to create nationally representative estimates of sexual behaviors, attitudes, and contraceptive use . The 200Contraceptive use was categorized by level of effectiveness for pregnancy prevention based on the percentage of females who experience pregnancy during the first year of typical use . The mosSelf-reported formal sex education and parent communication about birth control and how to say no to sex were evaluated. Data on receipt of formal sex education before first sex also were analyzed.Differences across racial/ethnic and age subgroups were assessed using chi-square tests without adjustment for multiple comparisons. Differences were considered statistically significant at p<0.05. All analyses were conducted using statistical software to account for the complex sample design of the NSFG.The rate of births per 1,000 teens aged 15–17 years declined 63%, from 38.6 in 1991 to 14.1 in 2012 . The perIn 2012, the birth rate per 1,000 teens aged 15–17 years varied by race/ethnicity, with the highest rates among Hispanics (25.5), followed by non-Hispanic blacks (21.9), American Indians/Alaska Natives (17.0), non-Hispanic whites (8.4), and Asians/Pacific Islanders (4.1) , with thIn 2012, among 305,388 births to teens aged 15–19 years, 86,423 (28.3%) were births to teens aged 15–17 years. The percentage of births to teens aged 15–19 years that were to teens aged 15–17 years declined significantly during the observation period, from 36% in 1991 to 28% in 2012, representing a 22% decrease (p<0.001) .During 2006–2010, among never-married female teens aged 15–17 years, 27.0%  had ever had sex, including 14.6% (CI = 10.3%–20.2%) of those aged 15 years, 28.5% (CI = 22.9%–34.8%) of those aged 16 years, and 38.6% (CI = 33.0%–44.6%) of those aged 17 years. Additionally, 18.0% of teens aged 15–17 years were currently sexually active (CI = 15.2%–21.2%), including 8.0% (CI = 5.2%–12.1%) of those aged 15 years, 16.5% (CI = 13.0%–20.7%) of those aged 16 years, and 29.7% (CI = 24.2%–35.9%) of those aged 17 years. No significant differences by race/ethnicity were observed in the percentage of female teens aged 15–17 years who were sexually experienced or currently sexually active.Among sexually experienced female teens aged 15–17 years, 22.7% (CI =16.7%–30.2%) used no contraceptive method at first sex; 62.0% (CI = 54.8%–68.7%) used a less effective method, and 15.3% (CI = 11.1%–20.8%) used a moderately or most effective method. Among those teens aged 15–17 years who were at risk for pregnancy at last sex, 40.4% (CI = 32.2%–49.1%) used a moderately or most effective method of birth control, 51.8% (CI = 43.3%–60.2%) used less effective methods, and 7.8% (CI = 4.5%–13.4%) used no method; 1.0% (CI = 0.3%–2.7%) used LARC methods at last sex. Additionally, 57.9% (CI = 49.8%–65.6%) of teens aged 15–17 years at risk for pregnancy received clinical birth control services in the past 12 months: 30.4% (CI = 23.8%–37.8%) received counseling about birth control, 35.2% (CI = 28.4%–42.7%) had a checkup or medical test related to birth control, and 51.7% (CI = 43.8%–59.4%) received a method or a prescription for birth control.The vast majority of females aged 15–17 years received formal sex education on either birth control or how to say no to sex: 90.9% (CI = 88.1%–93.1%); fewer (61.3% [CI = 56.9%–65.4%]) received information on both topics . In contThis report documents sharp declines in the birth rates for teens aged 15–17 years during 1991–2012; in parallel, the proportion of all births to teens aged 15–19 years that were to teens aged 15–17 years also has declined. However, approximately one in four births to a teen aged 15–19 years in 2012 was to a teen aged 15–17 years. There are substantial racial/ethnic disparities in births to younger teens with Hispanics, non-Hispanic blacks, and American Indians/Alaska Natives experiencing disproportionately higher rates . EffortsNumerous evidence-based sexual health education programs have proven effective in delaying sexual initiation or increasing contraceptive use . This reParents are a particularly strong influence on the sexual behavior of teens ; howeverAlthough 92% of younger female teens used some form of contraception the last time they had sex, the majority of sexually active female teens aged 15–17 years relied on methods of contraception that are among the least effective during typical use, primarily condoms without simultaneous use of a more effective method. Consistent and correct condom use should be encouraged among sexually active teens to prevent sexually transmitted infections, including human immunodeficiency virus infection. However, during typical use, condoms alone are not highly effective for pregnancy prevention.Only 1% of sexually active females aged 15–17 years were using LARCs, which have the lowest failure rate among reversible methods of contraception and are safe for use for females of all ages, including teens . In addiUse of more effective contraceptive methods by younger teens is limited, in part, because of the need to obtain these contraceptives from a health-care provider; the findings in this report suggest that slightly more than half of sexually active females aged 15–17 years received clinical birth control services in the past 12 months. Efforts that providers can take to increase use of these services by teens include ensuring that clinic services are youth-friendly and providing teen patients with confidential, respectful, and culturally competent services, with convenient office hours, and complete information about the most effective methods of contraception. Laws allowing minors to provide consent for health services and protecting their confidentiality vary by state. Improving confidentiality protections might decrease unintended births for teens ; profess*Although the birth rate of teens aged 15–17 years declined 63% during the period 1991–2012, about one in four teen births occurred to younger teens (those aged 15–17 years) in 2012.About one in four females teens aged 15–17 years have ever had sex. Among those who have, about eight in 10 had not received any formal sex education before the first time they had sex.About nine in 10 sexually active younger teens used some form of contraception the last time they had sex. However, only 1% used one of the two most effective reversible methods .Strategies to delay sexual initiation and increase the use of the most effective birth control methods include implementing evidence-based youth programs, helping parents talk to their teens about sex and contraception, and making sure that a sexually active younger teen can access reproductive health-care services.The findings in this report are subject to at least four limitations. First, only data on births were analyzed because more recent data on pregnancies  are not available. Second, births to teens aged <15 years, which also declined during this period, were not analyzed (The findings in this report suggest that fewer young teens are giving birth, the majority of younger female teens are not yet sexually active, and the vast majority of those who are sexually active report use of some method of contraception. Teens need the necessary knowledge, skills, and encouragement to make healthy decisions and engage in healthy behaviors. Continued efforts to prevent teen childbearing among this group should include developmentally appropriate, evidence-based approaches to further delay sexual initiation and introduce the most effective methods of contraception for those who are sexually active.


Ventilator-associated pneumonia (VAP) is a significant cause of hospital-related infections, one that must be prevented due to its high morbidity and mortality. The purpose of this study was to evaluate the incidence and risk factors in patients developing VAP in our intensive care units (ICUs).This retrospective cohort study involved in mechanically ventilated patients hospitalized for more than 48 hours. VAP diagnosed patients were divided into two groups, those developing pneumonia (VAP(+)) and those not (VAP(-)).\We researched 1560 patients in adult ICUs, 1152 (73.8%) of whom were mechanically ventilated. The MV use rate was 52%. VAP developed in 15.4% of patients. The VAP rate was calculated as 15.7/1000 ventilator days. Mean length of stay in the ICU for VAP(+) and VAP(-) patients were (26.7±16.3 and 18.1±12.7 days (p<0.001)) and mean length of MV use was (23.5±10.3 and 12.6±7.4 days (p<0.001)). High APACHE II and Charlson co-morbidity index scores, extended length of hospitalization and MV time, previous history of hospitalization and antibiotherapy, reintubation, enteral nutrition, chronic obstructive pulmonary disease, cerebrovascular disease, diabetes mellitus and organ failure were determined as significant risk factors for VAP. The mortality rate in the VAP(+) was 65.2%, with 23.6% being attributed to VAP.VAPs are prominent nosocomial infections that can cause considerable morbidity and mortality in ICUs. Patient care procedures for the early diagnosis of patients with a high risk of VAP and for the reduction of risk factors must be implemented by providing training concerning risk factors related to VAP for ICU personnel, and preventable risk factors must be reduced to a minimum. Intensive care units (ICUs) are life support units intended to care for patients requiring intensive care due to organ failure, that are equipped with advanced technology, where vital signs are monitored and where treatment is administered.The purpose of this study was to determine the incidence and risk factors in patients developing VAP in our ICUs.We received permission for present study from local ethics committee of Kanuni Education and Research Hospital, Turkey. and the study was performed retrospectively at the same hospital, which has a 605-bed capacity, including 46 adult ICU beds. Patients hospitalized in the ICU for longer than 48 hour and administered MV between January 1, 2011 and 31st December 2013 were included in the study. Our hospital contains four adult ICUs . Due to nurse shortages, the nurse-patient ratio in our ICUs ranges between 1:3 and 1:4, and may even rise to 1:6 on some nights. Patients’ demographic and clinical characteristics were recorded onto study forms by examination of medical files, infection control committee surveillance data, ICU records, pharmacy records and processing data.The Acute Physiology and Chronic Health Evaluation (APACHE) II scores used were those calculated in the first 24 hour of hospitalization.Descriptive statistical analysis was performed for all parameters. The Kolmogorov-Smirnov test was used to determine the eligibility of variables. Data in conformity with normal distribution were analyzed using Student’s t-test, and those not conforming to normal distribution were analyzed using the Mann Whitney-U test. Data obtained by measurements are given as mean ± standard deviation. Data obtained by counting are given as numbers (%); analyses were performed using the Chi-square test. P<0.05 was regarded as significant.MV was administered to 1152 (73.8%) of the 1560 patients with an ICU stay exceeding 48 hour. The MV use rate was 0.52. Two hundred fourteen VAP attacks occurred in 178 patients (15.4%) receiving MV. The VAP rate was 15.7 in 1000 ventilator days, and mean time to development of VAP was 13.2±8.6 days. Mean age of the VAP(+) patients was 67.8±21.1 and mean age of the VAP(-) patients was 69.4±18.1 (p=0.864). Mean length of stay in the ICU in VAP(+) patients was 26.7±16.3 days, and mean length of MV was 23.5±10.8 days. Mean length of stay in the ICU in VAP(-) patients was 18.1±12.7 days, and mean length of MV was 12.6±7.4 days (p<0.001) .Mean APACHE II score in the VAP(+) patients was 21.5±5.4 and mean APACHE II score in the VAP(-) patients was 19.2±4.9. APACHE II score elevation was statistically significantly correlated with VAP development (p<0.001). Charlson co-morbidity index in the VAP(+) patients was 3.9±1.6, compared to 2.7±3.0 in the VAP(-) patients. A statistically significant correlation was observed between Charlson co-morbidity index elevation and VAP development (p<0.001)In terms of underlying diseases, chronic obstructive pulmonary disease (COPD), diabetes mellitus (DM), cerebrovascular disease and organ failure levels differed significantly between the two groups . Previous hospitalization, a history of antibiotherapy, reintubation and enteral nutrition were assessed as significant risk factors for VAP (p<0.001).Acinetobacter species (31.0%), Pseudomonas aeruginosa (27.6%), Staphylococcus aureus (15.1%), Klebsiella species (6.5%) and Escherichia coli (5.6%)  . BactereOne hundred sixteen (65.2%) of the patients diagnosed with VAP died. Mortality attributed to VAP was 23.6% (n=42). In addition, 52.6% of VAP(-) patients died. A statistically significant correlation was observed between mortality of VAP(+) and VAP(-) patients (p=0.002).MV in ICUs is a life-saving medical procedure in the event of respiratory failure. More than 300,000 patients in the USA receive MV every year.Centers for Disease Control and Prevention data report an incidence of VAP of 0.0-5.8/1000 ventilator days in the ICUs of various hospitals.VAP prolongs length of hospitalization and duration of MVAPACHE II scoring is a system used to measure the severity of diseases in ICUs.Prolongation of stay in intensive care patients and a history of recurrent hospitalization are reported to affect development of infection.Patients monitored in the ICU receive antibiotics for postoperative surveillance, for prophylactic reasons based on infections, and for pre-emptive as well as therapeutic purposes. Off-label and inappropriate length of use of prophylactic antibiotics are not recommended since this will increase colonization by resistant pathogens and the risk of infection.Recurrent intubations increase the risk of VAP by leading to the aspiration of nosocomial bacteria colonizing the oropharynx.Although enteral nutrition is recommended for intensive care patients, it has been reported as a risk factor for VAP in several studies.Considering VAP development in terms of primary and underlying diseases, we observed significantly more VAP development in patients with disease, such as COPD, DM and organ failure. Previous studies have reported that underlying diseases, and particularly COPD and ARDS, lead to gram negative bacteria colonization, affect the mucociliary system, impair local and systemic defense mechanisms and affect the phagocytic functions of alveolar macrophages as well as neutrophils, thus leading to an increase in VAP development.Organ failures may predispose for VAP in association with deterioration of underlying condition and facilitation of bacterial translocation.14VAP has a direct effect on mortality in hospital-associated infections. Bacteremia (particularly Pseudomonas aeruginosa or Acinetobacter spp.), medical diseases, severity of primary disease, inadequate empirical treatment, prolonged hospitalization, and advanced age are reported to increase mortality rate.Pseudomonas aeruginosa (22.5%), Enterococcus fecalis (4.2%) and Candida albicans (4.2%) as VAP agents.Acinetobacter species (31.0%), Pseudomonas aeruginosa (27.6%), Staphylococcus aureus (15.1%), Klebsiella species (6.5%) and Escherichia coli (5.6%). These factors, known as multiple resistant pathogens, are generally involved in late onset of VAP. Ninety five percent of VAP in this study was late onset.The majority of VAP agents are microorganisms with high antibiotic resistance, such as Pseudomonas aeruginosa, Acinetobacter baumannii and Staphylococcus aureus.VAPs are nosocomial infections that cause significant morbidity and mortality in ICUs and that prolong hospitalization. These infections are more common in patients with APACHE II score and Charlson co-morbidity index elevation, with extended hospitalization and MV use and with underlying predisposing diseases. Reintubation increases the risk of VAP 9.3-fold. Guidelines must be adopted in the prevention of these infections, and every country, hospital and ICU must adopt infection control procedures in the light of its own local problems. Training must be provided for ICU personnel on the subject of VAP-related risk factors. Patients’ MV requirements must be assessed daily. The probability of reintubation must be reduced to a minimum, and prolonged MV must be prevented. Patients at high risk for VAP must be diagnosed early and patient care procedures to reduce risk factors must be implemented, and preventable risk factors must be reduced to a minimum.


Objective. To determine the accuracy of the Broselow Tape (BT) versions 2007 and 2011 in estimating weight among pediatric population. Methods. A cross-sectional study was conducted at King Fahad Medical City and six schools across Riyadh province on 1–143-month-old children. BT 2007 and 2011 estimated weights were recorded. Both tapes via the child's height produce an estimated weight, which was compared with the actual weight. Results. A total of 3537 children were recruited. The height (cm) of the subjects was 97.7 ± 24.1 and the actual weight (kg) was 16.07 ± 8.9, whereas the estimated weight determined by BT 2007 was 15.87 ± 7.56 and by BT 2011 was 16.38 ± 7.95. Across all the five age groups, correlation between actual weight and BT 2007 ranged between 0.702 and 0.788, while correlation between actual weight and BT 2011 ranged between 0.698 and 0.788. Correlation between BT 2007 and BT 2011 across all the five age groups ranged from 0.979 to 0.989. Accuracy of both the tape versions was adversely affected when age was >95 months and body weight was >26 kilograms. Conclusions. Our study showed that BT 2007 and 2011 provided accurate estimation of the body weight based on measured body height. However, 2011 version provided more precise estimate for weight.  The care and resuscitation of critically ill and injured children require a thorough and meticulous approach. Drug doses, equipment sizes, and intervention decisions in pediatric emergencies are often based on estimated body weights , 2. ImprA review of the literature showed contradictory data related to the accuracy of length-based measurements which may depend on the obesity rate of the population studied. A study conducted in 2002 in Victoria, Australia, concluded that length-based estimations were superior when compared with other calculation aids . SimilarA recent report suggests that length-to-weight estimate may be significantly underestimating weight in USA children due to rising childhood obesity . In viewA cross-sectional study was conducted between September 2012 and May 2013 to assess the accuracy of the BT versions 2007 and 2011 in estimating weight among pediatric population in Saudi Arabia.The study was performed in pediatric emergency and outpatient department outpatient clinicss at King Fahad Medical City (KFMC) and six elementary schools  across Al Riyadh province, Saudi Arabia.Inclusion criteria were children aged from 1 month to 143 months. Exclusion criteria were children needing resuscitation, children presented with severe dehydration, joint contractures, and chronic or endocrine diseases, children with length <46 or >143 cm (prerequisite for using the BT), and children whose parents refused to participate.Measurements were taken by five certified nurses. In addition, to standardize the performance of the data collectors, several training sessions on height and weight measurement techniques were provided with the use of same scales that were used in the study to measure the height and weight.In the pediatric emergency and outpatient departments, children younger than 1 year were weighed wearing a diaper only using Tronix Scale 4800 . Children 1 year of age or older were weighed wearing ambient clothing using Tronix Scale .The height of the children younger than 1 year or those unable to stand was measured in the supine position using Infantometer . Otherwise, standing length was measured by Stadiometer .In the schools, all measurements were performed with shoes removed and with children wearing light clothing. Standing length (cm) and weight (kg) were measured up to the first decimal place. Body weight was measured by Detecto medical scale  . All scales were calibrated by a biomedical engineer at KFMC according to manufacturer's instructions. BT 2007 and 2011 estimated weights were subsequently recorded. Both tapes via the child's height will produce an estimated weight, which can be directly compared with the patient's actual weight.Primary outcome measure was to check the accuracy of the 2007 and 2011 BT and thereby predict an accurate estimate of a child's weight within a certain agreement. The actual magnitude of the difference was determined as the difference between actual weight and estimated tape weight, with no regard to the sign.Distribution of these differences and anthropometric measurements were represented by descriptive statistics measures.Age was grouped into five classes: 1 to 11, 12 to 35, 36 to 59, 60 to 95, and 96 to 143 months. Actual weight was classified as less than 10, 10–20, 20–30, and more than 30 kilograms.Written informed consent was obtained from the parents/guardians of all children. This study also was approved by the Research Ethics Committee at KFMC, Riyadh, Saudi Arabia, and the administration of each participating school. IRB number was 12-079.t-test was used to measure the difference between actual weight and tape estimate. Linear regression models postulated difference in tape estimate from actual weight as a function of age. Intrascale correlation coefficients (ICC), Cronbach's Alpha, and Bland-Altman limits were used to determine internal consistency and reliability of agreements.Data was described as mean ± SD , median, and percentages. Chi-square test predicted the association between categorical variables. Paired n = 578) twice. Cronbach's Alpha and ICC determined the internal consistency of examiners. Statistical tests were performed using SPSS, version 22 .Reliability was measured by two different examiners measuring a subset of the children (P < 0.001). Moreover, BT 2007 underestimated weight compared to BT 2011, which tended to overestimate weight  of 48.1 ± 37.9, median age was 37 [1–143], and 59.3% were boys. We combined the results for boys and girls because separate gender analysis showed similar conclusions. The height (cm) of the subjects was 97.7 ± 24.1 [46–143], and the actual weight (kg) of the studied subjects was 16.07 ± 8.9 [1.7–79.2], whereas the estimated weight determined by BT 2007 was 15.87 ± 7.56 and by BT 2011 was 16.38 ± 7.95. The mean difference between actual weight and BT 2007 or BT 2011 was independently significant (e weight .P < 0.001) varied across the subsequent age groups between 1.1 and 4.6 (P < 0.001).Absolute magnitude of mean difference between actual weight and BT 2007 or BT 2011 had significantly ( and 4.6 . BMI wasP = 0.096) and (P = 0.740)), respectively. In 12- to 35-month-old children, the internal consistency for Tape 2007 was 0.880 and for Tape 2011 was 0.881, which are considered good estimates.Among 1- to 11-month-old children, BT 2011 was similar to 2007 version in such an agreement (ICC was 0.987). Moreover, the internal consistency for Tape 2007 was 0.817 and for Tape 2011 was 0.821. The mean difference between actual weight and BT 2007 or 2011 was not significant ((P < 0.001) and (P < 0.001)), respectively, while among 36- to 59-month-olds, the agreement between BT 2011 and 2007 versions was ICC = 0.983; moreover, the agreement between actual weight and BT 2007 was similar to the agreement between the actual weight and BT 2011, ICC = 0.711, 0.716, respectively.Moreover, the mean for actual weight was 11.09 ± 2.51; BT 2007 was 11.44 ± 2.54 and BT 2011 was 11.67 ± 2.69. The mean difference between actual weight and BT 2007 or BT 2011 was significant ((P < 0.001) and (P < 0.001)), respectively. The internal consistency for Tape 2007 was 0.800 and for Tape 2011 was 0.790 among 60- to 95-month-old children, which are considered good estimates. The mean of actual weight was 20.43 ± 5.23; BT 2007 was 20.52 ± 3.56 and BT 2011 was 21.10 ± 3.74. The mean difference between actual weight and BT 2007 was not significant (P = 0.530), while the mean difference between actual weight and BT 2011 was significant (P < 0.001). Among 96- to 143-month-old children the agreement between BT 2011 and 2007 versions was ICC = 0.984; moreover, the agreement between actual weight and BT 2007 was almost similar to the agreement between the actual weight and BT 2011, ICC = 0.702, 0.701, respectively.The internal consistency for Tape 2007 was 0.827 and for Tape 2011 was 0.822, which are considered good estimates. The intragroup variance between actual weight and BT 2007 or 2011 was significant ((P < 0.001) and (P < 0.001)), respectively.Furthermore, the internal consistency for Tape 2007 was 0.751 and for Tape 2011 was 0.728, which are considered good estimates. Mean for actual weight was 29.19 ± 8.96 [6.2–79.2]; BT 2007 was 27.13 ± 4.62 [7–34] and BT 2011 was 28.31 ± 5.06 [7–36]. The mean differences of actual weight and both versions of BT were significant  and (0.94) which affirmed high level of agreement and consistency in the measurements .Mean sign difference (95% CI) for 2007 and 2011 Tape was 0.2 [0.1–0.3] and −0.3 [−0.4–−0.2], respectively. However, mean absolute difference (magnitude with no regard to the sign) was 2.1 [2.0–2.2] and 2.2 [2.1–2.3], thereby indicating similarity in accuracy for both Tape versions .Across all the five age groups, correlation between actual weight and BT 2007 ranged between 0.702 and 0.788, while correlation between actual weight and BT 2011 ranged between 0.698 and 0.788. Correlation between BT 2007 and BT 2011 across all the five age groups ranged from 0.979 to 0.989. The meager variation between BT 2007 and BT 2011 across all the five age groups was statistically significant which is evidenced by the overestimated results of BT 2011 and large sample size. Accuracy of both tape versions was adversely affected when age was > 95 months and body weight was > 26 kilograms . Bland-AThe BT was developed on the basis of US population data. We conducted this study to determine the accuracy of the BT versions 2007 and 2011 in estimating weight among Saudi children. World Health Organization's 2006 growth standards suggest that genetic influences on childhood weight for length are minimal and, indeed, that breastfed children growing around the world in healthy communities are expected to attain similar heights and weights for given ages . ReportsThe accuracy of the tape was also stratified by gender and found to be similar for the 2007 and 2011 versions.The strength of our study is that the data were collected from tertiary referral center and elementary schools , distributed across Al Riyadh province, Saudi Arabia. Therefore, it is acceptable to assume that the enrolled children of this study were representative of the Saudi pediatric population. In addition, this study is one of the few studies that evaluate the accuracy of both BT 2007 and BT 2011. Moreover, a subset of children was chosen to evaluate intra- and interexaminers reliability. Each examiner measured the same child twice in this subset. The major strength predicted in this study was the high level of agreement and consistency within and between examiners, while the potential limitation in this study is that the study was conducted on children ≤ 12 years old.The BT has been found to be the most accurate method when compared with other available methods of weight estimation. Our study adds to the current literature in demonstrating that BT 2007 and 2011 provided accurate estimation of the body weight based on measured body height. However, 2011 version gave a more precise estimate of weight. The accuracy of both BT versions was adversely affected when age exceeded 95 months and weight was more than 26 kg. Health care professionals should consider this information when using the BT to estimate weight for pediatric resuscitation.


Diarrhea is a major cause of morbidity and mortality among Bhutanese children. The etiology of diarrhea is not well known due to the challenges of conducting routine surveillance with Bhutan’s modest research facilities. Establishing an etiology is crucial toward generating evidence that will contribute to policy discussions on a diarrheal disease control program. Our previous study, during 2010–2012, revealed that norovirus (NoV) is an important cause of diarrhea among Bhutanese children, and that GII.21 was the major genotype circulating at that time. In other countries, GII.4 is the major genotype responsible for NoV infections. In this update report, we provide new prevalence data to describe the progression of the transformation and distribution of the NoV genotype among Bhutanese children.From June 2013 through May 2014, diarrheal stool samples were collected at one national referral hospital in Thimphu, two regional referral hospitals in the eastern and central regions, and one general hospital in the western region of Bhutan. NoV was detected by reverse transcription–polymerase chain reaction (RT–PCR), by amplifying the capsid gene. The RT–PCR results were confirmed by nucleotide sequencing of the amplicons.The proportion of NoV-positive stool samples was 23.6% (147/623), of which 76.9% were NoV GII and the remainders were NoV GI. The median age of infected children was 15.5 months, with a fairly balanced female: male ratio. NoV GII was most prevalent in the colder months (late November–mid April) and NoV GI had the highest prevalence in the summer (mid April–late September). Nucleotide sequencing was successful in 99 samples of GII strains. The most common genotypes were GII.3 (42.6%), GII.4 Sydney 2012 (15.8%), and GII.4 unassigned (11.9%). No GII.21 was found in any child in the present study. Phylogenetic analysis showed that GII.3 strains in the present study belonged to an independent cluster in lineage B. These strains shared an ancestor with those from different countries and Bhutanese strains circulating during 2010.NoV remains an important cause of diarrhea among Bhutanese children. Genotype GII.3 from a single ancestor strain has spread, replacing the previously circulating GII.21. Current NoV genotypes are similar to the strains circulating worldwide but are primarily related to those in neighboring countries. NoV GII is prevalent during the cold season, while GI is prevalent during the summer. To develop a NoV infection control policy, further studies are needed. Norovirus (NoV) is a single-stranded positive-sense RNA virus with a genome of 7.7 kb. Based on the genetic differences of the capsid protein, NoV is divided into at least six (and sometimes seven) genogroups: GI–GVI. GI and GII are primarily responsible for human infection, although GIV has also been implicated in human diarrhea . With thBhutan is a small, developing country landlocked between India and China. About 14% of Bhutan’s population is concentrated in the capital Thimphu with the majority scattered sparsely throughout the country. Diarrhea is a major cause of illness and death among Bhutanese children; the morbidity rate from diarrhea in children under 5 years old is 314.6/1,000, while 13% of deaths are attributable to diarrhea . As partDiarrheal stool samples were collected from children under 5 years of age attending any of the four major hospitals in Bhutan: Jigme Dorji Wangchuk National Referral Hospital (JDWNRH) in the capital, Thimphu; Gelephu Regional Referral Hospital (GRRH) in Gelephu; Phuntsholing General Hospital (PGH) in Phuntsholing; and Mongar Regional Referral Hospital (MRRH) in Mongar. Verbal consent was obtained from each child’s guardian before collecting stool samples. Ethical approval was obtained from the Research Ethics Board of Health, Bhutan (REBH/2010/009). Diarrhea was defined as passing liquid stools at least three times in 24 hrs. Stool samples were collected and stored in the hospital’s freezer at –40°C until they were transported frozen to the Royal Centre for Disease Control, Thimphu, where they were stored at –80°C. The samples were then transferred by commercial courier to the laboratory at the Faculty of Medicine, Oita University in dry ice, where they were stored at –80°C until use.Stool samples were pretreated with phosphate-buffered solution to a final concentration of 10% (mass/volume). The samples were briefly vortexed, followed by centrifugation at 12000 rpm for 1 min. Supernatant was used for RNA extraction.RNA from fecal samples was extracted using the QIAamp Viral RNA Kit ; to avoid RNA degradation at each step, DNAse- and RNAse- free plastic wares were used. During RNA extraction, the surface was cleaned by spraying a RNAse decontamination solution followed by a RNase-free water rinse.NoV was detected by reverse transcription–polymerase chain reaction (RT–PCR) by amplifying the capsid gene at the C region . The RT–http://www.rivm.nl/mpf/norovirus/typingtool).We determined genogroups and genotypes by submitting nucleotide sequences to the Norovirus Genotyping Tool (https://blast.ncbi.nlm.nih.gov/Blast.cgi), multiple sequence alignment was carried out using ClustalW, and a phylogenetic tree was constructed using Mega 6 [Sequence identity was searched using the Basic Local Alignment Search Tool (BLAST)  were from JDWNRH, 82 (13.2%) from GRRH, 63 (10.1%) from MRRH, and 46 (7.4%) from PGH. The median age of the children was 15 months (range 3–60 months). The study samples included 283 (45.4%) from females and 341 (54.6%) from males. A total of 147 (23.6%) were NoV-positive, among which 34 (23.1%) were NoV GI and 113 (76.9%) were NoV GII. The median age of the NoV-positive children was 15.5 months (range 3–60 months); 73 (49.7%) female and 74 (50.3%) male.Whether NoV infection had a seasonal pattern was determined by plotting NoV cases detected during each month in Thimphu. NoV infection was found to be prevalent throughout the year, with a higher prevalence in the winter and spring (late November–mid April), and in the summer (mid April–late September) . NoV GIINucleotide sequencing was successful in 99 (87.6%) of 113 GII strains, with genotypes in the following order of prevalence: 43 (43.4%) GII.3; 16 (16.2%) GII.4 Sydney 2012; 10 (10.1%) GII.4 unassigned; 5 (5.1%) GII.15; 4 (4%) GII.13; 3 (3%) GII.6; 2 (2%) GII.17; 2 (2%) GII.22; 2 (2%) GII.2; 1 (1%) GII.14; and 11 (11.1%) undetermined genotypes. GII.3 was dominant in all regions, representing 28/66 (41.2%) in JDWNRH; 3/5 (60%) in PGH; 5/12 (41.7%) in GRRH; and 7/16 (43.7) in MRRH.When the genotypes of GII strains were analyzed based on month of detection , no genoPhylogenetic analysis showed that GII.3 strains in the present study belonged to lineage B . The strWorldwide, most GII infections are caused by GII.4, followed by GII.3 or GII.6 and then other genotypes, such as GII.2, GII.12, GII.13, GII.17, and GII.7, in varying proportions . ContrarAlthough the most prevalent NoV genotypes currently responsible for the majority of diarrheal cases are GII.4 and GII.3 , there ab, and Ley, while GII.3 is bound to only types A and B strongly and Leb weakly [In 2010, GII.3 was dominant in Bhutan, after which GII.21 continued to dominate for two years [b weakly . For theb weakly . Since tb weakly .The novel GII.17 (subcluster Kawasaki 2014) NoV, the predominant outbreak strain in Japan and China, has recently been reported from several countries across all continents –34. OnlyOnly one Sydney 2012 variant of GII.4 was identified in Bhutan in 2012 ; currentIn Bhutan, NoV is prevalent throughout the year with two peaks, one in the colder months, and one in summer. NoV GI was more prevalent during the summer compared with the colder months. We previously reported two peaks in the occurrence of diarrheal cases: one in the colder months and the other during the summer . We recoFrom the present study, we can conclude that the prevalence of NoV remains one of the important causes of diarrhea among Bhutanese children, and that the strains originating from an ancestor strain of GII.3 that has been spreading has replaced GII.21. Minor genotypes such as GII.6 also showed changes; the circulating subcluster of this genotype changed from subcluster b to a. Phylogenetic analysis showed that other NoV genotypes were similar to the strains circulating worldwide but were primarily related to those in neighboring countries. NoV GII is prevalent in the colder months, while GI is prevalent in the summer. Further surveillance is needed to determine the factors that trigger the dynamics of NoV genotype changes in Bhutanese children. This will help formulate informed policy to control this serious diarrheal disease.S1 TableThe GenBank accession number, country of origin and year of detection of norovirus GII strains from which the nucleotide sequences of the capsid gene at the C region were used for the construction of the phylogenetic tree.(DOCX)Click here for additional data file.


The purpose of this study is to compare the treatment outcome of different radiation doses of elective neck irradiation (ENI) in nasopharyngeal carcinoma (NPC) patients treated with intensity-modulated radiotherapy (IMRT).In total, 504 patients with nondisseminated NPC who underwent magnetic resonance imaging before radical IMRT between 2000 and 2008 were retrospectively reviewed. The patients were classified into 2 groups based on the ENI dose: low ENI when the ENI dose was 46 Gy (n = 446) and high ENI when the ENI doses were 50 to 60 Gy (n = 58). All the patients in both the groups received a median dose of 72 Gy to the gross tumor and involved nodes. The fraction size was 2 Gy per fraction. Matching was performed between low ENI and high ENI in a 2:1 ratio, and the matching criteria were N-stage, T-stage, treatment modality, pathology classification, sex, and age.P = 0.331), 89.0% and 83.9% (P = 0.235), 90.1% and 85.2% (P = 0.246), 86.8% and 76.6% (P = 0.056), 77.5% and 80.8% (P = 0.926), and 84.4% and 82.5% (P = 0.237), respectively. In the matched-pair analysis, the 5-year PFS, LC, RC, DMFS, OS, and CSS for matched low ENI and high ENI patients were 74.1% and 63.2% (P = 0.134), 92.0% and 83.9% (P = 0.152), 90.1% and 85.2% (P = 0.356), 86.2% and 76.6% (P = 0.125), 87.0% and 80.8% (P = 0.102), and 88.6% and 82.5% (P = 0.080), respectively. In the multivariable analysis for all patients, the ENI group was not a significant factor for PFS, LC, RC, DMFS, OS, and CSS.The median follow-up for all patients was 63.5 months. In all patients, the 5-year progression-free survival (PFS), local control (LC), regional control (RC), distant metastasis-free survival (DMFS), overall survival (OS), and cancer-specific survival (CSS) for low ENI and high ENI patients were 69.0% and 63.2% (A low ENI dose of 46 Gy in 23 fractions is feasible in NPC patients treated with IMRT, and this concept should be validated in the prospective studies. Elective neck irradiation (ENI) covering the nodal regions with potential microscopic disease is the standard practice for radiation therapy (RT) for NPC.,2 However, the elective radiation dose for prostate cancer, which is thought to be relatively radioresistant, is 46 to 50.4 Gy in conventional fractionation.,4 In addition, the textbook of radiotherapy written by Gilbert H. Fletcher stated that 45 Gy in conventional fractionation is adequate for treating the microscopic disease of NPC .The radiation dose of ENI for high-risk subclinical disease is 59.4 Gy in 33 fractions, according to Radiation Therapy Oncology Group studies of NPC.In our hospital, the ENI dose of NPC ranges from 46 to 60 Gy and is determined at the discretion of the treating radiation oncologist. This study was undertaken to evaluate the treatment outcome of different ENI doses and to determine if an ENI dose as low as 46 Gy in 23 fractions is adequate to eradicate the microscopic disease of NPC.22.118F]-fluorodeoxyglucose positron emission tomography was performed. A total of 437 (86.7%) patients underwent a positron emission tomography (PET) study before treatment; the details of the PET study have been previously published.,7 All patients were restaged according to the seventh edition of the American Joint Committee on Cancer (7th AJCC) staging system. The primary treatment consisted of RT alone for stage I disease and cisplatin-based concurrent chemoradiotherapy (CCRT) for stage II-IVb disease. Patients with advanced disease did not receive CCRT when medical comorbidities or patient refusal occurred. Thirty-one stage IVA-B patients participating in a randomized trial received epirubicin-based induction chemotherapy before CCRT. The median radiation dose to the gross tumor and nodes was 72 Gy , and IMRT was used in all patients.This study was approved by the Institutional Review Board of our hospital. In total, 504 patients with biopsy-proven, nondisseminated, newly diagnosed NPC who underwent magnetic resonance imaging (MRI) examination before radical intensity-modulated radiotherapy (IMRT) between November 2000 and December 2008 were retrospectively reviewed. The pretreatment evaluation included a head and neck MRI, a nasopharyngeal fiberoscopy, a bone scan, a chest X-ray, and an abdominal sonogram. The bone scan was optional when [2.2 The patient characteristics of the 2 ENI groups are summarized in Table The patients were divided into 2 groups according to the ENI radiation dose, low ENI, or high ENI, at the discretion of the treating radiation oncologist. In the low ENI group, the radiation dose to all subclinical diseases was 46 Gy in 23 fractions. In the high ENI group, the radiation dose was 60 Gy in 30 fractions to the high-risk subclinical disease (first-echelon nodes) and 50 Gy in 25 fractions to the low-risk subclinical disease . In the 446 patients of the low ENI group, the Ib region (the submandibular nodes) was not included in the elective radiation field because our previous study indicated that the involvement of the submandibular nodes is rare.2.3 In brief, all patients received MRI examination with or without PET study at 3 months after treatment, and a follow-up imaging study was performed when there was suspicion of disease recurrence or at least yearly in patients without clinical symptoms or signs. Disease recurrence was confirmed by biopsy to obtain tissues for histological confirmation if possible, and close clinical and image follow-up was pursued if a biopsy was not feasible or yielded a negative result. Complete restaging examinations, including PET, were highly recommended for patients with disease recurrence. Salvage treatment  was provided for relapsed patients, and the treatment type was based on patient preference and performance status.The details regarding the follow-up plan for all patients have been previously published.2.4χ2 test was used to compare the clinical features of the ENI groups. In multivariable analysis, the Cox proportional hazard model was used to test the independent significance. The following variables were included in the multivariable analysis: age (<50 years vs ≥50 years), gender , pathology (keratinizing vs nonkeratinizing), T category (T1 vs T2 vs T3 vs T4), N category (N0 vs N1 vs N2 vs N3), chemotherapy (none vs concurrent vs induction + concurrent), and the ENI group (low vs high). A P value of <0.05 was considered statistically significant. All statistical analyses were performed using SPSS  13.0 software .The following endpoints were evaluated: progression-free survival (PFS), local control (LC), regional control (RC), distant metastasis-free survival (DMFS), overall survival (OS), and cancer-specific survival (CSS). The failure of PFS was local, regional, or distant progression or death as a result of any cause. Survival was defined as the time between the date of RT initiation and the date of failure or last follow-up. The survival function was estimated using the Kaplan–Meier method. Univariate analysis was performed using the log-rank test. The 3P = 0.331), 89.0% and 83.9% (P = 0.235), 90.1% and 85.2% (P = 0.246), 86.8% and 76.6% (P = 0.056), 77.5% and 80.8% (P = 0.926), and 84.4% and 82.5% (P = 0.237), respectively , 92.0% and 83.9% (P = 0.152), 90.1% and 85.2% (P = 0.356), 86.2% and 76.6% (P = 0.125), 87.0% and 80.8% (P = 0.102), and 88.6% and 82.5% (P = 0.080), respectively , and all surviving patients underwent follow-up for at least 36 months. In all patients, the 5-year PFS, LC, RC, DMFS, OS, and CSS for low ENI and high ENI patients were 69.0% and 63.2%  had a regional recurrence as the first site of disease relapse. Among the 25 patients, 23 patients had neck failure in the initial gross nodal region, 20 were low ENI patients , and 3 in the high ENI group . No patients developed regional failure in the untreated level Ib region (the submandibular nodes). Two patients in the low ENI group  had a regional recurrence as the first site of disease relapse in the elective radiation field. One T4N1M0 male patient with initially right retropharyngeal gross node had an elective regional failure in the right level II lymph node, with 8 mm nodal size before the initial treatment with CCRT. He then received salvage surgery and was alive with disease 67.0 months after relapse. The other T1N3aM0 patient received RT alone as her initial treatment, had an initial 7 mm lymph node in the left supraclavicular fossa, experienced elective supraclavicular fossa regional failure with simultaneous distant metastasis. She received salvage chemotherapy and was dead due to disease 42.8 months after relapse. According to the initial treatment, the elective neck failure rate was 2.2% (1/46) for RT alone and 0.25% (1/400) for CCRT.4 In addition, in prostate cancer, which is relatively radioresistant, the elective radiation dose for the pelvic nodes is also 46 to 50.4 Gy in conventional fractionation.,4Our results demonstrated that there was no significant difference in treatment outcome between the low and high ENI groups with long-term follow-up. The elective neck failure rate was only 0.45% in the low ENI group. The ENI dose of 46 Gy in 23 fractions may be sufficient to eradicate the microscopic disease of NPC, consistent with the suggestion by Gilbert H Fletcher in his traditional textbook. A prospective randomized trial investigating a reduction of the ENI dose from 50 to 40 Gy in head and neck cancer revealed a significantly lower incidence of high-grade dysphagia in the low-dose arm without compromising disease control and survival. Chow et al reported that the cervical nodes from NPC are more radiosensitive to RT than the nodes from other head and neck cancers. The results of the prospective ENI dose deescalation trial for head and neck cancer may also be applicable to NPC.The benefit of lower ENI is the reduced radiation dose to the pharynx and larynx, which may decrease the probability of RT-associated dysphagia and laryngeal dysfunction. According to the Quantitative Analyses of Normal Tissue Effects in the Clinic report, the risk of dysphagia rapidly increases from 45 to 60 Gy.,14 has highly prognostic value in NPC, and the dose of ENI could be decided according to the EBV DNA titer. Xu et al showed that omitting chemotherapy in stage II NPC patients does not compromise the treatment outcome. So in patients with early stage and low plasma EBV DNA, avoid chemotherapy might be feasible to further reduce the toxicities of treatment.The plasma Epstein–Barr virus (EBV) DNA,17 In our study, nearly 90% of the low ENI group patients had received CCRT, and the concomitant chemotherapy may have served as an RT enhancer, increasing control of the microscopic disease. In our study, the elective neck failure rate was 2.2% (1/46) in RT alone and 0.25% (1/400) in CCRT. CCRT for advanced NPC has become a routine practice after several prospective randomized trials established its solid level I evidence, and only a few patients with stage I disease would be treated with RT alone. The RT-enhancing effects of concomitant chemotherapy increase the safety of a low dose of ENI.The radiotherapeutic dose equivalent of concomitant chemotherapy in head and neck cancer is 7.2 to 12 Gy in 2 Gy per fraction.,19 In our study, the level Ib region was not included in the elective radiation field in the low ENI group, and no patient developed a regional failure in the untreated level Ib. In a prospective study of 323 NPC patients without elective irradiation of the level Ib region, Lin et al reported no regional recurrence in the submandibular nodes during a 3-year follow-up period. It has also been reported that the incidence of pathologically proven level Ib microscopic involvement is very low (approximately 3%) in early T-stage node-positive oropharyngeal cancer patients with negative finding on CT scans. Omitting RT to the submandibular nodes will better spare the oral cavity and submandibular glands, which may improve patient's salivary function and reduce patient-reported xerostomia. The importance of sparing radiation to the submandibular glands has also been demonstrated by a prospective Radiation Therapy Oncology Group trial. The importance of the submandibular glands in RT-induced xerostomia and health-related quality of life cannot be underestimated.The involvement of submandibular nodes (level Ib) is rare in NPC, with an incidence of 2.2% to 3.1% in node-positive patients.There are several limitations of the current study, including the retrospective nature of the study design and the inclusion of only patients who completed treatment, which could have affected the outcomes. Nevertheless, strength of this study is that it has a large number of NPC patients treated by IMRT and with long-term follow-up.In conclusion, the present study shows that a low ENI dose of 46 Gy in 23 fractions without ENI to the submandibular nodes is feasible in NPC patients treated with IMRT, particularly in those undergoing concomitant chemotherapy. This idea needs to be further investigated in the future prospective studies.The authors thank for the help of statistical consultation (CLRPG3D0042) of the Biostatistical Center for Clinical Research (BCCR) in Chang Gung Memorial Hospital, Taoyuan, Taiwan. The authors also thank the members of the Head and Neck Oncology Team, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.


Oncotype Dx is used to determine the recurrence risk (RR) in patients with estrogen receptor positive (ER+) and lymph node negative (LN−) breast cancer. The RR is divided into low (0–17), intermediate (18–30), and high (31) to predict chemotherapy benefit. Our goal was to determine the association between histomorphology, immunohistochemistry, and RR. We retrospectively identified 536 patients with ER+ and LN− breast cancers that underwent Oncotype testing from 2006 to 2013. Tumor size ranged from 0.2 cm to 6.5 cm (mean = 1.3 cm) and was uniform in all 3 categories. The carcinomas were as follows: ductal = 63.2%, lobular = 11.1%, and mixed = 35.7%. The RR correlated with the Nottingham grade. Increasing RR was inversely related to PR positivity but directly to Her2 positivity. Of the morphologic parameters, a tubular(lobular) morphology correlated only with low-intermediate scores and anaplastic type with intermediate-high scores. Other morphologies like micropapillary and mucinous were uniformly distributed in each category. Carcinomas with comedo intraductal carcinoma were more likely associated with high RR. Forty-four patients with either isolated tumor cells or micrometastases were evenly distributed amongst the 3 RR. While there was only 1 ER discrepancy between our immunohistochemistry (3+ 80%) and Oncotype, up to 8% of PR+ cases  and 2% of HER2+ cases were undervalued by Oncotype. Oncotype Dx  is a commercially available multigene reverse transcription polymerase chain reaction (RT-PCR) assay that is used to quantify the risk of distant recurrence and predict the benefits of chemotherapy in patients with stage I or II estrogen receptor positive (ER+), Her2 negative, and lymph node negative (LN−) invasive breast cancer treated with tamoxifen . The resThe Oncotype Dx gene panel consists of 21 genes: 16 cancer genes and 5 reference genes. The cancer genes are comprised of a proliferation set , estrogen hormone receptor genes , HER2neu set , invasion set , and GSTM-1 (1 gene). An estimation of the Oncotype Dx RS can be achieved with routine histopathologic parameters including integrated mitotic activity and immunohistochemical protein expression of hormone receptors and HER2neu . This prUsing our pathology laboratory information system database, we retrospectively identified 536 patients with ER+ LN− breast cancers that underwent Oncotype DX testing at our institution from 2007 to 2013. Clinical information including age and tumor size was gathered in all cases. All cases were reviewed to evaluate Nottingham histologic grade . Histomorphology was examined for any unusual variants, and immunohistochemical staining  was checked on excision specimens. Hormone receptor scoring was performed using the percent of positive staining and intensity to calculate an Allred score; a score of 0–2 was considered negative, 3-4 weakly positive, and 5–8 strongly positive. Her2neu was scored as proposed by the most recent American Society of Clinical Pathology (ASCP) guidelines [http://www.R-project.org/). A statistically significant level of p value < 0.05 was defined. The Oncotype Dx data and data generated from the patient diagnosis reports from our institution were analyzed using chi-squared tests. Concordance statistics were also performed to identify any discrepancies between the results of both data sets. Each case was compared to identify discrepancies of ER, PR, and HER2neu hormone status. RS groups were stratified into three groups: low (0–17), intermediate (18–30), and high scores (>30). All histomorphological features of invasive, in situ, and benign disease were identified and compared to each recurrence risk group.Statistical analyses were performed using R version 3.0.3 (R Core Team (2013); R: A language and environment for statistical computing; R Foundation for Statistical Computing Vienna, Austria; ISBN 3-900051-07-0, URL The age of the patients ranged from 33 to 77 (mean = 58 years). The Oncotype Dx RS were correlated by RS and other parameters as summarized in Next, we studied the morphology of the carcinomas for the presence of any specific variant patterns and subclassified them by RS, respectively, as low, intermediate, and high as discussed below. Beginning with type, carcinomas were classified by RS as follows: invasive ductal: 187, 106, and 42; invasive lobular: 34, 21, and 5; mixed ductal and lobular: 80, 53, and 8. The invasive lobular components were further subdivided for the presence of variants and RS as follows: pleomorphic 17.4%, 21.7%, and 19.3% and histiocytoid 2.7%, 7.2%, and 1.8%. Other invasive carcinoma variant patterns included tubular and tubulolobular 16.4%, 8.9%, and 0%; micropapillary 14.7%, 16.7%, and 24.6%; mucinous 4.7%, 4.4%, and 3.5%; anaplastic 0%, 1.7%, and 7.0%. Associated DCIS, comedo type, was subdivided by score as follows: 3.3%, 6.1%, and 15.8%. Lymphatic invasion was subdivided by RS as follows: 24.1%, 18.9%, and 22.8%.Although Oncotype Dx is primarily utilized in patients who are N0, due to physician requests, our series also included a small subset of stage I or II ER+ patients that had ITCs (25 patients = 4.7%) and micrometastases (19 patients = 3.6%). The age of these patients ranged from 34 to 81 years (mean = 57) and the size of the tumors ranged from 0.6 cm to 3.0 cm (mean = 1.4 cm). The RS were as follows: 17 (38.6%) cases  were categorized as low, 21 (47.8%) as intermediate , and 6 (13.6%) as high RS . By histologic grade, they were classified as follows: moderately differentiated (Nottingham grade 2) = 26 and poorly differentiated (Nottingham grade 3) = 18. Histopathologic parameters including size, presence of DCIS, lymphovascular invasion, and size of isolated tumor cells or micrometastases did not show any correlation with the RS.Comparison of hormone analysis and HER2neu by immunohistochemistry (IHC) performed in our CAP approved laboratory and Oncotype Dx was done. Of note, the same paraffin block used for in house biomarker studies was used to cut additional blanks for Oncotype Dx. A corresponding h&e was also obtained for inspection prior to sending out the blanks. There was complete concordance of ER (99.8%) except for one case which was negative by Oncotype Dx but 3+ 80% by IHC. Progesterone receptor (PR) concordance rate was 91.4% and was distributed by RS as follows: low = 97.5%, intermediate = 76.0%, and high = 40.8%. There were 47 (8.7%) PR discrepant cases: 8 that were positive on Oncotype Dx and negative by IHC  and 38 that were negative by Oncotype Dx but positive by IHC. Of the latter, percentage positivity ranged from 1 to 95% . The majority (91%) had an intensity of 1+, with 2 cases that were 2+ and 2 cases that were 3+. Seventy-three cases (13.6%) were PR negative by Oncotype Dx and IHC and their respective RS were subdivided as follows: low RS 7 (2.6%), intermediate RS 37 (29.9%), and high RS 29 (59.2%). Of the poorly differentiated tumors, PR negativity was seen to stratify by RS as follows: low = 1.34%, intermediate = 5%, and high = 38.6%.Although Oncotype Dx is primarily utilized in patients who are Her2 negative, due to physician requests, our series also included a small subset of HER2 positive cases. Her2 was concordant in 98.3% cases and discrepant in 13 (2.7%) cases. Nine cases that were positive on IHC were either negative (5) or equivocal (4) on Oncotype Dx. Four cases that were negative on IHC were equivocal on Oncotype Dx. The Oncotype Dx positive cases were of predominantly high RS, with only 1.95% of intermediate score that was detected by IHC but not Oncotype Dx.It is well established that the Oncotype Dx RS can be used to quantify the risk of distant recurrence in patients with stages I and II ER+, Her2 negative, and LN negative invasive breast cancer who will be treated with tamoxifen . AlthougWe studied the grade and morphology of each case in an attempt to identify any specific morphological variant of the carcinoma. Few studies with limited numbers have attempted to correlate morphology with RS –12, two There was only 1 ER discrepancy between our IHC 3+ 80%) and Oncotype Dx; up to 8% of PR+ cases  and 2% of HER2neu+ cases were undervalued by Oncotype Dx. Several studies have commented on the discrepancy rates between Oncotype Dx and IHC for ER, PR, and HER2neu status. Studies report 93–100% concordance with ER and 86–94.2% PR concordance rates + 80% and, 14. OncStudies have shown that PR negativity has an inverse relationship with Oncotype Dx RS, independent of Nottingham score , 17. OurH score and mitotic grade, we found that the cases with PR H score > 250 and mitotic grade of 1 had low Oncotype Dx RS category and cases with PR H-score < 150 and mitotic grade of 3 were exclusive to high Oncotype Dx RS category. This indicates that Oncotype Dx may serve as a guide in predicting the utility of chemotherapy in patients with carcinomas that are ER+ with ITCs, since the biological potential of the latter is uncertain [It is well established that the Oncotype Dx RS helps guide the use of adjuvant therapy in patients with early stage ER+ LN− tumors, and this practice has been endorsed by both the National Comprehensive Cancer Network and American Society of Clinical Oncology . On the ncertain , 28.A limitation of our study is its retrospective nature with no follow-up and inherent selection bias on the part of the ordering physicians, as not all carcinomas that were ER+ LN− underwent Oncotype Dx testing. Secondly, while we did not have a formula to calculate a RS, we were able to use certain histologic features to predict the behavior of a carcinoma. Using standard pathologic parameters, one can predict that grades 1 and 2 carcinomas were associated with low to intermediate RS whereas grade 3 carcinomas had intermediate to high RS. In addition, certain morphologies such as lobular and tubulolobular are most likely to be associated with low to intermediate RS, whereas other variants such as mucinous and micropapillary lacked such an association and in fact distributed evenly in each of the three RS. Additionally PR− carcinomas associated with high mitotic rates were more likely to be poorly differentiated and have high RS. Carcinomas with ITCs and micrometastases predominated in the low to intermediate scores. This illustrates that, within the family of varied breast cancer grades and morphologies, there may be heterogeneity even amongst the subsets as seen by the spectrum of RS within each subset. This emphasizes that morphology and biomarkers need to be used in association with the RS to determine the use of adjuvant therapy particularly in the intermediate RS. In summary, this is the first largest study of its kind showing morphologic and IHC correlation with Oncotype Dx and in particular its relevance in patients with ITCs or micrometastases. Further studies are needed to address the clinical relevance of testing in this patient population.


Sexually Transmitted Infections (STIs) have always represented a public health concern in the military, yet most studies rely on self-reports among non-random samples of military populations. In addition, most of the studies exploring STI rates among the military focus on US service members. This paper assesses the prevalence and correlates of STIs in the French military using biomarkers and compares self-reported versus diagnosed STIs.Data are drawn from the COSEMIL study, a national sexual health survey conducted in the French military in 2014 and 2015. A random sample of 784 men and 141 women aged 18–57 years completed a self-administered questionnaire and provided biological samples for STI testing. We used logistic regression modeling to identify the correlates of STI diagnosis and self-reports.Chlamydia trachomatis. This rate was four times higher than the 12 months self-reported rate of 1.1% [0.6–2.3]. Reported STI rates were similar among men and women (1.1% versus 1.8%), but diagnosed STI rates were twice as high among females versus males . There were significant differences in the determinants of reported versus diagnosed STIs. In particular, age and sexual orientation were associated with reported STIs, but not with diagnosed STIs. Conversely, STI counseling and depression were associated with STI diagnosis but not with STI reports.The prevalence of diagnosed STIs was 4.7% [3.8–5.9], mostly due to This study underlines the need to use biomarkers in population-based surveys, given the differential and substantial underreporting of STIs. Results also highlight the need for programmatic adaptation to address gender inequalities in STI rates, by developing women’s health services in the French military. Addressing such needs not only benefits women but could also serve as a strategy to reduce overall STI rates as most military women have military partners, increasing the risk of internal transmission. Chlamydia trachomatis and Neisseria gonorrheae) are curable, yet untreated, these infections cause substantial sequelae, increasing the risk of pelvic inflammatory disease, infertility and ectopic pregnancy , with a ρ coefficient that did not differ from 0 , suggesting no selection bias. Among women, the Heckman prevalence rate was 11.3% [6.9–15.7] with a ρ coefficient significantly different from 0 , indicative of selection bias.The prevalence of diagnosed STIs was estimated at 4.7% [3.8–5.9], but varied substantially by sex  and age Chlamydia infections were the most common STIs detected with biological tests for men and women. Twenty-nine individuals were tested positive for Chlamydia trachomatis (3.4% 95%CI [2.4–5.0]), yielding a prevalence rate of 7.1% (95% CI [3.2–11.0]) for women and 3.0% (95% CI [1.7–4.4]) for men. Applying the Heckman model to these rates, the corrected Chlamydia trachomatis prevalence rate was 8.2% for women and 3.0% for men. Twelve individuals were positive for Mycoplasma genitalium, yielding a prevalence rate of 1.4% (95% CI [1.0–1.8]), with 3.3% (95% CI [0.5–6.1]) for women and 1.2% (95% CI [0.8–1.5]) for men. Finally, one test was positive for Neisseria gonorrhea and one for syphilis. There were no cases of HIV or active hepatitis B.Chlamydia infections were the most commonly reported STIs. Information collected from the last reported case of STI for men indicated that most infections were contracted in Mainland France (n = 10) and a majority of infections were transmitted through contact with a casual partner (n = 6). An equal number of men sought treatment with a military physician or with a civilian physician. Only one woman reported an STI in the past 12 months, which was acquired with a regular partner in Mainland France.Self- reported STIs in the last 12 months was evaluated at 1.1% [0.6–2.3], a rate that was four times lower (p<0.001) than diagnosed STI . Chlamydversus 1.8%). However, the variation according to age was also observed  precludes any analysis of associations for women and precludes multivariate analysis for men. Thus, we only present bivariate associations for men in Chlamydia trachomatis was the most common infection, with a prevalence of 7.1%  for women and 3.0%  for men. As reported in other military settings, STI rates in our military population were substantially higher than in the general population, especially for women, where the prevalence of Chlamydia trachomatis was almost three times higher than the 1.6% [1.0–2.5] diagnosed among French women aged 18 to 44 years [Chlamydia trachomatis was 2 times higher in our military population as compared to the 1.4% [0.8–2.6] prevalence among French men aged 18 to 44 years , 4 times higher than the 12 months self-reported STI rate evaluated at 1.1% . 44 years ,39,40. F44 years .versus self-reports) [The present study identifies a number of risk factors for STIs that fall into four categories , differ between measures (STI diagnosis reports) ,42 and dChlamydia rates between 2011 and 2014 [The highest burden of STIs in our study was observed among young servicewomen, with a prevalence reaching 12.7% among women under the age of 25 years. Such sex and age patterns have previously been reported among US military personnel ,40,43 leand 2014 . The FreSexual risk behaviors were commonly reported by servicemen who were 41% to indicate ever having had commercial sex and 29.6% to report multi-partnerships in the last 12 months. In addition, 36.7% of servicemen were classified as “risky drinkers” , yet thCurrent military preventive strategies seem unable to curtail social and regional disparities in STI acquisition, as we found a higher burden of STI diagnosis among the least educated service-members and those who were born in potential high STI endemic environments. Higher STI rates among less educated individuals were also found in the general population in France  as well A number of studies conducted in the military have described higher rates of STIs with respect to mental health issues (depression and post-traumatic stress) –55. In tOur study has several limitations. While prevalence of STIs was higher among women, the small sample of female recruits, despite their oversampling by 5 to 1, constrained our analysis of risk factors for STIs among women. Another limit relates to refusal rates, typical in population based studies  and theDespite these limitations, we believe the present study provides guidance to adapt military health services to address the current ecology of STIs in the Armed Forces, as well as important insights on the potential biases of using self-reports as the sole measure of STIs in population based studies.Results of this study underline the need to use STI biomarkers in population based studies, given the differential and substantial underreporting of STIs leading to biased results. The study also highlights the need for programmatic adaptation of the French military STI task force to address gender inequalities in STI infections, by developing women’s health services in the French military. Addressing military women’s health care needs not only benefits women themselves but may also serve as a general strategy to reduce STI rates as most women in the military partner with military men increasing the risk of internal transmission.S1 Appendix(DOCX)Click here for additional data file.


The replacement of cytology with human papillomavirus testing as the primary cervical screening test in England is imminent. In light of newly available evidence, we revised our previous estimates of the likely impact of primary human papillomavirus testing on incidence of cervical cancer.Using screening data on women aged 25–64 diagnosed with cervical cancer in England between 1988 and 2012, we previously reported that 38.8% had a negative test six months to six years prior to diagnosis. However, not all of these cancers would be prevented by human papillomavirus testing: for 1.0% the human papillomavirus positive test would come too late (within 18 months of diagnosis) to make a difference; 7.6% will have a negative human papillomavirus test (based on 79.9% sensitivity of human papillomavirus testing in cytology negative women); and 2.0% will develop cancer despite a positive human papillomavirus test. Additionally, we estimate that some women  whose cancers are currently prevented by cytology-based screening will have a false-negative human papillomavirus test.Overall, we estimate that 23.9% (95% CI: 19.3–27.6%) of current cases in women invited for screening could be prevented. Based on 2013 cancer incidence statistics, absolute numbers could be reduced by 487 (95% CI 394 to 563) or 3.4 (95% CI 2.8 to 4.0) per 100,000 women per year. Since then Ronco et al.3 have published a pooled analysis of randomised controlled trials with cervical cancer as an outcome, comparing HPV testing with cytology. They found that among women with a negative cytology screening test at entry, the rate ratio for invasive cervical carcinoma was 0.30 : 0.15–0.60). Here, we update our previous estimates of the impact of primary HPV testing on incidence of cervical cancer in England, in light of this new evidence, and taking into account cancers that will be diagnosed despite a previous positive HPV test.The intention to introduce primary human papillomavirus (HPV) testing in the United Kingdom was recently announced by the UK National Screening Committee.5We used a population-based case–control study of prospectively recorded cervical screening data (from 1988 onwards) for women with cervical cancer (ICD-10 C53) diagnosed aged 25 to 64 in England between April 2007 and March 2012. Data on screening were abstracted from routinely recorded cervical cytology records held on the National Cervical Screening Call/Recall System. After linking, the data were pseudonymised before being transferred to us for analysis. Details of the National Audit of Cervical Cancer have been published previously.Previously, we found that 38.8% (95% CI 37.8% to 39.8%) of women with cervical cancer had a negative cytology test resulting in routine recall  between six months and six years prior to their diagnosis. Here, we excluded the 1.0% of women whose only negative test within six years of diagnosis was within 18 months of diagnosis, on the grounds that a positive HPV test, together with a negative cytology test, would result in a repeat test a year later, and would probably not have led to the prevention (or even earlier diagnosis) of that cancer.6; (ii) there will be 70% (95% CI 40–85%) fewer cancers in HPV negative women compared with cytology negative women3; (iii) in women who are cytology positive, the sensitivity of HPV to pre-cancer will be 97.0% (95% CI 95.1–98.9%).7 These values result in a 93.0% (95% CI 88.0–98.0%) overall sensitivity of HPV testing for identifying women who have or would develop cervical cancer over the next six years, compared with an overall sensitivity of 96.5% (95% CI 93.0–100.0%) in the previous publication (see We modelled the likely results of HPV testing using the following scenario: (i) The overall sensitivity of English cytology to “pre-cancer” (i.e. disease that would lead to a cancer diagnosis over the next six years) is 76.6% (95% CI 65.1–85.1%)tion see .Table 1Of the women with negative cytology from 18 months to 6 years before diagnosis (37.8% of 8774 cases in the audit), 79.9% (95% CI 74.8–85.0%) would have been positive on the HPV test  cancer, despite a positive screen between 18 months and 6 years prior to diagnosis. From As HPV testing is to become the sole primary screening test in the UK, it is necessary to take into account the proportion of cancers currently prevented by cytology-based screening which would be missed by HPV testing. We estimate this number to be equal to 4.3% of the current total number of cancers .Taking all of these adjustments into account, we estimate that with HPV primary screening, the number of cervical cancers in women aged 25–64 in England might be reduced by 23.9% (corresponding to 38.8−(1.0 + 7. 6 + 2.0 + 4.3)). Taking into account the uncertainty in the figures combined to reach this percentage, we estimate the 95% confidence interval to be: 19.3% to 27.6% .8 for 2010 to estimate absolute risks. The rate then in women aged 25–64 was 13.0 per 100,000 women, with a total of 1801 cancers. The most recent data are for 20139 show 2039 cancers and a rate of 14.4 per 100,000 women. Applying a reduction of 23.9% to 2013 cancer incidence data yields a reduction of 487 (95% CI 394 to 563) cancers  in women aged 25–64 by introducing HPV primary testing.In our original publication, we estimated a maximum reduction of 587 cancers , using cancer statistics for EnglandWe believe that these updated estimates provide a more realistic estimate of the impact of switching to HPV testing in England. Nevertheless, other factors, such as vaccination (as of September 2015 the first vaccinated catch-up cohorts entered the screening programme) and falling screening coverage (particularly among older women) are not considered here and are likely to have an impact on the effectiveness of HPV primary screening.


Purpose. To evaluate the clinical and diagnostic characteristics of patients with newly diagnosed diabetic macular edema (DME) in Turkey in a real-life setting. Methods. A total of 945 consecutive patients (mean (SD) age: 61.3 (9.9) years, 55.2% male) with newly diagnosed DME were included. Data on patient demographics, comorbidities, ocular history, ophthalmic examination findings including type of DME, central macular thickness (CMT) via time domain (TD) and spectral domain (SD) optical coherence tomography (OCT), and planned treatments were recorded. Results. OCT (98.8%) and fundoscopy (92.9%) were the two most common diagnostic methods. Diffuse and focal DMEs were detected in 39.2% and 36.9% of cases, respectively. Laser photocoagulation (32.1%) and antivascular endothelial growth factors  were the most commonly planned treatments. The median CMT in the right eye was significantly greater in untreated than in treated patients [376.5 μm (range: 160–840) versus 342 μm (range: 146–999) (p = 0.002)] and in the left eye [370 μm (range: 201–780) versus 329 μm (range: 148–999) (p < 0.001)]. Conclusions. This study is the first large-scale real-life registry of DME patients in Turkey. SD-OCT and fundoscopy were the most common diagnostic methods. Laser photocoagulation and anti-VEGF therapy were the most common treatments. Diabetic macular edema (DME) is a major complication of diabetes mellitus that affects central vision. The symptoms of DME range from slight visual blurring to complete blindness if left untreated , 2. ReceThe worldwide prevalence of DME was reported as 6.81% among patients with diabetes . Other rn = 298), 9.7% in those with type 1 diabetes and 2.4% in those with type 2 diabetes , and planned pharmacological treatments  and nonpharmacological treatments .All patients were evaluated on a single visit, and data on demographics and medical history were recorded. This included history of diabetes , hypertension and receipt of antihypertensive treatment, vital signs, body mass index . The results indicated that at least 900 patients from 36 centers should be included to achieve a confidence level of more than 95% and a statistical power of 80%, based on the patient enrollment capacity of the study centers .U test was used to compare paired independent groups and the Kruskal-Wallis test was used for multiple comparisons of independent groups. In subgroup comparisons, when a nonnormal distribution was present, the Mann-Whitney U test, chi-square test, and Fisher's exact test were performed with the Bonferroni correction. For categorical variables, when the conditions for a chi-square test were present, the chi-square test was used to analyze paired and multiple groups. When the conditions for a chi-square condition were not present, Monte Carlo simulation was used for multiple group comparisons. All data are expressed as means and standard deviations (SDs), medians and minimum–maximum values, or percentages where appropriate. A p value less than 0.05 was considered statistically significant.Statistical analysis was performed using SPSS . When the data had nonnormal distributions, the Mann-Whitney We enrolled 945 consecutive patients , 96.4% with type 2 diabetes and 3.6% with type 1 diabetes .Most patients visited an ophthalmologist due to vision problems 52.2%) rather than due to referral  and fundus fluorescein angiography in 690 patients 73.0%) (Table .0% (TablIntraocular pressure was measured in 655 patients 69.3%); this was determined by a pneumatic method in 459 patients (70.1%) and an applanation method in 196 patients (29.9%). The mean (SD) intraocular pressure was 15.5 (3.3) mmHg in the right eye and 15.7 (3.8) mmHg in the left eye  ETDRS-BCVA was 63.3 (58.5) logMAR for the right eye and 68.4 (58.1) logMAR for the left eye in 36 patients. The mean (SD) Snellen score was 0.5 (0.3) for both eyes in 771 and in 769 patients (Table μm for both eyes (n = 1183) and a CMT greater than 300 μm was present in 66.6% of eyes. At diagnosis, the mean (SD) CMT of the right and left eyes was 384.6 (144.0) μm and 377.7 (136.6) μm, respectively. The mean (SD) CMT of the right and left eyes was 341.6 (129) μm and 342.0 (124.7) μm based on TD-OCT and 389.3 (145.2) μm and 381.5 (137.6) μm based on SD-OCT  CMT was 381.1 ± 140.4 Laser photocoagulation therapy (32.1%) and anti-VEGF therapy (31.8%) were the most commonly preferred planned treatments, followed by anti-VEGF + laser photocoagulation therapy (30.8%) Table .p = 0.005), to have a longer duration of diabetes (p < 0.001), to be active smokers (p < 0.001), and to have hypertension (p < 0.001) and dyslipidemia (p < 0.001)  and a CMT greater than 300 μm in both eyes (p < 0.001 for each). In addition, the median CMT was significantly greater in untreated than that in treated patients with diabetes in the right eye  and in the left eye   had greater improvement of visual acuity in patients treated with an intravitreal anti-VEGF agent [OCT was the most common method used for diagnosis of DME in our cohort (98.8%), followed by fundoscopy (92.9%). SD-OCT was used in most cases, and TD-OCT was only used in 10% of our patients. This seems notable given that pattern of edema classification on SD-OCT can have a significant impact on treatment decisions and subsequent visual outcome –25. Alsoy TD-OCT –28. Hency TD-OCT –28. RegaGF agent , 30.A previous case series indicated that diffuse DME was refractory to macular laser photocoagulation therapy . Thus, tμm, patients with diffuse DME and with a higher baseline CMT (>300 μm) were less likely to have received antidiabetic treatment, and there were significantly higher CMTs in untreated than treated patients with diabetes.Moreover, we found that 66.6% of the patients had baseline CMTs greater than 300 The two major nonsurgical treatments for diabetic retinopathy are retinal laser photocoagulation and pharmacologic approaches, including corticosteroids and VEGF inhibitors , 34. SevThe major strength of this observational study is that we examined the records of 945 patients with DME from 36 centers throughout Turkey. This means that our findings are probably generalizable to the overall population of Turkey. The main limitation of our study is its observational design, because nonrandomized allocation might have led to bias and confounding. Nevertheless, given the paucity of reliable information on DME in Turkey, our findings provide important baseline data for a large representative sample of DME patients from Turkey and thus constitute a valuable contribution. More importantly, this study is the most comprehensive real-life investigation of newly diagnosed DME that employed detailed analysis of baseline characteristics and of the different tools and techniques used for diagnosis.μm, and almost half of the patients had diffuse DME. A baseline CMT greater than 300 μm and diffuse DME were more common in those not receiving treatment for diabetes. The baseline data provided by the present registry provides a foundation for future studies of DME screening and treatment. It also could be used as a basis for prediction of treatment success and the likelihood of reducing visual impairment due to diabetes based on different patient characteristics.In conclusion, the present study is the first large-scale real-life registry of newly diagnosed DME patients in Turkey. Most of the patients in our cohort had type 2 diabetes, poor glycemic control, and concomitant systemic hypertension and were diagnosed with diabetes 10–19 years previously. A vision problem, rather than referral from another physician, was the most frequent reason for seeking care from an ophthalmologist. SD-OCT and fundoscopy were the most common diagnostic methods, and laser therapy and anti-VEGF therapy were the most common treatments. Two-thirds of patients had baseline CMT values greater than 300