Results of a randomised Phase II trial of olaparib, chemotherapy or olaparib and cediranib in patients with platinum-resistant ovarian cancer.

BACKGROUND: OCTOVA compared the efficacy of olaparib (O) versus weekly paclitaxel (wP) or olaparib + cediranib (O + C) in recurrent ovarian cancer (OC). AIMS: The main aim of the OCTOVA trial was to determine the progression-free survival (PFS) of olaparib (O) versus the oral combination of olaparib plus cediranib (O + C) and weekly paclitaxel (wP) in recurrent ovarian cancer (OC). METHODS: In total, 139 participants who had relapsed within 12 months of platinum therapy were randomised to O (300 mg twice daily), wP (80 mg/m2 d1,8,15, q28) or O + C (300 mg twice daily/20 mg daily, respectively). The primary endpoint was progression-free survival (PFS) of olaparib (O) versus olaparib plus cediranib (O + C) or weekly paclitaxel (wP). The sample size was calculated to observe a PFS hazard ratio (HR) 0.64 in favour of O + C compared to O (20% one-sided type I error, 80% power). RESULTS: The majority had platinum-resistant disease (90%), 22% prior PARPi, 34% prior anti-angiogenic therapy, 30% germline BRCA1/2 mutations. The PFS was increased for O + C vs O (O + C 5.4 mo (2.3, 9.6): O 3.7 mo (1.8, 7.6) HR = 0.73; 60% CI: 0.59, 0.89; P = 0.1) and no different between wP and O (wP 3.9 m (1.9, 9.1); O 3.7 mo (1.8, 7.6) HR = 0.89, 60% CI: 0.72, 1.09; P = 0.69). The main treatment-related adverse events included manageable diarrhoea (4% Grade 3) and hypertension (4% Grade 3) in the O + C arm. DISCUSSION: OCTOVA demonstrated the activity of O + C in women with recurrent disease, offering a potential non-chemotherapy option. TRIAL REGISTRATION: ISRCTN14784018, registered on 19th January 2018 http://www.isrctn.com/ISRCTN14784018 .

A meta-research study of randomized controlled trials found infrequent and delayed availability of protocols.

OBJECTIVES: Availability of randomized controlled trial (RCT) protocols is essential for the interpretation of trial results and research transparency. STUDY DESIGN AND SETTING: In this study, we determined the availability of RCT protocols approved in Switzerland, Canada, Germany, and the United Kingdom in 2012. For these RCTs, we searched PubMed, Google Scholar, Scopus, and trial registries for publicly available protocols and corresponding full-text publications of results. We determined the proportion of RCTs with (1) publicly available protocols, (2) publications citing the protocol, and (3) registries providing a link to the protocol. A multivariable logistic regression model explored factors associated with protocol availability. RESULTS: Three hundred twenty-six RCTs were included, of which 118 (36.2%) made their protocol publicly available; 56 (47.6% 56 of 118) provided as a peer-reviewed publication and 48 (40.7%, 48 of 118) provided as supplementary material. A total of 90.9% (100 of 110) of the protocols were cited in the main publication, and 55.9% (66 of 118) were linked in the clinical trial registry. Larger sample size (>500; odds ratio [OR] = 5.90, 95% confidence interval [CI], 2.75-13.31) and investigator sponsorship (OR = 1.99, 95% CI, 1.11-3.59) were associated with increased protocol availability. Most protocols were made available shortly before the publication of the main results. CONCLUSION: RCT protocols should be made available at an early stage of the trial.

Effect of Transcatheter Aortic Valve Implantation vs Surgical Aortic Valve Replacement on All-Cause Mortality in Patients With Aortic Stenosis: A Randomized Clinical Trial.

Importance: Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to surgical aortic valve replacement and is the treatment of choice for patients at high operative risk. The role of TAVI in patients at lower risk is unclear. Objective: To determine whether TAVI is noninferior to surgery in patients at moderately increased operative risk. Design, Setting, and Participants: In this randomized clinical trial conducted at 34 UK centers, 913 patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk due to age or comorbidity were enrolled between April 2014 and April 2018 and followed up through April 2019. Interventions: TAVI using any valve with a CE mark (indicating conformity of the valve with all legal and safety requirements for sale throughout the European Economic Area) and any access route (n = 458) or surgical aortic valve replacement (surgery; n = 455). Main Outcomes and Measures: The primary outcome was all-cause mortality at 1 year. The primary hypothesis was that TAVI was noninferior to surgery, with a noninferiority margin of 5% for the upper limit of the 1-sided 97.5% CI for the absolute between-group difference in mortality. There were 36 secondary outcomes (30 reported herein), including duration of hospital stay, major bleeding events, vascular complications, conduction disturbance requiring pacemaker implantation, and aortic regurgitation. Results: Among 913 patients randomized (median age, 81 years [IQR, 78 to 84 years]; 424 [46%] were female; median Society of Thoracic Surgeons mortality risk score, 2.6% [IQR, 2.0% to 3.4%]), 912 (99.9%) completed follow-up and were included in the noninferiority analysis. At 1 year, there were 21 deaths (4.6%) in the TAVI group and 30 deaths (6.6%) in the surgery group, with an adjusted absolute risk difference of -2.0% (1-sided 97.5% CI, -∞ to 1.2%; P < .001 for noninferiority). Of 30 prespecified secondary outcomes reported herein, 24 showed no significant difference at 1 year. TAVI was associated with significantly shorter postprocedural hospitalization (median of 3 days [IQR, 2 to 5 days] vs 8 days [IQR, 6 to 13 days] in the surgery group). At 1 year, there were significantly fewer major bleeding events after TAVI compared with surgery (7.2% vs 20.2%, respectively; adjusted hazard ratio [HR], 0.33 [95% CI, 0.24 to 0.45]) but significantly more vascular complications (10.3% vs 2.4%; adjusted HR, 4.42 [95% CI, 2.54 to 7.71]), conduction disturbances requiring pacemaker implantation (14.2% vs 7.3%; adjusted HR, 2.05 [95% CI, 1.43 to 2.94]), and mild (38.3% vs 11.7%) or moderate (2.3% vs 0.6%) aortic regurgitation (adjusted odds ratio for mild, moderate, or severe [no instance of severe reported] aortic regurgitation combined vs none, 4.89 [95% CI, 3.08 to 7.75]). Conclusions and Relevance: Among patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk, TAVI was noninferior to surgery with respect to all-cause mortality at 1 year. Trial Registration: isrctn.com Identifier: ISRCTN57819173.

Nonregistration, discontinuation, and nonpublication of randomized trials: A repeated metaresearch analysis.

BACKGROUND: We previously found that 25% of 1,017 randomized clinical trials (RCTs) approved between 2000 and 2003 were discontinued prematurely, and 44% remained unpublished at a median of 12 years follow-up. We aimed to assess a decade later (1) whether rates of completion and publication have increased; (2) the extent to which nonpublished RCTs can be identified in trial registries; and (3) the association between reporting quality of protocols and premature discontinuation or nonpublication of RCTs. METHODS AND FINDINGS: We included 326 RCT protocols approved in 2012 by research ethics committees in Switzerland, the United Kingdom, Germany, and Canada in this metaresearch study. Pilot, feasibility, and phase 1 studies were excluded. We extracted trial characteristics from each study protocol and systematically searched for corresponding trial registration (if not reported in the protocol) and full text publications until February 2022. For trial registrations, we searched the (i) World Health Organization: International Clinical Trial Registry Platform (ICTRP); (ii) US National Library of Medicine (ClinicalTrials.gov); (iii) European Union Drug Regulating Authorities Clinical Trials Database (EUCTR); (iv) ISRCTN registry; and (v) Google. For full text publications, we searched PubMed, Google Scholar, and Scopus. We recorded whether RCTs were registered, discontinued (including reason for discontinuation), and published. The reporting quality of RCT protocols was assessed with the 33-item SPIRIT checklist. We used multivariable logistic regression to examine the association between the independent variables protocol reporting quality, planned sample size, type of control (placebo versus other), reporting of any recruitment projection, single-center versus multicenter trials, and industry versus investigator sponsoring, with the 2 dependent variables: (1) publication of RCT results; and (2) trial discontinuation due to poor recruitment. Of the 326 included trials, 19 (6%) were unregistered. Ninety-eight trials (30%) were discontinued prematurely, most often due to poor recruitment (37%; 36/98). One in 5 trials (21%; 70/326) remained unpublished at 10 years follow-up, and 21% of unpublished trials (15/70) were unregistered. Twenty-three of 147 investigator-sponsored trials (16%) reported their results in a trial registry in contrast to 150 of 179 industry-sponsored trials (84%). The median proportion of reported SPIRIT items in included RCT protocols was 69% (interquartile range 61% to 77%). We found no variables associated with trial discontinuation; however, lower reporting quality of trial protocols was associated with nonpublication (odds ratio, 0.71 for each 10% increment in the proportion of SPIRIT items met; 95% confidence interval, 0.55 to 0.92; p = 0.009). Study limitations include that the moderate sample size may have limited the ability of our regression models to identify significant associations. CONCLUSIONS: We have observed that rates of premature trial discontinuation have not changed in the past decade. Nonpublication of RCTs has declined but remains common; 21% of unpublished trials could not be identified in registries. Only 16% of investigator-sponsored trials reported results in a trial registry. Higher reporting quality of RCT protocols was associated with publication of results. Further efforts from all stakeholders are needed to improve efficiency and transparency of clinical research.

Trends of Diabetes Mortality in Iran at National and Sub-National Levels from 1990 to 2015 and Its Association with Socioeconomic Factors.

Background: Following global commitments to prevent and control non-communicable diseases, we sought to estimate national and sub-national trends in diabetes mortality in Iran and assess its association with socioeconomic factors. Methods: In a systematic analytical study, to assess the correlation between diabetes mortality and socioeconomic factors, we used data obtained from the Death Registration System (DRS), the Spatio-temporal model and Gaussian Process Regression (GPR) levels and the diabetes mortality trends, which were estimated by sex, age and year at national and sub-national levels from 1990 to 2015. Results: Between the years 1990 and 2015, the age-standardized diabetes mortality rate (per 100,000) increased from 3.40 (95% UI: 2.33 to 4.99) to 7.72 (95% UI: 5.51 to 10.78) in males and from 4.66 (95% UI: 3.23 to 6.76) to 10.38 (95% UI: 7.54 to 14.23) in females. In 1990, the difference between the highest age-standardized diabetes mortality rate among males was 3.88 times greater than the lowest (5.97 vs. 1.54), and in 2015 this difference was 3.96 times greater (14.65 vs. 3.70). This provincial difference was higher among females and was 5.13 times greater in 1990 (8.41 vs. 1.64) and 5.04 times greater in 2015 (19.87 vs. 3.94). The rate of diabetes mortality rose with urbanization yet declined with an increase in wealth and years of schooling as the main socio-economic factors. Conclusion: The rising trend of diabetes mortality rate at the national level and the sub-national disparities associated with socioeconomic status in Iran warrant the implementation of specific interventions recommended by the '25 by 25' goal.

Reliability of Trial Information Across Registries for Trials With Multiple Registrations: A Systematic Review.

Importance: Clinical trial registries are important for gaining an overview of ongoing research efforts and for deterring and identifying publication bias and selective outcome reporting. The reliability of the information in trial registries is uncertain. Objective: To assess the reliability of information across registries for trials with multiple registrations. Evidence Review: For this systematic review, 360 protocols of randomized clinical trials (RCTs) approved by research ethics committees in Switzerland, the UK, Canada, and Germany in 2012 were evaluated. Clinical trial registries were searched from March to September 2019 for corresponding registrations of these RCTs. For RCTS that were recorded in more than 1 clinical trial registry, key trial characteristics that should be identical among all trial registries (ie, sponsor, funding source, primary outcome, target sample size, trial status, date of first patient enrollment, results available, and main publication indexed) were extracted in duplicate. Agreement between the different trial registries for these key characteristics was analyzed descriptively. Data analyses were conducted from May 1 to November 30, 2020. Representatives from clinical trial registries were interviewed to discuss the study findings between February 1 and March 31, 2021. Findings: The analysis included 197 RCTs registered in more than 1 trial registry (151 in 2 registries and 46 in 3 registries), with 188 trials in ClinicalTrials.gov, 185 in the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT), 20 in ISRCTN, and 47 in other registries. The agreement of key information across all registries was as follows: 178 of 197 RCTs (90%; 95% CI, 85%-94%) for sponsor, 18 of 20 (90%; 95% CI, 68%-99%) for funding source (funding was not reported on ClinicalTrials.gov), 154 of 197 (78%; 95% CI, 72%-84%) for primary outcome, 90 of 197 (46%; 95% CI, 39%-53%) for trial status, 122 of 194 (63%; 95% CI, 56%-70%) for target sample size, and 43 of 57 (75%; 95% CI, 62%-86%) for the date of first patient enrollment when the comparison time was increased to 30 days (date of first patient enrollment was not reported on EudraCT). For results availability in trial registries, agreement was 122 of 197 RCTs (62%; 95% CI, 55%-69%) for summary data reported in the registry and 91 of 197 (46%; 95% CI, 39%-53%) for whether a published article with the main results was indexed. Different legal requirements were stated as the main reason for inconsistencies by representatives of clinical trial registries. Conclusions and Relevance: In this systematic review, for a substantial proportion of registered RCTs, information about key trial characteristics was inconsistent across trial registries, raising concerns about the reliability of the information provided in these registries. Further harmonization across clinical trial registries may be necessary to increase their usefulness.

Randomised phase II trial of olaparib, chemotherapy or olaparib and cediranib in patients with platinum-resistant ovarian cancer (OCTOVA): a study protocol.

INTRODUCTION: Patients relapsing within 12 months of platinum-based chemotherapy usually have a poorer response to subsequent treatments. To date, extensive research into the mechanism of resistance to platinum agents in the treatment of ovarian cancer has not resulted in improved responses or longer survival. Further experimental work and clinical trials with novel agents are therefore justified to address this unmet need.Patients with ovarian, fallopian tube or primary peritoneal cancer that has relapsed within 12 months of platinum-based chemotherapy will be randomised with stratification for BReast CAncer gene (BRCA) status, prior poly (ADP-ribose) polymerase (PARP) exposure and prior antiangiogenic therapy into weekly paclitaxel (chemotherapy), olaparib or the combination of cediranib and olaparib. They will be followed until disease progression or unacceptable toxicity develops. Our trial design permits two investigations. We will compare the efficacy and tolerability of single-agent olaparib with weekly paclitaxel. We will also compare the efficacy and tolerability of olaparib with the combination of olaparib and cediranib. The required sample size of 138 participants (46 per arm) was calculated using a 20% one-sided type I error, 80% power and 15% dropout rate. Recruitment will last 34 months with a follow-up of 18 months. METHODS AND ANALYSIS: ETHICS AND DISSEMINATION: This study will be conducted under a UK Medicines and Healthcare Products Regulatory Agency Clinical Trials Authorisation. Approval to conduct the study was obtained from the responsible authority before beginning the study. The sponsor will retain ownership of all data arising from the trial. We aim to publish this research in a specialist peer-reviewed scientific journal on study completion. EudraCT number: 2016-000559-28, ethics reference number: 16/LO/2150. TRIAL REGISTRATION NUMBER: ISRCTN: ISRCTN14784018, clinicaltrials.gov: NCT03117933; Pre-results.

The Full Blood Count Blood Test for Colorectal Cancer Detection: A Systematic Review, Meta-Analysis, and Critical Appraisal.

INTRODUCTION: A full blood count (FBC) blood test includes 20 components. We systematically reviewed studies that assessed the association of the FBC and diagnosis of colorectal cancer to identify components as risk factors. We reviewed FBC-based prediction models for colorectal cancer risk. METHODS: MEDLINE, EMBASE, CINAHL, and Web of Science were searched until 3 September 2019. We meta-analysed the mean difference in FBC components between those with and without a diagnosis and critically appraised the development and validation of FBC-based prediction models. RESULTS: We included 53 eligible articles. Three of four meta-analysed components showed an association with diagnosis. In the remaining 16 with insufficient data for meta-analysis, three were associated with colorectal cancer. Thirteen FBC-based models were developed. Model performance was commonly assessed using the c-statistic (range 0.72-0.91) and calibration plots. Some models appeared to work well for early detection but good performance may be driven by early events. CONCLUSION: Red blood cells, haemoglobin, mean corpuscular volume, red blood cell distribution width, white blood cell count, and platelets are associated with diagnosis and could be used for referral. Existing FBC-based prediction models might not perform as well as expected and need further critical testing.

Trend of Appendicitis Mortality at National and Provincial Levels in Iran from 1990 to 2015.

BACKGROUND: Appendicitis is one of the most preventable causes of death worldwide. We aimed to determine the trend of mortality due to appendicitis by sex and age at national and provincial levels in Iran during 26 years. METHODS: Data were collected from Iran Death Registration System (DRS), cemetery databanks in Tehran and Esfahan, and the national population and housing censuses of Iran. The estimated population was determined for each group from 1990 to 2015 using a growth model. Incompleteness, misalignment, and misclassification in the DRS were addressed and multiple imputation methods were used for dealing with missing data. ICD-10 codes were converted to Global Burden of Disease (GBD) codes to allow comparison of the results with the GBD study. A Spatio-Temporal model and Gaussian Process Regression were used to predict the levels and trends in child and adult mortality rates, as well as cause fractions. RESULTS: From 1990 to 2015, 6,982 deaths due to appendicitis were estimated in Iran. The age-standardized mortality rate per 100000 decreased from 0.72 (95% UI: 0.46-1.12) in 1990 to 0.11 (0.07-0.16) in 2015, a reduction of 84.72% over the course of 26 years. The male: female ratio was 1.13 during the 26 years of the study with an average annual percent change of -2.31% for women and -2.63% for men. Among men and women, appendicitis mortality rate had the highest magnitude of decline in the province of Zanjan and the lowest in the province of Hormozgan. In 1990, the lowest age-standardized appendicitis-related mortality was observed in both women and men in the province of Alborz and the highest mortality rate among men were observed in the province of Lorestan. In 2015, the lowest mortality rates in women and men were in the province of Tehran. The highest mortality rates in women were in Hormozgan, and in men were in Golestan province. CONCLUSION: The mortality rate due to appendicitis has declined at national and provincial levels in Iran. Understanding the causes of differences across provinces and the trend over years can be useful in priority setting for policy makers to inform preventive actions to further decrease mortality from appendicitis.

National and sub-national patterns of mortality from stroke in the Iranian population (1990-2015): Complementary results from the NASBOD study.

BACKGROUND: Iran lacks a population level comprehensive assessment of stroke epidemiology. Using data from the NASBOD Study, we estimated the mortality of stroke among the Iranian population from 1990 to 2015. METHODS: Data were collected from all the available sources including the national death registration system and two major cemeteries. After addressing incompleteness of child and adult death data and by using mixed effect model, spatio-temporal model and Gaussian Process Regression, levels and trends of child and adult mortality were estimated. By considering cause fraction to these estimates; cause specific mortality was estimated. In these process wealth index, urbanization, and years of schooling were used as covariates. RESULTS: In 2015, the age-standardized stroke mortality rate due was 47.76 (95% UI: 34.68-65.03) for males and 40.16 (30.38-5 2.72) for females, per 100,000 population. Stroke occurrence for both ischemic and non-ischemic strokes showed decreasing trends in both sexes after 2001-2002, at national and sub-national levels. The highest and lowest mortality rates between provinces ranged from 52.11 (40.3-66.66) to 24.47 (18.71-31.79) in men and from 65.51 (47.13-89.41) to 30.43 (21.95-41.82) in women per 100,000 population. CONCLUSION: Although age-standardized rates of stroke mortality are falling, in the past three decades, the absolute number of people who have had a stroke has increased. Stroke mortality remains high in Iran.

National and Sub-National Pediatric Cancer Mortality in Iran, 2000-2015.

BACKGROUND: Cancer, a common disease in adulthood, is a rare albeit slowly increasing condition among children. Currently, limited data are available on the incidence, prevalence, and mortality of these diseases in many regions, including developing countries. Herein, we are reporting national and sub-national estimates on deaths due to childhood cancers between 2000 and 2015 in Iran. METHODS: Cancer mortality rates were estimated using the national death registration system's data after addressing its incompleteness and misclassification, using demographic (complete birth history and summary birth history) and statistical analysis (spatiotemporal, Gaussian process regression, and generalized linear mixed models). We included data from cemeteries of two cities (Tehran and Isfahan) that were not included in the death registration system. We used census data and household expenditure and income surveys for data on population and other covariates used in the modeling. RESULTS: The overall age-standardized death rate (ASDR) of childhood cancers have decreased by 69.52% (80.67-49.71) in Iran (equal to an annual percent change of -3.63 [-4.53- -2.24]), declining from 12.24 (95% UI: 10.52-14.49) in 2000 to 3.73 (2.8-5.29) deaths per 100000 in 2015. This decrement was equal to an annual percent change of 4.35% over these years. Leukemia, brain, and nervous system malignancies accounted for about 66% of all cancer-related mortalities among children and adolescents in 2015, which had a 10% increase compared to 2000. Moreover, trends at the sub-national level showed that the highest and lowest ASDR of childhood cancers ranged from 2.12 to 4.99 across provinces of Iran in 2015. CONCLUSION: Although the overall mortalities have decreased, there is still inequality in the distribution of the recorded deaths. This inequality should be addressed with the improvement of the quality of care and better access to pediatric hospitals and oncologists in these areas.

The trend of burn mortality in Iran - A study of fire, heat and hot substance-related fatal injuries from 1990 to 2015.

INTRODUCTION: Burn injuries are a major cause of preventable mortality worldwide. To implement preventive strategies, a detailed understanding of the rate and trend of fatal burn injuries is needed. The aim of this study was to determine the rate and trend of burn mortality at national and province level in Iran from 1990 to 2015. MATERIALS AND METHODS: The data were retrieved from various sources: the Death Registration System, cemetery databases, the Demographic and Health Survey and three national population and housing censuses. ICD-10 codes were converted to Global Burden of Disease (GBD) codes for comparability. After addressing the incompleteness of death data, statistical methods such as spatio-temporal modelling and Gaussian Process Regression (GPR) were applied to estimate the levels and trend of death and cause specific mortality. RESULTS: The number of deaths due to burning across Iran was 80,625, with a male to female ratio of 0.88, 0.94 and 1.14 in 1990, 1995 and 2015, respectively. The annual percentage change of age-standardized death rate from 1990 to 2015 was -5.42% and -4.22% in women and men, respectively. The burn-related age-standardized mortality rate decreased considerably from 5.97 in 1990 to 1.74 per 100,000 in 2015. The mortality rate due to burns was highest among those aged more than 85 years, especially in Ilam province. CONCLUSION: This study showed a decline in burn mortality in Iran from 1990 to 2015. Continued efforts to reduce the burden of burns are needed to accelerate this progress and prevent injuries.

Measuring Iran's success in achieving Millennium Development Goal 4: a systematic analysis of under-5 mortality at national and subnational levels from 1990 to 2015.

BACKGROUND: Child mortality as one of the key Millennium Development Goals (MDG 4-to reduce child mortality by two-thirds from 1990 to 2015), is included in the Sustainable Development Goals (SDG 3, target 2-to reduce child mortality to fewer than 25 deaths per 1000 livebirths for all countries by 2030), and is a key indicator of the health system in every country. In this study, we aimed to estimate the level and trend of child mortality from 1990 to 2015 in Iran, to assess the progress of the country and its provinces toward these goals. METHODS: We used three different data sources: three censuses, a Demographic and Health Survey (DHS), and 5-year data from the death registration system. We used the summary birth history data from four data sources (the three censuses and DHS) and used maternal age cohort and maternal age period methods to estimate the trends in child mortality rates, combining the estimates of these two indirect methods using Loess regression. We also used the complete birth history method to estimate child mortality rate directly from DHS data. Finally, to synthesise different trends into a single trend and calculate uncertainty intervals (UI), we used Gaussian process regression. FINDINGS: Under-5 mortality rates (deaths per 1000 livebirths) at the national level in Iran in 1990, 2000, 2010, and 2015 were 63·6 (95% UI 63·1-64·0), 38·8 (38·5-39·2), 24·9 (24·3-25·4), and 19·4 (18·6-20·2), respectively. Between 1990 and 2015, the median annual reduction and total overall reduction in these rates were 4·9% and 70%, respectively. At the provincial level, the difference between the highest and lowest child mortality rates in 1990, 2000, and 2015 were 65·6, 40·4, and 38·1 per 1000 livebirths, respectively. Based on the MDG 4 goal, five provinces had not decreased child mortality by two-thirds by 2015. Furthermore, six provinces had not reached SDG 3 (target 2). INTERPRETATION: Iran and most of its provinces achieved MDG 4 and SDG 3 (target 2) goals by 2015. However, at the subnational level in some provinces, there is substantial inequity. Local policy makers should use effective strategies to accelerate the reduction of child mortality for these provinces by 2030. Possible recommendations for such strategies include enhancing the level of education and health literacy among women, tackling sex discrimination, and improving incomes for families. FUNDING: Iran Ministry of Health and Education.

National and Subnational Patterns of Cause of Death in Iran 1990-2015: Applied Methods.

BACKGROUND: Causes of death statistics provide crucial health intelligence in national and international communities. An efficient death registration system provides reliable information for health policy system. In many developing countries, death registration systems face a degree of misclassification and incompleteness. There are many impediments to putting an estimate of cause-specific death rates. Addressing those challenges could prevent misleading results. METHODS: Our data was collected by Ministry of Health and Medical Education, Tehran and Isfahan cemeteries from 1995 to 2010. After converting ICD codes of Iran's death registration into GBD codes, 170 underlying causes of deaths were recognized in the available data. A wide range of methods were applied for preparing the data. We used several statistical models to estimate mortality rates in age-sex-province groups for all causes of deaths. The considerable number of combinations for age, sex, cause of death, year, and province variables made further complicated model selection and evaluation of the results. RESULTS: Totally, 58.91% of deaths were related to males. The majority of cases of death were classified as NCDs (77.83%) and injuries (14.80%). We extrapolated 71.76% and 14.71% of causes of death by mixed effect model, spline model with parameter 0.9 and 0.6, respectively. CONCLUSION: A comprehensive and unique registration system is able to solve many DRS issues. It is necessary to assess the quality and validity of cause of death data. Scientific methods like analyzing mortality level and cause-of-death data are used to provide an overview for better decisions.

The effectiveness of massage therapy in the treatment of infantile colic symptoms: A randomized controlled trial.

BACKGROUND: Infantile colic, cry-fuss and sleep problems are transient in the initial months of life, but they contribute to maternal depression, parenting stress and family mental health problems. In this randomized clinical trial, we aimed to explore the efficacy of massage therapy compared to rocking in reducing infantile colic symptoms including duration and number of cries, sleep duration and severity of infant colic. METHODS: This was a single blind RCT study with a one-week follow-up. One hundred colicky infants aged younger than 12 weeks old were randomly assigned into massage and rocking groups. Infants in the massage group received a massage for 15-20 minutes once during a day and once at night before sleeping for a week. In the control group, mothers rocked their infants gently for 5-25 minutes when the symptoms of colic appeared. Parents recorded the details of the colic symptoms in a diary every day. A GEE approach was applied to explore the effect of the intervention. RESULTS: Efficiency of massage therapy was significantly higher than rocking. At the end of the study, the mean number of daily cries was 4.26±1.40 in the massage and 6.9±2.14 the rocking groups (p<0.01). The mean of the severity score was 1.39±0.19 less in the massage group (p<0.01). Moreover, the mean differences of massage and rocking groups were -0.82±0.20 hour (p<0.01) and 0.72±0.35 (p= 0.04) in the duration of cries and duration of sleep, respectively. CONCLUSION: Massaging significantly improved colic symptoms during a one-week intervention for all outcomes. In addition, significant differences were found between the intervention and control groups in favor of massaging. Therefore, massage therapy is more effective than rocking for treating infant colic symptoms.

High Fasting Plasma Glucose Mortality Effect: A Comparative Risk Assessment in 25-64 Years Old Iranian Population.

BACKGROUND: High fasting plasma glucose (FPG) is one of the main leading risk factors of ischemic heart disease (IHD), stroke, and chronic kidney diseases (CKDs). We estimated population attributable fraction (PAF) and attributed death of these fatal outcomes of high FPG at national and subnational levels in 25-64 years old Iranian adult. METHODS: We used national and subnational data of the Non-Communicable Disease Surveillance Survey for exposure to risk factors in 2005 and 2011 among Iranian adults of 25-64 years old. For estimating the attributed death, using the death registration system data of Iran, we multiply the cause-specific PAFs by the number of outcome-specific deaths. RESULTS: In Iran, high FPG was responsible for about 31% of attributed total deaths of IHD, stroke, and CKD in 2011. The related attributed deaths had increased from 2005 to 2011. In females, the PAFs for the effect of high FPG on IHD, stroke, and CKD were higher in 2011 than 2005 in all age groups. In males, this increase has occurred in over 45 years old. The highest PAFs of high FPG outcomes mostly related to central provinces of Iran. The central region of Iran had the highest and the southeast of the country had the lowest levels of attributed deaths. CONCLUSIONS: Considering the global 25 × 25 targets for noncommunicable disease mortality reduction, high FPG as a leading risk factor of fatal outcomes should be more targeted through the dietary, behavioral, and pharmacological interventions in Iran.

Evaluation of the Trends of Stomach Cancer Incidence in Districts of Iran from 2000-2010: Application of a Random Effects Markov Model.

BACKGROUND: Stomach cancer is the fifth most common cancer and the third leading cause of death among cancers throughout the world. Therefore, stomach cancer outcomes can affect health systems at the national and international levels. Although stomach cancer mortality and incidence rates have decreased in developed countries, these indicators have a raising trend in East Asian developing countries, particularity in Iran. In this study, we aimed to determine the time trend of age-standardized rates of stomach cancer in different districts of Iran from 2000 to 2010. MATERIALS AND METHODS: Cases of cancer were registered using a pathology-based system during 2000-2007 and with a population-based system since 2008 in Iran. In this study, we collected information about the incidence of stomach cancer during a 10 year period for 31 provinces and 376 districts, with a total of 49,917 cases. We employed two statistical approaches (a random effects and a random effects Markov model) for modeling the incidence of stomach cancer in different districts of Iran during the studied period. RESULTS: The random effects model showed that the incidence rate of stomach cancer among males and females had an increasing trend and it increased by 2.38 and 0.87 persons every year, respectively. However, after adjusting for previous responses, the random effects Markov model showed an increasing rate of 1.53 and 0.75 for males and females, respectively. CONCLUSIONS: This study revealed that there are significant differences between different areas of Iran in terms of age-standardized incidence rates of stomach cancer. Our study suggests that a random effects Markov model can adjust for effects of previous. responses.

Mortality Attributable to Excess Body Mass Index in Iran: Implementation of the Comparative Risk Assessment Methodology.

BACKGROUND: The prevalence of obesity continues to rise worldwide with alarming rates in most of the world countries. Our aim was to compare the mortality of fatal disease attributable to excess body mass index (BMI) in Iran in 2005 and 2011. METHODS: Using standards implementation comparative risk assessment methodology, we estimated mortality attributable to excess BMI in Iranian adults of 25-65 years old, at the national and sub-national levels for 9 attributable outcomes including; ischemic heart diseases (IHDs), stroke, hypertensive heart diseases, diabetes mellitus (DM), colon cancer, cancer of the body of the uterus, breast cancer, kidney cancer, and pancreatic cancer. RESULTS: In 2011, in adults of 25-65 years old, at the national level, excess BMI was responsible for 39.5% of total deaths that were attributed to 9 BMI paired outcomes. From them, 55.0% were males. The highest mortality was attributed to IHD (55.7%) which was followed by stroke (19.3%), and DM (12.0%). Based on the population attributed fractions estimations of 2011, except for colon cancer, the remaining 6 common outcomes were higher for women than men. CONCLUSIONS: Despite the priority of the problem, there is currently no comprehensive program to prevention or control obesity in Iran. The present results show a growing need to comprehensive implications for national and sub-national health policies and interventional programs in Iran.

Equity Chasm in Megacities: Five Leading Causes of Death in Tehran.

BACKGROUND: Inequity in megacities is a real concern in public health perspective. Tehran is a megacity with more than 8 million population that is divided into 22 regions (counties) with considerable diversity in socioeconomic status. On the other hand, spatial cluster detection is an important tool in disease surveillance to identify areas of elevated risk and to generate hypotheses about disease or mortality etiology. The present research aims to identify high or low-risk clusters for five non-communicable leading causes of death in 22 regions of Tehran province. METHODS: Cause-specific mortality rates were extracted from Behesht-e-Zahra registry system for Tehran province in 2011. Spatial scan statistic as a most common method in spatial cluster detection was chosen to detect clusters with elevated risk of death. Given the observed and expected number death in each region, a log likelihood ratio (LLR) criterion was used to test whether a cluster is significant. RESULT: Two high-risk and two low-risk clusters were detected for each cause of death. All these clusters were statistically significant with P value less than 0.05. Mapping these clusters shows substantial differences between regions in Tehran. For mortality due to ischemic heart diseases, cerebrovascular diseases, hypertensive diseases, respiratory diseases, and stomach cancer, the high-risk clusters concentrated in southern half of Tehran and low-risk clusters were in northern half of Tehran. In the most situations, regions 2, 3 and 5 seemed to have lower rate of death comparing with other regions. On the other hand, regions, 16, 19 and 20 were in the high rate clusters. CONCLUSION: There was substantial disparity between regions of Tehran for five non-communicable causes of death studied in this article. Identifying factors affecting the observed differences is useful to set effective preventive interventions and can be investigated in future researches.

Tobacco Smoking Status and the Contribution to Burden of Diseases in Iran, 1990-2010: findings from the Global Burden of Disease Study 2010.

BACKGROUND: Tobacco smoking and exposure to second-hand smoke in the indoor environment are major public health risks worldwide. The aim of this paper is to report and critique a global assessment of smoking prevalence, smoking-attributable deaths, and disability adjusted life years (DALYs) extracted from GBD study 2010, by sex and age in Iran from 1990 to 2010. METHODS: The Global Burden of Disease (GBD) Study 2010 estimated the distributions of exposure and relative risks per unit of exposure by systematically reviewing and analyzing published and unpublished data. These assessments were used, together with estimates of death and DALYs due to specific risk factors, to calculate the attributed burden for each risk factor exposure compared with the theoretical-minimum-risk exposure. Uncertainties in the distribution of exposure, relative risks, and relevant outcomes were incorporated into estimates of attributable mortality and burden. In this study, our aim was to reformulate the GBD data, produce new graphs, and explain the results for Iran in greater detail. RESULTS: Between 1990 and 2010, the prevalence of tobacco smoking at all ages increased by 1% in men and declined by 2% in women in Iran, but the overall prevalence in the general population was unchanged (12%). A reduction was observed in the age-standardized death and DALY rates (per 100,000 population) attributed to tobacco smoking, including second-hand smoke. The attributed DALY rate was greater for Iranian men than for Iranian women. The highest rates of DALYs because of tobacco smoking were found in smoker men and women aged 70+, but exposure to second-hand smoke had the most significant burden in children under 5 years old. In 1990, the three leading disease burdens attributed to tobacco smoking, including second-hand smoke, were ischemic heart disease; communicable, maternal, neonatal, and nutritional disorders; and chronic respiratory diseases. In 2010, three leading burden of diseases attributed to tobacco smoking belonged to ischemic heart disease, chronic respiratory disease, and, and cerebrovascular disease, respectively. CONCLUSION: Despite a reduction in the rate of tobacco smoking, including second-hand smoke, since 1990, smoking exposure remained the fifth leading risk factor for deaths and DALYs in Iran in 2010. Overall, our data clearly show the need for new efforts in Iran to reduce the mortality and burden attributed to tobacco smoking.