Delivered rectum and bladder doses were different as compared to expected planned doses, with the magnitude of differences increasing with PTV margin. Daily setup variation during prostate IMRT yields differences in the actual vs. expected doses received by the prostate CTV, rectum, and bladder. The magnitude of these differences is significantly affected by the PTV margin utilized. It was found that when daily CBCT was used for soft‐tissue alignment of the prostate, a 3 mm PTV margin allowed for CTV to be covered for 99% of cases.Variations in daily setup and rectum/bladder filling lead to uncertainties in the delivery of prostate IMRT. The purpose of this study is to determine the optimal PTV margin for CBCT‐guided prostate IMRT based on daily CBCT dose calculations using four different margins. Five patients diagnosed with low‐risk prostate cancer were treated with prostate IMRT to 70 Gy in 28 fractions using daily CBCT for image guidance. The prostate CTV and OARs were contoured on all CBCTs. IMRT plans were created using 1 mm, 3 mm, 5 mm, and 7 mm CTV to PTV expansions. For each delivered fraction, dose calculations were generated utilizing the pretreatment CBCT translational shifts performed and dosimetric analysis was performed. One hundred and forty total treatment fractions (CBCT sessions) were evaluated. The planned prostate CTV V100% was 100% for all PTV margins. Based on CBCT analysis, the actual cumulative CTVs V100% were PACS numbers: 87.55.dk‐, 87.57.Q‐ I.Prostate cancer is the most commonly diagnosed male cancer worldwide, excluding skin cancer.Because of the high dose gradient achieved in IMRT, it is important to utilize an adequate PTV margin to ensure CTV coverage. Image‐guided radiation therapy (IGRT) is used in the daily treatment of prostate cancer to assist in precise dose delivery and to maximize the sparing of normal structures. Two important considerations during prostate radiotherapy, addressed with daily IGRT, include pretreatment organ motion and bladder/rectum filling.The use of cone‐beam computed tomography (CBCT) for IGRT allows for the reduction of daily setup errors. The traditional use of generous PTV margins during prostate IMRT may result in irradiation of unnecessarily large volumes of the rectum and bladder. Proper image guidance can reduce errors in radiotherapy delivery and allow for a reduction of the PTV margin, thereby achieving better dose conformation and possibly reducing rectal and bladder toxicity. However, variations in the daily setup and physiological changes in the volumes of the bladder and rectum can result in displacement and deformation of the prostate during treatment, consequently changing the dose distribution to the target and adjacent organs.The goal of this study was to determine the optimal PTV margin for adequate CTV coverage, while minimizing the dose received by the rectum and bladder during an entire radiotherapy course. Prior studies have determined PTV margins based on calculations using the van Herk formula;In this study, daily CBCT data was used to investigate the deviation in the delivered dose from the planned dose, for plans calculated with four different PTV margins. Although previous studies have investigated daily CBCT‐based dose calculations during prostate radiotherapy, our study is the first, to the best of our knowledge, that has rigorously evaluated four different PTV margins and utilized every CBCT acquired throughout the entire course of treatment (for each patient).II.A.This study was a retrospective analysis of five patients diagnosed with low‐ or intermediate‐risk prostate carcinoma (T1cN0M0). In these cases, the PTV did not include the full seminal vesicles.B.3 treatment planning system . CTV was the contoured prostate. PTVs with 1, 3, 5, and 7 mm uniform margins from the CTV were created. All patients were planned using nine fields with gantry angles of 0° (AP), 40°, 80°, 120°, 160°, 200°, 240°, 280°, and 320°, using 10 MV photon beam IMRT. The prescribed dose was 70 Gy in 28 fractions (2.5 Gy per fraction). For all plans it was ensured that more than 95% of PTV was receiving the full prescription dose, and the CTV was covered by 100% of the prescription dose. For OARs, the following constraints were used: 1) rectum: V70<10%,V60<25%, and V70<10 cc;2)) bladder: V70<10% and V65<20%; 3) femoral heads: V50<5% and V35<15%. For consistency between plans on the same patient with differing margins, all plans were produced by the same physicist. IMRT planning for four different margins  for one patient CT is shown in Fig 1. Additionally, plans were checked for consistency in the plan objectives. This involved ensuring that plans with larger margins resulted in higher rectum and bladder doses when compared to those on the same patient with tighter PTV margins. DVH for CTV, rectum, and bladder for four margins for one of the patients on CT used for treatment planning in Pinnacle is shown in Fig. 2. All plans were evaluated and approved by the treating physicians.Planning CT images were acquired using a Philips CT scanner . Patients were scanned supine with a vacuum bag and knee wedge for immobilization. Three‐mm CT slices were acquired from the top of the iliac crest to 7 cm below the ischium. For each patient, four IMRT plans were generated using the PinnacleC.All patients were treated on a TrueBeam linear accelerator . Prior to daily treatment, a kV‐CBCT of the pelvis was acquired using the standard "pelvis" mode settings: 125 kV, 80 mA, 13 ms, and full scan with half‐fan bowtie filter. An automatic match algorithm was used for the initial assessment of CBCT images and further verification was completed by a physician, with slight manual adjustments as deemed clinically necessary. Alignment was considered optimal when the posterior border of the prostate and the anterior surface of the rectum were in coincidence .D.Daily CBCTs, including treatment isocenters, of all patients were exported from the "offline review" module in Varian's ARIA chart record system, to MIM Maestro software . All contours and planned isocenters were transferred from the planning CT to the daily CBCT using image registration files, as shown in Fig. 3(c). The CTV was delineated on each CBCT. A rigid fusion between the planning CT and each CBCT was preformed using the translational shifts recorded in the image registration file of the patient's electronic chart. The CTV was then manipulated manually to take into account daily changes in the patient's anatomy that resulted in daily deformation of the prostate. To verify that these manual contour changes affected the prostate shape but not the volume, the volume of the CTV was recorded for each CBCT and compared to that of the planning CT. This method assumes that the prostate, on which the CTV is based, does not change in volume significantly from day to day. Additionally, the rectum, bladder, and femoral heads were contoured on each CBCT, according to RTOG guidelines.E.3. Plans utilizing the different PTV margins were transferred from the planning CT to the daily CBCT treatment isocenter. The MU and weight for each beam was kept unchanged: the beam arrangement at the CBCT treatment isocenter is shown in Fig. 3(c).CBCTs and structure files were transferred from MIM Maestro to Pinnacle3 to a spreadsheet using script files.For dose calculations, an anatomical site‐specific CT number to density calibration curve for CBCT calculation was used. The results of the CT number to density curve for the Philips Gemini CT and Varian OBI were in good agreement. A graphical comparison of CT to density curve for CT and daily CBCT is shown in Fig. 4. Raw data were exported from PinnacleIII.Twenty‐eight daily CBCTs were used from each of the five patients who underwent image‐guided IMRT, resulting in a total of 140 CBCT datasets analyzed. The volumes of the prostate, rectum, and bladder on daily CBCTs as compared to the planning CTs are shown in Table 1.A.The CTV dose on the planning CT (P‐CT) compared to the cumulative result of all daily CBCTs (cum. CBCT) for 140 CBCT datasets is shown in Table 2. The CTV V100% calculated on the planning CT using 1, 3, 5, and 7 mm margins was 100%. For CBCTs, however, the cumulative CTV V100% was 96.55% for 1 mm, 99.49% for 3 mm, 99.98% for 5 mm, and 99.99% for 7 mm PTV margins. Similarly, the cum. CBCT CTV V95% was 99.33% for 1 mm, 99.90% for 3 mm, 100% for 5 mm, and 100% for 7 mm PTV margins.>99%. The cum. CBCT CTV V95% was more than 99% for all four margins evaluated. The minimum cum. CBCT V100% was 78.87%, 90.43%, 97.50%, and 99.39% for 1, 3, 5, and 7 mm PTV margins, respectively .For 1 mm PTV margins, the superior–inferior and anterior–posterior aspects of the prostate were not covered by 100% of the prescription dose. However, for 3–7 mm PTV margins, CTV coverage increased to The cumulative dose analysis for all CBCTs demonstrated a very meaningful increase in CTV coverage as the margin was increased from 1 mm to 3 mm, with a smaller increase in CTV coverage as the PTV margin was further incrementally increased beyond 3 mm.B.Comparisons of the bladder dose for the planning CT vs. cum. CBCT for 1, 3, 5, and 7 mm PTV margins are shown in Table 3.mean±SD) for cum. CBCT was 3.39%±5.38%,7.79%±9.59%,12.04%±12.50%, and 14.26%±13.16% for 1, 3, 5, and 7 mm PTV margins, respectively. As the PTV margin was increased, more variations in the bladder dose on the daily CBCTs versus the planning CT were observed .The mean planned V70 Gy was 3.49%, 5.61%, 9.56%, and 11.82% for 1, 3, 5, and 7 mm PTV margins, respectively. The V70 Gy  was 4.45%±3.84%,8.17%±4.98%,11.59%±5.69%, and 16.61%±6.79% for 1, 3, 5, and 7 mm PTV margins, respectively.Increasing the PTV margin led to considerable increases in rectal V70 . The mean planned V70 Gy for 1, 3, 5, and 7 mm PTV margins was 0.97%, 4.37%, 7.86%, and 13.05%, respectively. The cum. CBCT V70 Gy ).The 7 mm PTV margins did not reach the passing criteria for best PTV margins  was 4.45%±3.84%,8.17%±4.98%,11.59%±5.69%, and %±6.79% for 1, 3, 5, and 7 mm PTV margins, respectively.Increasing the PTV margin led to considerable increases in rectal V70 . The mean planned V70 Gy for 1, 3, 5, and 7 mm PTV margins was 0.97%, 4.37%, 7.86%, and 13.05%, respectively. The cum. CBCT V70 Gy ).The 7 mm PTV margins did not reach the passing criteria for best PTV margins  was contoured, planned, and analyzed. The actual cumulative doses received by the prostate CTV, bladder, and rectum were compared to those determined based on the planning CT. For each CBCT dataset, four different dosimetric plans  were evaluated.The received CTV doses differed from those calculated on the planning CTs during the planning process. Specifically, the mean cumulative CTV doses were lower than those determined on the planning CTs, especially with 1 mm PTV margins; CTV coverage increased with a PTV margin of 3 mm. Further increases in PTV margins (5 mm and 7 mm), yielded cumulative CTV coverage similar to that on the planning CTs. Cumulative CBCT dose analysis demonstrated a large increase in CTV coverage as the PTV margin was increased from 1 mm to 3 mm, but no significant increases in CTV coverage when the PTV margin was further increased to 7 mm. Increasing the PTV margin also increased the dose delivered to the bladder and rectum.As the PTV margin was increased, more variations in the CBCT‐based bladder dose, compared to the planned dose, were observed. The actual cumulative doses received by the rectum were higher than the planned dose as the PTV margins were increased to 7 mm.There are known issues associated with the use of CBCT for daily dose calculations.In future work, we will be evaluating changes in CTV and OAR doses for planning CT/daily CBCT alignment based primarily on soft tissue landmarks versus bony anatomy within the pelvis versus prostate/rectum interface. It is possible that the PTV margin necessary may be dependent on the type of registration used when aligning daily CBCTs. For instance, one study has reported that margins for bony anatomy alignment were larger compared to soft tissue alignment.V.For prostate IMRT using daily CBCT for image guidance, a PTV margin of 1 mm is not sufficient to ensure acceptable prostate CTV coverage. A minimum PTV margin of 3 mm provides 100% CTV coverage for 99.49% of all treatments. Increasing the PTV margin to 5 mm achieved 100% CTV coverage for 99.98% of all CBCTs; however, the rectum V70 Gy almost doubled (compared to that received with a PTV margin of 3 mm). Considering both CTV coverage and OAR sparing, a uniform PTV margin of 3 mm, therefore, appears to be optimal for prostate radiotherapy.


The neglected zoonotic diseases (NZD) are an understudied group that are a major cause of illness throughout the developing world. In general, little is known about the prevalence and burden of NZDs in affected communities, particularly in relation to other infectious diseases with which they are often co-endemic. We describe the design and descriptive epidemiological outputs from an integrated study of human and animal zoonotic and non-zoonotic disease in a rural farming community in western Kenya.n = 983) and pigs (n = 91). People and animals were tested for infection or exposure to a wide range of zoonotic and non-zoonotic pathogens. Prevalence estimates, with adjustment for the complex study design, were derived. Evidence for spatial clustering in exposure or infection was identified using the spatial scan statistic.This cross-sectional survey involved 2113 people, their cattle  (36.3% (95% CI 32.8–39.9)), Entamoeba histolytica/dispar (30.1% (95% CI 27.5–32.8)), and Plasmodium falciparum (29.4% (95% CI 26.8–32.0)). Human infection with Taenia spp. was also prevalent (19.7% (95% CI 16.7–22.7)), while exposure to other zoonotic pathogens was comparatively rarer ; Coxiella burnetii, 2.2% (95% CI 1.5–2.9); Rift Valley fever, 0.5% (95% CI 0.2–0.8)). A low prevalence of exposure to Brucella spp. was observed in cattle (0.26% (95% CI 0–0.56). This was higher for Rift Valley fever virus (1.4% (95% CI 0.5–2.22)) and C. burnetii (10.0% (95% CI 7.7–12.2)). The prevalence of Taenia spp. cysticercosis was 53.5% (95% CI 48.7–58.3) in cattle and 17.2% (95% CI 9.1–25.3) in pigs. Mycobacterium bovis infection was found in 2.2% of cattle (95% CI 1.3–3.2), while the prevalence of infection with Mycobacterium spp. was 8.2% (95% CI 6.8–9.6) in people.There was a high prevalence of human parasitism in the community, particularly with hookworm Zoonotic infections in people and animals occur in the context of a wide range of co-endemic pathogens in a rural community in western Kenya. The wide diversity of pathogens under study provides a unique opportunity to explore the distribution and determinants of infection in a multi-pathogen, multi-host system. Zoonotic diseases are caused by a diverse group of pathogens that are transmissible from animals to humans. Several of these diseases, such as avian influenza and bovine spongiform encephalopathy, are extensively studied and are the focus of large scale and successful control efforts. Another group, the so-called neglected zoonotic diseases (NZDs), are under-researched and under-funded at several levels, and tend to be poorly understood . For theThe World Health Organization (WHO) has highlighted the inadequacy of the evidence base for decision making relating to zoonoses in resource poor settings . IdentifWe present here the outputs from a novel epidemiological investigation that sought to address some of these information gaps in the Lake Victoria Crescent zone of western Kenya. Disease-specific data on a number of neglected zoonotic infections were collected concurrently from domestic animals and people living in the same households. The “People, Animals and their Zoonoses” (PAZ) project is a collaborative venture between universities and research institutes in Europe and Kenya, and subscribes to the ‘One Health’  frameworWe selected a number of zoonotic diseases that were expected to cause a significant burden to livestock-keeping communities in the region . These wCo-infection with zoonotic and other pathogens is likely to be a frequent occurrence in poor communities in tropical and sub-tropical Africa, imposing a combined but typically unquantified burden. Such communities may be coping with a wide range of endemic infectious diseases in both people  and their animals (e.g. East Coast fever (ECF), helminthiasis, trypanosomiasis, bovine tuberculosis). These ‘co-factors” may exacerbate susceptibility to zoonotic agents in individuals or result in enhanced spread at a community level . To furtHere we describe the design of this integrated study of human and animal health. We report on the descriptive epidemiology of infection with a range of endemic diseases in people and animals, as well as on the demographic characteristics of the population under study that may influence its zoonotic disease risk.The study population was a mixed-farming community in western Kenya in an area broadly representative of the wider Lake Victoria Crescent ecosystem which spans Kenya, Uganda and Tanzania Fig. . This re2 zone defined by a semi-circle with a 45 km radius emanating from the county town of Busia (in which the study field station was situated) on the Kenyan border with Uganda  a cattle population of around 340,000 head and a domestic pig population of around 55,000 ).The study area was an approximately 3200 kmnda Fig. . This arThe study was cross-sectional, in which the primary sampling unit was the household , within which all eligible and consenting members and their livestock were recruited. The study sample size was powered to estimate the prevalence of zoonotic disease in cattle, with the human sample incidental to that for cattle, but expected to be larger. We used a standard error of 2% for the lowest expected prevalence of a bovine infection or exposure of 5%, and a design effect of 3 to inflate sample size estimates to account for expected clustering at the household level. The resulting cattle sample size of 1365 head were expected to be found in a random sample of 412 households, based on local estimates of herd size and the frequency of cattle ownership. Field data collection took place continually between August 2010 and July 2012.Random sampling of households was stratified by sub-location, the smallest administrative unit in Kenya. There were 143 sublocations in the study area at the time of the study, and the number of households to select per sublocation was proportional to the expected number of cattle in the sublocation, with a minimum of 1 and a maximum of 8. Sampling proportional to number of cattle in a sublocation ensured cattle (and cattle keeping households) had an equal probability of being selected across the whole study area. Cattle population data were available at the division level (the third administrative unit in Kenya at the time of design) from local Divisional Livestock Production Offices (DPLO) and, in the absence of any other information, were considered to be equally proportioned in each sub-location falling within each division’s boundary.A number of random points, ranging between 1 and 8, were generated in each sub-location using ArcMap 9.2  and the x and y co-ordinates entered into a Garmin eTrex hand-held geographical positioning system (GPS) via the DNR Garmin 5.4.1 extension for ArcView . The GPS device was used to locate the physical location of each generated random point whilst in the field, and the nearest human habitation within 300 m was selected for recruitment. Distance between the point and habitations was assessed using the path distance function on the GPS. Where two or more habitations were within the same distance from the random point, the household that was closest to a north bearing was selected. In the absence of a household within 300 m, or following the household head’s refusal to participate, a ‘back-up’ point was randomly generated and recruitment followed in the same manner. Households were recruited regardless of livestock ownership status.A household was defined as all people identified by the household head as being occupant at the time of recruitment and typically occupant (to the extent that food is regularly shared from the household pot(s)) within the past 4 weeks.On the sampling day, a detailed questionnaire was performed with the household head and covered data relating to household demography, access to services, known household level risk factors for infectious disease, and durable asset ownership. Each household occupant meeting the study inclusion criteria (5 years of age or older and not in the last trimester of pregnancy) was invited to participate and then interviewed on their education, occupation, food consumption history, contact with livestock and other animals, disease history and current state of health. When participants were less than 12 years of age, a guardian (preferably the mother) was asked to sit with them during questioning to assist with recall. Questionnaires were written in English and translated into the vernacular  during administration.Following the questionnaire, a physical exam was performed on all participants by a study clinician  who also collected samples for diagnostic testing. A maximum of 25 ml of venous blood was collected from the forearm into plain, heparin, EDTA and Quantiferon-TB Gold  tubes. Thin and thick blood smears were made using blood remaining in the butterfly apparatus following venous sampling. Participants were asked to provide a single faecal sample, collected from the first motion of the day into a collection pot left during recruitment.At the same time, a veterinary team undertook a ~ 100 item questionnaire on livestock owned by the household with the main animal keeper. Individual level risk factor and other data were collected for all bovine and porcine animals within a household that met the inclusion criteria (3 months or older and not in the latter stages of pregnancy). We also recorded data from a physical examination of each animal, including age based on dentition, sex, temperature, anaemia as assessed by FAMACHA scoring  and bodyAll data were recorded on a Personal Digital Assistant (PDA) data entry system (Aceeca MEZ1000 running the ‘Pendragon Forms’ software) and stored and managed in Microsoft Access databases. A barcode-based system was used to link biological samples to anonymised individuals and homesteads.The geographic co-ordinates and altitude were collected at a central point within the homestead using the GPS.Blood and faecal samples were tested for a wide range of infectious agents that were expected to be endemic in the study area.Cryptosporidium species [Taenia spp. [Faecal samples were prepared using standard protocols for the Kato-Katz and Formal Ether techniques , 23 and  species . Remaininia spp. .Thick and thin blood smears were stained using 10% Giemsa and examined under 100× magnification with an oil immersion objective lens. Haemoparasites observed were recorded qualitatively (present/absent) and semi-quantitatively on the basis of standard intensity scales .Trypanosomes and Ricketsiae  [The buffy coat and the red blood cell/buffy coat interface from centrifuged haematocrit tubes containing heparinised blood were examined under 100× oil immersion and at the 10× power for the presence of Method”) . The bufBrucella spp. ; a commercial ELISA (IgG)  for Coxiella burnetii (Q-fever); an in-house indirect ELISA for Rift Valley fever (RVF) (IgG) [Taenia solium (cysticercosis) [Mycobacterium spp. was assessed using a gamma–interferon assay .Blood collected in serum tubes was spun at 3000 rpm for 20 min, and aliquoted into 2 ml barcoded cryovials before serological testing, or storage at −40 °C for later analysis. Serological assays included a rapid immuno-chromatographic flow assay  for exposure to F) (IgG)  performeercosis)  suppliedBrucella in cattle . Cattle samples were tested for the presence of IgG antibodies to Coxiella burnetii using the Checkit Q fever ELISA (IDEXX). Rift Valley fever testing in cattle was performed using the ID Screen competitive ELISA . Cattle and pigs were tested for cysticercosis using the HP10-Ag ELISA. Heparinised blood from cattle was tested for M. bovis using the Bovigam®  in vitro gamma-interferon assay. Faeces were processed using the McMaster technique, Baermans technique and qualitative sedimentation technique [Blood and faecal samples were tested for a range of pathogens expected to be endemic in cattle and pigs in the study area including, where appropriate, the zoonotic pathogens tested for in people. A rapid immuno-chromatographic flow assay  was used for exposure to echnique  as well echnique  and examsvydesign procedure in the survey package [http://cran.r-project.org/). There were a large number of ‘singleton’ primary sampling units at the sublocation level (i.e. sublocations in which a single household was sampled), hence sublocations (n = 143) were aggregated by division (n = 17), which was used as a stratifying variable. A unique identifier was used for each household to account for clustering. Survey-adjusted prevalence and confidence intervals by age-group were derived for animals (cattle and pigs) and people.We used design-based inference to adjust individual infection prevalence estimates and their standard errors on the basis of the complex study design in which individuals were nested in households and households nested in sublocations. Adjustment was implemented using the  package  in R staπ, where π is the sampling probability for each individual in each division, estimated as the fraction of the number of individuals sampled and the total number of people/animals per division. The total population size per division was derived from the 2009 census for people (https://opendata.go.ke/) and from DPLO data for cattle. In the absence of reliable pig population data at the division level, sampling weights were not included in the estimation of porcine prevalence data, which was only adjusted on the basis of household-level clustering.Sampling weights were calculated as 1/survey package in R.The relationship between the prevalence of each human and animal infection and sex was assessed using the Wald statistic, as proposed by Koch et al.  for compwww.satscan.org). We used household-level infection  as the outcome of interest. A Bernoulli model was used with 999 iterations  and a cluster size up to a maximum of 20% of observations. Only those pathogens for which 10 or more households had at least one infected animal or human were included.Human and cattle exposure or infection risk was tested for evidence of spatial clustering using the spatial scan statistic  in SatScsparr package [The spatial distribution of household livestock  ownership and household tribal affiliation was examined using a kernel smoothing approach . For thi package  in R, usA total of 416 households were recruited, with a total sample size of 2113 people. The average reported household size was 7.6 (range 1 to 30) people , from which our average household sample size was 5.1 (range 1 to 21). Of all eligible individuals present in households (2917), we were able to recruit 72.4%. Cattle were kept in 55.3% of households, from which we sampled 983 animals. The average herd size per household was 4.9, and we were able to sample 87.8% out of all animals in sampled households. Pig keeping was less common (16.9% of households), with an average herd size of 2.6. The total pig sample size was 91.Isospora spp., Cyclospora spp., Dientamoeba fraglis, Trichostrongylus spp., Schistosoma bovis and Wucheria bancroti. Several infectious agents were highly prevalent, particularly hookworm  (36.3%), Plasmodium falciparum  (29.4%) and Entamoeba histolytica/dispar (30.1%). Males were at significantly elevated risk of infection with Strongyloides stercoralis, Schistosoma mansoni, hookworm, and P. falciparum. Females were at significantly elevated risk of infection with Taenia solium, Trichuris trichiura, E. histolytica/dispar and HIV  and a moderately low prevalence of seropositivity to Rift Valley fever virus (1.5%) and C. burnetii (2.2%). No cases of human African trypanosomiasis (HAT) were identified using microscopy. A higher prevalence of Mycobacterium spp. (due to zoonotic or non-zoonotic species) was observed (8.2%). Zoonotic or potentially zoonotic protozoal agents, including Cryptosporidium spp. and Balantidium coli and zoonotic trematodes, such as Fasciola spp., were also rare . Infection with Giardia spp., which may be transmitted from livestock, was also found at moderately low prevalence (3.2%). Infection with Taenia spp. was more common, with a prevalence of 19.7% for taeniasis  based on a copro-antigen (Copro-Ag) test, and a prevalence of 5.8% for cysticercosis (the presence of circulating antigens from a T. solium cysticerci).The risk of human exposure to zoonotic pathogens was relatively lower, with a very low prevalence of seropositivity to P. falciparum, where the prevalence in the youngest age group was 53.2% (95% CI 47.3–59.1) compared to 9.9% (95% CI 5.7–14.1) in those people more than 40 years. Hookworm showed the reverse relationship, with a prevalence in children 5–9 years of 26.8% (95% CI 21.1–32.5), whilst this was 45.3% (95% CI 39.3–51.2) in people more than 40 years.There was evidence of some age structure to the prevalence of infection for the common pathogens of people Fig. . This waC. burnetii declined with age: children in the 5–9 age group had a prevalence of seropositivity of 3.2% (95% CI 1.6–4.8) whilst this was 0.6% (95% CI 0–1.3) in adults 40 years and above.HIV and TB infection showed similar age profiles to each other Fig. , with riTaenia spp. infection, 1544 individuals with complete data for all pathogens were infected with or had exposure to an average of 1.94 infectious agents, with a range of 0 to 6 and a median of 2. Two hundred and twenty two individuals (14.4%) had an infection/exposure count of zero while 196 (12.7%) had 4 or more, 57 (3.7%) 5 or more and 13 (0.8%) had 6 concurrent infections/exposures.Out of a total of 22 possible infections  comparing households inside and outside identified cluster = 2.4, p-value = <0.001; RR = 2.1, p-value = 0.003), A. lumbricoides , Iodamoeba butschlii , HIV , S. mansoni , hookworm , T. solium  and P. falciparum .Household infection with ons Fig. , specifiStrongyle spp. (58.4%) and Theileria spp. (53.4%). Infection with Coccidia spp. (37.2%) and Fasciola gigantica (32.5%) was also very common. Male animals were more likely to be infected with Coccidia and Strongyle spp., while females were more likely to be infected with Calicophoron daubneyi. There was weaker evidence for an effect of sex on F. gigantica. Although infection with Dictyocaulus viviparous (lungworm) was relatively rare (2.1%), there was some evidence that males were at elevated risk . The prevalence of seropositivity to Rift Valley fever virus and Mycobacterium bovis were both moderately low . Ten per cent of animals were seropositive for Coxiella burnetii while over 50% of animals showed evidence of cysticercosis due to T saginata. Trypanosoma spp. infections were found in nearly 6% of animals. Of these 73.2% were considered to be non-zoonotic T. vivax, 12.5% T. theileri and 14.3% T. congo based on morphology.The prevalence of seropositivity to Strongyle, Coccidia and Trichuris spp. were most common in younger animals (75.5% (67.3–83.6), 57.3% (49.2–65.3), 14.6% (9.8–19.3) in animals less than 15 months, compared to 43.1% (36.1–50.1), 19.5% (14.4–24.5), 2.4% (0.4–4.4) in animals more than 42 months, respectively), whilst a reverse trend was seen for F. gigantica (11.5% (6.4–16.6) versus 42.6% (35.1–50.0))  compared to 13.7% (9.5–18.0) in animals aged more than 42 months. This was also the case for T. saginata, where the youngest age group had a prevalence of 33.6% (26.1–41.1) compared to 68.4% (62.4–74.3) in the oldest  and Trypansoma spp.  showed significant spatial clustering. Both clusters overlapped to a large extent, and were found on the border of Lake Victoria in the south west of the study area  having on Table . 17.2% oOut of the 9 infectious agents listed in Table The majority (69.4%) of study participants reported attaining at least primary level education. The main tribe was Luhya (50.2%) followed by Luo (21.9%), Teso (14.5%) and Samia (12.6%), with a small number of participants (0.7%) belonging to the Kikuyu, Saboat, Turkana, Kuria, Kalenjin, Pokot or Muganda tribes. The main tribal groups were highly spatially aggregated Fig. . The majMost households kept livestock 92.5%), with the most common species being chickens (87.2%). Goats were kept in 27.4% of households, sheep in 15.6% and ducks in 11.1%. Cats and dogs were also kept by many of the households . The spatial distribution of large and small ruminant and pig keeping households is shown in Fig. 2.5%, witIn addition to high rates of household livestock ownership, potentially important exposures for zoonotic transmission were common in this community. Almost half of the study participants reported taking animals out for grazing at least weekly (47.2%); 14.2% reported milking cattle at least weekly; 6.7% of households reported having direct involvement in animal parturition in the past year; 15% reported having direct involvement in the slaughter of animals in the past year; and 5% reported hunting in the past year. Most individuals (85.3%) reported regularly seeing rats around the household.Meat consumption was common in the community, with 86.2% of participants reporting eating meat . Reported sources included butcheries (89.6%), neighbours (13.4%), and more rarely from own animals (3.2%). Approximately 75% of respondents ate meat outside the home. Most study participants reported consuming cows milk (95%), with 87.4% reporting that they boil it before consumption. 4% of participants reported consuming goats milk. Animal blood was consumed by 20% of participants.Only 15.1% of respondents were aware that infectious diseases can be acquired from animals. Of these, 5.6% named anthrax as a zoonotic disease that could be acquired from cattle; 22.9% named brucellosis from cattle, but only 8.3% from sheep and goats; 12.3% reported that cattle were involved in sleeping sickness transmission; 10.6% that TB could be acquired from cattle; 18.3% that tapeworm could be acquired from meat; and 33.1% that rabies was transmitted from dogs.The “People, Animals and their Zoonoses” study uses a novel human and animal co-sampling approach, which moves away from the ‘one-host, one-pathogen, one-outcome’ paradigm. We report here on the prevalence of infection with a very wide range of pathogens of both people and livestock within a single community. We intend that this integrated survey of human and animal health will allow the development of evidence-based recommendations for the control of zoonotic and other diseases within this mixed farming area of Kenya. The methodology applied is one that can be repeated elsewhere in different communities and environments. Indeed, doing so would provide valuable multi-site data for comparative analysis.A number of infectious agents were highly prevalent within this community, and polyparasitism is common. We therefore repeat the findings from studies from a number of other communities in low income settings –38, and We show that infection risk is not homogeneous across the study area, and that spatial heterogeneities in the probability of household infection exist for several of the human and animal pathogens studied. Exploratory spatial analysis can provide a powerful means with which to identify spatially heterogeneous contextual effects. Such effects might explain why disease risk varies in individuals with the same individual characteristics, but living in different social or biophysical environments , 45. AltBrucella spp. transmission within this small holder farming community.Despite widespread livestock ownership, and regular reported contact with livestock, the prevalence of brucellosis, Q-fever and Rift Valley fever were all low in people. The prevalence of brucellosis was also extremely low in cattle. Bovine brucellosis is known to occur in Kenya, but is likely to have a highly heterogeneous distribution: a seroprevalence survey of cattle in three areas of Kenya revealed highest prevalence in pastoral areas of Samburu (15%), lowest in a tropical highland climate in Kiambu district (2%), adjacent to Nairobi in the central highlands of Kenya and intermediate prevalence in Kilifi district (10%), a lowland area on Kenya’s coast . Rates oBrucella spp. in cattle, and further work to explore the importance of cattle ownership and contact on human risk of infection will be enlightening. RVF virus has not previously been reported in western Kenya, although epidemics have occurred in neighboring regions [Much less work has been done on Q-fever in Kenya than on brucellosis, although a recent study indicated it was an important, but typically undiagnosed, cause of febrile illness in western Kenya . The pre regions . Further regions .Taenia spp. are highly prevalent in the study area, with the high levels of human taeniasis and bovine and porcine cysticercosis observed being an important public health concern [Taenia hydategena [T. solium prevalence in the pig population. The prevalence of T. hydategena in African pigs has historically been presumed to be low, although a recent study in Tanzania suggested a prevalence of 6.6% [Taenia saginata and solium [http://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0004223). Three adult Taenia spp. worms collected from individuals found to be tapeworm carriers based on microscopy in this study were identified as T. saginata by PCR at the Institute for Tropical Medicine in Antwerp, Belgium. An additional important output of this work is the identification of widespread lack of awareness of zoonotic disease; a series of health education messages about these diseases, particularly the risks associated with Taenia spp. and messages around food safety are likely to be valuable. concern . It shoudategena  which ma of 6.6% . The pre of 6.6% . The copd solium . HousehoKenya is undergoing rapid changes in livestock production in order to meet the demands of a growing, increasingly urban, population. This is leading to a trend towards the intensification of livestock production and wider marketisation of livestock products in many parts of the country, including in western Kenya . This coThis large, multi-disciplinary study provides a comprehensive overview of the prevalence of a wide range of pathogens of people and animals in a smallholder farming community in rural western Kenya. This integrated study fits very much within the one health paradigm, and will allow a range of hypotheses about human and animal disease in these linked populations to be tested. A major aim of future work will be to explore the determinants of individual and household infection with single and multiple pathogens in the context of a range of social, environmental and physical parameters. Our rich dataset will also allow exploration of conditions such as polyparasitism and parasite co-occurrence, and in particular how zoonotic pathogens fit into the broader ecology of endemic infectious disease in the study area.


Pediatric Phase I cancer trials are critical for establishing the safety and dosing of anti-cancer treatments in children. Their implementation, however, must contend with the rarity of many pediatric cancers and limits on allowable risk in minors. The aim of this study is to describe the risk and benefit for pediatric cancer Phase I trials.p < 0.001. The overall fatal (grade 5) AE rate was 2.09% (95% CI 1.45% to 2.72%). Across the 4,604 evaluated patients, there were 4,675 grade 3 and 4 drug-related AEs, with an average grade 3/4 AE rate per person equal to 1.32. Our study had the following limitations: trials included in our review were heterogeneous , and we relied on published data only and encountered challenges with the quality of reporting.Our protocol was prospectively registered in PROSPERO (CRD42015015961). We systematically searched Embase and PubMed for solid and hematological malignancy Phase I pediatric trials published between 1 January 2004 and 1 March 2015. We included pediatric cancer Phase I studies, defined as “small sample size, non‑randomized, dose escalation studies that defined the recommended dose for subsequent study of a new drug in each schedule tested.” We measured risk using grade 3, 4, and 5  drug-related adverse events (AEs) and benefit using objective response rates. When possible, data were meta-analyzed. We identified 170 studies meeting our eligibility criteria, accounting for 4,604 patients. The pooled overall objective response rate was 10.29% (95% CI 8.33% to 12.25%), and was lower in solid tumors, 3.17% (95% CI 2.62% to 3.72%), compared with hematological malignancies, 27.90% (95% CI 20.53% to 35.27%); Our meta-analysis suggests that, on the whole, AE and response rates in pediatric Phase I trials are similar to those in adult Phase I trials. Our findings provide an empirical basis for the refinement and review of pediatric Phase I trials, and for communication about their risk and benefit. Jonathan Kimmelman and colleagues report findings from their meta analysis that shows that adverse effects and response rates in phase 1 cancer clinical trials are similar for children as for adults. Phase I cancer clinical trials aim to determine the safety of a new drug, and present a high risk of serious adverse events with limited prospect of therapeutic benefit.National and international regulations establish limits on allowable risk for research involving children.Little is known about the level of risk and benefit in pediatric Phase I trials in oncology.We designed this systematic review with meta-analysis to establish the risk and benefit associated with pediatric Phase I studies in oncology, and to compare our results with those reported for Phase I adult studies in the literature.We systematically searched for pediatric Phase I cancer studies published between 1 January 2004 and 1 March 2015.We identified 170 studies with 4,604 patients meeting eligibility criteria.The pooled overall objective response rate was 10.29%, with a response rate of 3.17% for solid tumors and 27.90% for hematological malignancies.The overall rate of clearly reported fatal (grade 5) adverse events was 2.09%.The average grade 3/4 adverse event rate per person was equal to 1.32.Serious  adverse event and response rates for pediatric Phase I cancer studies were similar to those reported for adult studies.These data help to inform the assessment and ethical evaluation of, and communication about, risk for pediatric Phase I cancer protocols. Despite enormous strides in treating pediatric malignancies, childhood cancer remains the fourth leading cause of death in US children aged 1–18 years ,3. HowevPhase I trials in oncology aim at establishing dose, safety, and preliminary evidence of efficacy of new cancer drugs. Participants generally have advanced cancer and have exhausted standard therapeutic options. Because Phase I trials expose patients to unproven drugs and involve a high degree of uncertainty about risk, the ethical oversight approaches have been widely debated –12. In pLittle is known about the risk and benefit for pediatric Phase I trials and how well these trials comport with the ethical expectation that such studies offer a favorable balance of risk and therapeutic benefit. In 2005, Lee et al. suggested that the proportion of pediatric Phase I monotherapy trial participants experiencing drug-related fatalities was 0.5%, and the objective response rate was 9.6% . Since 2Our protocol was prospectively registered in PROSPERO (CRD42015015961) . We follWe systematically searched Embase and PubMed for articles and abstracts published between 1 January 2004 and 1 March 2015, using strategies that included key words and suggested MeSH and Emtree entry terms, their synonyms, and closely related words. Searches were not limited by language. The starting date of our search period was determined by the timing of the last study to our knowledge presenting data on the efficiency of pediatric Phase I trials in oncology . The fulWe included pediatric cancer Phase I studies, defined as “small sample size, non-randomized, dose escalation studies that defined the recommended dose for subsequent study of a new drug in each schedule tested” , as wellWe created and piloted an extraction form, and on the basis of the pilot we refined the form and prepared the final version. Data were extracted from each publication independently by 2 reviewers . All reviewers received training prior to extraction. Disagreements were resolved by discussion, and when necessary a third person, an arbiter, was involved . An experienced methodologist and experienced experimental oncologist had supervisory roles . In the case of duplicate publications for the same study, the results from full publication and, if possible, the most recent version were used in the extraction. Data were extracted using Google Forms. From each study, we extracted data related to study design, funding, reason for stopping the trial, patient characteristics, intervention, outcomes, and the timing of pediatric testing relative to adult testing. Because Phase I cancer studies do not generally have comparator arms or measure survival endpoints, we used objective response rate and the number of patients receiving recommended dose as proxies for therapeutic benefit –37.We defined objective response rate as the proportion of participants with partial or complete response as defined by authors of the included studies; for hematological malignancies, we considered any of the various methods of measuring response  as acceptable. For acute leukemias, we did not count partial responses in our assessment of objective response, since anything short of complete response is not considered a benefit for these malignancies. Toxicity and adverse events (AEs)  were measured as defined by the Common Toxicity Criteria version 2.0 and revised versions (Common Terminology Criteria for Adverse Events version 3.0 and version 4.0).Because large differences were observed in response rate between solid tumors and hematological malignancies, our meta-analysis was also stratified by type of cancer. For 9 studies that included both solid tumors and hematological malignancies, patients were separated for response analysis.I2 statistics were calculated to provide a measure of the proportion of overall variation attributable to between-study heterogeneity. Differences in response rate and grade 5 AE rate between categories of type of therapy, number of drugs, and number of types of malignancies were assessed using the Q test for heterogeneity in meta-regression. Pooled response and grade 5 AE rate were calculated for categories of publication year  to assess changes over time. p-Values for trend in response and grade 5 AE rate between 2004 and 2015 were obtained from meta-regression. Meta-analysis was conducted using the metafor package (R version 3.2.3); p < 0.05 was considered statistically significant.Pooled response rate and fatal (grade 5) AE rate were calculated within each stratum when more than 1 study provided data using meta-analytic methods. Modeling with random effects and the restricted maximum likelihood (REML) estimator was used to account for between-study heterogeneity. The average number of grade 3/4 AEs per person with 95% confidence interval was estimated using a Poisson regression model. In cases where a fatal event was not clearly described as treatment-related, we excluded it from our estimations of grade 5 AE rate. In order to compare risk and benefits, we analyzed a cohort of studies where both drug-related deaths (grade 5 AEs) and response were clearly reported.Our search identified a total of 7,061 citations for review. A total of 170 unique studies met full eligibility for extraction. Our sample included 74 studies of targeted drugs (43.53%), 72 studies testing classic chemotherapy (42.35%), and 24 studies testing a combination of the two (combined therapy) (14.12%). A full list of drugs tested is shown in Baseline characteristics of the 4,604 enrolled patients are provided in I2 = 74.49%; Tau2 [estimate of between-study variance] = 0.0007). The response rate for solid tumors among 3,569 patients was 3.17% (95% CI 2.62% to 3.72%), while the response rate for hematological malignancies among 780 patients was significantly higher: 27.90% (95% CI 20.53% to 35.27%); p < 0.001. Response rates varied according to the type of therapy used, significantly so in solid tumors (p = 0.0045), while in case of hematological malignancies this relation was at the limit of statistical significance (p = 0.1047). Higher response rates were observed in combined therapy trials: 44.12% (95% CI 26.30% to 61.94%) for hematological malignancies and 6.44% (95% CI 3.82% to 9.05%) for solid tumors. Response rates were similar for solid tumors tested with classical chemotherapy  and combined therapy .We defined objective response as the surrogate clinical benefit because objective response—the main read-out of treatment response used in Phase I trials—does not always predict improved survival. Objective response rates were reported in 167 of the 170 trials. There were 406 objective responses reported among 4,349 patients enrolled in the 167 trials . The poop < 0.001. Another significant difference between responses was related to the number of types of malignancies included in a study. The response rate was much higher in all interventions where 3 or fewer types of cancers were treated in comparison to the studies with 4 or more types of malignancies. The highest relative difference between responses was again identified in solid tumors. When 3 or fewer types of malignancies were included in a study, response rate was 15.01% (95% CI 6.70% to 23.32%). When 4 or more different malignancies were included in a study, response rate was 2.85% (95% CI 2.28% to 3.42%); p < 0.001.We also found significant differences in response rate related to the number of drugs used per study, regardless of the type of therapy . The resp = 0.25 for solid tumors, p = 0.64 for hematological malignancies) (We did not find significant linear time trends in objective response rates (nancies) . Table 3I2 = 0.0%; Tau2 = 0). This included 14 patients with solid tumors  and 23 patients with hematological malignancies . Differences in AE rates by type of therapy were not statistically significant. Grade 3/4 AEs were reported in 129 studies among 3,547 patients, with an average rate per person of 1.32 (95% CI 1.28 to 1.36). This included on average 1.34 (95% CI 1.22 to 1.47) grade 3/4 AEs per person with solid tumors and 1.22 (95% CI 1.12 to 1.31) grade 3/4 AEs per person with hematological malignancies. The highest average grade 3/4 AE rate per person was identified in patients with hematological malignancies tested with combined therapies: 2.75 (95% CI 2.46 to 3.07). We did not find significant linear time trends in fatal (grade 5) AEs  (p = 0.02) for hematological malignancies between 2004–2006  and 2007–2009 .A total of 70 of the 170 trials reported fatal (grade 5) AEs. We observed 37 grade 5 AEs clearly reported among 1,838 patients , suggestlogical) . Howeverp = 0.54) and hematological tumors . We also calculated the grade 5 AE rates in the subgroup of 66 studies, and the majority of the results were almost identical as in the 70 studies where grade 5 AEs were reported. We found that higher response rates were associated with higher grade 5 AE rates in hematological malignancies. We did not find this relationship in solid tumors.For direct risk and benefit evaluation, we identified a cohort of 66 studies out of the 170 where both objective responses and grade 5 AEs were reported . For senOur findings suggest that, on average, 1 in 10 children who enroll in pediatric Phase I trials experience objective response, while 1 in 50 die from drug-related AEs.p = 0.10), nor did we observe an obvious relationship between higher response rate and higher number of patients in expansion cohorts  AE and response rates as adult studies. In The overall death rate calculated in our systematic review was also higher in comparison with non-pediatric trials, though the size of the difference may be caused by differences in the calculation method ,40 S6 T. DespiteThe number of patients receiving doses recommended for subsequent testing can be interpreted as another proxy of therapeutic value for Phase I trials , though We found a significantly higher overall response rate in hematological malignancies than in solid tumors. This likely reflects different criteria used to assess response, differences in the biology of these malignancies, and that the former typically enroll a more homogeneous set of indications. The response rate was also higher in all interventions where 2 or more drugs were tested in comparison to the single-drug studies. The response rate was higher in all interventions where 3 or fewer types of malignancies were treated in comparison to the studies with 4 or more malignancies. This possibly indicates that studies where patients with a wider variety of malignancies are enrolled are based on a weaker research hypothesis regarding the efficacy of the tested agent against the specific malignancy. The average grade 3/4 AE rate per person was 1.32, which means that the typical patient was exposed to at least 1 major side effect of a therapy.Our findings should be interpreted in light of the following limitations. First, the trials analyzed in our review were very heterogeneous. We used broad inclusion criteria to summarize the global response rate and risk. To reduce heterogeneity, we separated therapy types  and cancer types . We also explored this heterogeneity using meta-regression. Second, we relied only on published data and on the quality of reporting. Many current studies illustrate discrepancies between clinical trial registry records and published articles –49. MoreIn adult Phase I cancer research, there is a lively debate as to whether access to treatments through trials is therapeutic ,11,24,52S1 PRISMA Checklist(DOCX)Click here for additional data file.S1 Fig(TIF)Click here for additional data file.S2 Fig(TIF)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S3 Table(DOCX)Click here for additional data file.S4 Table(DOCX)Click here for additional data file.S5 Table(DOCX)Click here for additional data file.S6 Table(DOCX)Click here for additional data file.


Background: Vitamin D deficiency is considered to be a public health problem. However, the nutrient status of vitamin D in Chinese children is unclear. The aim of this study was to describe the vitamin D status among children aged under 18 years in southeast China. Methods: Children who visited the Huzhou Maternal and Child Care Hospital from January 2012 to August 2015 were included in this large cross-sectional study. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were measured by electrochemiluminescence immunoassay. Vitamin D status was defined as deficiency (25(OH)D < 20 ng/mL), insufficiency (25(OH)D: 20–29 ng/mL) and sufficiency (25(OH)D ≥ 30 ng/mL). The association between relevant variables and vitamin D status was analyzed by a using generalized estimated equation model and a multivariate regression model. Results: 13,997 children aged under 18 years were included. Of these, 23.3% children suffered from low vitamin D status (deficiency and insufficiency), while 76.7% had a sufficient vitamin D status. The prevalence of low vitamin D status was 29.7% in winter and 23.4% in spring, which was higher than that in summer (21.4%) and autumn (19.9%). Clinical visiting children (32.1%) suffered more from low vitamin D than health examination children (17.6%). Additionally, age and season were independently and significantly associated with 25(OH)D concentrations, respectively. Conclusions: The deficiency and insufficiency status of vitamin D was very common among newborns and children aged one to 17 years. This indicates that more sunshine and vitamin D–fortified foods are necessary among Chinese children.  There is growing concern about vitamin D status (serum 25-hydroxyvitamin D (25(OH)D) concentration). Vitamin D deficiency is becoming a public health problem in both developed and developing countries ,2,3. It The high prevalence of vitamin D deficiency was reported in northern or southern regions, among adults and children. A recent study in Nepal found over 90% children aged one to five years have vitamin D deficiency (<20 ng/mL) between September and November . A studyPrevious studies have evaluated vitamin D status in young children and adolescents, but most of them focused only on several age groups of children with small sample sizes ,14,16. CHuzhou is situated in southeastern China at latitude of 30.86° N and characterized by a subtropical monsoon climate. It has abundant precipitation and plenty of sunshine (1871.73 h/year). According to the Sixth National Population Census, the resident population in Huzhou was 2.89 million; where 11.67% people aged 0 to 14 years old and 72.12% people aged 15 to 59 years old. The economic level of Huzhou is higher than the national average. The study was a large hospital based cross-sectional study. Children aged less than 18 years visited in Huzhou Maternal and Child Care Hospital from January 2012 to August 2015 were included in this study. From the decoded dataset of the hospital, we extracted the information including age, gender, visiting date, visiting type , and concentration of 25(OH)D. The children who went to hospital for health examination or seeking clinical service were defined as health examination and clinical visiting, respectively. The study protocol was approved by the Medical Ethical Committee of Zhejiang University School of Medicine.g for 3 min. The serum was separated and stored at −80 °C before analysis. Serum 25(OH)D concentrations were measured with Roche Elecsys modular analytics Cobas using an electrochemiluminescence immunoassay . Precision testing showed within-run coefficient of variations (CVs) of ≤7%, within-laboratory CVs of <9.5%, between-laboratory precision CVs of ≤10.1% [The 25-hydroxyvitamin D measurement is a routine examination in children’s health examination. First, 2 mL venous blood samples were collected after 8 h fasting. The blood samples were then centrifuged at 3600× f ≤10.1% . QualityCirculating 25(OH)D concentration was used for evaluating an individual’s vitamin D status . VitaminThe age variable was categorized into seven groups .The sampling season was defined as: spring (March to May), summer (June to August), autumn (September to November) and winter (December to February). p less than 0.05 was considered as statistically significant difference.Mean and standard deviations (mean ± SD) were used to express continuous variables. Frequencies and percentages (%) were reported for the categorical variables. Chi Square test was used to compare the difference in prevalence of vitamin D status  in various groups. Continuous variables were compared using analysis of variance (ANOVA). Meanwhile, generalized estimated equation modeling was used to detect the association of gender, season, age and visiting type with serum 25(OH)D concentrations considering repeated measurements. Multinomial logistic regression analysis was performed for those variables with vitamin D status (sufficient (>30 ng/mL), insufficient (20–30 ng/mL) and deficient (<20 ng/mL)). In order to compare the difference in vitamin D status between children of health examination and clinical visiting, and also to compare their results with the overall population, we repeated multiple regression models after stratifying by visiting type. Considering the effects of gender, season, age and visiting type on vitamin D status, all four variables included in the same models. Additionally, the figures were generated using the 25(OH)D concentration/percentage of low vitamin D respectively, for age groups stratified by gender, visiting type and season. All statistical analyses were performed by using the program package SAS version 9.4 . The A total of 13,997 children aged one day to 17 years were included in this study, including 7739 boys and 6258 girls. Of them, 8499 went to the hospital for a health examination, while 5498 for were there for a clinical visit. Overall, 23.28% children suffered from low vitamin D status (<30 ng/mL), while 6.43% had vitamin D deficiency (<20 ng/mL). When children were greater than one year old, the prevalence of vitamin D insufficiency and deficiency increased sharply with age.Among children, the vitamin D status significantly varied with age . Before The concentrations of serum 25(OH)D varied with season , and theVitamin D insufficiency occurred in 13.8% of the health examination children and in 21.6% of the clinical visiting children, and deficiency occurred in 3.8% of the health examination children compared to 10.5% of the clinical visiting children . The heap = 0.02) (The mean serum 25(OH)D concentrations were 40 ± 12 ng/mL in girls while they were 39 ± 12 ng/mL in boys. Girls had a higher vitamin D–sufficient status than boys  . However = 0.02) .Our results showed that 6.43% and 16.85% of children had a deficient and insufficient vitamin D status, respectively, and these problems were common in infants and children aged up to 17 years. Serum 25(OH)D was significantly associated with age, season, and visiting type. 2  and vitamin D3  are finally transferred into the biologically active form—1,25-dihydroxyvitamin D 2D). The form 1,25(OH) 2D is the most potent vitamin D metabolite. Because circulating serum 1,25(OH)2D is tightly regulated, concentrations of the 25(OH)D are the best measure of vitamin D nutritional status [Children’s metabolism is fast and needs extra energy to grow. A general diet may not meet the daily vitamin D requirement . Vitaminl status , and thiThe 25(OH)D concentration varies in different latitudes according to the duration of sunlight exposure. According to a study in Beijing, the prevalence of subclinical vitamin D deficiency (<5 ng/mL) was 45.2% in winter . In ShanThe results of studies about serum 25(OH)D concentrations in boys and girls are inconsistent. As with most previous studies in children ,10, we dThe sampling seasons were also associated with children’s vitamin D status. Our study revealed that the prevalence of vitamin D deficiency and insufficiency was highest in winter. Previous studies have also reported that the serum 25(OH)D concentration is lower in winter than in summer ,30, whicp < 0.05). Similar to the study in Nanjing, vitamin D deficiency occurred in 1.3% of healthy children and in 16.7% of sick children aged one to 10 years [In the present study, the serum 25(OH)D concentration in clinical visiting children was significantly lower than that in health examination children D concentrations. Another limitation was that the diagnostic criteria we used to assess vitamin D status was the Endocrine Society clinical practice guidelines, and different results may be derived if different guidelines are adopted. Furthermore, children’s regular health check-ups are required by the Chinese childrens’ health policy. Though this was a hospital-based survey, the study included 8499 children who went to the hospital for routine health examinations. Therefore, the participants of the health examination were representative of the children in south China.This study found that there is a high prevalence of vitamin D deficiency and insufficiency status in newborns and children aged one to 17 years in the south of China. The condition was more severe in winter, in sick children and in older children. It indicates that more sunshine and vitamin D–fortified foods are necessary among Chinese children.


Preterm birth (PTB) rates (11.4% in 2013) in the United States remain high and are a substantial cause of morbidity. Studies of prenatal exposure have associated particulate matter ≤ 2.5 μm in diameter (PM2.5) and other ambient air pollutants with adverse birth outcomes; yet, to our knowledge, burden and costs of PM2.5-attributable PTB have not been estimated in the United States.We aimed to estimate burden of PTB in the United States and economic costs attributable to PM2.5 exposure in 2010.Annual deciles of PM2.5 were obtained from the U.S. Environmental Protection Agency. We converted PTB odds ratio (OR), identified in a previous meta-analysis  to relative risk (RRs), to obtain an estimate that better represents the true relative risk. A reference level (RL) of 8.8 μg/m3 was applied. We then used the RR estimates and county-level PTB prevalence to quantify PM2.5-attributable PTB. Direct medical costs were obtained from the 2007 Institute of Medicine report, and lost economic productivity (LEP) was estimated using a meta-analysis of PTB-associated IQ loss, and well-established relationships of IQ loss with LEP. All costs were calculated using 2010 dollars.An estimated 3.32% of PTBs nationally  in 2010 could be attributed to PM2.5 (PM2.5 > 8.8 μg/m3). Attributable PTBs cost were estimated at $5.09 billion [sensitivity analysis (SA): $2.43–9.66 B], of which $760 million were spent for medical care (SA: $362 M–1.44 B). The estimated PM2.5 attributable fraction (AF) of PTB was highest in urban counties, with highest AFs in the Ohio Valley and the southern United States.PM2.5 may contribute substantially to burden and costs of PTB in the United States, and considerable health and economic benefits could be achieved through environmental regulatory interventions that reduce PM2.5 exposure in pregnancy.Trasande L, Malecha P, Attina TM. 2016. Particulate matter exposure and preterm birth: estimates of U.S. attributable burden and economic costs. Environ Health Perspect 124:1913–1918; http://dx.doi.org/10.1289/ehp.1510810 Preterm birth (PTB), defined as birth at < 37 weeks gestation, remains a substantial cause of early-life morbidity in the United States. In 2010, 35% of all infant deaths were attributable to preterm-related causes, with considerable disparities in rates across subpopulations . PretermAlthough PTB and the often associated low birth weight  are highly multifactorial  , most of2.5) among other pollutants with adverse birth outcomes, most especially LBW and PTB  in the United States—estimates that could be used by decision makers when regulatory interventions to reduce air pollution exposures are considered.A major barrier to reductions in outdoor air pollution is the perception that these reductions will undermine economic productivity . As with2.5 and PM10 (PM ≤ 10 μm), carbon monoxide, ozone, sulfur dioxide, and nitrogen dioxide. Recognizing that each of these air pollutants may independently contribute and/or modify the effects of exposure at an individual level, we used PM2.5 as a proxy for outdoor air pollution exposure, permitting use of a richer array of available measurements.Outdoor air pollution is a complex mixture including, most notably, PMIn the present analysis we adhered to the approach developed by the Institute of Medicine in assessing the “fractional contribution” of the environment to causation of illness, which is adapted below :Attributable Costs = Anthropogenic increment in preterm birth incidence × Births × Cost per preterm birth3, and incorporated a scenario with a 5.8-μg/m3 threshold in sensitivity analyses. We chose this approach because this was the reference level applied for other health effects of PM2.5 in the 2010 Global Burden of Disease estimates of PM2.5-attributable disease burden   of 100% was applied against the increment in cases and social costs of PTBs that could specifically be attributed to PM2.5.Because wildfires, dust storms, and volcanoes contribute to outdoor air pollution, reference levels (RL) were applied. We adopted an RL of 8.8 μg/ms level) . Above t2.5, the current limit set by the National Ambient Air Quality Standards is 12.0 μg/m3. Here we estimate effects of prenatal PM2.5 exposure on PTB occurring in the same year.Though studies have examined associations of outdoor air pollution with LBW , this as2.5-attributable increment in PTB, the rate of prematurity, and costs.Subsequent sections describe approaches to estimating the PM2.5 in 2008 for all ZIP codes in the conterminous United States as modeled by the EPA .We obtained daily averages of PM the EPA . Recogni3 for pregnancy-wide exposure, and an OR of 1.07  per 10 μg/m3 for third-trimester exposure. In this meta-analysis, six studies contributed to the estimates for PM2.5 and PTB; only studies that examined PTB (< 37 weeks completed gestation) as the major end point and that reported results from single-pollutant models were included. Combined estimates of the OR were calculated based on data from all studies selected using fixed- and random-effects models; unlike for PM10, no significant heterogeneity was detected for studies that reported findings for PM2.5. Another recent study also identified an OR of 1.16 per 10 μg/m3  as the best estimate, but varied the OR from 1.07 to 1.16 in subsequent sensitivity analyses.The most recent meta-analysis of English-language studies  estimate2.5 above the assumed RL (8.8 μg/m3). The calculation is also depicted in the following formula:For each decile of births within each county, the OR from the meta-analysis was applied as a base with the exponent corresponding to the increment of the county-specific average PMcounty-decile = ORmeta-analysis2.5 – RL)/10 μg/m3(decile of county-averaged PMORGiven that OR can overestimate relative risk (RR) and attributable fractions for common conditions such as PTB, we applied the formula described for estimating RR from OR and prevalence of PTB . For thi3 increase in PM2.5 and an RL of 8.8 μg/m3, the OR for the decile of births with the highest PM2.5 exposure would be estimated asFirst, we calculated the corresponding OR for each decile of exposure above the lowest decile. For example, using an OR of 1.15 (base case) for a 10-μg/m[(19.35 – 8.8)/10] = 1.16,OR = 1.15 3 is the PM2.5 concentration of the 90th percentile of the distribution for the county. Similarly, for the PM2.5 concentration related to second lowest decile (20th) of average daily exposure for Autauga County (8.06 μg/m3),where 19.35 μg/m[(8.06 – 8.8)/10] = 1.00.OR = 1.15 2.5 concentration less than the RL, the corresponding estimated OR of 1 indicates no increase in risk and, therefore, the corresponding decile of births is assumed to have no PTBs attributable to PM2.5.Because this decile has PMAfter deriving ORs for each decile, we use the formula by RR = 1.16/[(1 – 0.15) + (0.15 × 1.16)] = 1.13,where 0.15 is the PTB rate in that specific county. The range of RRs derived using these calculations was 1.06–1.18 (low–high scenarios).Next, we computed the attributable fraction of PTB for outdoor air pollution for each decile, using the formula published by PM2.5, county-decile = PrevalencePM2.5exposure × (RRcounty-decile – 1)/ [1 + PrevalencePM2.5exposure × (RRcounty-decile – 1)],AFwhere the exposure prevalence is set to 10% for each decile. For example, for the highest decile of exposure in Autauga County, AF = [0.1 × (1.13 – 1)]/{1 + [0.1 × (1.13 – 1)]} = 0.013. Finally, we summed the AF for each decile , and multiplied the resulting value by estimated number of preterm births for each county, as shown below:2.5 = 0.04 × 99.6 = 3.96, where 99.6 is the estimated number of preterm births in Autauga County. When aggregating AFs for each decile, a value of zero was assigned for AFs related to PM2.5 deciles below the RL (8.8 μg/m3), so that no cases of PTBs were attributed to those deciles of exposure.Cases of preterm births attributable to PM2.5-attributable premature births in 2010. Attributable PTBs in each county were aggregated to generate national estimates of attributable PTB.Births in each county were obtained from the CDC WONDER database, as were county-level PTB rates , and mulTwo direct costs of PTB were estimated: costs for treatment of PTB-associated medical conditions in the first 5 years of life, and costs after the first 5 years of life due to PTB-associated developmental disability. The direct health care costs in the first 5 years of life  were obtained from the 2.5-attributable PTB. PTB-associated IQ loss was calculated, using data from a systematic review that estimates an 11.9-point IQ decrement on average in PTB children   . The los5, 13.4) , and the3 was also examined.Recognizing uncertainty in the exposure–outcome relationship and RL, we performed sensitivity analyses. We used a range of ORs corresponding to different pregnancy-wide and third trimester–specific ORs (1.07–1.16) identified by the meta-analyses examining air pollution-PTB associations  to repre3 increment in PM2.5 and the reference level of 8.8 μg/m3, a median RR of 1.0031 was identified  with 63.4% of births having RR > 1 . These estimated numbers of attributable preterm births cost $760 million in medical care , and $4.33 billion  in lost economic productivity was also identified (based on estimated reductions in IQ and estimated consequences for productivity over a lifetime). In total, we estimated that $5.09 billion in PTB-related costs  could be attributed to PM2.5, with the sensitivity analysis producing a range in those costs of $2.43–9.66 billion.We examined 3,963,694 live births in the 48 contiguous United States, of which 475,368 (12%) were preterm births . Applying RR > 1 . We esti2.5 in New Mexico and Wyoming. California had the largest number of attributable preterm births  and costs ($692 million) in base case analyses , whereas only 0.12% of preterm births were attributable to PManalyses .2.5 AF of PTB was generally higher in major urban regions. Consistent with the state level results, the highest AFs (> 5%) were identified in the Ohio valley, the southern United States, southern California, southeastern Pennsylvania, New York City, and Chicago, Illinois.At the county level, the variability in attributable preterm births was greater than at the state level, as presented in 2.5 contributes significantly to preterm birth in the United States and translates into substantial economic loss over a lifetime. To our knowledge, this is the first time that such economic estimates are reported, and these suggest that considerable health and economic benefits can be gained through reductions in outdoor air pollution exposure in pregnancy.The main finding of this analysis suggests that exposure to PM2.5 has been associated with PTB in a number of studies, although with variable results, as highlighted in the meta-analysis by 2.5, which is a complex mixture of different chemicals, and may contribute to explaining the variable results obtained in these studies, with different mixtures leading to different outcomes (Exposure to PMoutcomes , also deoutcomes . In addi3 as reference levels, following the approach used by the 2010 Global Burden of Disease collaborators (2.5 insofar as anthropogenic sources can be limited, and no safe level of PM2.5 exposure has been identified. The estimated 15,808 preterm births can be considered preventable through strategies to reduce PM2.5 exposure, though future work can model reductions due to changes in vehicular and other emissions considering the impact of regulatory and other interventions as counterfactuals, so as to inform cost–benefit and other regulatory impact analyses.We used 5.8–8.8 μg/mborators . These l2.5-attributable preterm births provide a sense of the potential economic benefits that could be achieved by regulatory interventions aimed at reducing air pollution exposure during pregnancy. In addition, long-term health issues associated with preterm birth that prevent individuals from working translates into increased government expenditures for programs such as Supplemental Security Income, further adding to the economic costs shouldered by society as a whole (In our analysis we estimated loss of IQ related to preterm birth and its impact on earning potential, which can be considered the result of direct effects, such as lower cognitive capacities, and indirect effects due to diminished educational achievements and reduced ability to work . Estimat a whole . Last buThere are important limitations to the interpretation of our findings. The specific components of outdoor air pollution that contribute to prematurity and other adverse birth outcomes remain elusive, as do the mechanisms by which they produce effects. Although it is true that some studies to date have failed to find significant associations with adverse outcomes, exposure imprecision may have biased those estimates ; others 2.5 levels within the geographical area monitored by each site, or changes in residence during pregnancy. Data for ultrafine PM were not available, even though this form may pose a greater risk of adverse birth outcomes than PM2.5. PM2.5 measurements were estimated at the county level, and insofar as pregnancies are not evenly distributed by outdoor air pollution, our approach introduces some imprecision. We also estimated attributable PTB assuming homogeneity in the PTB rate across small population counties, which may have added imprecision in county-level estimates. We did not consider effects on maternal health, or possible stillbirths and birth defects that are plausible although less supported by the literature (Models are also only as good as their inputs. Stationary-monitor sites do not take into account variation in personal exposure levels, variations in PMterature .2.5 between 2009 and 2010 (Air pollution exposures over the period January–December 2008 can be expected to influence a broad period of pregnancies spanning at least 9 months later, with birth dates spanning September 2008–August 2009 and most births in 2009. We acknowledge some imprecision in selecting the 2010 birth year to extrapolate disease burden. In part, the intention was to bring estimates in line with other environmentally related disease burden estimates that use 2010 as a base , and ensand 2010 .2.5. Insofar as gestational age is not normally distributed, estimated PM2.5-induced shifts in gestational age may potentially result in larger effects on PTB than the estimates we modeled here. PTB data from CDC are also based on last menstrual period, when the definition is changing to clinically based obstetric estimates. A substantial literature suggests misclassification in both directions, with generally estimates based on last menstrual period producing higher PTB rates (We also examined PTB as a categorical outcome, when shifts in gestational age are more likely to occur due to PMTB rates , so our 2.5 may contribute substantially to the burden and costs of PTB in the United States. Because of the widespread exposure to PM2.5, considerable health and economic benefits could be achieved through regulatory interventions that reduce such exposure in pregnancy. Furthermore, the differential impact of air pollution by socioeconomic status and race/ethnicity, as suggested by Our estimates suggest that PM


Pathogen reduction technologies are among methods to eliminate transfusion transmitted infections. Mirasol method using riboflavin in combination with ultraviolet rays is one of them. The aims of this study were to investigate the effectiveness of Mirasol method to inactivate some model pathogens as well as examination of the sensitivity of plasma proteins after treatment.2) were employed to inactivate model pathogens. Four standard viruses were used in this study including Vesicular Stomatitis Virus (VSV), Herpes Simplex Virus1 (HSV-1), Bovine Viral Diarrhea Virus (BVDV) and Polio Virus. 50% Tissue Culture Infectious Dose (TCID50) and Reed–Muench Methods were used to estimate viruses’ titers. E. coli and Staphylococcus aureus were used as bacterial models. Four plasma proteins including factor V, VIII, fibrinogen and antithromin were used to determine their sensitivity to pathogen inactivation treatment.Riboflavin in 50μM concentration and ultraviolet (365 nm) in three different energy doses (3.6, 7.2, and 10.8 j/cm2 that is corresponding to Log 6.10 for BVDV, Log 6.09 for HSV-1, Log 6.62 for VSV and Log 3.36 for Polio. Bacterial reduction titer was Log 6.94 for E. coli and Log 7.00 for S. aureus. Indicator proteins for plasma activity were determined to be 75% for factor V, 88% for factor VIII, 52% for fibrinogen and 94% for antithrombin.The most pathogen reduction titre was determined for 15 minutes irradiation period equal to 10.8 J/cmResults showed that the employed method can inactivate most of the pathogens in fresh frozen plasma. The acceptable activities of selected plasma proteins remained after treatment. Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) and emerging or re-emerging viruses such as West Nile Virus or Chikungunya Virus which there is no method to detect them , have been developed to prevent transfusion transmitted infections. Some methods using photosensitisers as a key character, which absorb light energy and, in the ensuing electronically excited species, undergo redox reaction with surrounding molecules. Most current methods target nucleic acids and lead to pathogen inactivation .Riboflavin in combination with long wave Ultra Violet (UV) is one of the effective PRTs. Riboflavin as Vitamin B2, is an essential nutrient in humans and it is generally recognized as Safe (GRS) . The safBovine Viral Diarrhea Virus (BVDV), Herpes Simplex Virus 1 (HSV-I), Vesicular Stomatitis Virus (VSV) and Poliomyelitis Virus (Polio), to represent enveloped, non-enveloped and both RNA and DNA V Viruses were selected for this study. All four strains obtained from virus bank of Iranian Blood Transfusion Organization (IBTO)  .2.Madin-Darby Bovine Kidney (MDBK), African Green Monkey Kidney (Vero), and Cervix Carcinoma (HeLa) cell lines were used to propagate and quantify model viruses. All cell lines were obtained from National Cell Bank of Iran (NCBI), Pasteur Institute of Iran. The cells were grown in monolayers in Dulbecco Modified Eagle Medium (DMEM)  with 5% Fetal Bovine Serum (FBS) (Gibco) and 1% Pen-Strep (Sigma) at 37°C in a humid atmosphere of 5% CO50), were used to quantify viruses. Model viruses propagated in mono-layer cell lines and their infectivity titer were determined by Reed and Muench method employing 10 fold dilution series four replicate culture per dilution (6 according to WHO guidelines for PRT (Pathogen Reduction Technologies) (50% Tissue Culture Infectious Dose (TCIDdilution . Each viologies) . Then viE. coli (ATCC:25922) and S. aureus (ATCC: 25923). They cultured in nutrient agar for 24 hours at 37°C. Then a suspension of each organism was prepared in sterile phosphate buffer saline (PBS) (pH=7.4) to reach 106 CFU/ml.With respect to the most common bacterial contamination in blood transfusion two Gram-positive and Gram-negative bacteria were selected for this study: FFP samples have been obtained from IBTO. They were negative for HIV (Human Immunodeficiency Virus), HCV (Hepatitis C Virus) and HBV (Hepatitis B Virus) and stored at −20°C until used. All of them were O positive.To determine the quality of FFP before and after riboflavin and UV treatment, 4 plasma proteins including factor V, factor VIII, antithrombin and fibrinogen were selected as indicators to examine their concentration before and after treatment.Riboflavin was obtained from Darou Pakhsh Holding Co and stored at 25°C in dark before use. After that it was suspended in PBS and used in 50 μM final concentration in FFP samples.2 respectively.The source of irradiation was a UV Irradiator from HAMAMATSU (lighting lure series LC5 model). It could irradiate UV in 200–400 nm and its optimum irradiation was in 365nm. The energy dose in samples depends on their distance from the source as 12cm distance designed to reach optimum energy and also 3 different exposure times of 5, 10 and 15 minutes were employed to obtain different energy dose to identify optimum dose for inactivation of pathogens. The final calculated energy dose for each exposure time were 3.6, 7.2, and 10.8 j/cm6 TCID50 for virus and 106 CFU for bacteria per ml. Then riboflavin in a final concentration of 50μM was added to each sample  was used for data analysis.The original titer of BVDV, HSV, VSV and Polio Viruses were 6.54, 6.82, 7.07 and 6.66 respectively. Using riboflavin in 50μM final concentration in associated with UV in 365nm and in three different times reduced BVDV log in FFP samples to 6.10 .For HSV-1 best log reduction was 6.09 for 15 minutes irradiation, and VSV with the same exposure times showed a 6.62 log reduction. Polio virus was the most resistance virus that showed only a 3.36 log reduction after 15 minutes irradiation in presence of the riboflavin. The results were compared to the controls.E. coli was 107.7 CFU/ml and for S. aureus was 107.0 CFU/ ml. E. coli showed Log 6.94 CFU/ml reduction after 15 minutes treatment and S. aureus howed more sensitivity to riboflavin and UV treatment that log 7 CFU/ml reduction has been shown after 10 minutes (The original titer for  minutes .The results showed selected plasma proteins remained in normal range after riboflavin in combination with UV treatment except fibrinogen which was the most sensitive factor to this method. Antithrombin was the most resistance one. 2 were used. Marschner and Goodrich showed VSV titer reduced 6.3 Log using the Mirasol method in comparison with current study although they use Sindbis Virus as a model for HCV that showed a 3.2 log reduction, in this study BVDV model virus for HCV recommended by WHO guidelines was used and showed a 6.10 Log reduction using 10.8 j/cm2 energy dose (Blood-borne pathogens removal or reduction to the acceptable level always considered as a critical point in blood transfusion process. Although the efficiency of present methods, including screening blood donor and testing blood samples are useful to improve blood component quality, but still remain some risks, especially because of emerging or re-emerging viruses and critical window period for detection of some viruses , 5, 15. rgy dose .In current study Poliovirus employed as a model virus for non- enveloped that showed more resistant to this PRT method, in this way, other study shows Human B19 Parvo virus 5 Log reduction after using Mirasol method. There are no published data available on HSV and VSV reporting the sensitivity to riboflavin in combination with UV blood-borne pathogens removal or reduction to acceptance level .Staphylococcus epidermis, S. aureus and E. coli sensitivity to Mirasol method. In current study the same results for E. coli and S. aureus, was observed. However, E. coli showed high sensitivity to treatment, as more than 6 Log reduction after 15 minutes was observed (The bacterial selection in this study was based on their high contamination rate in blood transfusion. Previous studies showed observed , 11.Marsh and et al. showed antitrombin can save 90% of its activity after using the Mirasol method and is the most resistant protein and fibrinogen lost 30% of its activity and is the most sensitive one. The current results were near to it and all plasma factors remained in normal range after pathogen inactivation , 17.2 is the most effective energy dose, although, 7.2 J/cm2 still is remaining as an alternative to save more plasma proteins’ activity.The results showed the PRT treatment could inactivate most pathogens including both bacterial and viral contamination at the much closed level to WHO guideline, and is a safe and acceptable method for pathogen reduction in blood transfusion centers. A 10.8 J.cm


The management of cardiometabolic goals or “ABCs” , and cholesterol) ultimately determines the morbidity and mortality outcomes in patients with type 2 diabetes mellitus (T2DM). We sought to determine if patients with T2DM attending an urbanized public sector community health centre (CHC) were having their ABCs measured, were treated with appropriate cardioprotective agents and finally, were achieving guideline-based targets. n = 280) were females. Testing of ABCs occurred in 68.8% (n = 357) for HbA1c, 95.4% (n = 495) for BP, and 58.6% (n = 304) for LDL-C. Achievement of ABC targets was as follows: 19.3% (HbA1c < 7%), 22.0% (BP < 140/80 mmHg), and 56.3% (LDL-C < 2.5 mmol/l).  A cross-sectional record review of 519 patients was conducted between May and August 2015. The mean age was 54 years (SD: ±11.5) and 54% ( There were a significant number of patients who were not tested nor received adequate pharmacotherapy or achieved their ABC targets. This places these patients at an increased risk for the development of diabetes-related complications. Although the realities of resource constraints exist in South Africa's public sector settings, a wider implementation of evidence-based guidelines must be instituted in order to ensure better patient outcomes. Diabetes mellitus (DM) is a chronic-progressive, multifactorial condition leading to a host of serious complications. In 2015, it was estimated that 415 million people had diabetes. However, this figure is expected to rise to 642 million in the next 25 years , 4. ThusAs the rates of DM continue to rise, so too do concerns of the abilities of a healthcare system to deliver quality healthcare. Especially in lower resource settings such as those found in South Africa, the DM condition and its associated complications challenge healthcare systems. Therefore, using disease-specific indicators to measure the preventive treatment prescribed and quality of diabetes care available, we sought to benchmark a healthcare setting's performance . For thiOur study took place at the Hillbrow CHC between May and August 2015. This chosen setting is an academic provincial secondary level healthcare facility associated with the University of the Witwatersrand, Johannesburg, South Africa. The clinic offers emergency services, minor theatre procedures, polyclinic, outpatient services, psychology, and dental care .The cohort size consisted of 519 patients with previously diagnosed T2DM. In our study, T2DM was defined as patients >18 years of age and/or had “T2DM” written in their records and/or having evidence of a prescription which featured an oral hypoglycaemic/insulin. Patients who met one or more of the inclusion criteria of “having a positive diagnosis for T2DM” as above were included in the study. All of the data for this study was retrospectively abstracted from patient records. Patient's files were chosen in a consecutive manner based on appointments for the day, until the sample size needed was met. Data abstracted from patient records included the following: demographics, medical history, laboratory results, and pharmacological treatment prescribed.During the data collection period (May to August 2015), only the latest medical information was abstracted from the patient records. In the case where data was found to be missing from the latest records, we chose to include information from patient records as far back as 1 year from the time data collection commenced . The blood pressure measurements were assumed to have been conducted by nurses or doctors at the clinic and in line with the South African hypertension Guidelines . StandarFor the purposes of this retrospective study, macrovascular disease was considered present in patients who were previously diagnosed  with any one of the following: cardiovascular disease, ischaemic heart disease, coronary artery disease, stroke, or transient ischaemic attack. Guidelines recommend the detection of microvascular complications through eye examinations (to detect retinopathy), feet inspections (neuropathy), and microalbuminuria testing (nephropathy) . For ourThe target levels applied to each risk factor was obtained from the Society for Endocrinology, Metabolism and Diabetes of South Africa (SEMDSA) 2012 Guidelines, which was the latest at the time of the study. This included the following targets: HbA1c < 7.0%, systolic BP < 140 mmHg, diastolic BP < 80 mmHg, TC < 4.5 mmol/l, LDL-C < 2.5 mmol/l, HDL-C > 1.0 mmol/l (men), HDL-C > 1.2 mmol/l (women), and triglyceride < 1.7 mmol/l.t-test was used to explore key continuous measurements. Frequency tables for patient usage of chronic treatment used in glycaemia, hypertension, and lipid-lowering were produced. The % of patients achieving SEMDSA treatment targets for different clinical parameters was calculated. Microsoft Office Excel 2010  and Statistica version 13 (64-bit)  were used for the database and analysis. The University of the Witwatersrand's Human Research Ethics Committee approved the study prior to commencement.Patient records at the clinic lacked weight and height detail which unfortunately meant body mass index (BMI) calculations were not possible. Waist circumference and smoking status data were also poorly recorded and therefore excluded from the study. Our sample size calculations were based on the HbA1c, BP, and LDL-C measurements which we assumed would be similar to those levels found in a previous local T2DM population-based study in a nearby hospital . The conThere were a total of 519 patients whose records we retrospectively reviewed in this study. Over half the sample (53.9%) were female, and the mean age for the group was 53.9 years (SD: 11.5). All but four patients were of African descent .p = 0.46). The patients using combinations of orals/insulin had an HbA1c of 9.5% (±2.6). Similarly, 25.9% of patients who were on orals (no insulin), 14.5% of patients on a combination of orals/insulin, and 10.7% of those using insulin  achieved target levels of HbA1c of <7% (p = 0.09). Of the few patients (n = 9) who were not treated on oral nor insulin, only 1 achieved HbA1c < 7%. The biguanides, in the form of metformin (the 850 mg strength only), were the most frequently prescribed agents amongst the total users of oral hypoglycaemic agents in the study, 450/463 (97.2%). Between the two types of sulphonylurea (SU) agents available to patients at this clinic, the majority (86.2%) utilised glimepiride (4 mg strength most frequently) whilst fewer (13.8%) were on gliclazide (160 mg strength most frequently).In the study cohort, 162 (31.2%) of patients did not have HbA1c levels readily available in their records. Patients with HbA1c levels had a mean HbA1c of 9.1% (±2.6), a median of 8.5%, and 19.3% achieved target levels of <7% Tables . Monothen = 459/519 (88.4%). Only 24 (4.6%) patients had missing blood pressure measurements (p < 0.01) (p < 0.01). The average used 2.5 antihypertensive medications. Those not using antihypertensives had a mean BP of 126/78 mmHg versus 139/82 mmHg for patients on treatment (p < 0.01). The achievement of combined BP targets (<140/80 mmHg) by 1, 2, 3, or 4 combinations of antihypertensive classes was 22.3%, 22.3%, 18.3%, and 19.7%, respectively. ACE inhibitors were the most commonly utilised class of antihypertensives 403 (87.8%), followed by 300 (65.4%) users of diuretics, 262 (57.1%) users of calcium channel blockers and 89 (19.4%) on β-blockers.Almost the entire cohort was treated for hypertension, urements . Those wurements . Just ov < 0.01) . The comLipids level measurements were missing in just over 40% of patient records for all lipid categories . Over hap = 0.23).Simvastatin was the only statin available to patients at the clinic, and the 20 mg dosage was the most frequently prescribed in 122/133 (91.7%) of users. Fewer statin users achieved their LDL-C targets of <2.5 mmol/l  in comparison with those who were not using statins   which ultimately determines the morbidity and mortality outcomes in T2DM patients. The majority (83%) of South Africans access their healthcare within the public sector and, therefore, our study provides a necessary and important means by which to demonstrate the quality of care available to patients within the state sector.Evidence-based guidelines recommend that patients with T2DM be treated to an optimal HbA1c of <7%. Approximately two-thirds of our cohort (68.8%) had HbA1c measurements available. Disappointingly, only 1/5 of patients reached an HbA1c <7%. However, studies from other South African sites have also reported such unsatisfactory findings whereby as few as 11.2–15.6% achieved HbA1c < 7% , 11. In Results from the UKPDS indicated that the ideal HbA1c levels were best achieved through combinations of oral and insulin therapies as the T2DM progressed . With onHypertension remains the most common life-threatening risk factor for cardiovascular disease in developing countries . As manyOne of the key challenges associated with the treatment of hypertension is the asymptomatic and chronic nature of the condition . Poor meThe achievement of lipid targets in our study patients was superior to those of BP and HbA1c. One-half of patients in our study achieved LDL-C < 2.5 mmol/l as per the guideline recommendations. Our results demonstrate higher achievement rates of LDL-C targets in comparison with some other local , 13 and Compelling evidence suggests that optimal vascular protection is achieved through a multifactorial approach  thereby yielding risk reduction in patients with T2DM . Only thOur study had several limitations. Our analyses were confined to only those patient records available at the time of the study. Although consistent, the latest guidelines at the time of this study were used, thereby applying less stringent targets and making more patients appear to achieve their targets  . The treThe present study demonstrated that a large portion of patients had missing measurements and did not achieve guideline-based targets. Effective treatment and interventions can reduce risk in patients with T2DM. However, we found that a suboptimal level of preventative and therapeutic approaches was implemented at this setting. Improved risk factor testing and clinical inertia were some of the challenges observed, which have its ramifications in the quality of diabetes care delivered. Future interventions should focus on initiating more aggressive preventive strategies through an earlier use of combination therapy, addressing barriers to physician clinical inertia, or patient compliance to treatment.