Cumulative Number Of Days Research Articles

Climate variability and yield risk in South Asia’s rice–wheat systems: emerging evidence from Pakistan

Rice and wheat are the principal calorie sources for over a billion people in South Asia, although each crop is particularly sensitive to the climatic and agronomic management conditions under which they are grown. Season-long heat stress can reduce photosynthesis and accelerate senescence; if extreme heat stress is experienced during flowering, both rice and wheat may also experience decreased pollen viability and stigma deposition, leading to increased grain sterility. Where farmers are unable to implement within-season management adaptations, significant deviations from expected climatic conditions would affect crop growth, yield, and therefore have important implications for food security. The influence of climatic conditions on crop growth have been widely studied in growth chamber, greenhouse, and research station trials, although empirical evidence of the link between climatic variability and yield risk in farmers’ fields is comparatively scarce. Using data from 240 farm households, this paper responds to this gap and isolates the effects of agronomic management from climatic variability on rice and wheat yield risks in eight of Pakistan’s twelve agroecological zones. Using Just and Pope production functions, we tested for the effects of crop management practices and climatic conditions on yield and yield variability for each crop. Our results highlight important risks to farmers’ ability to obtain reliable yield levels for both crops. Despite variability in input use and crop management, we found evidence for the negative effect of both season-long and terminal heat stress, measured as the cumulative number of days during which crop growth occurred above critical thresholds, though wheat was considerably more sensitive than rice. Comparing variation in observed climatic parameters in the year of study to medium-term patterns, rice, and wheat yields were both negatively affected, indicative of production risk and of farmers’ limited capacity for within-season adaptation. Our findings suggest the importance of reviewing existing climate change adaptation policies that aim to increase cereal farmers’ resilience in Pakistan, and more broadly in South Asia. Potential agronomic and extension strategies are proposed for further investigation.

Spatial-statistical analysis of factors determining forest fires: a case study from Golestan, Northeast Iran

ABSTRACTIntermittent fires in Northeast Iran in the autumn of 2010 resulted in the burning of some valuable forest habitats. The objective of this study was to apply geographic information systems (GIS) to determine to what degree three key factors (environmental, climatic, and anthropogenic) influence the severity rating of fires in these forests. The forest fire sites were surveyed and imported into GIS. The severity of burnt areas was considered in relation to the three factors. Statistical functions were used to calculate the effect of the factors at each fire site. Logistic and stepwise regressions were used to determine the fire severity rating related to each factor. The results indicate that as the number of cumulative days after the onset of fire increased, the burnt areas also increased at a rate of 303.5 ha/day (R2 = 0.95). Consequently, forest density, daily mean wind speed, daily mean temperature and distance to roads were highly correlated with the daily severity rating of forest fires, and only daily temperature and forest density affected the size of the burnt areas. Prediction maps show that about 24% of the forests have high fire durability, amounting to 7% of the fire-sensitive area. The findings from this case indicate that GIS can be effectively employed in fire management to assess damage, and possibly to prevent future fires, thus assisting in the preservation of valuable forest resources.

Extreme dry spell detection and climatology over the Mediterranean Basin during the wet season

AbstractThe E‐OBS precipitation gridded data set v.10.0 is used to detect very long dry spell (VLDS) events over the entire Mediterranean Basin for the 1957–2013 period, during the wet season (September to April). The main objective is to characterize these events as climatic objects, in terms of location, spatial extent, duration, and temporal variability. In this study, 76 VLDS events were detected in the Mediterranean Basin and grouped into four spatial patterns: scattered localized (with 25 events), northeast Mediterranean (11 events), West Mediterranean (15 events), and southeast Mediterranean (25 events). Each pattern shows seasonality in events. Most of the scattered localized, northeast, and southeast events begin in September, at the beginning of the wet season. In contrast, most of the West Mediterranean events begin in the middle of the wet season. Over time, there is a slight but not significant increase in the cumulative number of days per season affected by VLDS events.

Influences of Cumulative Number of Days of Rainfall on Occurrence of Landslide

Influences of Cumulative Number of Days of Rainfall on Occurrence of Landslide

Influence of Cumulative Rainfall on the Occurrence of Landslides in Korea

This study presents the impact of cumulative rainfall on landslides, following the analysis of cumulative rainfall for 20 days before the landslide. For the 1520 landslides analyzed, the highest amount of average daily rainfall of 52.9mm occurred the day before the landslide, and the least amount of 6.1mm was experienced 20 days before the landslide. The least number of landslides (263 landslides) occurred when the cumulative rainfall is less than 20mm, and increased to 316 landslides in less than 30mm rainfall, 514 landslides in less than 80mm, 842 landslides in less than 150mm, and 678 landslides in 150mm and above. Considering the landslide occurrence in relation to the cumulative rainfall and the cumulative number of days, 986 landslides (64.9%) of the 1520 landslides were triggered by the 3 days cumulative rainfall for the 100mm rainfall and below, and 60% of landslides at the 5 days cumulative rainfall, indicating that the impact of cumulative rainfall on landslides was high in the 3 days and 5 days cumulative rainfall. More landslides occurred for the 101mm-200mm rainfall at the 10 days cumulative rainfall, more landslides for the 201mm-300mm rainfall at the 14 days cumulative rainfall, and more landslides for the 301mm-400mm rainfall at the 18 days cumulative rainfall. Three typologies of cumulative rainfall triggers are evident in Korea which includes: the early stacked rainfall accumulation type; the long-term intensive rainfall accumulation type; the continuous daily rainfall accumulation type. Cumulative rainfall is thus a major factor causing landslides. It is therefore imperative to take into consideration cumulative rainfall and the cumulative number of days as important triggers of landslides, as this could help contribute in landslide forecasting, thus putting in place measures to minimize the damage caused to life and property by landslides.

Application of effective drought index for quantification of meteorological drought events: a case study in Australia

Drought indices (DIs) that quantify drought events by their onset, termination, and subsequent properties such as the severity, duration, and peak intensity are practical stratagems for monitoring and evaluating the impacts of drought. In this study, the effective drought index (EDI) calculated over daily timescales was utilized to quantify short-term (dry spells) and ongoing drought events using drought monitoring data in Australia. EDI was an intensive DI that considered daily water accumulation with a weighting function applied to daily rainfall data with the passage of time. A statistical analysis of the distribution of water deficit period relative to the base period was performed where a run-sum method was adopted to identify drought onset for any day (i) with EDI i < 0 (rainfall below normal). Drought properties were enumerated in terms of (1) severity (AEDI ≡ accumulated sum of EDIi < 0), (2) duration (DS ≡ cumulative number of days with EDIi < 0), (3) peak intensity (EDImin ≡ minimum EDI of a drought event), (4) annual drought severity (YAEDI ≡ yearly accumulated negative EDI), and (5) accumulated severity of ongoing drought using event-accumulated EDI (EAEDI). The analysis of EDI signal enabled the detection and quantification of a number of drought events in Australia: Federation Drought (1897–1903), 1911–1916 Drought, 1925–1929 Drought, World War II Drought (1937–1945), and Millennium Drought (2002–2010). In comparison with the other droughts, Millennium Drought was exemplified as an unprecedented dry period especially in Victoria (EAEDI ≈ −4243, DS = 1946 days, EDImin = −4.05, and YAEDI = −4903). For the weather station tested in Northern Territory, the worst drought was recorded during 1925–1929 period. The results justified the suitability of effective drought index as a useful scientific tool for monitoring of drought progression, onset and termination, and ranking of drought based on severity, duration, and peak intensity, which allows an assessment of accumulated stress caused by short- and long-term (protracted) dry events.

Abstract POSTER-THER-1404: in vivo synergism between chemotherapy and the 3C23K monoclonal antibody directed against the anti-müllerian hormone type II receptor in ovarian cancer patient-derived xenografts

Abstract Purpose of the study: Müllerian inhibiting substance, also called anti-Müllerian hormone (AMH), belongs to the TGF-β family and plays a key role during sexual development. It has been shown that AMH inhibits proliferation and induces apoptosis of AMH type II receptor-positive tumor cells, and particularly progenitor cancer cells. Moreover, various reports have underlined expression of AMHRII in human gynecologic cancers including ovarian tumors. Based on these considerations, a humanized glyco-engineered monoclonal antibody (3C23K) capable of increasing effector cells engagement has been developed and tested in AMHR2 transfected xenografted cell lines. In order to document its activity in naturalistic models, we have initiated a preclinical study to assess AMHRII expression in a panel of ovarian cancer patient-derived xenografts (PDXs) and evaluate in vivo efficacy of 3C23K. Experimental procedures: AMHRII expression was studied in 14 ovarian cancers PDXs, using both flow cytometry (FC) and immunofluorescence (IF) analyses performed with alexaFluor488-conjugated 3C23K antibody on 300µm slices of xenograft fragments. In vivo efficacy of 3C23K alone (10 or 20 mg/kg twice a week, IP) or in combination with standard chemotherapy (CT) (carboplatin 66 mg/kg IP days 1-22 + paclitaxel 30 mg/kg IP days 1-22) has been planned to be evaluated in 4 AMHRII-positive ovarian cancers PDXs. One undifferentiated highly proliferative serous ovarian adenocarcinoma PDX, the OV54 model, has already been treated. On these 4 selected models, expression and quantification of AMHRII was or will be performed before and after treatments, as well as tumor-associated macrophages (TAMs) infiltrate. Summary of the data: Expression studies showed that over the 14 PDX tested, 6 (43%) were positive with at least 25% of tumor cells being positive, among these 3 expressed more than 50% of positive cells. This expression was confirmed by ex vivo IF with a profile comparable to that observed with fresh primary human ovarian tumors resected from stage IV patients. In vivo experiments (OV54 model) showed an intermediate efficacy of the 3C23K antibody administered alone, as well as a high and significant increase of CT antitumor effect. Synergistic effects were characterized by 50% of complete response (CR) when 3C23K (20mg/kg/inj.) was added to CT vs 10% CR with CT alone. The cumulative number of days under CR was 110 with 3C23K + CT vs 7 on CT alone. Impact on survival was consistent with a 90% survival at D37 with 3C23K + CT vs 60% survival on CT alone. We did not observe modification of AMHRII expression in OV54 tumors after 3C23K administration. Stromal FC analyses showed a high TAMs infiltrate of M2 type compatible with induction of Antibody Dependent Cell Phagocytosis by 3C23K. Conclusions: Using a panel of 14 ovarian cancer PDXs, we confirmed the expression of AMHRII in human ovarian cancers. Targeting this receptor by a specific monoclonal antibody, i.e. 3C23K, dramatically increases the efficacy of a standard chemotherapy. Our results therefore suggest that such combination could be further developed in ovarian cancer patients whose prognosis remains dismal. Citation Format: Fariba Némati, Jean-Marc Barret, Gérald Massonnet, Houcine Bougherara, Marie-Aude Le Frère-Belda, Jean-François Prost, Didier Decaudin. in vivo synergism between chemotherapy and the 3C23K monoclonal antibody directed against the anti-müllerian hormone type II receptor in ovarian cancer patient-derived xenografts [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-THER-1404.

195 The effect of aminoglycoside antibiotics therapy on audiovestibular function in cystic fibrosis patients at the All Wales Adult Cystic Fibrosis Centre (AWACFC)

Aims 1.To determine the prevalence and severity of audiovestibular (AV) disease in adult CF patients attending the AWACFC. 2.To examine any potential link between AV disease and number of days of IV aminoglycosides (AG) received and duration of nebulised AG. Method The annual reviews of patients attending the AWACFC between 2009 and 2014 were reviewed retrospectively. Patients who had reported AV symptoms and received an assessment at an AV clinic were included and their cumulative number of days of IV AG and the length of time receiving nebulised AG was collected. Results 30 (12 male) of the 254 (12%), with a mean (SD) age of 34.2 (8.9) years, had described AV symptoms and been seen in AV clinic. 19 of the 30 patients were found to have some sensorineural (SN) hearing loss. Patients with SN hearing loss had a greater mean number of days on IV AG (340 days) than those with measured normal hearing (247 days) but the least days nebulised AG. 7 patients had vestibular dysfunction (VD). Patients with VD had a greater mean number of days on IV AG than those with normal vestibular function (386 vs 152 days). Conclusion The prevalence of SN hearing loss in AWACFC is less than previous reports (CF Trust 2009) perhaps due to underreporting of symptoms. SN hearing loss and VD were associated with greater number of days on IV AG which concurs with previous studies (Mulheran 2001). The greater the number of days on nebulised AG conferred less hearing damage. This may be explained by nebulised AG being withheld during course of IV AG or by greater long term nebulised AG usage resulting in reduced need for more toxic IV courses of AG. However, patient adherence was not assessed.

Intravenous Immunoglobulin Post Allogeneic Stem Cell Transplantation Is Associated with Lower Levels of CMV Reactivation

▪IntroductionCytomegalovirus (CMV) reactivation is a common complication of allogeneic stem cell transplantation (ASCT), particularly within the first 100 days after stem cell infusion (D+100). It results in significant cost, morbidity and potentially mortality in the case of severe CMV disease.Intravenous polyvalent immunoglobulin (IVIg) has been used to support immunoglobulin levels post-ASCT in an attempt to reduce opportunistic infection and graft versus host disease (GVHD). Historically we employed routine IVIg therapy (0.5g/kg weekly for the first 12 weeks) as standard post-ASCT care. In July 2012 funding was withdrawn for IVIg for this indication.Since 2001 we have been using weekly quantitative polymerase chain reaction (PCR) analysis to monitor for CMV reactivation during the first 100 days after ASCT.We investigated whether the omission of post-ASCT IVIg altered the rate or consequences of CMV reactivation in the immediate post-ASCT setting.MethodsWe analysed sequential ASCT recipients from 2010 to 2014 and identified 100 patients who met the predetermined eligibility criteria. These subjects were then divided into two uniformly treated populations: ASCT recipients who either received (Group A, n=50) or did not receive (Group B, n=50) IVIg as part of their post-ASCT care.Inclusion criteria: matched adult unrelated or sibling donor source, age ≥18 years and CMV positive recipient by serology within 3 months prior to ASCT or CMV positive donor by serology.Exclusion criteria: CMV negative donor and recipient (D-/R-), umbilical cord donor source, death before day 100 or incomplete data available for analysis.CMV reactivation was defined as any detectable level by quantitative CMV PCR in the peripheral blood. The lower limit of detection for the assay was 20 copies/mL.A plasma CMV viral load of ≥400 copies/mL resulted in treatment with intravenous ganciclovir (5mg/kg twice daily) which was continued for a minimum of 2 weeks and was thereafter guided by weekly CMV viral load response. Patients with a CMV viral load of <400 copies/mL were observed with no specific treatment.CMV reactivation was recorded as minor (not requiring ganciclovir treatment) if CMV viral load remained <400 copies/mL and as major (requiring treatment) if CMV viral load reached ≥400 copies/mL within a single episode of infection. Time to first CMV reactivation and cumulative days of major CMV reactivation were also recorded.ResultsA total of 169 consecutive subjects were screened for study entry. Abstract 2482. Table 1:Cohort compositionsTotal screenedD-/R-Death <D+100Umbilical cord donorIncomplete dataTotal includedGroup A (IVIg)84206*8050Group B (non-IVIg)85215#8150*: 1 subject had active CMV infection at time of death#: 2 subjects had active CMV infection at time of deathDemographics were similar between Group A and Group B in terms of age (median 51.0 vs 48.5 years), sex (male: 33 vs 29) and transplant indication (acute leukaemia/MDS 28 vs 28; lymphoma 11 vs 11) and D+/R- transplants (9 vs 11).Comparing Group A and Group B, the number of subjects who had a CMV reactivation was 37 vs 39 and for minor reactivations the number was 28 vs 25. The median time to CMV infection was likewise similar: D+38 vs D+35.The number of patients with a major reactivation, however, was significantly different between Group A and Group B (13 vs 25 – RR 0.52, 95% CI [0.30-0.90], p 0.018), as was the cumulative number of days of major reactivation (181 vs 604 – RR 0.30, 95% CI [0.25-0.35], p <0.0001). The median number of days of major reactivation per patient was 13 vs 21 respectively.ConclusionRoutine IVIg use in the immediate post-ASCT period did not reduce the rate or latency of CMV reactivation but was associated with a lower magnitude of CMV reactivation and a reduced requirement for anti-CMV therapy. These findings suggest that the use of IVIg post-ASCT may assist in reducing CMV viral burden. DisclosuresNo relevant conflicts of interest to declare.

Large outbreak caused by methicillin resistant Staphylococcus pseudintermedius ST71 in a Finnish Veterinary Teaching Hospital--from outbreak control to outbreak prevention.

IntroductionThe purpose of this study was to describe a nosocomial outbreak caused by methicillin resistant Staphylococcus pseudintermedius (MRSP) ST71 SCCmec II-III in dogs and cats at the Veterinary Teaching Hospital of the University of Helsinki in November 2010 – January 2012, and to determine the risk factors for acquiring MRSP. In addition, measures to control the outbreak and current policy for MRSP prevention are presented.MethodsData of patients were collected from the hospital patient record software. MRSP surveillance data were acquired from the laboratory information system. Risk factors for MRSP acquisition were analyzed from 55 cases and 213 controls using multivariable logistic regression in a case-control study design. Forty-seven MRSP isolates were analyzed by pulsed field gel electrophoresis and three were further analyzed with multi-locus sequence and SCCmec typing.ResultsSixty-three MRSP cases were identified, including 27 infections. MRSPs from the cases shared a specific multi-drug resistant antibiogram and PFGE-pattern indicated clonal spread. Four risk factors were identified; skin lesion (OR = 6.2; CI95% 2.3–17.0, P = 0.0003), antimicrobial treatment (OR = 3.8, CI95% 1.0–13.9, P = 0.0442), cumulative number of days in the intensive care unit (OR = 1.3, CI95% 1.1–1.6, P = 0.0007) or in the surgery ward (OR = 1.1, CI95% 1.0–1.3, P = 0.0401). Tracing and screening of contact patients, enhanced hand hygiene, cohorting and barrier nursing, as well as cleaning and disinfection were used to control the outbreak. To avoid future outbreaks and spread of MRSP a search-and-isolate policy was implemented. Currently nearly all new MRSP findings are detected in screening targeted to risk patients on admission.ConclusionMultidrug resistant MRSP is capable of causing a large outbreak difficult to control. Skin lesions, antimicrobial treatment and prolonged hospital stay increase the probability of acquiring MRSP. Rigorous control measures were needed to control the outbreak. We recommend the implementation of a search-and-isolate policy to reduce the burden of MRSP.

Can EPS Development be Avoided with Early Interventions? The Potential Role of Tamoxifen—A Single-Center Study

Encapsulating peritoneal sclerosis (EPS) is a severe complication of peritoneal dialysis (PD). Identification of patients at high risk for EPS ("EPS-prone") and delivery of appropriate interventions might prevent its development. Our aim was to evaluate the clinical characteristics and outcomes of all EPS and EPS-prone patients diagnosed at our PD unit. For a 30-year period representing our entire PD experience, we retrospectively identified all patients with EPS (diagnosed according to International Society for Peritoneal Dialysis criteria) and all patients defined as EPS-prone because they met at least 2 established criteria (severe peritonitis, PD vintage greater than 3 years, severe hemoperitoneum, overexposure to glucose, and acquired ultrafiltration failure). Of 679 PD patients, we identified 20 with EPS, for an overall prevalence of 2.9%. Mean age at diagnosis was 50.2 ± 16.4 years, with a median PD time of 77.96 months (range: 44.36 - 102.7 months) and a median follow-up of 30.91 months (range: 4.6 - 68.75 months). Of patients with EPS, 10 (50%) received tamoxifen, 10 (50%) received parenteral nutrition, and 2 (10%) underwent adhesiolysis, with 25% mortality related to EPS. Another 14 patients were identified as EPS-prone. Median follow-up was 54.05 months (range: 11.9 - 87.04 months). All received tamoxifen, and 5 (36%) received corticosteroids; none progressed to full EPS. We observed no differences in baseline data between the groups, but the group with EPS had been on PD longer (84 ± 53 months vs 39 ± 20 months, p = 0.002) and had a higher cumulative number of days of peritoneal inflammation from peritonitis (17.2 ± 11.1 days vs 9.8 ± 7.9 days, p = 0.015). Overall mortality was similar in the groups. The incidence of EPS declined during our three decades of experience (5.6%, 3.9%, and 0.3%). Being a serious, life-threatening complication of PD, EPS requires high suspicion to allow for prompt diagnosis and treatment. Early detection of EPS-prone states and delivery of appropriate intervention might prevent EPS development. Tamoxifen seems to be a key strategy in prevention, but caution should be used in interpreting our results. Additional randomized controlled studies are needed.

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Introduction: The development of new onset acute kidney injury (AKI) and its impact on outcomes in the subarachnoid hemorrhage (SAH) population has not been well described. This patient population in particular is exposed to unique risk factors including hyperosmolar compounds and potentially multiple angiographic contrast exposures. Specific aim: To study the incidence and risk factors for developing AKI (based on Acute Kidney Injury Network criteria) and its impact on outcomes in the SAH population admitted to a large academic neurocritical care unit. Methods: This is an IRB-approved, retrospective study of patients admitted to a tertiary academic neurologic intensive care unit between 2006–12. The patient cohort included adult (age>18Y) patients admitted following SAH (aneurysmal and non aneurysmal etiologies). Marginal comparisons between patients that developed AKI during the study period and those who did not were conducted using the Wilcoxon rank sum test for continuous variables, and the Pearson Chi-square test for categorical variables. The overall increase in the odds of mortality for patients who developed AKI was summarized using an odds ratio. A nonparametric bootstrap method was used to construct 95% confidence intervals for the odds ratio of mortality, and the overall incidence of AKI. Cox proportional hazards regression, with time-varying covariates, was used to conduct an adjusted analysis of specific risk factors The primary endpoint was the development of AKI following admission to the ICU, up to 14 days post bleed. The secondary end point was hospital mortality. Results: The final cohort of patients included 1253 adults admitted with a diagnosis of SAH, out of which 133 patients (11%) developed new onset AKI. Patients in the AKI cohort were older (median age was 60Y versus 57Y; p-value: 0.046) and had a significantly higher prevalence of Diabetes Mellitus (29% Vs 16 %; p-value: <0.001) and preexisiting kidney disease (p-value: <0.001). Interestingly, in spite of repeated contrast exposure, notable on day 1 and then peaking at day 10, we did not observe a significant effect of contrast exposure after adjusting for other risk factors for AKI. The hazard ratio (HR) for cumulative days of contrast exposure was 1.0 (95% CI: 0.8, 1.2). For each day of mechanical ventilation, the hazard of developing AKI was increased by 12% (HR: 1.12; 95% CI: 1.05, 1.19; p-value: <0.001). Preexisting kidney disease and Diabetes increased the hazard of AKI by a factor of 2.35 (95% CI: 1.31, 4.19; p-value: 0.004) and 1.80 (95% CI: 1.22, 2.66; p-value: 0.003), respectively. The cumulative number of days in which serum osmolality was measured was not significantly associated with the hazard of AKI, in these data. The AKI cohort had an increased length of ICU stay 14.4 ± 9.3 days versus 11.2 ± 8.5 days (p-value: <0.001). Patients who developed AKI had a 2.36 (95% CI: 1.51, 3.69) fold increased odds of death compared to the patients who did not develop AKI. Conclusions: Conclusion: Mechanical ventilation, preexisting kidney disease and DM were independent risk factors for AKI following SAH. AKI-SAH is associated with a significant increased length of stay and significant increased risk of hospital mortality.

Prophylactic Indomethacin Worsens Short-Term Respiratory Outcomes in Extremely Low-Birth-Weight Infants

To compare the effects of prophylactic indomethacin versus expectant management on short-term respiratory outcomes in extremely low-birth-weight (ELBW) infants. This was a retrospective cohort study of ELBW infants with gestational age less than 28 weeks, born at a level III neonatal intensive care unit from 2004 to 2009. Patients were grouped based on whether they received prophylactic indomethacin or expectant treatment. The key outcome was the cumulative number of days of mechanical ventilation. Other outcomes were cumulative number of days supplemental oxygen and continuous positive airway pressure (CPAP) were required; duration of hospital stay; mortality; and other morbidities such as necrotizing enterocolitis and intraventricular hemorrhage. Multivariable linear regression was performed with treatment group and seven covariates, defined a priori, as predictor variables and cumulative number of days of mechanical ventilation as the outcome. There were 144 infants in the prophylaxis group and 221 infants in the expectant treatment group. At baseline, the Score for Neonatal Acute Physiology-Perinatal Extension, incidence of respiratory distress syndrome, and usage of antenatal corticosteroids were significantly higher in the prophylaxis group. The cumulative number of days of mechanical ventilation, supplemental oxygen, and CPAP were significantly higher in the prophylaxis group. On multivariable linear regression, after adjusting for confounders, use of prophylactic indomethacin (unstandardized β coefficient = 12.4; 95% confidence interval [CI]: 6.6, 18.1; p < 0.001), birth weight (β = -0.025; 95% CI: -0.05, -0.001; p = 0.043), and gestation (β = -4.5; 95% CI: -7.24, -1.8; p = 0.001) were the independent predictors of cumulative number of days of mechanical ventilation. ELBW infants who received prophylactic indomethacin had significantly longer cumulative number of days of mechanical ventilation, supplemental oxygen, and CPAP. Prophylactic indomethacin is an independent predictor of cumulative number of days of mechanical ventilation.

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Introduction: Over the last 10 years, animal models have raised concern about possible detrimental effects of some anesthetic drugs on the developing brain. There is controversy about whether the animal data can be extrapolated to humans. Hypothesis: We hypothesize that sedation/analgesia drugs used before, during and after infant cardiac surgery are associated with adverse neuro-developmental outcomes. Methods: A prospective follow-up project conducted in Western Canada including all infants age < 6 weeks having surgery for congenital heart disease (CHD) between April 2003 and December 2006 and without chromosomal abnormalities. Demographic and perioperative variables were collected prospectively. Sedation/analgesia variables were collected retrospectively. For each drug class (opioids, benzodiazepines, ketamine and chloral hydrate) we calculated: total cumulative dose received during hospitalization, average dose received per day, and cumulative number of days the patient received the drug. The following outcomes were assessed at age 4 years: Full Scale IQ (FSIQ), Performance IQ (PIQ), Verbal IQ (VIQ), Visual-Motor Integration (VMI), ABAS General Adaptive Composite (GAC) score. Multiple linear regression was used to analyze the data. Results: One hundred thirty five infants underwent surgery for CHD during the study period, 91 patients were available for the analysis. After adjusting for days on mechanical ventilation postoperatively and single ventricle repair, multiple linear regression analysis found that the total cumulative dose [58.8 (68.2) mg/kg] of benzodiazepines had a small but statistically significant association with lower VMI (Effect size -0.09; 95% CI -0.16, -0.02; P = 0.013), but not with FSIQ, PIQ, VIQ, or GAC. None of the other sedation/analgesia variables were associated with FSIQ, PIQ, VIQ, GAC, or VMI. Conclusions: This study is the continuation to age 4 years of a previously published follow-up project in children who underwent surgery for CHD in early infancy. Assessment of this cohort at an older age found a small but statistically significant negative association between benzodiazepine cumulative dose and VMI. No other association between sedation/analgesia drugs and outcomes were found.

A population-based study on the association between acute renal failure (ARF) and the duration of polypharmacy

BackgroundBecause of the rapid growth in elderly population, polypharmacy has become a serious public health issue worldwide. Although acute renal failure (ARF) is one negative consequence of polypharmacy, the association between the duration of polypharmacy and ARF remains unclear. We therefore assessed this association using a population-based database.MethodsData were collected from the Taiwan National Health Insurance Research Database (NHIRD) from 2003 through 2006. The case group included patients hospitalized for ARF during 2006, but not admitted due to trauma, surgery, burn trauma, car accident, transplantation, or infectious diseases; the control group included patients hospitalized without ARF. The cumulative number of days of polypharmacy (defined as more than 5 prescriptions per day) for 1 year prior to admission was determined, with patients further subdivided into 4 categories: less than 30 days, 31–90 days, 91–180 days, and over 181 days. The dependent variable was ARF, and the control variables were age, gender, comorbidities in patients hospitalized for ARF, stay in ICUs during ARF hospitalization and site of operation for prior admissions within one month of ARF hospitalization.ResultsOf 20,790 patients who were admitted to hospitals for ARF in 2006, 12,314 (59.23 %) were male and more than 60 % were older than 65 years. Of patients with and without ARF, 16.14 % and 10.61 %, respectively, received polypharmacy for 91–180 days and 50.22 % and 24.12 %, respectively, for over 181 days. A statistical model indicated that, relative to patients who received polypharmacy for less than 30 days, those who received polypharmacy for 31–90, 91–180 and over 181 days had odds ratios of developing ARF of 1.33 (p<0.001), 1.65 (p<0.001) and 1.74 (p<0.001), respectively.ConclusionsWe observed statistically significant associations between the duration of polypharmacy and the occurrence of ARF.

Two simple models for accounting mussel contamination with diarrhoetic shellfish poisoning toxins at Aveiro lagoon: Control by rainfall and atmospheric forcing

At Aveiro lagoon (Portuguese northwest coast) bivalve contamination with diarrhoetic shellfish poisoning toxins (DSTs), okadaic acid (OA) and dinophysistoxin-2 (DTX2), is a recurrent annual phenomenon seriously affecting seafood safety. The influence of meteorological parameters was studied to understand accumulation of DSTs in mussels, related to the blooming of the causative toxic microalgae, belonging to genus Dinophysis . Two simplified models were useful in predicting the accumulation of DSTs in blue mussels from this lagoon. Either the May river drainage or the rainfall accumulated from January through May could adequately predict the severity of OA accumulated from predation upon Dinophysis acuminata during June/July. In both cases a linear relationship was obtained, with correlation coefficients of 0.85 or greater. Winds with a west direction favour coastal concentration of Dinophysis acuta in Aveiro region. Both OA and DTX2 contamination increased exponentially in September/October with the cumulative number of days with W-wind orientation in the preceding August (correlation coefficients greater than 0.92). This relationship was attributed to the quadratic effect of wind stress on surface currents. August is a transitional month, when the continental runoff effect upon Dinophysis acuminata can still be observed and Dinophysis acuta advection may be promoted by westerly winds occurring in July. The frequency of periods with northerly winds in July can halt accumulation of toxins derived from Dinophysis acuta . ► Seasonality of DSP toxins in Aveiro lagoon mussels was reviewed. ► Rainfall and river drainage was linearly related to mean weekly OA levels in June + July. ► Continental runoff seems connected to Dinophysis acuminata blooming in this area. ► Westerly-oriented winds in August were exponentially related with September + October mean weekly OA and DTX2 levels. ► Predominance of west winds favours concentration of Dinophysis acuta in this area.

Benzodiazepine Use Among Patients With Schizophrenia in Taiwan: A Nationwide Population-Based Survey

Benzodiazepine Use Among Patients With Schizophrenia in Taiwan: A Nationwide Population-Based Survey

Neurodevelopmental outcome following exposure to sedative and analgesic drugs for complex cardiac surgery in infancy*

To determine whether sedation/analgesia drugs used before, during, and after infant cardiac surgery are associated with neurodevelopmental outcome. Animal models suggest detrimental effects of anesthetic drugs on the developing brain. Whether these results can be extrapolated to human neonates is unclear. This is a prospective follow-up project conducted in Western Canada. In all infants ≤6 weeks of age having surgery for congenital heart disease between April 2003 and December 2006, demographic and perioperative variables were collected prospectively. Sedation/analgesia variables were collected retrospectively. For each drug class (inhalationals, opioids, benzodiazepines, ketamine, and chloral hydrate), we calculated the cumulative dose received during hospitalization, average dose received per day, and cumulative number of days the patient received the drug. The outcomes at 18-24 months were as follows: General Adaptive Composite and motor scaled scores of the Adaptive Behavior Assessment System, significant mental, motor, and vocabulary delay. Multivariable logistic and linear regression was used to analyze the data. One hundred and thirty-five neonates underwent open heart surgery; 19 died, 16 had chromosomal abnormality, and five were lost to follow up, leaving 95 survivors for analysis. Multiple linear regression analysis found no evidence of an association between sedation/analgesia variables and ABAS-GAC score or motor scale score. Multiple logistic regression analysis found no evidence of an association between sedation/analgesia variables and significant mental, motor, or vocabulary delay. We found no evidence of an association between dose and duration of sedation/analgesia drugs during the operative and perioperative period and adverse neurodevelopmental outcomes.

Some Factors Affecting the Abortion Rate in Dairy Herds with High Incidence ofNeospora-Associated Abortions are Different in Cows and Heifers

The aim of this study was to determine if the factors affecting the abortion rate in dairy herds with high incidence of Neospora-associated abortions are different in pregnancies of cows and heifers chronically infected with Neospora caninum. In heifers (n = 229), an increase in the cumulative number of days with a mean relative humidity (RH) lower than 60% during the second trimester of gestation increases the risk of abortion. Yet, the likelihood of abortion was 7.6 times lower for pregnant heifers inseminated with Limousin bull semen, compared with those inseminated with Holstein-Friesian bull semen. In pregnancies of parous cows (n = 521), an increase in rainfall and in the cumulative number of days with a mean RH lower than 60% during the second trimester of gestation increased the abortion rate. However, in contrast, an increase in the lactation number produced a decrease in the abortion rate, with a likelihood of abortion 4.8 times lower for pregnant cows inseminated with Limousin bull semen, and three times lower for those inseminated with Belgian Blue bull semen, compared with dairy cows inseminated with Holstein-Friesian bull semen. Finally, the likelihood of abortion was 3.2 times lower for pregnancies of parous cows with low antibody titres against N. caninum (6-30 units) as compared to those with high antibody titres (>/=30 units), whereas in heifers this variable had no effect. The practical recommendations of the present study include the control of the cow environment during the second trimester of gestation, the priority of culling for parous cows with higher antibody titres against N. caninum and the insemination of Neospora-seropositive cows with semen from the Limousin breed.

Antibiotic Use and the Risk of Lung Cancer

Antibiotic use has been associated with an increased risk of cancer in epidemiologic studies. We evaluated the association between antibiotic use and the risk of primary lung cancer by conducting a prospective case-control study nested in a cohort of subjects who were 40 to 84 years old in 1995 to 2004, with at least 2 years of enrollment in The Health Improvement Network. There were 4,336 cases of primary lung cancer. A random sample of 10,000 controls was frequency matched to the cases for age, sex, and calendar year of diagnosis. Antibiotic exposure was measured by the total number of antibiotic prescriptions and the cumulative number of days on antibiotics since enrollment. We discounted exposure 1 year before the date of cancer diagnosis. Relative risks (RR) and 95% confidence intervals (95% CI) were estimated using conditional logistic regression. Smoking, chronic obstructive pulmonary disease, respiratory infections, body mass index, and health care utilization were introduced in the model. Compared with subjects with no prescription of antibiotics before the index date, the crude RR of lung cancer was 2.52 (95% CI, 2.25-2.83) among those who received 10 or more prescriptions. The corresponding RR was 1.31 (95% CI, 1.10-1.57) upon adjustment for confounders. We used directed acyclic graphs to illustrate that the observed higher risk of lung cancer among antibiotic users may be due to the increased frequency of infections in patients with subclinical cancer and to shared causes between cancer and infections. Current evidence is insufficient to support or refute a carcinogenic effect of antibiotics.