Osteoporosis management in adults with schizophrenia following index hip fracture event: a 10-year population-based retrospective cohort study, Ontario, Canada.

Little is known about the incidence of osteoporosis testing and treatment in individuals with schizophrenia, who may be more likely to fracture. Using competing risk models, we found that schizophrenia was associated with lower incidence of testing or treatment. Implications are for understanding barriers and solutions for this disadvantaged group. PURPOSE: Evidence suggests that individuals with schizophrenia may be more likely to experience hip fractures than the general population; however, little is known about osteoporosis management in this disadvantaged subpopulation. Our study objective was to compare bone mineral density (BMD) testing and pharmacologic treatment in hip fracture patients with versus without schizophrenia. METHODS: This was a retrospective population-based cohort study leveraging health administrative databases, and individuals aged 66-105 years with hip fracture between fiscal years 2009 and 2018 in Ontario, Canada. Schizophrenia was ascertained using a validated algorithm. The outcome was a composite measure of (1) pharmacologic prescription for osteoporosis; or (2) a BMD test. Inferential analyses were conducted using Fine-Gray subdistribution hazard regression, with mortality as the competing event. RESULTS: A total of 52,722 individuals aged 66 to 105 years who sustained an index hip fracture in Ontario during the study period were identified, of whom 1890 (3.6%) had schizophrenia. Hip fracture patients with vs without schizophrenia were more likely to be long-term care residents (44.3% vs. 18.1%; standardized difference, 0.59), frail (62.5% vs. 36.5%; standardized difference, 0.54) and without a primary care provider (9.2% vs. 4.8%; standardized difference, 0.18). In Fine-Gray models, schizophrenia was associated with a lower incidence of testing or treatment (0.795 (0.721, 0.877)). CONCLUSIONS: In this population-based retrospective cohort study, a schizophrenia diagnosis among hip fracture patients was associated with a lower incidence of testing or treatment, after accounting for mortality, and several enabling and predisposing factors. Further research is required to investigate barriers to osteoporosis management in this disadvantaged population.

Fragility fracture patients with a history of prior fractures more likely to present with multiple risk factors: findings from a province-wide fracture liaison service.

We examined the demographic characteristics and risk factors of FLS fragility fracture patients who had sustained prior fragility fracture(s) and found that this is an important high-risk subgroup that warrants further attention within FLS priority pathways in order to disrupt their fragility fracture cycle. PURPOSE: Our primary objective was to examine whether fragility fracture patients presenting to a provincial fracture liaison service (FLS) having a history of prior fractures, versus those without, differ in demographic characteristics and risk factors for future fracture. A secondary objective was to understand if those who report two or more prior fractures differ from those reporting one prior fracture. METHODS: This cohort study included fragility fracture patients aged 50 + enrolled in the Ontario FLS between July 2017 and September 2019. Patients with versus those without prior fractures were compared on age, sex, index fracture site, biological parents' history of hip fracture, current fracture due to a fall, history of feeling unsteady when walking, history of falls in the past year, smoking, oral steroid use, and comorbid chronic conditions. Pearson's chi-square, Fischer's exact, and analysis of variance tests were used to assess differences. RESULTS: Among 14,454 patients, 16.8% (n = 2428) reported a history of one or more prior fractures after the age of 40. They were significantly more likely to be older, female, with a higher number of comorbidities, with greater incidence of falls, and feel unsteady when walking. Compared to those with one prior fracture, patients with greater than one prior fracture were more likely to report falls in the past year and feel unsteady when walking. CONCLUSION: Findings suggest that FLS fragility fracture patients who had sustained prior fragility fracture are an important high-risk subgroup that warrants further attention within FLS priority pathways in order to disrupt their fragility fracture cycle.

Risk of colorectal cancer following CT-verified acute diverticulitis: a nationwide population-based cohort study.

AIM: Routine colonoscopy to exclude colorectal cancer (CRC) after CT-verified acute diverticulitis is controversial. This study aimed to compare the incidence of CRC in patients with acute diverticulitis with that in the general population. METHOD: Patients with an emergency admission for diverticular disease to any Norwegian hospital between 1 January 2008 and 31 December 2010 were included through identification in the Norwegian Patient Registry using International Classification of Diseases (ICD-10) codes K57.1-9. To estimate the age-specific distribution of CT-verified acute uncomplicated diverticulitis (AUD) and acute complicated diverticulitis (ACD) in this nationwide study population, numbers from the largest Norwegian emergency hospital were used. Patients diagnosed with CRC within 1 year following their admission for acute diverticulitis were detected through cross-matching with the Cancer Registry of Norway. Based on both Norwegian age-specific incidence of CRC and estimated age-specific distribution of CT-verified diverticulitis, standard morbidity ratios (SMRs) were calculated. RESULTS: A total of 7473 patients with emergency admissions for diverticular disease were identified (estimated CT-verified AUD n = 3523, ACD n = 1206); of these 155 patients were diagnosed with CRC within 1 year. Eighty had a CT-verified diverticulitis at index admission [41 AUD (51.3%); 39 ACD (49.7%)]. Compared with the general population, the SMR was 6.6 following CT-verified AUD and 16.3 following ACD, respectively. CONCLUSION: In the first year after CT-verified acute diverticulitis, especially after ACD, the risk of CRC is higher than in the general population. This probably represents misdiagnosis of CRC as acute diverticulitis. Follow-up colonoscopy should be recommended to all patients admitted with acute diverticulitis.

Respectful maternity care during childbirth in India: A systematic review and meta-analysis.

BACKGROUND: Respectful maternity care is a rightful expectation of women. However, disrespectful maternity care is prevalent in various settings. Therefore, a systematic review and meta-analysis were conducted to identify various forms of ill-treatment, determinants, and pooled prevalence of disrespectful maternity care in India. METHODS: A systematic review was performed in various databases. After quality assessment, seven studies were included. Pooled prevalence was estimated using the inverse variance method and the random-effects model using Review Manager Software. RESULTS: Individual study prevalence ranged from 20.9% to 100%. The overall pooled prevalence of disrespectful maternity care was 71.31% (95% CI 39.84-102.78). Pooled prevalence in community-based studies was 77.32% (95% CI 56.71-97.93), which was higher as compared to studies conducted in health facilities, this being 65.38% (95% CI 15.76-115.01). The highest reported form of ill-treatment was non-consent (49.84%), verbal abuse (25.75%) followed by threats (23.25%), physical abuse (16.96%), and discrimination (14.79%). Besides, other factors identified included lack of dignity, delivery by unqualified personnel, lack of privacy, demand for informal payments, and lack of basic infrastructure, hygiene, and sanitation. The determinants identified for disrespect and abuse were sociocultural factors including age, socioeconomic status, caste, parity, women autonomy, empowerment, comorbidities, and environmental factors including infrastructural issues, overcrowding, ill-equipped health facilities, supply constraints, and healthcare access. CONCLUSION: The high prevalence of disrespectful maternity care indicates an urgent need to improve maternity care in India by making it more respectful, dignified, and women-centered. Interventions, policies, and programs should be implemented that will protect the fundamental rights of women.

4xTrifolium ambiguum and 2xT. occidentale hybridise despite wide geographic separation and polyploidisation: implications for clover breeding.

KEY MESSAGE: The widely divergent species 4xTrifolium ambiguum and 2xT.occidentale are inter-fertile long after speciation (including polyploidisation) has occurred. Tri-species hybrids (T. repens × T. ambiguum × T. occidentale) have the potential to achieve introgression of stress resistant traits from both wild species into white clover. Trifolium ambiguum and T. occidentale are geographically, adaptionally and phenotypically contrasting species in the white clover section (Trifoliastrum) of the genus. T. ambiguum occurs as a high-altitude polyploid series (2x, 4x, 6x) in W Asia and NE Europe. T. occidentale is a diploid coastal species, occurring at sea level in W Europe. This study investigated hybridisation between 4xT. ambiguum and 2xT. occidentale and considered the significance of the hybrids for introgression breeding of white clover. Partially fertile F1 hybrids between 4xT. ambiguum and 2x and 4xT. occidentale were generated by embryo rescue. Hybrid plant morphology and fertility varied widely and hybrids generally expressed traits from both species. Advanced generation (F2-F5) 4x hybrids were highly fertile and constitute a new synthetic allotetraploid species. FISH analyses of 4x hybrids showed multivalent chromosome configurations with homoeologous associations between T. ambiguum and T. occidentale chromosomes. Crosses of the hybrids with T. repens produced fertile tri-species progeny. These very divergent species remain inter-fertile long after speciation (including polyploidisation) has occurred. Tri-species hybrids have the potential to achieve introgression of stress resistance traits from both wild species into white clover.

Severe maternal morbidity among women with a history of cesarean section at a tertiary referral teaching hospital in the southeast of Iran.

OBJECTIVES: Although the cesarean section (C-section) is known as a lifesaving procedure, it can also increase the risk of maternal mortality and morbidity. This study was conducted to achieve two objectives: (1) determination of maternal near miss (MNM) indicators and pregnancy outcomes among women with a history of C-section and (2) investigation of the women's experience of near miss events during childbirth to provide a deeper understanding of the weaknesses of care delivery process. STUDY DESIGN: The present study was conducted using a prospective cross-sectional study using the World Health Organization (organ system dysfunction-based) criteria. METHODS: All subjects were women at more than 22 weeks of gestation who gave birth in Ali ibn Abi Talib Hospital, Zahedan, Iran, and were referred to this hospital for childbirth or those within 42 days of pregnancy termination. Logistic regression was used to predict the risk factors for severe maternal outcomes (SMOs). RESULTS: Nearly 58% of all MNM cases were related to women with a history of C-section. The MNM ratio was estimated at 8.04 per 1000 live births. Moreover, the frequent causes of SMOs were reported as severe hemorrhage (58.3%), severe pre-eclampsia/eclampsia (27.8%), medical condition (8.3%), and sepsis or severe systemic infection (5.6%). Abnormally invasive placenta (61%) was the most common cause of severe hemorrhage. After adjustment for potential confounder variables, the hemoglobin level of <11 g/dl (odds ratio [OR] = 0.18, 95% confidence interval [CI] = 0.09-0.36) and place of residence (OR = 0.41, 95% CI = 0.19-0.90) remained as independent risk factors for SMOs in the final model of multivariate analysis. CONCLUSION: A risk assessment system is needed to diagnose and manage the risk factors for SMOs during prenatal care. In addition, there should be a continuous audit of the indication and number of C-sections performed across health facilities.

Equal treatment: no evidence of gender inequity in osteoporosis management in a coordinator-based fragility fracture screening program.

We evaluated gender imbalance in osteoporosis management in a provincial coordinator-based fracture prevention program and found no difference by gender in treatment of high-risk fragility fracture patients. This establishes that a systemic approach with interventions for all fragility fracture patients can eliminate the gender inequity that is often observed. INRODUCTION: The purpose of this study was to evaluate an Ontario-based fracture prevention program for its ability to address the well-documented gender imbalance in osteoporosis (OP) management, by incorporating its integrated fracture risk assessments within a needs-based evaluation of equity. METHODS: Fragility fracture patients (≥ 50 years) who were treatment naïve at screening and completed follow-up within 6 months of screening were studied. Patients who underwent bone mineral density (BMD) testing done in the year prior to their current fracture were excluded. All participants had BMD testing conducted through the Ontario OP Strategy Fracture Screening and Prevention program, thus providing us with fracture risk assessment data. Our primary study outcome was treatment initiation at follow-up within 6 months of screening. Gender differences were compared using Fisher's exact test, at p < 0.05. RESULTS: After adjusting for subsequent fracture risk, study participants did not show a statistically significant gender difference in pharmacotherapy initiation at follow-up (p > 0.05). 68.4% of women and 66.2% of men at high risk were treated within 6 months of screening. CONCLUSION: Needs-based analyses show no difference by gender in treatment of high-risk fragility fracture patients. An intensive coordinator-based fracture prevention model adopted in Ontario, Canada was not associated with gender inequity in OP treatment of fragility fracture patients after fracture risk adjustment.

Predicting CCHF incidence and its related factors using time-series analysis in the southeast of Iran: comparison of SARIMA and Markov switching models.

Crimean-Congo haemorrhagic fever (CCHF) is endemic in the southeast of Iran. This study aimed to predict the incidence of CCHF and its related factors and explore the possibility of developing an empirical forecast system using time-series analysis of 13 years' data. Data from 2000 to 2012 were obtained from the Health Centre of Zahedan University of Medical Sciences, Climate Organization and the Veterinary Organization in the southeast of Iran. Seasonal autoregressive integrated moving average (SARIMA) and Markov switching models (MSM) were performed to examine the potential related factors of CCHF outbreaks. These models showed that the mean temperature (°C), accumulated rainfall (mm), maximum relative humidity (%) and legal livestock importation from Pakistan (LIP) were significantly correlated with monthly incidence of CCHF in different lags (P < 0·05). The modelling fitness was checked with data from 2013. Model assessments indicated that the MSM had better predictive ability than the SARIMA model [MSM: root mean square error (RMSE) 0·625, Akaike's Information Criterion (AIC) 266·33; SARIMA: RMSE 0·725, AIC 278·8]. This study shows the potential of climate indicators and LIP as predictive factors in modelling the occurrence of CCHF. Our results suggest that MSM provides more information on outbreak detection and can be a better predictive model compared to a SARIMA model for evaluation of the relationship between explanatory variables and the incidence of CCHF.

The Mars 2020 Engineering Cameras and Microphone on the Perseverance Rover: A Next-Generation Imaging System for Mars Exploration.

The Mars 2020 Perseverance rover is equipped with a next-generation engineering camera imaging system that represents an upgrade over previous Mars rover missions. These upgrades will improve the operational capabilities of the rover with an emphasis on drive planning, robotic arm operation, instrument operations, sample caching activities, and documentation of key events during entry, descent, and landing (EDL). There are a total of 16 cameras in the Perseverance engineering imaging system, including 9 cameras for surface operations and 7 cameras for EDL documentation. There are 3 types of cameras designed for surface operations: Navigation cameras (Navcams, quantity 2), Hazard Avoidance Cameras (Hazcams, quantity 6), and Cachecam (quantity 1). The Navcams will acquire color stereo images of the surface with a 96 ∘ × 73 ∘ field of view at 0.33 mrad/pixel. The Hazcams will acquire color stereo images of the surface with a 136 ∘ × 102 ∘ at 0.46 mrad/pixel. The Cachecam, a new camera type, will acquire images of Martian material inside the sample tubes during caching operations at a spatial scale of 12.5 microns/pixel. There are 5 types of EDL documentation cameras: The Parachute Uplook Cameras (PUCs, quantity 3), the Descent stage Downlook Camera (DDC, quantity 1), the Rover Uplook Camera (RUC, quantity 1), the Rover Descent Camera (RDC, quantity 1), and the Lander Vision System (LVS) Camera (LCAM, quantity 1). The PUCs are mounted on the parachute support structure and will acquire video of the parachute deployment event as part of a system to characterize parachute performance. The DDC is attached to the descent stage and pointed downward, it will characterize vehicle dynamics by capturing video of the rover as it descends from the skycrane. The rover-mounted RUC, attached to the rover and looking upward, will capture similar video of the skycrane from the vantage point of the rover and will also acquire video of the descent stage flyaway event. The RDC, attached to the rover and looking downward, will document plume dynamics by imaging the Martian surface before, during, and after rover touchdown. The LCAM, mounted to the bottom of the rover chassis and pointed downward, will acquire 90 ∘ × 90 ∘ FOV images during the parachute descent phase of EDL as input to an onboard map localization by the Lander Vision System (LVS). The rover also carries a microphone, mounted externally on the rover chassis, to capture acoustic signatures during and after EDL. The Perseverance rover launched from Earth on July 30th, 2020, and touchdown on Mars is scheduled for February 18th, 2021.

A2A adenosine receptor deficiency leads to impaired tracheal relaxation via NADPH oxidase pathway in allergic mice.

A(2A) adenosine receptor (A(2A)AR) has been shown to suppress superoxide generation in leukocytes via the cAMP-protein kinase A (PKA) pathway. However, no study has yet explored the role of A(2A)AR in relation to NADPH oxidase in murine tracheas in vitro, which may lead to altered smooth muscle relaxation in asthma. Therefore, the present study evaluated the effects of A(2A)AR deficiency on the NADPH oxidase pathway in tracheas of A(2A) wild-type (WT) and A(2A) knockout (KO) mice. A(2A)WT mice were sensitized with ovalbumin (30 microg i.p.) on days 1 and 6, followed by 5% ovalbumin aerosol challenge on days 11, 12, and 13. A(2A)AR (gene and protein expression), cAMP, and phosphorylated PKA (p-PKA) levels were decreased in A(2A)WT sensitized mice compared with controls. A(2A)KO mice also showed decreased cAMP and p-PKA levels. A(2A)WT sensitized and A(2A)KO control mice had increased gene and protein expression of NADPH oxidase subunits (p47phox and gp91phox) compared with the controls. Tracheal relaxation to specific A(2A)AR agonist, 4-[2-[[6-amino-9-(N-ethyl-beta-d-ribofuranuronamidosyl)-9H-purin-2-yl]amino]ethyl]benzenepropanoic acid hydrochloride (CGS 21680), decreased in A(2A)WT sensitized mice compared with the controls, although it was absent in A(2A)KO mice. Pretreatment with NADPH oxidase inhibitors apocyanin/diphenyliodonium reversed the attenuated relaxation to CGS 21680 in A(2A)WT sensitized tracheas, whereas specific PKA inhibitor (9S,10S,12R)-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i] [1,6]benzodiazocine-10-carboxylic acid hexyl ester (KT 5720) blocked CGS 21680-induced relaxation. Tracheal reactive oxygen species (ROS) generation was also increased in A(2A)WT sensitized and A(2A)KO control mice compared with the controls. In conclusion, this study shows that A(2A)AR deficiency causes increased NADPH oxidase activation leading to decreased tracheal relaxation via altered cAMP-PKA signaling and ROS generation.

Anti-Obesity Effect of Arq Zeera and Its Main Components Thymol and Cuminaldehyde in High Fat Diet Induced Obese Rats.

Arq zeera is a distillate product that prepared from four different herbs namely Trachyspermum ammi L., apiaceae, Zingiber officinale Roxb., zingiberaceae, Carum carvi L.,apiaceae and Cuminum cyminum L., apiaceae. The present study aims to determine the antiobesity effect of arq zeera and its main components thymol and cuminaldehyde in high fat diet induced obese rats and to explore its mechanism of action. In current study, orlistat was used as positive controls. Male Wistar rats were fed with HFD for 42 days to induce obesity. HFD-fed rats were administered with arq zeera, thymol, cumic aldehyde, thymol + cuminaldehyde and orlistat for 28 days. During the course of treatment, body weight and food intake frequently observed and after end of treatments, liver weight, visceral fat pad weight, plasma lipid proflie, alanine aminotransferase, aspartate aminotransferase, glucose, insulin, leptin levels and pancreatic lipase activity were studied on all treated obese rats. The histopathology of liver was also studied. After the treatments of arq zeera and its main components, body weight, food intake, liver weight, visceral fat pad weight and the level of lipid profile, alanine aminotransferase, aspartate aminotranferase, glucose, insulin, and leptin were found to be decreased and pancreatic lipase inhibition were increased. Arq zeera showed more potential antiobesity effect than orlistat. According to our present findings, arq zeera and its main components possessed potent antiobesity effect on high fat diet -induced obese rats and excreted anti-obesity effect partly via hypolipidemic, hypoglycemic, hypoinsulinemic, hypoleptinemic and pancreatic lipase inhibition action.

Fast food consumption and overweight/obesity prevalence in students and its association with general and abdominal obesity.

Nowadays, the prevalence of both fast food consumption and overweight/obesity has been increased. This study aimed to estimate the prevalence of fast food consumption and to assess its association with abdominal and general obesity. In an analytical cross-sectional study, 300 students were selected randomly from two largest universities in Qom, center of Iran, studying in medical and basic sciences fields in 2015. Data collection was conducted by a modified version of NELSON's fast food questionnaire and anthropometric measures including Waist-Hip Ratio (WHR) and Body Mass Index (BMI). Chi-square, independent t-test, and multivariate logistic regression were used for statistical analysis. According to our results, 72.4% (67.4% in females vs 80.7% in males) had at least one type of fast food consumption in the recent month including sandwich 44.4%, pizza 39.7%, and fried chicken 13.8%, The obesity prevalence based on BMI and WHR was 21.3% (95% CI: 19.4, 23.2%) and 33.2% (95% CI: 0.7, 35.7), respectively. Fast food consumption was related to abdominal obesity as WHR (OR: 1.46, 95% CI: 1.11, 2.26), but was not related to general obesity as BMI (OR: 0.97, 95% CI: 0.63, 1.52). The prevalence of fast food consumption and obesity/overweight in Iranian student is high. Fast food consumption was associated with abdominal obesity based WHR, but did not related to general obesity based on BMI.

A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. Writing Committee for the Collaborative CML Prognostic Factors Project Group.

BACKGROUND: Interferon alfa is a conservative and widely used alternative to bone marrow transplantation in treatment of patients with early chronic myeloid leukemia (CML). A meta-analysis was conducted to develop a reliable prognostic scoring system for estimation of survival of patients with CML treated with interferon alfa. METHODS: Patients treated in prospective studies, including major randomized trials, were separated into learning and validation samples. Cox regression analysis and the minimum P-value approach were used to identify prognostic factors for patient survival and to discover groups in the learning sample with the greatest differences in survival. These findings were then validated by applying the new scoring system to patients in the validation sample. RESULTS: We collected data on 1573 patients who were participants in 14 studies involving 12 institutions; 1303 patients (learning sample, n = 981; validation sample, n = 322) were eligible for inclusion in this analysis, and their median survival time was 69 months (range, 1-117 months). Because two previously described prognostic scoring systems failed to discriminate risk groups satisfactorily, we developed a new scoring system that utilizes the following covariates: age, spleen size, blast count, platelet count, eosinophil count, and basophil count. Among 908 patients with complete data in the learning sample, three distinct risk groups were identified (median survival times of 98 months [n = 369; 40.6%], 65 months [n = 406; 44.7%], or 42 months [n = 133;14.6%]; two-sided logrank test, P< or =.0001). The ability of the new scoring system to discriminate these risk groups was confirmed by analysis of 285 patients with complete data in the validation sample (two-sided logrank test, P = .0002). CONCLUSIONS: A new prognostic scoring system for estimating survival of patients with CML treated with interferon alfa has been developed and validated through use of a large dataset.

Species differences in the effects of prostanoids on MAP kinase phosphorylation, myosin light chain phosphorylation and contraction in bovine and cat iris sphincter smooth muscle.

There is evidence from our own laboratory and that of others that EP-receptor ligands are strong contractile agonists in bovine iris sphincter and that FP-receptor agonists are strong contractile agonists in cat iris sphincter. Here, we have investigated the effects of prostaglandin (PG) receptor agonists of the FP-, EP-, TP- and DP-class on myosin light chain (MLC) phosphorylation, p42/p44 MAP kinase phosphorylation and contraction in the iris sphincter of bovine and cat. Using three signal transduction mechanism assays, namely MLC phosphorylation, MAP kinase phosphorylation and contraction, we demonstrated that in bovine iris sphincter the rank order of potency of the PG agonists in the contractile and MLC phosphorylation assays is as follows: E2>U46619>F2alpha>D2, and in cat F2alpha>D2>E2>U46619. In the MAP kinase assay, in bovine iris sphincter the rank order of potency is E2>F2alpha and in cat F2alpha>E2. These conclusions are supported by the following findings: (1) In the contractile assay, in the bovine sphincter the EC50s for PGF2alpha, PGE2, U46619 and PGD2 were found to be 1.4x10(-7), 5.0x10(-9), 9.0x10(-9) and 1.3x10(-6)M, respectively, and the corresponding values in the cat were 1.9x10(-8), 2.3x10(-7), 1.5x10(-6) and 6.9x10(-8)M, respectively. (2) In the MLC phophorylation assay, in the bovine sphincter PGF2alpha, PGE2, U46619 and PGD2 increased MLC phophorylation by 118%, 165%, 153% and 72%, respectively, and the corresponding values in cat were 175%, 99%, 90% and 95%, respectively. (3) In the MAP kinase assay, in the bovine iris sphincter PGF2alpha and PGE2, increased MAP kinase phosphorylation by 276% and 328%, respectively, and the corresponding values in cat were 308% and 245%, respectively. The data presented demonstrate pronounced species differences in the effects of the prostanoids on the MLC kinase signaling pathway in bovine and cat irides and furthermore confirm the existence of FP-receptors in that of the bovine.

Therapeutic progress and comparative aspects in chronic myelogenous leukemia (CML): interferon alpha vs. hydroxyurea vs. busulfan and expression of MMTV-related endogenous retroviral sequences in CML. German CML Study Group.

In summary, it can be expected that the availability of unrelated donors will increase the number of CML patients that can be treated curatively with allogeneic BMT. Hydroxyurea has replaced busulfan as first line treatment in CML since it prolongs survival. Ongoing randomized studies comparing IFN-based treatment regimens with standard chemotherapy or IFN-monotherapy probably will answer the question whether IFN can cure a small percentage of CML patients and whether this small percentage can be increased by additional chemotherapy. The present attempts to improve prognostic scores and to apply them to early treatment decisions will allow treatment adaptation more individually. The implications of endogenous retroviral sequences expressed in CML cells are not known now, but may be far reaching.

Analysis and validation of prognostic factors for CML. German CML Study Group.

The analysis and validation of prognostic factors is a decisive prerequisite with regard to the development and application of risk-adjusted therapies. Among others, the Sokal index 1 and Kantarjian's new staging system 2 were scores set up to assess the survival of every patient individually. By means of 504 Ph- and/or bcr-abl-positive patients of the German CML study I, we tried to validate both scores mentioned above. Whereas Kantarjian's staging system provided rather unsatisfactory results, the discrimination of different risk groups was more promising with respect to the Sokal index. Still, concerning the differentiation between risk groups for the interferon-alpha (IFN-alpha) treated patients of the German study I, the Sokal index also failed. Hence, we applied Cox stepwise regression technique and identified three prognostic factors for the IFN-alpha treated patients, i.e. eosinophils, erythroblasts (both in peripheral blood), and extramedullary manifestations. We developed our own score and found an encouraging 5-y survival rate of 90% (95% confidence interval (CI) 76-100%) for a certain low-risk group of 41 out of 120 IFN-alpha treated patients. With the need to validate our score and, if possible, not only to confirm the above result but also to identify other particular patient groups, we launched the European Prognostic Factors Project (E.P.F.P.). Within this project, our special interest will be dedicated to patient groups who might also benefit from a bone marrow transplantation.

Randomized study of the combination of hydroxyurea and interferon alpha versus hydroxyurea monotherapy during the chronic phase of chronic myelogenous leukemia (CML Study II). The German CML Study Group.

It is the long-term goal of the German CML Study Group and of the Süddeutsche Hämoblastosegruppe (SHG) to improve survival of patients with chronic myelogenous leukemia (CML). In a first randomized study (CML Study I) monotherapies with hydroxyurea or interferon alpha (IFN-alpha) were compared with a standard busulfan regimen with regard to duration of the chronic phase and survival. The main results of this study were published, 1-3 and a long-term follow up is planned. In a second randomized study the effect of the combination of IFN-alpha and hydroxyurea versus hydroxyurea monotherapy on survival is being investigated. This paper provides a first preliminary report on the study concept, patient recruitment, state of documentation and initial patients' characteristics 9 months after closure of the study.

The use of heat mount detectors in a large Iranian dairy herd.

Heat mount detectors were applied in a large Iranian dairy herd in an attempt to appraise their value for fertility improvement. A total of 100 cows with a recorded anoestrous period of at least 60 days were selected, 69 of them suffering from suboestrus or silent heat and 31 from true anoestrus due to inactive ovaries. The results indicate that inaccurate observation of heat is a major limiting factor in the reproductive performance of this herd and that heat detectors could be a valuable tool for improvement of oestrus detection and consequent reduction of the interval from calving to conception.

CART and logistic regression analyses of risk factors for first dose hypotension by an ACE-inhibitor.

Angiotensin converting enzyme inhibitors (ACEI) are established drugs for the treatment of congestive heart failure. Cases of symptomatic hypotension, especially on the first day of treatment, have been reported occasionally. The database we analysed consisted of 1,177 patients, mean age approximately 70 yrs, with congestive heart failure NYHA functional class II or III. These patients were treated and observed prospectively according to a uniform protocol, starting therapy with 2.5 mg enalapril and measuring blood pressure at hourly intervals for eight hours thereafter. 94.6% of the patients experienced no symptomatic hypotension, 4.75% moderate symptoms (e.g. dizziness, headache) and 0.59% severe symptoms (e.g. fainting, collapse, renal failure). For the analyses of risk factors a large number of baseline variables were analysed univariately to select those significant for inclusion in a multivariate stepwise logistic regression. Alternatively the CART-(classification and regression tree) technique was used. Both techniques showed diastolic blood pressure < or = 70 mmHg to be the single most significant risk factor. CART-analyses showed also pretreatment with nitrates and systolic blood pressure < or = 120 mmHg to be of prognostic relevance. Thus CART is a valuable complement when looking for prognostic factors.