A comparison of the dental status and treatment needs of older adults with and without chronic mental illness in Sevilla, Spain

Objectives: To study the dental status and treatment needs of institutionalized older adults with chronic mental illness compared to a non-psychiatric control sample. Study Design: The sample size was 100, in which 50 were psychogeriatric patients (study group; SG) classified according to DSM-IV, with a mean age of 69.6 ± 6.7 years, and 50 non-psychiatric patients (control group; CG), with a mean age of 68.3 ± 6.9 years. Clinical oral health examinations were conducted and caries were recorded clinically using the Decayed, Missing and Filled Teeth Index (DMFT). Results were analyzed statistically using the Student"s t-test or analysis of variance. Results: Caries prevalence was 58% and 62% in SG and CG, respectively. DMFT index was 28.3 ± 6.6 in SG and 21.4 ± 6.07 in CG (p < 0.01). Mean number of decayed teeth was higher in SG (3.1) compared to CG (1.8) (p=0.047). Mean number of missing teeth were 25.2 and 16.4 in SG and CG respectively (p<0.05). DMFT scores were higher in SG in all the age groups (p < 0.01). Mean number of teeth per person needing treatment was 3.4 in SG and 1.9 in CG (p= 0.037). The need for restorative dental care was significantly lower in the SG (0.8 teeth per person) than in the CG (1.7 teeth per person) (p = 0.043). Conclusions: Institutionalized psychiatric patients have significantly worse dental status and more dental treatment needs than non-psychiatric patients.

A prospective development study investigating focal irreversible electroporation in men with localised prostate cancer: Nanoknife Electroporation Ablation Trial (NEAT).

INTRODUCTION: Focal therapy may reduce the toxicity of current radical treatments while maintaining the oncological benefit. Irreversible electroporation (IRE) has been proposed to be tissue selective and so might have favourable characteristics compared to the currently used prostate ablative technologies. The aim of this trial is to determine the adverse events, genito-urinary side effects and early histological outcomes of focal IRE in men with localised prostate cancer. METHODS: This is a single centre prospective development (stage 2a) study following the IDEAL recommendations for evaluating new surgical procedures. Twenty men who have MRI-visible disease localised in the anterior part of the prostate will be recruited. The sample size permits a precision estimate around key functional outcomes. Inclusion criteria include PSA ≤ 15 ng/ml, Gleason score ≤ 4 + 3, stage T2N0M0 and absence of clinically significant disease outside the treatment area. Treatment delivery will be changed in an adaptive iterative manner so as to allow optimisation of the IRE protocol. After focal IRE, men will be followed during 12 months using validated patient reported outcome measures (IPSS, IIEF-15, UCLA-EPIC, EQ-5D, FACT-P, MAX-PC). Early disease control will be evaluated by mpMRI and targeted transperineal biopsy of the treated area at 6 months. DISCUSSION: The NEAT trial will assess the early functional and disease control outcome of focal IRE using an adaptive design. Our protocol can provide guidance for designing an adaptive trial to assess new surgical technologies in the challenging landscape of health technology assessment in prostate cancer treatment.

Two cilengitide regimens in combination with standard treatment for patients with newly diagnosed glioblastoma and unmethylated MGMT gene promoter: results of the open-label, controlled, randomized phase II CORE study.

BACKGROUND: Survival outcomes for patients with glioblastoma remain poor, particularly for patients with unmethylated O(6)-methylguanine-DNA methyltransferase (MGMT) gene promoter. This phase II, randomized, open-label, multicenter trial investigated the efficacy and safety of 2 dose regimens of the selective integrin inhibitor cilengitide combined with standard chemoradiotherapy in patients with newly diagnosed glioblastoma and an unmethylated MGMT promoter. METHODS: Overall, 265 patients were randomized (1:1:1) to standard cilengitide (2000 mg 2×/wk; n = 88), intensive cilengitide (2000 mg 5×/wk during wk 1-6, thereafter 2×/wk; n = 88), or a control arm (chemoradiotherapy alone; n = 89). Cilengitide was administered intravenously in combination with daily temozolomide (TMZ) and concomitant radiotherapy (RT; wk 1-6), followed by TMZ maintenance therapy (TMZ/RT→TMZ). The primary endpoint was overall survival; secondary endpoints included progression-free survival, pharmacokinetics, and safety and tolerability. RESULTS: Median overall survival was 16.3 months in the standard cilengitide arm (hazard ratio [HR], 0.686; 95% CI: 0.484, 0.972; P = .032) and 14.5 months in the intensive cilengitide arm (HR, 0.858; 95% CI: 0.612, 1.204; P = .3771) versus 13.4 months in the control arm. Median progression-free survival assessed per independent review committee was 5.6 months (HR, 0.822; 95% CI: 0.595, 1.134) and 5.9 months (HR, 0.794; 95% CI: 0.575, 1.096) in the standard and intensive cilengitide arms, respectively, versus 4.1 months in the control arm. Cilengitide was well tolerated. CONCLUSIONS: Standard and intensive cilengitide dose regimens were well tolerated in combination with TMZ/RT→TMZ. Inconsistent overall survival and progression-free survival outcomes and a limited sample size did not allow firm conclusions regarding clinical efficacy in this exploratory phase II study.

Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data.

BACKGROUND: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). METHODS: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. RESULTS: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 °C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). CONCLUSIONS: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.

Planning and reporting of quality-of-life outcomes in cancer trials.

BACKGROUND: Information about the impact of cancer treatments on patients' quality of life (QoL) is of paramount importance to patients and treating oncologists. Cancer trials that do not specify QoL as an outcome or fail to report collected QoL data, omit crucial information for decision making. To estimate the magnitude of these problems, we investigated how frequently QoL outcomes were specified in protocols of cancer trials and subsequently reported. DESIGN: Retrospective cohort study of RCT protocols approved by six research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We compared protocols to corresponding publications, which were identified through literature searches and investigator surveys. RESULTS: Of the 173 cancer trials, 90 (52%) specified QoL outcomes in their protocol, 2 (1%) as primary and 88 (51%) as secondary outcome. Of the 173 trials, 35 (20%) reported QoL outcomes in a corresponding publication (4 modified from the protocol), 18 (10%) were published but failed to report QoL outcomes in the primary or a secondary publication, and 37 (21%) were not published at all. Of the 83 (48%) trials that did not specify QoL outcomes in their protocol, none subsequently reported QoL outcomes. Failure to report pre-specified QoL outcomes was not associated with industry sponsorship (versus non-industry), sample size, and multicentre (versus single centre) status but possibly with trial discontinuation. CONCLUSIONS: About half of cancer trials specified QoL outcomes in their protocols. However, only 20% reported any QoL data in associated publications. Highly relevant information for decision making is often unavailable to patients, oncologists, and health policymakers.

Premature Discontinuation of Randomized Trials in Critical and Emergency Care: A Retrospective Cohort Study.

OBJECTIVES: Randomized clinical trials that enroll patients in critical or emergency care (acute care) setting are challenging because of narrow time windows for recruitment and the inability of many patients to provide informed consent. To assess the extent that recruitment challenges lead to randomized clinical trial discontinuation, we compared the discontinuation of acute care and nonacute care randomized clinical trials. DESIGN: Retrospective cohort of 894 randomized clinical trials approved by six institutional review boards in Switzerland, Germany, and Canada between 2000 and 2003. SETTING: Randomized clinical trials involving patients in an acute or nonacute care setting. SUBJECTS AND INTERVENTIONS: We recorded trial characteristics, self-reported trial discontinuation, and self-reported reasons for discontinuation from protocols, corresponding publications, institutional review board files, and a survey of investigators. MEASUREMENTS AND MAIN RESULTS: Of 894 randomized clinical trials, 64 (7%) were acute care randomized clinical trials (29 critical care and 35 emergency care). Compared with the 830 nonacute care randomized clinical trials, acute care randomized clinical trials were more frequently discontinued (28 of 64, 44% vs 221 of 830, 27%; p = 0.004). Slow recruitment was the most frequent reason for discontinuation, both in acute care (13 of 64, 20%) and in nonacute care randomized clinical trials (7 of 64, 11%). Logistic regression analyses suggested the acute care setting as an independent risk factor for randomized clinical trial discontinuation specifically as a result of slow recruitment (odds ratio, 4.00; 95% CI, 1.72-9.31) after adjusting for other established risk factors, including nonindustry sponsorship and small sample size. CONCLUSIONS: Acute care randomized clinical trials are more vulnerable to premature discontinuation than nonacute care randomized clinical trials and have an approximately four-fold higher risk of discontinuation due to slow recruitment. These results highlight the need for strategies to reliably prevent and resolve slow patient recruitment in randomized clinical trials conducted in the critical and emergency care setting.

Estimating extreme value cumulative distribution functions using bias-corrected kernel approaches

We propose a new kernel estimation of the cumulative distribution function based on transformation and on bias reducing techniques. We derive the optimal bandwidth that minimises the asymptotic integrated mean squared error. The simulation results show that our proposed kernel estimation improves alternative approaches when the variable has an extreme value distribution with heavy tail and the sample size is small.

Caracterització del temps de vol en relació amb variables biomecàniques de l’estirada en l’arrencada d’halterofília

L’objecte del present estudi és caracteritzar el temps de vol (Tv) de la fase aèria en l’exercici d’arrencada en halterofília. Es descriu el seu comportament en funció de l’increment progressiu de la càrrega i en relació a variables biomecàniques de l’estirada, així com la seva evolució en un cicle d’entrenament. Es va fer un test màxim de càrregues progressives amb set halterofilistes (n = 7) de competició. Mitjançant els sistemes de valoració Musclelab i Chronojump es van registrar els valors de: força (F), potència (P), velocitat (V), pic de velocitat (pV) i alçada relativa (Hrel ) de la barra en l’estirada, al costat del Tv del desplaçament dels peus de l’aixecador a l’entrada sota la barra. Es va observar una moderada correlació negativa (r = –0,561; p < 0,01) entre el Tv i la càrrega màxima del test (%1RMT). No es van trobar correlacions significatives per al Tv respecte a la resta de variables analitzades. El Tv disminuïa amb l’increment de la càrrega en rangs submàxims, i era de natura aleatòria amb l’ocupació de càrregues màximes. En un subgrup de la mostra (n = 4) es van valorar les mateixes variables passades vuit setmanes. El Tv, la Pmàx i el pV suggereixen ser variables suficientment sensibles per monitoritzar els canvis generats per l’entrenament en vuit setmanes, encara que la reduïda dimensió mostral no va permetre aconseguir diferències significatives. Aquests resultats destaquen la possibilitat de considerar el Tv i la P com a mesures de control en l’entrenament d’halterofilistes, preferentment en l’ús de càrregues submàximes.

Size Effect and Notch Size Effect in Metal Fatigue

It is a well known phenomenon that the constant amplitude fatigue limit of a large component is lower than the fatigue limit of a small specimen made of the same material. In notched components the opposite occurs: the fatigue limit defined as the maximum stress at the notch is higher than that achieved with smooth specimens. These two effects have been taken into account in most design handbooks with the help of experimental formulas or design curves. The basic idea of this study is that the size effect can mainly be explained by the statistical size effect. A component subjected to an alternating load can be assumed to form a sample of initiated cracks at the end of the crack initiation phase. The size of the sample depends on the size of the specimen in question. The main objective of this study is to develop a statistical model for the estimation of this kind of size effect. It was shown that the size of a sample of initiated cracks shall be based on the stressed surface area of the specimen. In case of varying stress distribution, an effective stress area must be calculated. It is based on the decreasing probability of equally sized initiated cracks at lower stress level. If the distribution function of the parent population of cracks is known, the distribution of the maximum crack size in a sample can be defined. This makes it possible to calculate an estimate of the largest expected crack in any sample size. The estimate of the fatigue limit can now be calculated with the help of the linear elastic fracture mechanics. In notched components another source of size effect has to be taken into account. If we think about two specimens which have similar shape, but the size is different, it can be seen that the stress gradient in the smaller specimen is steeper. If there is an initiated crack in both of them, the stress intensity factor at the crack in the larger specimen is higher. The second goal of this thesis is to create a calculation method for this factor which is called the geometric size effect. The proposed method for the calculation of the geometric size effect is also based on the use of the linear elastic fracture mechanics. It is possible to calculate an accurate value of the stress intensity factor in a non linear stress field using weight functions. The calculated stress intensity factor values at the initiated crack can be compared to the corresponding stress intensity factor due to constant stress. The notch size effect is calculated as the ratio of these stress intensity factors. The presented methods were tested against experimental results taken from three German doctoral works. Two candidates for the parent population of initiated cracks were found: the Weibull distribution and the log normal distribution. Both of them can be used successfully for the prediction of the statistical size effect for smooth specimens. In case of notched components the geometric size effect due to the stress gradient shall be combined with the statistical size effect. The proposed method gives good results as long as the notch in question is blunt enough. For very sharp notches, stress concentration factor about 5 or higher, the method does not give sufficient results. It was shown that the plastic portion of the strain becomes quite high at the root of this kind of notches. The use of the linear elastic fracture mechanics becomes therefore questionable.

Clinical usefulness of the Screen for Cognitive Impairment in Psychiatry (SCIP-S) scale in patients with type I bipolar disorder

Background: The relevance of persistent cognitive deficits to the pathogenesis and prognosis of bipolar disorders (BD) is understudied, and its translation into clinical practice has been limited by the absence of brief methods assessing cognitive status in Psychiatry. This investigation assessed the psychometric properties of the Spanish version of the Screen for Cognitive Impairment in Psychiatry (SCIP-S) for the detection of cognitive impairment in BD. Methods: After short training, psychiatrists at 40 outpatient clinics administered the SCIP three times over two weeks to a total of 76 consecutive type I BD admissions. Experienced psychologists also administered a comprehensive battery of standard neuropsychological instruments to clinical sample and 45 healthy control subjects. Results: Feasibility was supported by a brief administration time (approximately 15 minutes) and minimal scoring errors. The reliability of the SCIP was confirmed by good equivalence of forms, acceptable stability (ICC range 0.59 to 0.87) and adequate internal consistency (Chronbach's alpha of 0.74). Construct validity was granted by extraction of a single factor (accounting 52% of the variance), acceptable correlations with conventional neuropsychological instruments, and a clear differentiation between bipolar I and normal samples. Efficiency was also provided by the adequate sensitivity and specificity. Limitations: The sample size is not very large. The SCIP and the neurocognitive battery do not cover all potentially relevant cognitive domains. Also, sensitivity to change remains unexplored. Conclusion: With minimal training, physicians obtained a reliable and valid estimate of cognitive impairment in approximately 15 minutes from an application of the SCIP to type I BD patients.

Clinical usefulness of the Screen for Cognitive Impairment in Psychiatry (SCIP-S) scale in patients with type I bipolar disorder

Background: The relevance of persistent cognitive deficits to the pathogenesis and prognosis of bipolar disorders (BD) is understudied, and its translation into clinical practice has been limited by the absence of brief methods assessing cognitive status in Psychiatry. This investigation assessed the psychometric properties of the Spanish version of the Screen for Cognitive Impairment in Psychiatry (SCIP-S) for the detection of cognitive impairment in BD. Methods: After short training, psychiatrists at 40 outpatient clinics administered the SCIP three times over two weeks to a total of 76 consecutive type I BD admissions. Experienced psychologists also administered a comprehensive battery of standard neuropsychological instruments to clinical sample and 45 healthy control subjects. Results: Feasibility was supported by a brief administration time (approximately 15 minutes) and minimal scoring errors. The reliability of the SCIP was confirmed by good equivalence of forms, acceptable stability (ICC range 0.59 to 0.87) and adequate internal consistency (Chronbach's alpha of 0.74). Construct validity was granted by extraction of a single factor (accounting 52% of the variance), acceptable correlations with conventional neuropsychological instruments, and a clear differentiation between bipolar I and normal samples. Efficiency was also provided by the adequate sensitivity and specificity. Limitations: The sample size is not very large. The SCIP and the neurocognitive battery do not cover all potentially relevant cognitive domains. Also, sensitivity to change remains unexplored. Conclusion: With minimal training, physicians obtained a reliable and valid estimate of cognitive impairment in approximately 15 minutes from an application of the SCIP to type I BD patients.

Monitoring of mechanical sugarcane harvesting through control charts

ABSTRACT Statistical process control in mechanized farming is a new way to assess operation quality. In this sense, we aimed to compare three statistical process control tools applied to losses in sugarcane mechanical harvesting to determine the best control chart template for this quality indicator. Losses were daily monitored in farms located within Triângulo Mineiro region, in Minas Gerais state, Brazil. They were carried over a period of 70 days in the 2014 harvest. At the end of the evaluation period, 194 samples were collected in total for each type of loss. The control charts used were individual values chart, moving average and exponentially weighted moving average. The quality indicators assessed during sugarcane harvest were the following loss types: full grinding wheel, stumps, fixed piece, whole cane, chips, loose piece and total losses. The control chart of individual values is the best option for monitoring losses in sugarcane mechanical harvesting, as it is of easier result interpretation, in comparison to the others.

Soybean yield maps using regular and optimized sample with different configurations by simulated annealing

ABSTRACT This study aimed to compare thematic maps of soybean yield for different sampling grids, using geostatistical methods (semivariance function and kriging). The analysis was performed with soybean yield data in t ha-1 in a commercial area with regular grids with distances between points of 25x25 m, 50x50 m, 75x75 m, 100x100 m, with 549, 188, 66 and 44 sampling points respectively; and data obtained by yield monitors. Optimized sampling schemes were also generated with the algorithm called Simulated Annealing, using maximization of the overall accuracy measure as a criterion for optimization. The results showed that sample size and sample density influenced the description of the spatial distribution of soybean yield. When the sample size was increased, there was an increased efficiency of thematic maps used to describe the spatial variability of soybean yield (higher values of accuracy indices and lower values for the sum of squared estimation error). In addition, more accurate maps were obtained, especially considering the optimized sample configurations with 188 and 549 sample points.

Assessment of fetal risk associated with exposure to cancer chemotherapy during pregnancy: a multicenter study

The objective of the present study was to evaluate and quantify fetal risks involved in the administration of cancer chemotherapy during gestation, as well as to assess the long-term effects on the exposed children. In this retrospective, cohort study, we reviewed the records of women aged 15 to 45 years with a diagnosis of malignancy or benign tumors with malignant behavior at three reference services in the State of Rio Grande do Sul, Brazil, from 1990 to 1997. All patients with a diagnosis of pregnancy at any time during the course of the disease were selected, regardless of whether or not they received specific medication. Fetal outcomes of 14 pregnancies with chemotherapy exposure were compared to that of 15 control pregnancies in which these drugs were not used. Long-term follow-up of the exposed children was carried out. Fisher's exact test was used to compare the groups. Continuous variables were compared by the Wilcoxon-Mann-Whitney test. We found an increased rate of prematurity (6/8 vs 2/10; RR: 3.75; CI: 1.02-13.8; P = 0.03) in the exposed group. There was a trend to an increased fetal death rate (4/12 vs 0/10; P = 0.07) in the group exposed to chemotherapy. No malformations were detected in any child, which can be related to our small sample size as well as to the fact that most exposures occurred after the first trimester of pregnancy. Other larger, controlled studies are needed to establish the actual risk related to cancer chemotherapy during pregnancy.

Are the beneficial cardiovascular effects of simvastatin and metformin also associated with a hormone-dependent mechanism improving insulin sensitivity?

In addition to lipid-lowering and cardiovascular protective actions, statins may have beneficial effects on insulin sensitivity. The objective of the present study was to evaluate the effect of simvastatin therapy on insulin resistance and on leptin, adiponectin, and C-reactive protein (CRP) levels, as compared to metformin, in overweight pre-diabetic subjects. Forty-one subjects with BMI >25 kg/m² and impaired fasting glucose or impaired glucose tolerance were randomized to take simvastatin, 20 mg/day (N = 20) or metformin, 1.7 g/day (N = 21) for 16 weeks. Blood samples for the determination of metabolic, hormonal, and inflammatory parameters were obtained at baseline and after each treatment. After metformin therapy, significant reductions in mean BMI and waist circumference were observed, and after simvastatin treatment LDL and triglyceride levels were significantly reduced. Insulin resistance determined by the homeostasis model assessment decreased only with metformin. Independently of the type of medication, a significant decrease in CRP levels was detected from baseline to the end of the study. CRP showed a mean reduction of 0.12 ± 0.04 mg/dL (P = 0.002) over time. No change in leptin or adiponectin levels was induced by any therapy. The data suggest that a low dose of simvastatin does not affect insulin resistance in overweight pre-diabetic subjects and has no effect on leptin or adiponectin levels. Further studies including a larger sample size, higher doses of statins, and a placebo control group are necessary to confirm the present data.