Negative Treatment Effects Research Articles

Variable Influences of Water Availability and Rhizobacteria on the Growth of Schizachyrium scoparium (Little Bluestem) at Different Ages.

There is significant interest in understanding the role of plant growth-promoting rhizobacteria (PGPR) in alleviating different types of plant stress. Schizachyrium scoparium (little bluestem) is a moderately drought tolerant, perennial bunchgrass native to North America. The goal of this experiment was to evaluate whether the addition of a bacterial root isolate in the Pseudomonas genus promoted the growth of S. scoparium with changes in water availability. Pseudomonas are common rhizobacteria and have been shown to improve plant growth. It was hypothesized that plants inoculated with the PGPR strain would have greater growth and health, and would be less affected by shifts in water availability. Pseudomonas strains were isolated from the roots of native S. scoparium plants. After germination, S. scoparium seedlings were subjected to four treatment groups: low water; high water; low water with PGPR; and high water with PGPR. The experiment was run three times with plants at different starting ages; 14-, 28-, and 70-day-old plants. The effects of the water and PGPR treatments were variable between the experimental trials. There were no significant effects of the water treatments on plant growth in Trial 1 (14-day-old plants) or Trial 2 (28-day-old plants), however, there was a significant negative effect of the high watering treatment on the shoot length and biomass in Trial 3. High water availability was significantly associated with greater plant health in Trial 1, but appeared to reduce plant health in Trials 2 and 3. The PGPR treatment appeared to promote root growth and biomass in Trial 2, and was associated with greater plant health in all three trials, especially when paired with the low water treatment. Results from a permutational MANOVA indicate that plant growth was significantly different between the trials due to differences in the starting age of the plants and the duration of the experiments. Thus, methodological choices, such as plant life history stage and experiment duration, may affect the response of plants to PGPR in the rhizosphere. This research provides an insight into the interactions between PGPR and water availability on the growth and health of native plants.

SAT-272 A Phase 2 Comparison of a Stable Liquid Glucagon to Placebo for the Treatment of Congenital Hyperinsulinism

OBJECTIVE: A novel ready-to-use stable liquid Glucagon (CSIG; Xeris Pharmaceuticals) delivered continuously through a patch pump, was evaluated for the treatment of congenital hyperinsulinism (CHI). METHOD: This was a Phase 2, randomized, placebo-controlled, double-blind trial with open-label follow-up designed to assess the efficacy of CSIG to prevent hypoglycemia and lower intravenous glucose infusion rates (GIR), in subjects < 1 year of age with CHI. CSIG (5-20 μg/kg/hr) or matching placebo was delivered through a patch pump (Omnipod®; Insulet) as a continuous subcutaneous infusion, after the minimum GIR necessary to maintain euglycemia was established. Subjects did not receive other CHI-related medications. The study consisted of a baseline GIR stabilization phase (Period 1), a double-blind placebo-control parallel phase (Period 2), and an open-label CSIG single-arm active phase (Period 3). A positive clinical response was defined as a 33% reduction in GIR after 48 hours of study drug treatment. RESULT: A total of five subjects were screened for inclusion and enrolled in the study (intent-to-treat). The first enrolled subject’s medical history indicated a significant treatment resistance to reconstituted IV glucagon, in a previous CHI treatment session. The remaining 4 subjects were considered fully evaluable for clinical response (per-protocol). In Period 1, all subjects were able to obtain a stable GIR (range: 5.9 to 28.6 mg/kg/min). In Period 2, subjects assigned to blinded placebo had a GIR response that ranged from a 31% reduction to a 34% increase, while subjects assigned to blinded CSIG experienced GIR reductions of 53%-65%. In Period 3, the 4 evaluable subjects who received open label CSIG achieved reductions of 44%-66%, relative to baseline GIR. Total treatment time with CSIG in the study ranged from 4-72 hours. As a sole therapy during the blinded phase, treated subjects had a positive clinical response when administered CSIG treatment (2/2), compared to subjects given placebo (0/2). Open-label treatment resulted in a clinically meaningful GIR response in all evaluable subjects (4/4). There were no reported serious adverse events, no skin reactions, and no other negative treatment effects associated with study drug administration. Furthermore, there were no reports of occlusions, leakage or other pump issues in the study, or any instances of severe hypoglycemia during pump change-out. CONCLUSION: Glucose supplementation to prevent severe hypoglycemia and neurologic injury is critical in CHI. Reducing GIR while maintaining euglycemia reduces IV glucose-related complications in the management of CHI. As a sole therapy, CSIG achieved successful GIR reduction in a reliable manner, was safe and well tolerated. These results demonstrate that CSIG is a promising therapy in the treatment of CHI.

Physical Activity Promotion and Exercise in Pediatric Oncology - Structural Requirements and Financing Options Based on the Leipzig Movement Concept

Regular physical activity is an important requirement for the development and the general health in childhood and adolescence. However, patients during and after treatment for childhood cancer show high levels of physical inactivity, and only a marginal extent of physical activity. In addition to the negative side effects of treatment, this lack of physical activity and exertion has further negative implications for their health, such as decrease in physical performance and health related quality of life. In order to reduce these negative effects and provide access to regular physical activity for children and adolescents with cancer, childhood cancer patients should participate in targeted physical exercise therapy sessions at the treating hospital. Physical activity promotion for children and adolescents with cancer is an effective measure to enhance or preserve functional mobility, physical performance and health related quality of life. Both the behavioral level (person) and the setting (environment) should be taken into account for a sustainable implementation of physical activity promotion in the treatment of childhood cancer. The Leipzig Movement Concept promotes physical activity both during and after treatment for childhood cancer. On the basis of the modular concept, factors influencing physical activity in childhood cancer, alongside requirements for the successful and long-term implementation of physical activity programs and clinical exercise therapy are described. Furthermore financing options, based on Book V § 43 of the German Social Welfare Code, are presented.

Administration of Adipose Derived Mesenchymal Stem Cells and Platelet Lysate in Erectile Dysfunction: A Single Center Pilot Study.

Erectile dysfunction (ED) affects more than 30 million men; endothelial dysfunction plays a significant role in EDs pathogenesis. The aim of this study was to administer mesenchymal stem cells (MSC) derived from adipose tissue and platelet lysate (PL) into patients with erectile dysfunction. This pilot study enrolled eight patients with diagnosed ED. Patients enrolled were suffering from organic ED due to diabetes melitus, hypertension, hypercholesterolaemia, and Peyronie disease. The patients were distributed in 2 groups. Patients in group A received adipose derived mesenchymal stem cells (ADMSC) resuspended in PL while patients in group B received only PL. ADMSCs were isolated from patients’ adipose tissue and expanded. In addition, blood sampling was obtained from the patients in order to isolate platelet lysate. After the application of the above treatments, patients were evaluated with an International Index of Erectile Function (IIEF-5) questionnaire, penile triplex, and reported morning erections. After MSCs and PL administration, patients presented improved erectile function after 1 and 3 months of follow-up. A statistically significant difference was observed in the IIEF-5 score before and after administration of both treatments after the first month (p < 0.05) and the third month (p < 0.05). No statistically significant difference was observed in the IIEF-5 score between group A and B patients. All patients were characterized by improved penile triplex and increased morning erections. No severe adverse reactions were observed in any patient except a minor pain at the site of injection, which was in the limits of tolerability. The results of this study indicated the satisfactory use of MSCs and PL in ED. MSCs in combination with PL or PL alone seems to be very promising, especially without having the negative effects of the current therapeutic treatment.

Performance of the WHOQOL-BREF among Norwegian substance use disorder patients

BackgroundQuality of life (QoL) is an established outcome measure of substance use disorder treatment. The WHOQOL-BREF is the gold standard tool, but its appropriateness for particularly vulnerable patient populations must be further explored. This article examines the scaling qualities of the WHOQOL-BREF in a Norwegian substance use disorder population, and explores relationships with social and health variables.Methods107 participants in a larger national treatment study provided data during structured interviews. Item responses, responsiveness, and domain scaling qualities are reported. General linear models identified correlates of impaired QoL.ResultsThree out of four domains exhibited acceptable scaling qualities, while the social relationships domain had low internal validity. 59% of the variance in physical health QoL was explained in our model by the negative main or interaction effects of depression, unemployment, social isolation, smoking, residential treatment, and weight dissatisfaction. 52% of the variance in psychological health QoL was explained by depression and being single. Depression also had significant main effects in social relationships QoL (R2 = .27) and environment QoL (R2 = .39), and social isolation and exercise had further interaction effects in environment QoL.ConclusionsAfter one year in treatment, the impact of low social contact in reducing QoL, rather than specific substance use patterns, was striking. The social relationships domain is the shortest in the WHOQOL-BREF, yet social variables were important in other areas of QoL. Social support could benefit from more attention in treatment, as a lack of social support seems to be a strong risk factor for poor QoL in various domains. The WHOQOL-BREF exhibits otherwise satisfactory measurement characteristics and is an appropriate tool among this population.

Processing of Donor Human Milk: Update and Recommendations From the European Milk Bank Association (EMBA).

Background: A mother's own milk (MOM) is the gold standard for the feeding and nutrition of preterm and full term infants. When MOM is not available or there is not enough, donor human milk (DHM) should be used. Milk delivered to Human Milk Banks (HMBs) should be pasteurized to inactivate viral and bacterial agents. Currently, a pasteurization process at 62.5°C for 30 min (Holder pasteurization, HoP) is recommended in all international HMBs guidelines.State of the art: It is known that HoP affects some of the nutritional and biological components of human milk. Studies have demonstrated that temperature cycle in HoP is not always controlled or calibrated. A better check of these parameters in the pasteurizers on the market today may contribute to an improvement of the quality of HM, still maintaining some of the negative effects of the heat treatment of human milk. So, food industry, and dairy industry in particular, are evaluating innovative methodologies alternative to HoP to better preserve the nutritional and biological properties of fresh human milk, while assuring at least the same microbiological safety of HoP. The most studied processing techniques include High-Temperature-Short-Time (HTST) pasteurization, High Pressure Processing (HPP), and Ultraviolet-C (UV-C) irradiation. HTST is a thermal process in which milk is forced between plates or pipes that are heated on the outside by hot water at a temperature of 72°C for 5–15 s. HPP is a non-thermal processing method that can be applied to solid and liquid foods. This technology inactivates pathogenic microorganisms by applying a high hydrostatic pressure (usually 300–800 MPa) during short-term treatments (<5–10 min). UV irradiation utilizes short-wavelength ultraviolet radiation in the UV-C region (200–280 nm), which is harmful to microorganisms. It is effective in destroying the nucleic acids in these organisms, so that their DNA is disrupted by UV radiation.Aim: The aim of this paper is to present the EMBA recommendations on processing of HM, based on the most recent results obtained with these new technologies.Conclusions: Although research on the most promising technologies that will represent an alternative to HoP (HTST, HPP, UV-C) in the future is progressing, it is now important to recognize that the consistency and quality assurance of the pasteurizers on the market today represent a fundamental component that was previously lacking in the Holder approach.

The effects of perinatal bisphenol A exposure on thyroid hormone homeostasis and glucose metabolism in the prefrontal cortex and hippocampus of rats.

IntroductionBisphenol A (BPA) is an endocrine disruptor widely used to manufacture consumer goods. Although the thyroid hormone (TH) disrupting potential of BPA has been thought to be responsible for the neuropsychiatric deficits in the animals that experienced perinatal BPA exposure, the TH availability change at the level of specific brain structures has not been subject to systematic investigation.MethodsIn the present study the impacts of perinatal BPA exposure (0.1 mg/L in drinking water) spanning gestation and lactation on TH homeostasis in the prefrontal cortex (PFC) and hippocampus were assessed in male Sprague–Dawley rats at postnatal day 21 (PND21) and PND90. As TH regulates brain glucose metabolism at multiple levels，the effects of BPA treatment on glucose metabolism in the brain tissues were also assessed in adult rats.ResultsThe results showed heterogeneous changes in TH concentration induced by BPA between serum and brain tissues, additionally, in the BPA–treated pups, up–regulated expression of the TH transporter monocarboxylate 8 mRNA at PND21 and increased type 3 iodothyronine deiodinase mRNA expressions at PND21 and PND90 were observed. Meanwhile, decreased glucose metabolism was seen in the PFC and hippocampus, while deficits in locomotor activity, spatial memory and social behaviors occurred in BPA‐treated groups.ConclusionThese data support the concept that the developing brain possesses potent mechanisms to compensate for a small reduction in serum TH, such as serum hypothyrodism induced by BPA exposure, however, the long‐term negative effect of BPA treatment on TH homeostasis and glucose metabolism may be attributable to neuropsychiatric deficits after mature.

Negative Effects of Cyclic Palmitate Treatment on Glucose Responsiveness and Insulin Production in Mouse Insulinoma Min6 Cells Are Reversible.

Pancreatic β-cell failure is characterized by compromised insulin secretion in response to glucose, which ultimately results in hyperglycemia, the clinical hallmark of type 2 diabetes mellitus (T2DM). Acute exposure to plasma free fatty acids (FFAs) potentiates glucose stimulated insulin secretion (GSIS), while chronic exposure impairs GSIS, and the latter has been associated with the mechanism of β cell failure in obesity linked T2DM. By contrast, growth hormone (GH) signaling has been linked positively to GSIS in β cells. Numerous studies have examined chronic exposure of β cells to elevated FFAs both with in vivo cohorts and in vitro models. Little attention, however, has been given to the fluctuation of plasma FFA levels due to rhythmic effects that are affected by daily diet and fat intake. Mouse insulinoma Min6 cells were exposed to cyclic/daily palmitate treatment over 2 and 3 days to assess effects on GSIS. Cyclic/daily palmitate treatment with a period of recovery negatively affected GSIS in a dose-dependent manner. Removal of palmitate after two cycles/day resulted in reversal of the effect on GSIS, which was also reflected by relative gene expression involved in insulin biosynthesis (Ins1, Ins2, Pdx1, and MafA) and GSIS (glucose 2 transporter and glucokinase). Modest positive effects on GSIS and glucokinase transcript levels were also observed when Min6 cells were cotreated with human GH and palmitate. These observations indicate that like continuous palmitate treatment, cyclic exposure to palmitate can acutely impair GSIS over 48 and 72 h. However, they also suggest that the negative effects of short periods of exposure to FFAs on β cell function remain reversible.

The psychosocial health of children born after medically assisted reproduction: Evidence from the UK Millennium Cohort Study

The increasing number of children conceived through medically assisted reproduction (MAR, including IVF/ICSI, intrauterine insemination and ovulation induction) has led to concerns about the potential negative effects of fertility treatments on children’s psychosocial health. Some studies suggest that MAR children might be at higher risk of developing psychosocial problems when they enter adolescence. However, very few studies have examined the development of MAR children after childhood. Moreover, even though parental socio-economic characteristics are known to be highly correlated with children’s psychosocial development, most existing studies on the outcomes of MAR children did not take into account the selective characteristics of the couples who accessed fertility treatments. Using data from waves 1–6 of the UK Millennium Cohort Study, we compare the psychosocial health, as measured by the Strengths and Difficulties Questionnaire, of MAR children to that of naturally-conceived (NC) children, up to and including the age of 14. We control for a wide range of time-constant child and parental characteristics that might confound the association between MAR and the psychosocial health of children. Results from multilevel random intercept models that do not account for parental characteristics show that MAR children have a lower incidence of psychosocial problems than NC children. In models that control for parental characteristics, MAR children are found to have a higher incidence of psychosocial problems than NC children at age three, which suggests that high parental resource levels both explain the advantage of MAR children in unadjusted models, and mask the potentially adverse effects of MAR at young ages. However, in the fully adjusted models in which MAR children have more psychosocial problems at young age, the differences with respect to NC children decrease with age and become statistically and substantively negligible by end of follow-up at age 14. This result suggests that the use of MAR does not increase children’s risk of having psychosocial problems at the onset of adolescence.

Impaired Quality of Life After Radioiodine Therapy Compared to Antithyroid Drugs or Surgical Treatment for Graves' Hyperthyroidism: A Long-Term Follow-Up with the Thyroid-Related Patient-Reported Outcome Questionnaire and 36-Item Short Form Health Status Survey

Hyperthyroidism is known to have a significant impact on quality of life (QoL), at least in the short term. The purpose of the present study was to assess QoL in patients 6-10 years after treatment for Graves' disease (GD) with radioiodine (RAI) compared to those treated with thyroidectomy or antithyroid drugs (ATD) as assessed with both thyroid-specific Thyroid-Related Patient-Reported Outcome (ThyPRO) questionnaire and general (36-item Short Form Health Status) QoL survey. The study evaluated 1186 GD patients in a sub-cohort from an incidence study 2003-2005 who had been treated according to routine clinical practice at seven participating centers. Patients were included if they had returned the ThyPRO (n = 975) and/or the 36-item Short Form Health Status survey questionnaire (n = 964) and informed consent at follow-up. Scores from ThyPRO were compared to scores from a general population sample (n = 712) using multiple linear regression adjusting for age and sex as well as multiple testing. Treatment-related QoL outcome for ATD, RAI, and surgery were compared, including adjustment for the number of treatments received, sex, age, and comorbidity. Regardless of treatment modality, patients with GD had worse thyroid-related QoL 6-10 years after diagnosis compared to the general population. Patients treated with RAI had worse thyroid-related and general QoL than patients treated with ATD or thyroidectomy on the majority of QoL scales. Sensitivity analyses supported the relative negative comparative effects of RAI treatment on QoL in patients with hyperthyroidism. GD is associated with a lower QoL many years after treatment compared to the general population. In a previous small randomized controlled trial, no difference was found in patient satisfaction years after ATD, RAI, or surgery. Now, it is reported that in a large non-randomized cohort, patients who received RAI had adverse scores on ThyPRO and 36-item Short Form Health Status survey. These findings in a Swedish population are limited by comparison to normative data from Denmark, older age, and possibly a more prolonged course in those patients who received RAI, and a lack of information regarding thyroid status at the time of evaluation. The way RAI may adversely affect QoL is unknown, but since the results may be important for future considerations regarding treatment options for GD, they need to be substantiated in further studies.

Bone mineral density and vitamin D status in children with remission phase of steroid-sensitive nephrotic syndrome.

Children with idiopathic nephrotic syndrome are primarily treated with glucocorticoids (GCs), but long-term GC use can lead to undesired side effects. We investigated the bone mineral density (BMD) and 25-hydroxyvitamin D (25-OH D) levels in children with the remission phase of steroid-sensitive nephrotic syndrome (SSNS). This study included 32 patients with SSNS who had not received GC treatment in the last 6 months and a control group of 20 healthy children. Serum levels of calcium, phosphate, alkaline phosphatase, 25-(OH)D, and parathyroid hormone (PTH) were measured. BMD was determined in the lumbar spinal region using dual-energy X-ray absorptiometry (DEXA). Serum 25-(OH)D levels were lower in the SSNS patients than in the healthy children (P <0.05), with 22 patients (68.8%) having Z-scores <-1. The Z-scores were positively correlated with 25-(OH)D levels (r = 0.424, P <0.05). PTH levels were higher in patients with osteoporosis than in patients with Z-scores ≥-1 (P <0.05). Bone mineral content and BMD were positively correlated with the age of diagnosis (P <0.01). Receiver-operating characteristic curve analysis showed that the cutoff value of 25-(OH)D levels for predicting low BMD was 14.67 ng/mL with a sensitivity of 90% and a specificity of 64%. The area under the curve (AUC ± standard error) was 0.868 ± 0.064 (95% confidence interval: 0.742-0.994, P = 0.001). Decreased 25-(OH)D levels and the negative effects of long-term GC treatment on BMD persist in SSNS remission phase. Levels of 25-(OH)D <14.67 ng/mL could predict abnormal DEXA scans in children with SSNS remission phase.

Trabecular bone score and bone mineral density in patients with postsurgical hypoparathyroidism after total thyroidectomy for differentiated thyroid carcinoma

Although bone mineral density is reported to be increased in patients with postsurgical hypoparathyroidism (postsurgical HypoPT), the effect of HypoPT on trabecular bone score remains unknown. This study evaluated the long-term effects of HypoPT secondary to total thyroidectomy for differentiated thyroid cancer on trabecular bone score, bone mineral density, and bone turnover markers with a similar group of patients without HypoPT. Women with resected differentiated thyroid cancer and either postsurgical HypoPT (n = 25; 8 premenopausal and 17 postmenopausal) or euparathyroid function (n = 98; 14 premenopausal and 84 postmenopausal) were matched for age and body mass index. Patients received thyroid-stimulating hormone suppression during follow-up. The bone mineral density and trabecular bone score were analyzed using dual x-ray densitometry and Med-Imaps software at baseline (1-3 months postsurgery) and at the final study visit. Follow-up duration was similar in studied groups (median 10 years). Baseline bone mineral density and trabecular bone score were similar between HypoPT and non-HypoPT patients, regardless of menopausal status. At study end, postmenopausal HypoPT patients had greater bone mineral density versus the non-HypoPT patients at the lumbar spine, hip, and distal radius (P = .001), and a greater trabecular bone score (1.31 ± 0.09 vs 1.24 ± 0.12, P = .0184). Premenopausal patients with and without HypoPT had similar bone mineral density values at the final evaluation. The bone turnover markers (osteocalcin, bone-specific alkaline phosphatase, and β-crosslaps) were less in postmenopausal HypoPT patients, reflecting decreased bone turnover. Postmenopausal patients who underwent a total thyroidectomy for differentiated thyroid cancer with postsurgical HypoPT have greater trabecular bone score and bone mineral density compared with euparathyroid patients, suggesting that HypoPT protects against the negative effects of long-term thyroid-stimulating hormone suppression treatment on bone.

Antibacterial properties of combined non-thermal treatments based on bioactive edible coating, ozonation, and gamma irradiation on ready-to-eat frozen green peppers: evaluation of their freshness and sensory qualities

Antibacterial activity of an optimized formulation (edible coating), gaseous ozone, γ-irradiation treatments, and their combinations on ready-to-eat frozen pre-cut green peppers against Escherichia coli, Salmonella enteric, and Listeria innocua as foodborne pathogen bacteria, was assessed. In situ results showed that the antibacterial coating presented a large spectrum activity against Gram-positive and Gram-negative bacteria. In addition, ozone gaseous treatment at concentration of 10 ppm during 5 min allowed a total inhibition of E. coli after 4 days and a noticeable log reduction in Listeria and Salmonella during storage time. According to the obtained results, irradiation was the most effective technique to inhibit the growth of bacteria in alone or combined treatments. Different treatments had no significant impact on color parameters of pre-cut green peppers. Furthermore, no significant effect on chlorophyll content of pre-cut green peppers was also observed which is in accordance with the colorimetric results. Some statistical differences were noted in vitamin C content of pre-cut green peppers after coating treatment due to the additional ascorbic acid content in coating formulation, although no negative effect of treatments on the quality of pre-cut green peppers (total AA + DHA content) was observed. Furthermore, the sensory analysis confirmed that treatments had no significant effect (p > 0.05) on sensory attributes of peppers (color, odor, and taste).

Association between progression‐free survival and patients’ quality of life in cancer clinical trials

Quality of life outcomes provide essential information for patients and physicians in oncology care. However, the validity of progression-free survival (PFS) as a surrogate for quality of life, and the inclusion and reporting of quality of life endpoints in clinical trials, is unclear. We performed a retrospective study of phase III clinical trials of drugs for advanced or metastatic solid tumors published between 2010 and 2015. Correlation coefficient (r) and area under the ROC curve (AUC) for association between PFS and positive quality of life were evaluated. Of the 352 Phase 3 trials included, 190 (54%) included a quality of life endpoint, of which 23% did not report pre-specified quality of life outcomes; a total of 125,962 patients were enrolled in studies lacking, or not reporting, quality of life outcomes. Among the 147 trials that reported quality of life outcomes, 99 (67%) reported no effect, 38 (26%) reported a positive effect and 10 (7%) reported a negative effect of treatment on patients' global quality of life. The association between PFS and improvement in global quality of life was weak (r = 0.34; AUC = 0.72), as was the association between PFS and improvement in any domain of quality of life. In conclusion, PFS benefit was not strongly correlated with improvements in patients' quality of life, and, despite the palliative intent of treatments in the advanced/metastatic setting, the availability of quality of life data from clinical trials of cancer drugs was poor.

The moderating effect of functional social support on the association between unfair treatment and self-rated health: A study of the resilience of a community-based sample of Irish migrants in London

Despite research demonstrating the health promoting effects of social support, few studies have examined the moderating effect of functional social support on everyday unfair treatment for migrant communities. This study investigates whether functional social support moderates the association between unfair treatment and poor self-rated health for Irish migrants to the UK. Analysis of a purposive sample of Irish migrants in London was conducted ( n = 790). Interaction was analyzed via hierarchical logistic regression. Irish migrants who perceived unfair treatment were over three times more likely to report fair/poor health (odds ratio = 3.47, 95% confidence interval = 2.0–6.02). Higher levels of support in times of crisis were associated with reduced poor health. Higher levels of instrumental or practical support from neighbors moderated against the negative effect of unfair treatment on self-rated health (odds ratio = 0.29, 95% confidence interval = 0.08–0.96) and had a protective stabilizing effect. Instrumental support may have a protective-enhancing effect for female migrants. Results support other studies which indicate that instrumental support is most influential in the context of adversity. Interventions that promote neighborhood social capital may build resilience to unfair treatment for migrant communities in large cities.

The prognosis model of treatment efficiency for pulmonary tuberculosis in intensive phase of antituberculosis therapy

Search of ways to improve the treatment efficacy of pulmonary tuberculosis is the main task of phthisiology at the present stage of its development. According to our opinion, one of such way is the prediction of outcomes of anti-tuberculosis therapy intensive phase at its initial stage, which will allow to make correction of the treatment regimen opportunely.The aim of the study was to determine informative indicators for predicting the efficacy of treatment of patients with pulmonary tuberculosis in the intensive phase of anti-tuberculosis therapy. Based on the results, to create a model for predicting the efficacy of treatment for tuberculosis in the intensive phase for the correction of the treatment regimen.Materials and methods: 80 patients with active pulmonary tuberculosis, which were registered in categories 1 and 2, were examined. The patients were divided into groups: the first group of 30 patients with positive effect, the second group of 50 patients with delayed or negative treatment effect at the end of the intensive phase. The control group consisted of 20 healthy individuals. The sampling of diagnostic material was performed at the beginning of therapy. The results of clinical analysis of blood, as well as serum levels of neopterin, C-reactive protein, creatinine, ceruloplasmin, haptoglobin, seromukoid were evaluated. To achieve this goal, the nonparametric χ2 criterion and correspondent analysis were used.Results: There are 3 parameters with threshold values identified, which could be transformed into dichotomous indicators, of the 11 studied indices. These 3 variables are: the proportion of lymphocytes in the leukocyte formula, the content of neopterin, and seromucoids in the serum. Using correspondence analysis method, the formula to predict the result of the intensive phase from the initial values of the indicated variables was derived. Approbation of the formula showed high prediction accuracy (&gt;80 %) for both groups.Conclusions: With the help of the developed formula, which takes into account the initial indicators of serum neopterin and seromucoid and the proportion of lymphocytes in the leukocyte formula, the efficacy of treatment of pulmonary tuberculosis in the intensive phase of tuberculosis therapy can be predicted

Health-Related Quality of Life Outcomes in Newly Diagnosed Chronic Myeloid Leukemia Patients Treated with Dasatinib and Low Dose Pegylated Interferon

Background: Tyrosine kinase inhibitors (TKI) have revolutionized CML treatment but only a minority of patients are candidates to discontinue their TKI treatment, i.e. achieve treatment-free remission (TFR). Therefore, for the majority of patients TKI treatments are lifelong and it becomes critical to understand impact of therapy on patients' health-related quality of life (HRQoL).To obtain a maximal response for TFR, second generation TKIs like Dasatinib (DAS) induce deeper and faster responses than imatinib,and combination with pegylated forms of interferon-α2 have shown promising effect in several studies.Aims: To prospectively examine HRQoL outcomes in CML patients treated with DAS plus low-dose pegylated interferon- α2b (PegIFN).Methods: We have performed a single armed study (NordCML007) using DAS 100 mg OD from inclusion through the study including 40 patients, of these 31 were male. From month 3 (M3) low-dose PegIFN was added for one year until M15. We chose, based on previous experience, a dose of only 15 µg/week for 3 months and if tolerated, the dose was increased to 25 µg/week from M6. At M12, 80% of patients still took PegIFN and the mean administered dose was 18 µg/week. Side effects were moderate and fewer patients than expected developed pleural effusions in the combination period. Efficacy of the combination measured by BCR-ABL1 RQ-PCR was superior to the historical control DASISION, exemplified by M12 achievement of MMR, 46% vs 86% and MR4, 12% vs 46%.Before starting this project, concern was raised regarding tolerability of PegIFN. An acceptable tolerability of combined TKI+PegIFN is key for inclusion of combination treatment as standard of caretreatment. We did expect moderate negative effect of PegIFN treatment on HRQoL parameters. We assessed HRQoL with the well validated and widely used EORTC-QLQC30 questionnaire combined with the disease-specific CML module EORTC-CML24 at study inclusion and thereafter at 3, 6, 12 and at 18 months. Patient scoring was also compared with sex- and age-matched normative data.Results: Patients completed HRQOL questionnaires at baseline, M3 (DAS only), M6 and M12 (on combination) and finally at M18 (DAS only). About 80% of HRQOL forms were completed, withh 31-33 respondents at each time point. Most of these patients completed all forms. CML patients at baseline had statistically and clinically significant poorer scores for “Overall quality of life” (65 vs 77 points), “Role functioning” (72 vs 87 points), “Emotional functioning” (73 vs 82 points,) “Social functioning” (79 vs 91 points), “Fatigue” (32 vs 19 points) and “Insomnia” (25 vs 16 points) compared to matched normal populations (a difference of >5 pts is estimated to representa difference of clinically significance) During treatment, scoring of all modalities approached the normative (i.e. no statistical difference), except for “Fatigue”. Most of the improvement occurred during the first 3 months, i.e on DAS alone. Of note, HRQOL scores remained stable or improved further also with combination treatment, hence we observed no negative effect of low dose PegIFN treatment.Conclusions: These preliminary results suggest that low-dose PegIFN in combination with DAS has no detrimental effects on HRQOL over time. Rather we observed improvement with regard to CML disease specific HRQOL domains. The efficacy, safety and HRQoL data encourages further study of PegIFN in combination with 2nd generation TKIs. DisclosuresHjorth-Hansen:Bristol-Myers Squibb: Research Funding; Merck Sharp&Dohme: Research Funding. Mustjoki:Bristol-Myers Squibb: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Ariad: Research Funding; Celgene: Honoraria. Olsson-Strömberg:Merck Sharp and Dohme: Research Funding; Bristol-Myers-Squibb: Research Funding. Stentoft:Bristol-Myers Squibb: Research Funding; Merck Sharp&Dohme: Research Funding. Efficace:Orsenix: Consultancy; Incyte: Consultancy; Lundbeck: Research Funding; TEVA: Research Funding; AMGEN: Research Funding; Amgen: Consultancy; TEVA: Consultancy; Bristol Meyers Squibb: Consultancy; Seattle Genetics: Consultancy.

Optimizing bone wound healing using BMP2 with absorbable collagen sponge and Talymed nanofiber scaffold

BackgroundBone is a highly vascularized and resilient organ with innate healing abilities, however some bone injuries overwhelm these attributes and require intervention, such as bone tissue engineering strategies. Combining biomaterials and growth factors, such as bone morphogenetic protein 2 (BMP2), is one of the most commonly used tissue engineering strategies. However, use of BMP2 has been correlated with negative clinical outcomes including aberrant inflammatory response, poor quality bone, and ectopic bone.MethodsIn the present study, a novel poly-n-acetyl glucosamine (pGlcNAc, trade name Talymed) scaffold was utilized in addition to the commonly used acellular collagen sponge (ACS) BMP2 delivery system in a murine calvarial defect model to investigate whether the innate properties of Talymed can reduce the noted negative bone phenotypes associated with BMP2 treatment.ResultsComparison of murine calvarial defect healing between ACS with and without Talymed revealed that there was no measurable healing benefit for the combined treatment. Healing was most effective utilizing the traditional acellular collagen sponge with a reduced dose of BMP2.ConclusionsThe results of this investigation lead to the conclusion that excessive dosing of BMP2 may be responsible for the negative clinical side effects observed with this bone tissue engineering strategy. Rather than augmenting the currently used ACS BMP2 bone wound healing strategy with an additional anti-inflammatory scaffold, reducing the dose of BMP2 used in the traditional delivery system results in optimal healing without the published negative side effects of BMP2 treatment.

Clients’ Experiences With Internet-Based Psychological Treatments for Mental Disorders: Protocol for a Metasynthesis of Qualitative Studies

BackgroundGiven the rise of internet-based treatments as an effective therapeutic tool for psychological disorders, it is necessary to carry out research that examines clients’ experiences with this type of intervention. The qualitative methodology has been found to be useful for analyzing clients’ perceptions in terms of facilitators and barriers, acceptability, and negative effects of internet-based treatments. However, a lack of integration of these primary studies has prevented their findings from being applied to new research and in clinical practice.ObjectiveThe objective of this paper is to describe the protocol for a metasynthesis of qualitative studies exploring the experiences of clients who underwent an internet-based treatment.MethodsElliot and Timulak’s metasynthesis approach will be used to review and synthesize qualitative studies related to client experiences in terms of the barriers and facilitators they perceived when undergoing internet-based treatment. For each search string, the features in the Sample, Phenomenon of Interest, Design, Evaluation, Research type (SPIDER) tool will be considered. Electronic databases (PubMed, PsycINFO, and Web of Science) will be searched. Two independent reviewers will analyze the material in order to determine whether the eligibility criteria are fulfilled. Findings will make it possible to create a hierarchy of domains in terms of their relevance across all the primary studies. The data obtained from primary studies will be cross-analyzed using descriptive and interpretative procedures.ResultsThe search strategy is currently being conducted. First results are expected to be submitted for publication in 2019.ConclusionsWe will develop conceptual framework of the barriers and facilitators perceived by clients and propose their implications and recommendations for clinical practice, research, and training.Trial RegistrationPROSPERO CRD42018079894; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=79894 (Archived by WebCite at http://www.webcitation.org/73C6OtlS7).International Registered Report Identifier (IRRID)PRR1-10.2196/9722

Does Previous Failed Shockwave Lithotripsy Treatment Have an Influence on Retrograde Intrarenal Surgery Outcome?

Background: The prevalence of urolithiasis is nearly 20% and patients with urolithiasis constitute an essential part of the patients referred to the urology clinic. Many parameters should be considered for the management of renal stones and authors recommend extracorporeal shockwave lithotripsy (SWL), retrograde intrarenal surgery (RIRS), and percutaneous nephrolithotripsy (PNL), as treatment options. Among these techniques, SWL does not require general anesthesia, has 89% success rate for renal pelvic stones: 83% for upper caliceal stones, 84% for middle caliceal stones, and 68% for lower caliceal stones. In this study, we aimed to investigate whether the previously failed SWL treatment affects RIRS outcome. Methods: Patients who underwent RIRS for kidney stones between January 2012 and December 2017 in Diskapi Yildirim Beyazit Training and Research Hospital were reviewed retrospectively. Patients treated with primary RIRS (186 patients) were classified as Group 1. The outcomes of these patients were compared with those of 186 patients who underwent RIRS after failed SWL treatment using matched-pair analysis, and these patients were classified as Group 2. Results: The procedure success was defined as the sum of the stone-free and clinically insignificant residual fragments (CIRFs); final success rates were 90.3% and 91.9%, respectively. If we compare the final success rates, there was no statistically significant difference between both groups (P = .584). Conclusions: As a result, there is no negative effect of the previous unsuccessful SWL treatment on the RIRS success. Patients with CIRF should be followed up more carefully in terms of becoming symptomatic.