Differences In Treatment Protocols Research Articles

Spatial infection control in burn center organization: a burn center design experience for evidence-based architecture

PurposeThis study discusses that the necessary criteria and the solution approach taken to resolve the main spatial infection problems with a burn center design should be evaluated holistically to achieve spatial infection control in a burn center. The burn center design plays an important role in protecting severely burned patients from infection because the microbial flora of the hospital can affect the infection risk. In hospitals, sterilization and disinfection are the basic components of infection prevention; however, the prevention and control of infection for burn patients also requires the design of burn centers that adhere to a specific set of criteria that considers spatial infection control in addition to appropriate burn treatment methods and treatments. In this study, a burn facility converted from a burn unit into a burn center is introduced and the necessary design inputs for the transformation are discussed because there is no holistic study in the literature that delas with all the spaces that should be in a burn center and relations between spaces. This study aims to define the functional relations between each of the units and the spaces that change according to different sterilization demands in the burn center for ensuring spatial infection control. Furthermore, it aims to propose a method for ensuring continuity in the control of spatial infections.Design/methodology/approachThe burn care and health facilities guidelines are examined within the framework of spatial standards, together with a comprehensive literature review. The design method was based on the spread of microorganisms and the effect of human movement on space and spatial transitions in the burn center, according to all relevant literature reviews. To determine the extent to which the differences in treatment protocols of burn care guidelines were reflected in the space, interviews were conducted with burn facility officials. The plan–do–check–act (PDCA) method is also modeled to ensure the continuity of infection control in the burn center.FindingsThe burn center design findings are classified under three main headings, namely, location of the burn center in the hospital, spatial organization and physical features of the burn center and the air flowing system. The importance of the interactions among the criteria for spatial infection control has been revealed. Due to the physical space characteristics and air flow characteristics that change according to human movement and the way microorganisms spread, it has been seen that designing the air flow and architectural aspects together has an effective role in providing spatial infection control. Accordingly, a functional relation scheme for the center has been suggested. It is also proposed as a model to ensure the continuity of infection control in the burn center.Practical implicationsThis research presents spatial measures for infection control in burn centers for practitioners in health-care settings such as designers, engineers, doctors and nurses. The PDCA method also leads to continuity of infection control for hospital management.Originality/valueThis is the first study, to the best of the authors’ knowledge, to focus on developing the criteria for spatial infection control in burn center. Moreover, the aim is to create a function chart that encompasses the relationships between the units within the burn center design so that infection control can be coordinated spatially.

O-253 Impact of Covid-19 Infection on Male Seminal and Hormonal Parameters

Study questionTo assess possible effects of Covid-19 infection on male reproductive statusSummary answerCovid-19 negatively affect erectile function, spermatogenesis & improve over time, subclinical hypogonadism suspected due to decrease testosterone & increase LH, no enough evidence orchitis happen.What is known alreadyCovid-19 single-stranded enveloped RNA virus has two spike glycoproteins S & M. Molecular studies shows that Covid-19 infection rely on 2 factors; viral spikes binding to ACE2 receptors for entry, spikes binding to serine protease TMPRSS2 for viral protein priming. The key factors that mediate Covid-19 pathogenicity are highly expressed in urogenital organs. major symptoms of the COVID-19 pandemic are very high fever with a sudden surge in body temperature; fever can negatively affect male fertilityStudy design, size, durationprospective cohort study was conducted from August 2020 to May 2021. Fifty males survived COVID-19 infection (aged between 18-50 years) were recruited after approved diagnoses. Male having previous infertility issues, major systemic illness or with history of medication that could affect spermatogenesis or hormones were excluded. The tested variables were assessed sequentially on three occasions post-recovery in one month intervalParticipants/materials, setting, methodsfull history & medical examination, seminal fluid analysis abstinence (3-5) days samples collected by masturbation into sterile dry plastic dish placed in an incubator at 37C° to liquefy then do macro & microscopic examination according to WHO 5th ed. 5ml blood drown at day of SFA to perform (FSH, LH, Testosterone & Prolactin), scrotal ultrasound supine/standing position. Assessment repeated at 3 occasions with one month interval.Main results and the role of chanceSeventy-four percent of participants complained a variety degree of erectile dysfunction (mild, moderate and sever)post-COVID-19 infection. Mild and moderate erectile dysfunction was gradually improved after 30 and 60 days (p = 0.008, p = 0.002 respectively), the severity was reported to correlate with age. Seminal fluid parameters (sperm concentration, motility parameters and normal morphology) were at lowest value after one month post-recovery, afterwards improved gradually within time reaching the best value 3months post-recovery. Even though, progressive motility remained below normal value in all subjects, testosterone was lowest one month post-recovery; subsequently elevated progressively reaching the highest level after 3 months(p < 0.001). Whereas, LH was in highest level one month post-recovery, then declined during the second and third months (p < 0.001). Males (98%) had normal level of FSH during the study period. Highest level of prolactin was observed during the first and second months post-recovery; then all participants returned to normal levels 30 days post-recovery. Ultrasound examination revealed no testis swelling or tenderness was observed indicating no enough evidence of orchitisLimitations, reasons for cautionFurther investigations using larger population and longer following-up evaluation on reproductive functionality are required. Histopathological evaluation of testicular samples post-recovery is recommended.Additionally, infection severity and differences in treatment protocols used should be addressed. Psychological stress due to infection is another factor required to be includedWider implications of the findingsThis study can act as a starting point for investigating short and long term effects of COVID-19 infection on male fertility, which support Andrologists to set protocols for preventing the deterioration of reproductive situation and thus reduce future necessity for assisted reproductive technologiesTrial registration numbernot applicable

Clinical and molecular relevance of genetic variants in the non-coding transcriptome of patients with cytogenetically normal acute myeloid leukemia

Expression levels of long non-coding RNA (lncRNA) have been shown to associate with clinical outcome of patients with cytogenetically normal acute myeloid leukemia (CN-AML). However, the frequency and clinical significance of genetic variants in the nucleotide sequences of lncRNA in AML patients is unknown. Herein, we analyzed total RNA sequencing data of 377 younger adults (aged <60 years) with CN-AML, who were comprehensively characterized with regard to clinical outcome. We used available genomic databases and stringent filters to annotate genetic variants unequivocally located in the non-coding transcriptome of AML patients. We detected 981 variants, which are recurrently present in lncRNA that are expressed in leukemic blasts. Among these variants, we identified a cytosine-to-thymidine variant in the lncRNA RP5-1074L1.4 and a cytosine-to-thymidine variant in the lncRNA SNHG15, which independently associated with longer survival of CN-AML patients. The presence of the SNHG15 cytosine-to-thymidine variant was also found to associate with better outcome in an independent dataset of CN-AML patients, despite differences in treatment protocols and RNA sequencing techniques. In order to gain biological insights, we cloned and overexpressed both wild-type and variant versions of the SNHG15 lncRNA. In keeping with its negative prognostic impact, overexpression of the wild-type SNHG15 associated with higher proliferation rate of leukemic blasts when compared with the cytosine-to-thymidine variant. We conclude that recurrent genetic variants of lncRNA that are expressed in the leukemic blasts of CN-AML patients have prognostic and potential biological significance.

Clinical and molecular relevance of genetic variants in the non-coding transcriptome of patients with cytogenetically normal acute myeloid leukemia.

Expression levels of long non-coding RNA (lncRNA) have been shown to associate with clinical outcome of patients with cytogenetically normal acute myeloid leukemia (CN-AML). However, the frequency and clinical significance of genetic variants in the nucleotide sequences of lncRNA in AML patients is unknown. Herein, we analyzed total RNA sequencing data of 377 younger adults (aged <60 years) with CN-AML, who were comprehensively characterized with regard to clinical outcome. We used available genomic databases and stringent filters to annotate genetic variants unequivocally located in the non-coding transcriptome of AML patients. We detected 981 variants, which are recurrently present in lncRNA that are expressed in leukemic blasts. Among these variants, we identified a cytosine-to-thymidine variant in the lncRNA RP5-1074L1.4 and a cytosine-to-thymidine variant in the lncRNA SNHG15, which independently associated with longer survival of CN-AML patients. The presence of the SNHG15 cytosine-to-thymidine variant was also found to associate with better outcome in an independent dataset of CN-AML patients, despite differences in treatment protocols and RNA sequencing techniques. In order to gain biological insights, we cloned and overexpressed both wild-type and variant versions of the SNHG15 lncRNA. In keeping with its negative prognostic impact, overexpression of the wild-type SNHG15 associated with higher proliferation rate of leukemic blasts when compared with the cytosine-to-thymidine variant. We conclude that recurrent genetic variants of lncRNA that are expressed in the leukemic blasts of CN-AML patients have prognostic and potential biological significance.

Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI).

Monitoring of in vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI) is necessary to detect as well as reducethe incidence and severity of ovarian hyperstimulation syndrome (OHSS) whilst achieving the optimal ovarian response needed for assisted reproduction treatment. Traditional monitoring of ovarian hyperstimulation during in vitro fertilisation IVFand ICSItreatment has included transvaginal ultrasonography (TVUS) plus serum estradiol levels. The need for combined monitoring (using TVUS and serum estradiol) during ovarian stimulation in assisted reproduction is controversial. It has been suggested that combined monitoring is time consuming, expensive and inconvenient for women and that simplification of IVF and ICSI therapy by using TVUS only should be considered. OBJECTIVES: To assess the effect of monitoring controlled ovarian hyperstimulation (COH) in IVF and ICSI cycles in subfertile couples with TVUS only versus TVUS plus serum estradiol concentration, with respect to rates of live birth, pregnancy and OHSS. In this update conducted in March 2020, two review authorssearched the Cochrane Gynaecology and Fertility Group's Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, the National Research Register, and web-based trial registers. There was no language restriction applied. All references in the identified trials and background papers were checked and authors were contacted to identify relevant published and unpublished data. Only randomised controlled trials that compared monitoring with TVUS only versus TVUS plus serum estradiol concentrations in women undergoing COH for IVF and ICSI treatment were included. Two review authors (IK, AW) independently selected the studies, extracted data and assessed risk of bias. We resolved disagreements by discussion. Outcomes data were pooled and summary statistics were presented when appropriate. The quality of the evidence was rated using the GRADE methods. We did not identify any new eligible studies in this update in 2020. The evidence based on the six trials identified in 2014 remained unchanged. They included 781 women undergoing monitoring of COH with either TVUS alone or a combination of TVUS and serum estradiol concentration during IVF or ICSI treatment. None of the six studies reported our primary outcome of live birth rate. Two studies presented pregnancy rate per initiated cycle and per embryo transfer, respectively. Four studies reported pregnancy rate per woman with pooled data; we are uncertain of the effect ofmonitoring with TVUS only versus combined monitoring on clinical pregnancy rate per woman(odds ratio (OR) 1.10; 95% confidence interval (CI) 0.79 to 1.54; four studies; N = 617; I² = 5%; low quality evidence). This suggests in women with a 36% chance of clinical pregnancy using monitoring with TVUS plus serum estradiol, the clinical pregnancy rate using TVUS only would be between 31% and 46%. We are uncertain of any effectin the mean number of oocytes retrieved per woman (mean difference (MD) 0.32; 95% CI -0.60 to 1.24; five studies; N = 596; I² = 17%; low quality evidence). We are uncertain whethermonitoring with TVUS only versus combined monitoring affectedthe incidence of OHSS (OR 1.03; 95% CI 0.48 to 2.20; six studies; N = 781; I² = 0%; low quality evidence), suggesting that in women with a 4% chance of OHSS using monitoring with TVUS plus serum estradiol, the OHSS rate monitored by TVUS only would be between 2% and 8%. The cycle cancellation rate was similar in both arms of two studies (0/34 versus 1/31, 1/25 versus 1/25; OR 0.57; 95% CI 0.07 to 4.39; N = 115; I² = 0%; low quality evidence). The evidence was low quality for all comparisons. Limitations included imprecision and potential bias due to unclear randomisation methods, allocation concealment and blinding, as well as differences in treatment protocols. Quality assessment was hampered by the lack of methodological descriptions in several studies. This review update found no new randomised trials. Evidence from the six studies previously identified did not suggest that combined monitoring by TVUS and serum estradiol is more efficacious than monitoring by TVUS alone with regard to clinical pregnancy rates and the incidence of OHSS. The number of oocytes retrieved appeared similar for both monitoring protocols. The data suggest that both these monitoring methods are safe and reliable. However, these results should be interpreted with caution because the overall quality of the evidence was low. Results were compromised by imprecision and poor reporting of study methodology.The choice of one or the other method may depend upon the convenience of its use, and the associated costs.An economic evaluation of the costs involved with the two methods and the views of the women undergoing cycle monitoring would be welcome.

Subthreshold Diode Micropulse Laser Combined with Intravitreal Therapy for Macular Edema-A Systematized Review and Critical Approach.

Objective: intravitreal therapy for macular edema (ME) is a common clinical approach to treating most retinal vascular diseases; however, it generates high costs and requires multiple follow-up visits. Combining intravitreal anti–vascular endothelial growth factor (VEGF) or steroid therapy with subthreshold diode micropulse laser (SDM) application could potentially reduce the burden of numerous intravitreal injections. This review sought to explore whether this combination treatment is effective in the course of ME secondary to retinal vascular disease, and in particular, determine whether it is comparable or superior to intravitreal therapy alone. Materials and methods: the following terms and Boolean operators were used to search the PubMed literature database: subthreshold micropulse laser, subthreshold diode micropulse OR micropulse laser treatment AND anti-VEGF, anti-VEGF treatment, intravitreal steroids, OR combined therapy.This analysis included all studies discussing the combination of SDM and intravitreal anti-VEGF or steroid treatment. Results: the search revealed nine studies that met the inclusion criteria, including five comparing combined treatment and anti-VEGF treatment alone, four covering diabetic ME, and one covering ME secondary to branch retinal vein occlusion. All of these five studies suggested that combination therapy results in fewer intravitreal injections than anti-VEGF monotherapy with non-inferior functional and morphological outcomes. The remaining four studies report functional and morphological improvements after combined treatment; however, SDM alone was never superior to intravitreal-alone or combined treatment. There were substantial differences in treatment protocols and inclusion criteria between the studies. Conclusions: the available material was too scarce to provide a reliable assessment of the effects of combined therapy and its relation to intravitreal monotherapy in the treatment of ME secondary to retinal vascular disease. One assumption of note is that it is possible that SDM plus anti-VEGF might require fewer intravitreal injections than anti-VEGF monotherapy with equally good functional and morphological results. However, further randomized research is required to confirm this thesis.

Independent predictors of in-hospital and 1-year mortality rates in octogenarians with acute myocardial infarction.

Older age is known as a negative prognostic parameter in acute myocardial infarction (AMI) patients. In this study, we aimed to explore age-associated differences in treatment protocols, in-hospital and 1-year mortality. This cohort observational study included 277 consecutive AMI patients, separated into 2 groups according to whether their age was ≥80 years or not. We found that group I patients (aged ≥80 years) had a notably lower rate of percutaneous coronary intervention (PCI) performed (P < 0.0001) and a notably higher in-hospital death rate (P < 0.003). The multivariate logistic regression analysis found that three variables were independent predictors of in-hospital mortality: age ≥80 years (P < 0.0001), LVEF <40% (P < 0.0001), and Killip class ≥3 (P < 0.0001). The 1-year death rate was again significantly higher in group I patients (P < 0.001) and was independently predicted by the triple-vessel coronary artery disease (P = 0.004) and an LVEF <40% at admission (P = 0.001). The 1-year readmission rate was superior in group I (P < 0.01) and independently predicted by an age ≥80 years (P < 0.001), and an history of congestive heart failure (P < 0.0001) or permanent atrial fibrillation (P < 0.001). We concluded that patients aged ≥80 benefit less often from a PCI and have higher rates of in-hospital mortality, as well as of 1-year readmission and mortality rates.

Clinical characteristics and outcomes in acute myocardial infarction patients aged ≥65 years in Western Romania

Older age is known as a negative prognostic parameter in patients with acute myocardial infarction (AMI). In this study, we aimed to investigate age-related differences in treatment protocols, in-hospital and 1-year mortality. This retrospective observational single-center study enrolled consecutive AMI patients with an urgent percutaneous coronary intervention (PCI) as the main method of myocardial revascularization. The patients divided were divided by age into group I (≥65 years) and group II (<65 years). The primary endpoint was in-hospital mortality, the secondary endpoints were 1-year mortality and rehospitalization rates. Of the 522 admitted with AMI, 476 were enrolled in the study. The mean age was 67 ± 13 years; 62% were men. Group I patients had a significantly lower rate of performed PCI (65% vs. 79%, P < 0.001). 53 patients (12.3%) died during hospitalization, and this proportion was notably higher in the older population (20% vs. 6%, P < 0.0001). The cardiac causes of death were more frequent in group I patients (12% vs. 5.6%, P = 0.016). The multivariate logistic regression selected two variables as independent predictors for the risk of in-hospital death: age ≥65 years (P = 0.0170), and Killip class at admission (P < 0.0001). The 1-year mortality was 3.3%, slightly higher in group I patients (4.8% vs. 1.5%, P = 0.05). In conclusion, patients aged ≥65 years have three times higher in-hospital mortality, but similar 1-year mortality and readmission rates when compared with the younger patients. It is obvious that there is a large potential for improvement of the AMI care in this age group of patients.

DISTANT METASTASIS TO THE THYROID GLAND: CLINICAL REVIEW

Background. Metastasis to the thyroid from non-thyroid sites is an uncommon clinical presentation in oncology practice. Renal cell carcinoma is most common primary cancer, followed by breast cancer metastases, small cell lung carcinoma, colorectal cancer, malignant melanoma, malignancies of the gastrointestinal cancer. However, given that thyroid nodules are most common in women, and women with a history of urogenital malignancy are at higher risk of developing thyroid cancer, the possibility of metastatic thyroid cancer must be considered while evaluating a thyroid lump.&#x0D; Aim: to investigate patient management while finding distant metastases to the thyroid and identification of the most common complications.&#x0D; Material and methods. Identified reports of patients with thyroid metastasis were analyzed in the current literature review. Both clinical and autopsy series were included.&#x0D; Results. Metastases to the thyroid gland may be discovered at the time of diagnosis of the primary cancer, after preoperative investigation or due to histological examination of an operative specimen. In autopsy series, the most common primary site of metastatic thyroid tumors is lung cancer. In a clinical setting, renal cell carcinoma is the most common. Otherwise, when patients present with isolated metastases during follow-up of indolent disease, surgery might provide central neck control and even long-term cure. Prognosis may also vary according to the morphological features of primary cancer, time interval between initial diagnosis and metastasis and presence of extrathyroid invasion.&#x0D; Conclusions. Although the thyroid gland is highly vascularized, metastasis of malignant tumors to the thyroid is relatively rare and detection of metastasis shows a low frequency. A past history of malignant neoplasm should raise the index of suspicious of metastatic disease in patients with thyroid nodules with or without cervical lymphadenopathy. In such patients communication among clinicians treating the thyroid and the primary tumor is essential, as there are differences in treatment protocols and prognosis when compared to primary thyroid cancers. The setting is complex, and decisions must be made considering the localization of primary site, features of the primary tumor and comorbidities. Careful balancing of these factors influences effective patient management and long-term survival.

Long-Term Analysis of Secondary Bone Grafting in 79 Cleft Lip and Palate Patients By Cone Beam Commuted Tomography

Evaluating the outcomes of the alveolar bone grafting procedures in patients has been challenging for a multitude of reasons, including the limited number of patients, their demographic heterogeneity and complex anatomy, and differences in treatment protocols at various institutions. The purpose of this study was to use Cone Beam Computed Tomography (CBCT) analysis to evaluate the long-term radiographic outcomes of anterior iliac crest bone grafting (AICBG) on cleft lip patients who had an associated alveolar cleft with the aim to discover patient or clinical factors that influence the long-term radiographic success of the surgically repaired cleft sites. The records from 225 patients who underwent anterior iliac crest bone grafting by a single surgeon over 6 years at our institution were reviewed and 79 were selected after meeting criteria. Their most recent post-operative CBCT was analyzed using an adapted version of the assessment tools established by Suomalainen et al and Wangsrimongkol et al. The modifications allowed for quick and repeatable analysis, but were also strict in terms of defining favorable outcomes. Measurements were taken to evaluate the cleft sites vertically, horizontally and superiorly in terms of nasal support (for unilateral clefts only), then assigned corresponding scores of 0-4 to help determine radiographic success. The alveolar bone on the distal surface of the tooth mesial to the cleft was used for measurements. The sites were interpreted as poor (0 or 1), acceptable (2 or above), or favorable (3 or above). Similarly, clefts overall (vertical + horizontal) were poor (0-3), acceptable (4 or above) or favorable (5 or above). Statistical analysis was used to characterize patient demographics, subgroup comparisons, and to assess the association between specific factors and success. More specifically, univariate analyses and multivariate analyses were performed in effort to identify factors specifically predictive of favorable outcomes.

Low-Intensity Shockwave Therapy for Erectile Dysfunction.

Vasculogenic erectile dysfunction (ED) is one of the leading causes of male sexual dysfunction. In the past decade, multiple studies have examined the use of low-intensity extracorporeal shockwave therapy (Li-ESWT) for the treatment of ED. Investigate the efficacy of Li-ESWT for the treatment of ED. We reviewed the published literature, including randomized controlled trials (RCTs), meta-analyses, and select single-arm studies on the use of Li-ESWT for the treatment of ED. Changes in International Index of Erectile Function scores were evaluated in patients undergoing Li-ESWT. There is no consensus from RCTs on the efficacy of Li-ESWT for the treatment of ED. Published meta-analyses have shown significant improvement in International Index of Erectile Function-erectile function domain scores in men undergoing Li-ESWT, especially when compared to men receiving sham treatment. However, differences in treatment protocols limit the generalizability of these findings. Li-ESWT may be more beneficial in cases of mild ED or when combined with phosphodiesterase type 5 inhibitors in men with moderate to severe ED. The role of Li-ESWT in the treatment of non-vasculogenic ED remains poorly defined. Li-ESWT could be beneficial in specific sub-sets of men with vasculogenic ED. However, future RCTs should attempt to optimize treatment protocols and have more stringent inclusion criteria to confirm these findings. Rizk PJ, Krieger JR, Kohn TP, etal. Low-Intensity Shockwave Therapy for Erectile Dysfunction. Sex Med Rev 2018;6:624-630.

Cognitive behaviour therapy for chronic fatigue syndrome: Differences in treatment outcome between a tertiary treatment centre in the United Kingdom and the Netherlands

ObjectiveCognitive behaviour therapy (CBT) reduces fatigue and disability in chronic fatigue syndrome (CFS). However, outcomes vary between studies, possibly because of differences in patient characteristics, treatment protocols, diagnostic criteria and outcome measures. The objective was to compare outcomes after CBT in tertiary treatment centres in the Netherlands (NL) and the United Kingdom (UK), using different treatment protocols but identical outcome measures, while controlling for differences in patient characteristics and diagnostic criteria. MethodsConsecutively referred CFS patients who received CBT were included (NL: n=293, UK: n=163). Uncontrolled effect sizes for improvement in fatigue (Chalder Fatigue Questionnaire), physical functioning (SF-36 physical functioning subscale) and social functioning (Work and Social Adjustment Scale) were compared. Multiple regression analysis was used to examine whether patient differences explained outcome differences between centres. ResultsEffect sizes differed between centres for fatigue (Cohen's D NL=1.74, 95% CI=1.52–1.95; UK=0.99, CI=0.73–1.25), physical functioning (NL=0.99, CI=0.81–1.18; UK=0.33, CI=0.08–0.58) and social functioning (NL=1.47, CI=1.26–1.69; UK=0.61, CI=0.35–0.86). Patients in the UK had worse physical functioning at baseline and there were minor demographic differences. These could not explain differences in centre outcome. ConclusionEffectiveness of CBT differed between treatment centres. Differences in treatment protocols may explain this and should be investigated to help further improve outcomes.

MILD® is an Effective Treatment for Lumbar Spinal Stenosis with Neurogenic Claudication: MiDAS ENCORE Randomized Controlled Trial

Background: Lumbar spinal stenosis (LSS) is a common degenerative condition of the spine, which is a major cause of pain and functional disability for the elderly. Neurogenic claudication symptoms are a hallmark of LSS, where patients develop low back or leg pain when walking or standing that is relieved by sitting or lumbar flexion. The treatment of LSS generally begins with conservative management such as physical therapy, home exercise programs, and oral analgesics. Once these therapies fail, patients commonly move forward with interventional pain treatment options such as epidural steroid injections (ESIs) or MILD® as the next step. Objective: To assess improvement of function and reduction in pain for Medicare beneficiaries following treatment with MILD (treatment group) in LSS patients with neurogenic claudication and verified ligamentum flavum hypertrophy and to compare to a control group receiving ESIs. Study Design: Prospective, multi-center, randomized controlled clinical trial. Setting: Twenty-six US interventional pain management centers. Methods: Patients in this trial were randomized one to one into 2 study arms. A total of 302 patients were enrolled, with 149 randomized to MILD and 153 to the active control. Outcomes are assessed using the Oswestry Disability Index (ODI), Numeric Pain Rating Scale (NPRS) and Zurich Claudication Questionnaire (ZCQ). Primary efficacy is the proportion of ODI responders, tested for statistical superiority of the MILD group versus the ESI group. ODI responders are defined as patients achieving the validated Minimal Important Change (MIC) of ≥ 10 point improvement in ODI from baseline to follow-up. Similarly, secondary efficacy is the proportion of NPRS and ZCQ responders using validated MIC thresholds. Primary safety is the incidence of device- or procedure-related adverse events in each group. This report presents safety and efficacy results at 1-year follow-up. Outcomes at 2 years will be collected and reported for patients in the MILD group only. Results: At 1-year follow-up, ODI, NPRS, and all 3 ZCQ domains (Symptom Severity, Physical Function and Patient Satisfaction) demonstrated statistically significant superiority of MILD versus the active control. For primary efficacy, the 58.0% ODI responder rate in the MILD group was higher than the 27.1% responder rate in the epidural steroid group (P &lt; 0.001). The primary safety endpoint was achieved, demonstrating that there is no difference in safety between MILD and ESIs (P = 1.00). Limitations: There was a lack of patient blinding due to considerable differences in treatment protocols, and a potentially higher non-responder rate for both groups versus standard-of-care due to adjunctive pain therapy study restrictions. Study enrollment was not limited to patients that had never received ESI therapy. Conclusions: One-year results of this randomized controlled clinical trial demonstrate that MILD is statistically superior to ESIs in the treatment of LSS patients with neurogenic claudication and verified central stenosis due to ligamentum flavum hypertrophy. Primary and secondary efficacy outcome measures achieved statistical superiority in the MILD group compared to the control group. With 95% of patients in this study presenting with 5 or more LSS co-factors, it is important to note that patients with spinal co-morbidities also experienced statistically significant improved function that was durable through 1 year. Key words: MILD, minimally invasive lumbar decompression, interlaminar epidural steroid injections, ESI neurogenic claudication, ligamentum flavum, ENCORE, PILD, CED Study, LSS

MiDAS ENCORE: Randomized Controlled Clinical Trial Report of 6-Month Results

Patients suffering from neurogenic claudication due to lumbar spinal stenosis (LSS) often experience moderate to severe pain and significant functional disability. Neurogenic claudication results from progressive degenerative changes in the spine, and most often affects the elderly. Both the MILD® procedure and epidural steroid injections (ESIs) offer interventional pain treatment options for LSS patients experiencing neurogenic claudication refractory to more conservative therapies. MILD provides an alternative to ESIs via minimally invasive lumbar decompression. Prospective, multi-center, randomized controlled clinical trial. Twenty-six US interventional pain management centers. To compare patient outcomes following treatment with either MILD (treatment group) or ESIs (active control group) in LSS patients with neurogenic claudication and verified ligamentum flavum hypertrophy. This prospective, multi-center, randomized controlled clinical trial includes 2 study arms with a 1-to-1 randomization ratio. A total of 302 patients were enrolled, with 149 randomized to MILD and 153 to the active control. Six-month follow-up has been completed and is presented in this report. In addition, one year follow-up will be conducted for patients in both study arms, and supplementary 2 year outcome data will be collected for patients in the MILD group only. Outcomes are assessed using the Oswestry Disability Index (ODI), numeric pain rating scale (NPRS) and Zurich Claudication Questionnaire (ZCQ). Primary efficacy is the proportion of ODI responders, tested for statistical superiority of the MILD group versus the active control group. ODI responders are defined as patients achieving the validated Minimal Important Change (MIC) of =10 point improvement in ODI from baseline to follow-up. Similarly, secondary efficacy includes proportion of NPRS and ZCQ responders using validated MIC thresholds. Primary safety is the incidence of device or procedure-related adverse events in each group. At 6 months, all primary and secondary efficacy results provided statistically significant evidence that MILD is superior to the active control. For primary efficacy, the proportion of ODI responders in the MILD group (62.2%) was statistically significantly higher than for the epidural steroid group (35.7%) (P < 0.001). Further, all secondary efficacy parameters demonstrated statistical superiority of MILD versus the active control. The primary safety endpoint was achieved, demonstrating that there is no difference in safety between MILD and ESIs (P = 1.00). Limitations include lack of patient blinding due to considerable differences in treatment protocols, and a potentially higher non-responder rate for both groups versus standard-of-care due to study restrictions on adjunctive pain therapies. Six month follow-up data from this trial demonstrate that the MILD procedure is statistically superior to epidural steroids, a known active treatment for LSS patients with neurogenic claudication and verified central stenosis due to ligamentum flavum hypertrophy. The results of all primary and secondary efficacy outcome measures achieved statistically superior outcomes in the MILD group versus ESIs. Further, there were no statistically significant differences in the safety profile between study groups. This prospective, multi-center, randomized controlled clinical trial provides strong evidence of the effectiveness of MILD versus epidural steroids in this patient population. NCT02093520.

Monitoring of stimulated cycles in assisted reproduction (IVF and ICSI).

Traditional monitoring of ovarian hyperstimulation during in vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI) treatment has included transvaginal ultrasonography (TVUS) plus serum estradiol levels to ensure safe practice by reducing the incidence and severity of ovarian hyperstimulation syndrome (OHSS) whilst achieving the good ovarian response needed for assisted reproduction treatment. The need for combined monitoring (using TVUS and serum estradiol) during ovarian stimulation in assisted reproduction is controversial. It has been suggested that combined monitoring is time consuming, expensive and inconvenient for women and that simplification of IVF and ICSI therapy by using TVUS only should be considered. To assess the effect of monitoring controlled ovarian hyperstimulation (COH) in IVF and ICSI cycles in subfertile couples with TVUS only versus TVUS plus serum estradiol concentration, with respect to rates of live birth, pregnancy and OHSS. We searched the Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO, the National Research Register, and web-based trial registers such as Current Controlled Trials. The last search was conducted in May 2014. There was no language restriction applied. All references in the identified trials and background papers were checked and authors were contacted to identify relevant published and unpublished data. Only randomised controlled trials that compared monitoring with TVUS only versus TVUS plus serum estradiol concentrations in women undergoing COH for IVF and ICSI treatment were included. Three review authors independently selected the studies, extracted data and assessed risk of bias. They resolved disagreements by discussion with the rest of the authors. Outcomes data were pooled and summary statistics were presented when appropriate. The quality of the evidence was rated using the GRADE methods. With this update, four new studies were identified resulting in a total of six trials including 781 women undergoing monitoring of COH with either TVUS alone or a combination of TVUS and serum estradiol concentration during IVF or ICSI treatment.None of the six studies reported our primary outcome of live birth rate. Pooled data showed no evidence of a difference in clinical pregnancy rate per woman between monitoring with TVUS only and combined monitoring (odds ratio (OR) 1.10; 95% confidence interval (CI) 0.79 to 1.54; four studies; N = 617; I² = 5%; low quality evidence). This suggests that compared with women with a 34% chance of clinical pregnancy using monitoring with TVUS plus serum estradiol, the clinical pregnancy rate in women using TVUS only was between 29% and 44%.There was no evidence of a difference between the groups in the reported cases of OHSS (OR 1.03; 95% CI 0.48 to 2.20; six studies; N = 781; I² = 0%; low quality evidence), suggesting that compared with women with a 4% chance of OHSS using monitoring with TVUS plus serum estradiol, the OHSS rate in women monitored by TVUSS only was between 2% and 8%.There was no evidence of a difference between the groups in the mean number of oocytes retrieved pre woman (mean difference (MD) 0.32; 95% CI -0.60 to 1.24; five studies; N = 596; I² = 17%; low quality evidence).The evidence was low quality for all comparisons. Limitations included imprecision and potential bias due to unclear randomisation methods, allocation concealment and blinding, as well as differences in treatment protocols. Quality assessment was hampered by the lack of methodological descriptions in several studies. This review update found no evidence from randomised trials to suggest that combined monitoring by TVUS and serum estradiol is more efficacious than monitoring by TVUS alone with regard to clinical pregnancy rates and the incidence of OHSS. The number of oocytes retrieved appeared similar for both monitoring protocols. The data suggest that both these monitoring methods are safe and reliable. However, these results should be interpreted with caution because the overall quality of the evidence was low. Results were compromised by imprecision and poor reporting of study methodology. A combined monitoring protocol including both TVUS and serum estradiol may need to be retained as precautionary good clinical practice and as a confirmatory test in a subset of women to identify those at high risk of OHSS. An economic evaluation of the costs involved with the two methods and the views of the women undergoing cycle monitoring would be welcome.

Polymorphisms of the SLCO1B1 gene predict methotrexate‐related toxicity in childhood acute lymphoblastic leukemia

Methotrexate (MTX) is an important component of the therapy for childhood acute lymphoblastic leukemia. Treatment with high-dose MTX often causes toxicity, recommending a dose reduction and/or cessation of treatment. Polymorphisms in genes involved in the MTX metabolism have been associated with toxicity with controversial results. The discrepancies could be due to differences in treatment protocols among studies, small, or non-homogeneous populations or the use of different toxicity criteria. The aim of the present study was to analyze the possible correlation of polymorphisms of genes involved in the MTX metabolism with the toxicity during therapy with the well-established LAL/SHOP protocol. We analyzed 10 polymorphisms in seven genes (MTHFR, TS, SHMT1, RFC1, ABCB1, ABCG2, and SLCO1B1) from the MTX metabolism in 115 Spanish pediatric B-ALL patients, using MTX plasma concentration as an objective and quantifiable marker of toxicity. We confirmed the suitability of MTX plasma levels as a toxicity marker. We found a statistically significant association between MTX plasma concentration and the SLCO1B1 rs11045879 CC genotype (P = 0.030). The rs4149081 AA genotype, in the same gene, could also be an indicator for high-MTX plasma concentrations. We did not find any significant association in the other genetic polymorphisms analyzed. Identification of the rs4149081 and rs11045879 SLCO1B1 polymorphisms in children with ALL could be a useful tool for monitoring patients at risk of low-MTX clearance in order to avoid MTX-related toxicity.

Gamma Knife surgery for trigeminal neuralgia: a review of 450 consecutive cases

The success rates and side effects of Gamma Knife surgery (GKS) in patients with trigeminal neuralgia (TN) are not fully clear. A comparison of data across previous reports is hampered by differences in treatment protocols, lengths of follow-up, and outcome criteria. The purpose of this paper is to contribute to knowledge of the efficacy of GKS in TN by reviewing data in a large group of patients with this disorder, who were treated with a uniform treatment protocol and evaluated using a well-established pain scale and Kaplan-Meier analysis. The authors reviewed 450 treatments in 365 patents with medically refractory TN who were treated between June 2002 and October 2009 at the Gamma Knife Center Tilburg. In all patients 80 Gy was prescribed, with a single 4-mm isocenter located at the root entry zone (REZ). In 79 patients repeated GKS was performed using a uniform dose of 80 Gy, which was delivered, in a highly standardized manner, to a spot anterior to the position of the first treatment. Follow-up was obtained by reviewing the patients' medical records and conducting telephone interviews. Outcome was assessed using the Barrow Neurological Institute (BNI) pain scale and the BNI facial numbness scale. The median follow-up period was 28 months. In the idiopathic TN group, rates of adequate pain relief, defined as BNI Pain Scores I-IIIB, were 75%, 60%, and 58% at 1, 3, and 5 years, respectively. In the multiple sclerosis (MS)-related TN group the rates of adequate pain relief were 56%, 30%, and 20% at 1, 3, and 5 years, respectively. Repeated GKS was as successful as the first. An analysis of our treatment strategy of repeated GKS showed rates of adequate pain relief of 75% at 5 years in the idiopathic TN and 46% in the MS-related TN group. Somewhat bothersome numbness was reported by 6% of patients after the first treatment and by 24% after repeated GKS. Very bothersome numbness was reported in 0.5% after the first GKS and in 2% after the second treatment. In this study the authors analyzed outcomes of GKS in a large cohort of patients with TN; uniform treatment consisted of 80 Gy delivered to the REZ. The initial and long-term outcomes of pain relief and sensory dysfunction are comparable to recently published results at other institutions, where similar outcome criteria were used. These data should prove helpful to assist patients and clinicians in their TN management decisions.

High-quality embryos retain their implantation capability in overweight women

To assess the effect of obesity on implantation rate, pregnancy rate and course of pregnancy in young women undergoing IVF in whom only high-quality embryos were transferred, a cohort study included women attending the IVF unit in 2006-2007 with favourable parameters to achieve pregnancy (<38years, fewer than three IVF cycles, transfer of two high-quality embryos), grouped by body mass index (BMI). Of 230 women, 160 had a BMI ⩽25kg/m(2) (mean 21.6±2.2) and 73 had BMI >25kg/m(2) (mean 29.5±3.7). The overweight group had a higher consumption of gonadotrophins during stimulation. There were no between-group differences in treatment protocols, duration of gonadotrophin stimulation, maximal oestradiol concentrations, endometrial thickness and number of oocytes retrieved/fertilized, or in rates of pregnancy (51.3%, 52.1%), implantation (34.5%, 37.5%), multiple pregnancy, and abortion. Rate of gestational diabetes or pregnancy-induced hypertension was higher in the overweight group (23.3%, 8.2%; P=0.045). Within the overweight group, those with multiple pregnancies were at highest risk (31.3%, 6.9%; P=0.031). In conclusion, implantation and pregnancy rates are not compromised in overweight women when high-quality embryos are transferred. However, in overweight women, pregnancy complications remain high, mainly in those with multiple pregnancies.

Post-Remission MRD Kinetics in Children with Acute Lymphoblastic Leukaemia Receiving Augmented BFM Consolidation Compared with Other Regimens: Results of the Medical Research Council Trial UKALL2003.

The BFM group (Blood Nov 2007; 110a: 585) has reported that monitoring of postconsolidation MRD kinetics identifies a very high risk (MRD VHR) group of children with ALL, who might benefit from novel therapy and first remission allogeneic transplantation. We have compared the effect of consolidation regimen on post-remission MRD kinetics using a standardised quality controlled RQ-PCR assay of Ig and TCR patient specific rearrangements with a reproducible quantitative range of 10−4 in an attempt to identify a MRD VHR group, similar to that reported by the BFM.MRC UKALL 2003 is a randomised trial testing whether treatment can be stratified by MRD at weeks 4 and 11 in children and young adults (up to age 25 years) with ALL from the UK and Ireland. Initially, patients are stratified by NCI criteria, cytogenetics and early morphological marrow response to receive three (Regimen A) or four (Regimen B, additional daunorubicin) drug induction. Patients with MRD >10−4 at end of induction (EOI) (MRD High Risk) are randomised to continue previously assigned therapy (regimen A or B) or receive the more intensive regimen C. The regimens are of escalating intensity (A→C) and include either CCG modified BFM (A), standard BFM (B) or augmented BFM (C) consolidation, the latter containing pegylated-asparaginase (Peg-ASP; Oncospar, Medac UK, 1000 units/m2 i.m. days 16 and 44) and vincristine (1.5mg/m2 i.v. days 16, 23, 44, 51) in addition to standard BFM consolidation. Only patients with high risk cytogenetics or day 28 BM3 marrow are eligible for CR1 transplant.Of the134 patients with MRD > 10–4 at EOI, 101 were MRD negative, and 33 had detectable disease post-consolidation therapy (16 low MRD positive; <5×10−4, 17 high MRD positive; >5×10−4). Patients who received augmented BFM consolidation had more rapid clearance of MRD (Neg = 85%, low pos =7%, high pos =8%) than those who received CCG modified or standard BFM consolidation (Neg 65%, low pos =17%, high pos =17%) at week 11 – 15 of treatment (P=0.03 independent of age and white cell count). With median follow-up of 27 months, ten patients have relapsed, 7 in the negative group (3 year relapse Free Survival [RFS] 91.2% se=3.5) 1 in the low positive group (RFS 92.9% se = 6.9) and 2 in the high positive group (RFS 85.7% se = 9.4). The latter two were recipients of the lower intensity Regimens A (isolated CNS relapse) and B (isolated marrow relapse). The small numbers of post-consolidation high-positive patients do not permit us to identify a VHR group with a worse outcome than those patients with lower MRD levels. However, the early relapse risk (<15% at 3 years) for such patients appears to be much lower than that reported by the BFM group (>50% at 3 years). Differences in treatment protocol before and after consolidation may account for this disparity.In patients treated on the current UK childhood ALL protocol, we are unable to identify a VHR group on the basis of post-consolidation MRD. Augmented BFM consolidation obtains more rapid clearance of MRD than other regimens which, with longer follow-up, might be expected to translate into a better EFS.

Trends in Survival after Diagnosis with Hematologic Malignancy in Adolescence or Young Adulthood in the United States, 1981- 2005

Background: There are few population based studies of long-term survival of adolescents and young adults (AYA) with hematologic malignancies, mostly pertaining to patients diagnosed in the 1990s or earlier. Traditionally, survival in AYA with hematologic malignancies has been worse than survival for children with similar malignancies. Here, we use period analysis to obtain up-to-date information on survival expectations of AYA diagnosed with hematologic malignancies through the early 21st century.Methods: Period analysis was used to calculate 5- and 10-year relative survival for AYA aged 15–24 diagnosed with hematologic malignancies for five calendar periods from 1981–85 to 2001–2005, using data from the Surveillance, Epidemiology, and End Results (SEER) database. Results: Data from 9836 patients aged 15–24 included in the SEER database who were diagnosed with Hodgkin's lymphoma (HL), non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia (AML), and chronic myelocytic leukemia (CML) were analyzed. HL was the most common malignancy, accounting for about 50% of all hematologic maligancies in each calendar period examined.Survival strongly improved for each of the five hematologic malignancies. Increases in 10-year relative survival were as follows: HL, from 80.4 to 93.4%; NHL, from 55.6 to 76.2%; ALL, from 30.5 to 52.1%; AML, from 15.2 to 45.1%; CML, from 0 to 74.5% (p<0.0001 in all cases, see table). However, while survival improved steadily throughout the period examined for the lymphomas and CML, survival was stable during the late 1990s and early 21st century for the acute leukemias. Survival has not improved for AML since 1990–95 or for ALL since 1996–2000 (see table).Discussion: Survival expectations for AYA with hematologic malignancies have strongly improved since the 1980s. However, with the exception of HL, survival rates have not reached the levels observed for children diagnosed with the same malignancies. In particular, 10-year survival in children aged 10–14 with ALL was over 75% for the 2000–04 period1 compared to about 50% for AYA in 2001–05. Similarly, 10-year survival for children aged 0–14 diagnosed with acute non-lymphoblastic leukemia was about 60% in the 2000–04 period compared with less than 50% for AYA with AML in the 2001–05 period. Some caution must be used when comparing survival in AYA versus in children since survival estimates for children are for absolute survival, while those for AYA are for relative survival. However, relative survival in children and AYA is close to 100%, making the comparison relatively straightforward.Furthermore, survival estimates for the acute leukemias have not improved since the 1990s while survival for children continued to improve during the early 21st century. Reasons for the poorer survival observed may include differences in the biology of the malignancies, poorer compliance in AYA, differences in treatment protocols in children versus AYA, lower availability of clinical trials in AYA than in children, and low rates of health insurance in AYA patients, particularly after age 18. Further examination of the reasons for the poorer outcomes observed for AYA with acute leukemias may clarify this issue.1 Pulte D, Gondos A, Brenner H. Trends in 5- and 10-year survival after diagnosis with childhood hematologic malignancies in the United States, 1990–2004. Accepted JNCI 7/08.Table: 10-year relative survival 1981–85 to 2001–05 by hematologic malignancyDiagnosis1981– 851986–901991–951996–20002001–05Diff1p-val2PE3SE4PESEPESEPESEPESEHL80.41.582.61.486.91.288.91.293.41.0+13.0<0.0001NHL55.63.159.92.962.72.767.92.676.22.3+20.6<0.0001ALL30.54.135.84.042.13.951.63.952.13.7+21.6<0.0001AML15.23.422.34.143.64.739.54.045.14.0+29.9<0.0001CML0022.56.520.86.541.47.974.57.6+74.5<0.00011 Difference in survival, 1981–85 versus 2001–05.2 P-value for trend.3 Point estimate4 Standard error