Mo Duration Research Articles

A phase II study of tinostamustine in patients (pts) with advanced solid tumours.

3021 Background: The novel multi-action alkylating deacetylase inhibitor tinostamustine improves drug access to DNA strands within cancer cells, breaks them and counteracts damage repair. Tinostamustine was well tolerated with signals of efficacy during dose escalation in pts with advanced solid tumours (Mita et al. Cancer Res 2019;79[13 Suppl]:CT023). Methods: This was an open-label Phase I/II trial of single agent tinostamustine in pts with advanced solid tumours (NCT03345485). The Phase II primary endpoint was objective response rate (ORR: complete response + partial response [PR]) and the rate of stable disease ≥4 mo duration following the recommended Phase II dose (RP2D; 80 mg/m2 over 1 h on Day 1 & 15 of each 4-wk treatment cycle). Secondary endpoints included progression-free (PFS) and overall survival (OS), and duration of response. Eligible pts were ≥18 y with life expectancy ≥3 mo, Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤2, histologically confirmed diagnosis of advanced/metastatic soft tissue sarcoma (STS), small-cell lung (SCLC), triple-negative breast (TNBC), ovarian (OvCa) or endometrial cancer, progression following ≥1 prior line of therapy, with no other standard therapy with proven clinical benefit available or recommended. Results: 36 pts were enrolled and evaluable for response; mean ± SD age 59.6 ± 11.2 y, 83.3% female, 80.6% Caucasian, all ECOG PS ≤1, median of 3 (range 1–9) lines of prior therapy. At data cut-off (30 November 2022) pts had received a median of 2 (range 1–8) cycles of tinostamustine. 19 pts (52.8%) discontinued treatment due to progressive disease. One pt with synovial sarcoma (STS cohort; n=10) and one pt with OvCa (n=12) achieved a PR. Overall, 14 pts (38.9%) had stable disease ≥4 mo (0/4 SCLC; 3/10 STS; 3/4 TNBC; 5/12 OvCa; 3/6 endometrial cancer); Clinical Benefit Rate, 44.4% (95% CI: 27.9%, 61.9%). Median PFS and OS for all treated pts were 2.2 mo (95% CI 1.8, 3.3 mo) and 5.5 mo (95% CI 4.1, 15.0 mo), respectively. All pts experienced ≥1 treatment-emergent adverse event (TEAE), with 56.7% of events considered related to tinostamustine. Serious tinostamustine-related AEs were reported in 30.6% of pts (13 haematological events); 10 (27.8%) pts discontinued treatment due to TEAEs (platelet count decreased: 5 events in 3 pts, including 2 Grade 3 and 1 Grade 4; all other events n=1). Two pts experienced fatal TEAEs; n=1 each of intra-abdominal haemorrhage (considered related to study drug), hypoxia/dyspnoea (not study drug related). Conclusions: Tinostamustine demonstrated modest signals of efficacy, with 2 pts achieving a PR, and manageable tolerability in pts with advanced solid tumours for whom no other standard therapy with proven clinical benefit was available or recommended. Further studies are needed to fully explore the benefits of tinostamustine in solid tumours. Clinical trial information: NCT03345485 .

IN SITU GEL FORMULATION OF POTASSIUM NITRATE: A NOVEL APPROACH TO TREAT DENTIN HYPERSENSITIVITY

Objective: The objective of the present study was to develop an in situ gelling formulation of potassium nitrate for the treatment of dentin hypersensitivity (DH). Methods: Formulation was optimized using 32 full factorial design, wherein the concentration of two gelling agents, poloxamer 407 and chitosan (90% deacetylation) were the independent variables and formulation viscosity and gelation time were dependent variables. The trial formulations were evaluated for pH, spreadability, drug content, adherence time, and in vitro drug release, apart from viscosity and gelation time. Results: The optimized formulation containing 22% of poloxamer 407 and 0.5 % of chitosan exhibited a gelation time of less than 150 s, a viscosity of about 2450 cps, and thermoreversible sol-gel transition behavior. The novel in situ gel showed a pH of 4.58, and spreadability as 5.55 g. cm/s and adherence time 4.3 h. The formulation could sustain the drug release over a period of 4 h and it was found to be 81.83±1.03%. Accelerated stability studies conducted over 3 mo duration ensured good physical and chemical stability of the formulation. Conclusion: The optimized in situ gel formulation of potassium nitrate in the sol state is expected to allow easy and site-specific administration on the sensitive tooth. Upon application, the temperature-sensitive sol would get converted to a gel that would improve its retention time on the sensitive tooth and extend the duration of therapeutic action by sustaining the drug release.

Abstract OT2-26-01: Open-label, multinational, multicenter, phase 3b/4 study of trastuzumab deruxtecan (T-DXd) in patients with or without baseline brain metastasis with previously treated advanced/metastatic human epidermal growth factor receptor 2-positive breast cancer (HER2+ BC): DESTINY-Breast12

Abstract Background: HER2+ BC is associated with a high incidence (up to 50%) of brain metastasis (BM) despite advances in treatment (Zimmer AS et al. Cancer Rep (Hoboken). 2020;e1274; Hurvitz SA et al. Clin Cancer Res. 2019;25:2433-2441). Although several agents have been studied in patients (pts) with HER2+ BC with BM, an unmet medical need remains due to the poor prognosis in this pt population. In DESTINY-Breast01, T-DXd demonstrated efficacy in the overall population and preliminary efficacy in a pt subgroup with stable BM, with a confirmed objective response rate (ORR) of 61.4% and an extracranial confirmed ORR by independent central review (ICR) of 58.3%, respectively, median progression-free survival (PFS) of 19.4 and 18.1 mo, respectively, and median duration of response (DOR) of 20.8 and 16.9 mo, respectively (Modi S et al. Cancer Res. 2021. Abst PD3-06; Jerusalem G et al. Ann Oncol. 2020. Abst 138O). Here we describe a trial evaluating T-DXd in pts ± BM with previously treated advanced/metastatic HER2+ BC. Trial design: DESTINY-Breast12 (NCT04739761) is an open-label, multicenter, international (86 sites in the US, Europe, Australia, and Japan), phase 3b/4 study assessing the efficacy and safety of T-DXd 5.4 mg/kg q3w in pts with HER2+ BC ± BM. Pts will be enrolled in 1 of 2 cohorts (250 pts each): cohort 1 (−BM at baseline) and cohort 2 (+BM at baseline). Pts must have previously treated advanced/metastatic HER2+ BC that has progressed with ≥1 prior anti-HER2-based regimen and received ≤2 lines of therapy in the metastatic setting (excludes pts with prior tucatinib). Pts with BM must have untreated BM not needing immediate local therapy or previously treated stable or progressing BM. Primary endpoints are ORR in cohort 1 and PFS in cohort 2 (both by RECIST version 1.1 per ICR). Secondary endpoints in both cohorts are OS, DOR, time to progression, duration of subsequent therapy, PFS2, safety, and changes in symptoms, functioning, and QOL. Incidence of new symptomatic CNS metastasis (CNSM) is a secondary endpoint in cohort 1, and ORR and CNS ORR by RECIST 1.1 per ICR, CNS PFS and DOR, and time to new CNSM are secondary endpoints in cohort 2. Citation Format: Nancy U Lin, Eva Ciruelos, Guy Jerusalem, Volkmar Müller, Naoki Niikura, Giuseppe Viale, Emma Oscroft, Shawn Anand, Graham Walker, Nadia Harbeck. Open-label, multinational, multicenter, phase 3b/4 study of trastuzumab deruxtecan (T-DXd) in patients with or without baseline brain metastasis with previously treated advanced/metastatic human epidermal growth factor receptor 2-positive breast cancer (HER2+ BC): DESTINY-Breast12 [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-26-01.

Kaposiform Hemangioendothelioma with Kasabach–Merritt Phenomenon

A 3-y-3-mo old male child presented with massive hypertrophy and bluish-purple discoloration of the left upper limb and adjacent chest wall of 3 mo duration. There was no h/o fever, weight loss, painful large joint swelling, or any bleeding manifestations. He had spindle like nonprogressive, painless swelling of all fingers of the left hand since infancy. The child was moribund with microangiopathic hemolytic anemia, thrombocytopenia, and consumptive coagulopathy without sepsis. He received multiple transfusions of fresh frozen plasma (FFP), platelets, and packed RBC. Paradoxical worsening of symptoms with platelet transfusions and radiological evidences led to the diagnosis of a very rare congenital multifocal vascular tumor, kaposiform hemangioendothelioma (KHE) with Kasabach-Merritt phenomenon (KMP). The index case of KHE was multifocal with cutaneous lesions, osteolytic bony lesions of all phalanx and metacarpals of the left hand, and intrathoracic extension. It was successfully managed with a combination of steroid, vincristine and sirolimus.

Phase II study of SM-88 in Ewing's and other sarcomas.

e23505 Background: Sarcomas are rare heterogeneous malignancies. Once recurrent, cure is uncommon. SM-88 (racemetyrosine) is an amino acid analogue with no known cross resistance to typical sarcoma regimens. Based on previous anecdotal experience in Ewing’s (EWS) we initiated a Phase 2 trial (HopES) in EWS and other sarcomas (Ss) after >1 prior systemic therapy. We now report preliminary data after having met prespecified continuation criteria. Methods: Open label prospective trial in 2 separate cohorts (EWS and Ss) of oral SM-88 used with MPS conditioning agents (SM-88 920 mg, methoxsalen 10 mg, phenytoin 50 mg, sirolimus 0.5 mg) all daily until progression. Results: As of Feb 5 2021, 10 pts with incurable sarcomas were enrolled; 4 had high risk but stable EWS. Average age 43.9 yrs (13–77); 70% white; 20% female. Median number of prior regimens 4 (1–9); 70% received prior RT; 50% prior surgery. Median time from initial diagnosis 39.5 months with 50% T2 (40% unknown), 30% M1 (30% unknown). Prespecified futility stopping was exceeded (i.e., >1 of first 5 subjects/cohort) upon achieving clinical benefit in each. Stable disease was achieved in 75.0% (6/8 with available data). Time on treatment (TTx) exceeded last known TTx in 80% (95% CI 44.4–97.5). Median SM-88 TTx was 4.9 vs 2.9 mo for prior TTx (logrank HR 0.53; p=0.12). One EWS subject had unresectable disease that became resectable, was completely resected, and remained disease-free for ≥ 6 months. Prior to SM-88, longest TTx was 12 mo (on IT*) and shortest TTx 1 mo (on IEV*) vs SM-88 TTx of 11.9 mo. An angiosarcoma subject had a 21% reduction in the sum of all target lesions and exceeded all prior TTx (including 8 mo on Ap/N* with 12+ mo duration of treatment of SM-88). There were no serious drug-related AEs. ECOG performance remained stable for all. Conclusions: SM-88 has exceeded pre-specified futility in both cohorts (EWS maintenance and Ss salvage). HopES continues to enroll toward the planned total of 12 subjects to more precisely define its benefit in this ultra-orphan, extremely recalcitrant disease. This trial now confirms the previously reported clinical utility of oral SM-88 in EWS and other high-risk sarcomas. Based on durable response (>6mo), SD and prolonged TTx, SM-88 warrants additional investigation in this setting. Clinical trial information: NCT03778996. [Table: see text]

Total parathyroidectomy with forearm autotransplantation in secondary hyperparathyroidism patients: analysis of muscle, subcutaneous and muscle\u2009+\u2009subcutaneous method

BackgroundForearm autotransplantation after parathyroidectomy has turned into the standard method for secondary hyperparathyroidism (SHPT) treatment in chronic kidney disease patients. Our study aimed to explore the effects of three methods including muscle, subcutaneous and muscle + subcutaneous transplant methods on SHPT.MethodsSeventy five SHPT patients were enrolled and assigned into the muscle + subcutaneous (M + S) (n = 26), muscle (M) (n = 35), and subcutaneous (S) (n = 14) groups. The operation efficacy evaluation included preoperative and postoperative biological characteristics such as parathyroid hormone (PTH), serum phosphorus, serum calcium and alkaline phosphatase (ALP). The data were recorded from pre-operation time point to 1, 2, 3, 6, 12, 18, 24 month (mo) postoperation periods. After operation, short-form health survey (SF-36) scores was made for life quality identification at 1, 2, 3, 6, 12, 24 time points. Symptoms about SHPT including bone pain, fracture, pruritus, and coronary artery calcification were followed-up based on the scale.ResultsCompared with the preoperative record, all the M + S, M, and S groups showed postoperative decreased levels of PTH, serum phosphorus, serum calcium, calcium-phosphorus. In M + S group, the PTH and serum calcium level kept more steady compared with the M and S groups during a 24 mo duration observation. After this, a SF-36 score scale which represents the life quality show M + S group got more scores at 3, 6, 12, 18 and 24 mo points. At last, the incidence of SHPT associated symptoms including Bone pain, Fracture, Pruritus, and Coronary artery calcification in M + S group were decreased compared with M and S groups at 1, 3, 6, 12 and 24 mo post-operation time points.ConclusionM + S seems to be an efficient method for medical treatment of SHPT patients in the control of PTH and serum calcium. This mixed transplant strategy improves the biochemical characterizes compared with M and S groups in SHPT patients. Furthermore, the M + S method make beneficial on clinical outcomes and life quality of patients.

Efficacy of telemedicine on glycaemic control in patients with type 2 diabetes: A meta-analysis.

BACKGROUNDTelemedicine is defined as the delivery of health services via remote communication and technology. It is a convenient and cost-effective method of intervention, which has shown to be successful in improving glyceamic control for type 2 diabetes patients. The utility of a successful diabetes intervention is vital to reduce disease complications, hospital admissions and associated economic costs.AIMTo evaluate the effects of telemedicine interventions on hemoglobin A1c (HbA1c), systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), post-prandial glucose (PPG), fasting plasma glucose (FPG), weight, cholesterol, mental and physical quality of life (QoL) in patients with type 2 diabetes. The secondary aim of this study is to determine the effect of the following subgroups on HbA1c post-telemedicine intervention; telemedicine characteristics, patient characteristics and self-care outcomes.METHODSPubMed Central, Cochrane Library, Embase and Scopus databases were searched from inception until 18th of June 2020. The quality of the 43 included studies were assessed using the PEDro scale, and the random effects model was used to estimate outcomes and I2 for heterogeneity testing. The mean difference and standard deviation data were extracted for analysis.RESULTSWe found a significant reduction in HbA1c [-0.486%; 95% confidence interval (CI) -0.561 to -0.410, P < 0.001], DBP (-0.875 mmHg; 95%CI -1.429 to -0.321, P < 0.01), PPG (-1.458 mmol/L; 95%CI -2.648 to -0.268, P < 0.01), FPG (-0.577 mmol/L; 95%CI -0.710 to -0.443, P < 0.001), weight (-0.243 kg; 95%CI -0.442 to -0.045, P < 0.05), BMI (-0.304; 95%CI -0.563 to -0.045, P < 0.05), mental QoL (2.210; 95%CI 0.053 to 4.367, P < 0.05) and physical QoL (-1.312; 95%CI 0.545 to 2.080, P < 0.001) for patients following telemedicine interventions in comparison to control groups. The results of the meta-analysis did not show any significant reductions in SBP and cholesterol in the telemedicine interventions compared to the control groups. The telemedicine characteristic subgroup analysis revealed that clinical treatment models of intervention, as well as those involving telemonitoring, and those provided via modes of videoconference or interactive telephone had the greatest effect on HbA1c reduction. In addition, interventions delivered at a less than weekly frequency, as well as those given for a duration of 6 mo, and those lead by allied health resulted in better HbA1c outcomes. Furthermore, interventions with a focus on biomedical parameters, as well as those with an engagement level > 70% and those with a drop-out rate of 10%-19.9% showed greatest HbA1c reduction. The patient characteristics investigation reported that Hispanic patients with T2DM had a greater HbA1c reduction post telemedicine intervention. For self-care outcomes, telemedicine interventions that resulted in higher post-intervention glucose monitoring and self-efficacy were shown to have better HbA1c reduction.CONCLUSIONThe findings indicate that telemedicine is effective for improving HbA1c and thus, glycemic control in patients with type 2 diabetes. In addition, telemedicine interventions were also found to significantly improved other health outcomes as well as QoL scores. The results of the subgroup analysis emphasized that interventions in the form of telemonitoring, via a clinical treatment model and with a focus on biomedical parameters, delivered at a less than weekly frequency and 6 mo duration would have the largest effect on HbA1c reduction. This is in addition to being led by allied health, through modes such as video conference and interactive telephone, with an intervention engagement level > 70% and a drop-out rate between 10%-19.9%. Due to the high heterogeneity of included studies and limitations, further studies with a larger sample size is needed to confirm our findings.

Long-term outcomes of a prospective single institution study with multiagent chemotherapy and stereotactic body radiation therapy in locally advanced or recurrent pancreatic adenocarcinoma.

440 Background: We previously reported a multi-center study in which gemcitabine and stereotactic body radiation therapy (SBRT) were shown to be safe with outcomes comparable to chemoradiation in locally advanced pancreatic cancer (LAPC). This prospective clinical trial was developed to evaluate the efficacy of adding SBRT to multi-agent chemotherapy in LAPC. Herein, we report on the long-term survival outcomes. Methods: From 2012 to 2015, 48 patients (pts) were prospectively enrolled after multidisciplinary evaluation at a single high-volume pancreatic center. Pts received multi-agent chemotherapy (CTX) with modified mFOLFIRINOX (mFFX) or gemcitabine/abraxane followed by 5 fractions of SBRT (median 33 Gy; range, 25-33 Gy). At the time of fiducial placement, biopsies were obtained and DNA extracted for targeted sequencing using MSK-IMPACT. Kaplan-Meier curves were generated to compare survival outcomes by sub-group. Multivariate analysis (MVA) was performed to identify factors prognostic for survival. Results: 44 pts (91.7%) had LAPC disease and 4 (8.3%) had locally recurrent disease. The median follow-up interval was 21.5 months (mo) from diagnosis. CTX consisted of mFFX in 25 pts (52.1%) with 24 pts (50.0%) receiving therapy for a duration ≥4 mo. Of 44 pts with LAPC, 15 (34.1%) were surgically explored, and 11 (73.3%) achieved a margin-negative resection. From diagnosis and after completion of SBRT, respectively, the median overall survival (OS) was 21.6 (95% CI 16-29.7 mo) and 14.6 mo (95% CI: 11.6-23.0 mo); median progression free survival (PFS) was 13.2 (95% CI 11.9-18.1mo) and 6.4 mo (95% CI: 5-12.7 mo); median local PFS (LPFS) was 23.9 (95% CI 18.9-56.9 mo) and 15.8 mo (95% CI: 12.9-27.6 mo); and median distant metastasis free survival (DMFS) was 18.4 (95% CI 12.6-29.3 mo) and 8.5 mo (95% CI: 6.3-17.2 mo). Resected pts experienced better DMFS at 1-year (78% vs. 34%, p= 0.004) with an improved trend for 1-year OS (73% vs. 52%, p= 0.331). If CTX duration was ≥4 mo, 1-year OS (75% vs. 42%, p= 0.018), PFS (50% vs. 21%, p= 0.022), and DMFS (72% vs. 29%, p= 0.031) were significantly improved. In 44 LAPC pts, MVA confirmed ≥4 mo duration of CTX was associated with OS, PFS, and DMFS. Surgical resection was associated with improved DMFS, and CA19-9 level prior to SBRT was associated with PFS and LPFS. The most common mutations detected from biopsy specimens were KRAS (64.3%) , TP53 (50%), and SMAD4 (16.7%). Conclusions: In a prospective trial of pts with LAPC receiving multiagent CTX and SBRT, clinical outcomes were improved with longer durations of CT ( &gt; 4 mo). A high proportion of LAPC pts underwent margin negative resection with favorable outcomes. Future studies should focus on which pts are most likely to benefit from SBRT and surgery following multiagent CTX. In pts who cannot undergo resection, escalated doses of SBRT may be indicated. Clinical trial information: NCT01781728.

183. Operation is no better than nonoperative care in improving pain and disability in chronic low back pain: long term results of randomized controlled trials of western China

BACKGROUND CONTEXT Identifying subgroups of people who attain a nonoperative care or operation benefit from particular treatments has been identified as a high research priority for low back disorders. PURPOSE To identify characteristics related to nonoperative care or operation treatment effects in people with low back disorders undergoing either individualized physical therapy or operation. STUDY DESIGN/SETTING A prepared effect modifier analysis of the Specific Treatment of Problems of the Spine randomized controlled trial. PATIENT SAMPLE The trial involved 781 participants with low back pain and/or referred leg pain (≥6 wk, ≤6 mo duration) OUTCOME MEASURES Participants were randomly allocated to receive either an operation or two sessions of individualized physical therapy targeting pathoanatomical, psychosocial and neurophysiological factors. Univariate and multivariate linear mixed models determined the interaction between treatment group and potential effect modifiers (defined a priori) for the primary outcomes of back pain, leg pain (0–10 Numeric Rating Scale) and activity limitation (Oswestry Disability Index) over a 60-week follow-up. METHODS The trial involved 781 participants with low back pain and/or referred leg pain (≥6 wk, ≤6 mo duration), who satisfied criteria to be classified into five subgroups (with 487 participants classified into three subgroups relating to disc-related disorders, and 79 classified into the zygomorphous joint dysfunction subgroup), 215 patients were operated on. Participants were randomly allocated to receive either an operation or 2 sessions of individualized physical therapy targeting pathoanatomical, psychosocial, and neurophysiological factors. Univariate and multivariate linear mixed models determined the interaction between treatment group and potential effect modifiers (defined a priori) for the primary outcomes of back pain, leg pain (0–10 Numeric Rating Scale) and activity limitation (Oswestry Disability Index) over a 60-week follow-up. RESULTS Participants with higher levels of back pain, higher retro scores (indicative of higher risk of persistent pain) or longer duration of symptoms derived the largest benefits from individualized physical therapy relative to advice. Poorer coping also predicted larger benefits from individualized physical therapy in the university analysis.Operation is no better than non operative care in improving pain and disability in chronic low back pain CONCLUSIONS These findings suggest that people with low back disorders could be preferentially targeted for individualized physical therapy rather than an operation if they have higher back pain levels, longer duration of symptoms, or higher retro score. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Macrophyte-derived detritus in shallow coastal waters contributes to suspended particulate organic matter and increases growth rates of Mytilus edulis

Benthic suspension feeders, such as bivalves, potentially have several different food sources, including plankton and resuspended detritus of benthic origin. We hypothesised that suspension feeders are likely to feed on detritus if it is present. This inference would be further strengthened if there was a correlation between δ13C of suspension feeder tissue and δ13C of particulate organic matter (POM). Since detritus is characterised by high particulate organic matter (POC):chl a ratios, we would also predict a positive correlation between POM δ13C and POC:chl a. We hypothesised that increasing depth and greater distance from shore would produce a greater nutritional reliance by experimentally transplanted blue mussels Mytilus edulis on plankton rather than macrophyte-derived detritus. After deployments of 3 mo duration in 2 different years at depths from 3 to 40 m, M. edulis sizes were positively correlated with POM concentrations. POC:chl a ratios and δ13C of POM and M. edulis gill tissue decreased with increasing depth (and greater distance from shore). δ13C of POM was correlated with δ13C of M. edulis. Our results suggest that detritus comprised a large proportion of POM at shallow depths (&lt;15 m), that M. edulis ingested and assimilated carbon in proportion to its availability in POM, and that growth of M. edulis was higher where detritus was present and POM concentrations were higher.

Pediatric Persistent Pain: Associations Among Sensory Modulation, Attachment, Functional Disability, and Quality of Life.

Although attachment is associated with sensory modulation among children and adolescents and insecure attachment is associated with pain severity among adolescents, relationships among sensory modulation, attachment, and function have not previously been demonstrated in a clinical sample of children and adolescents with complex persistent pain. To investigate relationships among sensory modulation, attachment, function, and quality of life (QOL) in a pediatric population with persistent pain. Cross-sectional quantitative design. From October 2015 to July 2017, all children, adolescents, and parents attending a clinic for assessment completed questionnaires and were provided information and consent forms. Those who consented completed sensory modulation and attachment questionnaires. Tertiary pain management clinic. Children (ages 8-12 yr) and adolescents (ages 13-18 yr) with persistent pain (pain of >3 mo duration or a specific pain disorder) and the capacity to answer questionnaires independently. Standardized sensory modulation, attachment, pain intensity, functional disability, and QOL questionnaires. Hypotheses were generated before data collection. Of 152 children and adolescents, 114 children (30 girls, 9 boys) and adolescents (68 girls, 7 boys) met study criteria and consented to participate. Hierarchical multiple regression analyses revealed that sensory sensitivity predicted disability for children and adolescents, and attachment anxiety mediated the relationship between low registration and poorer school-related QOL. Behaviors related to insecure attachment patterns provide a mediating pathway from sensory modulation to functional disability; addressing such behaviors clinically may facilitate engagement in daily activities for children and adolescents with persistent pain. Results support the need to consider the interactions between sensory modulation and attachment when addressing functional abilities with occupational therapy treatment.

Vertebral Augmentation is Superior to Nonoperative Care at Reducing Lower Back Pain for Symptomatic Osteoporotic Compression Fractures: A Meta-Analysis.

This is a systematic review and meta-analysis. This study's goal was to (i) assess the clinical outcomes with and without vertebral augmentation (VA) for osteoporotic vertebral compression fractures (VCFs) with versus without correlating signs and symptoms; and (ii) acute (symptoms <3 mo duration) and subacute VCFs (3-6 mo duration) versus chronic VCFs (>6 mo). Previously, a randomized controlled trial in the New England Journal of Medicine concluded that vertebroplasty for osteoporotic VCFs provided no clinical benefit over sham surgery. However, the VCFs examined had no clinical correlation with symptom, physical examination, or imaging (magnetic resonance imaging/bone scan) findings. Nonetheless, the randomized controlled trial resulted in a reduction in VA performed in the United States. Currently, no consensus exists on VA versus nonoperative care for symptomatic VCFs (SVFs). A literature search was conducted for studies on VA and conservative management for VCFs. Meta-analysis was performed using the random-effects model. The primary outcome was improvement in lower back pain visual analog score. SVFs were defined as radiographic VCF with clinical correlation. Radiographic-alone VCF (RVF) was defined as radiographic VCF without clinical correlation. Thirteen studies totaling 1467 patients with minimum 6-month follow-up were found. Pain reduction was greater with VA over conservative management for SVFs (P<0.000001) and equivalent for RVFs (P=0.22). Subanalysis for acute/subacute SVFs and chronic SVFs showed that VA was superior to nonoperative care (P=0.0009 and 0.04, respectively). No difference was observed in outcomes between VA and nonoperative care for chronic RVF (P=0.22). VA is superior to nonoperative care in reducing lower back pain for osteoporotic VCFs with correlating signs and symptoms. VA had no benefit over nonoperative care for chronic VCFs that lacked clinical correlation. Lower back pain has many etiologies and patients should be clinically assessed before recommending VA.

Labyrinthitis Ossificans in a Cynomolgus Macaque (Macaca fascicularis).

Labyrinthitis is inflammation of the membranous and bony labyrinth of the inner ear. Typical portals of entry include hematogenous spread from the cochlear vasculature, passage of otitis media pathogens through the round window, and most commonly, meningogenic spread from the subarachnoid space. The sequela of chronic inner ear inflammation is labyrinthitis ossificans, in which inner ear structures are replaced by fibrous and osseous tissues. Labyrinthitis in humans has been reported concurrently with infection due to various viruses (for example, varicella–zoster, measles, mumps) and bacteria (for example, Treponema pallidum, Streptococcus pneumoniae) and may be associated with vertebrobasilar ischemia and meningitis. Profound sensorineural hearing loss is a common, serious complication of this disease. Here, we report a case of labyrinthitis ossificans in a cynomolgus macaque (Macaca fascicularis) with a potential infectious etiology. Historically, this animal had an indwelling femoral intravenous catheter for more than 4 y. He presented with a right-sided head tilt and incoordination of 2 mo duration. The macaque was treated with NSAID and antibiotics, which corrected the incoordination but not the head tilt. MRI revealed right-sided labyrinthitis, and euthanasia was elected due to clinical signs that were refractory to treatment. Gross pathology was unremarkable, but histopathology revealed chronic labyrinthitis ossificans with local fibroplasia and vestibuloauditory neuritis. We describe here the clinical features, imaging, and histologic lesions of labyrinthitis in a macaque.

ХВИЛЬОВА СТРУКТУРА ПОКАЗНИКІВ ГЕМОДИНАМІКИ ПРИ РІЗНОМУ ВИХІДНОМУ РІВНІ ЧАСТОТИ ДИХАННЯ У ЧОЛОВІКІВ

Introduction . It is expedient to investigate the features of wave structure of the oscillations of the stroke volume (SV) and duration of R-R interval by the different level of the main vegetative indicators such as respiratory rate and volume of cardiac output which are considered to be constant for each person according to the data of many studies. Purpose . To find out the features of the wave structure of oscillations of SV and duration of R-R interval in healthy young men with a different level of respiratory rate. Methods. The measurements are carried out on 120 healthy young men aged from 17 to 23 years. By the distribution of the initial value of the Mo duration of respiratory cycle men were divided into 3 groups: tachypnea (39 men) – with abnormally rapid breathing, normopnea (62 men) – with normal respiratory rate and bradypnea (19 men) - with abnormally slow breathing. Time series were analyzed with five-minutes implementations of successive stroke volume and R-R duration in the “Caspico” program. For the duration of cardiocycles were distinguished 3 main spectral components: HF (0,15-0,4 Hz), LF (0,04-0,15 Hz), VLF (0-0,04 Hz) and total power of the spectrum (TP), the power of high frequency oscillations in normalized units (HFnorm). These indicators for SV were respectively HF sv , LF sv , VLF sv , ТР sv and HFnorm sv . Results . People with low and high frequency of breathing in a state of rest are characterized by the relatively higher amplitude of oscillations of duration of R-R interval and stroke volume in the range of 0,04-0,15 Hz than normopnea. By bradypnea it is stipulated by a violation of respiratory periodicals in this frequency range and higher level of activation of parasympathetic link of the vegetative nervous system, by tachypnea it is stipulated by a number of factors: relatively higher level of blood-filling of organs in thorax, increase of sympathetic effects on the heart and increase of spontaneous baro-reflex sensitivity. By dosed load it is vice verse – relatively larger sympathetic activation is observed by bradypnea. Conclusion. Taking into account the output frequency of breathing can significantly improve the diagnostic value of the methods for analyzing of the variability of the stroke volume and heart rate.

Who Benefits Most From Individualized Physiotherapy or Advice for Low Back Disorders? A Preplanned Effect Modifier Analysis of a Randomized Controlled Trial.

A preplanned effect modifier analysis of the Specific Treatment of Problems of the Spine randomized controlled trial. To identify characteristics associated with larger or smaller treatment effects in people with low back disorders undergoing either individualized physical therapy or guideline-based advice. Identifying subgroups of people who attain a larger or smaller benefit from particular treatments has been identified as a high research priority for low back disorders. The trial involved 300 participants with low back pain and/or referred leg pain (≥6 wk, ≤6 mo duration), who satisfied criteria to be classified into five subgroups (with 228 participants classified into three subgroups relating to disc-related disorders, and 64 classified into the zygapophyseal joint dysfunction subgroup). Participants were randomly allocated to receive either two sessions of guideline based advice (n = 144), or 10 sessions of individualized physical therapy targeting pathoanatomical, psychosocial, and neurophysiological factors (n = 156). Univariate and multivariate linear mixed models determined the interaction between treatment group and potential effect modifiers (defined a priori) for the primary outcomes of back pain, leg pain (0-10 Numeric Rating Scale) and activity limitation (Oswestry Disability Index) over a 52-week follow-up. Participants with higher levels of back pain, higher Örebro scores (indicative of higher risk of persistent pain) or longer duration of symptoms derived the largest benefits from individualized physical therapy relative to advice. Poorer coping also predicted larger benefits from individualized physical therapy in the univariate analysis. These findings suggest that people with low back disorders could be preferentially targeted for individualized physical therapy rather than advice if they have higher back pain levels, longer duration of symptoms, or higher Örebro scores. 2.

A STUDY OF THERAPEUTIC RESPONSE AND ADVERSE EFFECTS OF INTRAVENOUS ERYTHROPOIETIN VERSUS SUBCUTANEOUS ERYTHROPOIETIN ON HEMODIALYSIS PATIENTS IN THE DEPARTMENT OF NEPHROLOGY OF OHRC

Objective: To study the efficacy of intravenous erythropoietin and subcutaneous erythropoietin in hemodialysis patients who have persistent anemia despite correction of iron therapy and to measure the outcomes in terms of raise in haemoglobin concentration and adverse events in both the groups.Methods: After ethical committee approval the current study was conducted at the Department of Hemodialysis of Owasi Hospital and Research Centre, Hyderabad a period of 6 mo duration. 60 patients undergoing hemodialysis were recruited into out study who had haemoglobin less than 10.0 despite corrected iron levels. Patients were divided into two groups for intravenous administration and subcutaneous administration of alpha erythropoietin. Patients were stratified into three sub-groups of mild, moderate and severe anaemia. Therapeutic response was recorded in the form of monthly hemoglobin and hemoatocrit. Of the 30 patients in the subcutaneous group, erythropoietin was given to 19 males and 11 females, while intravenous erythropoietin was administered to 17 males and 13 females in the other 30 patients.Results: The mean hemoglobin level in the subcutaneous group was 5.16 at the commencement of the study and in the intravenous group the mean hemoglobin was 5.0. In the subcutaneous group, the mean rise in the hemoglobin was rapidly achieved in 3 mo duration when compared to the intravenous group. Mean Systolic Blood pressure was higher in the intravenous group when compared to the subcutaneous group. Spillage of the drug was minimal in subcutaneous group when compared to the intravenous group.Conclusion: After correction of the iron deficiency, low dose of erythropoietin subcutaneously promised to maintain expected hemoglobin level above 10 g/dL with no adverse events compared to intravenous erythropoietin. Erythropoitin alpha at a dose of 4000 IU was enough to achieve the therapeutic target of Hemoglobin&gt;10.0 by administering subcutaneously accelerated hypertension was less when compared to Intravenous erythropieitn post dialysis. Hence we recommend to use erythropoietin subcutaneously rather than intravenously.

Paramedian Submandibular Approach for Removal of Foreign Bodies in the Pterygoid Muscle in Two Dogs.

The purpose of this report is to document a unique location of an oropharyngeal foreign body, diagnosed via contrast computed tomography (CT), as well as a novel surgical approach to the pterygoid muscle region. Oropharyngeal foreign objects are an uncommon but potentially serious disease that can lead to chronic abscessation and pain. Two dogs were presented with chronic complaints, including pain and inability to fully open the mouth for a 1 yr and 5 mo duration, respectively. There was no history or evidence of skin sinus or submandibular/cervical swelling on physical examination of either dog. Both dogs had normal oropharyngeal anatomy with the exception of an asymmetric contrast-enhancing lesion within the pterygoid muscle on CT imaging. As there were no gross abnormalities visible during surgery, the use of contrast CT was vital in order to isolate the focus of infection. A paramedian submandibular approach was used to explore this region, and in both cases, foreign material was successfully removed with subsequent resolution of clinical signs. The dogs were immediately free of clinical signs and showed no recurrence for at least 8 and 17 mo after the exploration, respectively. A novel surgical approach is described to remove oropharyngeal foreign objects and necrotic debris within the pterygoid muscle.

Abstract MP005: Do Worksite Wellness Programs Improve Dietary Behaviors and Adiposity? A Systematic Review and Meta-analysis

Introduction: Worksites are promising venues for promoting health, given considerable time spent at work and opportunities for environmental change. Yet, the impact of worksite wellness programs (WWPs) on diet and adiposity, as well as the most relevant WWP components, are not established. Methods: Following MOOSE and PRISMA guidelines, we conducted a systematic review and meta-analysis of the impact of multi-component WWP trials (RCT or quasi-experimental) on diet and adiposity. Data were extracted in duplicate and pooled using inverse variance random effects meta-analysis. Pre-specified sources of heterogeneity (study design, world region, worksite type, duration, WWP components) were analyzed by meta-regression and subgroup analysis. Funnel plots, Begg’s, and Egger’s tests evaluated potential publication bias. Results: From 6612 abstracts, we identified 48 studies assessing WWPs and diet or adiposity. Most were in the US (54%) or Europe (23%), with diet (64%) and exercise/weight loss (20%) as main targets. Intervention components were variable (Figure). Most common outcomes were intakes of fruits and vegetables (F&amp;V) (19 studies), total fat or fat subtypes (18), and dietary fiber (4); and BMI (35) and waist circumference (WC) (10). Median duration was 12 months (range: 1-48 mo). In pooled analyses, WWP increased intake of F&amp;V, especially fruits (Figure). Significant effects were not identified for dietary fiber, total fat, or fat subtypes. WWP also reduced BMI (Figure) and WC (-2.03 cm, 95% CI:-3.88,-0.20). Trial duration significantly modified effects on BMI (&lt;12 mo duration: -0.64 kg/m 2 ; 12+ mo: -0.16 kg/m 2 ; P-interaction=0.046); but not WC or F&amp;V intake. Additional findings for heterogeneity, including WWP components, and publication bias will be presented. Conclusions: These novel findings support effectiveness of WWP for increasing F&amp;V and reducing BMI and WC.

Assessing the effect of environmental factors on the spawning activity of the sea urchin Strongylocentrotus intermedius through video recording observations

MEPS Marine Ecology Progress Series Contact the journal Facebook Twitter RSS Mailing List Subscribe to our mailing list via Mailchimp HomeLatest VolumeAbout the JournalEditorsTheme Sections MEPS 588:101-119 (2018) - DOI: https://doi.org/10.3354/meps12436 Assessing the effect of environmental factors on the spawning activity of the sea urchin Strongylocentrotus intermedius through video recording observations Peter M. Zhadan1,*, Marina A. Vaschenko2, Sergey D. Ryazanov1 1V. I. Il’ichev Pacific Oceanological Institute, Far Eastern Branch, Russian Academy of Sciences, 43 Baltiyskaya Street, 690041 Vladivostok, Russia 2National Scientific Center of Marine Biology, A. V. Zhirmunsky Institute of Marine Biology, Far Eastern Branch, Russian Academy of Sciences, 17 Palchevsky Street, 690041 Vladivostok, Russia *Corresponding author: pzhadan@poi.dvo.ru ABSTRACT: We used video recordings of spawning behaviour of the sea urchin Strongylocentrotus intermedius conducted in parallel with an analysis of gonadal state and measurement of environmental variables (tidal level, phytoplankton, temperature, salinity and oxygen concentration) in situ to study the role of environmental factors in triggering sea urchin spawning. The observations were performed during 3 reproductive seasons, each of 2 mo duration, in 2 bays with different levels of phytoplankton (measured as chlorophyll a [chl a]). The only significant positive correlation found was between sea urchin spawning frequency and chl a concentration. Despite a high level of gonad maturity, sea urchin spawning was rarely recorded in the bay with low levels of chl a whereas mass spawning occurred in the bay with higher chl a concentration, with the peak of spawning activity centred around the full moon. Spawning was predominantly nocturnal. Immediately before and during spawning, males actively moved. Females began to spawn only when there were several spawning males nearby. In both sexes, each spawning event included several episodes of gamete release of different duration and with different intervals between them. The same male likely can participate in several spawning events. The following hierarchy of drivers of S. intermedius spawning activity was revealed: (1) increasing the phytoplankton concentration induced active motion and spawning in males, (2) both an elevated phytoplankton level and the presence of sperm stimulated spawning in females and (3) the night time and the new and full lunar phases increased the probability of spawning. KEY WORDS: Broadcast spawning · Echinoderms · Reproductive synchrony · Phytoplankton · Temperature · Circadian rhythm · Lunar cycle Full text in pdf format Supplementary material PreviousNextCite this article as: Zhadan PM, Vaschenko MA, Ryazanov SD (2018) Assessing the effect of environmental factors on the spawning activity of the sea urchin Strongylocentrotus intermedius through video recording observations. Mar Ecol Prog Ser 588:101-119. https://doi.org/10.3354/meps12436 Export citation RSS - Facebook - Tweet - linkedIn Cited by Published in MEPS Vol. 588. Online publication date: February 08, 2018 Print ISSN: 0171-8630; Online ISSN: 1616-1599 Copyright © 2018 Inter-Research.

3D Printed Surgical Instruments Evaluated by a Simulated Crew of a Mars Mission.

The first space-based fused deposition modeling (FDM) 3D printer became operational in 2014. This study evaluated whether Mars simulation crewmembers of the Hawai'i Space Exploration Analog and Simulation (HI-SEAS) II mission with no prior surgical experience could utilize acrylonitrile butadiene styrene (ABS) thermoplastic surgical instruments FDM 3D printed on Earth to complete simulated surgical tasks. This study sought to examine the feasibility of using 3D printed surgical tools when the primary crew medical officer is incapacitated and the back-up crew medical officer must conduct a surgical procedure during a simulated extended space mission. During a 4 mo duration ground-based analog mission, five simulation crewmembers with no prior surgical experience completed 16 timed sets of simulated prepping, draping, incising, and suturing tasks to evaluate the relative speed of using four ABS thermoplastic instruments printed on Earth compared to conventional instruments. All four simulated surgical tasks were successfully performed using 3D printed instruments by Mars simulation crewmembers with no prior surgical experience. There was no substantial difference in time to completion of simulated tasks with control vs. 3D printed sponge stick, towel clamp, scalpel handle, and toothed forceps. These limited findings support further investigation into the creation of an onboard digital catalog of validated 3D printable surgical instrument design files to support autonomous, crew-administered healthcare on Mars missions. Future work could include addressing sterility, biocompatibility, and having astronaut crew medical officers test a wider range of surgical instruments printed in microgravity during actual surgical procedures. Wong JY, Pfahnl AC. 3D printed surgical instruments evaluated by a simulated crew of a Mars mission. Aerosp Med Hum Perform. 2016; 87(9):806-810.