ABSTRACT
Glutamine is an astroglia-derived precursor of the neurotransmitter glutamate, and its astroglia-to-neuron transfer is controlled by distinct glutamine transporters on the astrocytic and neuronal sites. In this study, we focused on the role of astrocytic glutamine efflux-mediating system N transporter SN1 in the maintenance of glutamatergic neurotransmission by analyzing the electrophysiological parameters ex vivo in the brain slices from control mice and mice in which vivo-morpholino technique was used to diminish SN1 protein. The glutamatergic transmission was characterized by electrophysiological recordings, ultrastructure of neuron terminals, and determination of proteins related to glutamate synaptic transmission: synaptophysin, synaptotagmin, and vit1A. The space-restricted â¼51,5% reduction of SN1 protein did not affect the expression of the neuronal glutamine transporter SAT2. SN1 depletion resulted in a reduction of field potentials (FPs), unaltered frequency of spontaneous and miniature excitatory postsynaptic currents (sEPSCs/mEPSCs), and presented a tendency towards a decrease of long-term potentiation (LTP). Ultrastructurally, preserved number of synaptic vesicles, primarily localized centrally of the cell body, correlates with unchanged levels of synaptic proteins. Collectively, the study indicates that glutamatergic transmission proceeds relatively independently of the SN1 - mediated glutamine transfer to the synapse.
Subject(s)
Amino Acid Transport Systems, Neutral , Amino Acid Transport Systems, Neutral/metabolism , Animals , Frontal Lobe/metabolism , Glutamic Acid , Glutamine , Mice , Synaptic TransmissionSubject(s)
Immunotherapy/adverse effects , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Lymphadenopathy/etiology , Neoplasm, Residual/drug therapy , Abdomen/pathology , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols , Disease Progression , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Lymph Nodes/pathology , Male , Middle Aged , Prognosis , Proportional Hazards Models , Prospective Studies , Treatment OutcomeABSTRACT
While guidelines support metformin as a therapeutic option for diabetic patients with mild-to-moderate renal insufficiency, the frequency and outcomes of metformin use in kidney transplant recipients are not well described. We integrated national U.S. transplant registry data with records from a large pharmaceutical claims clearinghouse (2008-2015). Associations (adjusted hazard ratio, 95% LCL aHR95% UCL ) of diabetes regimens (with and excluding metformin) in the first year post-transplant with patient and graft survival over the subsequent year were quantified by multivariate Cox regression, adjusted for recipient, donor, and transplant factors and propensity for metformin use. Among 14 144 recipients with pretransplant type 2 diabetes mellitus, 4.7% filled metformin in the first year post-transplant; most also received diabetes comedications. Compared to those who received insulin-based regimens without metformin, patients who received metformin were more likely to be female, have higher estimated glomerular filtration rates, and have undergone transplant more recently. Metformin-based regimens were associated with significantly lower adjusted all-cause (aHR 0.18 0.410.91 ), malignancy-related (aHR 0.45 0.450.99 ), and infection-related (aHR 0.12 0.320.85 ) mortality, and nonsignificant trends toward lower cardiovascular mortality, graft failure, and acute rejection. No evidence of increased adverse graft or patient outcomes was noted. Use of metformin-based diabetes treatment regimens may be safe in carefully selected kidney transplant recipients.
Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Graft Rejection/mortality , Insurance, Pharmaceutical Services/statistics & numerical data , Kidney Failure, Chronic/mortality , Kidney Transplantation/mortality , Metformin/therapeutic use , Postoperative Complications , Adolescent , Adult , Child , Diabetes Mellitus, Type 2/drug therapy , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/drug therapy , Graft Rejection/epidemiology , Graft Survival , Humans , Hypoglycemic Agents/therapeutic use , Kidney Failure, Chronic/drug therapy , Kidney Failure, Chronic/surgery , Kidney Function Tests , Male , Middle Aged , Prognosis , Registries/statistics & numerical data , Retrospective Studies , Risk Factors , Survival Rate , Transplant Recipients , United States , Young AdultABSTRACT
Direct-acting antiviral medications (DAAs) have revolutionized care for hepatitis C positive (HCV+) liver (LT) and kidney (KT) transplant recipients. Scientific Registry of Transplant Recipients registry data were integrated with national pharmaceutical claims (2007-2016) to identify HCV treatments before January 2014 (pre-DAA) and after (post-DAA), stratified by donor (D) and recipient (R) serostatus and payer. Pre-DAA, 18% of HCV+ LT recipients were treated within 3 years and without differences by donor serostatus or payer. Post-DAA, only 6% of D-/R+ recipients, 19.8% of D+/R+ recipients with public insurance, and 11.3% with private insurance were treated within 3 years (P < .0001). LT recipients treated for HCV pre-DAA experienced higher rates of graft loss (adjusted hazard ratio [aHR] 1.34 1.852.10 , P < .0001) and death (aHR 1.47 1.681.91 , P < .0001). Post-DAA, HCV treatment was not associated with death (aHR 0.34 0.671.32 , P = .25) or graft failure (aHR 0.32 0.641.26 , P = .20) in D+R+ LT recipients. Treatment increased in D+R+ KT recipients (5.5% pre-DAA vs 12.9% post-DAA), but did not differ by payer status. DAAs reduced the risk of death after D+/R+ KT by 57% (0.19 0.430.95 , P = .04) and graft loss by 46% (0.27 0.541.07 , P = .08). HCV treatment with DAAs appears to improve HCV+ LT and KT outcomes; however, access to these medications appears limited in both LT and KT recipients.
Subject(s)
Antiviral Agents/therapeutic use , Graft Survival , Hepacivirus/drug effects , Hepatitis C/drug therapy , Kidney Transplantation/economics , Liver Transplantation/economics , Waiting Lists/mortality , Adolescent , Adult , Aged , Female , Follow-Up Studies , Hepatitis C/virology , Humans , Kidney Transplantation/mortality , Liver Transplantation/mortality , Male , Middle Aged , Prognosis , Registries , Retrospective Studies , Risk Factors , Survival Rate , Tissue Donors/supply & distribution , Transplant Recipients , Young AdultSubject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Mantle-Cell/drug therapy , Salvage Therapy , Adenine/analogs & derivatives , Follow-Up Studies , Humans , International Agencies , Lymphoma, Mantle-Cell/pathology , Piperidines , Prognosis , Pyrazoles/administration & dosage , Pyrimidines/administration & dosage , Sirolimus/administration & dosage , Sirolimus/analogs & derivatives , Survival RateABSTRACT
Evolving literature suggests that the epidemic of prescription opioid use affects the transplant population. We examined a novel database wherein national U.S. transplant registry records were linked to a large pharmaceutical claims warehouse (2007-2015) to characterize prescription opioid use before and after kidney transplant, and associations (adjusted hazard ratio, 95%LCL aHR95%UCL ) with death and graft loss. Among 75 430 eligible patients, 43.1% filled opioids in the year before transplant. Use was more common among recipients who were women, white, unemployed, publicly insured, and with longer pretransplant dialysis. Of those with the highest level of pretransplant opioid use, 60% continued high-level use posttransplant. Pretransplant opioid use had graded associations with one-year posttransplant outcomes; the highest-level use predicted 46% increased risk of death (aHR 1.28 1.461.66 ) and 28% increased risk of all-cause graft failure (aHR 1.17 1.281.41 ). Effects of high-level opioid use in the first year after transplant were stronger, predicting twice the risk of death (aHR 1.93 2.242.60 ) and 68% higher all-cause graft failure risk (aHR 1.50 1.681.89 ) over the subsequent year; increased risk persisted over five years. While associations may, in part, reflect underlying conditions or behaviors, opioid use history is relevant in assessing and providing care to transplant candidates and recipients.
Subject(s)
Analgesics, Opioid/adverse effects , Graft Rejection/mortality , Graft Survival , Kidney Failure, Chronic/mortality , Kidney Transplantation/mortality , Opioid-Related Disorders/drug therapy , Postoperative Complications/mortality , Adolescent , Adult , Delayed Graft Function , Female , Follow-Up Studies , Graft Rejection/etiology , Humans , Kidney Failure, Chronic/surgery , Kidney Transplantation/adverse effects , Male , Middle Aged , Postoperative Complications/etiology , Prognosis , Registries , Retrospective Studies , Risk Factors , United States , Young AdultABSTRACT
We report a study of displacement by xenon of a monolayer of sulphur hexafluoride initially condensed on a graphite surface. Earlier work showed that, below 112 K, Xe displaces SF6 almost completely in a first-order transition. Working at higher temperatures, we show that this system has a simple eutectic-like phase diagram, at least for SF6 not too dilute. In our experiment, both adsorbates are in equilibrium with their respective vapors in a cold cell. In our infrared reflection-absorption spectroscopy measurements, the SF6 coverage on the surface is monitored by the frequency shift due to dynamic dipole coupling of the collective mode of the strong SF6 ν3 vibrational resonance. Simulations relate this frequency shift to the SF6 areal density. Below T ≈ 134 K, with increasing Xe pressure, a small amount Xe dissolves in the solid SF6 monolayer preceding its displacement by a solid predominantly Xe monolayer in a first-order transition. Above 134 K, there is a weaker first-order transition to a mixed liquid monolayer, followed by continuous increase in Xe concentration. If the initial SF6 monolayer is near its melting line, the melting transition on adding Xe appears to become continuous.
ABSTRACT
To investigate immuno-chemotherapy for elderly immuno-competent patients (⩾65 years) with newly diagnosed primary central nervous system lymphoma, we conducted a multicentre single-arm trial. One cycle consisted of rituximab (375 mg/m2, days 1, 15, 29), high-dose methotrexate (3 g/m2 days 2, 16, 30), procarbazine (60 mg/m2 days 2-11) and lomustine (110 mg/m2, day 2)-R-MPL protocol. Owing to infectious complications, we omitted lomustine during the study and consecutive patients were treated with the R-MP protocol. Three cycles were scheduled and repeated on day 43. Subsequently, patients commenced 4 weekly maintenance treatment with procarbazine (100 mg for 5 days). Primary end point was complete remission (CR) after 3 cycles. We included 107 patients (69 treated with R-MPL and 38 with R-MP). In all, 38/107 patients achieved CR (35.5%) and 15 (14.0%) achieved partial remission. R-MP was associated with a lower CR rate (31.6%) compared with R-MPL (37.7%), but respective 2-year progression-free survival (All 37.3%; R-MP 34.9%; R-MPL 38.8%) and overall survival (All 47.0%; R-MP 47.7%; R-MPL 46.0%) rates were similar. R-MP was associated with less ⩾grade 3 toxicities compared with R-MPL (71.1% vs 87.0%). R-MP is more feasible while still associated with similar efficacy compared with R-MPL and warrants further improvement in future studies.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Central Nervous System Neoplasms/drug therapy , Lymphoma/drug therapy , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Central Nervous System Neoplasms/diagnosis , Central Nervous System Neoplasms/mortality , Female , Humans , Immunologic Factors/administration & dosage , Lymphoma/diagnosis , Male , Methotrexate/administration & dosage , Neoplasm Staging , Proportional Hazards Models , Quality of Life , Remission Induction , Treatment Outcome , Tumor BurdenABSTRACT
Implications of opioid use in living kidney donors for key outcomes, including readmission rates after nephrectomy, are unknown. We integrated Scientific Registry of Transplant Recipients data with records from a nationwide pharmacy claims warehouse and administrative records from an academic hospital consortium to quantify predonation prescription opioid use and postdonation readmission events. Associations of predonation opioid use (adjusted odds ratio [aOR]) in the year before donation and other baseline clinical, procedural, and center factors with readmission within 90 days postdonation were examined by using multivariate logistic regression. Among 14 959 living donors, 11.3% filled one or more opioid prescriptions in the year before donation. Donors with the highest level of predonation opioid use (>305 mg/year) were more than twice as likely as nonusers to be readmitted (6.8% vs. 2.6%; aOR 2.49, 95% confidence interval 1.74-3.58). Adjusted readmission risk was also significantly (p < 0.05) higher for women (aOR = 1.25), African Americans (aOR = 1.45), spouses (aOR = 1.42), exchange participants (aOR = 1.46), uninsured donors (aOR = 1.40), donors with predonation estimated glomerular filtration rate <60 mL/min/1.73 m2 (aOR = 2.68), donors with predonation pulmonary conditions (aOR = 1.54), and after robotic nephrectomy (aOR = 1.68). Predonation opioid use is independently associated with readmission after donor nephrectomy. Future research should examine underlying mechanisms and approaches to reducing risks of postdonation complications.
Subject(s)
Analgesics, Opioid/therapeutic use , Drug Prescriptions/statistics & numerical data , Kidney Failure, Chronic/surgery , Kidney Transplantation/methods , Living Donors , Patient Readmission/statistics & numerical data , Tissue and Organ Harvesting/methods , Adult , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Survival , Humans , Kidney Function Tests , Male , Nephrectomy , Prognosis , Registries , Risk FactorsABSTRACT
AIM: Hartmann's procedure (HP) is commonly used for the emergency treatment of complicated sigmoid diverticulitis (CSD). It is intended to restore intestinal continuity; however, in practice, reversal is not carried out in all patients. It is important to know the frequency of reversal and the impact of patient-related factors on the decision for reversal. METHOD: A retrospective study was conducted on all patients who underwent HP for CSD at a tertiary referral hospital between 1 May 2005 and 31 December 2010. We assessed the frequency of reversal over time and the prognostic factors affecting the decision for reversal. RESULTS: Of 67 patients [median age 76 (interquartile range: 68-81) years] who had HP for CSD, 28 (42%) underwent reversal. The cumulative incidence of reversal after 48 weeks was 48% (95% CI: 36-62%). Reversal was less likely in elderly patients [hazard ratio (HR) per decade increase = 0.43; 95% CI: 0.26-0.71], with cardiac insufficiency or coronary heart disease (HR = 0.60; 95% CI: 0.26-1.40) and with preoperative immunosuppression or chemotherapy (HR = 0.31; 95% CI: 0.07-1.33). There was no apparent effect of these factors on mortality. CONCLUSION: Approximately half of the patients having HP for CSD undergo reversal within 48 weeks of the initial operation. The finding that age, cardiac or coronary heart disease and preoperative immunosuppression or chemotherapy have an impact on the decision for reversal is relevant to healthcare professionals and patients.
Subject(s)
Colon, Sigmoid/surgery , Colostomy/methods , Diverticulitis, Colonic/surgery , Patient Selection , Reoperation/statistics & numerical data , Age Factors , Aged , Aged, 80 and over , Anastomosis, Surgical , Female , Humans , Male , Preoperative Period , Prognosis , Reoperation/methods , Retrospective StudiesABSTRACT
The mammalian target of rapamycin (mTOR) is a protein kinase involved in the phosphatidylinositol 3-kinase (PI3K)/AKT signalling pathway. It plays a pivotal role in the control of cell proliferation, survival, and angiogenesis with multiple and frequent dysregulations of this pathway in human tumors. Temsirolimus is an intravenous drug, specifically inhibiting the mTOR pathway. Bendamustine is well known for its clinical activity in indolent non-Hodgkin-lymphoma (NHL) and has lately shown clinical activity in mantle cell lymphoma (MCL). Here, we present a case report of temsirolimus in combination with bendamustine and rituximab leading to a CR in a pretreated male. In addition, our in vitro data underlines the additive and synergistic efficacy in cell growth reduction of temsirolimus combined with bendamustine in MCL cell lines and in DLBCL cell lines. Furthermore, as an underlying mechanism of this additive, effects on cell cycle inhibition and apoptosis induction could be identified.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bendamustine Hydrochloride/administration & dosage , Lymphoma, Mantle-Cell/diagnosis , Lymphoma, Mantle-Cell/drug therapy , Sirolimus/analogs & derivatives , Aged , Antineoplastic Agents/administration & dosage , Cell Line, Tumor , Drug Synergism , G1 Phase/drug effects , G1 Phase/physiology , Humans , Male , Rituximab/administration & dosage , Sirolimus/administration & dosageABSTRACT
Effects of the 5-HT(7) receptor antagonist SB 269970, administered for 14 days (1.25 mg/kg), were studied in ex vivo slices of rat hippocampus. To activate the 5-HT(7) receptor, 5-carboxamidotryptamine (5-CT, 200 nM) was applied in the presence of WAY 100635 (2 µM), a 5-HT(1A) receptor antagonist. In contrast to control preparations, no 5-HT(7) receptor-mediated increase in excitability nor depolarization and an increase in the input resistance of CA1 and CA3 pyramidal neurons were present in slices prepared from rats treated with SB 269970. The treatment also abolished the stimulatory effect of 5-HT(7) receptor activation on spontaneous excitatory postsynaptic currents recorded from CA1 stratum radiatum/lacunosum-moleculare interneurons. These data demonstrate that repeated administration of SB 269970 impairs the reactivity of the CA1 hippocampal neuronal network to 5-HT(7) receptor activation.
Subject(s)
Hippocampus/drug effects , Phenols/pharmacology , Receptors, Serotonin/metabolism , Serotonin Antagonists/pharmacology , Sulfonamides/pharmacology , Animals , Excitatory Postsynaptic Potentials/drug effects , Hippocampus/metabolism , Interneurons/drug effects , Interneurons/metabolism , Male , Membrane Potentials/drug effects , Pyramidal Cells , Rats , Rats, Wistar , Serotonin/analogs & derivatives , Serotonin/pharmacologyABSTRACT
In this phase I/II study, we explored the combination of Temsirolimus with Bendamustine and Rituximab (BeRT) in patients with r/r follicular lymphoma (FL) or mantle cell lymphoma (MCL). Patients with 1-3 prior therapies received Bendamustine (90 mg/m(2), day 1+2) and Rituximab (375 mg/m(2), day 1) with Temsirolimus in doses from 25 to 75 mg added on day 1, 8, 15 of a 28-day cycle. Fifteen (11 MCL, 4 FL) patients were included in the phase I. Median age was 73 years and median pretreatment number was 2. No formal dose-limiting toxicity was observed. Dominant non-hematological side effects were fatigue in 11 (73%), nausea in 9 (60%), mucositis in 7 (47%) and vomiting in 6 patients (40%). Cough, diarrhea, pyrexia and rash were observed in five patients (33%) each. Grade 3/4 events included leukopenia in 6 (40%), neutropenia in 4 (27%) and thrombocytopenia in 2 patients (13%). An objective response was observed in 14/15 patients (93%), including 5 complete response (33%; all MCL). After a median follow-up of 19 months, 67% of patients are without signs of progression. Temsirolimus can be safely added to BR with promising preliminary activity. Recruitment in phase II is ongoing.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Follicular/drug therapy , Lymphoma, Mantle-Cell/drug therapy , Neoplasm Recurrence, Local/drug therapy , Aged , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Bendamustine Hydrochloride , Feasibility Studies , Female , Follow-Up Studies , Humans , Lymphoma, Follicular/mortality , Lymphoma, Follicular/pathology , Lymphoma, Mantle-Cell/mortality , Lymphoma, Mantle-Cell/pathology , Male , Maximum Tolerated Dose , Middle Aged , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Nitrogen Mustard Compounds/administration & dosage , Prognosis , Prospective Studies , Remission Induction , Rituximab , Safety , Sirolimus/administration & dosage , Sirolimus/analogs & derivatives , Survival RateABSTRACT
Sirolimus has anti-carcinogenic properties and can be included in maintenance immunosuppressive therapy following kidney transplantation. We investigated sirolimus effects on cancer incidence among kidney recipients. The US transplant registry was linked with 15 population-based cancer registries and national pharmacy claims. Recipients contributed sirolimus-exposed time when sirolimus claims were filled, and unexposed time when other immunosuppressant claims were filled without sirolimus. Cox regression was used to estimate associations with overall and specific cancer incidence, excluding nonmelanoma skin cancers (not captured in cancer registries). We included 32,604 kidney transplants (5687 sirolimus-exposed). Overall, cancer incidence was suggestively lower during sirolimus use (hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.70-1.11). Prostate cancer incidence was higher during sirolimus use (HR = 1.86, 95% CI = 1.15-3.02). Incidence of other cancers was similar or lower with sirolimus use, with a 26% decrease overall (HR = 0.74, 95% CI = 0.57-0.96, excluding prostate cancer). Results were similar after adjustment for demographic and clinical characteristics. This modest association does not provide strong evidence that sirolimus prevents posttransplant cancer, but it may be advantageous among kidney recipients with high cancer risk. Increased prostate cancer diagnoses may result from sirolimus effects on screen detection.
Subject(s)
Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/surgery , Kidney Transplantation , Neoplasms/epidemiology , Sirolimus/therapeutic use , Adult , Female , Follow-Up Studies , Glomerular Filtration Rate , Graft Rejection/drug therapy , Humans , Incidence , Kidney Function Tests , Male , Middle Aged , Prognosis , Registries , Risk Assessment , United States/epidemiologyABSTRACT
Corticotropin-releasing hormone (CRH)-synthesizing parvocellular neuroendocrine neurons of the hypothalamic paraventricular nucleus (PVN) play a key role in the activation of the hypothalamic-pituitary-adrenal axis (HPA). It is well known that excitatory and inhibitory inputs that regulate the activity of these neurons may undergo stress-related modifications; however, the effect of repeated restraint stress on the function of glutamatergic and GABAergic synapses on PVN parvocellular neuroendocrine neurons has not been fully understood so far. Adolescent male Wistar rats were subjected to restraint lasting 10 min and repeated twice daily for 3 days. Brain slices were prepared 24 hours after the last restraint session and were studied ex vivo. Whole-cell patch-clamping was used to record spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs) from parvocellular neuroendocrine neurons of the PVN. Repeated restraint stress resulted in an increase in the mean frequency of sEPSCs and in a decrease in the rise time and the decay time constant of sEPSCs. There was no change in the mean amplitude of sEPSCs. The parameters characterizing sIPSCs also remained unaltered. In addition, the injected current vs. spiking rate ratio of parvocellular neurons was decreased. In conclusion, restraint stress, repeated for 3 days, selectively enhances excitatory synaptic inputs to parvocellular neurons of the PVN, these modifications being accompanied with a decrease in the intrinsic excitability of PVN neuroendocrine parvocellular neurons.
Subject(s)
Paraventricular Hypothalamic Nucleus/physiology , Stress, Physiological/physiology , Animals , Excitatory Amino Acid Antagonists/pharmacology , Excitatory Postsynaptic Potentials , GABA Antagonists/pharmacology , Glutamic Acid/physiology , Inhibitory Postsynaptic Potentials , Kynurenic Acid/pharmacology , Male , Neurons/physiology , Picrotoxin/pharmacology , Rats , Rats, Wistar , Restraint, PhysicalABSTRACT
The established marker for tubular damage, urinary n-acetyl-beta-d-glucosaminidase is significantly increased in type 1 and 2 diabetes patients and is related to albuminuria and other diabetic complications. In this cross sectional study of type 2 diabetes patients with a history of albuminuria, we studied the relationship between excretion of n-acetyl-beta-d-glucosaminidase in urine and diabetic neuropathy.160 type 2 diabetes patients were screened for diabetic peripheral neuropathy and cardiovascular autonomic neuropathy. N-acetyl-beta-d-glucosaminidase excretion was detected in 24 h urine samples.Urinary excretion of n-acetyl-beta-d-glucosaminidase correlated significantly with -glucose control (fasting glucose r=0.18; p=0.04; HbA1c r=0.20; p=0.02) and urine albumin excretion (r=0.22; p=0.01). Binary regression analyses showed that increased urinary n-acetyl-beta-d-glucosaminidase concentration is an independent predictor for presence of clinical symptoms of peripheral neuropathy (OR 1.8 [95%CI 1.2-2.74] and vibration deficiency [OR 1.7; 95% CI 1.2-2.66]. There was also a significant negative association between urinary n-acetyl-beta-d-glucosaminidase and E/I-Ratio (r=-0.21, p<0.02) as well as the 30:15-Ratio (r=-0.24; p<0.01) of heart rate variability. Furthermore, increased n-acetyl-beta-d-glucosaminidase excretion independently predicted cardiovascular autonomic diabetic neuropathy with an OR for decreased E/I-Ratio of 1.7 [95%CI 1.1-2.75]; (p<0.02) and 30:15-Ratio:OR 2.4 [95% CI 1.26-4.45]; (p<0.01).Urinary n-acetyl-beta-d-glucosami-nidase excretion is an independent marker for diabetic peripheral and cardiovascular autonomic neuropathy in type 2 diabetic patients.
Subject(s)
Acetylglucosaminidase/urine , Diabetes Mellitus, Type 2/urine , Diabetic Neuropathies/urine , Aged , Albuminuria/urine , Female , Humans , Male , Middle AgedABSTRACT
This survey was undertaken to explore the variation in the functional constitution of pain clinics in Europe. In addition, we also explored the amount of training which doctors practicing pain medicine typically receive. Approximate hospital charges for common pain interventions and the source of funding were also surveyed. Members of the British Pain Society (Interventional Pain Medicine-Special Interest Group) and other pain physicians in Europe responded through the online questionnaire tool "Survey Monkey." About 215 requests were sent; 82 pain practitioners from 13 countries in Europe responded. This survey indicates that chronic pain interventions are primarily funded either through government or insurance companies. The primary chronic pain service members continue to be anesthesiologists, combined with specialist nurses and physiotherapists. There appears to be some consistency, both with regard to working in a multidisciplinary team, and the training required to become a pain specialist. More than half of the respondents reported the cost of common interventions like caudal epidural steroid injection (ESI), transforaminal ESI, 3 level medial branch blocks, and 6 level facet joint injections to fall under the 500 range ($645). Two thirds of the respondents reported the cost of 4-joint radiofrequency lumbar denervation to be less than 1,500 ($1,935). Good practice should ensure an adequate duration of training, and development of a pain faculty to ensure standards of assessments across the continent. A more detailed, large scale survey is perhaps required to map the availability of chronic pain services and understand the health economics in pain medicine across Europe.
Subject(s)
Chronic Pain/therapy , Data Collection , Pain Management/economics , Pain Management/methods , Education, Medical , Europe , Humans , PhysiciansSubject(s)
Bone and Bones , Choristoma/diagnosis , Neck , Otorhinolaryngologic Diseases/diagnosis , Choristoma/pathology , Choristoma/surgery , Diagnosis, Differential , Humans , Male , Middle Aged , Neck/pathology , Neck/surgery , Otorhinolaryngologic Diseases/pathology , Otorhinolaryngologic Diseases/surgeryABSTRACT
OBJECTIVE: Since 2007, the use of erythropoiesis-stimulating agents (ESAs) to treat anemia in cancer patients receiving chemotherapy has been increasingly restricted in the USA. This study assessed hemoglobin (Hb) decline over time among chemotherapy patients. METHODS: Episodes of chemotherapy care were identified in a large US-oncology electronic medical record database; weekly Hb levels were computed in the first 8 weeks. Unadjusted and adjusted proportions of patient-weeks with Hb decline>1 g/dl (i.e. representing clinically significant decline) within 1 or 2 weeks were analyzed. RESULTS: Between 2006 and 2009, unadjusted proportions of patient-weeks with Hb decline>1 g/dl increased (1-week, from 12.7% to 14.9%; 2-week, from 19.3% to 26.3%). Adjusted 1-week proportions in 2007 were similar to 2006, but increased in 2008 (odds ratio [OR] 1.135; 95% confidence intervals [CI] 1.067, 1.208) and in 2009 (OR 1.235; 95% CI 1.094, 1.395). Adjusted 2-week proportions had the same pattern. CONCLUSIONS: Since restrictions on ESA use were introduced in the USA, more patients have experienced a clinically significant Hb decline after chemotherapy initiation. Initiating anemia therapy at the earliest indicated opportunity may help reduce the risk of such declines.