Propofol for endotracheal intubation in neonates: a dose-finding trial

ObjectiveTo find propofol doses providing effective sedation without side effects in neonates of different gestational ages (GA) and postnatal ages (PNA).Design and settingProspective multicentere dose-finding study in 3 neonatal intensive care units.PatientsNeonates with a PNA <28 days requiring non-emergency endotracheal intubation.InterventionsNeonates were stratified into 8 groups based on GA and PNA. The first 5 neonates in every group received a dose of 1.0 mg/kg propofol. Based on sedative effect and side effects, the dose was increased or decreased in the next 5 patients until the optimal dose was found.Main outcome measuresThe primary outcome was the optimal single propofol starting dose that provides effective sedation without side effects in each age group.ResultsAfter inclusion of 91 patients, the study was prematurely terminated because the primary outcome was only reached in 13% of patients. Dose-finding was completed in 2 groups, but no optimal propofol dose was found. Effective sedation without side effects was achieved more often after a starting dose of 2.0 mg/kg (28%) than after 1.0 mg/kg (3%) and 1.5 mg/kg (9%). Propofol-induced hypotension occurred in 59% of patients. Logistic regression analyses showed that GA and PNA did not predict effective sedation or the occurrence of hypotension.ConclusionsEffective sedation without side effects is difficult to achieve with propofol and the optimal dose in different age groups of neonates could not be determined. The sedative effect of propofol and the occurrence of hypotension are unpredictable and show large inter-individual variability in the neonatal population.

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Treatment of Immune-Mediated Thrombocytopenia Purpura with Concurrent IVIg and Platelet Transfusion: A Retrospective Review of 40 Patients.

Blood ◽

10.1182/blood.v108.11.3972.3972 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3972-3972

Author(s):

Joseph E. Spahr ◽

Neeraj Agarwal ◽

George M. Rodgers

Keyword(s):

Platelet Count ◽

Side Effects ◽

Retrospective Review ◽

Combined Treatment ◽

Age Groups ◽

Optimal Dose ◽

Active Bleeding ◽

Bleeding Complications ◽

Platelet Counts ◽

Immune Mediated

Abstract Introduction: In January 2000, two patients with severe Immune-Mediated Thrombocytopenia (ITP) at our institution were successfully treated with prolonged infusions of IVIg and platelets. The dose of IVIg was 1 g/kg given by continuous infusion over 24 hours with concurrent platelets (1 pheresis unit every 8 hours). Based on these preliminary results, we evaluated this protocol in a larger series of 40 ITP patients. Methods: We performed an IRB-approved retrospective review of adult hospitalized patients with ITP treated with this regimen from January 2000 - December 2005. Patients with clinically significant thrombocytopenia and either active bleeding, need for anticoagulation, or requirement for a surgical procedure received the combined treatment. The subjects received IVIg and platelets as described above. Additional treatments, such as steroids, immunosupressives, or rituximab, as well as splenectomy were utilized at the discretion of the hematologist overseeing their care. Results: The average age of patients treated was 52 years. The majority of patients ranged from 20–80 years old, but 12.5% were older than 80 years. The average pretreatment platelet count was 10,000/μl, with an increase to 55,000/μl after 24 hours, and 69,000/μl after 48 hours. By 72 hours, the average platelet count had begun to decline, although the platelet count remained at an acceptable level (58,200/μl). After 24 hours, 62.7% of patients had a platelet count > 50,000/μl. Bleeding was controlled initially in all patients, and those requiring a procedure experienced no bleeding complications. Over half of the patients (52.5%) required additional treatments for recurrent or refractory ITP, and 32.5% of the patients underwent splenectomy. Six of the 21 patients requiring later retreatment (29%) received IVIg and platelets again in a similar fashion. The average retreatment platelet counts after 24 and 48 hours were 53,000/μl and 49,000/μl respectively, with clinical improvement in bleeding in all patients. No side effects of the combined treatment were noted. The response rates for the 3 IVIg products used were similar. Discussion: For ITP, IVIg and platelets are considered to be first line treatment for patients with very low platelet counts, active bleeding, or those requiring urgent procedures. There is limited literature on the optimal dose and schedule for administration of IVIg and platelets. Our approach for administration of IVIg and platelets concurrently was associated with minimal side effects, resolution of bleeding, ability to safely undergo procedures, and rapid restoration of adequate platelet counts. Additionally, elderly patients had equivalent benefit with no increased side effects, indicating that this regimen is appropriate and safe for patients of all age groups.

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Oral (po) and Intravenous (iv) Clofarabine for Patients (pts) with Myelodysplastic Syndrome (MDS)

Blood ◽

10.1182/blood.v112.11.222.222 ◽

2008 ◽

Vol 112 (11) ◽

pp. 222-222 ◽

Cited By ~ 3

Author(s):

Stefan Faderl ◽

Guillermo Garcia-Manero ◽

Farhad Ravandi ◽

Gautam Borthakur ◽

Zeev Estrov ◽

...

Keyword(s):

High Risk ◽

Optimal Dose ◽

Infectious Complications ◽

Dose Finding ◽

Two Phase ◽

Phase Ii Studies ◽

Starting Dose ◽

Grade 3 ◽

Secondary Mds

Abstract Clofarabine (CLO) is a second generation deoxyadenosine nucleoside analog with activity in pts with acute myeloid leukemia (AML). Early reports also suggested activity in MDS, but the role of CLO in MDS has not been defined. To evaluate the activity and safety of CLO in MDS we designed two phase II studies of IV CLO and PO CLO, respectively. Pts were eligible with MDS and ≥5% blasts or IPSS intermediate-2 and high-risk, CMML, and RAEB-t by FAB. Hematopoietic growth factor support prior to and during the study was permitted. In the IV study pts were adaptively randomized (based on response) to receive CLO 15 or 30 mg/m2 IV over 1 hr. daily × 5 every 4–6 weeks. For the PO study, the starting dose of CLO was 40 mg/m2 orally daily × 5 every 4–6 weeks (oral bioavailability assumed ~ 50%, based on preclinical data), which was decreased to 30 mg/m2 orally daily × 5 after 6 pts had been treated on the higher dose. Sixty-one pts (6 RA/RARS/RCMD, 17 RAEB-1, 16 RAEB-2, 11 CMML, 11 RAEB-t) were treated. Forty-two pts (69%) had high- or intermediate-2 risk disease by IPSS. Thirty-six pts received IV CLO and 25 PO CLO. Median age was 67 yrs (range 25–89) (IV) and 70 yrs (54–86) (PO). Overall, > 80% of pts were older than 60 yrs. Approximately 1/3 of pts had secondary MDS: 13 (36%) (IV) and 8 (32%) (PO), respectively. Seventeen (47%) (IV) and 10 (40%) (PO) of pts had unfavorable cytogenetics (by IPSS definition). Thirty-nine (64%) pts failed prior hypomethylator therapy with either decitabine or azacitidine (22 [61%] pts on IV and 17 [68%] pts on PO CLO). Responses of 60 evaluable pts (one pt refused continuation of therapy on D4 of first course) are summarized in the Table: Response (%) Route Dose (mg/m2) N CR CRp HI PO 40/30 24 7 (29) 2 (8) 3 (13) IV 15 20 7 (35) 3 (15) - 30 16 4 (25) 2 (13) - Total - 60 18 (30) 7 (12) 3 (5) Six pts (10%) died on study (all IV CLO; most commonly related to infectious complications). All pts were evaluable for toxicities. Common AEs were nausea, vomiting, skin rash, hyperbilirubinemia and transaminase elevations. Toxicities ≥ grade 3 were rare. Acute renal failure occurred in 7 pts (2 IV [15 mg/m2], 3 IV [30 mg/m2], 2 PO). Myelosuppression and hospitalizations for neutropenic fever were common, but prolonged myelosuppression (> 42 days) was rare. In conclusion, CLO has activity in pts with higher-risk MDS. Optimal dose and schedule for PO and IV CLO remain to be defined. Lower doses of CLO are also associated with responses. Additional dose finding trials are underway to define the MTD and DLT of IV and PO CLO in high-risk MDS.

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Novel cryoballoon 180° ablation system for treatment of Barrett’s esophagus-related neoplasia: a first-in-human study

Endoscopy ◽

10.1055/a-1381-7562 ◽

2021 ◽

Author(s):

Anouk Overwater ◽

Sanne N. van Munster ◽

Wouter B. Nagengast ◽

Roos E. Pouw ◽

Jacques J. G. H. M. Bergman ◽

...

Keyword(s):

Barrett’S Esophagus ◽

Barrett's Esophagus ◽

Human Study ◽

Dose Finding ◽

The Novel ◽

Single Session ◽

Technical Success ◽

Serious Adverse Events ◽

Technical Success Rate ◽

Starting Dose

Abstract Background The novel 180° cryoballoon (CbAS180) enables semicircumferential treatment over a length of 3 cm per application. This first-in-human study evaluates its feasibility, efficacy, and safety for the treatment of Barrett’s esophagus (BE) neoplasia. Methods This multicenter study consisted of dose-finding and extension phases. Dose-finding started with the lowest dose possible (1.0 mm/s). For each dose, six patients were treated circumferentially over a 3-cm length. The dose was increased until the median BE regression was ≥ 60 % without serious adverse events (SAEs). In the extension phase, the dose was confirmed in 19 new patients. The outcomes were technical success, BE regression after one treatment, and SAEs. Results 25 patients (median Prague C0M3) were included (6 dose-finding/19 extension). In two patients, the CbAS180 could not be applied because of unstable balloon positioning. The technical success rate was 96 % (22 /23). In the six dose-finding patients, the starting dose resulted in median BE regression of 94 % (95 % confidence interval [CI] 60 %–97 %) without SAEs and was thus considered effective. Overall median BE regression was 80 % (95 %CI 60 %–90 %). Conclusion Single-session CbAS180 seems feasible, safe, and effective, and is a promising technique for the treatment of patients with BE neoplasia.

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Design and Main Results of STURDY: A Randomized Clinical Trial of Four Vitamin D3 Doses to Prevent Falls in Older Adults

Innovation in Aging ◽

10.1093/geroni/igaa057.2737 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 759-759

Author(s):

Lawrence Appel ◽

Jennifer Schrack ◽

Erin Michos ◽

Christine Mitchell ◽

Stephen Juraschek ◽

...

Keyword(s):

Vitamin D ◽

Vitamin D3 ◽

Primary Outcome ◽

Vitamin D Supplementation ◽

Dose Finding ◽

High Dose ◽

Hazard Ratios ◽

Risk Of Falls ◽

Event Rates ◽

And Control

Abstract STURDY was a Bayesian, response-adaptive trial with dose-finding and confirmatory stages. Participants (n=688; ≥70years with serum 25(OH)D of 10-29ng/mL) were randomized to 200 (control), 1000, 2000, or 4000 IU/day of vitamin D3. The primary outcome was time to first fall or death over 2 years. During dose-finding, the best non-control dose was determined to be 1000IU/day based on higher primary outcome event rates in the 2000 and 4000IU/day doses than the 1000IU/day dose (posterior probability of being best dose=0.90; hazard ratios[HR] were 1.86 [95%CI: 1.16-2.97] and 1.68 [95%CI: 1.05-2.69], respectively). Participants were then switched from other non-control doses to 1000IU/day, and event rates did not differ between the pooled higher doses and control groups (HR=1.02, P=0.84). There was no heterogeneity by baseline 25(OHD). In conclusion, high-dose vitamin D supplementation ≥1000IU/day did not prevent falls. Whether vitamin D doses >2000IU/day increase the risk of falls is uncertain.

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Phase 1 and Phase 2 Studies of Salmonella enterica Serovar Paratyphi A O-Specific Polysaccharide-Tetanus Toxoid Conjugates in Adults, Teenagers, and 2- to 4-Year-Old Children in Vietnam

Infection and Immunity ◽

10.1128/iai.68.3.1529-1534.2000 ◽

2000 ◽

Vol 68 (3) ◽

pp. 1529-1534 ◽

Cited By ~ 48

Author(s):

Edward Y. Konadu ◽

Feng-Ying C. Lin ◽

Vô Anh Hó ◽

Nguyen Thi Thanh Thuy ◽

Phan Van Bay ◽

...

Keyword(s):

Side Effects ◽

Bactericidal Activity ◽

Tetanus Toxoid ◽

Salmonella Enterica ◽

Phase 1 ◽

Geometric Mean ◽

Age Groups ◽

Significant Rise ◽

Phase 2 ◽

Specific Polysaccharide

ABSTRACT Salmonella enterica serovar Paratyphi A O-specific polysaccharide (O-SP) was activated with 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) and bound to tetanus toxoid (TT) with adipic acid dihydrazide as a linker (SPA-TT1) or directly (SPA-TT2). In mice, these two conjugates elicited high levels of immunoglobulin G (IgG) anti-lipopolysaccharide (LPS) in serum with bactericidal activity (E. Konadu, J. Shiloach, D. A. Bryla, J. B. Robbins, and S. C. Szu, Infect. Immun. 64:2709–2715, 1996). The safety and immunogenicity of the two conjugates were then evaluated sequentially in Vietnamese adults, teenagers, and 2- to 4-year-old children. None of the vaccinees experienced significant side effects, and all had preexisting LPS antibodies. At 4 weeks after injection, there were significant increases of the geometric mean IgG and IgM anti-LPS levels in the adults and teenagers: both conjugates elicited a greater than fourfold rise in the IgG anti-LPS level in serum in ≥80% of the volunteers. SPA-TT2 elicited slightly higher, though not statistically significantly, levels of IgG anti-LPS than did SPA-TT1 in these age groups. Accordingly, only SPA-TT2 was evaluated in the 2- to 4-year-old children. On a random basis, one or two injections were administered 6 weeks apart to the children. No significant side effects were observed, and the levels of preexisting anti-LPS in serum were similar in children of all ages. A significant rise in the IgG anti-LPS titer was elicited by the first injection (P = 0.0001); a second injection did not elicit a booster response. Representative sera from all groups had bactericidal activity that could be adsorbed by S. enterica serovar Paratyphi A LPS.

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Study of a New Analgesic Compound in the Treatment of Tension Headache*

Journal of International Medical Research ◽

10.1177/030006057600400112 ◽

1976 ◽

Vol 4 (1) ◽

pp. 74-78 ◽

Cited By ~ 7

Author(s):

J Borges ◽

C Zavaleta

Keyword(s):

Side Effects ◽

Pharmacological Activity ◽

Clinical Success ◽

Tension Headache ◽

Symptomatic Treatment ◽

Blind Study ◽

Effective Combination ◽

Significant Difference ◽

Starting Dose ◽

Single Blind

The effect of a new analgesic compound ( propoxyphene, acetaminophen, caffeine, hydroxyzine) was investigated in a single-blind study comparing it with plain acetaminophen administered to forty patients with tension headache. For the study, patients were assigned to one of two groups of twenty each. Starting dose for each group was one to two tablets followed by one tablet every four to six hours. The results show that 90% clinical success was obtained with the analgesic compound, while a 45% success was obtained with plain acetaminophen. This is a statistically significant difference. Side-effects observed with analgesic compound were primarily drowsiness and dizziness of mild intensity; acetaminophen caused gastro-intestinal alterations ( nausea, vomiting) and dizziness of greater severity. Therapy was withdrawn in 20% of patients taking acetaminophen because of side-effects. The dosage of analgesic compound required to control each episode of tension headache way smaller than that of acetaminophen. These results can be explained by a possible potentiation of pharmacological activity of the compound's components. It can be concluded that the analgesic compound is a new and effective combination for the symptomatic treatment of tension headache.

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Optimal dose-finding study of antithrombin III for the treatment of acute DIC

Nihon Kyukyu Igakukai Zasshi ◽

10.3893/jjaam.19.1011 ◽

2008 ◽

Vol 19 (11) ◽

pp. 1011-1022

Author(s):

Masahiro Okashiro ◽

Takahisa Kawashima ◽

Noboru Ishii ◽

Yusuke Itagaki ◽

Yukiko Watanabe ◽

...

Keyword(s):

Antithrombin Iii ◽

Optimal Dose ◽

Dose Finding ◽

Finding Study ◽

Dose Finding Study

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Age affects pigeon memory capacity, but not representation of serial order, during a locomotor sequential-learning task

10.21203/rs.3.rs-289410/v1 ◽

2021 ◽

Author(s):

Christina Meier ◽

Parisa Sepehri ◽

Debbie M. Kelly

Keyword(s):

Cognitive Processing ◽

Age Groups ◽

Serial Order ◽

Memory Capacity ◽

Learning Task ◽

Individual Variability ◽

Sequential Learning ◽

Choice Test ◽

Age Related ◽

Recall Memory

Abstract Aging affects individuals of every species, with sometimes detrimental effects on memory and cognition. The simultaneous-chaining task, a sequential-learning task, requires subjects to select items in a predetermined sequence, putting demands on memory and cognitive processing capacity. It is thus a useful tool to investigate age-related differences in these domains. Pigeons of three age groups (young, adult and aged) completed a locomotor adaptation of the task, learning a list of four items. Training began presenting only the first item; additional items were added, one at a time, once previous items were reliably selected in their correct order. Although memory capacity declined noticeably with age, not all aged pigeons showed impairments compared to younger pigeons, suggesting that inter-individual variability emerged with age. During a subsequent free-recall memory test, when all trained items were presented alongside novel distractor items, most pigeons did not reproduce the trained sequence in the absence of reinforcement. During a further forced-choice test, when pigeons were given a choice between only two of the trained items, all three age groups showed evidence of an understanding of the ordinal relationship between items by choosing the earlier item, indicating that complex cognitive processing, unlike memory capacity, remained unaffected by age.

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Evaluation of the effectiveness of transcranial electrostimulation in treatment of neuropsychiatric disorders

Journal of Novel Physiotherapy and Rehabilitation ◽

10.29328/journal.jnpr.1001041 ◽

2021 ◽

Vol 5 (2) ◽

pp. 019-026

Author(s):

Hakobyan Gagik ◽

Sekoyan Eduard ◽

Shoman Karyna ◽

Ekaterina Krasnopeeva

Keyword(s):

Side Effects ◽

Vascular Dementia ◽

Flexible Substrate ◽

Age Groups ◽

Adhesive Layer ◽

Neuropsychiatric Disorders ◽

Controlled Study ◽

Double Blind ◽

Transcranial Electrostimulation ◽

Clinical Diagnoses

Objectives: Evaluation of the effectiveness the method of transcranial electrostimulation in treatment of neuropsychiatric disorders with the use of a patches by the company “Aganyan”. Materials and methods: The study was a double-blind, randomized, placebo-controlled study, participated 106 patients with neuropsychiatric disorders. All participants in were divided into tables according to gender, age and diagnosis. Each subject was given the “Aganyan” patches and a special brochure, in which the method of application was indicated in detail. The wearable patch includes a flexible substrate, a binder an adhesive layer, with an electrode foil attached to it. Patients applied one patch behind each ear. The patches were applied for eight hours every third day for three months. To assess the effectiveness of therapy in patients the following tests were used: The Montreal Cognitive Assessment Scale; MMSE Scale: Concise Mental Status Scale; diaries of observation of the patient’s condition to identify side effects; special brochures in which the subjects independently indicated the effects of the “Aganyan” patches. Tests were performed before and after the use of the “Aganyan” patches. Results: When using the patches of the “Aganyan” company, none of the participants in the study had any side effects; According to the results of the Montreal test according to the criterion of memory and the MMSE test, the effectiveness of the patch was noted in patients with all clinical diagnoses. The greatest positive dynamics was revealed according to the results of the Montreal test according to the criterion of memory in patients with migraine (30%), insomnia (31%), vascular dementia (32%), and according to the results of the MMSE test in patients with diagnoses: cerebrovascular disease: consequences of a cerebral infarction brain (31%), vascular dementia (56%). Conclusion: The patches of “Aganyan” company have proven its effectiveness through electrical stimulation with low-intensity current in patients in different age groups with different clinical diagnoses.

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The Effect of Sevoflurane Anesthesia for Dental Procedure on Neurodevelopment in Children: A Prospective, Equivalence, Controlled Trial

10.21203/rs.3.rs-78114/v1 ◽

2020 ◽

Author(s):

Pinping Zhou ◽

Chao Zhang ◽

Guijin Huang ◽

Yuan Hu ◽

Wenzhu Ma ◽

...

Keyword(s):

General Anesthesia ◽

Local Anesthesia ◽

Primary Outcome ◽

Controlled Trial ◽

Age Groups ◽

Outcome Data ◽

Clinical Trial Registry ◽

General Anesthesia Group ◽

Anesthesia Group ◽

Significant Difference

Abstract Background: Dental procedures under general anesthesia (DGA) was found to improve the oral health-related quality of children's life. However, some parents and pediatricians expressed concern about the neurotoxicity of general anesthesia. The purpose of this trial was to investigate whether DGA in children has an adverse effect on neurodevelopment.Methods: In this prospective, assessor-masked, controlled, equivalence trial, we recruited 340 children younger than 7 years who were undergoing caries treatment between Feb 1, 2019, and Aug 31, 2019, without factors affecting neurodevelopment. They received either sevoflurane-based general anesthesia or awake-local anesthesia. The Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition was used to evaluate the neurodevelopment of children at six months after surgery, and the Full-Scale IQ (FSIQ) was selected as the primary outcome. Predefine the 95% CI of a difference in means within five (1/3 SD) as the equivalence margin.Results: The outcome data were obtained from 129 children in the general anesthesia group and 144 in the local anesthesia group. The median length of general anesthesia was 130 min (IQR 110 – 160). There was equivalence in means of FSIQ score between the general anesthesia group and the local anesthesia group (local minus general anesthesia 0.46, 95% CI -2.35 to 1.61). There was no significant difference in FSIQ scores between different age groups and different anesthesia durations. Only the mother's education could affect the primary outcome.Conclusions: In this trial, prolonged DGA with a sevoflurane-only anesthetic in preschool children, does not adversely affect neurodevelopment at six months after surgery compared with awake-local anesthesia. Trial registration: Chinese Clinical Trial Registry, ChiCTR1800015216. Registered Mar 15 2018, http://www.chictr.org.cn/showproj.aspx?proj=24830.

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