360 results on '"T. Connell"'
Search Results
252. THE EFFECTS OF TREATMENT WITH THE EMULSIONS OF RAGWEED EXTRACT ON ANTIBODY TITERS
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J T, CONNELL and W B, SHERMAN
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Antigen-Antibody Reactions ,Hemagglutination ,Humans ,Rhinitis, Allergic, Seasonal ,Emulsions ,Hemagglutination Tests ,Ambrosia ,Skin Tests - Published
- 1963
253. Abnormal eosinophils, eosinophilia and basophilia in methimazole neutropenia
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J T, Connell
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Heart Failure ,Immunoassay ,Cytoplasm ,Methimazole ,Neutrophils ,Guinea Pigs ,Imidazoles ,Jaundice ,Antigen-Antibody Complex ,Middle Aged ,Cytoplasmic Granules ,Hyperthyroidism ,Antibodies ,Basophils ,Eosinophils ,Leukocyte Count ,Antithyroid Agents ,Eosinophilia ,Animals ,Humans ,Female ,Drug Eruptions ,Agranulocytosis - Published
- 1969
254. The anaphylactic reaction
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J T, Connell
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Humans ,Emergencies ,Anaphylaxis - Published
- 1970
255. Antibody studies in constitutional reactions resulting from injections of ragweed pollen extract
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Phyllis A. Myers, John T. Connell, and William B. Sherman
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Ragweed ,biology ,business.industry ,Plant Extracts ,General Medicine ,Skin test ,Pharmacology ,Antigens, Plant ,biology.organism_classification ,Asymptomatic ,Antibodies ,Antigen-Antibody Reactions ,Titer ,Ragweed pollen extract ,Immunology ,Blocking antibody ,biology.protein ,Medicine ,Humans ,Pollen ,In patient ,medicine.symptom ,Antibody ,Ambrosia ,business - Abstract
1.1. Skin sensitizing antibody titers of patients having constitutional reactions to ragweed were significantly higher than those found in any group of skin test, positive, symptomatic or asymptomatic, treated or untreated patients. 2.2. Blocking antibody titers of patients who had constitutional reactions were lower than those found in the group of patients treated with high doses of aqueous extract and in patients who had received the ragweed emulsion, but were comparable to those found in patients receiving a similar amount of aqueous ragweed extract. 3.3. Hemagglutinating titers were similar in patients who had constitutional reactions and in those patients receiving low amounts of aqueous ragweed extract but were less than the post-repository group and the group treated with high doses of aqueous extract. more...
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- 1962
256. ISOLATION AND CHARACTERIZATION OF ALLERGENS FROM RAGWEED POLLEN. II
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P. S. Norman, T. P. King, and J. T. Connell
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Electrophoresis ,Chromatography ,Immunodiffusion ,Glycoside Hydrolases ,Chemistry ,Plant Extracts ,Research ,Allergens ,Antigens, Plant ,Isolation (microbiology) ,medicine.disease_cause ,Biochemistry ,Ragweed pollen ,Pollen ,medicine ,Hypersensitivity ,Animals ,Glycoside hydrolase ,Rabbits ,Antigens ,Plant Proteins ,Skin Tests - Published
- 1964
257. Treatment of bronchial asthma
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J T, Connell
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Humans ,Tracheotomy ,Asthma - Published
- 1966
258. Effectiveness of topical nasal decongestants
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J T, Connell
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Adult ,Male ,Clinical Trials as Topic ,Adolescent ,Airway Resistance ,Oxymetazoline ,Common Cold ,Rhinitis, Allergic, Seasonal ,Middle Aged ,Respiratory Function Tests ,Placebos ,Nasal Decongestants ,Nasal Mucosa ,Phenylephrine ,Humans ,Female ,Rhinitis - Published
- 1969
259. The Nature of Toxin: The Antigens of Corynebacterium diphtheriae and Bacillus megatherium and their Relation to Toxin
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L. E. Holly, C. C. Warden, and J. T. Connell
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Corynebacterium diphtheriae ,Bacillus megatherium ,Antigen ,biology ,Toxin ,medicine ,Articles ,Bioinformatics ,biology.organism_classification ,medicine.disease_cause ,Molecular Biology ,Microbiology - Published
- 1921
260. Allergic rhinitis. Human experimental model
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J T, Connell
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Humans ,Rhinitis, Allergic, Seasonal ,Models, Biological - Published
- 1970
261. Long-acting antihistamine-decongestant evaluation
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John T. Connell
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Ragweed ,medicine.medical_specialty ,medicine.drug_class ,medicine.medical_treatment ,Medicine ,Humans ,Rhinitis ,Clinical Trials as Topic ,biology ,business.industry ,Masks ,Rhinitis, Allergic, Seasonal ,General Medicine ,Environmental exposure ,Hospital employees ,biology.organism_classification ,medicine.disease ,Ragweed pollen ,Decongestant ,Long acting ,Otorhinolaryngology ,Immunology ,Emergency medicine ,Histamine H1 Antagonists ,Hay fever ,Surgery ,Antihistamine ,business - Abstract
THE CLINICAL evaluation of the effectiveness and duration of sustained-action antihistamine and decongestant medications is difficult to accomplish because of the all-too-familiar phenomena of widely changing subjective symptoms and of rapidly changing environmental exposure to ever-varying allergens and/or irritants. In addition, final evaluation rests with the patient's subjective determinations or the physician's appraisal made from relatively meager observations. Using a new objective technique, the effect of a sustained-action antihistamine and decongestant medication (Allerest Time Capsules) was studied during environmental exposure to ragweed pollen. Method Six hospital employees who had ragweed hay fever were selected for testing on the basis of availability. All of these individuals performed their usual jobs in the hospital during the experiments. Tests were performed during the ragweed pollinating season. Because subjects were in the same general area, environmental ragweed pollen concentration was assumed to be the same for all. An increase or decrease in symptoms more...
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- 1967
262. SKIN-SENSITIZING ANTIBODY TITER. III. RELATIONSHIP OF THE SKIN-SENSITIZING ANTIBODY TITER TO THE INTRACUTANEOUS SKIN TEST, TO THE TOLERANCE OF INJECTIONS OF ANTIGENS, AND TO THE EFFECTS OF PROLONGED TREATMENT WITH ANTIGEN
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J T, CONNELL and W B, SHERMAN
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Immune Sera ,Hypersensitivity ,New York ,Humans ,Rhinitis, Allergic, Seasonal ,Antigens ,Antibodies ,Skin Tests - Published
- 1964
263. Reciprocal nasal congestion-decongestion reflex
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J T, Connell
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Hypersensitivity, Immediate ,Placebos ,Nasal Decongestants ,Reflex ,Humans ,Pollen ,Rhinitis, Allergic, Seasonal ,Allergens ,Nose - Published
- 1968
264. Quantitative intranasal pollen challenges. 3. The priming effect in allergic rhinitis
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J T, Connell
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Adult ,Antigen-Antibody Reactions ,Time Factors ,Humans ,Pollen ,Rhinitis, Allergic, Seasonal ,Environmental Exposure ,Nose - Published
- 1969
265. A study of immunological responses of a normal individual to injections of ragweed pollen emulsified in mineral oil adjuvant
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John T. Connell and J.Prochazka Fisher
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Allergy ,medicine.medical_treatment ,Booster dose ,medicine.disease_cause ,Antigen ,Pollen ,Hypersensitivity ,Medicine ,Humans ,Mineral Oil ,Mineral oil ,integumentary system ,biology ,business.industry ,Plant Extracts ,General Medicine ,Allergens ,Antigens, Plant ,medicine.disease ,Titer ,Immunology ,biology.protein ,Antibody ,business ,Adjuvant ,medicine.drug - Abstract
One normal test subject was sensitized to ragweed pollen antigen emulsified in Freund's adjuvant. Immediate and delayed types of sensitivity were induced. The immediate type of sensitivity was recalled after each booster dose of antigen. Reappearance of the whealing skin reactions after a massive reinjection of antigen in emulsion was accompanied by a marked decrease of the delayed skin reactions. Serum antibodies were determined by various techniques, and the titers followed through 40 weeks. more...
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- 1963
266. Role of antibodies in allergic diseases
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J T, Connell
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Hypersensitivity, Immediate ,Antibody Formation ,Humans ,Antibodies ,Skin Tests - Published
- 1969
267. POLLEN COUNTS AND AIR POLLUTION: TECHNICS IN PREPARATION AND PRODUCTION
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J T, CONNELL
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Air Pollution ,Research ,Pollen ,Allergens - Published
- 1965
268. Quantitative intranasal pollen challenge. II. Effect of daily pollen challenge, environmental pollen exposure, and placebo challenge on the nasal membrane
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J T, Connell
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Placebos ,Nasal Mucosa ,Immune Tolerance ,Humans ,Pollen ,Rhinitis, Allergic, Seasonal ,Environmental Exposure ,Seasons ,Antibodies ,Skin Tests - Published
- 1968
269. SKIN SENSITIZING ANTIBODY. I. RELATIONSHIP OF THE SKIN SENSITIZING ANTIBODY TITER TO THE OCCURRENCE OF SYMPTOMS IN UNTREATED PERSONS WITH A POSITIVE RAGWEED SKIN TEST
- Author
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J T, CONNELL and W B, SHERMAN
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Humans ,Pollen ,Rhinitis, Allergic, Seasonal ,Allergens ,Ambrosia ,Antibodies ,Skin Tests - Published
- 1963
270. Comparison between skin-sensitizing antibody titers and leukocyte sensitivity measurements as an index of the severity of ragweed hay fever
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John T. Connell, Philip S. Norman, and Lawrence M. Lichtenstein
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Ragweed ,Skin sensitizing antibody ,Rhinitis, Allergic, Seasonal ,General Medicine ,Environmental exposure ,Biology ,medicine.disease ,biology.organism_classification ,In vitro ,Antibodies ,Titer ,chemistry.chemical_compound ,chemistry ,Immunology ,medicine ,biology.protein ,Leukocytes ,Hay fever ,Humans ,Antibody ,Histamine ,Skin Tests - Abstract
The ability of two techniques, in vitro measurements of leukocytic sensitivity to ragweed antigen E and P-K titrations of skin-sensitizing antibody (SSA), have been compared in regard to their ability to predict the clinical severity of ragweed hay fever in 24 allergic patients. The former proved to be more accurate and the correlation with the degree of patient symptomatology was highly significant. The level of SSA was observed to increase following environmental exposure to ragweed pollen. A similar effect was noted in vitro, in that the leukocytes of some patients which had lost the ability to release a high percentage of their total histamine were observed to undergo a partial or complete recovery of this ability subsequent to the ragweed season. more...
- Published
- 1967
271. C-reactive protein in pregnancy and contraception
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John T. Connell and Elizabeth B. Connell
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Adult ,medicine.medical_specialty ,Chlormadinone Acetate ,Latex ,medicine.medical_treatment ,Population ,Physiology ,Lynestrenol ,Chlormadinone acetate ,chemistry.chemical_compound ,Pregnancy ,Internal medicine ,medicine ,Humans ,education ,Maternal-Fetal Exchange ,education.field_of_study ,biology ,Progestogen ,Dimethisterone ,business.industry ,C-reactive protein ,Obstetrics and Gynecology ,Mestranol ,Megestrol ,medicine.disease ,Blood Protein Electrophoresis ,Microspheres ,Pregnancy Complications ,Endocrinology ,C-Reactive Protein ,Contraception ,chemistry ,Megestrol acetate ,biology.protein ,Female ,Norethindrone ,business ,medicine.drug ,Contraceptives, Oral ,Intrauterine Devices - Abstract
C-reactive protein (CRP) is a complex glycoprotein found in serum. It is an abnormal, nonspecific, acute-phase protein seen in pregnancy and with tissue injury and necrosis. Sera from 4 groups of patients were studied for CRP. Thirteen per cent of an unselected control group had CRP. Sixty per cent of sera from pregnant patients contained CRP, but sustained increase with advancing pregnancy was not observed. Ninety-two per cent of patients receiving combination contraceptive preparations, 52 per cent receiving sequential contraceptive preparations, and 14 per cent receiving continuous low-dosage progestogen therapy without added estrogen developed CRP. CRP was present in the sera of some patients using intrauterine contraceptive devices (IUD's), and the number of positive reactions appeared to increase with the increased length of use of a device. These data could support a local biochemical contraceptive mechanism of action. Since CRP is apparently produced only by the liver, this study suggests that the IUD may, in addition, produce a systemic stimulus. more...
- Published
- 1971
272. Elective single embryo transfer- the power of one
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Matthew T. Connell, John M. Csokmay, Amy M. Lee, and Aaron K. Styer
- Subjects
0301 basic medicine ,medicine.medical_specialty ,medicine.medical_treatment ,Reproductive medicine ,Single Embryo Transfer ,Review ,In-vitro fertilization ,Multiple Gestation ,Elective single embryo transfer ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Twin gestation assisted reproductive technology ,General Environmental Science ,Pregnancy ,030219 obstetrics & reproductive medicine ,In vitro fertilisation ,business.industry ,Obstetrics ,medicine.disease ,Embryo transfer ,030104 developmental biology ,Infertility ,embryonic structures ,General Earth and Planetary Sciences ,Gestation ,business ,Live birth - Abstract
Despite the highest historical live birth success rates for couples undergoing in vitro fertilization (IVF), there has been an epidemic of iatrogenic twin and higher order gestation conceived from this treatment. Continued improvement in cryopreservation techniques have allowed preservation of supernumerary embryos for use in future cycles, and refinements in culture systems and embryo selection have resulted in the transfer of fewer embryos while maintaining favorable pregnancy rates. The voluntary transfer of a single high quality embryo, elective single embryo transfer (eSET), has significantly reduced multiple gestation rates and maximized the rate of singleton pregnancy without compromising overall success rates. Although eSET is the standard of care in several developed countries, utilization in the United States has been slow. States with mandated IVF insurance have seen decreases in preterm birth rates yielding down stream health care savings. Herein, the evolution and future applications of this practice to reduce the risk of iatrogenic twins is reviewed. more...
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273. Safety and efficacy of loratadine (Sch-29851): a new non-sedating antihistamine in seasonal allergic rhinitis
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R J, Dockhorn, A, Bergner, J T, Connell, C J, Falliers, S V, Grabiec, J M, Weiler, and M K, Shellenberger
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Placebos ,Clinical Trials as Topic ,Random Allocation ,Time Factors ,Double-Blind Method ,Cyproheptadine ,Histamine Antagonists ,Humans ,Rhinitis, Allergic, Seasonal ,Capsules ,Clemastine ,Loratadine - Abstract
Loratadine, a new antihistamine in the non-sedating class, was evaluated for efficacy and safety in treatment of allergic rhinitis in a multicentered study. Loratadine was found to be both safe and efficacious. When administered to patients with seasonal allergic rhinitis, a single daily oral dose of 10 mg is comparable in efficacy to clemastine, 1 mg, given twice daily. The incidence of sedation with loratadine is comparable to placebo and significantly lower than with clemastine. The incidence of anticholinergic side effects with loratadine is low and in this study was comparable to placebo and clemastine. more...
274. Editorial
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John T. Connell and Larry E. Duberstein
- Subjects
Otorhinolaryngology - Published
- 1987
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275. 41 Studies of rebound phenomena and oxymetazoline
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John T. Connell and M.Inez Linzmayer
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business.industry ,Anesthesia ,Immunology ,Oxymetazoline ,medicine ,Immunology and Allergy ,business ,medicine.drug - Published
- 1988
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276. Present Status of the Treatment of Hypertension
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John T. Connell, Richard J. Greenwood, and Donald A. Dupler
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Ganglionic blocking agent ,Lightheadedness ,business.industry ,Nausea ,General Medicine ,Hydralazine ,Reserpine ,Rash ,Hydrochlorothiazide ,Anesthesia ,Joint pain ,Hypertension ,medicine ,medicine.symptom ,business ,Antihypertensive Agents ,medicine.drug - Abstract
Most hypertension can be controlled if treatment is begun early and continued on a long-term basis. Forty-nine patients with blood pressures of 170/100 mm. Hg or greater were studied. All received reserpine; 39 who failed to exhibit an adequate response had hydrochlorothiazide added. Ten patients who did not respond to this combination were given hydralazine in addition; three had an excellent response, five good, one fair, and one none. No significant side-effects were caused by reserpine. Reactions to hydrochlorothiazide included nausea, lightheadedness, and mild skin rash. One patient had skin rash, joint pain, and an elevated blood urea nitrogen level due to hydralazine, which had to be discontinued. Patients who do not respond to this combination of drugs may improve with the use of ganglionic blocking agents or guanidine sulfate. Experience with the latter is too small to warrant evaluation. more...
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- 1960
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277. Asthmatic Deaths
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John T. Connell
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Pathophysiology of asthma ,Pathology ,medicine.medical_specialty ,business.industry ,Degranulation ,General Medicine ,respiratory system ,Mast cell ,medicine.disease ,respiratory tract diseases ,Bronchospasm ,medicine.anatomical_structure ,Edema ,Immunology ,Bronchial Spasm ,Medicine ,medicine.symptom ,business ,Homeostasis ,Asthma - Abstract
The number of mast cells in the bronchial walls of patients who died of asthma was compared to that in walls of nonasthmatic patients. Mast cells are normal components of bronchial wall and contain chemical mediators which can cause changes in bronchial muscle tone and glandular secretion. Physiological amounts of mediator released by normal stimuli may constitute a local homeostatic mechanism for control of some bronchial functions. Unphysiological quantities released by abnormal stimuli could cause bronchospasm, secretion, and edema leading to obstruction typical of that found in asthma. Degranulated mast cells cannot be identified in tissue sections. There were fewer mast cells in bronchi of patients who died of asthma than in those of nonasthmatic patients, which suggests that marked degranulation of mast cells occurred, and is one mechanism associated with the pathophysiology of asthma. more...
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- 1971
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278. Management of therapeutic unfractionated heparin in COVID‐19 patients: A retrospective cohort study
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Lachelle D. Weeks, Katelyn W. Sylvester, Jean M. Connors, and Nathan T. Connell
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bleeding ,coronavirus ,coronavirus 2019 ,COVID‐19 ,SARS‐CoV‐2 ,therapeutic anticoagulation ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Abstract Background Patients hospitalized with severe acute respiratory syndrome coronavirus 2 infection are at risk for thrombotic complications necessitating use of therapeutic unfractionated heparin (UFH). Full‐dose anticoagulation limits requirements for organ support interventions in moderately ill patients with coronavirus disease 2019 (COVID‐19). Given this benefit, it is important to evaluate response to therapeutic anticoagulation in this population. Objectives The aim of this study was to assess therapeutic UFH infusions and associated bleeding risk in patients with COVID‐19. Patients/Methods This retrospective cohort study includes patients at Brigham and Women’s Hospital, Boston, Massachusetts, receiving weight‐based nursing‐nomogram titrated UFH infusion during a 10‐week surge in COVID‐19 hospitalizations. Of 358 patients on therapeutic UFH during this interval, 97 (27.1%) had confirmed COVID‐19. Patient characteristics, laboratory values, and information regarding UFH infusion and bleeding events were obtained from the electronic medical record. Results Patients who were COVID‐19 positive had fewer therapeutic activatrd partial thromboplastin times (aPTTs) compared to COVID‐19–negative patients (median rate, 40.0% vs 53.1%; P more...
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- 2021
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279. Family history of autoimmune disease in relation to time-to-pregnancy, pregnancy loss, and live birth rate
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Torie C. Plowden, Matthew T. Connell, Micah J. Hill, Pauline Mendola, Keewan Kim, Carrie J. Nobles, Daniel L. Kuhr, Noya Galai, Karen J. Gibbins, Robert M. Silver, Brian Wilcox, Lindsey Sjaarda, Neil J. Perkins, Enrique F. Schisterman, and Sunni L. Mumford more...
- Subjects
Autoimmune disease ,Family history ,Pregnancy loss ,Spontaneous abortion ,Live birth ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Several autoimmune conditions have adverse effects on reproductive outcomes, but the relationship between family history of autoimmune disease in women without these conditions and pregnancy is uncertain. The objective of this study was to determine if there is an association between a family history of an autoimmune condition and time-to-pregnancy (TTP), pregnancy loss, and live birth. This was a prospective cohort study from a RCT of 1228 adult women ages 18–40, who were healthy, had no history of infertility, were actively attempting to conceive, and had one or two prior pregnancy losses. Of these, 1172 women had data available regarding family history of autoimmune conditions. Women with an affected first-degree relative had similar TTP when compared to those without a FHx (fecundability odds ratio 0.90, 95% confidence interval [CI] 0.70, 1.15). Women with an affected first-degree relative had a lower likelihood of live birth (relative risk [RR] 0.83, 95% CI 0.69, 0.99). Among women who achieved pregnancy, FHx of autoimmune disease was associated with a higher likelihood of pregnancy loss (RR 1.49, 95% CI 1.10, 2.03). Women who had a first-degree relative with an autoimmune disease had a similar TTP as unaffected women but a lower likelihood of live birth and higher risk of pregnancy loss. This information may encourage clinicians to evaluate women with a family history of autoimmune conditions prior to pregnancy and highlights the need for further studies to ascertain the effects of autoimmunity and pregnancy. more...
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- 2020
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280. Relative biological effectiveness of clinically relevant photon energies for the survival of human colorectal, cervical, and prostate cancer cell lines.
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Li J, Chabaytah N, Babik J, Behmand B, Bekerat H, Connell T, Evans M, Ruo R, Vuong T, and Abbasinejad Enger S
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- Humans, Male, Female, Uterine Cervical Neoplasms radiotherapy, Colorectal Neoplasms radiotherapy, Colorectal Neoplasms pathology, HeLa Cells, HCT116 Cells, Cell Line, Tumor, Photons therapeutic use, Relative Biological Effectiveness, Cell Survival radiation effects, Prostatic Neoplasms radiotherapy, Prostatic Neoplasms pathology
- Abstract
Objective. Relative biological effectiveness (RBE) differs between radiation qualities. However, an RBE of 1.0 has been established for photons regardless of the wide range of photon energies used clinically, the lack of reproducibility in radiobiological studies, and outdated reference energies used in the experimental literature. Moreover, due to intrinsic radiosensitivity, different cancer types have different responses to radiation. This study aimed to characterize the RBE of clinically relevant high and low photon energies in vitro for three human cancer cell lines: HCT116 (colon), HeLa (cervix), and PC3 (prostate). Approach. Experiments were conducted following dosimetry protocols provided by the American Association of Physicists in Medicine. Cells were irradiated with 6 MV x-rays, an
192 Ir brachytherapy source, 225 kVp and 50 kVp x-rays. Cell survival post-irradiation was assessed using the clonogenic assay. Survival fractions were fitted using the linear quadratic model, and survival curves were generated for RBE calculations. Main results. Cell killing was more efficient with decreasing photon energy. Using 225 kVp x-rays as the reference, the HCT116 RBESF0.1 for 6 MV x-rays,192 Ir, and 50 kVp x-rays were 0.89 ± 0.03, 0.95 ± 0.03, and 1.24 ± 0.04; the HeLa RBESF0.1 were 0.95 ± 0.04, 0.97 ± 0.05, and 1.09 ± 0.03, and the PC3 RBESF0.1 were 0.84 ± 0.01, 0.84 ± 0.01, and 1.13 ± 0.02, respectively. HeLa and PC3 cells had varying radiosensitivity when irradiated with 225 and 50 kVp x-rays. Significance. This difference supports the notion that RBE may not be 1.0 for all photons through experimental investigations that employed precise dosimetry. It highlights that different cancer types may not have identical responses to the same irradiation quality. Additionally, the RBE of clinically relevant photons was updated to the reference energy of 225 kVp x-rays., (Creative Commons Attribution license.) more...- Published
- 2024
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281. Risk and Protective Factors of Self-harm and Suicidality in Adolescents: An Umbrella Review with Meta-Analysis.
- Author
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Richardson R, Connell T, Foster M, Blamires J, Keshoor S, Moir C, and Zeng IS
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- Adolescent, Female, Humans, Male, Adolescent Behavior psychology, Bullying psychology, Bullying statistics & numerical data, Protective Factors, Risk Factors, Suicide psychology, Suicide statistics & numerical data, Self-Injurious Behavior psychology, Self-Injurious Behavior epidemiology, Suicidal Ideation
- Abstract
Suicide remains the second most common cause of death in young people aged 10-24 years and is a growing concern globally. The literature reports a vast number of factors that can predispose an adolescent to suicidality at an individual, relational, community, or societal level. There is limited high-level research identifying and understanding these risk and protective factors of adolescent suicidality. The present study used an umbrella review and meta-analysis to synthesize evidence from the review literature in the past 20 years on risk and protective factors of self-harm and suicidality (behavior and ideation) in adolescents. The umbrella review included 33 quantitative reviews with 1149 individual studies on suicidality and self-harm. Based on the data synthesis, it compared the public health impact of exposure on the population of the identified exposure. Bullying victimization was the most attributed environmental exposure for suicidality. The other identified significant school and individual factors were sleeping disturbance, school absenteeism, and exposure to antidepressants. Several significant vulnerable young populations were identified with significantly higher prevalence of suicidality, including lesbian, gay, bisexual, transgender, queer (or questioning) youth and those with mental health disorders, problem behaviors, previous suicidality, self-harm, and gender (female). A person-centered approach emphasizing connectedness and bully-free school environments should be a priority focus for schools, health professionals, and public health policymakers., (© 2024. The Author(s).) more...
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- 2024
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282. Comparison of mechanical properties and host tissue response to OviTex™ and Strattice™ surgical meshes: author reply.
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Lombardi J, Stec E, Edwards M, Connell T, and Sandor M
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- Humans, Herniorrhaphy, Biocompatible Materials, Surgical Mesh adverse effects, Hernia, Ventral surgery
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- 2024
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283. Antimicrobial and Adjuvant Potencies of Di- n -alkyl Substituted Diazalariat Ethers.
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Patel MB, Spikes H, Bailey RS, Connell T, Gill H, Gokel MR, Harris R, Meisel JW, Negin S, Yin SA, and Gokel GW
- Abstract
Lariat ethers are macrocyclic polyethers-crown ethers-to which sidearms are appended. 4,13-Diaza-18-crown-6 having twin alkyl chains at the nitrogens show biological activity. They exhibit antibiotic activity, but when co-administered at with an FDA-approved antibiotic, the latter's potency is often strongly enhanced. Potency enhancements and resistance reversals have been documented in vitro for a range of Gram-negative and Gram-positive bacteria with a variety of antimicrobials. Strains of E. coli and Staphylococcus aureus having resistance to a range of drugs have been studied and the potency enhancements (checkerboards) are reported here. Drugs included in the present study are ampicillin, cefepime, chlortetracycline, ciprofloxacin, doxycycline, kanamycin, minocycline, norfloxacin, oxycycline, penicillin G, and tetracycline. Enhancements of norfloxacin potency against S. aureus 1199B of up to 128-fold were observed. The properties of these lariat ethers have been studied to determine solubility, their membrane penetration, cytotoxicity and mammalian cell survival, and their effect on bacterial efflux pumps. It is shown that in some cases, the lariat ethers have complex antimicrobials with considerable selectivity. Based on these observations, including 1:1 complexation between lariat ethers and antimicrobials and the cytotoxicity of the MeI salts showing a separation index of 32-fold, they hold significant potential for further development. more...
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- 2023
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284. Inborn Errors of Immunity in Children With Invasive Pneumococcal Disease: A Multicenter Prospective Study.
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Phuong LK, Cheung A, Agrawal R, Butters C, Buttery J, Clark J, Connell T, Curtis N, Daley AJ, Dobinson HC, Frith C, Hameed NS, Hernstadt H, Krieser DM, Loke P, Ojaimi S, McMullan B, Pinzon-Charry A, Sharp EG, Sinnappurajar P, Templeton T, Wen S, Cole T, and Gwee A more...
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- Child, Humans, Infant, Child, Preschool, Prospective Studies, Streptococcus pneumoniae, Pneumococcal Vaccines, Incidence, Pneumococcal Infections prevention & control, Sepsis, Immunologic Deficiency Syndromes complications
- Abstract
Background: In settings with universal conjugate pneumococcal vaccination, invasive pneumococcal disease (IPD) can be a marker of an underlying inborn error of immunity. The aim of this study was to determine the prevalence and characterize the types of immunodeficiencies in children presenting with IPD., Methods: Multicenter prospective audit following the introduction of routinely recommended immunological screening in children presenting with IPD. The minimum immunological evaluation comprised a full blood examination and film, serum immunoglobulins (IgG, IgA and IgM), complement levels and function. Included participants were children in whom Streptococcus pneumoniae was isolated from a normally sterile site (cerebrospinal fluid, pleura, peritoneum and synovium). If isolated from blood, features of sepsis needed to be present. Children with predisposing factors for IPD (nephrotic syndrome, anatomical defect or malignancy) were excluded., Results: Overall, there were 379 episodes of IPD of which 313 (83%) were eligible for inclusion and 143/313 (46%) had an immunologic evaluation. Of these, 17/143 (12%) were diagnosed with a clinically significant abnormality: hypogammaglobulinemia (n = 4), IgA deficiency (n = 3), common variable immunodeficiency (n = 2), asplenia (n = 2), specific antibody deficiency (n = 2), incontinentia pigmenti with immunologic dysfunction (n = 1), alternative complement deficiency (n = 1), complement factor H deficiency (n = 1) and congenital disorder of glycosylation (n = 1). The number needed to investigate to identify 1 child presenting with IPD with an immunologic abnormality was 7 for children under 2 years and 9 for those 2 years old and over., Conclusions: This study supports the routine immune evaluation of children presenting with IPD of any age, with consideration of referral to a pediatric immunologist., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.) more...
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- 2023
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285. Comparison of mechanical properties and host tissue response to OviTex™ and Strattice™ surgical meshes.
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Lombardi J, Stec E, Edwards M, Connell T, and Sandor M
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- Animals, Sheep, Swine, Surgical Mesh adverse effects, Herniorrhaphy, Collagenases, Hernia, Ventral surgery, Biological Products
- Abstract
Purpose: This study compared the in vitro/benchtop and in vivo mechanical properties and host biologic response to ovine rumen-derived/polymer mesh hybrid OviTex™ with porcine-derived acellular dermal matrix Strattice™ Firm., Methods: OviTex 2S Resorbable (OviTex 2S-R) and Strattice morphology were examined in vitro using histology and scanning electron microscopy; mechanical properties were assessed via tensile test; in vivo host biologic response and explant mechanics were evaluated in a rodent subcutaneous model. Separately, OviTex 1S Permanent (OviTex 1S-P) and Strattice were evaluated in a primate abdominal wall repair model., Results: OviTex 2S-R demonstrated layer separation, whereas Strattice retained its structural integrity and demonstrated higher maximum load than OviTex 2S-R out-of-package (124.8 ± 11.1 N/cm vs 37.9 ± 5.5 N/cm, p < 0.001), 24 h (55.7 ± 7.4 N/cm vs 5.6 ± 3.8 N/cm, p < 0.001), 48 h (45.3 ± 14.8 N/cm vs 2.8 ± 2.6 N/cm, p = 0.003), and 72 h (29.2 ± 10.5 N/cm vs 3.2 ± 3.1 N/cm, p = 0.006) following collagenase digestion. In rodents, inflammatory cell infiltration was observed between OviTex 2S-R layers, while Strattice induced a minimal inflammatory response. Strattice retained higher maximum load at 3 (46.3 ± 27.4 N/cm vs 9.5 ± 3.2 N/cm, p = 0.041) and 6 weeks (28.6 ± 14.1 N/cm vs 7.0 ± 3.0 N/cm, p = 0.029). In primates, OviTex 1S-P exhibited loss of composite mesh integrity whereas Strattice integrated into host tissue with minimal inflammation and retained higher maximum load at 1 month than OviTex 1S-P (66.8 ± 43.4 N/cm vs 9.6 ± 4.4 N/cm; p = 0.151)., Conclusions: Strattice retained greater mechanical strength as shown by lower susceptibility to collagenase degradation than OviTex 2S-R in vitro, as well as higher maximum load and improved host biologic response than OviTex 2S-R in rodents and OviTex 1S-P in primates., (© 2023. The Author(s).) more...
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- 2023
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286. Health of children who experienced Australian immigration detention.
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Tosif S, Graham H, Kiang K, Laemmle-Ruff I, Heenan R, Smith A, Volkman T, Connell T, and Paxton G
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- Infant, Humans, Child, Emigration and Immigration, Retrospective Studies, Australia epidemiology, Autism Spectrum Disorder, Refugees psychology
- Abstract
Background: Australian immigration policy resulted in large numbers of children being held in locked detention. We examined the physical and mental health of children and families who experienced immigration detention., Methods: Retrospective audit of medical records of children exposed to immigration detention attending the Royal Children's Hospital Immigrant Health Service, Melbourne, Australia, from January 2012 -December 2021. We extracted data on demographics, detention duration and location, symptoms, physical and mental health diagnoses and care provided., Results: 277 children had directly (n = 239) or indirectly via parents (n = 38) experienced locked detention, including 79 children in families detained on Nauru or Manus Island. Of 239 detained children, 31 were infants born in locked detention. Median duration of locked detention was 12 months (IQR 5-19 months). Children were detained on Nauru/Manus Island (n = 47/239) for a median of 51 (IQR 29-60) months compared to 7 (IQR 4-16) months for those held in Australia/Australian territories (n = 192/239). Overall, 60% (167/277) of children had a nutritional deficiency, and 75% (207/277) had a concern relating to development, including 10% (27/277) with autism spectrum disorder and 9% (26/277) with intellectual disability. 62% (171/277) children had mental health concerns, including anxiety, depression and behavioural disturbances and 54% (150/277) had parents with mental illness. Children and parents detained on Nauru had a significantly higher prevalence of all mental health concerns compared with those held in Australian detention centres., Conclusion: This study provides clinical evidence of adverse impacts of held detention on children's physical and mental health and wellbeing. Policymakers must recognise the consequences of detention, and avoid detaining children and families., Competing Interests: A/Prof Paxton has provided advice to Department of Home Affairs (previously the Department of Immigration and Border Protection) through the Minister’s Council for Asylum Seekers and Detention (2015-2018), the Home Affairs Independent Medical Advisors Panel (previously the Independent Health Advisors Panel, from 2014-ongoing) and the Health Subcommittee of the Joint Advisory Committee for Nauru Regional Processing (2013–2016). GP also chairs a working group on immunisation in refugee and asylum seeker populations for the Victorian Department of Health (from 2015). The Royal Children’s Hospital Immigrant Health Service is funded by the Victorian Department of Health., (Copyright: © 2023 Tosif et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.) more...
- Published
- 2023
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287. Prospective Study of Clinical Outcomes From a Breast Implant Assessment Service.
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Masoumi E, Seow C, Deva AP, Cuss A, Chow O, Davies M, Lajevardi S, Connell T, Magnusson M, Beath K, Isacson D, and Deva AK
- Subjects
- Female, Humans, Adult, Prospective Studies, Silicone Gels adverse effects, Implant Capsular Contracture etiology, Pain etiology, Breast Implants adverse effects, Breast Implantation adverse effects, Contracture complications, Contracture surgery
- Abstract
Background: Breast augmentation remains the commonest cosmetic surgical procedure worldwide, in spite of recent regulatory action., Objectives: The aim of this study was to evaluate women with breast implants attending a breast implant assessment clinic and to capture clinical and implant data in women presenting to the service., Methods: Patients were enrolled prospectively between January 2018 and December 2021. Clinical, implant, and practitioner data were recorded. Patients reported satisfaction on size, shape, and overall outcome as well as the presence or pain. Radiological evaluation, where indicated, was performed and data were included on these findings., Results: A total of 603 patients were assessed. Their mean age was 42.7 years and mean age at implantation was 29.1 years. The most common complications were capsular contracture followed by pain, waterfall deformity, and double bubble, with rupture/contracture rates increasing after the 10-year mark. The risk of double bubble was significantly lower if patients were operated on by certified practitioners (odds ratio = 0.49, P = 0.011). There was almost universally poor awareness of the risks of breast implants in patients presenting for evaluation., Conclusions: This study has shown benefit in a breast implant assessment clinic to gather information on adverse events and patient-reported outcomes following breast implant surgery. Having appropriately trained and certified practitioners perform cosmetic augmentation significantly lowers the risk of implant malposition and deformity. Any adverse event occurring within 5 years of initial surgery should be flagged as a mandatory reportable clinical indicator and trigger further investigation., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Aesthetic Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.) more...
- Published
- 2023
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288. Not just a chalazion-focal eyelid and orbital infection with Saksaenea vasiformis in an immunocompetent child.
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Phuong LK, Connell T, MacGregor D, and Elder JE
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- Child, Preschool, Diagnosis, Differential, Eyelids pathology, Humans, Male, Chalazion diagnosis, Chalazion pathology, Orbital Cellulitis diagnosis
- Abstract
We present the case of a 2-year-old immunocompetent boy who presented with subacute right-sided orbital cellulitis due to Saksaenea vasiformis infection. Initial differential diagnoses included chalazion and localized soft tissue malignancy. There was no history of trauma. Immunological review and investigations were unremarkable. He was treated with a total of 3 months of antifungal therapy. Following resolution, he had two episodes of spontaneously resolving localized eyelid erythema at 2 and 8 months., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2022
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289. Rigid and Deformable Image Registration for Radiation Therapy: A Self-Study Evaluation Guide for NRG Oncology Clinical Trial Participation.
- Author
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Rong Y, Rosu-Bubulac M, Benedict SH, Cui Y, Ruo R, Connell T, Kashani R, Latifi K, Chen Q, Geng H, Sohn J, and Xiao Y
- Subjects
- Algorithms, Humans, Phantoms, Imaging, Radiotherapy Planning, Computer-Assisted, Neoplasms diagnostic imaging, Neoplasms radiotherapy, Radiation Oncology
- Abstract
Purpose: The registration of multiple imaging studies to radiation therapy computed tomography simulation, including magnetic resonance imaging, positron emission tomography-computed tomography, etc. is a widely used strategy in radiation oncology treatment planning, and these registrations have valuable roles in image guidance, dose composition/accumulation, and treatment delivery adaptation. The NRG Oncology Medical Physics subcommittee formed a working group to investigate feasible workflows for a self-study credentialing process of image registration commissioning., Methods and Materials: The American Association of Physicists in Medicine (AAPM) Task Group 132 (TG132) report on the use of image registration and fusion algorithms in radiation therapy provides basic guidelines for quality assurance and quality control of the image registration algorithms and the overall clinical process. The report recommends a series of tests and the corresponding metrics that should be evaluated and reported during commissioning and routine quality assurance, as well as a set of recommendations for vendors. The NRG Oncology medical physics subcommittee working group found incompatibility of some digital phantoms with commercial systems. Thus, there is still a need to provide further recommendations in terms of compatible digital phantoms, clinical feasible workflow, and achievable thresholds, especially for future clinical trials involving deformable image registration algorithms. Nine institutions participated and evaluated 4 commonly used commercial imaging registration software and various versions in the field of radiation oncology., Results and Conclusions: The NRG Oncology Working Group on image registration commissioning herein provides recommendations on the use of digital phantom/data sets and analytical software access for institutions and clinics to perform their own self-study evaluation of commercial imaging systems that might be employed for coregistration in radiation therapy treatment planning and image guidance procedures. Evaluation metrics and their corresponding values were given as guidelines to establish practical tolerances. Vendor compliance for image registration commissioning was evaluated, and recommendations were given for future development., (Copyright © 2021 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2021
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290. Accessing Alternative Response Payways: A Multi-Level Examination of Family and Community Factors on Race Equity.
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Connell T
- Subjects
- Black or African American, Child, Child Abuse prevention & control, Child Protective Services methods, Child, Preschool, Family, Family Characteristics, Female, Humans, Male, New York epidemiology, Poverty, Race Factors, Residence Characteristics, Socioeconomic Factors, Child Abuse statistics & numerical data, Child Welfare
- Abstract
Background: Although research has identified factors associated with child welfare involvement, less attention has been paid to how Black families are assigned to types of child welfare responses. The advent of alternative response pathways allows child protection workers to assign child abuse and neglect responses to families based on the type and seriousness of the maltreatment, history of prior reports and age of the child., Objective: The effects of family and community characteristics on alternative response pathways are examined by exploring decision-making at two points in the child welfare system: access to an alternative response child welfare system and assignment to either an investigative or alternative response pathway., Participants and Setting: Black and White families reported for child abuse and neglect (N = 31,802) in New York State were studied., Methods: Using data from the National Child Abuse and Neglect Data System matched with New York State county socioeconomic indicators, logistic and multi-level analyses examined the effect of county-level variables on family characteristics., Results: The analysis determined that Black children and families were not assigned to alternative response pathways similarly to White families especially in counties where indication rates were higher., Conclusion: Findings imply that Black families involved in the child welfare system may benefit from increased access to culturally responsive interventions that target neighborhoods with high indication rates., (Copyright © 2020 Elsevier Ltd. All rights reserved.) more...
- Published
- 2020
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291. Structuring ward rounds to enhance education.
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Gray AZ, Modak M, Connell T, and Enright H
- Subjects
- Consultants, Focus Groups, Hospitals, Humans, Surveys and Questionnaires, Teaching Rounds
- Abstract
Background: Ward rounds are a fundamental part of hospital culture and teaching on rounds has a long tradition. Yet evidence points towards increasing difficulties in delivering ward round education in complex heath care settings. Drawing on the literature and gaps identified in our own hospital setting we hypothesised that a tool for structuring ward rounds could improve the educational experience on rounds without adding a time burden to already busy consultants., Methods: We used a developmental evaluation approach to develop a framework and evaluate a tool for improving ward round education. The ward round framework STIC (Set, Target, Inspect and Close) and ward round tool was developed through an iterative process of reviewing and piloting in a clinical department and was evaluated against Moore's outcome levels drawing on quantitative and qualitative data. Surveys of consultants were used to quantify uptake, acceptability and usefulness of the ward round tool. Focus groups of trainee doctors evaluated their experience of ward round education., Results: The majority of consultants used the ward round tool and found it accessible, and useful to enhance education, without extending ward round time. Trainee doctors had seen the ward round tool in use and reflected that it provided structure, focused their learning opportunities, gave clarity to the agenda and provided closure. Unintended benefits were seen for enhanced team work., Conclusions: We present a structured framework STIC and tool for ward rounds that incorporates education, which is acceptable to consultants and is perceived to enhance education for trainees and to strengthen team work. Understanding our framework STIC and our ward round tool's applicability in other settings, scalability and impact and the perspective of patients, would be valuable extensions of this work. We present a structured framework STIC and tool for ward rounds that incorporates education, which is acceptable to consultants and is perceived to enhance education for trainees and to strengthen team work., (© 2019 John Wiley & Sons Ltd and The Association for the Study of Medical Education.) more...
- Published
- 2020
- Full Text
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292. Topic analysis of Road safety inspections using latent dirichlet allocation: A case study of roadside safety in Irish main roads.
- Author
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Roque C, Lourenço Cardoso J, Connell T, Schermers G, and Weber R
- Subjects
- Built Environment statistics & numerical data, Humans, Ireland, Probability, Safety, Accidents, Traffic prevention & control, Built Environment standards
- Abstract
Under the Safe System framework, Road Authorities have a responsibility to deliver inherently safe roads and streets. Addressing this problem depends on knowledge of the road network safety conditions and the number of funds available for new road safety interventions. It also requires the prioritisation of the various interventions that may generate benefits, increasing safety, while ensuring that reasonable steps are taken to remedy the deficiencies detected within a reasonable timeframe. In this context, Road Safety Inspections (RSI) are a proactive tool for identifying safety issues, consisting of a regular, systematic, on-site inspection of existing roads, covering the whole road network, carried out by trained safety expert teams. This paper aims to describe how topic modelling can be effectively used to identify co-occurrence patterns of attributes related to the run-off-road crashes, as well as the corresponding patterns of road safety interventions, as described in the RSI reports. We apply latent Dirichlet allocation (LDA), a widespread method for fitting a topic model, to analyse the topics mentioned in RSI reports, divided into two groups: problems found; and proposed solutions. For this study, 54 RSI gathered over six years (2012-2017) were analysed, covering 4011 km of Irish roads. The results indicate that important keywords relating to the "forgiving roadside" and "clear zone" concepts, as well as the relevant European technical standards (CEN-EN1317 and EN 12,767), are absent from the extracted latent topics. We also found that the frequency of topics related to roadside safety is higher in the problems record set than in the solutions record set, meaning that problems are more easily identified and related to the roadside area than interventions may be. This paper presents methodological empirical evidence that the LDA is appropriate for identifying the co-occurrence patterns of attributes related to the ROR crashes in road safety inspections' reports, as well as the interventions' patterns associated with these crashes. Also, it provides valuable information aimed to determine the extent to which national road authorities in Europe and their contractors are currently capable of implementing and maintaining compliance with roadside standards and guidelines throughout the life cycle of roads., (Copyright © 2019 Elsevier Ltd. All rights reserved.) more...
- Published
- 2019
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293. Breast Implant Selection: Consensus Recommendations Using a Modified Delphi Method.
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Magnusson MR, Connell T, Miroshnik M, Layt C, Ashton M, Deva AK, Farrow H, and Januszkiewicz J
- Abstract
Background: Geographical differences in breast implant selection approaches exist, and clinical data to guide the process are limited. Developing knowledge of implant-related risk factors further complicates the process. This analysis aimed to establish expert consensus on considerations for breast implant selection in Australia and New Zealand based on practice patterns in those countries., Methods: A modified Delphi method was used to gain consensus from experts in breast augmentation surgery in Australia and New Zealand. Panelists anonymously completed an initial questionnaire on current considerations in implant selection, discussed a summary of their responses in a live meeting, and completed a final consensus survey based on their live recommendations., Results: Seven panelists completed the final consensus survey. Consensus recommendations included ensuring consideration of proper surgical technique (pocket formation, positioning of implant) and patient tissue and anatomical characteristics, weighing relative expected results of various surface textures, sizes, and degrees of cohesivity, and careful contemplation of the migration risk., Conclusions: This modified Delphi exercise provided consensus recommendations on the key factors involved in implant selection from the perspective of plastic surgeons with practices in Australia and New Zealand. A primary recommendation was that the choice of implant for each patient should be individualized to patient tissue and anatomical characteristics. more...
- Published
- 2019
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294. Pulmonary Mycobacterium abscessus complex in children with cystic fibrosis: A practical management guideline.
- Author
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Andrew EC, Connell T, Robinson P, Curtis N, Massie J, Robertson C, Harrison J, Shanthikumar S, Bryant PA, Starr M, Steer A, Ranganathan S, and Gwee A
- Subjects
- Child, Comorbidity, Cystic Fibrosis diagnosis, Cystic Fibrosis drug therapy, Female, Humans, Male, Mycobacterium Infections, Nontuberculous diagnosis, Practice Guidelines as Topic, Prognosis, Treatment Outcome, Anti-Bacterial Agents therapeutic use, Cystic Fibrosis epidemiology, Mycobacterium Infections, Nontuberculous drug therapy, Mycobacterium Infections, Nontuberculous epidemiology, Mycobacterium abscessus isolation & purification
- Abstract
The treatment of Mycobacterium abscessus complex (MABSC) pulmonary infections is an emerging challenge in patients with cystic fibrosis (CF). Multidrug therapy for prolonged durations is required and carries the significant burden of drug-related toxicity, cost and selective pressure for multiresistant bacteria. International guidelines acknowledge that clinical and in vitro data to support treatment regimens are limited, particularly in children. As part of a collaboration between the infectious diseases and respiratory units at our institution, we have developed a modified treatment guideline that aims to balance the aims of MABSC eradication and slowing disease progression with minimising drug toxicity and resistance. The outcomes of this treatment approach will be monitored and reported. In this manuscript, we discuss the available evidence for treatment choices and present our treatment guideline for paediatric patients with CF and MABSC infection., (© 2019 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).) more...
- Published
- 2019
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295. The immune mediated role of extracellular HMGB1 in a heterotopic model of bladder cancer radioresistance.
- Author
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Ayoub M, Shinde-Jadhav S, Mansure JJ, Alvarez F, Connell T, Seuntjens J, Piccirillo CA, and Kassouf W
- Subjects
- Animals, Cell Line, Tumor, Cell Proliferation, Forkhead Transcription Factors metabolism, Glycyrrhizic Acid pharmacology, HMGB1 Protein antagonists & inhibitors, Macrophages pathology, Mice, Inbred C57BL, Myeloid-Derived Suppressor Cells metabolism, T-Lymphocytes, Regulatory metabolism, Tumor Microenvironment, Urinary Bladder Neoplasms genetics, Urinary Bladder Neoplasms pathology, HMGB1 Protein metabolism, Radiation Tolerance, Urinary Bladder Neoplasms immunology, Urinary Bladder Neoplasms radiotherapy
- Abstract
Radical cystectomy (RC) together with bilateral pelvic lymph node dissection remains the standard treatment for muscle invasive bladder cancer (MIBC). However, radiation-based treatments such as tri-modal therapy (TMT) involving maximally performed transurethral resection of bladder tumor (TURBT), radiotherapy (XRT), and a chemosensitizer represent an attractive, less invasive alternative. Nevertheless, 25-30% of MIBC patients will experience local recurrence after TMT and half will develop metastasis. Radioresistance of tumor cells could potentially be one of the causes for local recurrence post treatment. High mobility group box-1 (HMGB1) was shown to play a role in bladder cancer radioresistance through its intracellular functions in promoting DNA damage repair and autophagy. Recently, HMGB1 was found to be passively released from irradiated tumor cells. However, less is known about the involvement of extracellular HMGB1 in impairing radiation response and its exact role in modulating the tumor immune microenvironment after XRT. We identified a novel mechanism of bladder cancer radioresistance mediated by the immunological functions of HMGB1. The combination of radiation plus extracellular HMGB1 inhibition markedly improved the radiation response of tumors and resulted in marked changes in the immune landscape. Moreover, combining radiation and HMGB1 inhibition significantly impaired tumor infiltrating MDSCs and TAMs -but not Tregs- and shifted the overall tumor immune balance towards anti-tumoral response. We conclude that extracellular HMGB1 is involved in bladder cancer radioresistance through promoting pro-tumor immune mechanisms. more...
- Published
- 2019
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296. Mycobacteria-Specific Mono- and Polyfunctional CD4+ T Cell Profiles in Children With Latent and Active Tuberculosis: A Prospective Proof-of-Concept Study.
- Author
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Tebruegge M, Ritz N, Donath S, Dutta B, Forbes B, Clifford V, Zufferey C, De Rose R, Robins-Browne RM, Hanekom W, Graham SM, Connell T, and Curtis N
- Subjects
- Antigens, Bacterial immunology, Bacterial Proteins immunology, Cells, Cultured, Child, Diagnosis, Differential, Disease Progression, Flow Cytometry, Humans, Immunophenotyping, Latent Tuberculosis diagnosis, Lymphocyte Activation, Proof of Concept Study, Prospective Studies, T-Cell Antigen Receptor Specificity, Biomarkers metabolism, CD4-Positive T-Lymphocytes immunology, Cytokines metabolism, Latent Tuberculosis immunology
- Abstract
Background: Current immune-based TB tests, including the tuberculin skin test (TST) and interferon-gamma release assays (IGRA), have significant limitations, including the inability to distinguish between latent TB infection (LTBI) and active TB. Few biomarkers with the potential to discriminate between these two infection states have been identified. Objective: To determine whether functional profiling of mycobacteria-specific T cells can distinguish between TB-infected and -uninfected children, and simultaneously discriminate between LTBI and active TB. Methods: One hundred and forty-nine children with suspected active TB or risk factors for LTBI were recruited at the Royal Children's Hospital Melbourne. Whole-blood stimulation assays, using ESAT-6, CFP-10, PPD, and heat-killed M. tuberculosis as stimulants, were done, followed by intracellular cytokine staining and flow cytometric analysis. Results: Eighty-two participants in the well-defined diagnostic categories 'uninfected individuals' (asymptomatic, TST 0 mm / IGRA-; n = 61), LTBI (asymptomatic, TST ≥10 mm / IGRA+, normal chest radiograph; n = 15), or active TB [microbiologically-confirmed ( n = 3) or fulfilling stringent criteria ( n = 3)] were included in the final analysis. The proportions of mycobacteria-specific single-positive TNF-α+ and double-positive IFN-γ+/TNF-α+ CD4+ T cells were significantly higher in participants with active TB than in those with LTBI and uninfected individuals. Additionally, the frequency of IL-17-expressing CD4+ T cells, predominately with single-positive IL-17+ and double-positive IL-2+/IL-17+ phenotypes, was higher in participants with active TB than in the other two groups. Conclusions: The frequencies and functional profiles of mycobacteria-specific CD4+ T cells differ significantly both between TB-infected and TB-uninfected children, and between LTBI and active TB. Although confirmation in further studies will be required, these findings indicate that functional profiling of mycobacteria-specific CD4+ T cells could potentially be exploited for novel immune-based TB assays that enable the distinction between infection states based on a blood sample alone. more...
- Published
- 2019
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297. Ionizing Radiation in Interventional Cardiology and Electrophysiology.
- Author
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Al Kharji S, Connell T, Bernier M, and Eisenberg MJ
- Subjects
- Cardiology, Documentation, Humans, Informed Consent, Occupational Exposure adverse effects, Patient Education as Topic, Radiation Dosage, Radiation Exposure adverse effects, Radiation Protection methods, Unnecessary Procedures, Occupational Exposure prevention & control, Radiation Exposure prevention & control, Radiation, Ionizing, Radiography, Interventional
- Abstract
Fluoroscopy-guided procedures constitute a major part in the practice of cardiology. These procedures are also a source of human-made ionizing radiation. Although the benefits of performing the procedure surpass the radiogenic risks in most cases, the risks are not negligible. Exposure to ionizing radiation may lead to tissue injuries and potential increase in risk of cancer. Both patients and operating physicians are exposed to these risks in variable degrees. The institution of radiation safety practices alone significantly reduces radiation exposure. Beyond the interventional laboratory, increasing physicians' awareness to health-related risks of ionizing radiation is crucial in reducing unnecessary testing and increases receptiveness to patient risks. Incorporating the radiogenic risks of a future procedure in patient-informed consent also increases patients' awareness to potential consequences. Innovation in imaging technology resulted in a plethora of alternate modalities. Electroanatomical mapping, magnetic navigation systems, robotic and magnetic resonance imaging (MRI)-assisted techniques are examples of clinically used modalities that limit the exposure of patients and operating physicians to radiation. Documentation of patients' exposure in their medical records is essential. Tracking of patients' cumulative exposure can be implemented at an institutional level. Identifying patients with the highest exposure would help shed light on a blind spot in our current practice, as the implications are unclear., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2019
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298. Breast Reconstruction Following Breast Implant-Associated Anaplastic Large Cell Lymphoma.
- Author
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Lamaris GA, Butler CE, Deva AK, Miranda RN, Hunt KK, Connell T, Lipa JE, and Clemens MW
- Subjects
- Adult, Aged, Breast Implantation adverse effects, Breast Implantation methods, Breast Neoplasms pathology, Breast Neoplasms surgery, Cohort Studies, Device Removal methods, Female, Humans, Lymphoma, Large-Cell, Anaplastic pathology, Mastectomy methods, Middle Aged, Prognosis, Retrospective Studies, Risk Assessment, Tertiary Care Centers, Treatment Outcome, Breast Implants adverse effects, Breast Neoplasms etiology, Lymphoma, Large-Cell, Anaplastic etiology, Lymphoma, Large-Cell, Anaplastic surgery, Mammaplasty methods
- Abstract
Background: Standard of care treatment of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) involves surgical resection with implant removal and complete capsulectomy. We report a case series of BIA-ALCL reconstruction with proposals for timing and technique selection., Methods: We retrospectively reviewed and prospectively enrolled all BIA-ALCL patients at 2 tertiary care centers and 1 private plastic surgery practice from 1998 to 2017. Demographics, treatment, reconstruction, pathology staging, patient satisfaction, and oncologic outcomes were reviewed., Results: We treated 66 consecutive BIA-ALCL patients and 18 (27%) received reconstruction. Seven patients (39%) received immediate reconstruction, and 11 (61%) received delayed reconstruction. Disease stage at presentation was IA (T1N0M0 disease confined to effusion or a layer on luminal side of capsule with no lymph node involvement and no distant spread) in 56%, IB in 17%, IC (T3N0M0 cell aggregates or sheets infiltrating the capsule, no lymph node involvement and no distant spread) in 6%, IIA (T4N0M0 lymphoma infiltrating beyond the capsule, no lymph node involvement and no distant spread) in 11%, and III in 11%. Types of reconstruction included smooth implants (72%), immediate mastopexy (11%), autologous flaps (11%), and fat grafting (6%). Outcomes included no surgical complications, but 1 patient progressed to widespread bone metastasis (6%); ultimately, all patients achieved complete remission. Ninety-four percent were satisfied/highly satisfied with reconstructions, whereas 6% were highly unsatisfied with immediate smooth implants., Conclusions: Breast reconstruction following BIA-ALCL management can be performed with acceptable complications if complete surgical ablation is possible. Immediate reconstruction is reserved for disease confined to capsule on preoperative positive emission tomography/computed tomography scan. Genetic predisposition and bilateral cases suggest that BIA-ALCL patients should not receive textured implants. Autologous options are preferable for implant adverse BIA-ALCL patients. Patients with extensive disease at presentation should be considered for 6- to 12-month delayed reconstruction with interval positive emission tomography/computed tomography evaluation. more...
- Published
- 2019
- Full Text
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299. Barriers to antenatal psychosocial assessment and depression screening in private hospital settings.
- Author
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Connell T, Barnett B, and Waters D
- Subjects
- Adult, Australia epidemiology, Depression psychology, Female, Humans, Middle Aged, Poverty psychology, Pregnancy, Pregnancy Complications psychology, Psychiatric Status Rating Scales, Risk Assessment, Attitude of Health Personnel, Depression diagnosis, Hospitals, Private statistics & numerical data, Mass Screening methods, Pregnancy Complications diagnosis, Prenatal Care
- Abstract
Problem: The evidence of benefit for antenatal psychosocial assessment and depression screening has been sufficient to lead the implementation of screening in public hospitals in all states of Australia. Details of the implementation of perinatal screening in private obstetric settings is less well known., Aim: As any successful implementation relies on the identification of local barriers, we aimed to determine what perceived or actual barriers may exist for the implementation of evidence-based perinatal screening interventions in private obstetric care, and specifically within small private hospitals., Method: The integrative literature review method offers a structured systematic approach to organise, synthesize and critique research from a range of sources. This method was used to determine what barriers have been identified in implementing psychosocial assessment and depression screening with women receiving obstetric care in private hospital settings., Findings: The integrative review findings suggest that barriers to implementing psychosocial screening in the private sector are similar to those experienced in the public sector but may also be influenced by the corporate focus of private services. Barriers were identified among health professionals, within the personal and psychosocial context of women and their families, and at provider or system level., Conclusion: Once identified, barriers can be systematically addressed to enhance the success of implementing psychosocial and depression screening in the private sector. Screening is likely to be influenced by the business models and operating systems of private service providers. Health professionals working within this environment need more support to conduct perinatal assessment within this context., (Copyright © 2017 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.) more...
- Published
- 2018
- Full Text
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300. Clinician modifiable factors associated with better quality of life in children with acquired brain injury undergoing rehabilitation.
- Author
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Connell T, Paterson J, Roberts RM, Raghavendra P, Sawyer M, and Russo RN
- Subjects
- Adaptation, Psychological, Adolescent, Child, Child, Preschool, Correlation of Data, Exercise physiology, Female, Humans, Male, Social Behavior Disorders etiology, Social Skills, Brain Injuries psychology, Brain Injuries rehabilitation, Quality of Life psychology
- Abstract
Objectives: To identify clinician-modifiable factors related to quality of life (QOL) in children with acquired brain injury (ABI)., Participants and Methods: Thirty-nine children attending an ABI rehabilitation program (5-18 years) were assessed using the Personality Inventory for Children-2, Vineland Adaptive Behavior Scale-2, Handicap-Related Problems for Parents Inventory and Children's Assessment of Participation and Enjoyment. The Pediatric Quality of Life Inventory was completed by children and parents six months later., Results: Children with lower levels of internalising and externalising behaviours, health and social skill problems, and higher family functioning had significantly higher levels of total QOL (child and parent rated) (r = -.47 to -.79). In addition, children with higher levels of adaptive behaviour had significantly higher parent rated total QOL (r = .46). Measures of mother's stressors had moderate but not statistically significant relationships with the child's total QOL (r = -.31 to -.35). There were moderate and statistically significant relationships between measures of participation in physical activities and total QOL as rated by children (r = .42-.48) but not parents (r = .11-.30)., Conclusions: These findings suggest potential targets to be investigated in future clinical research in rehabilitation following ABI in children to optimise QOL. more...
- Published
- 2018
- Full Text
- View/download PDF
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