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1.
J Neonatal Perinatal Med ; 17(1): 1-5, 2024.
Article in English | MEDLINE | ID: mdl-38393923

ABSTRACT

BACKGROUND: The aim of our study is to describe maternal and neonatal morbidity and mortality in patients undergoing trial of labor after cesarean from the Consortium on Safe Labor. METHODS: This was a secondary analysis of the Consortium on Safe Labor database, a retrospective cohort study over a 7 year study period. Maternal and neonatal outcomes were evaluated based on desired delivery mode: planned elective repeat cesarean delivery or trial of labor after cesarean. RESULTS: Of 9858 patients in our analysis, our study population had 4400 patients (45%) who desired trial of labor after cesarean and 5458 patients (55%) who desired elective repeat cesarean delivery. Women who attempted trial of labor after cesarean compared to those who had an elective repeat cesarean delivery were more likely to have an obstetric hemorrhage (adjusted odds ratio 1.6; 95% CI 1.3 -2.0) and blood transfusion (adjusted odds ratio 2.3; 95% CI 1.6 -3.2). CONCLUSION: Maternal morbidity in women undergoing trial of labor after cesarean was predominantly hemorrhage-related.


Subject(s)
Labor, Obstetric , Trial of Labor , Pregnancy , Infant, Newborn , Humans , Female , Retrospective Studies , Hemorrhage
2.
J Neonatal Perinatal Med ; 16(3): 375-385, 2023.
Article in English | MEDLINE | ID: mdl-37718867

ABSTRACT

OBJECTIVE: The objective of this study is to develop a model that will help predict the risk of blood transfusion using information available prior to delivery. STUDY DESIGN: The study is a secondary analysis of the Consortium on Safe Labor registry. Women who had a delivery from 2002 to 2008 were included. Pre-delivery variables that had significant associations with transfusion were included in a multivariable logistic regression model predicting transfusion. The prediction model was internally validated using randomly selected samples from the same population of women. RESULTS: Of 156,572 deliveries, 5,463 deliveries (3.5%) required transfusion. Women who had deliveries requiring transfusion were more likely to have a number of comorbidities such as preeclampsia (6.3% versus 4.1%, OR 1.21, 95% CI 1.08-1.36), placenta previa (1.8% versus 0.4%, OR 4.11, 95% CI 3.25-5.21) and anemia (10.6% versus 5.4%, OR 1.30, 95% CI 1.21-1.41). Transfusion was least likely to occur in university teaching hospitals compared to community hospitals. The c statistic was 0.71 (95% CI 0.70-0.72) in the derivation sample. The most salient predictors of transfusion included type of hospital, placenta previa, multiple gestations, diabetes mellitus, anemia, asthma, previous births, preeclampsia, type of insurance, age, gestational age, and vertex presentation. The model was well-calibrated and showed strong internal validation. CONCLUSION: The model identified independent risk factors that can help predict the risk of transfusion prior to delivery. If externally validated in another dataset, this model can assist health care professionals counsel patients and prepare facilities/resources to reduce maternal morbidity.

3.
Hernia ; 21(5): 767-770, 2017 10.
Article in English | MEDLINE | ID: mdl-28735364

ABSTRACT

BACKGROUND: Umbilical hernias present commonly during pregnancy secondary to increased intra-abdominal pressure. As a result, umbilical hernia incarceration or strangulation may affect pregnant females. The purpose of this study is to detail the operative management and 30-day outcomes of umbilical hernias in pregnant patients using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). METHODS: All female patients undergoing umbilical hernia repair during pregnancy were identified within the ACS-NSQIP. Preoperative patient variables, intraoperative variables, and 30-day patient morbidity and mortality outcomes were investigated using a variety of statistical tests. RESULTS: A total of 126 pregnant patients underwent umbilical hernia repair from 2005 to 2014; 73 (58%) had incarceration or strangulation at the time of surgical intervention. The majority of patients (95%) underwent open umbilical hernia repair. Superficial surgical site infection was the most common morbidity in patients undergoing open umbilical hernia repair. CONCLUSIONS: Based on review of the ACS-NSQIP database, the incidence of umbilical hernia repair during pregnancy is very low; however, the majority of patients required repair for incarceration of strangulation. When symptoms develop, these hernias can be repaired with minimal 30-day morbidity to the mother. Additional studies are needed to determine the long-term recurrence rate of umbilical hernia repairs performed in pregnant patients and the effects of surgical intervention and approach on the fetus.


Subject(s)
Hernia, Umbilical/surgery , Herniorrhaphy , Pregnancy Complications/surgery , Adult , Databases, Factual , Female , Herniorrhaphy/adverse effects , Humans , Middle Aged , Pregnancy , Quality Improvement , United States
4.
Eur J Vasc Endovasc Surg ; 54(1): 5-11, 2017 07.
Article in English | MEDLINE | ID: mdl-28279653

ABSTRACT

OBJECTIVES: Surgeons have multiple grafts options available for the endovascular treatment of abdominal aortic aneurysm (EVAR), and some hypothesize that suprarenal fixation endografts may result in higher rates of renal complications than infrarenal endografts. This study aimed to compare the outcomes of contemporary suprarenal and infrarenal endografts. METHODS: The Targeted Vascular Module of the National Surgical Quality Improvement Project was utilised to identify patients undergoing EVAR for infrarenal aneurysm from 2011 to 2013. Pre-operative and operative variables and 30 day outcomes were compared among suprarenal (Zenith and Endurant) and infrarenal fixation devices (Excluder). Renal complications included creatinine increase > 2 mg/dL or new dialysis, as defined by NSQIP. Multivariate regression was completed to account for patient demographics, comorbidities, and operative characteristics. RESULTS: A total of 3587 patients were evaluated including 2273 (63%) with suprarenal grafts and 1314 (37%) with infrarenal grafts. Patients with suprarenal grafts were less commonly white (84% vs. 88%, p < .01) and more commonly male (83% vs. 80%, p = .03). There were no differences in age or comorbidities. Renal complications (1.1% vs. 0.1%, p < .01) and length of stay more than 2 days (34% vs. 25%, p < .01) occurred more commonly after suprarenal fixation. After adjustment, suprarenal grafts had significantly higher rates of renal complications (OR, 12.0; 95% CI, 1.6-91) and length of stay more than 2 days (OR, 1.4; 95% CI, 1.2-1.7). CONCLUSION: Overall rates of renal complications following EVAR are low. Patients selected for suprarenal stent grafts are at increased risk of renal complications and prolonged length of stay, which may be due to selection bias, deployment techniques, or the presence of a bare stent overlying the renal arteries. Further studies are necessary to evaluate the mechanism and duration of renal dysfunction and important long-term outcomes of interest.


Subject(s)
Aortic Aneurysm, Abdominal/surgery , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis , Endovascular Procedures/adverse effects , Endovascular Procedures/instrumentation , Kidney Diseases/etiology , Stents , Aged , Aged, 80 and over , Aortic Aneurysm, Abdominal/diagnostic imaging , Biomarkers/blood , Chi-Square Distribution , Creatinine/blood , Female , Humans , Kidney Diseases/diagnosis , Kidney Diseases/therapy , Length of Stay , Male , Multivariate Analysis , Odds Ratio , Prosthesis Design , Registries , Renal Dialysis , Risk Factors , Time Factors , Treatment Outcome
5.
Int J Obstet Anesth ; 28: 3-11, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27717635

ABSTRACT

BACKGROUND: The appropriate dose of intrathecal morphine for post-cesarean analgesia is unclear. With the inclusion of routine non-steroidal anti-inflammatory drugs, the required dose of morphine may be significantly less than the 200-300µg common a decade ago. We performed a two-center, prospective, randomized, blinded trial comparing three doses of intrathecal morphine, combined with routine intravenous ketorolac, in 144 healthy women undergoing elective cesarean delivery. METHODS: Patients received an intrathecal injection of hyperbaric bupivacaine 12mg, fentanyl 15µg and a randomized dose of 50, 100, or 150µg morphine in a volume of 2.2mL. Patients received intravenous ketorolac 30mg before leaving the operating room and 15mg intravenously every 6h for the duration of the study (24h). All received postoperative patient-controlled intravenous morphine. The primary endpoint was total intravenous morphine administered postoperatively over 24h, analyzed using mixed model regression. RESULTS: There were no differences between dose groups (or institutions) in intravenous morphine use over 24h. Visual analog scale scores for pain and nausea did not differ. Pruritus was greater in the 100 and 150µg groups than the 50µg group at 6h and 12h, but there was no difference between groups in nausea or pruritus treatments. Respiratory depression or significant sedation did not occur. CONCLUSION: The dose-response relationship of intrathecal morphine for multimodal post-cesarean analgesia suggests that 50µg produces analgesia similar to that produced by either 100µg or 150µg.


Subject(s)
Analgesia/methods , Cesarean Section , Ketorolac/administration & dosage , Morphine/pharmacology , Pain, Postoperative/drug therapy , Adult , Analgesics, Opioid/administration & dosage , Analgesics, Opioid/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Dose-Response Relationship, Drug , Female , Humans , Injections, Spinal , Morphine/administration & dosage , Prospective Studies , Treatment Outcome
6.
Int J Oral Maxillofac Surg ; 45(6): 764-8, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26969301

ABSTRACT

To further define potential factors that may contribute to stone formation in salivary glands (sialolithiasis), a retrospective chart review was performed of patients diagnosed with sialolithiasis between March 1, 1998 and February 29, 2012. Information on salivary gland stone number, location and size, medical history, medications, and serum electrolyte levels were collected. Associations between electrolyte levels and stone characteristics (such as stone number and size) were examined. Fifty-nine patients were identified; their median age was 58 years (range 25-89 years) and most were male (95%). Salivary stones were most commonly located in the submandibular glands (83%). Thirty-five patients (59%) had a smoking history, with 16 (27%) reported as current smokers. There was a significant association between current smoker status and stone size (mean largest stone size 12.4±8.8mm vs. 7.5±4.8mm in current smokers vs. non-smokers; P=0.03). Serum sodium levels (r=0.32, P=0.014) and serum potassium levels (r=0.31, P=0.017) showed significant positive correlations with stone size. While the aetiology of sialolithiasis remains unclear, smoking (which can contribute to reduced saliva flow) and higher serum sodium levels (which can reflect volume depletion) are associated with larger salivary stones.


Subject(s)
Potassium/blood , Salivary Gland Calculi/blood , Smoking/adverse effects , Sodium/blood , Adult , Aged , Aged, 80 and over , Electrolytes/blood , Female , Humans , Male , Middle Aged , Retrospective Studies , Salivary Gland Calculi/etiology , Salivary Gland Calculi/pathology , Submandibular Gland , Submandibular Gland Diseases/blood , Submandibular Gland Diseases/etiology
7.
Eur J Trauma Emerg Surg ; 41(4): 405-11, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26038005

ABSTRACT

PURPOSE: Etomidate is a commonly used agent for rapid sequence induction (RSI) in trauma due to its limited hemodynamic effects. Given a recent nationwide shortage of etomidate, alternative induction agents may be required. Propofol is a frequent substitute; however, concern exists regarding its potential hypotensive effects. The study attempts to determine the hemodynamic effects of propofol and etomidate following RSI in trauma bay. METHODS: A retrospective study was performed on 76 consecutive trauma patients requiring RSI at a single academic medical center. Patients were stratified by age, gender, mechanism of injury, Injury Severity Score (ISS), and Glasgow Coma Scale (GCS). Pre-induction and post-induction hemodynamic parameters were evaluated, and a multivariate regression analysis was performed. RESULTS: The mean age was 42, ISS was 13, and GCS was 9.8. The mean dose of propofol was 127 ± 5 mg and the mean dose of etomidate was 21 ± 6 mg. Patients who received propofol were younger and had a lower ISS. The etomidate group had significantly increased post-induction systolic blood pressure but no difference in mean arterial pressure or heart rate when compared to pre-induction parameters. The propofol group had no significant changes in any post-induction parameter compared to pre-induction parameter. CONCLUSION: RSI with propofol did not result in hypotension in our patient population, suggesting that a reduced dose of propofol may represent a reasonable alternative to etomidate in hemodynamically stable trauma patient. Further research is warranted to assess the safety of propofol in the acutely injured patient.


Subject(s)
Anesthetics, Intravenous/administration & dosage , Critical Care/methods , Propofol/administration & dosage , Wounds and Injuries/drug therapy , Academic Medical Centers , Acute Disease , Adult , Anesthesia Recovery Period , Cohort Studies , Etomidate/administration & dosage , Etomidate/adverse effects , Female , Follow-Up Studies , Glasgow Coma Scale , Hemodynamics/physiology , Humans , Injury Severity Score , Intubation, Intratracheal , Male , Middle Aged , Propofol/adverse effects , Retrospective Studies , Risk Assessment , Treatment Outcome , Wounds and Injuries/diagnosis , Wounds and Injuries/surgery
8.
Mol Psychiatry ; 17(9): 887-905, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22584867

ABSTRACT

We have used a translational convergent functional genomics (CFG) approach to identify and prioritize genes involved in schizophrenia, by gene-level integration of genome-wide association study data with other genetic and gene expression studies in humans and animal models. Using this polyevidence scoring and pathway analyses, we identify top genes (DISC1, TCF4, MBP, MOBP, NCAM1, NRCAM, NDUFV2, RAB18, as well as ADCYAP1, BDNF, CNR1, COMT, DRD2, DTNBP1, GAD1, GRIA1, GRIN2B, HTR2A, NRG1, RELN, SNAP-25, TNIK), brain development, myelination, cell adhesion, glutamate receptor signaling, G-protein-coupled receptor signaling and cAMP-mediated signaling as key to pathophysiology and as targets for therapeutic intervention. Overall, the data are consistent with a model of disrupted connectivity in schizophrenia, resulting from the effects of neurodevelopmental environmental stress on a background of genetic vulnerability. In addition, we show how the top candidate genes identified by CFG can be used to generate a genetic risk prediction score (GRPS) to aid schizophrenia diagnostics, with predictive ability in independent cohorts. The GRPS also differentiates classic age of onset schizophrenia from early onset and late-onset disease. We also show, in three independent cohorts, two European American and one African American, increasing overlap, reproducibility and consistency of findings from single-nucleotide polymorphisms to genes, then genes prioritized by CFG, and ultimately at the level of biological pathways and mechanisms. Finally, we compared our top candidate genes for schizophrenia from this analysis with top candidate genes for bipolar disorder and anxiety disorders from previous CFG analyses conducted by us, as well as findings from the fields of autism and Alzheimer. Overall, our work maps the genomic and biological landscape for schizophrenia, providing leads towards a better understanding of illness, diagnostics and therapeutics. It also reveals the significant genetic overlap with other major psychiatric disorder domains, suggesting the need for improved nosology.


Subject(s)
Genetic Association Studies/statistics & numerical data , Genetic Predisposition to Disease/genetics , Genomics/statistics & numerical data , Schizophrenia/genetics , Animals , Case-Control Studies , Databases, Genetic/statistics & numerical data , Disease Models, Animal , Genomics/methods , Humans , Mental Disorders/genetics , Polymorphism, Single Nucleotide/genetics , Reelin Protein , Schizophrenia/diagnosis
9.
Am J Med Genet B Neuropsychiatr Genet ; 153B(2): 663-674, 2010 Mar 05.
Article in English | MEDLINE | ID: mdl-19806613

ABSTRACT

SNAP25 occurs on chromosome 20p12.2, which has been linked to schizophrenia in some samples, and recently linked to latent classes of psychotic illness in our sample. SNAP25 is crucial to synaptic functioning, may be involved in axonal growth and dendritic sprouting, and its expression may be decreased in schizophrenia. We genotyped 18 haplotype-tagging SNPs in SNAP25 in a sample of 270 Irish high-density families. Single marker and haplotype analyses were performed in FBAT and PDT. We adjusted for multiple testing by computing q values. Association was followed up in an independent sample of 657 cases and 411 controls. We tested for allelic effects on the clinical phenotype by using the method of sequential addition and 5 factor-derived scores of the OPCRIT. Nine of 18 SNPs had P values <0.05 in either FBAT or PDT for one or more definitions of illness. Several two-marker haplotypes were also associated. Subjects inheriting the risk alleles of the most significantly associated two-marker haplotype were likely to have higher levels of hallucinations and delusions. The most significantly associated marker, rs6039820, was observed to perturb 12 transcription-factor binding sites in in silico analyses. An attempt to replicate association findings in the case-control sample resulted in no SNPs being significantly associated. We observed robust association in both single marker and haplotype-based analyses between SNAP25 and schizophrenia in an Irish family sample. Although we failed to replicate this in an independent sample, this gene should be further tested in other samples.


Subject(s)
Schizophrenia/genetics , Synaptosomal-Associated Protein 25/genetics , Alleles , Axons , Case-Control Studies , Dendrites/pathology , Family Health , Genetic Markers , Haplotypes , Humans , Ireland , Models, Genetic , Phenotype , Polymorphism, Genetic
10.
Bone Marrow Transplant ; 45(1): 31-7, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19543325

ABSTRACT

In a single-center study, we analyzed the outcomes of 66 patients with advanced hematological malignancies receiving two reduced-intensity conditioning regimens for allogeneic transplantation: fludarabine and low-dose TBI (flu/TBI, n=25), or fludarabine, antithymocyte globulin and BU (flu/ATG/BU, n=41). The selection criteria were based on the hypothesis that flu/TBI patients were expected to achieve autologous recovery in the event of non-engraftment. Sixty-three patients (95%) engrafted. Regimen-related mortality at day 100 and 1 year was 6 and 15%, respectively. With median follow-up of 50.4 months, survival did not differ by regimen. Multivariate analysis confirmed that the type of regimen did not affect relapse. In patients achieving full donor chimerism by day 30, those conditioned with flu/TBI showed greater overall survival (P=0.02). Engraftment failure occurred in two patients (3%), both of whom received flu/TBI. We conclude that conditioning with flu/TBI or flu/ATG/BU yields comparable survival and remission outcomes. By contrast to our hypothesis, patients receiving flu/TBI who subsequently failed engraftment did not achieve autologous recovery. Yet, rapid attainment of full donor chimerism after flu/TBI is associated with greater survival than after flu/ATG/BU. Further, larger prospective randomized studies are required to define the advantage of one regimen over the other.


Subject(s)
Antilymphocyte Serum/administration & dosage , Busulfan/administration & dosage , Hematopoietic Stem Cell Transplantation/methods , Myeloablative Agonists/therapeutic use , Transplantation Conditioning/methods , Vidarabine/analogs & derivatives , Whole-Body Irradiation/methods , Adolescent , Adult , Aged , Clinical Protocols , Female , Hematologic Neoplasms/therapy , Humans , Male , Middle Aged , Prospective Studies , Vidarabine/therapeutic use
11.
Otolaryngol Clin North Am ; 34(6): 1065-77, viii, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11728932

ABSTRACT

Tumors arising in the vicinity of the skull base are relatively uncommon; however, lesions that may be successfully treated by radiotherapy and radiosurgery include temporal bone chemodectomas, schwannomas, juvenile angiofibromas, pituitary adenomas, and meningiomas. This article reviews treatment techniques and results and discusses the pertinent literature.


Subject(s)
Radiosurgery , Skull Base Neoplasms/radiotherapy , Skull Base Neoplasms/surgery , Angiofibroma/radiotherapy , Angiofibroma/surgery , Humans , Meningeal Neoplasms/radiotherapy , Meningeal Neoplasms/surgery , Meningioma/radiotherapy , Meningioma/surgery , Neurilemmoma/radiotherapy , Neurilemmoma/surgery , Paraganglioma, Extra-Adrenal/radiotherapy , Paraganglioma, Extra-Adrenal/surgery , Pituitary Neoplasms/radiotherapy , Pituitary Neoplasms/surgery
12.
Am J Otolaryngol ; 22(6): 387-90, 2001.
Article in English | MEDLINE | ID: mdl-11713722

ABSTRACT

PURPOSE: To evaluate the outcomes of definitive radiotherapy in the treatment of clinical stage T4 cutaneous carcinomas of the head and neck. PATIENTS AND METHODS: Between October 1964 and September 1997, 85 patients with 88 biopsy-proven clinical AJCC stage T4 carcinomas of the skin of the head and neck received radiotherapy with curative intent. A total of 43 lesions were previously untreated, and 45 were recurrent after other treatment modalities. Histologic types of carcinoma included squamous cell (37 lesions), basal cell (41 lesions), and metatypical basal (basosquamous) cell (10 lesions). Minimum follow-up was 2 years. The product-limit method was used to determine the rates of disease control, severe late complications, and survival. Multivariate analyses included histology, previous treatment, involvement of bone or nerve, number of structures invaded, node stage, external beam dose, and overall treatment time. RESULTS: At 5 years, the rates of local control after radiotherapy and ultimate local control after salvage surgery were 53% and 90%, respectively. Local control rates were better for patients having previously untreated lesions (P =.05). Regional and ultimate regional control rates were 93% and 100%, respectively, and were better for previously untreated lesions (P <.01), basal cell histology or its metatypical variant (P =.04), and absence of bone invasion (P =.08). At 5 years, the risk of severe late complications was 17%, the risk of distant metastasis was 5%, and the overall absolute and cause-specific survival probabilities were 56% and 76%, respectively. CONCLUSION: Radiotherapy alone results in a relatively high probability of cure for selected patients with T4 skin cancers.


Subject(s)
Carcinoma, Basal Cell/radiotherapy , Carcinoma, Squamous Cell/radiotherapy , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/radiotherapy , Salvage Therapy , Skin Neoplasms/pathology , Skin Neoplasms/radiotherapy , Adult , Aged , Carcinoma, Basal Cell/mortality , Carcinoma, Basal Cell/pathology , Carcinoma, Basal Cell/surgery , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Disease-Free Survival , Dose Fractionation, Radiation , Female , Follow-Up Studies , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/surgery , Humans , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Probability , Retrospective Studies , Risk Assessment , Skin Neoplasms/mortality , Skin Neoplasms/surgery , Survival Rate , Treatment Outcome
13.
Am J Otolaryngol ; 22(6): 383-6, 2001.
Article in English | MEDLINE | ID: mdl-11713721

ABSTRACT

PURPOSE: This is a retrospective analysis of 50 patients with squamous cell carcinoma of the head and neck treated with radiotherapy (RT) to the primary site and bilateral neck followed by a planned bilateral neck dissection approximately 4 to 6 weeks after completion of RT. PATIENTS AND METHODS: Between November 1964 and March 1997, 50 patients underwent bilateral neck dissections after RT, with minimum 2-year follow-up. Forty-eight patients had bilateral positive neck nodes. RESULTS: At 5 years, the rates of neck disease control, local-regional control, and cause-specific survival were 76%, 70%, and 39%, respectively. Five severe complications developed after surgery, and 1 developed after RT. CONCLUSIONS: Radiotherapy followed by a planned bilateral neck dissection resulted in a high rate of local-regional control with acceptable morbidity. The likelihood of severe complications after simultaneous (as opposed to staged) neck dissection was not significantly different (P =.24).


Subject(s)
Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/surgery , Head and Neck Neoplasms/radiotherapy , Head and Neck Neoplasms/surgery , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/pathology , Combined Modality Therapy , Disease-Free Survival , Female , Follow-Up Studies , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/pathology , Humans , Male , Multivariate Analysis , Neoplasm Staging , Probability , Radiation Dosage , Radiotherapy, Adjuvant/methods , Retrospective Studies , Surgical Procedures, Operative/methods , Survival Rate , Treatment Outcome
14.
Int J Cancer ; 96(5): 261-9, 2001 Oct 20.
Article in English | MEDLINE | ID: mdl-11582578

ABSTRACT

The purpose of this article is to clarify the decision points that are important to consider when evaluating the ethics of a placebo-controlled trial. The ethical requirements for research involving human subjects are reviewed, and the rationale for and potential problems with concomitant placebo control are explained. A series of case discussions are used to illustrate each decision point. The critical decision points in the evaluation of the ethics of a placebo-controlled trial are as follows: (i) Is placebo being used in place of standard therapy? (ii) Is standard therapy likely to be effective? (iii) Is the toxicity of standard therapy such that patients routinely refuse this treatment? (iv) Could the use of placebo result in severe suffering or irreversible harm? (v) Is the variability in the placebo response such that it is reasonable to consider other options for the control group? (vi) Would a reasonable person with an average degree of altruism and risk aversiveness agree to participate in this study? The algorithm presented in this article gives researchers and research monitors (such as Institutional Review Board members) the tools they need to evaluate the ethics of a study that uses concomitant placebo control.


Subject(s)
Clinical Trials as Topic/methods , Algorithms , Ethics, Medical , Humans , Placebos , Random Allocation
15.
J Clin Oncol ; 19(20): 4029-36, 2001 Oct 15.
Article in English | MEDLINE | ID: mdl-11600604

ABSTRACT

PURPOSE: The end results after radiation therapy for T1-T2N0 glottic carcinoma vary considerably. We analyze patient-related and treatment-related parameters that may influence the likelihood of cure. PATIENTS AND METHODS: Five hundred nineteen patients were treated with radiation therapy and had follow-up for >or= 2 years. Three patients who were disease-free were lost to follow-up at 7 months, 21 months, and 10.5 years. No other patients were lost to follow-up. RESULTS: Local control rates at 5 years after radiation therapy were as follows: T1A, 94%; T1B, 93%; T2A, 80%; and T2B, 72%. Multivariate analysis of local control revealed that the following parameters significantly influenced this end point: overall treatment time (P < .0001), T stage (P = .0003), and histologic differentiation (P = .013). Patients with poorly differentiated cancers fared less well than those with better differentiated lesions. Rates of local control with laryngeal preservation at 5 years were as follows: T1A and T1B, 95%; T2A, 82%; and T2B, 76%. Cause-specific survival rates at 5 years were as follows: T1A and T1B, 98%; T2A, 95%; and T2B, 90%. One patient with a T1N0 cancer and three patients with T2N0 lesions experienced severe late radiation complications. CONCLUSION: Radiation therapy cures a high percentage of patients with T1-T2N0 glottic carcinomas and has a low rate of severe complications. The major treatment-related parameter that influences the likelihood of cure is overall treatment time.


Subject(s)
Carcinoma, Squamous Cell/radiotherapy , Glottis/pathology , Laryngeal Neoplasms/radiotherapy , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/pathology , Female , Humans , Laryngeal Neoplasms/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Radiotherapy Dosage , Survival Analysis
16.
Otolaryngol Clin North Am ; 34(5): 1007-20, vii-viii, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11557452

ABSTRACT

Paragangliomas of the head and neck may be treated successfully with surgery, radiation therapy, or stereotactic radiosurgery. The choice of treatment depends on the location and extent of the tumor, the presence of multiple tumors, the age and health of the patient, and the preference of the patient and attending physician. This article reviews the role of radiation therapy in the treatment of patients with paragangliomas of the head and neck.


Subject(s)
Head and Neck Neoplasms/radiotherapy , Paraganglioma/radiotherapy , Radiotherapy/methods , Female , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/mortality , Humans , Male , Paraganglioma/diagnosis , Paraganglioma/mortality , Prognosis , Radiation Dosage , Radiation Injuries/prevention & control , Radiotherapy/adverse effects , Survival Analysis , Treatment Outcome
17.
J Anxiety Disord ; 15(4): 345-57, 2001.
Article in English | MEDLINE | ID: mdl-11474819

ABSTRACT

There has been controversy over the most appropriate way to define symptom clusters for posttraumatic stress disorder (PTSD). We tested the factor structure of the Impact of Event Scale (IES) in a sample of 195 male combat veterans with chronic PTSD by using confirmatory factor analysis. The two-factor model including Intrusion (i.e., unwanted memories of the event) and Avoidance (i.e., attempts to avoid reminders and numbing of emotional responsiveness) deviated significantly from good fit. However, a four-factor model, including Intrusion and Effortful Avoidance subscales, as well as Sleep Disturbance and Emotional Numbing subscales, fit significantly better. Correlations with other PTSD measures are explored and implications for the conceptualization of PTSD are discussed.


Subject(s)
Stress Disorders, Post-Traumatic/diagnosis , Veterans/psychology , Aged , Factor Analysis, Statistical , Humans , Male , Middle Aged , Reproducibility of Results , Stress Disorders, Post-Traumatic/psychology , Surveys and Questionnaires
18.
Am J Otolaryngol ; 22(4): 261-7, 2001.
Article in English | MEDLINE | ID: mdl-11464323

ABSTRACT

Squamous cell carcinoma metastatic to the neck from an unknown head and neck primary site is relatively uncommon and presents a challenging diagnostic and therapeutic dilemma. Diagnostic evaluation includes fine-needle aspiration of the neck mass, chest roentgenography, computed tomography, and/or magnetic resonance imaging of the head and neck, followed by panendoscopy and biopsies. The primary tumor will be detected in approximately 40% of patients; approximately 80% of cancers are located in the base of the tongue or tonsillar fossa. Management options include treatment of the neck alone or both sides of the neck and the potential head and neck primary sites. The latter approach is associated with better long-term control above the clavicles. The 5-year survival rate is approximately 50% after treatment and is influenced by the extent of neck disease. In this article, we review the pertinent literature.


Subject(s)
Carcinoma, Squamous Cell/secondary , Head and Neck Neoplasms/secondary , Neoplasms, Unknown Primary , Biopsy, Needle , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/radiotherapy , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/radiotherapy , Humans , Lymph Nodes/pathology , Magnetic Resonance Imaging , Neoplasms, Unknown Primary/diagnosis , Neoplasms, Unknown Primary/radiotherapy , Tomography, Emission-Computed , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray Computed
19.
Am J Otolaryngol ; 22(3): 172-5, 2001.
Article in English | MEDLINE | ID: mdl-11351285

ABSTRACT

PURPOSE: To analyze 15 patients treated with radiation therapy for juvenile nasopharyngeal angiofibroma (JNA) between June 1975 and March 1996. MATERIALS AND METHODS: All patients had a 2.5-year minimum follow-up. All patients had advanced disease (Chandler stage III or stage IV); two thirds of the patients had intracranial extension. RESULTS: Local control after radiotherapy was obtained in 13 of 15 patients (85%). Two patients had local recurrences, and both were salvaged with surgery for an ultimate local control rate of 100%. Late complications included cataracts in 3 patients, delayed transient central nervous system (CNS) syndrome in 1 patient, and a basal cell carcinoma of the skin in 1 patient. Of 15 patients, 13 (85%) had a complete response (CR) on physical examination following radiation therapy. The median time to CR was 13 months (range, 1 to 39 months). Of 6 patients with residual disease in more than 24 months, 2 (33%) had a recurrence, whereas no patient achieving CR in less than 24 months experienced a recurrence. CONCLUSIONS: Radiotherapy is an effective treatment for advanced JNA. Tumor regression usually occurs slowly over several months. JNAs that are slow to regress (greater than 2 years) may have an increased risk of recurrence.


Subject(s)
Angiofibroma/radiotherapy , Nasopharyngeal Neoplasms/radiotherapy , Adolescent , Adult , Angiofibroma/diagnosis , Child , Child, Preschool , Disease Progression , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Nasopharyngeal Neoplasms/diagnosis , Neoplasm Staging , Radiotherapy Dosage , Retrospective Studies , Tomography, X-Ray Computed
20.
Int J Radiat Oncol Biol Phys ; 50(2): 359-66, 2001 Jun 01.
Article in English | MEDLINE | ID: mdl-11380222

ABSTRACT

PURPOSE: The present study presents the experience at the University of Florida with treatment of unselected patients with carcinomas of the soft palate with radiation therapy (RT) alone or followed by planned neck dissection. METHODS AND MATERIALS: One hundred seven patients treated with curative intent with RT alone or followed by neck dissection from 1965 to 1996 were included in the study. All patients had follow-up for at least 2 years. No patients were lost to follow-up. RESULTS: Local control rates at 5 years were 86% for T1, 91% for T2, 67% for T3, and 36% for T4 carcinomas. T-stage and overall treatment time significantly affected local control in multivariate analysis. Nodal control rates at 5 years were 86% for NO, 76% for N1, 61% for N2, and 67% for N3 carcinomas. Overall treatment time and planned neck dissection significantly affected nodal control in multivariate analysis. Ultimate local-regional control rates at 5 years were 90% for Stage I, 92% for Stage II, 84% for Stage III, and 60% for Stage IV disease. Overall treatment time and planned neck dissection significantly affected ultimate local-regional control in multivariate analysis. The overall survival rate at 5 years was 42% for all patients. Overall stage, overall treatment time, and planned neck dissection significantly affected overall survival in multivariate analysis. The cause-specific survival rate at 5 years was 70% for all patients. Overall treatment time and planned neck dissection significantly affected cause-specific survival in multivariate analysis. Three patients sustained severe postoperative complications and 3 patients sustained severe late complications. Sixteen patients had synchronous and 14 patients had metachronous carcinomas of the head and neck mucosal sites. CONCLUSION: For limited carcinomas of the soft palate, RT (alone or followed by planned neck dissection) results in relatively high local-regional control and survival rates. For advanced carcinomas of the soft palate, local-regional control and survival rates are relatively low and local-regional recurrence rates are substantial. Advanced carcinomas of the soft palate may be better treated with RT and concomitant chemotherapy.


Subject(s)
Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/surgery , Palatal Neoplasms/radiotherapy , Palatal Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/pathology , Combined Modality Therapy , Female , Humans , Male , Middle Aged , Multivariate Analysis , Neck Dissection , Neoplasm Staging , Palatal Neoplasms/pathology , Palate, Soft/pathology , Palate, Soft/surgery
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