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1.
Clin Transl Radiat Oncol ; 45: 100730, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38317679

ABSTRACT

Purpose/objectives: The growing use of stereotactic body radiotherapy (SBRT) in metastatic cancer has led to its use in varying anatomic locations. The objective of this study was to review our institutional SBRT experience for axillary metastases (AM), focusing on outcomes and process. Materials/methods: Patients treated with SBRT to AM from 2014 to 2022 were reviewed. Cumulative incidence functions were used to estimate the incidence of local failure (LF), with death as competing risk. Kaplan-Meier method was used to estimate progression-free (PFS) and overall survival (OS). Univariate regression analysis examined predictors of LF. Results: We analyzed 37 patients with 39 AM who received SBRT. Patients were predominantly female (60 %) and elderly (median age: 72). Median follow-up was 14.6 months. Common primary cancers included breast (43 %), skin (19 %), and lung (14 %). Treatment indication included oligoprogression (46 %), oligometastases (35 %) and symptomatic progression (19 %). A minority had prior overlapping radiation (18 %) or surgery (11 %). Most had prior systemic therapy (70 %).Significant heterogeneity in planning technique was identified; a minority of patient received 4-D CT scans (46 %), MR-simulation (21 %), or contrast (10 %). Median dose was 40 Gy (interquartile range (IQR): 35-40) in 5 fractions, (BED10 = 72 Gy). Seventeen cases (44 %) utilized a low-dose elective volume to cover remaining axilla.At first assessment, 87 % had partial or complete response, with a single progression. Of symptomatic patients (n = 14), 57 % had complete resolution and 21 % had improvement. One and 2-year LF rate were 16 % and 20 %, respectively. Univariable analysis showed increasing BED reduced risk of LF. Median OS was 21.0 months (95 % [Confidence Interval (CI)] 17.3-not reached) and median PFS was 7.0 months (95 % [CI] 4.3-11.3). Two grade 3 events were identified, and no grade 4/5. Conclusion: Using SBRT for AM demonstrated low rates of toxicity and LF, and respectable symptom improvement. Variation in treatment delivery has prompted development of an institutional protocol to standardize technique and increase efficiency. Limited followup may limit detection of local failure and late toxicity.

2.
Clin Oncol (R Coll Radiol) ; 35(2): e173-e181, 2023 02.
Article in English | MEDLINE | ID: mdl-36470682

ABSTRACT

AIMS: Accelerated hypofractionated radiotherapy is used at our institution for non-small cell lung cancer (NSCLC) patients not eligible for stereotactic body radiotherapy or chemoradiotherapy. The purpose of this study was to report clinical outcomes of delivering 60 Gy in 15 fractions for these patients. MATERIALS AND METHODS: All NSCLC patients who received 60 Gy in 15 fractions were reviewed. Outcomes of interest were local failure, regional failure, distant progression, overall survival and treatment-associated toxicities. RESULTS: In total, 111 patients were included. The median age was 78.8 years and most tumours were adenocarcinoma (n = 55, 49.6%). Sixty-five patients (58.6%) were N0. The cumulative incidence of local failure at 12 and 24 months in the N0 cohort was 5.2% and 14.2%, respectively, compared with 11.5% and 14.8% for N+ patients. Tumour size >35 mm predicted for local failure (hazard ratio 2.706, 95% confidence interval 1.002-7.307, P = 0.0494). Distant progression at 12 and 24 months in N0 patients was 13.7% and 24.3% compared with 24.6% and 33.5% in N+ patients. In N0 patients, larger tumour size was associated with increased risk of distant progression. The median overall survival was 38.1 months in N0 patients versus 31.7 months in N+ patients. The most common toxicity was radiation pneumonitis (n = 6, 6.4%). The incidence of any grade 3 toxicity was 10.3% at ≥1 year. There were no deaths or hospitalisations attributed to treatment. CONCLUSIONS: Accelerated hypofractionated radiotherapy is well tolerated and resulted in favourable clinical outcomes in various stages of NSCLC patients.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Radiosurgery , Radiotherapy, Conformal , Humans , Aged , Lung Neoplasms/radiotherapy , Lung Neoplasms/drug therapy , Carcinoma, Non-Small-Cell Lung/radiotherapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Radiosurgery/adverse effects , Radiosurgery/methods , Radiotherapy, Conformal/methods , Chemoradiotherapy/adverse effects , Chemoradiotherapy/methods , Treatment Outcome
3.
Clin Transl Radiat Oncol ; 33: 159-164, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35243027

ABSTRACT

BACKGROUND: Studies reporting SBRT outcomes in oligometastatic patients with adrenal gland metastases (AGM) are limited. Herein, we present a multi-institutional analysis of oligometastatic patients treated with SBRT for AGM. MATERIAL/METHODS: The Consortium for Oligometastases Research (CORE) is among the largest retrospective series of patients with oligometastases. Among CORE patients, those treated with SBRT for AGM were included. Clinical and dosimetric data were collected. Adrenal metastatic burden (AMB) was defined as the sum of all adrenal GTV if more than one oligometastases is present.Competing risk analysis was used to estimate actuarial cumulative local recurrence (LR) and widespread progression (WP). Kaplan-Meier method was used to report overall survival (OS), local recurrence-free survival (LRFS), and progression-free survival (PFS). Treatment related toxicities were also reported. RESULTS: The analysis included 47 patients with 57 adrenal lesions. Median follow-up was 18.2 months. Median LRFS, PFS, and OS were 15.3, 5.3, and 19.1 months, respectively. A minimum PTV dose BED10 > 46 Gy was associated with an improved OS and LRFS. A prescribed BED10 > 70 Gy was an independent predictor of a lower LR probability. AMB>10 cc was an independent predictor of a lower risk for WP. Only one patient developed an acute Grade 3 toxicity consisting of abdominal pain. CONCLUSION: SBRT to AGM achieved a satisfactory local control and OS in oligometastatic patients. High minimum PTV dose and BED10 prescription doses were predictive of improved LR and OS, respectively. Prospective studies are needed to determine comprehensive criteria for patients SBRT eligibility and dosimetric planning.

4.
Curr Oncol ; 24(3): 153-160, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28680274

ABSTRACT

BACKGROUND: In contrast with other major chronic conditions such as heart disease and stroke, cancer care does not routinely integrate evidence-based rehabilitation services within the standard continuum. The objectives of the present project were to develop a rehabilitation planning consultation (rpc) for survivors of head-and-neck (hn) cancer, to test its feasibility, and to make refinements. METHODS: Using intervention mapping, the rpc-alpha was developed by examining potential theoretical methods and practical applications relative to the program objectives. During feasibility testing, a single case series was conducted with survivors of hn cancer who had completed their cancer treatment within the preceding 11 months; iterative refinements were made after each case. RESULTS: The rpc-alpha was led by a rehabilitation professional and was based on self-management principles. The initial consultation included instruction in a global cognitive strategy, goal-setting, introduction to available resources, action planning, and coping planning. A follow-up consultation was conducted a few weeks later. Of 9 participants recruited, 5 completed post-intervention assessments. Participants reported that the rpc helped them to make rehabilitation plans. CONCLUSIONS: The rpc was feasible to use and satisfactory to a small group of hn cancer survivors. A pilot test of the refined version is in process.

5.
J Otolaryngol Head Neck Surg ; 45(1): 42, 2016 Aug 02.
Article in English | MEDLINE | ID: mdl-27485726

ABSTRACT

BACKGROUND: The literature reports various treatment methodologies, such as trans-oral laser microsurgery, radiation therapy, total/partial laryngectomies, and concurrent radiation chemotherapy for patients with early larynx cancer. However, at the forefront of early glottis treatment is trans-oral laser microsurgery and radiation therapy, likely due to better functional and survival outcomes. Here we conduct the largest Canadian head-to-head comparison of consecutive patients treated with either radiation therapy or trans-oral laser microsurgery. Additionally, we compare these two treatments and their 5-year survival rates post treatment to add to the existing literature. METHODS: Charts of patients who were diagnosed with early glottic cancer between 2006 and 2013 were reviewed. Seventy-five patients were identified, and split into 2 groups based on their primary treatment, trans-oral laser microsurgery and radiation therapy. Kaplan-Meier survival curves, life-tables, and the log-rank statistic were reported to determine if there was a difference between the two treatment groups and their disease-specific survival, disease-free survival, and total laryngectomy-free survival. Additionally, each different survival analysis was stratified by potential confounding variables, to help conclude which treatment is more efficacious in this population. RESULTS: The 5-year disease-specific survival rate is 93.3 % σ = 0.063 and 90.8 % σ = 0.056 for patients treated with trans-oral laser microsurgery and radiation therapy, respectively (χ (2) < 0.001, p = 0.983). The disease free survival rate is 60.0 % (σ =0.121) for patients treated with trans-oral laser microsurgery, and 67.2 % (σ = 0.074) for those who received RT (χ (2) = 0.19, p = 0.663). Additionally, the total laryngectomy-free survival rate is 84.1 % (σ = 0.1) and 79.1 % (σ = 0.072) for patients' early glottic cancer treated by trans-oral laser microsurgery and radiation therapy, respectively (χ (2) = 0.235, p = 0.628). Chi-square analysis of age-group versus treatment group (χ (2) = 6.455, p = 0.04) and T-stage versus treatment group (χ (2) = 11.3, p = 0.001) revealed a statistically significant relationship, suggesting survival analysis should be stratified by these variables. However, after stratification, there was no statistically significant difference between the trans-oral laser microsurgery and radiation therapy groups in any of the survival analyses. CONCLUSION: No difference was demonstrated in the 5-year disease-specific survival, disease-free survival, and total laryngectomy-free survival, between the RT and TLM treatment groups. Additionally, both groups showed similar 5-year survival after stratifying by confounding variables.


Subject(s)
Glottis/surgery , Laryngeal Neoplasms/radiotherapy , Laryngeal Neoplasms/surgery , Laser Therapy/methods , Microsurgery/methods , Adult , Aged , Aged, 80 and over , Female , Humans , Laryngeal Neoplasms/mortality , Laryngectomy , Male , Middle Aged , Retrospective Studies , Survival Analysis , Survival Rate
6.
Clin Oncol (R Coll Radiol) ; 28(1): 28-35, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26129745

ABSTRACT

AIMS: To determine the incidence and predictive factors of rib fracture and chest wall pain after lung stereotactic ablative radiotherapy (SABR). MATERIALS AND METHODS: Patients were treated with lung SABR of 48-60 Gy in four to five fractions. The treatment plan and follow-up computed tomography scans of 289 tumours in 239 patients were reviewed. Dose-volume histogram (DVH) metrics and clinical factors were evaluated as potential predictors of chest wall toxicity. RESULTS: The median follow-up was 21.0 months (range 6.2-52.1). Seventeen per cent (50/289) developed a rib fracture, 44% (22/50) were symptomatic; the median time to fracture was 16.4 months. On univariate analysis, female gender, osteoporosis, tumours adjacent (within 5 mm) to the chest wall and all of the chest wall DVH metrics predicted for rib fracture, but only tumour location adjacent to the chest wall remained significant on the multivariate model (P < 0.01). The 2 year fracture-free probability for those adjacent to the chest wall was 65.6%. Among those tumours adjacent to the chest wall, only osteoporosis (P = 0.02) predicted for fracture, whereas none of the chest wall DVH metrics were predictive. Eight per cent (24/289) experienced chest wall pain without fracture. CONCLUSIONS: None of the chest wall DVH metrics independently predicted for SABR-induced rib fracture when tumour location is taken into account. Patients with tumours adjacent (within 5 mm) to the chest wall are at greater risk of rib fracture after lung SABR, and among these, an additional risk was observed in osteoporotic patients.


Subject(s)
Lung Neoplasms/surgery , Radiation Injuries/etiology , Radiosurgery/adverse effects , Rib Fractures/etiology , Adult , Aged, 80 and over , Dose-Response Relationship, Radiation , Female , Humans , Incidence , Male , Middle Aged , Radiation Injuries/epidemiology , Radiosurgery/methods , Risk Factors , Thoracic Wall/radiation effects , Tomography, X-Ray Computed/adverse effects
7.
Cell Death Differ ; 22(12): 1893-905, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26450453

ABSTRACT

A significant effort is made by the cell to maintain certain phospholipids at specific sites. It is well described that proteins involved in intracellular signaling can be targeted to the plasma membrane and organelles through phospholipid-binding domains. Thus, the accumulation of a specific combination of phospholipids, denoted here as the 'phospholipid code', is key in initiating cellular processes. Interestingly, a variety of extracellular proteins and pathogen-derived proteins can also recognize or modify phospholipids to facilitate the recognition of dying cells, tumorigenesis and host-microbe interactions. In this article, we discuss the importance of the phospholipid code in a range of physiological and pathological processes.


Subject(s)
Phospholipids/metabolism , Cell Membrane/metabolism , Disease Progression , Host-Pathogen Interactions , Humans , Neoplasms/metabolism , Neoplasms/pathology , Reactive Oxygen Species/metabolism , Signal Transduction , Tumor Microenvironment
8.
Clin Oncol (R Coll Radiol) ; 26(11): 713-9, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25085765

ABSTRACT

AIMS: We report the outcomes of a large lung stereotactic ablative body radiotherapy (SABR) programme for primary non-small cell lung cancer (NSCLC) and pulmonary metastases. The primary study aim was to identify factors predictive for local control. MATERIALS AND METHODS: In total, 311 pulmonary tumours in 254 patients were treated between 2008 and 2011 with SABR using 48-60 Gy in four to five fractions. Local, regional and distant failure data were collected prospectively, whereas other end points were collected retrospectively. Potential clinical and dosimetric predictors of local control were evaluated using univariate and multivariate analyses. RESULTS: Of the 311 tumours, 240 were NSCLC and 71 were other histologies. The 2 year local control rate was 96% in stage I NSCLC, 76% in colorectal cancer (CRC) metastases and 91% in non-lung/non-CRC metastases. Predictors of better local control on multivariate analysis were non-CRC tumours and a larger proportion of the planning target volume (PTV) receiving ≥100% of the prescribed dose (higher PTV V100). Among the 45 CRC metastases, a higher PTV V100 and previous chemotherapy predicted for better local control. CONCLUSIONS: Lung SABR of 48-60 Gy/four to five fractions resulted in high local control rates for all tumours except CRC metastases. Covering more of the PTV with the prescription dose (a higher PTV V100) also resulted in superior local control.


Subject(s)
Colorectal Neoplasms/surgery , Kidney Neoplasms/surgery , Lung Neoplasms/surgery , Neoplasm Recurrence, Local/diagnosis , Radiation Pneumonitis/diagnosis , Radiosurgery , Adenocarcinoma/mortality , Adenocarcinoma/secondary , Adenocarcinoma/surgery , Adenocarcinoma, Bronchiolo-Alveolar/mortality , Adenocarcinoma, Bronchiolo-Alveolar/secondary , Adenocarcinoma, Bronchiolo-Alveolar/surgery , Adult , Aged , Aged, 80 and over , Carcinoma, Large Cell/mortality , Carcinoma, Large Cell/secondary , Carcinoma, Large Cell/surgery , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/secondary , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/secondary , Carcinoma, Squamous Cell/surgery , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Dose Fractionation, Radiation , Female , Follow-Up Studies , Humans , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/etiology , Neoplasm Recurrence, Local/mortality , Neoplasm Staging , Prognosis , Prospective Studies , Radiation Pneumonitis/etiology , Radiation Pneumonitis/mortality , Radiotherapy Planning, Computer-Assisted , Retrospective Studies , Survival Rate
9.
Med Phys ; 39(7Part4): 4641, 2012 Jul.
Article in English | MEDLINE | ID: mdl-28516627

ABSTRACT

Partial volume correction (PVC) is often needed to correct for limited spatial resolution in quantitative Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) studies. In conventional region-based PVC methods, spill over between regions segmented from coregistered computed tomography (CT) or magnetic resonance (MR) images is accounted for by calculating regional spread functions (RSFs) in a geometric transfer matrix (GTM) framework. This paper describes a new analytically derived symmetric GTM (sGTM) method that considers spill over between RSFs rather than between regions. The sGTM is mathematically equivalent to Labbe's method, however it is region-based rather than voxel-based and it avoids handling large matrices. The sGTM method was validated using an MR-based 3D digital brain phantom and a physical phantom containing spheres 5 mm to 30 mm in diameter. The sGTM method was compared to the GTM method in terms of accuracy, precision, noise propagation, and robustness, i.e. effects of mis-registration or point spread function (PSF) estimation errors. The results showed that the sGTM method has accuracy similar to that of the GTM method, and within 5% of the true value. However, the sGTM method showed better precision and noise propagation than the GTM method, especially for spheres smaller than 13 mm. Moreover, the sGTM method was more robust than the GTM method when misregistration or errors in estimates of PSF occurred. In conclusion, the sGTM method was analytically derived and validated and shown to exhibit better noise characteristics and robustness compared to the GTM method.

10.
Clin Oncol (R Coll Radiol) ; 22(10): 868-73, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20650620

ABSTRACT

AIMS: To determine the value of routine follow-up in detecting and salvaging recurrence after radical treatment of locally advanced head and neck squamous cell carcinoma and to identify clinical or pathological prognostic factors that predicted for survival. MATERIALS AND METHODS: A retrospective medical chart review was conducted at the Odette Cancer Centre between January 2000 and May 2006. Two hundred and twenty-three patients with advanced (stage III or IV) squamous cell carcinoma of the head and neck who were treated with curative intent were reviewed. Recurrences were divided into local, regional or distant recurrences. The detection method for each recurrence was categorised as self or physician detected. A self-detected recurrence arose from symptoms that led to investigations that confirmed a recurrence (even if initiated at the time of a routine visit), whereas a physician-detected recurrence was found during the routine follow-up examination and was asymptomatic. RESULTS: There was no evidence to suggest a significant improvement in disease-free or overall survival in the physician-detected versus patient-detected groups. Regional and distant recurrences were only detected by physicians in one-fifth of cases and, overall, patients self-detected their own recurrence in two-thirds of the cases that experienced disease progression within the sample. Of the 12 clinical/pathological variables considered, only the response to treatment and perineural invasion were associated with survival. CONCLUSIONS: Current surveillance methods do not appear to improve cancer control in the stage III/IV head and neck squamous cell carcinoma population. However, technological advances and biomarker development may lead to surveillance technique enhancements. Also, post-treatment follow-up remains important for the evaluation of treatment results, emotional support and management of late complications. Among the clinical and pathological factors considered, only the treatment response and perineural invasion predicted survival.


Subject(s)
Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/therapy , Head and Neck Neoplasms/diagnosis , Head and Neck Neoplasms/therapy , Neoplasm Recurrence, Local/diagnosis , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/pathology , Combined Modality Therapy , Disease-Free Survival , Female , Follow-Up Studies , Head and Neck Neoplasms/pathology , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Prognosis , Retrospective Studies , Treatment Outcome
11.
Cell Death Differ ; 17(3): 381-97, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20019744

ABSTRACT

Phagocytosis serves as one of the key processes involved in development, maintenance of tissue homeostasis, as well as in eliminating pathogens from an organism. Under normal physiological conditions, dying cells (e.g., apoptotic and necrotic cells) and pathogens (e.g., bacteria and fungi) are rapidly detected and removed by professional phagocytes such as macrophages and dendritic cells (DCs). In most cases, specific receptors and opsonins are used by phagocytes to recognize and bind their target cells, which can trigger the intracellular signalling events required for phagocytosis. Depending on the type of target cell, phagocytes may also release both immunomodulatory molecules and growth factors to orchestrate a subsequent immune response and wound healing process. In recent years, evidence is growing that opsonins and receptors involved in the removal of pathogens can also aid the disposal of dying cells at all stages of cell death, in particular plasma membrane-damaged cells such as late apoptotic and necrotic cells. This review provides an overview of the molecular mechanisms and the immunological outcomes of late apoptotic/necrotic cell removal and highlights the striking similarities between late apoptotic/necrotic cell and pathogen clearance.


Subject(s)
Apoptosis , Necrosis , Phagocytosis , Animals , Apoptosis/immunology , Apoptosis/physiology , Complement Activation/immunology , Humans , Immunity, Innate/immunology , Necrosis/immunology , Phagocytosis/immunology , Phagocytosis/physiology
12.
Oncogene ; 27(21): 3060-5, 2008 May 08.
Article in English | MEDLINE | ID: mdl-18059340

ABSTRACT

Apoptin, a small protein from the chicken anemia virus, has attracted attention because of its specificity in killing tumor cells. Localization of apoptin in the nucleus of tumor cells has been shown to be vital for proapoptotic activity, however, targeted expression of apoptin in the nucleus of normal cells does not harm the cells, indicating that nuclear localization of apoptin is insufficient for its cytotoxicity. Here, we demonstrate for the first time that apoptin interacts with the SH3 domain of p85, the regulatory subunit of phosphoinositide 3-kinase (PI3-K), through its proline-rich region. Apoptin derivatives devoid of this proline-rich region do not interact with p85, are unable to activate PI3-K, and show impaired apoptosis induction. Moreover, apoptin mutants containing the proline-rich domain are sufficient to elevate PI3-K activity and to induce apoptosis in cancer cells. Downregulation of p85 leads to nuclear exclusion of apoptin and impairs cell death induction, indicating that interaction with the p85 PI3-K subunit essentially contributes to the cytotoxic activity of apoptin.


Subject(s)
Capsid Proteins/physiology , Phosphatidylinositol 3-Kinases/metabolism , Capsid Proteins/genetics , Capsid Proteins/metabolism , Cell Line, Tumor , Humans , Mutation , Protein Binding
13.
J Clin Pharm Ther ; 32(1): 21-9, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17286786

ABSTRACT

BACKGROUND: Older adults frequently have conditions requiring oral anticoagulation. Although clearly benefiting from oral anticoagulation, they are at increased risk for bleeding complications. Regular monitoring to optimize anticoagulation and to reduce the chance of major bleeding complications is required. The impact of oral anticoagulation monitoring by pharmacists in patients older than 75 years of age has not been described well. OBJECTIVE: To compare warfarin therapy prescribed and monitored by physicians to a pharmacist-monitored anticoagulation service in a cohort of older veterans. METHODS: Retrospective chart review utilizing the Houston VA Medical Center's pharmacy database. Among all outpatients aged 75 years or older filling warfarin prescriptions between 1 March 2003 to 1 March 2005, and who were either monitored in a pharmacist's clinic or not, 103 patients per group were randomly selected. Information on demographics, indication for and length of warfarin therapy, INR values, and thromboembolic and bleeding events were abstracted. Differences were analysed using chi-squared test, Fisher's Exact test, and unpaired Student t-test. RESULTS: A total of 1521 patients (440 in the pharmacist-monitored group, 1081 in the traditionally monitored group) met our inclusion criteria. One hundred and three patients per group were randomly selected for chart review. Although no significant difference in percentage of therapeutic INR values (48.1% pharmacist group, 46.4% conventional group) or in the incidence of major bleeding events was found, thromboembolic events occurred significantly less frequently in the pharmacist-monitored group (2 events vs. 12 events, P = 0.01). Minor bleeding events were more frequent in the pharmacist-monitored group (50 vs. 17, P < 0.01). However, time to follow-up after a sub- or supra-therapeutic INR was significantly shorter in the pharmacist monitored group (22 days vs. 68 days, and 14 days vs. 32 days, respectively). CONCLUSION: Pharmacist-monitored anticoagulation was associated with reduced thromboembolic events, an increase in minor bleeding events, and no difference in major bleeding events. Overall such monitoring by pharmacists should be recommended for older adults.


Subject(s)
Anticoagulants/adverse effects , Anticoagulants/therapeutic use , Drug Monitoring/methods , Hemorrhage/chemically induced , Pharmacists , Thromboembolism/drug therapy , Warfarin/adverse effects , Warfarin/therapeutic use , Aged , Aged, 80 and over , Ambulatory Care , Cohort Studies , Female , Humans , International Normalized Ratio , Male , Retrospective Studies , Veterans
14.
J Clin Pharm Ther ; 30(2): 173-8, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15811171

ABSTRACT

BACKGROUND: Orthostatic hypotension (OH) is defined as a reduction of systolic blood pressure of at least 20 mmHg, or diastolic blood pressure of at least 10 mmHg from a sitting to a standing position. It is a common physical finding among older adults and associated with significant morbidity and mortality. Use of medications that have the potential to induce OH, particularly concomitant use of several of such medications, is a major factor for the development of OH. OBJECTIVES: To describe the prevalence of symptomatic and asymptomatic OH in veterans aged 75 years and older attending a geriatric clinic, and to assess the association between OH and the number of potentially causative medications used. METHODS: Charts of all patients who attended a VA geriatric clinic (Michael E. DeBakey VA Medical Center) during the period of 1 June 2002 to 1 June 2003 were reviewed retrospectively for (i) the use of potentially causative medications, i.e. medications that were reported to cause OH in at least 1% of the general population and that were available in the VA formulary, (ii) the presence or absence of OH, and (iii) the presence or absence of symptomatic OH. Patients with primary autonomic dysfunction, Parkinson's disease, and patients who were unable to stand, or who had no assessment for both sitting and standing blood pressure for other reasons were excluded. RESULTS: A total of 505 individual patients attended the clinic during the study period, and 342 patients fit the inclusion criteria. About 189 of these patients (55%) had OH. Among patients with OH, 61 patients (33%) were symptomatic, including 52 patients who had falls. The prevalence of OH in patients receiving zero, one, two, and three or more potentially causative medications was 35, 58, 60 and 65% respectively. Receiving hydrochlorothiazide was associated with the highest prevalence of OH (65%), followed by receiving lisinopril (60%), trazodone (58%), furosemide (56%) and terazosin (54%). CONCLUSION: The prevalence of OH is very high in older veterans and significantly related to the number of concurrent causative medications used. Providers should be educated to reduce the amount of potentially causative medications in the elderly and better assess patients in which use of such medications is necessary to avoid symptomatic OH.


Subject(s)
Drug Therapy/classification , Hypotension, Orthostatic/chemically induced , Hypotension, Orthostatic/epidemiology , Veterans/statistics & numerical data , Aged , Aged, 80 and over/statistics & numerical data , Antidepressive Agents/adverse effects , Antidepressive Agents/chemistry , Antidepressive Agents/therapeutic use , Antipsychotic Agents/adverse effects , Antipsychotic Agents/chemistry , Antipsychotic Agents/therapeutic use , Female , Furosemide/adverse effects , Furosemide/therapeutic use , Health Services for the Aged/organization & administration , Hospitals, Veterans/organization & administration , Humans , Hydrochlorothiazide/adverse effects , Hydrochlorothiazide/therapeutic use , Lisinopril/adverse effects , Lisinopril/therapeutic use , Male , Outpatients/statistics & numerical data , Patient Selection , Prazosin/adverse effects , Prazosin/analogs & derivatives , Prazosin/therapeutic use , Prevalence , Retrospective Studies
16.
J Diabetes Complications ; 12(1): 18-23, 1998.
Article in English | MEDLINE | ID: mdl-9442810

ABSTRACT

The aim of our study was to compare ambulatory blood pressure monitoring (ABPM) measures (mean systolic/diastolic blood pressure, diurnal rhythm, and pressure burden) in matched normo- and microalbuminuric (IDDM) adolescents and healthy controls. Twenty-four hour monitoring was undertaken in 39 normotensive (normal clinic blood pressure measurements) IDDM adolescents (22 normo- and 17 microalbuminuric subjects) and 23 controls. Subjects were matched for age, bodymass index, gender, and IDDM duration. Microalbuminuria was diagnosed on the basis of a urinary albumin excretion rate greater than 15 but less than 200 micrograms/min in two of the three 24-h urine collections. The microalbuminuric patients differed from the normoalbuminuric subjects and controls in having higher mean 24-h and overnight systolic pressure, loss of systolic diurnal rhythm and increased systolic and diastolic pressure burden. There were no differences between the three groups in diastolic blood pressure. The normoalbuminuric group differed from the controls only with respect to an increased systolic pressure burden. Microalbuminuric IDDM adolescents show similar, albeit milder changes in ABPM, to those reported in adults with microalbuminuria. We postulate that these milder changes represent an earlier phase to that observed in the adult population and that taken together, the adolescent and adult data suggests a specific order in the development of ABPM changes in diabetic subjects.


Subject(s)
Albuminuria/physiopathology , Blood Pressure Monitoring, Ambulatory , Diabetes Mellitus, Type 1/physiopathology , Diabetic Nephropathies/physiopathology , Adolescent , Adult , Albuminuria/complications , Analysis of Variance , Child , Circadian Rhythm , Diabetes Mellitus, Type 1/complications , Diabetic Nephropathies/complications , Female , Humans , Hypertension/etiology , Male
17.
Metabolism ; 43(5): 591-8, 1994 May.
Article in English | MEDLINE | ID: mdl-8177047

ABSTRACT

We have previously shown that human circulating mononuclear cells (CMCs) respond to physiological concentrations of insulin with a rapid increase in glucose transport rate. The responding cells were found to be the monocytes, and cells derived from individuals with insulin-dependent diabetes mellitus (IDDM) had lower basal and insulin-stimulated glucose transport rates. Of interest, both cell types were found to express the GLUT1 but not the typical insulin-responsive GLUT4 transporter isoform. To further study the mechanisms responsible for stimulation of transport in these cells, we investigated (1) the response to insulin-like growth factor-I (IGF-I) and insulin-mimetic agents, and (2) the expression of other glucose transporter isoforms in CMCs of nondiabetic and IDDM individuals. The time course of insulin-stimulated glucose uptake in CMCs was rapid, reaching a plateau within 30 minutes. CMCs showed a dose-dependent and highly sensitive increase in glucose uptake to IGF-I (maximal response reached at 0.1 to 0.5 nmol/L IGF-I). The IGF-I dose-response curve was similar for CMCs of control and IDDM individuals, but both the basal and maximal response to IGF-I were lower in the diabetic group (P < .01). CMCs did not respond to vanadate, lithium, hydrogen peroxide, or short incubation (1 hour) with metformin, but glucose uptake increased in response to peroxides of vanadate and longer-duration (14 hours) metformin incubations. The glucose transporter isoforms of separated monocytes and lymphocytes were further investigated by Northern blotting of total RNA with a GLUT3-specific cDNA probe and by Western blotting of total membranes using GLUT3-specific antiserum.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Diabetes Mellitus, Type 1/blood , Glucose/metabolism , Monocytes/metabolism , Monosaccharide Transport Proteins/metabolism , Nerve Tissue Proteins , Adolescent , Adult , Biological Transport , Blotting, Northern , Female , Glucose Transporter Type 3 , Humans , Insulin/blood , Insulin-Like Growth Factor I/pharmacology , Lymphocytes/metabolism , Male , Metformin/pharmacology , Middle Aged , Monosaccharide Transport Proteins/genetics , RNA, Messenger/metabolism , Reference Values , Time Factors
18.
Fertil Steril ; 51(4): 682-4, 1989 Apr.
Article in English | MEDLINE | ID: mdl-2924936

ABSTRACT

A prospective randomized study was conducted in 47 couples with infertility due to subnormal semen to compare luteinizing hormone (LH)-timed intrauterine insemination with LH-timed natural intercourse. No pregnancy occurred in 114 cycles of intrauterine insemination with washed sperm. Only one patient conceived during 1 of the 124 natural intercourse cycles. The only complication that occurred after intrauterine insemination was mild abdominal cramp in 3 cycles. The authors conclude that intrauterine insemination is not useful in the management of subfertility due to oligoasthenospermia.


Subject(s)
Insemination, Artificial, Homologous , Insemination, Artificial , Luteinizing Hormone/blood , Oligospermia/physiopathology , Adult , Female , Humans , Male , Pregnancy
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