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American Journal of Hypertension Sep 2016Central aortic blood pressure (CBP) and CBP-derived parameters are independent predictors of cardiovascular risk. Angiotensin II receptor blockers (ARBs) or... (Comparative Study)
Comparative Study Randomized Controlled Trial
Comparative Study of the Efficacy of Olmesartan/Amlodipine vs. Perindopril/Amlodipine in Peripheral and Central Blood Pressure Parameters After Missed Dose in Type 2 Diabetes.
BACKGROUND
Central aortic blood pressure (CBP) and CBP-derived parameters are independent predictors of cardiovascular risk. Angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors plus calcium channel blockers are the recommended first-line treatments in hypertensive diabetic patients; however, the effect in reducing CBP when a dose is skipped has not been established yet. The aim was to determine whether the fixed-dose combination of olmesartan/amlodipine (OLM/AML) provides equal efficacy and safety as the perindopril/AML (PER/AML) combination in reducing CBP, augmentation index (AIx), and pulse wave velocity (PWV) when a drug dose is missed.
METHODS
In this noninferiority, randomized, double-blind, double-dummy parallel group, controlled design trial, 88 patients received either OLM 20-40mg/AML 5-10mg (41 patients) or PER 4-8mg/AML 5-10mg (47 patients) for 24 weeks. The main endpoint was the aortic systolic BP (SBP) after 24 weeks of treatment at 48 hours from the last administration.
RESULTS
The OLM/AML combination reached the noninferiority criteria in reducing central systolic BP after 24 weeks of treatment and after the missed dose, compared to the PER/AML combination (-17 and -8mm Hg, respectively). Peripheral BP, AIx, and PWV were significantly lower in both groups after 24 weeks of treatment and 48 hours after the missed dose, observing a trend to a greater reduction in CBP-derived parameters in the OLM/AML group.
CONCLUSIONS
The OLM/AML combination is safe, well tolerated, and not inferior to the combination of PER/AML in lowering CBP and CBP-derived parameters in diabetic patients. OLM/AML provides longer-lasting efficacy in terms of CBP reduction compared to PER/AML.
Topics: Aged; Amlodipine; Antihypertensive Agents; Blood Pressure; Diabetes Mellitus, Type 2; Female; Humans; Hypertension; Imidazoles; Male; Middle Aged; Perindopril; Pulse Wave Analysis; Tetrazoles
PubMed: 27220840
DOI: 10.1093/ajh/hpw033 -
Journal of Hypertension Feb 2016Combination therapy is needed to control blood pressure (BP) in a large number of hypertensive patients with diabetes mellitus. Adherence to treatment is a major... (Comparative Study)
Comparative Study Randomized Controlled Trial
INTRODUCTION
Combination therapy is needed to control blood pressure (BP) in a large number of hypertensive patients with diabetes mellitus. Adherence to treatment is a major clinical problem; therefore, the time duration of the antihypertensive action of a drug determines BP control when a dose is skipped.
OBJECTIVES
The aim was to determine whether the fixed-dose combination of olmesartan/amlodipine provides equal efficacy and safety as the perindopril/amlodipine combination when a drug dose is missed.
METHODS
In this noninferiority trial with a randomized, double-blind, double-dummy parallel group, controlled design, 260 patients received either olmesartan 20-40 mg/amlodipine 5-10 mg or perindopril 4-8 mg/amlodipine 5-10 mg for 24 weeks. The main outcome was the sitting office DBP after 24 weeks of treatment at 48 h from last administration.
RESULTS
The olmesartan/amlodipine combination reached noninferiority criteria in reduction of office DBP after 24 weeks of treatment and after the missed dose, compared with the perindopril/amlodipine combination (-11.7 and -10.5 mmHg, respectively). Office SBP and pulse pressure were significantly lower in both groups after 24 weeks of treatment and 48 h after the missed dose, observing a trend to greater SBP reduction in the olmesartan/amlodipine group.
CONCLUSIONS
The combination olmesartan/amlodipine is safe, well tolerated, and as effective as the combination of perindopril/amlodipine in the control of essential hypertension in patients with diabetes mellitus. A missed dose does not leave the patients unprotected in both treatments; however, a faster control with less dose increment is observed with olmesartan/amlodipine.
Topics: Adult; Aged; Amlodipine; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Combinations; Essential Hypertension; Female; Humans; Hypertension; Imidazoles; Male; Medication Adherence; Middle Aged; Perindopril; Tetrazoles; Treatment Outcome
PubMed: 26867060
DOI: 10.1097/HJH.0000000000000793 -
Vaccine Nov 2022In 2018, CDC recommended a highly efficacious adjuvanted recombinant zoster vaccine (RZV) as a 2-dose series for prevention of herpes zoster (HZ) for immunocompetent...
In 2018, CDC recommended a highly efficacious adjuvanted recombinant zoster vaccine (RZV) as a 2-dose series for prevention of herpes zoster (HZ) for immunocompetent persons age ≥ 50 years, with the 2nd dose recommended 2-6 months after the 1st dose. We estimated second-dose RZV series completion in the U.S. among 50-64-year-olds using two administrative databases. Second-dose RZV series completion was ∼70% within 6-months and 80% within 12-months of first dose. Among those who received only 1 RZV dose with at least 12 months of follow-up time, 96% had a missed opportunity for a second-dose vaccination, defined as a provider or pharmacy visit, among whom 36% had a visit for influenza or pneumococcal vaccination within 2-12 months of their first-dose of RZV. We found that RZV series completion rates in 50-64-year-olds was high. Availability of RZV at pharmacies has potentially helped increase series completion, but missed opportunities remain.
Topics: Adult; Humans; United States; Herpes Zoster Vaccine; Herpes Zoster; Vaccines, Synthetic; Influenza Vaccines; Influenza, Human
PubMed: 36347721
DOI: 10.1016/j.vaccine.2022.10.065 -
European Journal of Clinical... Nov 2022To determine the influences of one or two consecutive missed topiramate (TPM) doses on TPM pharmacokinetics and to suggest the proper TPM replacement dosing schemes...
PURPOSE
To determine the influences of one or two consecutive missed topiramate (TPM) doses on TPM pharmacokinetics and to suggest the proper TPM replacement dosing schemes using Monte Carlo simulations.
METHODS
Monte Carlo simulations were performed for various replacement dosing schemes using the parameters from the published population pharmacokinetic models. The lowest percentage of deviation of simulated concentrations outside the reference range of 5-20 mg/L from the compliance scenario for each replacement dosing scheme was used as a criterion for choosing the proper replacement dosing scheme.
RESULTS
For the one missed dose, the replacement with an immediate regular dose and a partial dose resulted in the lowest and highest percentages of concentration below 5 mg/L, respectively. While the opposite results were observed for the upper bound of the reference range (20 mg/L). For the two consecutive missed doses, the replacement with one and a half-missed doses resulted in a lower percentage of deviation of concentrations below 5 mg/L from the compliance scenario than the replacement with one regular dose.
CONCLUSIONS
For the one missed dose, taking an immediate regular dose might be suitable for patients who require higher TPM levels, while for patients who require lower TPM levels, an immediate partial dose could be used. For the two consecutive missed doses, an immediate one and a half regular dose might be suitable. However, these results were merely based on simulations; thus, they should be used alongside the clinician's justification based on seizure control.
Topics: Anticonvulsants; Drug Administration Schedule; Fructose; Humans; Monte Carlo Method; Topiramate
PubMed: 36121498
DOI: 10.1007/s00228-022-03390-3 -
Journal of Pediatric and Adolescent... Apr 2016To examine human papillomavirus (HPV) series completion in older adolescents and assess vaccination completion opportunities missed by providers. DESIGN, SETTING,...
STUDY OBJECTIVE
To examine human papillomavirus (HPV) series completion in older adolescents and assess vaccination completion opportunities missed by providers. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Electronic medical records were queried for women 18-24 years old who initiated the HPV vaccine in the Adolescent Medicine, Young Mother's, or Family Planning clinics at Children's Hospital Colorado from January 1, 2010-December 31, 2012. Clinic visits during appropriate dosing intervals of HPV vaccine at which the second (4-14 weeks after first dose) or third (21-40 weeks after first dose and >12 weeks after second dose) doses were not administered were counted as "missed opportunities."
RESULTS
A total of 1072 female adolescents initiated the HPV series during the study period; 20.9% completed the series within 1 year. Of these, 33.7% who did not receive their second dose had at least 1 missed opportunity and 25.5% who received the second but not the third had a missed opportunity. Women who initiated the vaccine in the Family Planning clinic were less likely to have missed opportunities than those in other adolescent clinics (36.2% vs 56.4%; P < .001).
CONCLUSION
A significant number of female adolescents who initiated the HPV vaccine attended clinic visits at which opportunities for vaccine continuation and completion were missed. This emphasizes the importance of provider awareness of vaccine updates at every adolescent visit. Our overall completion rate is significantly lower than published rates and might reflect older adolescents' inexperience in managing their own preventive health care. Our results clearly identify the need for provider and patient interventions to improve vaccine series completion.
Topics: Adolescent; Adolescent Behavior; Ambulatory Care Facilities; Colorado; Female; Health Behavior; Humans; Immunization Schedule; Medication Adherence; Papillomaviridae; Papillomavirus Infections; Papillomavirus Vaccines; Vaccination; Young Adult
PubMed: 26300233
DOI: 10.1016/j.jpag.2015.08.003 -
Clinical Drug Investigation Apr 2014Resurgence of multidrug-resistant tuberculosis (MDR-TB) has raised a renewed interest in para-aminosalicylic acid (PAS) and other efficacious drugs. A gastro-resistant...
BACKGROUND AND OBJECTIVES
Resurgence of multidrug-resistant tuberculosis (MDR-TB) has raised a renewed interest in para-aminosalicylic acid (PAS) and other efficacious drugs. A gastro-resistant granule formulation (PAS-GR) was designed to be better tolerated than earlier forms of PAS, with fewer adverse effects from reduced production of meta-aminophenol. PAS release from PAS-GR granules is slower than with earlier formulations. Pharmacokinetic data are, however, limited and only a few studies have assisted in defining the best PAS-GR dose regimen. Interest in refining the latter continues and recent data contributed in better defining the optimal PAS-GR dose regimen in adults and children. The present paper draws on these recent studies, synthesizes pharmacokinetic results from different population groups, and draws comparisons with in vitro data and the results of earlier pharmacokinetic studies in order to discuss the most appropriate dosing regimen for PAS-GR.
METHODS
A comparative in vitro dissolution study was carried out with a 1 g acid PAS equivalent of various formulations of PAS and PAS-GR and in vitro-in vivo correlations. Retrospective comparisons between recent and earlier clinical studies were also gathered to clarify the dose regimen of PAS-GR in adults and children.
RESULTS
Exposure after a 4 g twice- or three times daily dose regimen in adult MDR-TB patients confirmed that both dose regimens can be used. The twice-daily dose regimen does not, however, confer any safety margin over the potentiality of "too" high plasma concentrations after a three times daily dose regimen and may lead to under-dosage when a dose is missed, as compliance often decreases over time.
CONCLUSIONS
Based on available data and practical considerations, a 4 g three times daily dose regimen of PAS-GR should be the preferred dose in hospital settings, where it remains the best regimen to cover the around-the-clock suppression of mycobacteria based on the minimal inhibitory concentration for PAS. In MDR-TB adults and in hospital settings, there is no safety advantage in administering a regimen of 4 g twice daily. As compliance is critical to the effectiveness of the treatment, a 4 g three times daily dose regimen may be more forgiving if the patient misses a dose.
Topics: Adolescent; Adult; Aminosalicylic Acid; Chemistry, Pharmaceutical; Child; Child, Preschool; Clinical Trials as Topic; Drug Administration Schedule; Humans; Infant; Middle Aged; Retrospective Studies; Solubility; Tuberculosis, Multidrug-Resistant; Young Adult
PubMed: 24488376
DOI: 10.1007/s40261-014-0172-7 -
IEEE Transactions on Medical Imaging Dec 2017We present a new method for on-line radiation dose optimization in repeat computer tomography (CT) scanning. Our method uses the information of the baseline scan during...
We present a new method for on-line radiation dose optimization in repeat computer tomography (CT) scanning. Our method uses the information of the baseline scan during the repeat scanning to significantly reduce the radiation dose without compromising the repeat scan quality. It automatically registers the patient to the baseline scan using fractional scanning and detects in sinogram space the patient regions where changes have occurred without having to reconstruct the repeat scan image. It scans only these regions in the patient, thereby considerably reducing the necessary radiation dose. It then completes the missing values of the sparsely sampled repeat scan sinogram with those of the fully sampled baseline sinogram in regions where no changes were detected and computes the repeat scan image by standard filtered backprojection reconstruction. Experiments on a patient scan with simulated changes yield a mean recall of 98% using <19% of a full dose. Experiments on real CT scans of an abdomen phantom produce similar results, with a mean recall of 94.5% and only 14.4% of a full dose more than the theoretical optimum. As hardly any changed rays are missed, the reconstructed images are practically indistinguishable from a full dose scan. Our method successfully detects small, low contrast changes and produces an accurate repeat scan reconstruction using three times less radiation than an image space baseline method.
Topics: Abdomen; Algorithms; Head; Humans; Image Processing, Computer-Assisted; Phantoms, Imaging; Radiation Dosage; Tomography, X-Ray Computed
PubMed: 28880162
DOI: 10.1109/TMI.2017.2747520 -
The Journal of Antimicrobial... Jun 2016To describe the patterns of systemic antibiotic use and missed-dose days and detail the prescription, dispensing and administration of frequently used hospital-initiated...
OBJECTIVES
To describe the patterns of systemic antibiotic use and missed-dose days and detail the prescription, dispensing and administration of frequently used hospital-initiated antibiotics among Ugandan inpatients.
METHODS
This was a prospective cohort of consented adult inpatients admitted on the medical and gynaecological wards of the 1790 bed Mulago National Referral Hospital.
RESULTS
Overall, 79% (603/762; 95% CI: 76%-82%) of inpatients received at least one antibiotic during hospitalization while 39% (300/762; 95% CI: 36%-43%) had used at least one antibiotic in the 4 weeks pre-admission; 1985 antibiotic DDDs, half administered parenterally, were consumed in 3741 inpatient-days. Two-fifths of inpatients who received at least one of the five frequently used hospital-initiated antibiotics (ceftriaxone, metronidazole, ciprofloxacin, amoxicillin and azithromycin) missed at least one antibiotic dose-day (44%, 243/558). The per-day risk of missed antibiotic administration was greatest on day 1: ceftriaxone (36%, 143/398), metronidazole (27%, 67/245), ciprofloxacin (34%, 39/114) and all inpatients who missed at least one dose-day of prescribed amoxicillin and azithromycin. Most patients received fewer doses than were prescribed: ceftriaxone (74%, 273/371), ciprofloxacin (90%, 94/105) and metronidazole (97%, 222/230). Of prescribed doses, only 62% of ceftriaxone doses (1178/1895), 35% of ciprofloxacin doses (396/1130) and 27% of metronidazole doses (1043/3862) were administered. Seven percent (13/188) of patients on intravenous metronidazole and 6% (5/87) on intravenous ciprofloxacin switched to oral route.
CONCLUSIONS
High rates of antibiotic use both pre-admission and during hospitalization were observed, with low parenteral/oral switch of hospital-initiated antibiotics. Underadministration of prescribed antibiotics was common, especially on the day of prescription, risking loss of efficacy and antibiotic resistance.
Topics: Adolescent; Adult; Anti-Bacterial Agents; Cohort Studies; Drug Prescriptions; Female; Hospitalization; Humans; Inpatients; Length of Stay; Male; Medication Adherence; Middle Aged; Prospective Studies; Self Administration; Uganda; Young Adult
PubMed: 26945712
DOI: 10.1093/jac/dkw025 -
European Journal of Nuclear Medicine... Feb 2022This study was to evaluate the effects of an ultra-low dose of [18F]-FDG on the image quality of total-body PET/CT and its lesion detectability in colorectal cancer...
PURPOSE
This study was to evaluate the effects of an ultra-low dose of [18F]-FDG on the image quality of total-body PET/CT and its lesion detectability in colorectal cancer (CRC).
METHODS
Sixty-two CRC patients who underwent total-body PET/CT (uEXPLORER, United Imaging Healthcare, Shanghai, China) with an ultra-low dose (0.37 MBq/kg) of [18F]-FDG were enrolled in this retrospective study. The PET images were reconstructed with the entire 15-min dataset first and then split into 13-, 8-, 5-, 4-, 3-, 2-, and 1-min duration groups to simulate fast scanning images. For simplicity, the images reconstructed with the data from 15 to 1 min were referred to as G15, G13, and so on until G1. Subjective image quality was assessed with 5-point Likert scales. The objective image quality parameters included the SUVmax, SUVmean, and signal-to-noise ratio (SNR) of the liver and blood pool and the SUVmax and tumor-to-background ratio (TBR) of the lesions. G15 served as the control to evaluate lesion detectability.
RESULTS
A total of 62 patients (43 men, 19 women; age 41-88, mean ± SD 64.0 ± 10.9 years) with 64 CRC primary tumor lesions and 10 low-grade intraepithelial neoplasia (LGIN) lesions were enrolled in this study. The subjective scores were highest for G15 (4.5 ± 0.5) and then decreased from G13 (4.3 ± 0.4) to G8 (3.7 ± 0.5). The liver SNR increased with the extension of acquisition time from G8 (17.2 ± 2.8) to G13 (20.6 ± 3.4) and G15 (21.9 ± 3.4). The liver SNR of G8 was not significantly different from that of G13 (p = 0.15) and was significantly different from that of G15 (p = 0.001). All 64 CRC lesions could be identified in all image groups, even on G1. One of ten LGINs was missed on G1, G2, and G3, and one LGIN was missed on G1, G2, G3, and G4. G15 served as the control, and 100% (48/48) lymph nodes could be found on G13 and G8 compared to 93.8% (45/48) lymph nodes on G5 and G4, 85.4% (41/48) lymph nodes on G3, 81.3% (39/48) lymph nodes on G2, and 77.1% (37/48) lymph nodes on G1. For liver metastases, there were no missed liver lesions on G13 and G8 and 3, 4, 6, 7, and 9 missed liver lesions on G5, G4, G3, G2, and G1, respectively. For other areas of metastasis, including the lung, peritoneum, and ovaries, there were no missed lesions in any group.
CONCLUSIONS
Total-body PET/CT with an ultra-low dose of [18F]-FDG can maintain satisfactory image quality and lesion detectability in CRC.
Topics: Adult; Aged; Aged, 80 and over; China; Colorectal Neoplasms; Female; Fluorodeoxyglucose F18; Humans; Liver Neoplasms; Male; Middle Aged; Positron Emission Tomography Computed Tomography; Positron-Emission Tomography; Radiopharmaceuticals; Retrospective Studies; Tomography, X-Ray Computed
PubMed: 34462790
DOI: 10.1007/s00259-021-05537-3 -
Bulletin of Mathematical Biology Dec 2021Medication adherence is a well-known problem for pharmaceutical treatment of chronic diseases. Understanding how nonadherence affects treatment efficacy is made...
Medication adherence is a well-known problem for pharmaceutical treatment of chronic diseases. Understanding how nonadherence affects treatment efficacy is made difficult by the ethics of clinical trials that force patients to skip doses of the medication being tested, the unpredictable timing of missed doses by actual patients, and the many competing variables that can either mitigate or magnify the deleterious effects of nonadherence, such as pharmacokinetic absorption and elimination rates, dosing intervals, dose sizes, and adherence rates. In this paper, we formulate and analyze a mathematical model of the drug concentration in an imperfectly adherent patient. Our model takes the form of the standard single compartment pharmacokinetic model with first-order absorption and elimination, except that the patient takes medication only at a given proportion of the prescribed dosing times. Doses are missed randomly, and we use stochastic analysis to study the resulting random drug level in the body. We then use our mathematical results to propose principles for designing drug regimens that are robust to nonadherence. In particular, we quantify the resilience of extended release drugs to nonadherence, which is quite significant in some circumstances, and we show the benefit of taking a double dose following a missed dose if the drug absorption or elimination rate is slow compared to the dosing interval. We further use our results to compare some antiepileptic and antipsychotic drug regimens.
Topics: Anticonvulsants; Humans; Mathematical Concepts; Medication Adherence; Models, Biological; Treatment Outcome
PubMed: 34928435
DOI: 10.1007/s11538-021-00976-3