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Journal of Public Health Management and... 2019Since 2007, 2 doses of varicella vaccine have been routinely recommended, with a catch-up second dose recommended for those who received only 1 prior dose.
CONTEXT
Since 2007, 2 doses of varicella vaccine have been routinely recommended, with a catch-up second dose recommended for those who received only 1 prior dose.
OBJECTIVE
To examine varicella vaccination coverage with 2 or more doses and the proportions of adolescents with evidence of immunity to varicella (≥2 doses of vaccine or varicella history) during 2007-2014. To assess timing of second-dose receipt, factors associated with 2 or more vaccine doses, and missed second-dose opportunities during 2014.
DESIGN, SETTING, AND PARTICIPANTS
We used data from the 2007-2014 National Immunization Survey-Teen (NIS-Teen), which collects information on adolescents aged 13 to 17 years in the United States.
RESULTS
From 2007 to 2014, varicella vaccination coverage with 2 or more doses increased from 8.3% to 66.9% in 13- to 15-year-olds and from 3.6% to 56.7% in 16- to 17-year-olds. The proportions with evidence of immunity also increased from 68.0% to 84.1% (13- to 15-year-olds) and 78.6% to 83.4% (16- to 17-year-olds). In 2014, 13.4% of 13- to 15-year-olds and 3.2% of 16- to 17-year-olds had received their second dose at 4 to 6 years of age. Factors most significantly associated with lower coverage with 2 or more doses were not having an 11- to 12-year well-child visit, not receiving an adolescent vaccine, and residence in a state with no 2-dose immunization school entry requirement. Seventy-seven percent of 1-dose vaccinated adolescents had 1 or more missed opportunities to receive their second dose; if were they not missed, 2-dose coverage would have increased from 79.5% to 94.8%.
CONCLUSIONS
Levels of varicella vaccination coverage with 2 or more doses and the proportion of adolescents with evidence of immunity increased from 2007 to 2014, though 16% lacked evidence of immunity in 2014. Although catch-up campaigns have succeeded, missed vaccination opportunities persist.
Topics: Adolescent; Chickenpox; Chickenpox Vaccine; Female; Herpesvirus 3, Human; Humans; Immunization Programs; Male; Surveys and Questionnaires; United States; Vaccination
PubMed: 29889179
DOI: 10.1097/PHH.0000000000000819 -
International Journal of Cancer Jul 2021Adjuvant chemotherapy regimens take months to complete. Despite this, studies evaluate chemotherapy adherence via measures assessed at the end of treatment (eg, number... (Comparative Study)
Comparative Study Randomized Controlled Trial
Adjuvant chemotherapy regimens take months to complete. Despite this, studies evaluate chemotherapy adherence via measures assessed at the end of treatment (eg, number of patients missing any dose, relative dose intensity [RDI]). This approach ignores information like the timing of treatment delays. We propose longitudinal cumulative dose (LCD) to integrate impacts of dose reductions, missed doses and dose delays over time. We obtained data from the 2246 participants in the MOSAIC trial randomized to FOLFOX (all three agents) or 5-FU/LV (only 5-fluorouracil and leucovorin). We evaluated proportions of patients stopping treatment early and reducing, missing or delaying a dose in each arm for each chemotherapy agent at each cycle. We calculated LCD, the fraction of the final standard dose a participant reached by a given day, for each participant and each agent and compared it over time and at 24 weeks between treatment arms. Participants randomized to FOLFOX were more likely to stop treatment, reduce doses, miss doses or delay cycles; these differences increased over time. Median LCD for oxaliplatin in the FOLFOX arm at 24 weeks was 77%. The LCD for 5-fluorouracil differed between arms (FOLFOX arm median: 81%; 5-FU/LV arm median: 96%). Visualizing LCD highlighted the timing of deviations from standard administration in a way RDI could not, with major differences in 5-fluorouracil LCD across treatment arms beginning after the sixth dose. Further evaluation of LCD and its impacts on clinical outcomes may clarify mechanisms for heterogeneous patient outcomes.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Colonic Neoplasms; Dose-Response Relationship, Drug; Female; Fluorouracil; Humans; Leucovorin; Male; Medication Adherence; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Treatment Outcome; Young Adult
PubMed: 33729546
DOI: 10.1002/ijc.33565 -
Neuropsychiatric Disease and Treatment 2013Paliperidone palmitate (PP) is a long-acting injectable formulation of an atypical antipsychotic, paliperidone. Its dose can be expressed in milligram or milligram...
BACKGROUND
Paliperidone palmitate (PP) is a long-acting injectable formulation of an atypical antipsychotic, paliperidone. Its dose can be expressed in milligram or milligram equivalents (mg eq) of active paliperidone (39, 78, 117, 156, and 234 mg of PP correspond to 25, 50, 75, 100, and 150 mg eq of paliperidone). The recommended initiation dosing regimen for PP is 150 [day 1]/100[day 8] mg eq. Labeling guidance allowed a ± 2 day window for the day 8 injection that provides more flexibility with patient scheduling and avoids missing the day 8 initiation dose. Recently, expansion of the day 8 dosing window from ±2 to ±4 days has been approved in the United States based on results obtained from the model-based simulations and review of safety data presented here.
METHODS
The predicted exposure for the recommended initiation regimen of PP was compared with day 1/day 4, and day 1/day 12 dosing scenarios; each scenario was compared with the highest clinically evaluated initiation regimen (150[day 1]/150[day 8] mg eq) and to the recommended 6 mg/day oral dose of extended-release paliperidone.
RESULTS
Simulated exposures with PP 150 mg eq on day 1 and 100 mg eq on days 4, 8, or 12 overlap considerably, with ±3 ng/mL variation in median maximum plasma concentrations. Based upon pharmacokinetic bridging/bracketing, the peak concentration with PP 150/100 mg eq [days 1/4] was lower than that with the highest initiation regimen. Exposures for PP 150 mg eq on day 1 and 100 mg eq on days 4, 8, or 12 were maintained close to those of 6 mg of paliperidone extended-release.
CONCLUSION
These simulations indicate that using the expanded dosing window of ±4 days has little effect on paliperidone exposure. A review of the overall pattern of treatment-emergent adverse events did not identify any new safety risks associated with the expanded dosing window.
PubMed: 23723704
DOI: 10.2147/NDT.S40836 -
Journal of Human Hypertension Feb 2010Most patients inadvertently miss an occasional dose of antihypertensive therapy, and hence drugs that provide sustained blood-pressure (BP) reduction beyond the 24-h... (Comparative Study)
Comparative Study Randomized Controlled Trial
Most patients inadvertently miss an occasional dose of antihypertensive therapy, and hence drugs that provide sustained blood-pressure (BP) reduction beyond the 24-h dosing interval are desirable. The primary objective of this study was to compare the 24-h mean ambulatory BP reductions from baseline after a simulated missed dose of the direct renin inhibitor aliskiren, irbesartan or ramipril. In this double-blind study, 654 hypertensive patients (24-h mean ambulatory diastolic BP (MADBP) >or=85 mm Hg) were randomized 1:1:1 to once-daily aliskiren 150 mg, irbesartan 150 mg or ramipril 5 mg. Doses were doubled after 2 weeks. At day 42, patients were again randomized equally within each group to receive 1 day of placebo ('missed dose') on either day 42 or day 49. Patients with a successful 24-h ambulatory BP measurement at baseline and on day 42/49 were included in the analyses. The 24-h mean ambulatory systolic BP (MASBP)/MADBP reductions from baseline after a missed dose of aliskiren 300 mg (9.3/7.0 mm Hg) were similar to irbesartan 300 mg (9.5/7.3 mm Hg) and significantly larger than ramipril 10 mg (7.1/5.0 mm Hg, P
missed dose (1.0/0.7 mm Hg for 24-48-h vs 0-24-h MASBP/MADBP) was significantly lower than with irbesartan (3.6/2.2 mm Hg, P<0.01) or ramipril (4.0/2.6, P<0.0001). This equates to maintenance of 91/91% of the MASBP/MADBP-lowering effect with aliskiren, greater than irbesartan (73/77%) or ramipril (64/65%). The incidence of adverse events was similar across treatments (32.9-36.0%), although ramipril treatment was associated with an increased incidence of cough (ramipril, 6.1%; aliskiren, 0.5%; irbesartan, 1.8%). Aliskiren 300 mg provided a sustained BP-lowering effect beyond the 24-h dosing interval, with a significantly smaller loss of BP-lowering effect in the 24-48 h period after dose than irbesartan 300 mg or ramipril 10 mg. Topics: Adult; Aged; Amides; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Biphenyl Compounds; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Brazil; Canada; Double-Blind Method; Drug Administration Schedule; Europe; Female; Fumarates; Humans; Hypertension; Irbesartan; Male; Medication Adherence; Middle Aged; Ramipril; Tetrazoles; Time Factors; Treatment Outcome
PubMed: 19458624
DOI: 10.1038/jhh.2009.38 -
International Journal of Radiation... Nov 2011Prolongation of treatment time with radiation therapy (RT) is associated with inferior disease control for many rapidly proliferating tumors, but it is uncertain whether...
Prolongation of total treatment time because of infrequently missed days of treatment is not associated with inferior biochemical outcome after dose-escalated radiation therapy for prostate cancer.
PURPOSE
Prolongation of treatment time with radiation therapy (RT) is associated with inferior disease control for many rapidly proliferating tumors, but it is uncertain whether the same effect is seen in prostate cancer.
METHODS AND MATERIALS
596 patients underwent with curative-intent RT for adenocarcinoma of the prostate. By National Comprehensive Cancer Network criteria, men were classified as having low-risk (30%), medium-risk (40%), or high-risk (30%) disease. The median RT dose was 72 Gy. Androgen-deprivation therapy (ADT) was used in 45%. The idealized treatment time was defined as the total elapsed time (including weekends) to complete treatment if started on a Monday. Missed days of treatment, defined as the number of days beyond the idealized treatment time, was recorded for all patients. Missed days were added to the end of therapy resulting in a longer treatment time. Analysis was conducted for missed days and other standard prognostic variables against freedom from biochemical failure (FFBF).
RESULTS
The median number of missed days was 2 (range, -3 to 22). With a median follow-up of 51 months, men with 5 or more missed days had similar 4-year FFBF rates (79% vs. 83% in men with <5 missed days, p = 0.0809), especially in the subset of men receiving 74 Gy or greater (89% for both groups, p = 0.8008). Analysis of missed days was performed for the subsets of dose, ADT, and risk category. Men without ADT had a lower FFBF rate with more missed days (p = 0.0030), but this association was not seen in men treated to a dose of 74 Gy or greater (p = 0.7425). On multivariate analysis, dose (p = 0.0010), T stage (p = 0.0145), and prostate-specific antigen level (p < 0.0001) were associated with FFBF, but Gleason score (p = 0.1351) and missed days (p = 0.3767) were not.
CONCLUSIONS
Slight prolongation of treatment time (e.g., ≤7 days) was not associated with inferior FFBF, especially in men receiving an RT dose of 74 Gy or greater.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Analysis of Variance; Androgen Antagonists; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy Dosage; Radiotherapy, Intensity-Modulated; Risk Assessment; Time Factors; Withholding Treatment
PubMed: 20932666
DOI: 10.1016/j.ijrobp.2010.06.054 -
Epilepsy & Behavior : E&B Jul 2019This study investigated the effect of delayed or missed doses on the pharmacokinetics (PK) of lamotrigine (LTG) in children with epilepsy and established remedial dosing...
OBJECTIVE
This study investigated the effect of delayed or missed doses on the pharmacokinetics (PK) of lamotrigine (LTG) in children with epilepsy and established remedial dosing recommendations for nonadherent patients.
METHODS
The Monte Carlo simulation based on a published LTG population PK model was used to assess the effect of different scenarios of nonadherence and the subsequently administered remedial regimens. The following three remedial approaches were investigated for each delayed dose: A) A partial dose was administered immediately, and the regular dose was administered at the next scheduled time. B) The delayed dose was administered immediately, followed by a partial dose at the next scheduled time. C) The delayed and partial doses were coadministered immediately, the next scheduled dose was skipped, and the regular dosing was resumed at the subsequent scheduled time. The most appropriate remedial regimen was that with the shortest deviation time from the individual therapeutic window.
RESULTS
The effect of nonadherence on PK was dependent on the delay duration and daily dose, and the recommended remedial dose was related to the delay duration and concomitant antiepileptic drugs. Remedial dosing strategies A and B were almost equivalent, whereas C showed a larger PK deviation time. If one dose was missed, double doses were not recommended for the next scheduled time.
CONCLUSIONS
Simulations provide quantitative insight into the remedial regimens for nonadherent patients, and clinicians should select the optimal regimen based on the status of patients.
Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Drug Administration Schedule; Epilepsy; Female; Humans; Lamotrigine; Male; Monte Carlo Method
PubMed: 31132614
DOI: 10.1016/j.yebeh.2019.04.007 -
Annals of Allergy, Asthma & Immunology... May 2012Practical issues dealing with the administration of allergen immunotherapy (AIT) by European and US allergists are not well known. Several concerns are only partially...
BACKGROUND
Practical issues dealing with the administration of allergen immunotherapy (AIT) by European and US allergists are not well known. Several concerns are only partially covered by guidelines.
OBJECTIVE
To survey AIT practice patterns among worldwide members of the American Academy of Allergy, Asthma and Immunology (AAAAI).
METHODS
A web-based survey was conducted among AAAAI members on dosing, dose adjustment after missed doses, and duration of AIT.
RESULTS
A total of 1,201 replies (24.7% response rate of which 10% of responses were from non-US and non-Canada members). A total of 57% to 65% of the US-Canadian dosing falls within the recommended Practice Parameter ranges (9.4%-19% too low). Dose adjustment after missed doses is based on time elapsed since the last administered dose by 77% of US-Canadian and 58% of non-US-Canadian allergists. Doses are reduced when a patient comes in more than 14 days for 5 weeks after the last administration and initial dosing restarted after more than 30 days for 12 weeks since last administration during the build-up or maintenance stage. After missing 1 to 3 doses, the dosing schedules were mostly followed (build-up phase: repeat last dose, reduce by 1 dose, reduce by 2doses; maintenance phase: reduce by 1 dose, reduce by 2 doses, reduce by 3 doses). AIT is prescribed for a median of 3 years by non-US-Canadian allergists but for a median of 5 years by 75% of US-Canadian allergists. Main reasons for continuing beyond 5 years were "after stopping, symptoms reappeared" or "patient afraid to relapse."
CONCLUSION
Many patients receive less than recommended doses. Two areas in which to plan further research are establishment of an optimal dose-adjustment plan for missed applications and exploration of the maximum appropriate duration of immunotherapy.
Topics: Allergens; Allergy and Immunology; Canada; Desensitization, Immunologic; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Health Care Surveys; Humans; Hypersensitivity; Internet; Male; Practice Guidelines as Topic; Practice Patterns, Physicians'; Surveys and Questionnaires; Time; United States
PubMed: 22541411
DOI: 10.1016/j.anai.2012.03.009 -
Medicine and Science in Sports and... Feb 2020While general guidelines (such as CONSORT or Consensus on Exercise Reporting Template) exist to enhance the reporting of exercise interventions in the field of exercise...
PURPOSE
While general guidelines (such as CONSORT or Consensus on Exercise Reporting Template) exist to enhance the reporting of exercise interventions in the field of exercise science, there is inadequate detail facilitating the standardized reporting of resistance training adherence in the oncology setting. The purpose of this study was to apply a novel method to report resistance training dose, adherence, and tolerance in patients with cancer.
METHODS
A total of 47 prostate cancer patients (70.1 ± 8.9 yr, body mass index, 28.6 ± 4.0) with bone metastatic disease completed an exercise program for 12 wk. We assessed traditional metrics of adherence (attendance and loss to follow-up), in addition to novel proposed metrics (exercise-relative dose intensity, dose modification, and exercise interruption). Total training volume in kilograms (repetitions × sets × training load (weight)) was calculated for each patient.
RESULTS
Attendance assessed from traditional metrics was 79.5% ± 17.0% and four patients (9%) were lost to follow-up. The prescribed and actual cumulative total dose of resistance training was 139,886 ± 69,150 kg and 112,835 ± 83,499 kg, respectively, with a mean exercise-relative dose intensity of 77.4% ± 16.6% (range: 19.4% -99.4%). Resistance training was missed (1-2 consecutive sessions) or interrupted (missed ≥3 consecutive sessions) in 41 (87%) and 24 (51%) participants, respectively. Training dose was modified (reduction in sets, repetitions, or weight) in 40 (85%) of patients. Importantly, using attendance as a traditional metric of adherence, these sessions would have all counted as adherence to the protocol.
CONCLUSIONS
Traditional reporting metrics of resistance training in exercise oncology may overestimate exercise adherence. Our proposed metrics to capture resistance training dose, adherence, and tolerance may have important applications for future studies and clinical practice.
Topics: Aged; Bone Neoplasms; Exercise Therapy; Fatigue; Follow-Up Studies; Humans; Male; Middle Aged; Patient Compliance; Prostatic Neoplasms; Resistance Training; Retrospective Studies; Weight Lifting
PubMed: 31436734
DOI: 10.1249/MSS.0000000000002127 -
Blood May 2017Ibrutinib, an oral inhibitor of Bruton's tyrosine kinase (BTK), at a once-daily dose of 420 mg achieved BTK active-site occupancy in patients with chronic lymphocytic...
Ibrutinib, an oral inhibitor of Bruton's tyrosine kinase (BTK), at a once-daily dose of 420 mg achieved BTK active-site occupancy in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) that was maintained at 24 hours. It is unknown if intermittent interruption of ibrutinib therapy contributes to altered clinical outcomes. We therefore evaluated the effect of ibrutinib dose adherence on patient outcomes in the phase 3 RESONATE trial. The overall mean dose intensity (DI) was 95% with median treatment duration of ∼9 months. Pharmacokinetic assessment of ibrutinib exposure at 420-mg dose suggested similar exposure regardless of patient weight or age. As assessed by independent review committee, patients with higher DI experienced longer median progression-free survival (PFS) compared with those with lower DI regardless of del17p and/or status. Of 79 patients requiring a drug hold, treatment was restarted at the original dose in 73 (92%) patients. Mean duration of a missed-dose event was 18.7 days (range, 8-56). Patients missing ≥8 consecutive days of ibrutinib had a shorter median PFS vs those missing <8 days (10.9 months vs not reached). These results support sustained adherence to once-daily ibrutinib dosing at 420 mg as clinically feasible to achieve optimal outcomes in patients with previously treated CLL. The trial was registered at www.clinicaltrials.gov as #NCT01578707.
Topics: Adenine; Agammaglobulinaemia Tyrosine Kinase; Antineoplastic Agents; Disease-Free Survival; Dose-Response Relationship, Drug; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Mutation; Patient Compliance; Piperidines; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Pyrazoles; Pyrimidines; Tumor Suppressor Protein p53
PubMed: 28373262
DOI: 10.1182/blood-2016-12-737346 -
Journal of Pharmacokinetics and... Aug 2022Missed doses, late doses, and other dosing irregularities are major barriers to effective pharmacotherapy, especially for the treatment of chronic conditions. What...
Missed doses, late doses, and other dosing irregularities are major barriers to effective pharmacotherapy, especially for the treatment of chronic conditions. What should a patient do if they did not take their last dose at the prescribed time? Should they take it late or skip it? In this paper, we investigate the pharmacokinetic effects of taking a late dose. We consider a single compartment model with linear absorption and elimination for a patient instructed to take doses at regular time intervals. We suppose that the patient forgets to take a dose and then realizes some time later and must decide what remedial steps to take. Using mathematical analysis, we derive several metrics which quantify the effects of taking the dose late. The metrics involve the difference between the drug concentration time courses for the case that the dose is taken late and the case that the dose is taken on time. In particular, the metrics are the integral of the absolute difference over all time, the maximum of the difference, and the maximum of the integral of the difference over any single dosing interval. We apply these general mathematical formulas to levothyroxine, atorvastatin, and immediate release and extended release formulations of lamotrigine. We further show how population variability can be immediately incorporated into these results. Finally, we use this analysis to propose general principles and strategies for dealing with dosing irregularities.
Topics: Anticonvulsants; Delayed-Action Preparations; Humans
PubMed: 35726046
DOI: 10.1007/s10928-022-09812-0