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Declaration of funding interests : The authors report the following: S. Dutko, M. Burroughs and W. Now at Warner Chilcott. Now at Novartis. Now at jkalbrecht gmail. Table S1. SVR rates with varying adherence rates in previous relapsers or previous partial responders. Table S2. Discontinuations due to treatment failure vs.

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Table S3. Impact on SVR rates of adherence to t. Table S4. Table S6. Impact on resistance of adherence to the t. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries other than missing content should be directed to the corresponding author for the article. Volume 38 , Issue 1. If you do not receive an email within 10 minutes, your email address may not be registered, and you may need to create a new Wiley Online Library account.

If the address matches an existing account you will receive an email with instructions to retrieve your username. Original Article Free Access. Search for more papers by this author. Tools Request permission Export citation Add to favorites Track citation. Share Give access Share full text access. Share full text access. Please review our Terms and Conditions of Use and check box below to share full-text version of article. Summary Background Adherence to therapeutic regimens affects the efficacy of peginterferon alfa P and ribavirin R therapy in patients with chronic hepatitis C virus genotype 1.

Conclusions The achievement of an SVR is more dependent on adherence to the assigned duration of treatment than adherence to the t. Thirty seven and six patients with nongenotype 1 or missing data in previously untreated patients and patients who failed previous therapy, respectively. Figure 1 Open in figure viewer PowerPoint.

Figure 2 Open in figure viewer PowerPoint. Figure 3 Open in figure viewer PowerPoint. Per cent of patients who adhered to the t. The percentage of patients with varying levels of adherence to the t. Figure 4 Open in figure viewer PowerPoint. Sustained virological responses SVR in patients by adherence to the t.

The SVR rates for patients with varying levels of adherence to the t. Adherence to the amount of doses for each drug P, R and BOC was defined as the total dose of drug received by the patient divided by the expected total drug dose where the expected total drug dose was based on the actual treatment duration. Adherence b Adherence to the assigned duration of the dosing regimen and adherence to the t.

Adherence to t. Impact of adherence before or after treatment week 8 on SVR rates and resistance Varying rates of adherence to t. Discussion The present retrospective analysis of two large registration trials indicates that adherence to duration of treatment with P plus R plus BOC is an important factor associated with achieving SVR in patients with chronic hepatitis C genotype 1 infection.

Acknowledgements Declaration of personal interests : We thank all the patients, health care providers and investigators involved in the study. Table S5. Impact on resistance of adherence to duration of therapy. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med ; : 21 — Citing Literature. Volume 38 , Issue 1 July Pages In the rehabilitation stage, it is important to accurately understand or estimate realistic individual external doses so that individuals can make informed decisions based on their radiological protection to return to restricted areas.

The government has recently stressed the importance of considering individual external dose data collected from personal dosimeters. For example, in November , the Nuclear Regulation Authority recommended that people wear personal dosimeters once they return to their original home in order to safeguard against radiation exposure [ 7 ]. In July , the Ministry of the Environment proposed a new policy that will determine decontamination needs by using radiation exposure data collected using personal dosimeters [ 8 ].

Individual external dose monitoring has been conducted in several municipalities in Fukushima [ 4 , 9 ] and provides realistic external dose values for individuals. Most of the monitoring programs in Fukushima use glass badge dosimeters to obtain the individual external dose. Although glass badge dosimeters are useful in large-scale personal monitoring and can obtain large amounts of data safely and quickly, they clearly cannot identify when and where significant external dose occurs.

In order to take appropriate countermeasures against unacceptable doses from external irradiation and to develop an individual external dose model applicable to the affected Fukushima areas, it is important to identify when, where, and how much external exposure occurs, and to quantitatively relate individual external dose and ambient dose rates to different behavior patterns of individuals living in Japanese-style homes. Accurate information on individual external doses is needed by the government policymakers, by people providing health care and radiation dose mitigation advice, and especially by affected citizens.

Several studies have attempted to use personal dosimeters in conjunction with personal diaries to understand realistic individual external dose levels related to time-activity patterns in Fukushima [ 6 , 10 , 11 ]. Takahara et al. A group of students at Fukushima High School conducted a study to compare the external radiation exposure levels experienced by students and teachers in Japan, Belarus, France, and Poland, and found that external radiation doses in Fukushima were comparable to those in other parts of Japan and in Europe [ 11 ].

Although these studies contributed valuable information towards understanding realistic individual external dose levels and their variabilities in relation to time-activity patterns in Fukushima, little attention has been given to obtaining radiation exposure information applicable to the prediction of future individual external doses of people with different time-activity patterns. Moreover, we attempted to determine the ranges of parameters applicable to the estimation of future cumulative external doses of individuals by considering time-activity patterns.

Eighty-seven residents of Fukushima Prefecture participated in our study. The locations of the homes are shown in Fig 1. The study was conducted over approximately 3—day periods between September and March On measurement days, the airborne-monitoring-based ambient dose rates at the homes of the participants ranged from 0. In the figure, circles, triangles, and rectangles represent the homes of subjects who participated in the individual external dose measurements once, twice, and three or more times, respectively.

Ambient dose rates adjusted to as of September 28, are based on the 7th airborne monitoring survey conducted between August 27 and September 28, Maps created using ArcGIS Personal dosimeters incorporating GPS receivers with time-activity diaries and a GIS were used to determine when, where, and how much external exposure occurred. The D-Shuttle was used to determine the hourly and total external dose Fig 2.

The D-Shuttle consists of a silicon semiconductor and can measure total dose ranges of 0.

The values measured by the D-Shuttle are expressed as personal dose equivalent Hp Since Hp 10 values measured under the conditions of the affected areas in Fukushima are known to be comparable with the effective dose of isotropic ISO or rotational ROT irradiation geometries [ 13 , 14 ], we regarded the individual dose measured by D-shuttle to be a realistic indicator of the effective dose from external radiation exposure. Several municipalities in the special decontamination areas in Fukushima provide D-Shuttle to their residents to measure and understand individual external dose for their own use.

Definition and general considerations

Moreover, D-Shuttle is recognized as a good communication tool for understanding individual external doses in affected areas [ 15 ]. In this study, the i-gotUs were set to record latitude and longitude every 5 seconds. In addition to GPS, self-reported weekly time-activity and location diary data were used to fill any gaps in the GPS data, and to determine indoor and outdoor positions. The GPS and time-activity diary data were used to determine the location and activity of the subjects.

The 7th airborne monitoring survey was used to determine the ambient dose [ 12 ]. In relating the individual external dose measured by D-Shuttle with the ambient dose determined based on the 7th airborne monitoring survey, the values of the ambient dose were adjusted for the study periods by taking into account physical decay. Both the individual external dose measured by D-Shuttle and the ambient dose determined based on the 7th airborne monitoring survey include doses resulting from artificial radionuclides i.

In the analyses of the relationship between the individual external dose and ambient dose, the additional doses resulting from artificial radionuclides were used. Estimation of the ambient dose for the individual external dose measurement was adjusted for the study period, and the physical decay of only artificial radionuclides was taken into account.

To calculate additional individual external dose and additional ambient dose, 0. Individual external dose data measured by the D-Shuttle, GPS receiver data with time-activity diaries, and ambient dose rate data were collated into a database by matching the associated timestamps from each device, thereby integrating the data into a common array using ESRI ArcGIS The collated data were anonymized then available for post processing and analysis. Written informed consent was obtained from all subjects prior to conducting the study. Eighty-seven residents participated in our study between September and March ; 30 individuals participated multiple times, providing total participants.

The data from individuals living in less affected areas and away from Fukushima at the time of the study were eliminated, leaving the data from participants for analysis. Details of study participants and exposure durations are summarized in S1 Table. The participants consisted of 70 full-time farmers, 8 part-time farmers, 35 office workers, 6 housewives, 6 self-employed workers and 17 individuals with an unspecified occupation. Our results indicate that people spent a substantial portion of the time at home and this agrees well with time-activity patterns in Fukushima reported elsewhere [ 10 , 16 ].

The median and mean of the individual external doses measured by D-shuttle were 0.

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Table 1 lists summary statistics for individual external doses obtained using D-shuttle. The distributions of individual external doses for each person were generally lognormally distributed. More than 6-fold differences were observed in the mean and GM of the individual external doses of participants.

The individual external dose measurements obtained using D-shuttle by the Fukushima High School students [ 11 ] demonstrated that median hourly individual external doses ranged between 0. Other individuals with higher than average individual external doses included a retired person living in a relatively higher ambient dose area, and a farmer working at a non-remediated orchard.

The relationship between the average additional external individual dose obtained using D-shuttle and the average additional ambient dose estimated based on the air-borne monitoring survey, and the relationship between the reduction factor RF and the average additional ambient dose, are presented in Fig 4.

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  • The RF is defined as the ratio of the additional individual external dose to the additional ambient dose. The raw data used to analyze these relationships are provided in S3 Table. Individual external dose data, making it possible to locate position and relate the ambient dose data, were used in this analysis.

    These results indicate that the average additional individual external doses were significantly lower than the average additional ambient doses estimated based on the air-borne monitoring survey. The exposure while at home was estimated to be the lowest mostly due to the building shielding effect. The mean values of the RFs were 0. Previous studies also demonstrated that the levels of individual external doses directly measured using a personal dosimeter were substantially lower than levels estimated using the government-proposed equation [ 5 , 6 ].

    The RFs reported in these studies were on average about 0. The reasons for this discrepancy include the values of background doses used to estimate additional dose, consideration of decay in the ambient dose determination, and differences in number and type of participants. The first, second and third rows represent the results for data from the total study period, while at home, and while outdoors, respectively.

    Individual external dose, expressed as Hp 10 values, measured in affected areas in Fukushima have previously been reported to be comparable with the ISO or ROT irradiation geometries [ 13 , 14 ]. Earlier published evidence showed that the values of Hp 10 were about 0.

    In the current study, most of the RFs were derived from outdoor data in which the mean value was 0. There can be several reasons for such discrepancies and variabilities among the RFs. The airborne monitoring-based ambient dose rates, which used in the current study, are considered as an aerial average, and not the ambient dose rates based on the point locations of individuals. The airborne monitoring data were obtained using high-sensitivity radiation detectors installed on helicopters: second-by-second measurements are taken of gamma rays emitted from radioactive substances deposited in circles of a diameter approximately twice the flight altitude target altitude: to m and centered around ground locations directly below the flight trajectory [ 18 ].

    If a helicopter flies at an altitude of approximately m above the ground, the system measures the average value of the radiation in a circle in m radius on the ground [ 18 ]. A dedicated software program was used to determine the hourly ambient dose rate 1 m above the ground surface at each location based on the value of gamma rays measured in the air and the reading from the survey meter on the ground [ 18 ]. Therefore, the airborne monitoring-based ambient dose rates, therefore, may be over or under estimations of the actual ambient dose rates measured on the ground near the locations of individuals.

    The reasons for very low RFs obtained in this study can be due to several factors such as decontamination activity, and the behavior and locations of individuals. If an individual stays or works in a decontaminated area and the airborne monitoring system does not detect the decrease in radiation level of the decontamination area, the values for individual external dose can be much lower than the airborne monitoring-based ambient dose rates.

    In addition, an individual working for a long period of time on tarmacked surfaces or in farm trucks could be exposed to a low individual external doses. Quantifications of the effects of these factors on RFs remain a future challenges. People are not typically standing motionless outdoors, but rather spend time both outdoors and indoors where there is some sort of radiation shielding.

    The mean RF for time spent at home obtained in this study was 0. The median reduction factor with an interquartile range for wooden houses, which is the ratio of indoor ambient dose rate to outdoor ambient dose rate, has been reported to be 0. Since the methods for calculating home RFs in our study and the reported reduction factors are different, it is not possible to directly compare our home RFs and the reported reduction factors.

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    The reported reduction factors are defined as the ratio of indoor ambient dose rate to outdoor ambient dose rate, while the home RFs in our study are defined as the ratio of additional individual dose rate to airborne-based additional ambient dose rate. Since decontamination works has been conducted in the most of houses in the affected areas in Fukushima, the outdoor ambient dose rate measured at decontaminated points around a house are considered to be lower than the airborne-based ambient dose rate.

    Moreover, the values of Hp 10 were about 0. Taking these relationships and variability of RFs into account, our estimated home RFs are comparable to those reported in previous studies [ 10 , 19 ] and can be used to estimate individual external dose during time spent at home based on the airborne-based ambient dose. In the current study, we used publicly available ambient dose rate data estimated from the airborne monitoring survey provided by the Japanese government. The current study relates the individual external doses to the publicly available ambient dose rates and with the activity-patterns of the individuals.

    The results provide, from a practical viewpoint, valuable information for understanding and estimating realistic individual external doses in the affected areas in Fukushima, especially for evacuees who want to know their individual external doses after returning to their original homes.