Development of an Irish national policy for the management of pregnant or potentially pregnant patients that are referred for a procedure involving the use of ionising radiation.

OBJECTIVES: The management of pregnant or potentially pregnant patients who are referred for medical imaging procedures involving ionising radiation has proven to be a challenge for healthcare providers in Ireland. This has been confirmed by a number of regulatory agencies including the Environmental Protection Agency who have reported poor compliance with legislation, inadequate documentation and sub-optimal patient care. METHODS: An expert group was established to examine the issues that were at the root of these problems and produce recommendations for improvement. The issues highlighted by the group included a lack of clarity and consensus around a number of workflow issues such as exam categorisation, criteria to reasonably rule out pregnancy, dealing with paediatric patients and a protocol to allow urgent high fetal dose examinations to proceed when pregnancy cannot be excluded. The absence of a standardised national pregnancy declaration form was also identified as a contributory factor to poor regulatory compliance. RESULTS: The group produced a pregnancy policy template that healthcare providers could adopt which clarified the issues that were identified and included a standardised adult and paediatric pregnancy declaration form. The implementation of the policy template was subsequently assessed via a survey of a number of radiology departments and a representative referrer group. CONCLUSIONS: The results of these surveys revealed a substantial uptake of the template along with overall satisfaction with the contents. They also demonstrated a reduction in the use of the clinical waiver system which had been highlighted as a cause of sub-optimal patient care. KEY POINTS: • The management of pregnant or potentially pregnant patients referred for medical imaging procedures involving ionising radiation is challenging. • A new national pregnancy policy template was developed by an expert group and has been widely adopted by healthcare institutions in Ireland.

Patient cumulative radiation exposure-the potential for unintended consequences.

Several recent publications have sought to highlight the benefits of tracking patient radiation exposure and how it can be used to strengthen the justification and optimization processes to enhance patient safety. In some cases, authors promote the use of dose tracking to keep medical prescribers aware of the patients' cumulative exposure, presumably with a view to influencing the justification process. Inclusion of patient dose history in the justification process can be problematic for reasons that are not always well understood by medical prescribers. Our paper seeks to highlight these issues and attempts to provide some clarification. Key Points • Care must be taken in how cumulative radiation exposure is interpreted as it pertains to the justification process.

Correction: An Indirect Comparison of Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate and Abacavir/Lamivudine + Dolutegravir in Initial Therapy.

[This corrects the article DOI: 10.1371/journal.pone.0155406.].

An Indirect Comparison of Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate and Abacavir/Lamivudine + Dolutegravir in Initial Therapy.

OBJECTIVES: The objective of this analysis is to perform an indirect comparison of elvitegravir, cobicistat, emtricitabine and tenofovir DF (E/C/F/TDF) to abacavir/lamivudine and dolutegravir (ABC/3TC + DTG) by using 2 trials evaluating each of these regimens in comparison to efavirenz, emtricitabine and tenofovir DF (EFV/FTC/TDF). METHODS: An indirect comparison was performed by using a generalization of Bucher's methodology to calculate risk differences. Two phase III clinical trials (GS-US-236-0102 and SINGLE-described above) were used. RESULTS: Results of the indirect comparison showed no statistically significant risk difference of the efficacy endpoint of achieving HIV RNA < 50 copies/mL between E/C/F/TDF and ABC/3TC + DTG for the ITT population at weeks 48, 96 and 144: respectively -3.7% (CI95% = [-10.8%; 3.4%]), -5.2% (CI95% = [-13.2%; 2.8%]) and -3.1% (CI95% = [-12.0%; 5.7%]). There was no statistically significant differences in the risk difference for serious adverse events (5.7% (CI95% = [-2.2%; 12.3%])), drug related adverse event (2.7% (CI95% = [-7.0%;12.4%])), drug related serious adverse event (0.8% (CI95% = [-1.6%;3.2%])) and death (0.5% (CI95% = [-0.8%;1.8%])), respectively, between E/C/F/TDF and ABC/3TC + DTG. A significant difference was found for discontinuation due to adverse events with a higher rate for E/C/F/TDF (difference = 8.6% (CI95% = [3.3%; 13.9%])). There was also no statistically significant risk difference of the viral resistance of 1.2% (CI95% = [-1.2; 3.7]) between E/C/F/TDF and ABC/3TC + DTG at week 48, 1.7% at week 96 (CI95% = [-1.1; 4.5]) and 2.2% (CI95% = [-1.0; 5.4]) at week 144.

Doses under automatic exposure control (AEC) for direct digital radiographic (DDR) X-ray systems.

Current guidelines quote tolerances for automatic exposure control (AEC) device performance for X-ray systems as 'Baseline ± X %'. However, in the situation where a baseline figure has not yet been achieved, as in the case of commissioning assessments, this tolerance is not relevant. The purpose of this work is to provide mean doses for direct digital radiography (DDR) X-ray system, operating in AEC, against which comparisons can be made. Dose measurements have been recorded under AEC operation on 29 DDR detectors from three different manufacturers. Two different testing protocols were examined: (1) water equivalent phantoms in front of the DDR detector and (2) aluminium block at the tube head. The average patient exit dose, using the aluminium block was 4.6 µGy with the antiscatter grid in place and 4.0 µGy with the grid removed. Using the water phantoms, the average dose was measured at 17.1 µGy with the antiscatter grid in place and 5.4 µGy with grid removed. Based on these results, it is clear that different testing configurations significantly impact on the measured dose.

Beliefs about antiretroviral therapy, treatment adherence and quality of life in a 48-week randomised study of continuation of zidovudine/lamivudine or switch to tenofovir DF/emtricitabine, each with efavirenz.

Adherence may be facilitated by reducing perceptual and practical barriers to antiretroviral therapy (ART). Practical barriers include the complexity of daily dosing, while perceptual barriers include perceptions of the need for treatment and concerns about adverse effects. The study aim was to assess the effect of switching zidovudine plus lamivudine twice-daily (Combivir, CBV) to once-daily tenofovir DF plus emtricitabine (Truvada, TVD), each plus efavirenz (EFZ), on adherence, beliefs about ART and quality of life (QoL). Subjects stable on CBV + EFV were randomised 1:1 to continue this regimen or switch to TVD + EFV. Adherence was measured using the Medication Adherence Self-Report Inventory at 4, 12, 24 and 48 weeks. Beliefs about ART (perceptions of necessity and concerns about adverse effects), treatment intrusiveness and QoL were measured by questionnaire at baseline 4, 12, 24 and 48 weeks. Viral load was assessed at each visit. Two hundred and thirty-four subjects initiated treatment. At week 48, the proportion of subjects reporting high adherence (≥95% taken as prescribed) was significantly greater in the TVD arm (p=0.049). Low adherence (reporting taking <95% as prescribed, discontinuing the study or having missing data) was associated with doubts about necessity (p=0.020), stronger concerns about adverse effects (p=0.010), greater treatment intrusiveness (p=0.010) and poorer mental health related QoL (p=0.008). At week 48, both concerns about ART (p=0.038) and treatment intrusiveness (p=0.004) were lower among those who switched to TVD. Furthermore, there was a decline in both concerns about ART (p=0.007) and treatment intrusiveness (p=0.057) over the 48 weeks among those who switched to TVD. There were no significant differences in necessity beliefs, QoL or viral load between randomised groups. Switching from CBV to TVD may improve patient reported outcomes including slightly better adherence, a greater reduction in concerns about adverse effects and less treatment intrusiveness.

A randomized comparative trial of continued zidovudine/lamivudine or replacement with tenofovir disoproxil fumarate/emtricitabine in efavirenz-treated HIV-1-infected individuals.

BACKGROUND: Long-term antiretroviral therapy dramatically reduces HIV-related morbidity and mortality but is also associated with metabolic and morphological changes and requires high levels of adherence. METHODS: A randomized, 48-week, open-label, comparative study of continuation of twice-daily zidovudine/lamivudine or replacement with once-daily tenofovir disoproxil fumarate/emtricitabine in individuals on successful efavirenz-based antiretroviral therapy. Limb fat mass was assessed by dual x-ray absorptiometry in a subset of participants through week 48. RESULTS: Two hundred thirty-four individuals were randomized and treated (117 each to continue or switch) with 206 subjects completing 48 weeks of study. Five percent subjects in the continue group and 3% subjects in the switch group discontinued due to adverse events. By intent-to-treat, missing = failure analysis, no differences in virological efficacy were observed at any time point (week 48 <50 copies/mL continue 85%, switch 88%). At week 24, switching was associated with significant increases in hemoglobin (mean difference 0.37 g/dL, 95% confidence interval: 0.15 to 0.58 g/dL, P < 0.001) and significant declines in total cholesterol and triglycerides. In the dual x-ray absorptiometry substudy (n = 100), fat was preserved or increased in the switch group but declined in the continue group (mean difference 448 g, 95% confidence interval: 57 to 839 g, P = 0.025). Individuals with longer exposure to zidovudine and lower baseline limb fat experienced less limb fat increase after switching. No differences in renal adverse events were observed between groups. CONCLUSIONS: Switching from zidovudine/lamivudine to tenofovir disoproxil fumarate/emtricitabine in persons on efavirenz therapy maintains virological control, establishes a once-daily regimen, results in improvements in hemoglobin and key lipid parameters, and preserves and restores limb fat relative to continuation of zidovudine/lamivudine.

Ethical issues in medico-legal exposures.

The Medical Exposure Directive (MED) 97/43/Euratom defines medico-legal procedures as 'procedures performed for insurance or legal purposes without a medical indication'. The term 'medico-legal exposures' covers a wide range of possible types of exposures, very different in nature, for which the only feature in common is the fact that the main reason for performing them does not relate directly to the health of the individual being exposed to ionising radiation. The key issue in medico-legal exposures is justification. Balancing the advantages and disadvantages of such exposures is complex because not only can these be difficult to quantify and hence compare, but often the advantage may be to society whereas the disadvantage is usually to an individual. This adds an additional layer of ethical complexity to the problem and one, which requires input from a number of sources beyond the established radiation protection community. Because medico-legal exposures are considered to be medical exposures, they are not subject to dose limits. In medico-legal exposures where the benefit is not necessarily to the individual undergoing the exposure, the question must be asked as to whether or not this is an appropriate framework within which to conduct such exposures. This paper looks at the current situation in Europe, highlighting some of the particular problems that have arisen, and tries to identify the areas, which require further clarification and guidance.

A randomized comparative trial of tenofovir DF or abacavir as replacement for a thymidine analogue in persons with lipoatrophy.

BACKGROUND: Long-term antiretroviral therapy, while dramatically reducing HIV-related morbidity and mortality, is associated with metabolic and morphological changes. Peripheral fat loss, lipoatrophy, appears most associated with prolonged therapy with thymidine nucleoside analogues. METHODS: A randomized, open-label, comparative study of switching from a thymidine nucleoside analogue to either tenofovir disoproxil fumarate (DF) or abacavir in 105 individuals on successful antiretroviral therapy with clinically evident moderate to severe lipoatrophy. RESULTS: Individuals were randomized to tenofovir DF (52) or abacavir (53). The switch was well tolerated and the majority of patients completed 48 weeks of study. One individual in the tenofovir DF group and three in the abacavir group discontinued due to drug-related adverse events. Both groups similarly maintained virological control. Limb fat mass increased similarly in both groups: mean increases by week 48 of 329 and 483 g in tenofovir DF and abacavir groups, respectively [mean 95% confidence interval for difference, -154.3 (range -492.8 to 184.3)]. This change from baseline was statistically significant in both groups (tenofovir DF, P = 0.01; abacavir, P = 0.0001). Mean total cholesterol, low density lipoprotein cholesterol and triglycerides improved modestly with switching to tenofovir DF but were unchanged with abacavir. The changes in these parameters were significantly greater in the tenofovir DF arm relative to abacavir. CONCLUSIONS: Switching from a thymidine nucleoside analogue to either tenofovir DF or abacavir leads to significant improvement in limb fat mass over 48 weeks. Tenofovir DF may have modest advantages over abacavir for changes in lipids. Peripheral lipoatrophy, when clinically apparent, resolves slowly following treatment switching.