Focusing on fidelity: narrative review and recommendations for improving intervention fidelity within trials of health behaviour change interventions.

Background: Interventions to change behaviour have substantial potential to impact positively on individual and overall public health. Despite an increasing focus on health behaviour change intervention research, interventions do not always have the desired effect on outcomes, while others have diluted effects once implemented into real-life settings. There is little investment into understanding how or why such interventions work or do not work. Methodological inadequacies of trials of behavioural interventions have been previously suggested as a barrier to the quality and advancement of behavioural research, with intervention fidelity acknowledged as a key area for improvement. However, there is much ambiguity regarding the terminology and conceptualisation of intervention fidelity and a lack of practical guidance regarding how to address it sufficiently, particularly within trials of complex behavioural interventions. Objectives: This article outlines specific issues concerning intervention fidelity within trials of health behaviour change interventions and suggests practical considerations and specific recommendations for researchers, with examples from the literature presented. Conclusions: Recommendations pertain to (1) clarifying how fidelity is defined and conceptualised, (2) considering fidelity beyond intervention delivery, (3) considering strategies to both enhance and assess fidelity, (4) making use of existing frameworks and guidance, (5) considering the quality and comprehensiveness of fidelity assessment strategies, (6) considering the balance between fidelity and adaptation and (7) reporting the use of fidelity enhancement and assessment strategies and their results. Suggestions for future research to improve our understanding of, and ability to, address fidelity in behaviour change interventions are also provided.

Behaviour change in diabetes: behavioural science advancements to support the use of theory.

Behaviour is central to the management of diabetes, both for people living with diabetes and for healthcare professionals delivering evidence-based care. This review outlines the evolution of behavioural science and the application of theoretical models in diabetes care over the past 25 years. There has been a particular advancement in the development of tools and techniques to support researchers, healthcare professionals and policymakers in taking a theory-based approach, and to enhance the development, reporting and replication of successful interventions. Systematic guidance, theoretical frameworks and lists of behavioural techniques provide the tools to specify target behaviours, identify why ideal behaviours are not implemented, systematically develop theory-based interventions, describe intervention content using shared terminology, and evaluate their effects. Several examples from a range of diabetes-related behaviours (clinic attendance, self-monitoring of blood glucose, retinal screening, setting collaborative goals in diabetes) and populations (people with type 1 and type 2 diabetes, healthcare professionals) illustrate the potential for these approaches to be widely translated into diabetes care. The behavioural science approaches outlined in this review give healthcare professionals, researchers and policymakers the tools to deliver care and design interventions with an evidence-based understanding of behaviour. The challenge for the next 25 years is to refine the tools to increase their use and advocate for the role of theoretical models and behavioural science in the commissioning, funding and delivery of diabetes care.

'It's an important part, but I am not quite sure that it is working': educators' perspectives on the implementation of goal-setting within the 'DAFNE' diabetes structured education programme.

AIM: To explore educators' perspectives on the implementation of goal-setting and action-planning strategies within a structured diabetes self-management education programme. METHODS: Ten semi-structured interviews were conducted with diabetes self-management education providers delivering the 'Dose Adjustment for Normal Eating' (DAFNE) programme to people with Type 1 diabetes throughout Ireland. A pre-designed topic guide, focused on exploring educators' experiences of delivery and application and views on usefulness of goal-setting strategies, was used in all interviews. The interviews were recorded, transcribed and analysed using thematic analysis. RESULTS: Five main themes were identified: 'people need a plan', discussing perspectives on goal-setting's value; 'the power of the group', highlighting the impact a group format has on goal-setting practices; 'diversity and individuality', discussing differences in DAFNE participants' and educators' engagement with goal-setting; 'goal-setting's fit', exploring perspectives on how well goal-setting fits within diabetes self-management education and follow-up care; and 'feelings of inadequate psychological knowledge', addressing challenges experienced in the delivery of goal-setting components. CONCLUSION: While educators saw benefits in the implementation of goal-setting and planning strategies within diabetes self-management education, concerns about how well goal-setting currently fits within diabetes self-management education and follow-up care were evident. Additionally, many educators experienced the delivery of goal-setting and action-planning strategies as challenging and would value additional training opportunities.

Parental experiences and perceptions of infant complementary feeding: a qualitative evidence synthesis.

BACKGROUND: Interventions to prevent childhood obesity increasingly focus on infant feeding, but demonstrate inconsistent effects. A comprehensive qualitative evidence synthesis is essential to better understand feeding behaviours and inform intervention development. The aim of this study is to synthesize evidence on perceptions and experiences of infant feeding and complementary feeding recommendations. METHODS: Databases CINAHL, EMBASE, MEDLINE, PsycINFO, Academic Search Complete, SocIndex and Maternity and Infant Care were searched from inception to May 2017. Eligible studies examined parents' experiences of complementary feeding of children (<2 years). Data were synthesized using thematic synthesis. RESULTS: Twenty-five studies met inclusion criteria for review. Four key themes emerged. 'Guidelines and advice' highlights variety and inconsistencies between sources of complementary feeding information. 'Stage of weaning' describes infant feeding as a process involving different stages. 'Knowing and trying' outlines parents' engagement in feeding approaches based on instinct, prior experience or trial and error. 'Daily life' highlights problematic cost and time constraints for parents. DISCUSSION: Parents predominantly understand and want to engage in healthy feeding processes. Consideration of infant feeding as a process that changes over time is necessary to support parents. Provision of clear, consistent information and guidance from trusted sources on when, what and how to feed is also essential.

Perceptions and experiences of taking oral medications for the treatment of Type 2 diabetes mellitus: a systematic review and meta-synthesis of qualitative studies.

AIMS: To explore patients' perceptions and experiences of taking oral medications for the pharmacological management of Type 2 diabetes mellitus. METHODS: Cinahl, EMBASE, Medline and PsycINFO databases were searched in 2014 to identify qualitative studies exploring patients' perceptions or experiences of taking medications for the management of Type 2 diabetes. Key concepts and themes were extracted and synthesized using meta-ethnography. RESULTS: Eight studies were included. Primary study findings were synthesized to develop three higher-order constructs that moved beyond the results of individual studies. The first construct, Medications for diabetes: a necessary evil, outlines how patients' negative perceptions of medication risks co-exist with a resounding view that medications are beneficial. Passive patients but active experimenters highlights the contrast between patients' passive acceptance of medication prescriptions and the urge to actively experiment and adjust doses to optimize medication use in daily life. Finally, Taking oral medication for Type 2 diabetes: a unique context describes features specific to the Type 2 diabetes medication experience, including lack of symptoms and the perceived relationship between medication and diet, which may influence adherence. CONCLUSIONS: Medication-taking for Type 2 diabetes is a unique adherence context, which requires the development of condition-specific interventions. The present findings indicate patients understand the need for medications but adjust dosage and timing in their daily lives. This review suggests providers should acknowledge patient preferences in the development of management strategies, and highlights an opportunity to direct the motivation evident in patients' experimentation towards potentially more beneficial medication-taking behaviours.

Effects of interventions promoting monitoring of medication use and brief messaging on medication adherence for people with Type 2 diabetes: a systematic review of randomized trials.

AIMS: To assess the impact of interventions promoting the monitoring of medication use and brief messaging to support medication adherence in patients with Type 2 diabetes mellitus, and to investigate the extent of theory use to guide intervention development. METHODS: We systematically searched for controlled trials, published from 1990 onwards in Medline, Embase, CINAHL, PsycINFO and the Cochrane library, that evaluated interventions based on monitoring and brief messaging to support medication adherence in patients with Type 2 diabetes, to examine the effectiveness of such interventions. RESULTS: A total of 11 trials, comparing 15 interventions, were identified. Only a small minority presented a low risk of bias. Three interventions were based on delivering brief messages, six were based on monitoring medication adherence, and six used both strategies. Messaging interventions included the use of short message service text messages, web-based feedback, and messages delivered through monitoring devices. Monitoring interventions included remote self-reporting of medication and telephone calls with healthcare staff. Improvements in medication adherence were observed in six interventions, although effect sizes were generally moderate. Only two interventions improved both adherence and clinical outcomes. A meta-analysis of five trials (eight interventions) combining monitoring and messaging strategies showed that the pooled difference in medication adherence between intervention and control was moderate and not statistically significant [standardized mean difference = 0.22 (95% CI -0.05; 0.49)]. Only four trials were based on explicit theoretical frameworks. CONCLUSIONS: Although interventions based on messaging and monitoring have the potential to improve medication adherence in patients with Type 2 diabetes, evidence of their efficacy is limited and additional high-quality, theory-based research is needed.

Inhibition of ganciclovir-susceptible and -resistant human cytomegalovirus clinical isolates by the benzimidazole L-riboside 1263W94.

The average 50% inhibitory concentration (IC(50)) values for AD169 were 0.22 +/- 0.09 microM 1263W94 and 5.36 +/- 0.12 microM ganciclovir. For 35 human cytomegalovirus (HCMV) clinical isolates the average IC(50) was 0.42 +/- 0.09 microM 1263W94, and for 26 ganciclovir-susceptible HCMV clinical isolates the average IC(50) was 3.78 +/- 1.62 microM ganciclovir. Nine HCMV clinical isolates that were resistant to ganciclovir were completely susceptible to 1263W94.

Susceptibilities of human cytomegalovirus clinical isolates to BAY38-4766, BAY43-9695, and ganciclovir.

BAY38-4766 and BAY43-9695 are nonnucleosidic compounds with activities against human cytomegalovirus (HCMV). Two phenotypic assays were used to determine the drug susceptibilities of 36 HCMV clinical isolates to the BAY compounds and ganciclovir. Using either assay, both BAY compounds at a concentration of approximately 1 microM inhibited the replication of all 36 HCMV clinical isolates, including 11 ganciclovir-resistant clinical isolates, by 50%.

Dietary titanium and infant growth.

Dietary titanium as TiO2+ improved animal growth during infancy while inhibiting the metabolism of intestinal bacteria. TiO2+ was also found capable of inhibiting human cytomegalovirus in tissue culture. These and other findings indicate TiO2+ improves infant growth by acting as an antibacterial and antiviral agent. The behavior of TiO2+ stands in contrast to that of TiO2, which is inert.

Analysis of virus-infected cells by flow cytometry.

Flow cytometry has been used to study virus-cell interactions for many years. This article critically reviews a number of reports on the use of flow cytometry for the detection of virus-infected cells directly in clinical samples and in virus-infected cultured cells. Examples are presented of the use of flow cytometry to screen antiviral drugs against human immunodeficiency virus (HIV), human cytomegalovirus, and herpes simplex viruses (HSV) and to perform drug susceptibility testing for these viruses. The use of reporter genes such as green fluorescent protein incorporated into HIV or HSV or into cells for the detection of the presence of virus, for drug susceptibility assay, and for viral pathogenesis is also covered. Finally, studies on the use of flow cytometry for studying the effect of virus infection on apoptosis and the cell cycle are summarized. It is hoped that this article will give the reader some understanding of the great potential of this technology for studying virus cell interactions.

Environmental tobacco smoke exposure and small-for-gestational-age birth.

The aim of this analysis was to examine the effect of environmental tobacco smoke exposure on the risk of small-for-gestational-age (SGA) birth. The study population included 2,283 nonsmokers from a nested cohort study undertaken in southern Connecticut from 1988 to 1992. The duration and intensity of exposures incurred at multiple locations during the third trimester of pregnancy were measured by postpartum interview. The effect of exposure on birth weight and on incidence of SGA birth was assessed by multivariate logistic and linear regression. An estimated 26.5% of the women had been exposed to environmental tobacco smoke for at least 1 hour per week during the third trimester. The median duration of exposure among the exposed over all locations was 5 hours per week. The adjusted odds ratio for SGA birth in exposed mothers compared with unexposed mothers, using a dichotomous exposure variable, was 0.82 (95% confidence interval: 0.51, 1.33). The adjusted birth weight difference associated with exposure was -1.2 g (95% confidence interval: -43.3, 41.0). No effect of environmental tobacco smoke exposure on fetal growth was seen in this relatively homogeneous upper middle class group of women exposed at low levels. This is reassuring for women exposed at low levels, but it does not exclude the possibility of an effect in women exposed to higher levels of environmental tobacco smoke.

Antiviral drug susceptibility assays: going with the flow.

This review describes the procedures for the use of fluorochrome labeled monoclonal antibodies and flow cytometry for the detection and quantification of virus infected cells. The application of this technology for (1) identifying virus infected cells in clinical specimens obtained from human cytomegalovirus (HCMV) and human immunodeficiency virus (HIV) infected individuals; (2) screening antiviral compounds active against HCMV, HDSV and HIV; and (3) performing drug susceptibility testing for HCMV, HSV and HIV clinical isolates are reviewed. The flow cytometry drug susceptibility assay is rapid, quantitative, and easily performed. It should be considered by anyone interested in performing drug susceptibility testing for any virus for which there are reliable monoclonal antibodies.

Rapid ganciclovir susceptibility assay using flow cytometry for human cytomegalovirus clinical isolates.

Rapid, quantitative, and objective determination of the susceptibilities of human cytomegalovirus (HCMV) clinical isolates to ganciclovir has been assessed by an assay that uses a fluorochrome-labeled monoclonal antibody to an HCMV immediate-early antigen and flow cytometry. Analysis of the ganciclovir susceptibilities of 25 phenotypically characterized clinical isolates by flow cytometry demonstrated that the 50% inhibitory concentrations (IC50s) of ganciclovir for 19 of the isolates were between 1.14 and 6.66 microM, with a mean of 4.32 microM (+/-1.93) (sensitive; IC50 less than 7 microM), the IC50s for 2 isolates were 8.48 and 9.79 microM (partially resistant), and the IC50s for 4 isolates were greater than 96 microM (resistant). Comparative analysis of the drug susceptibilities of these clinical isolates by the plaque reduction assay gave IC50s of less than 6 microM, with a mean of 2.88 microM (+/-1.40) for the 19 drug-sensitive isolates, IC50s of 6 to 8 microM for the partially resistant isolates, and IC50s of greater than 12 microM for the four resistant clinical isolates. Comparison of the IC50s for the drug-susceptible and partially resistant clinical isolates obtained by the flow cytometry assay with the IC50s obtained by the plaque reduction assay showed an acceptable correlation (r2 = 0.473; P = 0.001), suggesting that the flow cytometry assay could substitute for the more labor-intensive, subjective, and time-consuming plaque reduction assay.

Flow cytometric determination of ganciclovir susceptibilities of human cytomegalovirus clinical isolates.

A flow cytometric assay has been developed for the measurement of susceptibilities to ganciclovir of laboratory strains and clinical isolates of human cytomegalovirus (HCMV). The assay uses fluorochrome-labeled monoclonal antibodies to HCMV immediate-early and late antigens to identify HCMV-infected cells and flow cytometry to detect and quantitate the number of antigen-positive cells. By this assay, the 50 and 90% inhibitory concentrations (IC50 and IC90, respectively) of ganciclovir for the AD169 strain of HCMV were 1.7 and 9.2 microM, respectively, and the IC50 for the ganciclovir-resistant D6/3/1 derivative of the AD169 strain was greater than 12 microM. The ganciclovir susceptibilities of 17 HCMV clinical isolates were also determined by flow cytometric analysis of the effect of ganciclovir on late-antigen synthesis in HCMV-infected cells. The average IC50 of ganciclovir for drug-sensitive HCMV clinical isolates was 3.79 microM (+/-2.60). The plaque-reduction assay for these clinical isolates yielded an average IC50 of 2.80 microM (+/-1.46). Comparison of the results of the flow cytometry assays with those obtained from the plaque-reduction assays demonstrated acceptable bias and precision. Flow cytometric and plaque-reduction analysis of cells infected with ganciclovir-resistant clinical isolates failed to show a reduction in the percentage of late-antigen-positive cells or PFU, even at 96 microM ganciclovir. The flow cytometric assay for determining ganciclovir susceptibility of HCMV is quantitative, and objective, and potentially automatable, and its results are reproducible among laboratories.

Spontaneous abortion and exposure to electric blankets and heated water beds.

We conducted a prospective study (N = 2,967) to evaluate the relation of spontaneous abortion with use of electrically heated beds (electric blankets and heated water beds) during pregnancy. At interview, 61.5% of women were at less than 12 weeks gestation, and 38.5% were between 13 and 16 weeks; thus, very early pregnancy losses would have been excluded. Information regarding exposure to electric beds was obtained for the month of conception and the 7 days before interview. Electric blanket use at conception was associated with an increased risk of spontaneous abortion in the unadjusted analysis [relative risk (RR) = 1.84; 95% confidence interval (CI) = 1.08-3.13], but adjustment for other factors reduced the risk slightly [odds ratio (OR) = 1.74; 95% CI = 0.96-3.15]. Heated water bed use was not associated with an increased risk of spontaneous abortion at conception (OR = 0.59; 95% CI = 0.33-1.07) or at interview (OR = 0.63; 95% CI = 0.36-1.12). Measures of dose response (daily use, hours of use, or temperature setting) were not associated with increased risk. Wire code data were obtained for the first, or only, house lived in during pregnancy. Women living in homes classified as "very high" or "ordinary high" current configuration were not at greater risk than women living in homes with buried wires. Nor was there any trend for increased risk of spontaneous abortion by wire code category. This study does not support the hypothesis that use of electric beds or residence in a high current configuration home increases the risk of spontaneous abortion; however, it indicates that electric blanket use at the time of conception and in early pregnancy may be associated with a slight increase in risk of pregnancy loss.

Exposure to electromagnetic fields during pregnancy with emphasis on electrically heated beds: association with birthweight and intrauterine growth retardation.

Several animal and human studies indicate that fetal growth may be retarded following exposure to electromagnetic fields (EMF). We conducted a prospective study (N = 2,967) to evaluate the relation of birthweight and fetal growth retardation with use of electrically heated beds (electric blankets and heated water beds) during pregnancy. A "nested" study design allowed monitoring of exposure at different stages of pregnancy using both direct and indirect methods. We assessed EMF exposure using personal monitors, home measurement, video display terminal use, and wire code. Exposure to EMF during pregnancy, either at conception, at < or = 16 weeks, or in the third trimester, showed no important relation to risk of low birth-weight or fetal growth retardation. This result was the same whether we used subjective measures of exposure or direct measurement. Use of video display terminals at home or work, exposure to > or = 2.0-milligauss fields as measured by home or personal monitors, and home wire code were unrelated to the reproductive outcomes studied. A time-weighted analysis of electric bed use, which accounted for strength of EMF exposure and hours of use, also showed evidence of no meaningful increase in risk. None of the exposure measures showed a dose response relation to risk. We conclude that risk of low birth-weight and intrauterine growth retardation is not increased after electrically heated bed use during pregnancy.

Uses of flow cytometry in virology.

This article reviews some of the published applications of flow cytometry for in vitro and in vivo detection and enumeration of virus-infected cells. Sample preparation, fixation, and permeabilization techniques for a number of virus-cell systems are evaluated. The use of flow cytometry for multiparameter analysis of virus-cell interactions for simian virus 40, herpes simplex viruses, human cytomegalovirus, and human immunodeficiency virus and its use for determining the effect of antiviral compounds on these virus-infected cells are reviewed. This is followed by a brief description of the use of flow cytometry for the analysis of several virus-infected cell systems, including blue tongue virus, hepatitis C virus, avian reticuloendotheliosis virus, African swine fever virus, woodchuck hepatitis virus, bovine viral diarrhea virus, feline leukemia virus, Epstein-Barr virus, Autographa californica nuclear polyhedrosis virus, and Friend murine leukemia virus. Finally, the use of flow cytometry for the rapid diagnosis of human cytomegalovirus and human immunodeficiency virus in peripheral blood cells of acutely infected patients and the use of this technology to monitor patients on antiviral therapy are reviewed. Future prospects for the rapid diagnosis of in vivo viral and bacterial infections by flow cytometry are discussed.

Novel oral combination chemotherapy in the treatment of intermediate-grade and high-grade AIDS-related non-Hodgkin's lymphoma.

PURPOSE: To determine the toxicity, response, and survival rate of orally administered combination chemotherapy in patients with AIDS-related intermediate- and high-grade non-Hodgkin's lymphoma. Secondary objectives included prospective quality-of-life assessment and quantitation of cell-associated p24 antigen (p24 Ag) by flow cytometry. PATIENTS AND METHODS: Eighteen patients with biopsy-proven lymphoma were treated with oral chemotherapy consisting of lomustine (CCNU) 100 mg/m2 on day 1, etoposide 200 mg/m2 on days 1 through 3; cyclophosphamide 100 mg/m2 on days 22 through 31, and procarbazine 100 mg/m2 on days 22 through 31 at 6-week intervals. A variety of clinical assessments were performed: prospective quality-of-life assessment using the Functional Living Index-Cancer (FLIC) and Brief Symptom Inventory (BSI) instruments; indirect immunofluorescence with flow cytometry to measure cell-associated p24 antigen; and price of the oral regimen compared with two other intravenous combination chemotherapy regimens. RESULTS: The overall objective response rate using Eastern Cooperative Oncology Group (ECOG) criteria was 61% (95% confidence interval, 39% to 84%), with seven complete remissions (39%) and four partial remissions (22%). The median survival duration was 7 months, with a range of 11 days to 36 months. The treatment-related mortality rate was 11%. One patient developed CNS progression. Myelosuppression was the most frequent and severe toxicity encountered. Predictor variables of performance status (PS), prior history of thrush, and CD4 lymphocyte count were found to be of prognostic value. In a separate analysis, scores on the three subscales of the BSI were also found to be predictive of complete response. The price of this regimen is several thousand dollars less than that of other intravenous combination chemotherapy regimens. CONCLUSION: This regimen is active in patients with AIDS-related non-Hodgkin's lymphoma. Because it is important to design systemic cytotoxic chemotherapy regimens that are cost-effective, considerate of quality-of-life issues, and efficacious in this patient population, this approach should be compared with standard intravenous combination chemotherapy regimens in randomized controlled clinical trials.

Rapid detection of herpes simplex virus in clinical samples by flow cytometry after amplification in tissue culture.

Murine monoclonal antibodies (MAbs) against herpes simplex virus type 1 and 2 (HSV-1 and -2, respectively) nuclear antigens were used to identify cells infected with HSV-1 or -2 by indirect immunofluorescence in conjunction with flow cytometry after virus amplification of MRC-5 cell monolayers. The results indicate that MAbs Q1, Q2, and H-640 detect HSV-1- and HSV-2-infected cells, MAb SD-1 detects HSV-2- but not HSV-1-infected cells, and MAb 58-S detects HSV-1- but not HSV-2-infected cells. MAb Q1, which detects HSV-1- as well as HSV-2-infected cells, was used to detect HSV-infected cells after inoculation and overnight (16- to 20-h) incubation of MRC-5 monolayers with clinical samples suspected of containing HSV. In comparing the efficiency of flow cytometry with cytopathic effect (CPE) in tissue culture for detecting HSV in clinical samples, HSV was detected by flow cytometry in 77% of the cases where HSV was detected by CPE in tissue culture. In many cases, flow cytometry detected HSV from 1 to 3 days before HSV was detected by CPE.