Compliance and Persistence in Pediatric and Adult Patients Receiving Growth Hormone Therapy

ObjectiveTo identify key factors that influence compliance and persistence in patients receiving growth hormone (GH) therapy and to promote the development of interventions to support continuous GH use.MethodsA 134-question survey was conducted involving 158 adult patients, 326 adolescents or teens, and 398 parents of children currently receiving or previously treated with GH. Questions explored perceptions about GH deficiency and treatment outcomes, quality of training received for administration of injections, and disruptions affecting compliance and persistence with therapy. Compliance was defined by a categorical assessment of frequency of missed GH doses for specific reasons. Persistence was defined as continuing GH therapy with no interruption.ResultsOn the basis of their responses to questions about potential reasons for missing GH doses, patients were categorized by level of compliance into 3 segments—highly compliant, occasionally noncompliant, or noncompliant and skeptical. Noncompliance with GH therapy (that is, classification in one of the last 2 segments) ranged from 64% to 77% among the 3 age-groups evaluated, with teens having the highest rate of noncompliance. Misperceptions about the consequences of missed GH doses, discomfort with injections, dissatisfaction with treatment results, and inadequate contact with health-care providers (along with other factors) were strongly associated with noncompliance. Survey questions related to these factors were considered useful for identifying patients requiring additional support or intervention to improve compliance.ConclusionRoutine education should emphasize therapeutic end points and their relationship to compliance with GH therapy in an effort to convince and empower patients with GH deficiency to use self-care strategies to achieve their treatment goals. (Endocr Pract. 2008;14: 143-154)     

Cystic fibrosis carrier population screening in the primary care setting.

To determine the receptivity of prenatal care providers and their patients to carrier testing for cystic fibrosis (CF), we offered free carrier screening, followed by genetic counseling of carriers, to all prenatal care providers in Rochester, NY, for all their female patients of reproductive age, pregnant or not. Of 124 prenatal care providers, only 37 elected to participate, but many of these offered screening only to pregnant women. The acceptance rate among pregnant women was approximately 57%. The most common reasons for accepting screening were to obtain reassurance (50.7%) and to avoid having a child with CF (27.8 %). The most common reasons for declining screening were not intending to terminate a pregnancy for CF (32.4%) and believing that the chance of having a CF child was very low (32.2%). Compared with decliners, acceptors were more likely to have no children, regarded having a child with CF as more serious, believed themselves more susceptible to having such a child, knew more about CF, would be more likely to terminate a pregnancy if the fetus were shown to have CF, and more strongly supported offering CF screening to women of reproductive age. Of 4,879 women on whom results were obtained, 124 were found to be carriers. Of these 124 carriers, the partners of 106 were tested. Of the five at-risk couples, four requested prenatal diagnosis and one requested neonatal diagnosis. No woman found to be a carrier whose partner tested negative requested prenatal diagnosis. Except for the imperfect knowledge of those testing negative, none of the adverse outcomes predicted for CF carrier testing in the general population were observed in this study.     

Physician management of hypercholesterolemia. A randomized trial of continuing medical education.

To determine the effect of continuing medical education (CME) on compliance with the recommendations of the National Cholesterol Education Program Expert Panel on high serum cholesterol levels in adults, we randomly assigned primary physicians in 174 practices to 3 groups, 2 that underwent either standard or intensive CME and a control group. The standard CME group was offered a free 3-hour seminar on high serum cholesterol levels; the intensive CME group was offered in addition follow-up seminars and free office materials. After 18 months, we audited 13,099 medical records from the 140 practices that remained in the study. There were no significant differences (P > .15) in screening for high serum cholesterol or compliance with guidelines between the groups receiving continuing medical education (51% screening; 33% compliance) and the control group (57% screening; 37% compliance). In the prespecified subgroup of patients with hypercholesterolemia, there was a trend toward a modest benefit from the continuing medical education interventions: compliance was 21% in the control group, 23% in the standard CME group, and 27% in the intensive CME group (P = .07 overall). These results emphasize the need for better ways to change behavior in practicing physicians and the importance of studying the implementation of preventive health recommendations.     

Genetic immunization by jet injection of targeted pDNA-coated nanoparticles

Genetic immunization strategies have largely focused on the use of "naked" plasmid DNA or the gene gun. However, there remains a clear need to further improve the efficiency and/or cost of potential DNA vaccines. The theoretical basis of our research is to rationally design genetic immunization methodologies for nanoparticle-based delivery systems of plasmid DNA, perhaps in combination with already commercially available needle-free devices, such as the Biojector 2000. These methodologies may both reduce the dose of pDNA required and enhance the breadth and depth of protective immune responses (i.e., humoral and cellular). The purpose of this article is to provide detailed experimental methods to (1) engineer and characterize pDNA-coated cationic nanoparticles (<100nm) directly from oil-in-water microemulsion precursors and (2) enhance both the breadth and depth of immune responses after immunization of mice with pDNA-coated nanoparticles by different routes of administration, including intradermal, using a needle-free jet injection device.     

Insulin Pen Injection Devices for Management of Patients with Type 2 Diabetes: Considerations Based on an Endocrinologist’s Practical Experience in the United States

ObjectiveTo review the features of several insulin pens currently available in the United States, discuss the validity of concerns about certain pen devices, and provide specific training information for clinicians to increase the accuracy of insulin administration and patient satisfaction with the use of insulin pens.MethodsThe published literature on insulin pens and Internet-available, product-specific information are reviewed. In addition, special practical considerations regarding insulin pen selection based on personal experience in a high-volume endocrinology practice are highlighted by presentation of case vignettes.ResultsFor some patients with diabetes, the need for performance of self-injection can be a barrier to acceptance of insulin therapy. Insulin pen devices provide a delivery option that may be more acceptable and more convenient to use in comparison with traditional vials and syringes and thus may promote patient compliance, which can enhance the ability to achieve and maintain glycemic control. When choosing a specific insulin pen for an individual patient, the clinician should consider the patient’s insulin regimen, lifestyle, and factors that may affect the ability to use a particular device, such as motor dexterity and visual acuity.ConclusionInsulin pens offer convenience and can potentially increase patient satisfaction and compliance with therapy. Because certain characteristics of a given insulin pen may make it preferable for specific patients, it is important for clinicians to be aware of individual needs. Provision of thorough training for patients in the correct use of insulin pens is important because user error can affect pen performance and accuracy of the dose administered. Manufacturers should be notified of any recurring problems. (Endocr Pract. 2007;13:672-678)     

Non-compliance with growth hormone treatment in children is common and impairs linear growth

Background

GH therapy requires daily injections over many years and compliance can be difficult to sustain. As growth hormone (GH) is expensive, non-compliance is likely to lead to suboptimal growth, at considerable cost. Thus, we aimed to assess the compliance rate of children and adolescents with GH treatment in New Zealand.

Methods

This was a national survey of GH compliance, in which all children receiving government-funded GH for a four-month interval were included. Compliance was defined as ≥85% adherence (no more than one missed dose a week on average) to prescribed treatment. Compliance was determined based on two parameters: either the number of GH vials requested (GHreq) by the family or the number of empty GH vials returned (GHret). Data are presented as mean ± SEM.

Findings

177 patients were receiving GH in the study period, aged 12.1±0.6 years. The rate of returned vials, but not number of vials requested, was positively associated with HVSDS (p<0.05), such that patients with good compliance had significantly greater linear growth over the study period (p<0.05). GHret was therefore used for subsequent analyses. 66% of patients were non-compliant, and this outcome was not affected by sex, age or clinical diagnosis. However, Maori ethnicity was associated with a lower rate of compliance.

Interpretation

An objective assessment of compliance such as returned vials is much more reliable than compliance based on parental or patient based information. Non-compliance with GH treatment is common, and associated with reduced linear growth. Non-compliance should be considered in all patients with apparently suboptimal response to GH treatment.     

Regret on Choice of Colorectal Cancer Screening Modality Was Associated with Poorer Screening Compliance: A 4-Year Prospective Cohort Study

Purpose

Very few studies examined the issue of regret on choosing colorectal cancer (CRC) screening tests. We evaluated the determinants of regret and tested the hypothesis that regret over screening choices was associated with poorer screening compliance.

Methods

A bowel cancer screening centre invited all Hong Kong citizens aged 50-70 years who were asymptomatic of CRC to participate in free-of-charge screening programmes. Upon attendance they attended health seminars on CRC and its screening, and were offered an option to choose yearly faecal immunochemical test (FIT) for up to four years vs. one direct colonoscopy. They were not allowed to switch the screening option after decision. A self-administered, four-item validated survey was used to assess whether they regretted over their choice (> 2 = regretful from a scale of 0 [no regret]-5 [extreme regret]). A binary logistic regression model evaluated if initial regret over their choice was associated with poorer programme compliance.

Results

From 4,341 screening participants who have chosen FIT or colonoscopy, 120 (2.8%) regretted over their decision and 1,029 (23.7%) were non-compliant with the screening programme. Younger subjects and people who felt pressure when making their decision were associated with regret. People who regretted their decision were 2.189 (95% C.I. 1.361-3.521, p = 0.001) times more likely to be non-compliant with the programme.

Conclusions

This study is the first to show that regret over the initial CRC screening choice was associated with later non-compliance. Screening participants who expressed regret over their choice should receive additional reminders to improve their programmatic compliance.     

A field study of the choice and continuity of use of three contraceptive methods in a rural area of Thailand

A field study was conducted in order to determine the preference for and the continuation rates achieved with 2 previously available contraceptives (the OC and the IUD) and a newly introduced method (depromedroxyprogesterone acetate, or DMPA) in a rural area of Thailand. Women were offered a free choice of method after the presentation of balanced educational material. 73.8% of all women chose DMPA; this preference was not influenced by the educational lecture. 16.9% of the women chose the OC and 9.3% chose the IUD. Women perceived the injection as a convenient method when compared to the OC and the IUD, but the primary preference for DMPA appeared to be mostly due to ill-defined personal factors and the influence of friends. The 1-year life-table continuation rates with DMPA (75.5%/100) women were significantly higher than the continuation rate achieved with the IUD (66.5/100 women). The continuation rates with the OC were 72/100 women, but the excessively high loss to follow-up with the OC made interpretation of results difficult. When women are offered a free choice of contraceptive methods under a quasiexperimental situation, useful information can be gathered on the potential value of new methods for an ongoing family planning program.     

Pharmacokinetics of recombinant human growth hormone administered by cool.click™ 2, a new needle-free device,compared with subcutaneous administration using a conventional syringe and needle

Background

Growth hormone (GH) is used to treat growth hormone deficiency (GHD, adult and paediatric), short bowel syndrome in patients on a specialized diet, HIV-associated wasting and, in children, growth failure due to a number of disorders including Turner's syndrome and chronic renal failure, and in children born small for gestational age. Different brands and generic forms of recombinant human growth hormone (r-hGH) are approved for varying indications in different countries. New ways of administering GH are required because the use of a needle and syringe or a device where a patient still has to insert the needle manually into the skin on a daily basis can lead to low adherence and sub-optimal treatment outcomes. The objective of this study was to assess the relative bioavailability of r-hGH (Saizen^®, Merck Serono) administered by a new needle-free device, cool.click? 2, and a standard needle and syringe.

Methods

The study was performed with 38 healthy volunteers who underwent pituitary somatotrope cell down-regulation using somatostatin, according to a randomized, two-period, two-sequence crossover design. Following subcutaneous administration of r-hGH using cool.click? 2 or needle and syringe, pharmacokinetic parameters were analysed by non-compartmental methods. Bioequivalence was assessed based on log-transformed AUC and C_max values.

Results

The 90% confidence intervals for test/reference mean ratio of the plasma pharmacokinetic variables C_max and AUC_0-inf were 103.7–118.3 and 97.1–110.0, respectively, which is within the accepted bioequivalence range of 80–125%. r-hGH administered by cool.click? 2 is, therefore, bioequivalent to administration by needle and syringe with respect to the rate and extent of GH exposure. Treatment using cool.click? 2 was found to be well tolerated. With cool.click? 2 the t_max was less (3.0 hours) than for needle and syringe delivery (4.5 hours), p = 0.002 (Friedman test), although this is unlikely to have any clinical implications.

Conclusion

These results demonstrate that cool.click? 2 delivers subcutaneous r-hGH exposure that is bioequivalent to the conventional mode of injection. The new device has the additional advantage of being needle-free, and should help to increase patient adherence and achieve good therapeutic outcomes from r-hGH treatment.

     

Choosing between conventional and hypofractionated prostate cancer radiation therapy: Results from a study of shared decision-making

AimTo evaluate patient choice of prostate cancer radiotherapy fractionation, using a decision aid.BackgroundRecent ASTRO guidelines recommend patients with localised prostate cancer be offered moderately hypofractionated radiation therapy after discussing increased acute toxicity and uncertainty of long-term results compared to conventional fractionation.Materials and methodsA decision aid was designed to outline the benefits and potential downsides of conventionally and moderately hypofractionated radiation therapy. The aid incorporated the ASTRO guideline to outline risks and benefits.ResultsIn all, 124 patients with localised prostate cancer were seen from June-December 2018. Median age was 72 (range 50–90), 49.6 % were intermediate risk (50.4 % high risk). All except three patients made a choice using the aid; the three undecided patients were hypofractionated. In all, 33.9 % of patients chose hypofractionation: falling to 25.3 % for patients under 75 years, 24.3 % for patients living within 30 miles of the cancer centre, and 14.3 % for patients with baseline gastrointestinal symptoms. On multivariate analysis, younger age, proximity to the centre, and having baseline gastrointestinal symptoms significantly predicted for choosing conventional fractionation. Insurance status, attending clinician, baseline genitourinary symptoms, work/carer status, ECOG, cancer risk group and driving status did not impact choice. Reasons for choosing conventional fractionation were certainty of long-term results (84 %) and lower acute bowel toxicity (51 %).ConclusionsMost patients declined the convenience of moderate hypofractionation due to potentially increased acute toxicity, and the uncertainty of long-term outcomes. We advocate that no patient should be offered hypofractionation without a thorough discussion of uncertainty and acute toxicity.     

Do Pediatric Hospitals Improve Operative Efficiency?

BackgroundIn recent years there has been a push towards developing free standing pediatric facilities to provide care specifically towards pediatric patients. The purpose of this study was to determine if moving pediatric cases from a general hospital to a dedicated pediatric facility improved the quality and efficiency of surgical procedures.MethodsA retrospective review of pediatric patients undergoing posterior spinal fusion (PSF) was performed. All procedures were performed by one orthopaedic surgeon (SLW) from 2015 to 2019. The procedures were performed at a general hospital (GH) the first two years, and at a pediatric hospital (PH) the subsequent years. Data extracted included patient sex, age, and procedure type as well as procedure duration, operative turnover time, hospital length of stay, transfusion requirements, and operative delay. Exclusively pediatric adolescent idiopathic scoliosis (AIS) patients undergoing PSF were included due to the high volume and consistent surgical procedures therefore limiting confounding variables.ResultsA total of five hundred PSF pediatric procedures were performed during the time period. After excluding non-adolescent idiopathic scoliosis cases, a total of 208 procedures were reviewed (105 at GH; 103 at PH). There was no statistical difference between the groups in regards to operative time (GH: 200 min, PH: 200 min; p=0.91), room turnover time (GH: 38 min, PH: 38 min; p=0.801), or rate of transfusion (GH: 20% PH: 30%; p=0.09). Length of stay was significantly shorter in the PH cohort compared to the GH cohort (4.35 vs. 3.84 days, p=0.0001). However, a smaller proportion of cases at the PH started on time compared to the GH (34% vs. 58%; p=0.0005).ConclusionOverall, this study demonstrated that AIS procedures at the PH did show a statistically significant reduction in hospital length of stay. However, timely start of the procedure was less likely at this particular facility. Level of Evidence: III     

Intranasal activity of the growth hormone releasing peptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 in conscious dogs

This series of experiments was conducted to evaluate the growth hormone (GH) releasing activity of intranasally administered His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6, SK&F 110679) in conscious dogs. Intranasal administration of GHRP-6 increased plasma growth hormone levels in the conscious dog in a dose-related manner. Doses of 0.25 and 0.5 mg/kg produced GH levels of 11.3 +/- 4.8 ng/ml and 28.6 +/- 8.0 ng/ml, respectively. Peak levels were observed 15 minutes after dosing and GH levels were elevated for up to 105 minutes after intranasal dosing. Intranasal administration of isotonic saline did not produce any change in basal (negligable) GH levels. When GHRP-6 was given by the intravenous route, a maximal dose of 0.5 mg/kg, produced a peak plasma GH concentration of 60.8 +/- 10.5 ng/ml. Saline had no effect on GH levels when given intravenously. Using the intravenous and intranasal GH response data (i.e., area under the time-response curves), the intranasal bioavailability of GHRP-6 was estimated to be 34.4 to 44.9%. The results of these studies suggest that significant activity and excellent bioavailability can be achieved when GHRP-6 is administered by the intranasal route to conscious dogs. Based on these results, the intranasal activity of GHRP-6 should be evaluated in man. The successful intranasal administration of this peptide in man should provide GH therapy with reduced patient discomfort and better patient compliance when compared to presently available parenterally administered remedies.     

Randomised trial of compliance with screening for colorectal cancer.

A randomised trial of compliance with screening for colorectal cancer by means of the haemoccult test was conducted in Farnborough and Basingstoke districts. In each of the 14 participating practices (41 general practitioners) 25 852 men and women aged between 40 and 70 years were randomly allocated by household to one of six groups. The group determined the method of invitation to screening: a letter and the test were sent to the patient, or a letter with an appointment to attend the surgery was sent, or during a routine consultation the general practitioner invited patients to participate, and some patients received an educational booklet about bowel disorders and screening. Of the 17 824 people who were offered screening, 7545 (42%) complied. Compliance was significantly affected by the method of invitation, but not by whether an educational booklet was received, and was highest (57%) in the group that was offered the haemoccult test during a routine consultation (the "opportunistic" approach). In this group the compliance rate achieved by individual general practitioners ranged from 26% to 82%. Compliance was significantly higher in Farnborough, in the older (55-70) age group, in women, and in households in which two or more people were offered screening. The higher compliance in Farnborough may be explained by the higher proportion of older people and by the higher proportion of people living in households of two or more in the population that was offered screening. The fact that the screening programme in Farnborough was offered to the whole community and that the researcher may have acted as a facilitator were probably also important. One per cent of the patients screened had a positive test, and 24 (38%) of the 63 patients who were positive and were investigated in hospital had neoplastic disease. The yield was 1.2 cancers and 1.2 benign adenomas (1 cm or larger in size) per 1000 people screened. This low yield is likely to be a consequence of the relatively young age group screened.     

An Update on Insulin Injection Devices

Background: Over the past 15 years, it has become clear that better glycemic control can lead to a substantial reduction in diabetic complications and that such control often requires the use of insulin therapy. However, a number of barriers exist to starting such therapy in patients with diabetes mellitus (DM). Many of these barriers to treatment are related to the use of a syringe to inject the medication. In the past ~20 years, various "pen" devices have become available that help to reduce the stigma associated with insulin injection, allowing more patients to achieve the glycemic control that they require.Objectives: This article provides an overview of the various pen devices available in the United States for subcutaneous insulin delivery and discusses the benefits these devices can provide to patients; their disadvantages are also discussed. Third-party reimbursement for these devices is highlighted.Methods: A MEDLINE search was performed (1980-2007) to identify relevant articles (English-language only) using appropriate key terms, including insulin pen and insulin delivery device. Technical specifications and availability information for the various pen devices were obtained directly from their manufacturers. Insurance coverage data were provided by major national insurance carriers.Results: There are a number of excellent pen devices available for administering each of the currently offered basal and bolus insulin analogues as well as neutral protamine Hagedorn and regular insulins. These devices range from disposable pens—which are supplied to the patient prefilled from the pharmacy, used until empty, and then discarded—to refillable digital pens, some of which have the ability to “remember” prior insulin doses. Data from various studies indicate that both patients and their physicians generally prefer insulin pens over the traditional vial and syringe delivery method. These devices are simple to use, allow patients to be more discreet in social situations, can easily be carried in a shirt pocket or purse, do not need to be refrigerated while in use, are associated with a lesser degree of injection anxiety, and may even be more accurate at lower doses. They may also be the preferred delivery system for the visually impaired, given their larger displays and the audible/tactile “click” produced each time the dose is increased by 1 U. Insulin pens lead to increased patient confidence and satisfaction and improved attitude toward insulin therapy. Most major insurance plans provide some coverage for the disposable pens as well as the cartridges for refillable pens, but this is often under tier 2 and some insurers may require prior authorization.Conclusions: Insulin pens provide DM patients with a number of advantages over a vial and syringe and can often help them overcome major barriers to the initiation of insulin therapy. The use of insulin pens leads to increased patient compliance and potential improvements in glycosylated hemoglobin, but data on glycemic control are not available. The pens should be offered to virtually all patients who require insulin therapy, except in instances in which these pens are financially prohibited.     

Liquid growth hormone: preservatives and buffers

Growth hormone (GH) treatment is a successful medical therapy for children and adults with GH deficiency as well as for growth retardation due to chronic renal disease, Turner syndrome and in children born small for gestational age. For all of these conditions, treatment is long term and patients receive daily subcutaneous injections of GH for many years. Patient compliance is therefore of critical importance to ensure treatment benefit. One of the major factors influencing compliance is injection pain. Besides the injection device used, pain perception and local tissue reaction following injection are dependent on the preservative used in the formulation and the concentration of GH. Injection pain may also be related to the buffer substance and injection volume. A liquid formulation of GH, Norditropi SimpleXx, has been developed that dispenses with the need for reconstitution before administration. The formulation uses phenol (3 mg/ml) as a preservative (to protect product from microbial degradation or contamination) and histidine as a buffer. Alternative preservatives used in other GH formulations include m-cresol (9 mg/ml) and benzyl alcohol (3-9 mg/ml). Buffering agents include citrate and phosphate. Phenol has been successfully used as a preservative in drug formulations for more than 50 years and is considered a safe and effective agent which complies with strict international requirements for preservatives in drug formulations. In toxicological studies, no or only mild local reactions have been observed following subcutaneous administration of phenol (7.5 mg/ml), m-cresol (3-4 mg/ml) and benzyl alcohol (9 mg/ml). No general toxicity reactions were observed after subcutaneous administration of these agents. Clinical evaluation of the preservatives and buffers used in Norditropin SimpleXx showed that pain perception was similar between formulations containing phenol and benzyl alcohol, whereas m-cresol was associated with more painful injections than benzyl alcohol. Furthermore, patients reported more pain following injection of a citrate-buffered solution than after a histidine-buffered solution. More pain was also reported following large volume injections and following injections with solutions containing high protein concentrations. In summary, optimization of the preservative and buffer content of a liquid GH formulation may reduce injection pain and lead to improved patient compliance.     

Interrupter airway and tissue resistance: errors caused by valve properties and respiratory system compliance.

The interrupter technique is used to determine airway and tissue resistance. Their accuracy is influenced by the technical properties of the interrupter device and the compliance of the respiratory system. We investigated the influence of valve characteristics and respiratory system compliance on the accuracy of determining airway and tissue resistance by means of a computer simulation. With decreasing compliance we found increasing errors in both airway and tissue resistance determination of up to 34 and 71%, respectively. On this basis we developed a new occlusion valve, with special emphasis on rapid closing time and tightness in the closed state to improve the accuracy of resistance determination. The newly developed occlusion device greatly improves the accuracy of airway and tissue resistance determination. We conclude that respiratory system compliance is a limiting factor for the accuracy of the interrupter technique. To apply the interrupter technique in patients with extremely low respiratory system compliances, we need sophisticated technical devices.     

Patient Preferences Regarding Device Reuse and Potential of Devices for Reuse - A Study in a Veteran Population

BackgroundMany cardiac patients need and undergo device implants. Veterans’ preferences regarding post-mortem handling of devices are not known. Cardiac patients in low- and middle-income countries who need but cannot afford devices rely on donations. Charitable organizations have successfully provided devices for reuse to such patients.ObjectiveWe estimated the number of devices with potential for possible reuse in a veteran population.MethodsBetween January and December 2008, at a tertiary medical center, veterans with implanted cardiac devices were surveyed using a questionnaire for their preferences regarding post-mortem handling. One choice was donation to charity for reuse. Although altruistic, it is unclear what percent of such devices have reuse potential. Retrospective chart review of veterans who underwent device implants between 1992 and 2007 identified a cohort of patients with Implantable Cardiac Defibrillators (ICDs) who had died by April 31st 2009. In this cohort, ICDs implanted in the year preceding the patient’s death were counted as having reuse potential.Results94 of 97 veterans completed the survey. 56% were unaware of how devices are handled after death. The top three preferences for postmortem handling were: return to manufacturer, return to hospital and donation for reuse. 88% were willing to sign an advance device directive. Retrospective review identified 161 veterans who had received 301 ICDs. Of these, 77 ICDs (25%) had median reuse potential of 3.1 years.ConclusionIn a VA cohort of deceased patients a substantial proportion of devices had reuse potential. Further research is needed to direct health policy.     

Patient choice significantly affects mastectomy rates in the treatment of breast cancer

Mastectomy rates may be affected by patient choice. 203 patients who had a Total Mastectomy for breast cancer were invited to complete questionnaires at routine follow up clinics to ascertain if they had been offered a choice of Breast Conserving Surgery (BCS), and to establish the reasons for their preference. Questionnaires were checked against medical and nursing records to confirm the reasons for the patients' choice of mastectomy. 130 patients (64%) chose to have a mastectomy, reporting that they felt safer (n = 119); wanted to decrease the risk of further surgery (n = 87) and/or wished to avoid radiotherapy (n = 34). Some were advised not to have BCS if they had a large tumour size, central or multifocal tumours and/or associated extensive microcalcification on mammography (n = 29). 24 patients had BCS as first operation but had repeat surgery for involved or narrow excision margins. Despite being advised that there is no difference between survival rates of this and breast conserving surgery, many patients still feel safer with mastectomy.     

Needle-free jet injection of DNA and protein vaccine of the far-eastern subtype of tick-borne encephalitis virus induces protective immunity in mice

Tick-borne encephalitis virus (TBEV) causes severe encephalitis in humans. It is endemic in one area of Japan; however no commercial vaccine is available in that country. In this Japan-based study, the efficacy of subviral particles (SPs) of TBEV administered by needle-free injector was evaluated as a vaccine candidate. Inoculation with SP-encoding DNA by needle-free injector induced neutralizing antibodies more efficiently than when administered by needle and syringe, and mice vaccinated with one dose by needle-free injector survived challenge with a lethal dose of TBEV. These results suggest that SP vaccines delivered by needle-free injector can protect against TBEV infection.