The effect of combining therapeutic drug monitoring of antihypertensive drugs with personalised feedback on adherence and resistant hypertension: the (RHYME-RCT) trial protocol of a multi-centre randomised controlled trial.

BACKGROUND: Adherence to antihypertensive drugs (AHDs) is important for adequate blood pressure control. Not taking these drugs as prescribed is one of the main underlying causes for resistant hypertension (RH), which in turn leads to an increased risk of cardiovascular events, stroke and kidney damage. Therefore, correct identification of patients that are non-adherent to AHDs is crucial to improve clinical outcome. For this goal, therapeutic drug monitoring is the most reliable method. The primary objective of this trial is to investigate whether monitoring of drug concentrations with a dried blood spot (DBS) sampling method combined with personalised feedback leads to a decrease in prevalence of RH after 12 months due to an increase in adherence. Secondary objectives include the difference over time in the number of required AHDs as well as the defined daily dose (DDD). Lastly, the cost-utility of SoC versus the intervention in RH is determined. METHODS: This is a multi-centre single-blinded randomised controlled trial (RHYME-RCT). First, at an eligibility visit, DBS sampling, to monitor drug concentrations in blood, and a 24-h ambulatory blood pressure measurement (24-h ABPM) are performed simultaneously. Patients with a daytime systolic blood pressure (SBP) > 135 and/or diastolic blood pressure (DBP) > 85 mmHg are randomised to SoC or intervention + SoC. The intervention is performed by the treating physician and includes information on drug concentrations and a comprehensive personalised feedback conversation with the use of a communication tool. The follow-up period is one year with visits at 3, 6 and 12 months randomisation and includes 24-h ABPM and DBS sampling. DISCUSSION: This will be the first trial that focusses specifically on patients with RH without taking into account suspicion of non-adherence and it combines monitoring of AHD concentrations to identify non-adherence to AHDs with a comprehensive feedback to improve non-adherence. Furthermore, if this trial shows positive outcomes for the intervention it can be directly implemented in clinical practice, which would be a great improvement in the treatment of RH. TRIAL REGISTRATION: RHYME-RCT is registered in the Dutch Trial Register on 27/12/2017 (NTR6914) and can be found in the International Clinical Trials Registry Platform.

Transfusion of incompatible blood to a patient with alloanti-Sc1.

Sc1 is a high-prevalence blood group antigen that is part of the Scianna blood group system. The clinical significance of Scianna antibodies is not well understood because of their rarity; there are only a handful of cases in the literature. This scarcity of information can make it difficult to decide on the best course of action when transfusing a patient with alloantibodies to Scianna blood group antigens. We describe a case of an 85-year-old woman presenting with melena and a hemoglobin of 66 g/L. Upon request for crossmatched blood, a panreactive antibody was found, later elucidated to be alloanti-Sc1. Because of the urgent nature of the transfusion, the patient was transfused with 2 incompatible, presumed Sc1+, red blood cell units with no evidence of an acute or delayed transfusion reaction. This case has been shared with the International Society of Blood Transfusion Rare Donor Working Party, via their Outcome of Incompatible Transfusion form, and adds to the body of evidence on clinical significance of antibodies to the antigens of the Scianna blood group system.

Use of granulocyte transfusions among haematology units in England and North Wales.

OBJECTIVES: To establish the current use of granulocyte transfusions in haematology patients and explore interest in further research. BACKGROUND: Granulocytes may be used for the treatment of severe infection in neutropenic patients or for primary or secondary prophylaxis. Clinical utility of granulocyte transfusions is unclear, and recent studies have demonstrated equivocal outcomes. Pooled granulocytes are the main granulocyte product used in England and Wales, but there are no data on the patterns of use and little consensus on accepted indications. METHODS: A survey was distributed to UK hospitals delivering intensive chemotherapy. Clinical scenarios were posed, with further questions on clinician experience of using granulocytes, availability of the product, barriers to use and interest in further research. RESULTS: The response rate was 57%; 34·9% of all responses were from allogeneic stem cell transplant centres. Paediatric centres comprised 9·5% respondents, and 19% centres had access to apheresis granulocytes. Of respondents, 58·7% had used granulocytes in the last 3 years, 89·2% of whom used granulocytes to treat refractory infection. There was little consensus on use of granulocytes in the given clinical scenarios even when patients clearly met national guideline criteria. Paediatric centres were overall more likely to recommend granulocyte use. The most frequently identified barrier to use of granulocytes was lack of evidence of effect. Of the respondents, 75% indicated a willingness to participate in further research. CONCLUSION: There remains a lack of consistency about use of granulocytes, which is unsurprising given the lack of clinical data to support their efficacy. We did, however, demonstrate a willingness to participate in further research.

Ultrasound in EMG-Guided Biopsies: A Prospective, Randomized Pilot Trial.

INTRODUCTION: At our institution, core muscle biopsies are performed on muscles selected using electromyography (EMG). Ultrasound (US) guidance is not used routinely. The aim of this study was to determine if US guidance of EMG selected muscles would increase the diagnostic yield of the biopsy as compared to the current practice standards. METHODS: Two trained physicians performed 40 randomized biopsies (US guided or traditional approach). The amount of tissue obtained in each biopsy was recorded (volume and mass), along with the final pathologic diagnosis in each case and incidence of complications. RESULTS: Forty patients were studied. Sixteen muscle biopsies were done with US guidance; 50% had a definitive diagnosis, and 38% did not. In the non-US guidance group, 58% had a definitive diagnosis, and 33% did not. CONCLUSIONS: US did not provide any additive advantage when used to guide biopsy in a muscle previously selected for biopsy with EMG. Muscle Nerve 54: 786-788, 2016.

Reporting Organ Trafficking Networks: A Survey-Based Plea to Breach the Secrecy Oath.

Patients travel worldwide to purchase kidneys. Transplant professionals can play a role in identifying kidney purchase. However, due to the tension between their rights and obligations, a lack of understanding and knowledge exists on how to prevent and report purchase. We present the results of a national survey that describes transplant professionals' experiences, attitudes, behaviors, conflicts of duties, legal knowledge and needs for guidelines toward patients who purchase kidneys abroad. Second, we clarify professionals' rights and obligations regarding organ purchase and propose actions that they can take to report purchase. Of the 100/241 (42%) professionals who treated patients who traveled to a country outside the European Union for a kidney transplant, 31 (31%) were certain that patients purchased kidneys. Sixty-five (65%) had suspicions that patients had bought kidneys. The majority reported a conflict of duties. Eighty percent reported a need for guidelines. Professionals can help prevent organ purchase by disclosing information about organ trafficking networks to law enforcement. Such disclosure can support the investigation and prosecution of networks. We offer key components for guidelines on disclosure of these networks.

Mental health among living kidney donors: a prospective comparison with matched controls from the general population.

The impact of living kidney donation on donors' mental health has not been sufficiently nor comprehensively studied. Earlier studies demonstrated that mental health did not change in the majority of donors, however they often lacked a suitable control group and/or had other methodological limitations. Consequently, it remains unclear whether changes in mental health found among a minority of donors reflect normal fluctuations. In this study we matched 135 donors with individuals from the general Dutch population on gender and baseline mental health and compared changes in mental health over time. Mental health was measured using the Brief Symptom Inventory and Mental Health Continuum Short Form. Primary analyses compared baseline and 6 months follow-up. Secondary analyses compared baseline and 9 (controls) or 15 months (donors) follow-up. Primary multilevel regression analyses showed that there was no change in psychological complaints (p = 0.20) and wellbeing (p = 0.10) over time and donors and controls did not differ from one another in changes in psychological complaints (p = 0.48) and wellbeing (p = 0.85). Secondary analyses also revealed no difference in changes between the groups. We concluded that changes in mental health in the short term after donation do not significantly differ from normal fluctuations found in the Dutch general population.

Home-based family intervention increases knowledge, communication and living donation rates: a randomized controlled trial.

Our aim was to develop and test an educational program to support well-informed decision making among patients and their social network regarding living donor kidney transplantation (LDKT). One hundred sixty-three patients who were unable to find a living donor were randomized to standard care or standard care plus home-based education. In the education condition, patients and members of their social network participated in home-based educational meetings and discussed renal replacement therapy options. Patients and invitees completed pre-post self-report questionnaires measuring knowledge, risk perception, communication, self-efficacy and subjective norm. LDKT activities were observed for 6 months postintervention. Patients in the experimental group showed significantly more improvements in knowledge (p < 0.001) and communication (p = 0.012) compared with the control group. The invitees showed pre-post increases in knowledge (p < 0.001), attitude toward discussing renal replacement therapies (p = 0.020), attitude toward donating a kidney (p = 0.023) and willingness to donate a kidney (p = 0.039) and a decrease in risk perception (p = 0.003). Finally, there were significantly more inquiries (29/39 vs. 13/41, p < 0.001), evaluations (25/39 vs. 7/41, p < 0.001) and actual LDKTs (17/39 vs. 4/41, p = 0.003) in the experimental group compared with the control group. Home-based family education supports well-informed decision making and promotes access to LDKT.

Anti-D prophylaxis: past, present and future.

The new British Committee for Standards in Haematology (BCSH) guidelines for the use of anti-D immunoglobulin in pregnancy provide a welcome clarification of the use of anti-D in ectopic pregnancy and after red cell salvage during caesarean section, of dosing with different preparations and distinguishing non-immune and immune anti-D. The routine use of anti-D prophylaxis (RAADP) to prevent Rhesus (Rh) D alloimmunisation during the third trimester is well established and requires careful and well-audited local implementation to achieve the maximum public health benefit. In the UK, such scrutiny may be provided by the reporting of failed anti-D prophylaxis at women who have produced an immune anti-D that is detectable for the first time in the current pregnancy through the voluntary Serious Hazards of Transfusion reporting scheme (SHOT). Application of fetal RHD genotyping would avoid giving anti-D to RhD negative women carrying an RhD negative fetus. RAADP is directed by fetal RHD genotyping in some countries in Northern Europe led by the Netherlands and Denmark. The economic case for RAADP directed by fetal RHD genotyping needs to be carefully evaluated and in England is under consideration by National Institute for Health and Clinical Excellence (NICE). Possible future developments include the use of monoclonal anti-D preparations, now in advanced clinical trials, and also testing the hypothesis that directed RAADP from early in the second trimester may further reduce anti-D immunisation.

Antihypertensive drug concentration measurement combined with personalized feedback in resistant hypertension: a randomized controlled trial.

BACKGROUND: Adherence to antihypertensive drugs (AHDs) is crucial for controlling blood pressure (BP). We aimed to determine the effectiveness of measuring AHD concentrations using a dried blood spot (DBS) sampling method to identify nonadherence, combined with personalized feedback, in reducing resistant hypertension. METHODS: We conducted a multicenter, randomized, controlled trial (RHYME-RCT, ICTRP NTR6914) in patients with established resistant hypertension. Patients were randomized to receive either an intervention with standard of care (SoC) or SoC alone. SoC consisted of BP measurement and DBS sampling at baseline, 3 months (t3), 6 months (t6), and 12 months (t12); AHD concentrations were measured but not reported in this arm. In the intervention arm, results on AHD concentrations were discussed during a personalized feedback conversation at baseline and t3. Study endpoints included the proportion of patients with RH and AHD adherence at t12. RESULTS: Forty-nine patients were randomized to receive the intervention+SoC, and 51 were randomized to receive SoC alone. The proportion of adherent patients improved from 70.0 to 92.5% in the intervention+SoC arm ( P  = 0.008, n  = 40) and remained the same in the SoC arm (71.4%, n  = 42). The difference in adherence between the arms was statistically significant ( P  = 0.014). The prevalence of resistant hypertension decreased to 75.0% in the intervention+SoC arm ( P  < 0.001, n  = 40) and 59.5% in the SoC arm ( P  < 0.001, n  = 42) at t12; the difference between the arms was statistically nonsignificant ( P  = 0.14). CONCLUSION: Personalized feedback conversations based on DBS-derived AHD concentrations improved AHD adherence but did not reduce the prevalence of RH.

Oncoplastic surgery for breast cancer based on tumour location and a quadrant-per-quadrant atlas.

BACKGROUND: The majority of published techniques for oncoplastic surgery rely on an inverted-T mammoplasty, independent of tumour location. These techniques, although useful, cannot be adapted to all situations. A quadrant-per-quadrant atlas of mammoplasty techniques for large breast cancers was developed in order to offer breast surgeons a technique dependent on tumour location, which reduces the risk of postoperative complications and delay to adjuvant therapy. METHODS: From 2005 to 2010, a series of eligible women with breast cancer were treated by quadrant-specific oncoplastic techniques. All complications and any delay to adjuvant treatment were recorded prospectively, along with local and distant cancer recurrences. Cosmetic outcome was evaluated using a five-point scale. RESULTS: A total of 175 patients were analysed. The median tumour size, after histological examination, was 25 (range 4-90) mm. Twenty-three patients (13.1 per cent) had involved margins. Seventeen of these patients were treated by mastectomy and three had a re-excision. Complications occurred in 13 patients (7.4 per cent), which led to a delay to adjuvant treatment in three (1.7 per cent). After a median follow-up of 49 (range 23-96) months, three patients had developed a local recurrence. The mean score after cosmetic evaluation was 4.6 of 5. CONCLUSION: A quadrant-per-quadrant approach to oncoplastic techniques for breast cancer was developed that tailors the mammoplasty for each tumour location. This panel of techniques should be a useful guide for breast surgeons, and extends the possibilities for breast conservation for large or poorly limited cancers, with a low complication rate and good cosmetic results.

Reducing the incidence of TRALI in the UK: the results of screening for donor leucocyte antibodies and the development of national guidelines.

BACKGROUND AND OBJECTIVES: Transfusion-related acute lung injury (TRALI) is associated with the passive transfusion of leucocyte antibodies in blood products. Blood Transfusion Services have adopted a number of different strategies for reducing the incidence of TRALI, but, while these have been successful, TRALI has not been completely eliminated. Many Transfusion Services have introduced leucocyte antibody screening of donors to further reduce TRALI. This report describes the results of donor leucocyte antibody screening within NHS Blood and Transplant and the guidelines that have been developed for Transfusion Services within the United Kingdom (UK) to reduce the incidence of TRALI. MATERIALS AND METHODS: Blood samples from newly recruited female apheresis donors were tested for human leucocyte antigens (HLA) class I and class II antibodies and granulocyte-specific antibodies. RESULTS: A total of 1157 female donors were evaluated. Three hundred and fifteen (27·23%) donors had HLA class I or II antibodies and were returned to red cell component donation. Fifty-seven (6·77%) of the remaining 842 donors were found to have granulocyte-specific antibodies of which 11 (1·31%) had HNA-specific antibodies. A total of 818 donors (70·70%) were accepted for platelet apheresis, 336 donors (29·04%) were returned to red cell component donation, and three donors with HNA-3a antibodies (0·26%) were deferred from therapeutic donation. CONCLUSIONS: Female donors with leucocyte antibodies were identified in a stratified screening programme. Donors with antibodies were either directed to red cell donation or deferred. This process, combined with other measures that have already been introduced, is anticipated to further reduce the incidence of TRALI.

For love or money? Attitudes toward financial incentives among actual living kidney donors.

Due to lengthening waiting lists for kidney transplantation, a debate has emerged as to whether financial incentives should be used to stimulate living kidney donation. In recent surveys among the general public approximately 25% was in favor of financial incentives while the majority was opposed or undecided. In the present study, we investigated the opinion of living kidney donors regarding financial incentives for living kidney donation. We asked 250 living kidney donors whether they, in retrospect, would have wanted a financial reward for their donation. We also investigated whether they were in favor of using financial incentives in a government-controlled system to stimulate living anonymous donation. Additionally, the type of incentive deemed most appropriate was also investigated. In general almost half (46%) of the study population were positive toward introducing financial incentives for living donors. The majority (78%) was not in favor of any kind of reward for themselves as they had donated out of love for the recipient or out of altruistic principles. Remarkably, 60% of the donors were in favor of a financial incentive for individuals donating anonymously. A reduced premium or free health insurance was the preferred incentive.

Encouraging psychological outcomes after altruistic donation to a stranger.

In a growing number of transplant centers worldwide, altruistic donors are accepted to anonymously donate a kidney to a stranger. An important hesitation to expand these transplantation programs is the fear of evoking psychological distress in the altruistic donor after donation. To what extent this fear is justified has not yet been systematically investigated. In this study, 24 altruistic donors were interviewed on average 2 years after donation. Lifetime mental health history, current psychological complaints, satisfaction with and impact of the donation on well-being, motives for donation, communication with recipient and donation experience were assessed. Altruistic donors report a considerable positive impact of donation on psychological well-being, whereas negative impact was limited. Satisfaction with donation was very high. Although a history of a psychiatric diagnosis was ascertained in almost half of the donors, psychological complaints before and after donation were comparable to national average norm scores. Motives for donation were genuine and the experience of donation generally conformed to their expectations. In conclusion, living kidney donation to a stranger does not appear to exacerbate psychological complaints. Moreover, altruistic donors report considerable satisfaction and personal benefit. The exceptional gift of altruistic donors can contribute toward solving the current organ shortage issue.

Altruistic donor triggered domino-paired kidney donation for unsuccessful couples from the kidney-exchange program.

Between January 2000 and July 2009, 132 individuals inquired about altruistic kidney donation to strangers. These donors were willing to donate to genetically and emotionally unrelated patients. Some altruistic donors wished to donate to a specific person, but most wished to donate anonymously. In domino-paired donation, the altruistic donor donates to the recipient of an incompatible couple; the donor of that couple (domino-donor) donates to another couple or to the waiting list. In contrast to kidney-exchange donation where bilateral matching of couples is required, recipient and donor matching are unlinked in domino-paired donation. This facilitates matching for unsuccessful couples from the kidney-exchange program where blood type O prevails in recipients and is under-represented in donors. Fifty-one altruistic donors (39%) donated their kidney and 35 domino-donors were involved. There were 29 domino procedures, 24 with 1 altruistic donor and 1 domino-donor, 5 with more domino-donors. Eighty-six transplantations were performed. Donor and recipient blood type distribution in the couples limited allocation to blood type non-O waiting list patients. The success rate of domino-paired donation is dependent on the composition of the pool of incompatible pairs, but it offers opportunities for difficult to match pairs that were unsuccessful in the kidney-exchange program.