Automatic VMAT technique to treat glioblastoma: A two years’ experience

PurposeThe present work aims to guide the physicist in order to start automated planning for the VMAT treatment of glioblastoma multiforme (GBM) by giving a recipe that was set up and tested during a long-term (two years) evaluation.MethodsAn automatic technique in AutoPlanning module of the Pinnacle3 (Philips Medical Systems, Fitchburg, WI) treatment planning system was created and validated by comparing dose distributions of automatic plans (APs) and manual plans (MPs) and by performing a blind AP-MP comparison on a cohort of 20 patients. Automatic technique was then applied to 145 patients and failures were recorded i.e. the number of times for which dose distributions produced by the automatic module were not suitable for treatment.ResultsEach of the 20 APs considered in the validation step was clinically acceptable and proved to be better (15 cases) or equal (5 cases) respect to MPs. A statistically significant improvement in brain stem, optic pathways, cochleae, pituitary gland and scalp sparing was observed for APs, while no statistically significant differences were recorded in target coverage or plan parameters. For only 5 cases out of the 145 plans the operator intervention was needed in order to obtain a clinical acceptable plan, while for the remaining 140 plans the automatic created solution was suitable.ConclusionsA straightforward automatic procedure has been created and tested in our clinic. The AutoPlanning technique proposed represents a reliable tool to improve treatment planning efficiency and the recipe, here presented, could be simply imported to every radiotherapy center.     

Transition from paediatric to adult care of adolescent patients with congenital heart disease: a pathway to optimal care

Introduction

Adolescents with congenital heart disease transition from a paediatric to an adult setting. This is associated with loss-to-follow-up and suboptimal care. Increasing numbers of patients justify a special program. In this study we evaluated the cooperative program between paediatric and adult cardiology departments in a tertiary referral centre.

Methods

In this retrospective study, patients with congenital heart disease with at least one appointment scheduled at the transition program between January 2010 and January 2015 were included. They were seen by a paediatric cardiologist at the age of 15 years in the paediatric department and from age 18 to 25 in the adult department. Demographic and medical data were collected from the electronic patient files.

Results

A total of 193 patients (105 males, 88 females) were identified. Sex distribution was almost equal. Most patients were 18–21 years of age. The largest group, 128 patients (67?%), lived within 50 kilometres of our hospital. Paediatric cardiologists referred 157 (81?%) of patients. General practitioners and cardiologists from outside our centre were important referrers for patients lost to follow-up, together accounting for 9?%. A total of 34 (18?%) patients missed an appointment without notification. Repeat offenders, 16 of 34 patients, formed a significant minority within this group. A total of 114 (59?%) patients were attending school, 46 (24?%) were employed, and 33 (17?%) patients were inactive. Activities are in line with capabilities. A nurse practitioner was involved with the 7?% with complex and psychosocial problems. Moderately severe congenital heart defects formed the largest patient category of 102 (53?%) patients. In 3?% of patients the diagnosis had to be revised or was significantly incomplete. In 30 (16?%) patients, cardiac diagnosis was part of a syndrome. Of the 193 patients, 117 (92?%) were in NYHA class I, with 12 (6?%) and 4 (2?%) patients falling into classes II and III, respectively.

Conclusions

A viable transition program can be built by collaboration between paediatric and adult cardiology departments with the same treating physician taking care of patients between 15 and 25 years of age. General practitioners are important in returning lost-to-follow-up patients to specialised care. Nurse practitioners are essential in the care for patients with complex congenital heart disease.

     

Leptin: A new predictor of outcome in the patients undergoing traditional on-pump CABG surgery?

Leptin, a 16 kDa peptide product of the obese gene, is an adipocyte-derived cytokine-like molecule which is structurally related to the IL-6 cytokine family. Through its interaction with its receptor Ob-R, a member of the class I cytokine receptor family which is ubiquitously expressed including endothelium, vascular smooth muscle and myocardium, leptin plays a role in a wide range of biological responses such as control of body weight and energy expenditure, neuroendocrine function, angiogenesis, bone formation, modulating immune responses. More and more studies indicated that leptin may be involved in the acute stress response to severe illness and surgery by way of its interaction with hypothalamic–pituitary–adrenal axis and the inflammatory cytokine system. Systemic inflammatory response (SIR) is one of the common complications after on-pump coronary artery bypass grafting in which the severity of SIR directly correlates with the outcome and prognosis. We based our hypothesis on that leptin may participate in the acute stress-SIR induced by on-pump coronary artery bypass grafting and its levels and secretion patterns might be related to the extent of activation of SIR and might serve as marker of the severity and predict the outcome.     

Cardiac dyssynchrony and response to cardiac resynchronisation therapy in heart failure: can genetic predisposition play a role?

Cardiac resynchronisation therapy (CRT) is an accepted treatment for heart failure patients with depressed left ventricular (LV) function and dyssynchrony. However, despite better clinical outcome and improved cardiac function after CRT in the majority of eligible heart failure patients, a large proportion of implanted patients do not seem to benefit clinically from this therapy. In this review we consider whether genetic factors may play a role in modulating response to CRT and summarise the few genetic studies that have investigated the role of genetic variation in candidate genes.     

Phylogeography’s past,present, and future: 10 years after

Approximately 20 years ago, Avise and colleagues proposed the integration of phylogenetics and population genetics for investigating the connection between micro- and macroevolutionary phenomena. The new field was termed phylogeography. Since the naming of the field, the statistical rigor of phylogeography has increased, in large part due to concurrent advances in coalescent theory which enabled model-based parameter estimation and hypothesis testing. The next phase will involve phylogeography increasingly becoming the integrative and comparative multi-taxon endeavor that it was originally conceived to be. This exciting convergence will likely involve combining spatially-explicit multiple taxon coalescent models, genomic studies of natural selection, ecological niche modeling, studies of ecological speciation, community assembly and functional trait evolution. This ambitious synthesis will allow us to determine the causal links between geography, climate change, ecological interactions and the evolution and composition of taxa across whole communities and assemblages. Although such integration presents analytical and computational challenges that will only be intensified by the growth of genomic data in non-model taxa, the rapid development of “likelihood-free” approximate Bayesian methods should permit parameter estimation and hypotheses testing using complex evolutionary demographic models and genomic phylogeographic data. We first review the conceptual beginnings of phylogeography and its accomplishments and then illustrate how it evolved into a statistically rigorous enterprise with the concurrent rise of coalescent theory. Subsequently, we discuss ways in which model-based phylogeography can interface with various subfields to become one of the most integrative fields in all of ecology and evolutionary biology.     

Donepezil can improve daily activities and promote rehabilitation for severe Alzheimer’s patients in long-term care health facilities

Background

Cholinesterase inhibitors can delay the progression of Alzheimer’s disease (AD). Several clinical trials of the drug in moderate to severe AD have consistently reported clinically positive effects. A combining effect with psychosocial intervention was reported in mild to moderate AD patients. Since a therapeutic approach or rehabilitation combined with cholinesterase inhibitors for severe AD patients remains controversial, we performed a prospective intervention for patients in Long-Term Care Health Facilities (LTCHF).

Methods

Two LTCHFs (N1, N2) were enrolled. N1 is a 126-bed facility that does not treat with donepezil but rather with psychosocial intervention (reality orientation and reminiscence). N2 is a 150-bed facility with a 50-bed special dementia unit, in which the physician can prescribe donepezil. On top of the similar psychosocial intervention, rehabilitation is performed in N2. Thirty-two severe AD patients (MMSE <?6) in N1 and N2 (16 vs. 16) were compared for the effect of donepezil (10 mg/d for 3 months) with or without psychosocial intervention (n =?8 vs. 8 for each facility). The Vitality Index was used to assess daily activities and the introduction of rehabilitation.

Results

The response ratio (MMSE 3+) of donepezil was 37.5% in N2. The combination of donepezil with the psychosocial intervention improved the Vitality Index total score, and Communication, Eating, and Rehabilitation subscores (Wilcoxon, p =?0.016, 0.038, 0.023, and 0.011, respectively). Most of them were smoothly introduced to rehabilitation, and the proportion of accidental falls decreased. Psychosocial intervention in N1 without the drug only improved the total score (Wilcoxon, p =?0.046).

Conclusions

A combined therapeutic approach of donepezil and psychosocial intervention can have a positive effect, even for severe patients through the introduction of rehabilitation and decreasing accidental falls. However, these findings require replication in a larger cohort.

     

The importance of margins status after breast conservative surgery and radiotherapy in node positive patients: a follow-up of 10–15 years

Background

Margin status is the main factor determining local recurrence (LR) after wide excision and radiotherapy for breast cancer. The aim of the study is to evaluate if positive margins are as great a risk factor for LR in node-positive as in node-negative patients, since the major risk in the former group is dissemination and whether there is a correlation between nodal status and margins in relation to prognosis.

Methods

773 patients underwent WLE and radiotherapy between 1988 and 1992 and were followed-up (> 10 years) to determine LR rates according to margin and nodal status. Margins were assessed by cavity-shave biopsies and the axilla was staged by sampling or clearance.

Results

461 patients were node negative and 312 node positive. In the node-negative group 415 patients had negative margins and 46 positive: LR after > 10 years was 12 % and 28 % respectively. Among the 312 patients in the node positive group, 267 were margin negative and 45 positive; the LR rate was 12 % and 18 % respectively. In the node negative-group there was a statistically significant difference between the positive and the negative margins with higher relapse rate and lower overall survival (p < 0.001), whereas in the node-positive group the equivalent comparison didn't show any statistical difference.

Conclusion

Although re-excision should be always recommended, in node-negative patients positive margins are associated with a statistically higher LR rate and lower overall survival while in node-positive disease margins might be of less importance in determining prognosis as dissemination is more likely to occur.

     

Patients’ attitudes to the summary care record and HealthSpace: qualitative study

Objective To document the views of patients and the public towards the summary care record (SCR, a centrally stored medical record drawn from the general practice record) and HealthSpace (a personal health organiser accessible through the internet from which people can view their SCR), with a particular focus on those with low health literacy, potentially stigmatising conditions, or difficulties accessing health care.Design 103 semistructured individual interviews and seven focus groups.Setting Three early adopter primary care trusts in England where the SCR and HealthSpace are being piloted. All were in areas of relative socioeconomic deprivation.Participants Individual participants were recruited from general practice surgeries, walk-in centres, out of hours centres, and accident and emergency departments. Participants in focus groups were recruited through voluntary sector organisations; they comprised advocates of vulnerable groups and advocates of people who speak limited English; people with HIV; users of mental health services; young adults; elderly people; and participants of a drug rehabilitation programme.Methods Participants were asked if they had received information about the SCR and HealthSpace and about their views on shared electronic records in different circumstances.Results Most people were not aware of the SCR or HealthSpace and did not recall receiving information about it. They saw both benefits and drawbacks to having an SCR and described a process of weighing the former against the latter when making their personal choice. Key factors influencing this choice included the nature of any illness (especially whether it was likely to lead to emergency care needs); past and present experience of healthcare and government surveillance; the person’s level of engagement and health literacy; and their trust and confidence in the primary healthcare team and the wider NHS. Overall, people with stigmatising illness were more positive about the SCR than people who claimed to speak for “vulnerable groups.” Misconceptions about the SCR were common, especially confusion about what data it contained and who would have access to it. Most people were not interested in recording their medical data or accessing their SCR via HealthSpace, but some saw the potential for this new technology to support self management and lay care for those with chronic illness.Conclusion Despite an extensive information programme in early adopter sites, the public remains unclear about current policy on shared electronic records, though most people view these as a positive development. The “implied consent” model for creating and accessing a person’s SCR should be revisited, perhaps in favour of “consent to view” at the point of access.     

A comparison of patients’ heart rate variability and blood flow variability during surgery based on the Hilbert–Huang Transform

Previous studies have indicated that heart rate variability (HRV) is considered to be one of the effective parameters for assessing autonomous nervous system activity. Therefore, HRV can be used to detect the state of patients during surgery, even for estimating depth of anaesthesia (DOA). However, the heartbeat can be affected by anaesthesia drugs, breathing rate and electric influence during surgery, which can result in inaccurate information about the patient. To contend with this problem, blood flow variability (BFV) is proposed in this paper as an indicator to monitor the patient's status when HRV is not appropriate. In our experiments, thirty patients undergoing ear, nose, and throat (ENT) surgery with different anaesthetics are used to compare the efficiency and validity between the fast Fourier transform (FFT) and the Hilbert–Huang transform (HHT). Of another thirty patients, twenty patients accepted ENT surgery, of which ten have received Atropine, while the others have not. The other ten patients who have accepted abdominal surgery with an electric knife were compared with the previously mentioned ten patients who did not receive an Atropine injection for ENT surgery. As a result, the FFT that is applied in this study was replaced with the HHT for analysing the data in a particular frequency range of sympathetic and parasympathetic divisions, because of the lesser response of the results that were analysed by FFT for intubation. Also, BFV is proven to be a useful indicator for assisting doctors to assess the state of the patients instead of HRV during the operation in comparison with HRV under drugs (i.e., Atropine and Glycopyrrolate) and diathermy effects (i.e., high frequency interference from electric knife).     

Cardiovascular risk and attitudes to lifestyle: what do patients think?

OBJECTIVE--To examine the relation between subjects'' level of cardiovascular risk and their beliefs about the harmfulness of their smoking habit, current diet, and level of exercise, together with their stated desire to modify such behaviour. DESIGN--Self administered postal health and life-style questionnaire followed by a structured health check conducted by a nurse. SETTING--Five general practices in Luton and Dunstable, Bedfordshire. SUBJECTS--5803 people aged 35-64 years enrolled in the OXCHECK trial who attended for a health check before 1 March 1992. MAIN OUTCOME MEASURES--Perceived risk to health of lifestyle behaviours, desire to modify behaviour, and a reported serious attempt to modify behaviour in the preceding year. RESULTS--A high proportion of smokers and those who were physically inactive perceived their behaviour to be harmful (1020; (76%; 95% confidence interval 74% to 79%) and 350 (74%; 70% to 78%) respectively) and wished to modify it (1212 (79%; 77% to 81%) and 375 (74%; 71% to 78%) respectively). In contrast, only 289 (45%; 41% to 48%) of obese people and 188 (14%; 12% to 16%) of people with a high dietary fat intake perceived their current diet to be harmful. The more cardiovascular risk factors present, the more likely subjects were to perceive a health risk attached to their diet and lack of exercise (p < 0.01 in both cases) and to want to improve their diet. CONCLUSION--Awareness of the health risk from smoking and motivation to stop is high. Further efforts are required, however, to educate the public about the risks associated with a high dietary fat intake. Although the health risks of inactivity were widely recognised, motivation to take more exercise needs to be increased.     

Conditional economic incentives and motivational interviewing to improve adolescents’ retention in HIV care and adherence to antiretroviral therapy in Southeast Nigeria: study protocol for a cluster randomised trial

Background

Adolescent HIV patients face enormous difficulty in accessing HIV care services. Given their vulnerability to risk-taking behaviour, this group also have worse treatment outcomes compared to other age groups. Poor treatment outcomes will impact negatively on HIV/AIDS management and control particularly in sub-Saharan Africa (SSA) as more than eight out of ten of the world’s HIV-infected adolescents live in this region of the world. Limited evidence exists on the effectiveness of service delivery interventions to support adolescents’ retention on antiretroviral therapy (ART) and adherence to ART. This trial is designed to evaluate the impact of conditional economic incentive and motivational interviewing on adolescents’ retention in HIV care and adherence to ART in Anambra State, Southeast Nigeria.

Methods/design

The study will be a cluster randomised controlled trial that will be conducted in selected HIV treatment hospitals in Anambra State, Nigeria. Based on sample size calculation, 12 HIV treatment hospitals from Anambra will be selected for the study. Six HIV treatment hospitals each will be randomised to either the intervention or the control arm. A structured adherence support scheme termed the ‘Incentive Scheme’ will be applied to the intervention arm while the control arm will receive routine HIV care (usual care). Additionally, patients in the intervention arm will receive motivational interviewing at baseline and following initiation of antiretroviral therapy (ART), they will receive a gift voucher of US$5.6 when HIV viral load (VL) is <?20 copies/mL at 12?weeks, a gift voucher of US$2.8 if the VL remains suppressed for the next 3?months, and the next 6?months, and finally a gift voucher of US$5.6 if the VL remains <?20 copies/mL at 1?year. All gift vouchers will be conditional not only on VL results but attending the motivational interviews. The primary outcome for the trial will be the difference between groups in the proportion with HIV VL suppression (≤?20 copies/mL) by 12?months and then 24?months after withdrawal of incentive.

Discussion

The findings of this proposed trial will provide evidence on the feasibility of applying conditional economic incentives combined with motivational interviewing to improve retention and adherence to antiretroviral therapy of adolescents living with HIV in Nigeria and possibly in other sub-Saharan African countries.

Trial registration

Registered in the Pan African Clinical Trials Registry, ID: PACTR201806003040425. Registered on 2 February 2018.

     

Treatment of massive hypertriglyceridemia resistant to PUFA and fibrates: a possible role for the coenzyme Q10?

OBJECTIVE: To describe the effect of CoQ10 (added to either a fibrate, or PUFA or association of both) in patients affected by massive hypertriglyceridemia (MHTG) resistant to fibrates and PUFA. DESIGN: Open, sequential, comparative intervention study. SETTING: Specialised centres for dyslipidemia management. SUBJECTS: 15 subjects (mean age: 45.1 +/- 12.5 years) affected by MHTG and hyporesponsive to either fibrates, or PUFA, or fibrates-PUFA association, and 15 age-matched subjects regularly responders to PUFA and fenofibrate treatment. INTERVENTIONS: Treatment for periods of 6 weeks each with the following consecutive treatments: CoQ10 150 mg/day, PUFA 3000 mg/day, fenofibrate 200 mg/day, PUFA 3000 mg/day + fenofibrate 200 mg/day, PUFA 3000 mg/day + CoQ10 150 mg/day, fenofibrate 200 mg/day + CoQ10 150 mg/day, and finally, fenofibrate 200 mg/day + PUFA 3000 mg/day + CoQ10 150 mg/day. RESULTS: CoQ10 supplementation improved, in the control group, systolic and diastolic blood pressure, creatinine and Lp(a) plasma levels, both during fenofibrate and/or PUFA treatment. In MHTG group, CoQ10 supplementation significantly improved TG, TC, Lp(a), uric acid and blood pressure during fenofibrate treatment, but only Lp(a) and blood pressure during PUFA treatment. Fenofibrate appeared to have better effect on hsCRP and gamma-GT plasma levels than PUFA. No significant change was observed in any group and under any treatment in regards to homocysteinemia, PAI-1, or t-PA. CONCLUSION: Even though the mechanism of action through which the effects were obtained is yet to be elucidated, adding CoQ10 to fenofibrate could improve the drug's efficacy in MHTG patients not responding to fenofibrate alone.