Paediatric haematologists’ attitudes regarding haematopoietic cell transplantation as treatment for sickle cell disease

Beginning early in childhood, patients with sickle cell disease [SCD; a group of genetic haemoglobin disorders characterized by the sickle or HbS mutation (HBB E7V)] are at risk of life-threatening and debilitating health events. Despite the high morbidity and mortality of this disease, haematopoietic cell transplantation (HCT), a curative therapy for SCD, remains underutilized. A variety of factors, including the limited availability of suitable donors, play a role in this trend, but do not fully explain the low frequency with which this therapy is employed. The objective of this study was to identify paediatric haematologists’ attitudes about HCT as a treatment option for SCD, and to describe the impact of these attitudes on their practices of discussing HCT with families of children affected by this disease. A nationwide survey of paediatric haematologists in the United States was conducted between February and May 2016. Two hundred and eighty-seven surveys were included in the final analysis (response rate 20%). On average, respondents reported informing 42% of families about HCT as a treatment option (N = 248, 95% confidence interval: 38–46). Clinician attitudes about the cost and safety of HCT were associated with practices of discussing this therapy with families. These findings suggest that clinician attitudes and referral practices may play a role in the underutilization of this therapy in the SCD population.     

Bone and mineral disorders after kidney transplantation: Therapeutic strategies

Mineral and bone diseases (MBD) are common in patients with chronic kidney disease who undergo kidney transplantation. The incidence, types and severity of MBD vary according to the duration of chronic kidney disease, presence of comorbid conditions and intake of certain medications. Moreover, multiple types of pathology may be responsible for MBD. After successful reversal of uremia by kidney transplantation, many bone and mineral disorders improve, while immunosuppression, other medications, and new and existing comorbidities may result in new or worsening MBD. Chronic kidney disease is also common after kidney transplantation and may impact bone and mineral disease. In this article, we reviewed the prevalence, pathophysiology, and impact of MBD on post-transplant outcomes. We also discussed the diagnostic approach; immunosuppression management and potential treatment of MBD in kidney transplant recipients.     

Qualitative inquiry: a method for validating patient perceptions of palliative care while enrolled on a cancer clinical trial

Background

The terminally ill person’s autonomy and control are important in preserving the quality of life in situations of unbearable suffering. Voluntary stopping of eating and drinking (VSED) at the end of life has been discussed over the past 20 years as one possibility of hastening death. This article presents a ‘systematic search and review’ of published literature concerned with VSED as an option of hastening death at the end of life by adults with decision-making capacity.

Methods

Electronic databases PubMed, EBSCOhost CINAHL and Ovid PsycINFO were systematically searched. Additionally, Google Scholar was searched and reference lists of included articles were checked. Data of the included studies were extracted, evaluated and summarized in narrative form.

Results

Overall, out of 29 eligible articles 16 were included in this review. VSED can be defined as an action by a competent, capacitated person, who voluntarily and deliberately chooses to stop eating and drinking with the primary intention of hastening death because of the persistence of unacceptable suffering. An estimated number of deaths by VSED was only provided by one study from the Netherlands, which revealed a prevalence of 2.1% of deaths/year (on average 2800 deaths/year). Main reasons for patients hastening death by VSED are: readiness to die, life perceived as being pointless, poor quality of life, a desire to die at home, and the wish to control the circumstances of death. The physiological processes occurring during VSED and the supportive care interventions could not be identified through our search.

Conclusions

The included articles provide marginal insight into VSED for hastening death. Research is needed in the field of theory-building and should be based on qualitative studies from different perspectives (patient, family members, and healthcare workers) about physiological processes during VSED, and about the prevalence and magnitude of VSED. Based on these findings supportive care interventions for patients and family members and recommendations for healthcare staff should be developed and tested.     

Polygenic inheritance of Tourette syndrome,stuttering, attention deficit hyperactivity,conduct, and oppositional defiant disorder: The additive and subtractive effect of the three dopaminergic genes—DRD2, DβH,and DAT1

Polymorphisms of three different dopaminergic genes, dopamine D₂ receptor (DRD2), dopamine β-hydroxylase (DβH), and dopamine transporter (DAT1), were examined in Tourette syndrome (TS) probands, their relatives, and controls. Each gene individually showed a significant correlation with various behavioral variables in these subjects. The additive and subtractive effects of the three genes were examined by genotyping all three genes in the same set of subjects. For 9 of 20 TS associated comorbid behaviors there was a significant linear association between the degree of loading for markers of three genes and the mean behavior scores. The behavior variables showing the significant associations were, in order, attention deficit hyperactivity disorder (ADHD), stuttering, oppositional defiant, tics, conduct, obsessive-compulsive, mania, alcohol abuse, and general anxiety-behaviors that constitute the most overt clinical aspects of TS. For 16 of the 20 behavior scores there was a linear progressive decrease in the mean score with progressively lesser loading for the three gene markers. These results suggest that TS, ADHD, stuttering, oppositional defiant and conduct disorder, and other behaviors associated with TS, are polygenic, due in part to these three dopaminergic genes, and that the genetics of other polygenic psychiatric disorders may be deciphered using this technique. © 1996 Wiley-Liss, Inc.     

In vitro factor VIII recovery during the delivery of ultra-pure factor VIII concentrate by continuous infusion

Factor VIII (FVIII) replacement by continuous infusion has been advocated as a cost-effective method for maintaining stable plasma levels of FVIII in the hemophilia A patient during surgery or life-threatening hemorrhage. Continuous delivery of monoclonal or recombinant FVIII concentrates to our pediatric patients using a traditional delivery system (dilution in normal saline of 2–10 U/ml infused at a rate of 20 ml/hr) has frequently yielded higher than expected factor usage to achieve desired levels and unexpected variability in plasma levels under presumed steady-state conditions. To determine if diminished in vitro FVIII recovery was responsible for these observations, a study of four ultrapure concentrates during 8 hr of in vitro continuous delivery was performed using four delivery systems. When reconstituted concentrate was added to normal saline in polyvinylchloride bags at a concentration of 10 U/ml (method IA), monoclonal products showed a stable recovery of 84–109% of time 0 levels. Recombinant product recovery dropped to 57–76% of time 0 levels before reapproximating the time 0 level at 2 hr. The addition of 10 mg/ml human albumin to the bags (method IB) did not improve recoveries. When reconstituted concentrate was delivered undiluted (method IIA), the early drop in recombinant recovery was eliminated; stable recovery of 78–117% of time 0 level was achieved with all products. In using method IA, a large discrepancy was seen between the actual time 0 recoveries and those expected based on vial assays, most striking for recombinant products (49–57% of expected). Method IIA allowed 75–90% recovery; addition of 20 mg/ml albumin of reconstituted but undiluted concentrate (method IIB) maximized recovery at 85–98% of expected. © 1996 Wiley-Liss, Inc.     

Assessing depression in fibromyalgia patients

Purpose. This study investigated the relationships among four methods of detecting depression in patients with fibromyalgia. Methods. Data were obtained from 100 women (mean age 43 years) who had been diagnosed with fibro-myalgia. Instruments included a computerized Diagnostic Interview Schedule (C-DIS), Beck Depression Inventory (BDI), an adjusted “disease-free” BDI (BDI-A), and Minnesota Multiphasic Personality Inventory depression subscale (MMPI-D). Chance-corrected concordance, sensitivity, specificity, and accuracy among the four methods were calculated. Results. The C-DIS detected 22% and BDI-A 29% with current major depression. The BDI and MMPI-D yielded higher estimates of 55% of the 44%, respectively. Agreement on the diagnosis among the four methods was significantly greater than chance. When compared with the C-DIS, the BDI was the most sensitive instrument and the BDI-A most specific. Conclusions. The C-DIS and BDI-A appear to be more reliable methods for determining the presence of major depression in women with fibromyalgia than are the MMPI-D or standard BDI.     

Real-World Treatment Patterns and Clinical Effectiveness of Palbociclib Plus an Aromatase Inhibitor as First-Line Therapy in Advanced/Metastatic Breast Cancer: Analysis from the US Syapse Learning Health Network

This retrospective single-arm study assessed real-world treatment patterns and clinical outcomes in patients with hormone receptor—positive/human epidermal growth factor receptor 2—negative (HR+/HER2−) advanced/metastatic breast cancer (A/MBC) who received palbociclib plus an aromatase inhibitor as first-line therapy in US community health systems. Using electronic health records from the Syapse Learning Health Network, 242 patients were identified as having received first-line palbociclib plus an aromatase inhibitor between 3 February 2015, and 31 July 2019 (data cutoff 1 February 2020) resulting in a minimum potential 6-month follow-up period. In total, 56.6% of patients had de novo A/MBC at initial breast cancer diagnosis, 50.8% had bone-only disease, and 32.2% had visceral disease. Median follow-up was 22.4 months. Disease progression (26.4%) and intolerance/toxicity (14.9%) were the main reasons for treatment discontinuation. The median (95% CI) real-world progression-free survival was 31.7 (27.9—not estimable (NE)) months and 2-year estimated overall survival (OS) rate was 78.0%. In total, 25.6% of patients died; however, OS data are limited by the small population size and insufficient follow-up time. These real-world effectiveness outcomes complement findings from other real-world studies and randomized controlled trials and support palbociclib plus an aromatase inhibitor as first-line therapy for HR+/HER2− A/MBC.     

Managing Opioid Withdrawal for Hospital Patients in Custody

Dr. Brown, a hospitalist, admits Mark, a patient transferred from a local jail for management of cellulitis. The patient, who was taken into custody two days prior to hospital admission, has a history of intravenous heroin use. Mark explains that he had been prescribed buprenorphine‐naloxone maintenance therapy for opioid use disorder for several years prior to being arrested and had not used other opioids during that time. As a policy, the jail where Mark is detained does not prescribe opioid agonists, and his maintenance therapy was stopped upon his arrival there. Dr. Brown discovers that Mark is diaphoretic and appears distressed. Mark's symptoms suggest to Dr. Brown that, in addition to having cellulitis, Mark is actively withdrawing from opioids. Mark tells Dr. Brown that he has felt “horrible” since his buprenorphine‐naloxone therapy was stopped and that he now has intense cravings for opioids. He asks Dr. Brown to help alleviate the withdrawal symptoms. Dr. Brown, who is accustomed to treating opioid withdrawal with opioid replacement therapy, wonders if she should initiate ORT for Mark while he is in the hospital.