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BACKGROUND: Integration of oncology and palliative care (PC) should be the standard model of care for patients with advanced cancer. An expert panel developed criteria that constitute integration. This study determined whether the PC service within this Health Service, which is considered to be fully "integrated", could be benchmarked against these criteria. METHODS: A survey was undertaken to determine the perceived level of integration of oncology and palliative care by all health care professionals (HCPs) within our cancer centre. An objective determination of integration was obtained from chart reviews of deceased patients. Integration was defined as >70% of all respondents answered "agree" or "strongly agree" to each indicator and >70% of patient charts supported each criteria. RESULTS: Thirty-four HCPs participated in the survey (response rate 69%). Over 90% were aware of the outpatient PC clinic, interdisciplinary and consultation team, PC senior leadership, and the acceptance of concurrent anticancer therapy. None of the other criteria met the 70% agreement mark but many respondents lacked the necessary knowledge to respond. The chart review included 67 patients, 92% of whom were seen by the PC team prior to death. The median time from referral to death was 103 days (range 0-1347). The level of agreement across all criteria was below our predefined definition of integration. CONCLUSION: The integration criteria relating to service delivery are medically focused and do not lend themselves to interdisciplinary review. The objective criteria can be audited and serve both as a benchmark and a basis for improvement activities.

A 12-year-old boy currently is followed by multiple sub-specialists for problems caused by the chromosome 22q11.2 deletion syndrome (22q11DS) (Figure). He was born via spontaneous vaginal delivery, weighing 3033 g, to a 31-year-old G3P3 mother after a full-term pregnancy complicated only by mild polyhydramnios. Family history was non-contributory. Apgar scores were 8 at 1 minute and 9 at 5 minutes. With the exception of a weak cry, the results of the infant’s initial examination were unremarkable, and he was moved to the well-baby nursery. Shortly thereafter, a cardiac murmur was noted, the cardiology department was consulted, and the child was transferred to a local tertiary care facility with a diagnosis of tetralogy of Fallot. Stable, he was discharged home at 3 days of life. Figure Mild dysmorphic facial features of a boy aged 11 years with 22q11.2DS, including a short forehead, hooded eyelids with upslanting palpebral fissures, malar flatness, bulbous nasal tip with hypoplastic alae nasi, and protuberant ears. At 5 days of life, he had jerky movements. On presentation to the local emergency department, his total calcium level was 4.7 mg/dL, and later partial hypoparathyroidism was diagnosed. At that time, a consulting geneticist suggested the diagnosis of chromosome 22q11DS. Weeks later, the family received a telephone call confirming the diagnosis with fluorescence in situ hybridization (FISH). No additional information about the diagnosis, prognosis, etiology, or recurrence risk was provided until the child was 5 months of age, when he underwent cardiac repair at a third hospital, where a comprehensive 22q11DS program was in operation. In the interim, the child had feeding difficulties requiring supplemental nasogastric tube feeds, nasal regurgitation, and gastroesophageal reflux, while the parents searched the internet for reliable information about their son’s diagnosis. Subsequent notable abnormalities and interventions included: recurrent otitis media with bilateral myringotomy tube placement at 6 months; angioplasty with left pulmonary artery stent placement after the identification of pulmonary artery stenosis with bilateral pleural effusions at age 6 years; chronic upper respiratory infections with significant T cell dysfunction requiring live viral vaccines to be held until age 7 years; velopharyngeal incompetence necessitating posterior pharyngeal flap surgery at 7 years; enamel hypoplasia and numerous caries resulting in 3 separate dental procedures under general cardiac anesthesia beginning at age 7 years; multiple cervical and thoracic vertebral anomalies with thoracic levoconvex scoliosis and upper lumbar dextroscoliosis requiring growing rod placement at age 11 years with subsequent rod extension at ages 11.5 and 12 years; postoperative hypocalcemia; short stature; constipation; and persistent idiopathic thrombocytopenia. Pertinent negative test results included normal renal ultrasound scanning and parental 22q11.2 deletion studies. On physical examination, the boy’s height and weight have consistently tracked just below the fifth percentile, with no evidence of growth hormone deficiency. His head circumference is within reference range at the 25th percentile. Dysmorphic features include: a low anterior hairline; hooded eyelids; malar flatness; normally formed but protuberant ears with attached lobes; a mildly deviated nose with a bulbous nasal tip and hypoplastic alae nasi; asymmetric crying facies with a thin upper lip; mild micrognathia; a sacral dimple; and soft tissue syndactyly of the second and third toes. Developmentally, the boy had mild delays in achieving motor milestones, sitting at 11 months and walking at 18 months. However, he exhibited significant delays in the emergence of language: he never babbled, spoke his first words at age 3 years, and only achieved full conversational speech at 7 years. However, he had relative strengths in receptive language and communicated appropriately by the use of sign language. Now quite conversant, he is mainstreamed in the seventh grade with resource room supports. Moreover, he is affable, but exhibits anxiety and perseverations. Lastly, despite numerous medical, academic, and social challenges, he participates in assisted athletics, is an avid wrestling fan, and enjoys travel. However, his exceptionally supportive parents, siblings, and extended family continue to worry about his long-term outcome and transition of care as he approaches adulthood. As demonstrated by this boy’s complicated course, practical multi-system guidelines are needed to assist the general practitioner and specialists in caring for patients with 22q11DS. Although still under-recognized, detection, including in the prenatal setting, is increasing. Moreover, the phenotypic spectrum is highly variable, and patients may present at any age. Thus, initial guidelines developed by an international panel of experts present the best practice recommendations currently available across the lifespan, with a major focus on the changing issues through childhood development.

Obesity, type 2 diabetes mellitus (DM) and metabolic syndrome (MS) are common in patients with heart failure (HF). Studies investigating the association between known biomarkers and adiposity in patient populations are limited. The aim of the present study was to investigate the association between C-reactive protein (CRP) and leptin with adiposity in a sub-group of overweight/obese patients with HF, DM and/or MS. A total of 36 patients (mean age, 56.72±9.78 years; ranging between 27 and 76 years of age; 80.6% male; 52.8% Caucasian) were enrolled and their height, weight, waist circumference and body composition (e.g. percentage body fat and lean mass), as well as the levels of CRP and leptin, were assessed. The results demonstrated that there was a significant association between CRP and leptin, CRP and body mass index (BMI) and gender and percentage body fat (P

Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly influence the risk of developing colorectal cancer (CRC). To enhance power to identify additional loci with similar effect sizes, we conducted a meta-analysis of two GWA studies, comprising 13,315 individuals genotyped for 38,710 common tagging SNPs. We undertook replication testing in up to eight independent case-control series comprising 27,418 subjects. We identified four previously unreported CRC risk loci at 14q22.2 (rs4444235, BMP4; P = 8.1 x 10(-10)), 16q22.1 (rs9929218, CDH1; P = 1.2 x 10(-8)), 19q13.1 (rs10411210, RHPN2; P = 4.6 x 10(-9)) and 20p12.3 (rs961253; P = 2.0 x 10(-10)). These findings underscore the value of large sample series for discovery and follow-up of genetic variants contributing to the etiology of CRC.

OBJECTIVE: To identify risky sexual behaviours and demographic factors that place high-school pupils at risk of HIV and AIDS. METHODS: A cross-sectional study was undertaken to explore factors influencing the sexual behaviour of high-school pupils (mean age 15.4 years; SD 1.11). Structured self-reported questionnaires were completed by all grade 10 pupils (N=805) at all the Wentworth, Durban, public high schools. RESULTS: Significant gender differences in sexual practices were reported, such as males being more likely to engage in sexual activity than females (OR 4.92; p

Evidence-based practice in medicine promotes the performance of medicine based upon proven and validated practice. The CARE-PARTNER system presented here is a computerized knowledge-support system for stem-cell post-transplant long-term follow-up (LTFU) care on the WWW, which means that it monitors the quality of the knowledge both of its own knowledge-base and of its users. Its aim is to support the evidence-based practice of the LTFU clinicians and of the home-town physicians who actually care for the transplanted patients. Currently, three fundamental characteristics of CARE-PARTNER are accountable for its knowledge-support function: the quality of its knowledge-base, its availability on the WWW, and its learning from experience capability. As a matter of fact, the integration of a case-based reasoner in the reasoning framework enables the system to introspectively study its results, and to learn from its successes and failures, thus confronting the quality of the guidelines and pathways it reuses to the reality and complexity of the clinical cases.

OBJECTIVE: To determine the effect of the results of clinical trials on the behaviour of patients and physicians, the authors ascertained the proportion of patients participating in the Canadian Atrial Fibrillation Anticoagulation (CAFA) study who started or continued warfarin therapy at the end of the study and identified factors affecting the decision to use or not use warfarin. The CAFA study was a double-blind, randomized, placebo-controlled, multicentre study to evaluate the efficacy of warfarin in preventing stroke among patients with nonrheumatic atrial fibrillation. Recruitment and follow-up were stopped early because two other similar studies had shown a decrease in the rate of stroke among patients treated with warfarin. DESIGN: Mail survey 21 months after the end of the study. PARTICIPANTS: The personal physicians of 336 patients who had participated in the CAFA study. OUTCOME MEASURES: Type of antithrombotic therapy the patients had received since the CAFA study ended for patients who were not receiving warfarin, the reasons they were not. RESULTS: Questionnaires concerning 254 (76%) of the patients who had participated in the study were returned. Since the end of the CAFA study, 153 (60%) of these patients had been treated continually with warfarin, 14 (6%) had been treated with warfarin but had subsequently stopped taking it, 59 (23%) had taken acetylsalicylic acid (ASA) continually, 5 (2%) had been taking ASA but had subsequently stopped taking it, and 23 (9%) had not taken either drug. The responding physicians stated that 58 (67%) of the patients who were not treated with warfarin did not wish to take the drug. The patients who had received warfarin during the CAFA trial were more likely to be treated with warfarin after the trial (75%) than were those who had received a placebo (56%) (p = 0.001). The probability of the patients' being treated with warfarin also depended on which study centre they had been treated in (p = 0.001). CONCLUSIONS: Of the patients in the CAFA study for whom questionnaires were received, only 167 (66%) had been treated with warfarin after the end of the study. The patients were more likely to have been treated with warfarin after the study if they had received warfarin during the study. The positive results of clinical trials, on their own, are not enough to fully change the behaviour of patients and physicians.

The flash lamp excitation of coumarin dye to produce light energy of the specific wavelength of 504 nm is the basis for the new wave of pulsed dye lasers. Numerous urological applications have been developed. Treatment of ureteral and renal calculi has proven to be an atraumatic and effective treatment modality. Most recently, this technology has been applied to the endoscopic treatment of biliary calculi. The authors review the most recent treatment techniques in both biliary and urinary stone disease.

A technetium-labeled monoclonal antibody was administered to 52 patients with non-small cell lung carcinoma, either to stage the mediastinum preoperatively or to detect distant metastases. Results from planar and tomographic imaging are compared to CT and histologic confirmation. Differences in detection rates and predictive values between imaging modalities are discussed. The authors conclude that imaging with a technetium-labeled monoclonal antibody is safe and accurate and may be useful for staging patients with either operable or inoperable non-small cell lung cancer.

To investigate the use, understanding, trust and influence of the internet and other sources of health information used by the next of kin (NOK) of patients admitted to the intensive care unit (ICU).Multicentre structured survey.The ICUs of 13 public and private Australian hospitals.NOK who self-identified as the primary surrogate decision maker for a patient admitted to the ICU.The frequency, understanding, trust and influence of online sources of health information, and the quality of health websites visited using the Health on the Net Foundation Code of Conduct (HONcode) for medical and health websites.There were 473 survey responses. The median ICU admission days and number of ICU visits by the NOK at the time of completing the survey was 3 (IQR, 2-6 days) and 4 (IQR, 2-7), respectively. The most commonly reported sources of health information used very frequently were the ICU nurse (55.6%), ICU doctor (38.7%), family (23.3%), hospital doctor (21.4%), and the internet (11.3%). Compared with the 243 NOK (51.6%) not using the internet, NOK using the internet were less likely to report complete understanding (odds ratio [OR], 0.57; 95% CI, 0.38-0.88), trust (OR, 0.34; 95% CI, 0.19-0.59), or influence (OR, 0.58; 95% CI, 0.38-0.88) associated with the ICU doctor. Overall, the quality of the 40 different reported websites accessed was moderately high.A substantial proportion of ICU NOK report using the internet as a source of health information. Internet use is associated with lower reported understanding, trust and influence of the ICU doctor.

Bicycle helmet wearing is currently not legally enforced in Ireland and little is known about the self-reported practice amongst young children. The principal aim of this study was to assess self-reported helmet wearing amongst a sample (n = 314) of primary school children (aged 8-13 years) attending disadvantaged schools in Dublin. Approximately 86% of the sample owned a bike and provided a response to the question on helmet use. The findings indicate that helmet wearing is not a widespread practice (50.4%; 136/270 report never wearing helmets). As children get older, reported practice is also less likely with 67% (27/40) of 12/13 year-olds compared to 38% (31/81) of 8/9 year-olds reporting never wearing protective headgear. Regardless of age, more girls (61%; 82/135) than boys (39%; 52/135) indicated always/sometimes using helmets when cycling. Conversely, the findings show that (mandatory) seatbelt wearing is standard practice for the majority (93%; 252/270). The findings relating to helmet wearing add further to the debate around the mandatory introduction of protective headgear for cyclists.

A submicroscopic deletion of chromosome 22q11.2 has been identified in the majority of patients with the DiGeorge, velocardiofacial, and conotruncal anomaly face syndromes, and in some patients with the Opitz G/BBB and Cayler cardiofacial syndromes. We have been involved in the analysis of DiGeorge syndrome and related diagnoses since 1982 and have evaluated a large number of patients with the deletion. We describe our cohort of 250 patients whose clinical findings help to define the extremely variable phenotype associated with the 22q11.2 deletion and may assist clinicians in providing genetic counseling and guidelines for clinical management based on these findings.

Sex and cystic fibrosis status have been previously diagnosed separately at the single cell level. We have developed a sensitive, reliable, accurate and rapid (within 5-6 h) system for the simultaneous diagnosis of sex, cystic fibrosis and a DNA 'fingerprint' within a single reaction from a variety of single cells. As contamination cannot be totally excluded, particularly at the single cell level, DNA 'fingerprinting' can be used to assess the risk of contamination. High sensitivity with single cells is combined with very high specificity (estimated matching probability of 10(-7)-10(-8)), allowing the source of the amplified cell to be identified with a very high degree of probability. Fluorescent primers were multiplexed for six tetranucleotide microsatellite sequences to determine the DNA fingerprint; the amelogenin gene was used to diagnose sex, and primers for the CFTR region were used to determine cystic fibrosis (CF) status. Analysis of the fluorescent product was undertaken using an automated DNA sequencer with Genescan software. This technique has many applications such as prenatal and preimplantation diagnosis, forensic identification of small or degraded samples, and detection of contamination sources. DNA fingerprints of single haploid spermatozoa and other cells can be assessed, so ensuring the detection of both diploid and haploid contamination during preimplantation diagnosis.

Rubella virus (RuV) has recently been found in association with granulomatous inflammation of the skin and several internal organs in patients with inborn errors of immunity (IEI). The cellular tropism and molecular mechanisms of RuV persistence and pathogenesis in select immunocompromised hosts are not clear. We provide clinical, immunological, virological, and histological data on a cohort of 28 patients with a broad spectrum of IEI and RuV-associated granulomas in skin and nine extracutaneous tissues to further delineate this relationship. Combined immunodeficiency was the most frequent diagnosis (67.8%) among patients. Patients with previously undocumented conditions, i.e., humoral immunodeficiencies, a secondary immunodeficiency, and a defect of innate immunity were identified as being susceptible to RuV-associated granulomas. Hematopoietic cell transplantation was the most successful treatment in this case series resulting in granuloma resolution; steroids, and TNF-α and IL-1R inhibitors were moderately effective. In addition to M2 macrophages, neutrophils were identified by immunohistochemical analysis as a novel cell type infected with RuV. Four patterns of RuV-associated granulomatous inflammation were classified based on the structural organization of granulomas and identity and location of cell types harboring RuV antigen. Identification of conditions that increase susceptibility to RuV-associated granulomas combined with structural characterization of the granulomas may lead to a better understanding of the pathogenesis of RuV-associated granulomas and discover new targets for therapeutic interventions.

BACKGROUND: There is uncertainty about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in individuals with rare inborn errors of immunity (IEI), a population at risk of developing severe coronavirus disease 2019. This is relevant not only for these patients but also for the general population, because studies of IEIs can unveil key requirements for host defense. OBJECTIVE: We sought to describe the presentation, manifestations, and outcome of SARS-CoV-2 infection in IEI to inform physicians and enhance understanding of host defense against SARS-CoV-2. METHODS: An invitation to participate in a retrospective study was distributed globally to scientific, medical, and patient societies involved in the care and advocacy for patients with IEI. RESULTS: We gathered information on 94 patients with IEI with SARS-CoV-2 infection. Their median age was 25 to 34 years. Fifty-three patients (56%) suffered from primary antibody deficiency, 9 (9.6%) had immune dysregulation syndrome, 6 (6.4%) a phagocyte defect, 7 (7.4%) an autoinflammatory disorder, 14 (15%) a combined immunodeficiency, 3 (3%) an innate immune defect, and 2 (2%) bone marrow failure. Ten were asymptomatic, 25 were treated as outpatients, 28 required admission without intensive care or ventilation, 13 required noninvasive ventilation or oxygen administration, 18 were admitted to intensive care units, 12 required invasive ventilation, and 3 required extracorporeal membrane oxygenation. Nine patients (7 adults and 2 children) died. CONCLUSIONS: This study demonstrates that (1) more than 30% of patients with IEI had mild coronavirus disease 2019 (COVID-19) and (2) risk factors predisposing to severe disease/mortality in the general population also seemed to affect patients with IEI, including more younger patients. Further studies will identify pathways that are associated with increased risk of severe disease and are nonredundant or redundant for protection against SARS-CoV-2. ispartof: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY vol:147 issue:2 pages:520-531 ispartof: location:United States status: published

Herpes zoster (HZ) can have a substantial impact on quality of life (QoL). The vaccine efficacy (VE) of a recombinant zoster vaccine (RZV) was 68.2% (95% confidence interval [CI], 55.6% to 77.5%) in a phase 3 study in adult autologous hematopoietic stem cell transplant (HSCT) recipients (NCT01610414). Herein, we report the impact of RZV on patients' QoL. Autologous HSCT recipients were randomized 1:1 to receive 2 doses of RZV or placebo, given 1 to 2 months apart. QoL was measured by the Short Form Survey-36 and Euro-QoL-5 Dimension at baseline, 1 month, and 1 year postdose 2 and during suspected HZ episodes with the Zoster Brief Pain Inventory (ZBPI). The RZV impact on ZBPI burden of illness and burden of interference scores was estimated. The 2 scores were calculated from the area under the curve (days 0 to 182) of the ZBPI worst pain and ZBPI activities of daily living scores, respectively, assuming a score of 0 for patients not having a confirmed HZ episode. The ZBPI maximum worst pain score was significantly lower in the RZV than placebo group (mean: 5.8 versus 7.1, P = .011). Consequently, the VE estimates for HZ burden of illness (82.5%; 95% CI, 73.6 to 91.4) and burden of interference (82.8%; 95% CI, 73.3 to 92.3) were higher than the HZ VE estimate (ie, 68.2%). RZV showed significantly better QoL scores than placebo 1 week following rash onset among patients with confirmed HZ. In addition to reducing the risk of HZ and its complications, RZV significantly reduced the impact of HZ on patients' QoL in those who developed breakthrough disease. (C) 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

BACKGROUND: CD40 ligand (CD40L) deficiency, an X-linked primary immunodeficiency, causes recurrent sinopulmonary, Pneumocystis and Cryptosporidium species infections. Long-term survival with supportive therapy is poor. Currently, the only curative treatment is hematopoietic stem cell transplantation (HSCT). OBJECTIVE: We performed an international collaborative study to improve patients' management, aiming to individualize risk factors and determine optimal HSCT characteristics. METHODS: We retrospectively collected data on 130 patients who underwent HSCT for CD40L deficiency between 1993-2015. We analyzed outcome and variables' relevance with respect to survival and cure. RESULTS: Overall survival (OS), event-free survival (EFS), and disease-free survival (DFS) were 78.2%, 58.1%, and 72.3% 5 years after HSCT. Results were better in transplantations performed in 2000 or later and in children less than 10 years old at the time of HSCT. Pre-existing organ damage negatively influenced outcome. Sclerosing cholangitis was the most important risk factor. After 2000, superior OS was achieved with matched donors. Use of myeloablative regimens and HSCT at 2 years or less from diagnosis associated with higher OS and DFS. EFS was best with matched sibling donors, myeloablative conditioning (MAC), and bone marrow-derived stem cells. Most rejections occurred after reduced-intensity or nonmyeloablative conditioning, which associated with poor donor cell engraftment. Mortality occurred mainly early after HSCT, predominantly from infections. Among survivors who ceased immunoglobulin replacement, T-lymphocyte chimerism was 50% or greater donor in 85.2%. CONCLUSION: HSCT is curative in patients with CD40L deficiency, with improved outcome if performed before organ damage development. MAC is associated with better OS, EFS, and DFS. Prospective studies are required to compare the risks of HSCT with those of lifelong supportive therapy. ispartof: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY vol:143 issue:6 pages:2238-2253 ispartof: location:United States status: published

Eighty-eight children 0.5 to 17 years of age (median, 9 years of age) received an unrelated donor marrow transplant for treatment of chronic myeloid leukemia (CML; n = 16), acute lymphoblastic leukemia (ALL) in first or second remission (9 = 15) or more advanced stage (n = 28), acute myeloid leukemia (AML; n = 13), or other hematologic diseases (n = 16) between June 1985 and April 1993. All patients were conditioned with cyclophosphamide and total body irradiation and received a combination of methotrexate and cyclosporine as graft-versus-host disease (GVHD) prophylaxis. Fourty-six patients received transplants from HLA-identical donors and 42 patients received transplants from donors who were minor-mismatched at one HLA-A or B or D/DRB1 locus. The Kaplan-Meier estimates of disease-free survival and relapse were 75% and 0% for patients with CML, 47% and 20% for ALL in first or second remission, 10% and 60% for ALL in relapse or third remission, 46% and 46% for AML in first remission (n = 1) or more advanced disease (n = 12), and 29% and 69% for other diseases. HLA disparity was not significantly associated with lower disease-free survival, but the results suggest more relapses in HLA-matched recipients and there was significantly more transplant-related mortality in mismatched recipients (51% v 24%, P = .04). Most deaths were due to infections associated with acuteor chronic GVHD and occurred within the first 2 years after transplantation. Granulocyte engraftment occurred in all evaluable patients. Sixty-three percent of HLA-matched and 57% of HLA-mismatched recipients were discharged home disease-free at a median of 98 and 103 days, respectively, after transplantation (P = not significant [NS]). The incidence of grades Il-IV acute GVHD was 83% in HLA-matched and 98% in HLA-mismatched recipients (P = .009). The incidence of chronic GVHD was 60% in HLA-matched and 69% in HLA-mismatched recipients (P = NS). One or multiple late adverse events such as cataracts, osteonecrosis of the hip or knee, restrictive or obstructive pulmonary disease, and hypothyroidism have occurred in 11 of 33 (33%) surviving patients. Immunosuppression was discontinued in 58% of surviving patients, including all 12 patients surviving more than 3.2 years, all of whom have a Lansky or Karnofsky score of 100%. These data show that marrow transplantation from fully or partially HLA-matched unrelated donors can be effective therapy for children with hematologic disorders and that pretransplantation disease status and posttransplantation GVHD remain important factors affecting patient outcome. (C) 1995 by The American Society of Hematology.