Life-shortening Condition Research Articles

Patient-Reported Outcomes in Idiopathic Pulmonary Fibrosis Research

Patient-reported outcomes (PROs) include questionnaires or surveys that ask patients for their perceptions about things like symptoms they are experiencing or quality of life. For incurable, morbid, life-shortening conditions like idiopathic pulmonary fibrosis (IPF), PROs are particularly germane: They elucidate for clinicians and researchers what it is like for patients to live with such a disease, and they may detect important treatment effects not captured by other metrics (eg, pulmonary physiology). However, a relative paucity of research on PROs in IPF has left significant knowledge gaps in this area and contributed to the timidity investigators have about using PROs as prominent outcomes in IPF drug trials. Additional research on existing instruments is needed to establish or bolster their basic psychometric properties in IPF. When PROs are used as end points in therapeutic trials, analyzing PRO response data can be challenging, but these challenges can be overcome with a transparent, thoughtful, and sophisticated statistical approach. In this article, we discuss some of the basics of PRO assessment, existing knowledge gaps in IPF-related PRO research, and the potential usefulness of using PROs in IPF trials and conclude by offering specific recommendations for an approach to analyzing repeated-measures PRO data from IPF trials.

Differences in perceptions of palliative care needs for children with neurological conditions

ObjectivesTo explore paediatric subspecialities' roles and their perceptions of the need for palliative care among children with long term neurological conditions (LTNC) compared with paediatric palliative care specialists. To examine...

Treating cystic fibrosis infection, inflammation and ion channels

chloride and hyperabsorption of sodium ions results in a reduction in the height of airways surface liquid and subsequent dysfunctional mucociliary clearance. This defect results in chronic infection, which drives inflammation and subsequent lung destruction from proteolytic enzymes primarily from host neutrophils [5]. To significantly perturb this pathogenesis the current strategies are to optimize the clearance of infected mucus, reduce inflammation and treat acute and chronic infection [4]. However the ultimate goal is to find therapies that will correct the basic defect using strategies, such as gene therapy or small molecule correctors and potentiators [6,7]. In this edition of Therapy these issues are explored by a number of experts in the field. In most developed countries CF is diagnosed in the neonatal period following newborn screening programs. This allows for early preventative interventions which, if effective, could be disease modifying by preventing early infection [8]. Wainwright and colleagues discuss the importance of developing a proper evidence base for such interventions, in spite of the difficulty of designing studies in infants and small children where surrogate measures of lung function, for example, are difficult [9,10]. Therapies that correct the basic defect are likely to be most effective in this early stage of disease development. It is critically important that clinical trial design and outcome measures are developed to determine whether the exciting new therapies, such as potentiators and correctors, are truly disease modifying. There are a range of exciting new approaches with small molecules to modulate CFTR function, discussed by de Boeck and Cuppens [11]. Disease modifying drugs are currently in In this issue of Therapy, cystic fibrosis (CF), one of the most devastating autosomal recessive disorders in man is discussed. This condition, which was only properly recognized in the 1940s, had a very poor prognosis at that time with most children dying in their first decade of life [1]. Since then the introduction of multidisciplinary center care, the use of effective pancreatic enzyme replacement therapy and antipseudomonal antibiotics has progressively improved outcomes. Median survival in most developed countries is now around 40 years and the anticipated median survival for children born in the current decade is into the sixth decade of life [2]. This success has been achieved by improving nutrition and controlling infection and inflammation by optimizing the clearance of infected mucus from the airway and using aggressive antibiotic therapy. However, CF remains a life-shortening condition with median age of death still stubbornly in the mid-to-late 20s. New and transformative therapies are therefore required for this condition.

Home based volunteers – bridging the gap between respite visits

IntroductionThe project was conceived as a result of two observations. The hospice receives many applications from people keen to volunteer directly with children and young adults. Secondly the Care Team...

Ethics in the Treatment of Advanced Heart Failure: Palliative Care and End-of-Life Issues

Advanced heart failure (HF) is a life-shortening condition, yet there are increasing treatments and implantable devices available to clinicians to manage patients with advanced HF. Planning for adverse events and the end of life, formulated as "preparedness planning," can be integrated into HF care early in illness. Discussions that acknowledge the uncertainty of HF course and length of life and incorporate patient and family goals and values facilitates this planning. Clear processes for weighing potential benefits and burdens of interventions and therapies should accompany decision-making. Device implantation decision-making can acknowledge alternative avenues of care to the device and identify situations in which the device might be deactivated in the future. Symptom assessment and management potentially improve quality of life in patients with advanced HF. Management of symptoms should integrate HF therapies as well as other treatments. Collaboration between HF providers, palliative care clinicians, and, if appropriate, hospice clinicians will improve care for HF patients and their families.

A 50% higher prevalence of life-shortening chronic conditions among cancer patients with low socioeconomic status

Background:Comorbidity and socioeconomic status (SES) may be related among cancer patients.Method:Population-based cancer registry study among 72 153 patients diagnosed during 1997–2006.Results:Low SES patients had 50% higher risk of serious comorbidity than those with high SES. Prevalence was increased for each cancer site. Low SES cancer patients had significantly higher risk of also having cardiovascular disease, chronic obstructive pulmonary diseases, diabetes mellitus, cerebrovascular disease, tuberculosis, dementia, and gastrointestinal disease. One-year survival was significantly worse in lowest vs highest SES, partly explained by comorbidity.Conclusion:This illustrates the enormous heterogeneity of cancer patients and stresses the need for optimal treatment of cancer patients with a variety of concomitant chronic conditions.

Early bronchiectasis in cystic fibrosis detected by surveillance CT

There is emerging evidence that cystic fibrosis lung disease begins early in infancy. Newborn screening allows early detection and surveillance of pulmonary disease and the possibility of early intervention in this life-shortening condition. We report two children with cystic fibrosis who underwent a comprehensive assessment from diagnosis that included measurement of lung function, limited-slice high-resolution CT and BAL performed annually. Early aggressive surveillance enabled significant lung disease and bronchiectasis to be detected during the first few years of life and led to a change in management, highlighting a clinical role for CT scanning during the preschool years in children with cystic fibrosis.

Population‐based carrier screening for cystic fibrosis in Victoria: The first three years experience

Cystic fibrosis (CF) is the most common inherited, life-shortening condition affecting Australian children. The carrier frequency is one per 25 and most babies with CF are born to parents with no family history. Carrier testing is possible before a couple has an affected infant. To report the outcomes of a carrier screening program for CF. Carrier screening was offered to women and couples planning a pregnancy, or in early pregnancy, through obstetricians and general practitioners in Victoria, Australia. Samples were collected by cheek swab and posted to the laboratory. Twelve CFTR gene mutations were tested. Carriers were offered genetic counselling and partner testing. Carrier couples were offered prenatal testing by chorionic villous sampling (CVS) if pregnant. The number of people tested, carriers detected and pregnancy outcomes were recorded from January 2006 to December 2008. A total of 3200 individuals were screened (3000 females). One hundred and six carriers were identified (one per 30, 95% confidence interval one per 25, one per 36). All carrier partners were screened, and nine carrier couples identified (total carriers 115). Ninety-six individuals (83%) were carriers of the p.508del mutation. Of the nine carrier couples, six were pregnant at the time of screening (five natural conception and one in vitro fertilisation) and all had CVS (mean gestation 12.5 weeks). Two fetuses were affected, three were carriers and one was not a carrier. Termination of pregnancy was undertaken for the affected fetuses. Carrier screening for CF by obstetricians and general practitioners by cheek swab sample can be successfully undertaken prior to pregnancy or in the early stages of pregnancy.

Parental Depression Following the Early Diagnosis of Cystic Fibrosis: A Matched, Prospective Study

To assess risks for parental depression following the diagnosis of cystic fibrosis (CF) in a child. Matched cohort study in NW England; 45 parental couples with a child diagnosed with CF were compared with 45 control couples matching for age, sex, and position in the family of the index child. The Beck Depression Inventory (BDI-II) with a clinical cut-off > or = 13 for dysphoria (mild depression) was the main outcome. A stratified analysis was conducted using the Mantel-Haenszel risk-ratio estimator (RR(MH)) with eight strata for each of the matching variable combinations. Heterogeneity was found within the dataset. Parents with a child with CF < or = 9 months of age at baseline had an elevated prospective risk of depression (mothers RR(MH) [95% confidence interval (CI)] = 2.6[1.05,6.42], fathers RR(MH) [95%CI] = 2.26 [0.97,5.28]). The absence of a group effect for depression at follow-up after adjusting for the matching (mothers RR(MH) [95%CI] = 1.1 [0.59,2.05], fathers RR(MH) [95%CI] = 1.42 [0.66,3.08]) masked this heterogeneity. This hypothesis-generating finding suggests that parents may be more vulnerable to depression when their child is diagnosed with a life-shortening condition during the first few months of life. Mood in parents of infants diagnosed early needs to be monitored longitudinally and preventative strategies devised.

Pediatric Do-Not-Attempt-Resuscitation Orders and Public Schools: A National Assessment of Policies and Laws

Some children living with life-shortening medical conditions may wish to attend school without the threat of having resuscitation attempted in the event of cardiopulmonary arrest on the school premises. Despite recent attention to in-school do-not-attempt-resuscitation (DNAR) orders, no assessment of state laws or school policies has yet been made. We therefore sought to survey a national sample of prominent school districts and situate their policies in the context of relevant state laws. Most (80%) school districts sampled did not have policies, regulations, or protocols for dealing with student DNARs. A similar majority (76%) either would not honor student DNARs or were uncertain about whether they could. Frequent contradictions between school policies and state laws also exist. Consequently, children living with life-shortening conditions who have DNARs may not have these orders honored if cardiopulmonary arrest were to occur on school premises. Coordinated efforts are needed to harmonize school district, state, and federal approaches in order to support children and families' right to have important medical decisions honored.

The Challenge of DNAR Orders in Schools

The target article provides us with an excellent survey of the practices of school districts in dealing with DNAR orders for children with life-shortening conditions and the important consideration...

Heart disease prevalence in school children in two Colorado communities.

THE FREQUENCIES of heart disease in children of school age are obtained by delineation of a school population at risk of disease. Examinations are performed upon either the whole population or a sample selected from it. Earlier surveys concentrated upon the entity, rheumatic heart disease, a sequela of acute rheumatic fever. This chronic, progressive, life-shortening condition was apparently more common and more severe in western Europe and North America during the early part of this century and the two previous centuries than it is today. Acute rheumatic fever seems to be declining noticeably in severity.70 Rheumatic heart disease mortality rates also seem to have fallen over this same period of time.65 It would be interesting to know whether rheumatic heart disease prevalence rates are lower, too. Unfortunately, direct numerical comparisons cannot be made freely because auscultatory diagnostic criteria have been significantly refined, especially during recent years.72 Improved diagnosis was probably largely due to increasingly successful cardiac surgery, which demanded accurate preoperative diagnosis. As rheumatic fever is becoming less severe, typical cases are fewer. and the diagnosis is probably more difficult in a larger proportion of cases now than in years past. All are familiar with the one-third to one-half of cases of chronic rheumatic heart disease (RHD) which have never experienced an attack of acute rheumatic fever. One may legitimately wonder whether such cases are actually caused by rheumatic fever (undiagnosed or subclinical) or whether a whole spectrum of inflammatory agents can cause endocarditis with valvular deformities. Silber has reported cases of acute and chronic myocarditis with heart murmurs simulating those of RHD, and it is his belief that the label of RHD is too loosely applied in the absence of a positive history of rheumatic stigmata.73 Saphir reports the same phenomena.75 Endocardial elastomyofibrosis occurs predominantly in young adults but has been reported in adolescents and could easily be misdiagnosed as RHD.74 Brucellosis can cause chronic progressive aortic valvular stenosis, although this infection is thought to be rare in children.69 Studies with experimental animals suggest that