Use of adenine base editing and homology-independent targeted integration strategies to correct the cystic fibrosis causing variant, W1282X.

Small molecule drugs known as modulators can treat ~90% of people with cystic fibrosis (CF), but do not work for premature termination codon variants such as W1282X (c.3846G>A). Here we evaluated two gene editing strategies, Adenine Base Editing (ABE) to correct W1282X, and Homology-Independent Targeted Integration (HITI) of a CFTR superexon comprising exons 23-27 (SE23-27) to enable expression of a CFTR mRNA without W1282X. In Flp-In-293 cells stably expressing a CFTR expression minigene bearing W1282X, ABE corrected 24% of W1282X alleles, rescued CFTR mRNA from nonsense mediated decay and restored protein expression. However, bystander editing at the adjacent adenine (c.3847A>G), caused an amino acid change (R1283G) that affects CFTR maturation and ablates ion channel activity. In primary human nasal epithelial cells homozygous for W1282X, ABE corrected 27% of alleles, but with a notably lower level of bystander editing, and CFTR channel function was restored to 16% of wild-type levels. Using the HITI approach, correct integration of a SE23-27 in intron 22 of the CFTR locus in 16HBEge W1282X cells was detected in 5.8% of alleles, resulting in 7.8% of CFTR transcripts containing the SE23-27 sequence. Analysis of a clonal line homozygous for the HITI-SE23-27 produced full-length mature protein and restored CFTR anion channel activity to 10% of wild-type levels, which could be increased three-fold upon treatment with the triple combination of CF modulators. Overall, these data demonstrate two different editing strategies can successfully correct W1282X, the second most common class I variant, with a concomitant restoration of CFTR function.

Investigation of CFTR Function in Human Nasal Epithelial Cells Informs Personalized Medicine.

We broaden the clinical versatility of human nasal epithelial (HNE) cells. HNEs were isolated from 10 participants harboring cystic fibrosis transmembrane conductance regulator (CFTR) variants: 9 with rare variants (Q359R [n = 2], G480S, R334W [n = 5], and R560T) and 1 harboring R117H;7T;TG10/5T;TG12. Cultures were differentiated at the air-liquid interface. CFTR function was measured in Ussing chambers at three conditions: baseline, ivacaftor, and elexacaftor + tezacaftor + ivacaftor (ETI). Four participants initiated modulators. Q359R HNEs had 5.4% (% wild-type) baseline CFTR function and 25.5% with ivacaftor. With therapy, sweat [Cl-] decreased and symptoms resolved. G480S HNEs had 4.1% baseline and 32.1% CFTR function with ETI. Clinically, forced expiratory volume in 1 second increased and sweat [Cl-] decreased (119 to 46 mmol/L) with ETI. In vitro cultures derived from 5 participants harboring R334W showed a moderate increase in CFTR function with exposure to modulators. For one of these participants, ETI was begun in vivo; symptoms and forced expiratory volume in 1 second improved. The c.1679G>C (R560T) HNEs had less than 4% baseline CFTR function and no modulator response. RNA analysis confirmed that c.1679G>C completely missplices. A symptomatic patient harboring R117H;7T;TG10/5T;TG12 exhibited reduced CFTR function (17.5%) in HNEs, facilitating a diagnosis of mild CF. HNEs responded to modulators (ivacaftor: 32.8%, ETI: 55.5%), and, since beginning therapy, lung function improved. We reaffirm HNE use for guiding therapeutic approaches, inform predictions on modulator response (e.g., R334W), and closely assess variants that affect splicing (e.g., c.1679G>C). Notably, functional studies in HNEs harboring R117H;7T;TG10/5T;TG12 facilitated a diagnosis of mild CF, suggesting the use for HNE functional studies as a clinical diagnostic test.

Challenging the dogma of the healthy heterozygote: Implications for newborn screening policies and practices.

Heterozygous (carrier) status for an autosomal recessive condition is traditionally considered to lack significance for an individual's health, but this assumption has been challenged by a growing body of evidence. Carriers of several autosomal recessive disorders and some X-linked diseases are potentially at risk for the pathology manifest in homozygotes. This minireview provides an overview of the literature regarding health risks to carriers of two common autosomal recessive conditions on the Recommended Uniform Screening Panel: sickle cell disease [sickle cell trait (SCT)] and cystic fibrosis (CF). We also consider and comment on bioethical and policy implications for newborn blood screening (NBS). Health risks for heterozygotes, while relatively low for individuals, are often influenced by intrinsic (e.g., other genomic variants or co-morbidities) and extrinsic (environmental) factors, which present opportunities for personalized genomic medicine and risk counseling. They create a special challenge, however, for developing screening/follow-up policies and for genetic counseling, particularly after identification and reporting of heterozygote status through NBS. Although more research is needed, this minireview of the SCT and CF literature to date leads us to propose that blanket terms such as "healthy heterozygotes" or "unaffected carriers" should be superseded in communications about NBS results, in favor of a more nuanced paradigm of setting expectations for health outcomes with "genotype-to-risk." In the molecular era of NBS, it remains clear that public health needs to become better prepared for the full range of applied genetics.

The CFTR variant profile of Hispanic patients with cystic fibrosis: Impact on access to effective screening, diagnosis, and personalized medicine.

Hispanic patients comprise an appreciable and increasing proportion of patients with cystic fibrosis (CF) in the United States (US). Hispanic patients with CF are known to have increased morbidity and mortality compared to non-Hispanic white patients with CF, and ongoing investigations are underway to identify contributing factors amenable to intervention in order to address the disparate health outcomes. One contributing factor is the different CF transmembrane conductance regulator (CFTR) variant profile observed in Hispanic patients with CF. The most common CFTR variant, p.Phe508del (legacy name F508del), is proportionally underrepresented in Hispanic patients with CF. This difference has implications for prenatal screening, newborn screening (NBS), and CFTR variant-specific therapeutic options. In particular, the recent approval of a highly effective CFTR modulator for patients carrying at least one copy of F508del, elexacaftor/tezacaftor/ivacaftor triple combination therapy, underscores the potential for unequal access to personalized treatment for Hispanic patients with CF. We report the CFTR variant profiles of Hispanic patients with CF and non-CF Hispanic infants with a false-positive New York State CF NBS at a single center in New York City over a 5-year study period, as an opportunity to address the racial and ethnic disparities that currently exist in CF screening, diagnosis, and treatment. In addition to the previously documented disparate prevalence of the CFTR variant F508del in Hispanic patients, we observed two CFTR variants, p.His609Arg (legacy name H609R) and p.Thr1036Asn (legacy name T1036N), frequently identified in our Hispanic patients of Ecuadorian and Mexican ancestry, respectively, that are not well-described in the US population. The presence of population-specific and individually rare CFTR variants in Hispanic patients with CF further accentuates the disparity in health outcomes, as these CFTR variants are often absent from prenatal and NBS CFTR variant panels, potentially delaying diagnosis, and without an approved CFTR variant-specific therapy.

Practice variation of genetic counselor engagement in the cystic fibrosis newborn screen-positive diagnostic resolution process.

Families of infants with a positive newborn screen for cystic fibrosis (CFNBS+) have well-characterized genetic counseling needs, including understanding the implications of diagnostic categorization. However, degree of involvement of genetic counselors (GCs) in the CFNBS+ diagnostic resolution process varies. This project explored GC engagement with US CF care centers in the diagnostic resolution process for CFNBS+ infants. Surveys were emailed to 713 Cystic Fibrosis Foundation-accredited CF center directors and clinic coordinators and 4,517 GCs. Respondents from institutions providing CFNBS+ diagnostic resolution were categorized by level of engagement between the CF center and GC: GC is part of or embedded in CF center (GC-engaged); GC is independent of CF center but receives CFNBS+ referrals (GC-referral); GC is uninvolved (non-engaged)] in CF center or CFNBS+ diagnostic resolution process. Responses from 125 CF center directors and clinic coordinators (17.5%) and 174 GCs (3.8%) were received. Analysis targeted responses from 84 center directors and clinic coordinators and 52 GCs, estimated to represent 24%-48% and 29% of 175 pediatric CF care centers, respectively. Nearly 40% of CF center directors or clinic coordinators never refer CFNBS+ infants to GCs. Respondents from GC-engaged CF centers reported that GCs provide unique and valuable services, understand CF at a high level, improve efficiency of the CFNBS+ diagnostic resolution process, and should be part of the CF care team; respondents from non-engaged CF centers reported negative views of GCs' value and knowledge (all p < .05). GCs engaged with CF centers were more likely to report that their services were valued by and accessible to CF centers (both p < .05). At all levels of engagement with CF centers, GCs were comfortable discussing CF genotype-phenotype correlation, variants of unknown significance, quality of life, and therapies. These results highlight a need to address practice variation in CFNBS+ genetic counseling and improve access to GCs' services.

Trajectories of caregiver burden in families of adult cystic fibrosis patients.

ABSTRACTObjectives:Little is known about the experience of family caregivers of adults with cystic fibrosis (CF). This information is important for the identification of caregivers at risk for burden. METHODS: This was a longitudinal analysis of survey data obtained from caregivers of adult CF patients participating in an early intervention palliative care trial. Caregivers completed the validated Brief Assessment Scale for Caregivers (BASC) repeatedly over a 28-month period. Mixed-effects modeling evaluated multivariate associations with positive and negative caregiver perceptions over time. RESULTS: Of the 54 caregivers, 47.9% were spouses. The mean age was 50.9 years (SD = 13.2); 72.2% were women; 75.9% were married; and 63.0% were employed. At baseline, the BASC revealed large variations in positive and negative perceptions of caregiving. Although average scores over time were unchanging, variation was greater across caregivers than within caregivers (0.49 vs. 0.27, respectively). At baseline, the positive impact of caregiving in the sample was higher than the negative impact. Multivariate analysis revealed that patients' baseline pulmonary function and their full-time employment status predicted caregiver burden over time. SIGNIFICANCE OF RESULTS: Caregivers of CF patients varied in their positive and negative caregiving experiences, although burden levels in individual caregivers were stable over time. When the disease was advanced, caregivers of CF patients experienced more overall burden but also more positive impact. This suggests that the role of caregivers may become more meaningful as disease severity worsens. In addition, full-time patient employment was associated with lower caregiver burden regardless of disease severity. This suggests that burden in CF caregivers may be predicted by financial strain or benefits conferred by patient employment. These associations require further investigation to determine whether highly burdened caregivers can be identified and assisted using tailored interventions.

Effect of esomeprazole versus placebo on pulmonary exacerbations in cystic fibrosis.

BACKGROUND: Gastro esophageal reflux (GER) is common in cystic fibrosis (CF) and may contribute to lung disease. Approximately 50% of patients with cystic fibrosis are being treated with proton pump inhibitors (PPIs). METHODS: In a randomized controlled study in adults, we compared treatment with esomeprazole 40 mg twice daily versus placebo in patients with CF and frequent respiratory exacerbations over a thirty-six week treatment period to determine effect on time to first exacerbation and other health related outcomes. RESULTS: 17 patients without symptoms of GER were randomized and 15 completed the study. 13 subjects underwent 24 hour ambulatory pH probe monitoring; 62% had pH probe evidence of GER. Forty one percent of subjects had a pulmonary exacerbation during the study. There was no significant difference in time to first pulmonary exacerbation (log rank test p = 0.3169). Five of nine subjects in the esomeprazole group compared with 2 of eight subjects in the placebo group experienced exacerbations (esomeprazole vs. placebo: odds ratio = 3.455, 95% CI = (0.337, 54.294), Fisher's exact test: p = 0.334). There was no change in Forced Expiratory Volume in one second, Gastroesophageal Symptom Assessment Score or CF Quality of Life score between the two treatment groups. CONCLUSIONS: There was a trend to earlier exacerbation and more frequent exacerbations in subjects randomized to esomeprazole compared with placebo. The effect of proton pump inhibitors on pulmonary exacerbations in CF warrants further investigation. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov, NCT01983774.

Molecular testing for cystic fibrosis carrier status practice guidelines: recommendations of the National Society of Genetic Counselors.

PURPOSE: To provide practice recommendations for genetic counselors whose clients are considering cystic fibrosis (CF) carrier testing or seeking information regarding CF molecular test results. The goals of these recommendations are to: 1) Provide updated information about the natural history, diagnosis, and treatment of CF and related conditions. 2) Supplement genetic counselors' knowledge and understanding of the available carrier screening and diagnostic testing options. 3) Describe the current state of genotype/phenotype correlations for CFTR mutations and an approach to interpreting both novel and previously described variants. 4) Provide a framework for genetic counselors to assist clients' decision-making regarding CF carrier testing, prenatal diagnosis, and pregnancy management. Disclaimer The practice guidelines of the National Society of Genetic Counselors (NSGC) are developed by members of the NSGC to assist genetic counselors and other health care providers in making decisions about appropriate management of genetic concerns; including access to and/or delivery of services. Each practice guideline focuses on a clinical or practice-based issue, and is the result of a review and analysis of current professional literature believed to be reliable. As such, information and recommendations within the NSGC practice guidelines reflect the current scientific and clinical knowledge at the time of publication, are only current as of their publication date, and are subject to change without notice as advances emerge.In addition, variations in practice, which take into account the needs of the individual patient and the resources and limitations unique to the institution or type of practice, may warrant approaches, treatments and/or procedures that differ from the recommendations outlined in this guideline. Therefore, these recommendations should not be construed as dictating an exclusive course of management, nor does the use of such recommendations guarantee a particular outcome. Genetic counseling practice guidelines are never intended to displace a health care provider's best medical judgment based on the clinical circumstances of a particular patient or patient population.Practice guidelines are published by NSGC for educational and informational purposes only, and NSGC does not "approve" or "endorse" any specific methods, practices, or sources of information.

When chronicity meets cyclicity: The cultivation of embodied knowledge and selfhood by cis-gender women with cystic fibrosis.

This article offers the case of cystic fibrosis (CF), a multi-system disease, to illustrate how individuals with chronic illness cultivate and apply embodied knowledge to optimize their well-being. We identified three interrelated processes that occur when disease chronicity and menstrual cyclicity meet: 1) knowledge production with a period-tracking app; 2) application of embodied knowledge to manage life with menstrual-related CF symptoms; 3) cultivation of the body-self as a menstruating woman with CF. These dynamic processes capture how cis-gender women with CF attune to their bodies, navigate their illness, and situate themselves within their lifeworlds. Genetic conditions like CF are apt for studying these processes because adults have managed their disease for decades, with longitudinal experience that often exceeds that of their clinicians. Our evidence elucidates the co-constitutive nature of chronic disease, gendered subjectivity, and biological processes in flux. We explored the menstrual cyclicity of chronic disease symptoms by having 72 participants track their CF symptoms across 4 menstrual cycles on a customized period-tracking app. We performed semi-structured interviews with 20 participants to understand how they interpreted these cyclical CF symptoms. We learned that digital tracking attuned participants to monthly fluctuations in CF symptoms. They applied this knowledge to manage their lives and shape their sense of self. We argue that women with CF produce distinct embodied knowledge during their reproductive years, shaping their illness experience, disease management, overall health, quality of life, and selfhood. The dynamics we describe may reflect broader patterns by which women with other chronic illnesses experience their bodies and understand themselves in the world.

Genetic counseling access and service delivery in New York State is variable for parents of infants with complex CFTR genotypes conferring uncertain phenotypes.

BACKGROUND: New York State (NYS) utilizes a three-tiered cystic fibrosis newborn screening (CFNBS) algorithm that includes cystic fibrosis transmembrane conductance regulator (CFTR) gene sequencing. Infants with >1 CFTR variant of potential clinical relevance, including variants of uncertain significance or varying clinical consequence are referred for diagnostic evaluation at NYS cystic fibrosis (CF) Specialty Care Centers (SCCs). AIMS: As part of ongoing quality improvement efforts, demographic, screening, diagnostic, and clinical data were evaluated for 289 CFNBS-positive infants identified in NYS between December 2017 and November 2020 who did not meet diagnostic criteria for CF and were classified as either: CFTR-related metabolic syndrome/CF screen positive, inconclusive diagnosis (CRMS/CFSPID) or CF carriers. RESULTS: Overall, 194/289 (67.1%) had CFTR phasing to confirm whether the infant's CFTR variants were in cis or in trans. Eighteen complex alleles were identified in cis; known haplotypes (p.R117H+5T, p.F508del+p.L467F, and p.R74W+p.D1270N) were the most common identified. Thirty-two infants (16.5%) with all variants in cis were reclassified as CF carriers rather than CRMS/CFSPID. Among 263 infants evaluated at an NYS SCC, 70.3% were reported as having received genetic counseling about their results by any provider, with 96/263 (36.5%) counseled by a certified genetic counselor. CONCLUSION: Given the particularly complex genetic interpretation of results generated by CFNBS algorithms including sequencing analysis, additional efforts are needed to ensure families of infants with a positive CFNBS result have CFTR phasing when needed to distinguish carriers from infants with CRMS/CFSPID, and access to genetic counseling to address implications of CFNBS results.

Cystic Fibrosis Foundation Evidence-Based Guideline for the Management of CRMS/CFSPID.

A multidisciplinary committee developed evidence-based guidelines for the management of cystic fibrosis transmembrane conductance regulator-related metabolic syndrome/cystic fibrosis screen-positive, inconclusive diagnosis (CRMS/CFSPID). A total of 24 patient, intervention, comparison, and outcome questions were generated based on surveys sent to people with CRMS/CFSPID and clinicians caring for these individuals, previous recommendations, and expert committee input. Four a priori working groups (genetic testing, monitoring, treatment, and psychosocial/communication issues) were used to provide structure to the committee. A systematic review of the evidence was conducted, and found numerous case series and cohort studies, but no randomized clinical trials. A total of 30 recommendations were graded using the US Preventive Services Task Force methodology. Recommendations that received ≥80% consensus among the entire committee were approved. The resulting recommendations were of moderate to low certainty for the majority of the statements because of the low quality of the evidence. Highlights of the recommendations include thorough evaluation with genetic sequencing, deletion/duplication analysis if <2 disease-causing variants were noted in newborn screening; repeat sweat testing until at least age 8 but limiting further laboratory testing, including microbiology, radiology, and pulmonary function testing; minimal use of medications, which when suggested, should lead to shared decision-making with families; and providing communication with emphasis on social determinants of health and shared decision-making to minimize barriers which may affect processing and understanding of this complex designation. Future research will be needed regarding medication use, antibiotic therapy, and the use of chest imaging for monitoring the development of lung disease.

Reproductive Counseling and Care in Cystic Fibrosis: A Multidisciplinary Approach for a New Therapeutic Era.

With the advent of highly effective modulator therapies, many people with cystic fibrosis (CF) are living longer, healthier lives. Pregnancy rates for women with CF more than doubled between 2019 and 2021, reflecting increases in both planned and unplanned pregnancies. For men with CF, CF-associated infertility can be mitigated with assistive reproductive technology, yet patient knowledge of these challenges and options is variable. Preconception and prenatal counseling for individuals with CF and for parents of children with CF who wish to expand their families requires nuanced discussions to promote informed reproductive decisions, drawing from a combination of standard practice recommendations and CF-specific assessments. This review article synthesizes the current literature and practice recommendations regarding reproductive counseling and care in CF, outlining the role of genetic counseling, carrier screening, teratogen counseling, in vitro fertilization and pre-implantation genetic diagnosis, and careful assessment and management of cystic fibrosis-related diabetes when present. Via a multidisciplinary, patient-centered approach, clinicians can support adults with CF and parents of children with CF as they make informed reproductive decisions and embark on family planning.

Diagnostic and Communication Challenges in Cystic Fibrosis Newborn Screening.

As of December 2009, cystic fibrosis (CF) newborn screening (NBS) is performed in all 50 US states and the District of Columbia. Widespread implementation of CF newborn screening (CFNBS) in the US and internationally has brought about new and varied challenges. Immunoreactive trypsinogen (IRT) remains the first, albeit imperfect, biomarker used universally in the screening process. Advances in genetic testing have provided an opportunity for newborn screening programs to add CFTR sequencing tiers to their algorithms. This in turn will enable earlier identification of babies with CF and improve longer-term outcomes through prompt treatment and intervention. CFTR sequencing has led to the ability to identify infants with CF from diverse ethnic and racial backgrounds more equitably while also identifying an increasing proportion of infants with inconclusive diagnoses. Using the evolution of the New York State CF newborn screening program as a guide, this review outlines the basic steps in a universal CF newborn screening program, considers how to reduce bias, highlights challenges, offers guidance to address these challenges and provides recommendations for future consideration.

Center-level self-study identifies opportunities to advance equity in cystic fibrosis clinical trial participation.

Clinical trials are a necessary tool for evaluating the effectiveness of newly developed treatments and interventions for cystic fibrosis (CF). Prior work demonstrated a proportional underrepresentation of people with CF (pwCF) identifying as part of a minoritized racial or ethnic group in clinical trials. In order to establish a baseline for improvement efforts, we undertook a center-level self-study to evaluate if the racial and ethnic backgrounds of pwCF participating in clinical trials at our CF Center in New York City reflect our overall patient diversity (N = 200; 55 pwCF identifying as part of a minoritized racial or ethnic group and 145 pwCF identifying as non-Hispanic White). A smaller proportion of pwCF identifying as part of a minoritized racial or ethnic group participated in a clinical trial as compared to pwCF identifying as non-Hispanic White (21.8% vs. 35.9%, P = 0.06). A similar trend was present for pharmaceutical clinical trials (9.1% vs. 16.6%, P = 0.3). When limiting the study population to the pwCF most likely to be eligible for a CF pharmaceutical clinical trial, a larger proportion of pwCF identifying as part of a minoritized racial or ethnic group participated in a pharmaceutical clinical trial as compared to pwCF identifying as non-Hispanic White (36.4% vs. 19.6%, P = 0.2). No pwCF identifying as part of a minoritized racial or ethnic group participated in an offsite clinical trial. Efforts to improve the racial and ethnic diversity of pwCF in clinical trials, both onsite and offsite, will require a shift in how recruitment opportunities are identified and communicated to pwCF.

Genetic counseling access for parents of newborns who screen positive for cystic fibrosis: Consensus guidelines.

INTRODUCTION: A risk associated with cystic fibrosis newborn screening (CFNBS) is parental misunderstanding of genetic information generated by the over 6600 positive screens reported annually in the United States. CFNBS algorithms incorporating DNA analysis can generate genetic information that requires clinical interpretation and has significance for the newborn, parents, and other relatives. Engagement between CF care centers and trained genetic counseling providers, such as licensed and/or certified genetic counselors (GCs), is variable and limited in providing information to CFNBS positive (CFNBS+) families. METHODS: Using a modified Delphi process, a workgroup of CFNBS experts developed recommendation statements for engagement of genetic counseling services in CF care centers where CFNBS + diagnostic evaluations are performed. Statements were assessed over three rounds of surveys, one face-to-face meeting, and through public feedback. RESULTS: Seventeen statements achieved >80% consensus (range: 82%-100%). The workgroup affirmed prior CFF policy statements recommending genetic counseling for parents of infants with CFNBS+. The remaining statements addressed infrastructure and logistics of genetic counseling services, including defining appropriate training for genetic counseling providers and counseling content, establishing a path to equal access to genetic counseling providers across CF care centers, and setting a standard for client-centered CFNBS genetic counseling that is respectful of diverse patient needs and autonomy. CONCLUSIONS: Implementation of client-centered genetic counseling for CFNBS+ families in CF care centers by providers with expertise in both CF and genetic counseling will require efforts to further define core concepts, enhance the education of providers, and develop opportunities for access via telemedicine.

Bridging the Gap between Scientific Advancement and Real-World Application: Pediatric Genetic Counseling for Common Syndromes and Single-Gene Disorders.

Screening and diagnostic testing for single-gene disorders and common syndromes in the pediatric setting frequently generate data that are challenging to interpret, and the ability to diagnose genetic conditions has outpaced the development of successful treatments or cures. Genetic testing is now integrated purposefully into a variety of primary and specialty care clinics, creating an increased requirement for genetic literacy among providers and patients, as well as a growing need to incorporate genetic counseling services into mainstream clinical practice. The practice of pediatric genetic counseling encompasses a unique combination of skills and training designed to address the evolving psychological, social, educational, medical, and reproductive concerns of patients and their families, which complements the multidisciplinary services of physicians, nurses, and other allied health professionals caring for patients with pediatric-onset genetic conditions. The potential range of genetic counseling needs in the pediatric setting transcends the diagnostic period. The sustained nature of pediatric care presents opportunities for development of trusting and longstanding professional relationships that permit the evolving genetic counseling needs of patients and families to be met. A discussion of cystic fibrosis, a common autosomal recessive single-gene disorder with an increasingly broad clinical spectrum and genotype-phenotype variability, serves as a useful case study to illustrate the current and emerging genetic counseling practices, goals, and challenges impacting patients and their families.

Addressing the burden of illness in adults with cystic fibrosis with screening and triage: An early intervention model of palliative care.

BACKGROUND: Novel models that improve generalist-level palliative care for cystic fibrosis (CF) are needed to address the burden of this illness. A screening-and-triage model has the potential to identify clinical problems requiring immediate follow-up by CF professionals. This study describes such a model and its immediate impact on care delivery for CF patients during a two-year period. METHODS: Eligible adults completed monthly online screening for sources of distress. If results revealed one or more "indicators of concern" on two consecutive screenings, this triggered an attempted triage by a social worker. Completed triages led to prompt follow-up by CF professionals for clinical problems, if indicated. Process data were summarized and generalized linear mixed models were used to evaluate baseline patient characteristics (symptom distress, quality of life, and sociodemographics) associated with the need for prompt follow-up. RESULTS: A total of 1,015 monthly surveys were completed by 74 patients; 634 (66 patients) had >1 indicators of concern; and 164 surveys (46 patients) had >1 indicators for two consecutive surveys (e.g., global distress, pain, dyspnea, and psychological symptoms). The 164 attempted triages yielded 84 completed triages (51.2%), of which 39 (46.4%) required prompt follow-up. In multivariable analyses, older patients and those with higher symptom distress at baseline were more likely to require prompt follow-up (p < .05). CONCLUSIONS: Web-based screening that assesses varied domains of distress or burden can identify a subset of CF patients whose clinical problems may benefit from immediate medical or psychological attention. Additional investigations should improve screening efficiency.

Perinatal transfer of genetic information: developing an algorithm for reporting cystic fibrosis prenatal test results to the newborn screening program.

PURPOSE: This study explored the feasibility of statewide reporting of cystic fibrosis fetal diagnostic testing results to the newborn screening program through the birth hospital. METHODS: We evaluated trends in offering and documenting cystic fibrosis carrier screening among prenatal care providers through a survey of 100 medical records of patients who gave birth at St. Vincent's Hospital Manhattan. The hospital's protocol for reporting human immunodeficiency virus testing history to the state program was delineated and adapted in developing an algorithm for cystic fibrosis. Feedback from hospital staff with regard to data transcription and the prospect of transferring cystic fibrosis prenatal information was obtained. RESULTS: Of 98 patients who had prenatal records made available to the birth hospital, 62% had cystic fibrosis carrier screening, 14% declined screening, and 24% had no documentation of their screening history. The hospital staff viewed the transcription of information as relatively simple; however, missing information is a common occurrence that delays the process and results in incomplete data transfer. CONCLUSIONS: Perinatal transfer of cystic fibrosis prenatal information modeled on the system used for reporting human immunodeficiency virus testing history is feasible. However, it will require standardized reporting of cystic fibrosis screening and testing history on the mother's prenatal records among prenatal care providers.