Introduction of a collaborative quality improvement program in the French cystic fibrosis network: the PHARE-M initiative

Background

An agreement, signed in 2007 by the 49 French Cystic Fibrosis Centers, included a commitment to participate, within the next 5 years, in a care quality assessment and improvement program (QIP). The objective was to roll out in the French Cystic Fibrosis (CF) care network a QIP adapted from the US program for Accelerating Improvement in Cystic Fibrosis Care developed by The Dartmouth Institute Microsystem Academy (TDIMA) and customized by the US CF Foundation between 2002 and 2013.

Methods

The French national team at the Nantes-Roscoff CF Center of Expertise was trained at TDIMA and visited US CF centers involved in US Learning and Leadership Collaboratives (LLCs). It introduced the PHARE-M QIP in France by transposing the Action Guide and material. A PHARE-M LLC1 including seven centers, underwent two external assessments. Adjustments were made, then a PHARE-M LLC2 was rolled out at seven more centers in two regions. On-site coaching was strengthened. The teams’ satisfaction was assessed and further adjustments were made. In 2014, the program sought recognition as a continuing education program for healthcare professionals.

Results

Ninety-six trainees including 14 patients/parents from the 14 CFCs volunteered to participate, test and adapt the program during LLC1 and LLC2 sessions. Comparison of patient outcomes collected in the Registry report by CF center, reflection on potential best practices, selection by each team of an improvement theme, implementation of improvement actions, and exchanges between teams fostered the adhesion of the teams. The program strengthened quality of care, interdisciplinary functioning and collaboration with patients/parents at the centers. The satisfaction expressed by the teams increased over time. A post-PHARE-M cycle maintains the focus on continuous quality improvement (CQI). In 2015, PHARE-M was recognized as a continuing professional development program in healthcare.

Conclusions

The PHARE-M is a complex intervention in multidisciplinary teams working in a variety of hospital settings. A confluence of factors motivated teams to engage in the program. Involving Patient/Parent in quality improvement (QI) work and developing patient therapeutic education for self-management appeared to be complementary approaches to improve care. Incorporating the program into hospital continuing education insures its sustainability. Transparency of Patient Registry indicators per center published in a brief lapse of time is required to effectively support CQI. The impact of the PHARE-M on patient outcomes after 3 years is the subject of a research program funded by the French Ministry of Health whose results will be available in 2017.

     

Lessons from an audit of unplanned pregnancies.

To determine the effectiveness of contraceptive use a two year audit of pregnant women registered in one group practice was carried out. The methods of contraception used by women with unplanned pregnancies were studied and the rates of failure assessed. Of the 518 pregnancies during the study, 187 (36%) were unplanned. Unplanned pregnancies were most common in the 15-19 age group (54 out of 187), and women aged under 25 used contraceptives less reliably than women aged 25 and over. The combined pill was the most effective method of contraception in all age groups. The methods that resulted in most unplanned pregnancies were the sheath in women aged 25 and over and incorrect use of oral contraceptive or no contraception in those aged under 25. The fear of side effects was an important reason why women did not use the combined pill, being cited by 22 out of 134 women, and inappropriate medical advice was cited by a further 20 women. More discussion between doctors and patients and readily available information on the use of oral contraceptives might help to reduce the number of unplanned pregnancies.     

Quality of care in cystic fibrosis: assessment protocol of the French QIP PHARE-M

Background

The PHARE-M care quality improvement program, modeled on the US Cystic Fibrosis Quality Improvement Program, was introduced at 14 cystic fibrosis centers (CFCs) in the French Cystic Fibrosis Network between 2011 and 2013. The pilot phase assessments attested the progressive adherence of the teams and improvements in care management. The PHARE-M Performance research project aims at assessing in 2015 the impact of the PHARE-M program on patient health indicators at trained versus untrained centers. It also sought to identify contextual factors that could account for variability in the performance of the PHARE-M among the trained centers.

Methods

A mixed methodology combining:

• a quantitative experimental study: a comparison, using a mixed model for repeated data (from 2011 to 2015), of the average changes over time in forced expiratory volume in 1 s (FEV1) and body mass index (BMI) between two groups of patients included in a closed cohort (non-transplant patients, continuous follow-up at one participating CFC, and a CF-causing mutation), one having benefitted from the PHARE-M program and the other not having done so, and
• a realistic study: a characterization of the impact on care management and an identification of mechanisms through which the PHARE-M intervention improved the team’s effectiveness in different CFC contexts; this required modeling the intervention, context, and impact on care management with respect to the criteria of the chronic care model (CCM); this was done using a self-administered questionnaire given to professionals and patients/parents supplemented with focus groups.

Conclusion

Although the study population was controlled, it may be difficult to establish a causal relationship between the differences in the changes over time in patient health indicators in the two groups of patients and the PHARE-M intervention as it is often the case in complex interventions rolled out in adaptive environments. The analysis of factors associated with variations in the impact of the PHARE-M at the different trained CFCs required the adoption of instruments validated in other contexts; these could be useful for assessing the performance of other interventions in healthcare practices at CFCs in France.

     

Lessons from patient and parent involvement (P&PI) in a quality improvement program in cystic fibrosis care in France

Background

Quality Improvement Programs (QIP) in cystic fibrosis (CF) care have emerged as strategies to reduce variability of care and of patient outcomes among centres facilitating the implementation of Best Practices in all centres. The US CF Foundation developed a Learning and Leadership Collaborative program which was transposed in France in 2011. Patient and parent involvement (P&PI) on the local quality teams (QTs) is one dimension of this complex intervention. The conditions and effects of this involvement needed to be evaluated.

Methods

In all settings, patients and parents were recruited by their centre care team. They were trained to QI method and tools and contributed their own expertise to improve the process of care. This involvement has been analyzed in the frame of the whole process evaluation. Observations and interviews conducted during the course of the first training year explored the motivations of the patients and parents to participate and the vision of the health care teams. A research study was carried out after three years with the patients/parents and the professionals to assess the French QIP’s effectiveness using a questionnaire to report their opinions on various components of the program, including their experience of P&PI. Responses were analyzed in view of identifying consensus and dissensus between the two groups.

Results

At the introduction of the program, P&PI was an opportunity for healthcare providers to reflect on their conceptions of these individuals both as patients and as healthcare system users. Curiosity about the teams’ functioning, the various center organizations and outcomes led patients to overcome their initial barriers to participation. Seventy-six people including 12 patients/parents from the 14 pilot centres responded to the questionnaire after 3 years. Consensus between professionals and patients/parents was high on most items characterizing the performance of the QIP, QT effectiveness and QT functioning. Patients, parents and professionals agreed on the main characteristics of care such as an optimized organization, multidisciplinary care and patient-centredness. Regarding the use of patient electronic records, the use of care guidelines or the organization of support in the patient community, responses were not consensual amongst patients/parents and a source of dissensus between the two groups. All agreed that the French QIP created good conditions for their involvement. In the end, both groups agreed that it was difficult to attribute the paternity of some changes specifically to any member in the team.

Discussion

Perspectives such as an educational framework to develop the skills and behaviors of professionals engaged in collaborative practice with patients and families and large patient experience surveys could be used to capture patients’ experience of care in the improvement work.

Conclusion

Success factors for patient/parent long-term involvement in QIPs have been identified. Answers to questions raised by the stakeholders about the feasibility, efficiency and usefulness of P&PI in this CF QIP could be given but new questions arose about the sustainability of continuous quality improvement over time.

     

Risks of fetal cystic fibrosis based on linkage disequilibrium data

Summary First-trimester prenatal diagnosis of cystic fibrosis depends on tissues being available from a previous affected child for determination of the phase relationship of DNA markers. If no such tissues are available, it is possible to estimate the risks of a couple producing an affected child from the distribution of haplotypes showing linkage disequilibrium with the cystic fibrosis gene. We have calculated all the fetal risk subsets from the various parental haplotype combinations for the restriction fragment length polymorphisms identified by the KM. 19/PstI and XV-2c/TaqI systems. We conclude that only in a limited number of parental combinations are the fetal risks sufficiently high or sufficiently low to be used in prenatal diagnosis.     

Use of linkage disequilibrium data in prenatal diagnosis of cystic fibrosis

Summary The authors report a case of 11;17 translocation associated with recurrent spontaneous abortions, and request contact with colleagues who have observed similar cases.     

Use of linkage disequilibrium data in prenatal diagnosis of cystic fibrosis

Summary Parents at risk of bearing a child with cystic fibrosis, and who have no living affected child, often use prenatal diagnosis based on microvillar enzyme assay in second-trimester amniotic fluid samples. If enzyme levels are abnormal and the pregnancy is terminated, it is possible in principle to use the fetal tissues to establish the phase relationship of linked DNA markers for a subsequent first-trimester prenatal diagnosis. However, the probability of a fetus being affected after an abnormal microvillar enzyme test may be no greater than 80%. The strong linkage disequilibrium between haplotypes at the D7S23 locus and the cystic fibrosis gene may be used to increase this probability. If fetal tissues are homozygous for the 6.6-kb band defined by pKM.19 and PstI and also homozygous for the 2.1-kb band with pXV-2c and TaqI, the chance of being affected increases from 80% to between 95% and 97%. We regard this as being sufficiently certain for use in phase determination.     

Identification of common cystic fibrosis mutations in African-Americans with cystic fibrosis increases the detection rate to 75%.

Cystic fibrosis (CF)--an autosomal recessive disorder caused by mutations in CF transmembrane conductance regulator (CFTR) and characterized by abnormal chloride conduction across epithelial membranes, leading to chronic lung and exocrine pancreatic disease--is less common in African-Americans than in Caucasians. No large-scale studies of mutation identification and screening in African-American CF patients have been reported, to date. In this study, the entire coding and flanking intronic sequence of the CFTR gene was analyzed by denaturing gradient-gel electrophoresis and sequencing in an index group of 82 African-American CF chromosomes to identify mutations. One novel mutation, 3120+1G-->A, occurred with a frequency of 12.3% and was also detected in a native African patient. To establish frequencies, an additional group of 66 African-American CF chromosomes were screened for mutations identified in two or more African-American patients. Screening for 16 "common Caucasian" mutations identified 52% of CF alleles in African-Americans, while screening for 8 "common African" mutations accounted for an additional 23%. The combined detection rate of 75% was comparable to the sensitivity of mutation analysis in Caucasian CF patients. These results indicate that African-Americans have their own set of "common" CF mutations that originate from the native African population. Inclusion of these "common" mutations substantially improves CF mutation detection rates in African-Americans.     

A chaperone trap contributes to the onset of cystic fibrosis

Protein folding is the primary role of proteostasis network (PN) where chaperone interactions with client proteins determine the success or failure of the folding reaction in the cell. We now address how the Phe508 deletion in the NBD1 domain of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein responsible for cystic fibrosis (CF) impacts the binding of CFTR with cellular chaperones. We applied single ion reaction monitoring mass spectrometry (SRM-MS) to quantitatively characterize the stoichiometry of the heat shock proteins (Hsps) in CFTR folding intermediates in vivo and mapped the sites of interaction of the NBD1 domain of CFTR with Hsp90 in vitro. Unlike folding of WT-CFTR, we now demonstrate the presence of ΔF508-CFTR in a stalled folding intermediate in stoichiometric association with the core Hsps 40, 70 and 90, referred to as a 'chaperone trap'. Culturing cells at 30 C resulted in correction of ΔF508-CFTR trafficking and function, restoring the sub-stoichiometric association of core Hsps observed for WT-CFTR. These results support the interpretation that ΔF508-CFTR is restricted to a chaperone-bound folding intermediate, a state that may contribute to its loss of trafficking and increased targeting for degradation. We propose that stalled folding intermediates could define a critical proteostasis pathway branch-point(s) responsible for the loss of function in misfolding diseases as observed in CF.     

Proteomic analysis of nasal cells from cystic fibrosis patients and non-cystic fibrosis control individuals: search for novel biomarkers of cystic fibrosis lung disease

Potential biological markers for cystic fibrosis (CF) lung disease were identified by comparative proteomics profiling of nasal cells from deletion of phenylalanine residue 508 (F508del)-homozygous CF patients and non-CF controls. From the non-CF 2-DE gels, 65 spots were identified by MS, and a reference 2-DE map was thus established. The majority of those correspond to ubiquitously expressed proteins. Consistent with the epithelial origin of this tissue, some of the identified proteins are epithelial markers (e.g. cytokeratins, palate lung and nasal epithelium clone protein (PLUNC), and squamous cell carcinoma antigen 1). Comparison of this protein profile with the one similarly obtained for CF nasal cells revealed a set of differentially expressed proteins. These included proteins related to chronic inflammation and some others involved in oxidative stress injury. Alterations were also observed in the levels of cytoskeleton proteins, being probably implicated with cytoskeleton organization changes described to occur in CF-airways. Lower levels were found for some mitochondrial proteins suggesting an altered mitochondrial metabolism in CF. Differential expression was also found for two more enzymes that have not been previously associated to CF. Further studies will clarify the involvement of such proteins in CF pathophysiology and whether they are targets for CF therapy.     

Cystic-fibrosis-like disease unrelated to the cystic fibrosis transmembrane conductance regulator

Cystic fibrosis (CF) is considered to be a monogenic disease caused by molecular lesions within the cystic fibrosis transmembrane conductance regulator (CFTR) gene and is diagnosed by elevated sweat electrolytes. We have investigated the clinical manifestations of cystic fibrosis, CFTR genetics and electrophysiology in a sibpair in which the brother is being treated as having CF, whereas his sister is asymptomatic. The diagnosis of CF in the index patient is based on highly elevated sweat electrolytes in the presence of CF-related pulmonary symptoms. The investigation of chloride conductance in respiratory and intestinal tissue by nasal potential difference and intestinal current measurements, respectively, provides no evidence for CFTR dysfunction in the siblings who share the same CFTR alleles. No molecular lesion has been identified in the CFTR gene of the brother. Findings in the investigated sibpair point to the existence of a CF-like disease with a positive sweat test without CFTR being affected. Other factors influencing sodium or chloride transport are likely to be the cause of the symptoms in the patient described. Received: 25 August 1997 / Accepted: 20 January 1998     

CFTR in cystic fibrosis and cholera: from membrane transport to clinical practice

We have used a brief analysis of transport via cystic fibrosis (CF) transmembrane conductance regulators (CFTRs) in various organ systems to highlight the importance of basic membrane transport processes across epithelial cells for first-year medical students in physiology. Because CFTRs are involved in transport both physiologically and pathologically in various systems, we have used this clinical correlation to analyze how a defective gene leading to defective transport proteins can be directly involved in the symptoms of cholera and CF. This article is a "Staying Current" approach to transport via CFTRs including numerous helpful references with further information for a teaching faculty member. The article follows our normal presentation which begins with a discussion of the involvement of CFTR transport in the intestine and how cholera affects intestinal transport, extends to CFTR transport in various organ systems in CF, and concludes with the logic behind many of the treatments that improve CF. Student learning objectives are included to assist in assessment of student understanding of the basic concepts.