Establishing a community pharmacy-based fall prevention service - An implementation study

Background: Community pharmacists are in the position to contribute to fall prevention, but this is not yet common practice. Objective: The aim of this study was to evaluate the implementation of a community pharmacy-based fall prevention service. Methods: A fall prevention service, consisting of a fall risk screening and assessment including a medication review, was implemented in pharmacies during three months. A preparative online training was provided to the pharmacy team to enhance adoption of the service. Included patients were aged ≥70 years, using ≥5 drugs of which ≥1 fall risk-increasing drug. The implementation process was quantitively assessed by registering medication adaptations, recommendations, and referrals. Changes in patient scores on the Short Fall Efficacy Scale-International (FES-I) and a fall prevention knowledge test were documented at one month follow-up. Implementation was qualitatively evaluated by conducting semi-structured interviews with pharmacists before and after the project, based on the consolidated framework of implementation research. Results: The service was implemented in nine pharmacies and 91 consultations were performed. Medication was adapted of 32 patients. Patients' short FES-I scores were significantly higher at follow-up (p = 0.047) and patients’ knowledge test scores did not differ (p = 0.86). Pharmacists experienced the following barriers: lack of time, absence of staff, and limited multidisciplinary collaboration. Facilitators were training, motivated staff, patient engagement, and project scheduling. Conclusion: The service resulted in a substantial number of medication adaptations and lifestyle recommendations, but many barriers were identified that hamper the sustained implementation of the service

Patients' experience with a community pharmacy fall prevention service

BACKGROUND: Pharmacists can contribute to fall prevention, by offering services such as fall risk screenings, counselling, and medication reviews. Patient acceptance of the role of pharmacists in fall prevention is crucial. OBJECTIVES: The aim of this study was to explore patients' experience with a community pharmacy fall prevention service. METHODS: Interviews were conducted with patients one month after they participated in a pharmacy fall prevention service, in the Netherlands. Patient inclusion criteria for the service were: age ≥ 70 years, use of ≥5 drugs including ≥1 fall risk-increasing drug. The service included a fall risk screening followed by counselling and a medication review. The semi-structured interview guide was based on the consolidated framework for implementation research and included the following topics: outcomes, patient's motivation, and contact with the pharmacy technician. RESULTS: Of the 91 participants of the fall prevention service, 87 patients were interviewed with a median age of 78.0 years (first quartile [Q1] - third quartile [Q3]: 74.0-84.75) and 46.3% were female. Many patients expressed positive feedback about receiving a medication review. Most patients whose medication was deprescribed expressed to be positive about this. Others were reassured about the appropriateness of their medication use. Patients reported that the service enhanced their awareness about fall prevention. Only a few patients were motivated to adapt their lifestyle. Patients appreciated the attention and contact. CONCLUSIONS: Patients see a potential benefit for a community pharmacy falls prevention service, including a medication review. Patient education appeared to enhance their fall risk awareness

Haploinsufficiency of ARFGEF1 is associated with developmental delay, intellectual disability, and epilepsy with variable expressivity

ADP ribosylation factor guanine nucleotide exchange factors (ARFGEFs) are a family of proteins implicated in cellular trafficking between the Golgi apparatus and the plasma membrane through vesicle formation. Among them is ARFGEF1/BIG1, a protein involved in axon elongation, neurite development, and polarization processes. ARFGEF1 has been previously suggested as a candidate gene for different types of epilepsies, although its implication in human disease has not been well characterized. International data sharing, in silico predictions, and in vitro assays with minigene study, western blot analyses, and RNA sequencing. We identified 13 individuals with heterozygous likely pathogenic variants in ARFGEF1. These individuals displayed congruent clinical features of developmental delay, behavioral problems, abnormal findings on brain magnetic resonance image (MRI), and epilepsy for almost half of them. While nearly half of the cohort carried de novo variants, at least 40% of variants were inherited from mildly affected parents who were clinically re-evaluated by reverse phenotyping. Our in silico predictions and in vitro assays support the contention that ARFGEF1-related conditions are caused by haploinsufficiency, and are transmitted in an autosomal dominant fashion with variable expressivity. We provide evidence that loss-of-function variants in ARFGEF1 are implicated in sporadic and familial cases of developmental delay with or without epilepsy

SRSF1 Haploinsufficiency Is Responsible for a Syndromic Developmental Disorder Associated with Intellectual Disability

SRSF1 (also known as ASF/SF2) is a non-small nuclear ribonucleoprotein (non-snRNP) that belongs to the arginine/serine (R/S) domain family. It recognizes and binds to mRNA, regulating both constitutive and alternative splicing. The complete loss of this proto-oncogene in mice is embryonically lethal. Through international data sharing, we identified 17 individuals (10 females and 7 males) with a neurodevelopmental disorder (NDD) with heterozygous germline SRSF1 variants, mostly de novo, including three frameshift variants, three nonsense variants, seven missense variants, and two microdeletions within region 17q22 encompassing SRSF1. Only in one family, the de novo origin could not be established. All individuals featured a recurrent phenotype including developmental delay and intellectual disability (DD/ID), hypotonia, neurobehavioral problems, with variable skeletal (66.7%) and cardiac (46%) anomalies. To investigate the functional consequences of SRSF1 variants, we performed in silico structural modeling, developed an in vivo splicing assay in Drosophila, and carried out episignature analysis in blood-derived DNA from affected individuals. We found that all loss-of-function and 5 out of 7 missense variants were pathogenic, leading to a loss of SRSF1 splicing activity in Drosophila, correlating with a detectable and specific DNA methylation episignature. In addition, our orthogonal in silico, in vivo, and epigenetics analyses enabled the separation of clearly pathogenic missense variants from those with uncertain significance. Overall, these results indicated that haploinsufficiency of SRSF1 is responsible for a syndromic NDD with ID due to a partial loss of SRSF1-mediated splicing activity

SRSF1 Haploinsufficiency Is Responsible for a Syndromic Developmental Disorder Associated With Intellectual Disability

SRSF1 (also known as ASF/SF2) is a non-small nuclear ribonucleoprotein (non-snRNP) that belongs to the arginine/serine (R/S) domain family. It recognizes and binds to mRNA, regulating both constitutive and alternative splicing. The complete loss of this proto-oncogene in mice is embryonically lethal. Through international data sharing, we identified 17 individuals (10 females and 7 males) with a neurodevelopmental disorder (NDD) with heterozygous germline SRSF1 variants, mostly de novo, including three frameshift variants, three nonsense variants, seven missense variants, and two microdeletions within region 17q22 encompassing SRSF1. Only in one family, the de novo origin could not be established. All individuals featured a recurrent phenotype including developmental delay and intellectual disability (DD/ID), hypotonia, neurobehavioral problems, with variable skeletal (66.7%) and cardiac (46%) anomalies. To investigate the functional consequences of SRSF1 variants, we performed in silico structural modeling, developed an in vivo splicing assay in Drosophila, and carried out episignature analysis in blood-derived DNA from affected individuals. We found that all loss-of-function and 5 out of 7 missense variants were pathogenic, leading to a loss of SRSF1 splicing activity in Drosophila, correlating with a detectable and specific DNA methylation episignature. In addition, our orthogonal in silico, in vivo, and epigenetics analyses enabled the separation of clearly pathogenic missense variants from those with uncertain significance. Overall, these results indicated that haploinsufficiency of SRSF1 is responsible for a syndromic NDD with ID due to a partial loss of SRSF1-mediated splicing activity

Patients' experience with a community pharmacy fall prevention service

Background: Pharmacists can contribute to fall prevention, by offering services such as fall risk screenings, counselling, and medication reviews. Patient acceptance of the role of pharmacists in fall prevention is crucial. Objective(s): The aim of this study was to explore patients' experience with a community pharmacy fall prevention service. Methods: Interviews were conducted with patients one month after they participated in a pharmacy fall prevention service, in the Netherlands. Patient inclusion criteria for the service were: age ≥ 70 years, use of ≥5 drugs including ≥1 fall risk-increasing drug. The service included a fall risk screening followed by counselling and a medication review. The semi-structured interview guide was based on the consolidated framework for implementation research and included the following topics: outcomes, patient's motivation, and contact with the pharmacy technician. Results: Of the 91 participants of the fall prevention service, 87 patients were interviewed with a median age of 78.0 years (first quartile [Q1] – third quartile [Q3]: 74.0–84.75) and 46.3% were female. Many patients expressed positive feedback about receiving a medication review. Most patients whose medication was deprescribed expressed to be positive about this. Others were reassured about the appropriateness of their medication use. Patients reported that the service enhanced their awareness about fall prevention. Only a few patients were motivated to adapt their lifestyle. Patients appreciated the attention and contact. Conclusions: Patients see a potential benefit for a community pharmacy falls prevention service, including a medication review. Patient education appeared to enhance their fall risk awareness

Establishing a community pharmacy-based fall prevention service - An implementation study

Background: Community pharmacists are in the position to contribute to fall prevention, but this is not yet common practice. Objective: The aim of this study was to evaluate the implementation of a community pharmacy-based fall prevention service. Methods: A fall prevention service, consisting of a fall risk screening and assessment including a medication review, was implemented in pharmacies during three months. A preparative online training was provided to the pharmacy team to enhance adoption of the service. Included patients were aged ≥70 years, using ≥5 drugs of which ≥1 fall risk-increasing drug. The implementation process was quantitively assessed by registering medication adaptations, recommendations, and referrals. Changes in patient scores on the Short Fall Efficacy Scale-International (FES-I) and a fall prevention knowledge test were documented at one month follow-up. Implementation was qualitatively evaluated by conducting semi-structured interviews with pharmacists before and after the project, based on the consolidated framework of implementation research. Results: The service was implemented in nine pharmacies and 91 consultations were performed. Medication was adapted of 32 patients. Patients' short FES-I scores were significantly higher at follow-up (p = 0.047) and patients’ knowledge test scores did not differ (p = 0.86). Pharmacists experienced the following barriers: lack of time, absence of staff, and limited multidisciplinary collaboration. Facilitators were training, motivated staff, patient engagement, and project scheduling. Conclusion: The service resulted in a substantial number of medication adaptations and lifestyle recommendations, but many barriers were identified that hamper the sustained implementation of the service

Patients' experience with a community pharmacy fall prevention service

BACKGROUND: Pharmacists can contribute to fall prevention, by offering services such as fall risk screenings, counselling, and medication reviews. Patient acceptance of the role of pharmacists in fall prevention is crucial. OBJECTIVES: The aim of this study was to explore patients' experience with a community pharmacy fall prevention service. METHODS: Interviews were conducted with patients one month after they participated in a pharmacy fall prevention service, in the Netherlands. Patient inclusion criteria for the service were: age ≥ 70 years, use of ≥5 drugs including ≥1 fall risk-increasing drug. The service included a fall risk screening followed by counselling and a medication review. The semi-structured interview guide was based on the consolidated framework for implementation research and included the following topics: outcomes, patient's motivation, and contact with the pharmacy technician. RESULTS: Of the 91 participants of the fall prevention service, 87 patients were interviewed with a median age of 78.0 years (first quartile [Q1] - third quartile [Q3]: 74.0-84.75) and 46.3% were female. Many patients expressed positive feedback about receiving a medication review. Most patients whose medication was deprescribed expressed to be positive about this. Others were reassured about the appropriateness of their medication use. Patients reported that the service enhanced their awareness about fall prevention. Only a few patients were motivated to adapt their lifestyle. Patients appreciated the attention and contact. CONCLUSIONS: Patients see a potential benefit for a community pharmacy falls prevention service, including a medication review. Patient education appeared to enhance their fall risk awareness

Xq28 duplication including MECP2 in six unreported affected females: what can we learn for diagnosis and genetic counselling?

International audienceDuplication of the Xq28 region, involving MECP2 (dupMECP2), has been primarily described in males with severe developmental delay, spasticity, epilepsy, stereotyped movements and recurrent infections. Carrier mothers are usually asymptomatic with an extremely skewed X chromosome inactivation (XCI) pattern. We report a series of six novel symptomatic females carrying a de novo interstitial dupMECP2, and review the 14 symptomatic females reported to date, with the aim to further delineate their phenotype and give clues for genetic counselling. One patient was adopted and among the other 19 patients, seven (37%) had inherited their duplication from their mother, including three mildly (XCI: 70/30, 63/37, 100/0 in blood and random in saliva), one moderately (XCI: random) and three severely (XCI: uninformative and 88/12) affected patients. After combining our data with data from the literature, we could not demonstrate a correlation between XCI in the blood or duplication size and the severity of the phenotype, or explain the presence of a phenotype in these females. These findings confirm that an abnormal phenotype, even severe, can be a rare event in females born to asymptomatic carrier mothers, making genetic counselling difficult in couples at risk in terms of prognosis, in particular in prenatal cases