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Background: Evidence for the efficacy of nusinersen in adults with 5q-associated spinal muscular atrophy (SMA) has been demonstrated up to a period of 16 months in relatively large cohorts but whereas patients reach a plateau over time is still to be demonstrated. We investigated the efficacy and safety of nusinersen in adults with SMA over 38 months, the longest time period to date in a large cohort of patients from multiple clinical sites., Methods: Our prospective, observational study included adult patients with SMA from Germany, Switzerland, and Austria (July 2017 to May 2022). All participants had genetically-confirmed, 5q-associated SMA and were treated with nusinersen according to the label. The total Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM) scores, and 6-min walk test (6 MWT; metres), were recorded at baseline and 14, 26, and 38 months after treatment initiation, and pre and post values were compared. Adverse events were also recorded., Findings: Overall, 389 patients were screened for eligibility and 237 were included. There were significant increases in all outcome measures compared with baseline, including mean HFMSE scores at 14 months (mean difference 1.72 [95% CI 1.19-2.25]), 26 months (1.20 [95% CI 0.48-1.91]), and 38 months (1.52 [95% CI 0.74-2.30]); mean RULM scores at 14 months (mean difference 0.75 [95% CI 0.43-1.07]), 26 months (mean difference 0.65 [95% CI 0.27-1.03]), and 38 months (mean difference 0.72 [95% CI 0.25-1.18]), and 6 MWT at 14 months (mean difference 30.86 m [95% CI 18.34-43.38]), 26 months (mean difference 29.26 m [95% CI 14.87-43.65]), and 38 months (mean difference 32.20 m [95% CI 10.32-54.09]). No new safety signals were identified., Interpretation: Our prospective, observational, long-term (38 months) data provides further real-world evidence for the continuous efficacy and safety of nusinersen in a large proportion of adult patients with SMA., Funding: Financial support for the registry from Biogen, Novartis and Roche., Competing Interests: SB, ZU, MH, TK, KM, BI, JB, MTM, TB, BS, SF, CS, MTo, AG, MTue, MS, CR, PB, MFB, CK, KPS, SG, ST, JN, RS, MWeb, GW and OvV declare no conflicts of interest. RG has received personal fees from Biogen and Hoffmann-La Roche and served on advisory boards from Biogen, Hoffmann-La Roche, ITF Pharma, Zambon and research support from Biogen, outside of the submitted work. CDW has received personal fees from Biogen and Hoffmann–La Roche outside of the submitted work. AO has received speaker fees from Biogen outside of the submitted work. OSK received academic research support from the Hannover Medical School (MHH) and the German Neuromuscular Society “Deutsche Gesellschaft fuer Muskelkranke” (DGM e.V.), 2019–2021 (grant no. Sc 23/1); and received honoraria as a speaker and/or funding for travel expenses from the German Neuromuscular Society “Deutsche Gesellschaft fuer Muskelkranke (DGM e.V.), Biogen GmbH, Biermann Verlag GmbH, and MK + S—Medizin, Kommunikation & Service GmbH, outside the submitted work. SP has received speaker fees, non-financial support and research support from Biogen, Roche, AL-S Pharma, Amylyx, Cytokinetics, Ferrer, ITF-Pharma, Zambon, and Sanofi and served on advisory boards of Amylyx, Biogen, Roche, Zambon and ITF Pharma outside of the submitted work. MCW has served on advisory boards for Avexis, Biogen, Grünenthal, Novartis, Pfizer, PharNext, PTC Therapeutics, Roche, Santhera, Sarepta, Ultragenyx, Wave Sciences, received funding for Travel or Speaker Honoraria from Biogen, Novartis, PTC Therapeutics, Santhera, and worked as an ad-hoc consultant for Affinia, Audentes Therapeutics, Avexis, Biogen, BridgeBio, Edgewise, Fulcrum, Grünenthal, ML Bio, Novartis, Pfizer, PharNEXT, PTC Therapeutics, Roche. MWei has received advisory board and consultant honoraria from Biogen and Hoffmann-La Roche, and speaker honoraria and travel support for conference attendance from Biogen, outside of the submitted work. MW is a member of the European Reference Network for Neuromuscular Diseases (ERN EURO-NMD). MF has received a speaker honorarium and non-financial support from Biogen outside the submitted work. HSL is receiving advisory fees from Biogen but has no financial or non-financial conflict of interest to declare related to the content of this manuscript. IC has received research grants and speaker fees from Biogen and Hoffmann-La Roche, outside of the submitted work. PL has received honoraria for advisory boards and consultancies from Stadapharm, Abbvie, Alexion, Bial, ITF Pharma, Desitin, Novartis, Woolsey Pharma outside the scope of this work. MD has received personal fees as speaker/consultant from Biogen and Roche, outside of the submitted work. Aha received research grants from Novartis Gene Therapies, and advisory board honoraria and speaker fees from Biogen, Roche, and Novartis. AR has received advisory board honoraria from Biogen outside of the submitted work. DZ received compensation from Biogen for participation on advisory boards, from Novartis for consultancy work, and travel compensation from Angelini Pharma outside of the submitted work. JCK has received personal fees from Biogen and Roche for advisory boards and development of educational material outside of this study. AHe has received personal fees and non-financial support from Biogen and Desitin for advisory board meetings outside the reported work. CK has received advisory board honoraria from Biogen, Roche and Ipsen Pharma, speaker honoraria from Biogen and unrestricted travel grants from Ipsen outside of the submitted work. SN has received financial support for consultancy and lecturing from Allergan, Hormosan, Lilly, Lundbeck, Novartis, Teva and Medscape, research support from Novartis, all outside of the submitted work. AM has received advisory board honoraria from Hormosan and Sanofi, outside of the submitted work. CN has received personal fees from Biogen and Hoffmann–La Roche outside of the submitted work. HCL received honoraria for speaking and advisory board engagements or academic research support Biogen. MG has received an advisory board honorarium from Hoffmann-La Roche and a speaker fee from Novartis outside of the submitted work. AP received compensation for advisory boards, training activities and research grants from Novartis and Biogen. JK received compensation for clinical research and/or consultancy activities from Biogen, Novartis, Roche and ScholarRock. GB has received research grants from PTC, advisory board honoraria and speaker fees from Biogen, Hoffmann-La Roche, Novartis, Pfizer, PTC and personal fees from Roche outside of the submitted work. PM has received honorary as an advisory board member from Biogen unrelated to this work. GMzH received compensation for serving on scientific advisory boards (Alexion, Roche, LFB) and speaker honoraria (Alexion). WL received advisory board honoraria and speaker fees from Biogen and Roche outside of the submitted work MFB has received honoraria from Biogen, Roche and Novartis as an advisory board member and for lectures from Novartis. US has received honoraria for counseling at advisory boards and invited talks for Biogen, Novartis and Roche. WMF has received compensation for scientific advisory boards for Biogen, Novartis, PTC, Sarepta, Sanofi-Aventis, Roche and Cytokinetics and received travel expenses and speaker fees from Biogen, Novartis, PTC, Roche, Sarepta and Sanofi-Aventis. HLo received support for research projects and clinical trials from Amplo Biotechnology, AMO Pharma, argenx, Biogen, Desitin, Fulcrum Therapeutics, Harmony Biosciences, KYE Pharmaceuticals, Milo Biotechnology, Novartis, Pfizer, PTC Therapeutics, Hoffman-La Roche Limited, Sanofi-Genzyme, Santhera, Sarepta, Satellos, Spark Therapeutics and Ultragenyx. HL is the Editor-in-chief for the Journal of Neuromuscular Diseases (IOS Press). CK has received compensation for lectures and advisory boards as well as research funds from Biogen, Roche and Novartis. ACL is a member of Advisory Boards of Roche Pharma AG, Biogen, Alector and Amylyx. He received compensation for talks from Biologix, the German Society of Neurology, Biogen, Springer Medicine, Amylyx and the company Streamed Up! GmbH. He is involved in trials which are sponsored by Amylyx, Ferrer International, Novartis Research and Development, Mitsubishi Tanabe, Apellis Pharmaceuticals, Alexion, Orion Pharma, the European Union, BMBF, Biogen and Orphazyme, Ionis Pharmaceuticals, QurAlis and Alector. TH has received research grants, advisory board honoraria and speaker fees from Biogen, Hoffmann-La Roche, Novartis and personal fees from Roche and Novartis outside of the submitted work., (© 2024 The Author(s).)

Background: Specialist palliative care (SPC) includes care for incurably ill patients and their family caregivers at home or on a palliative care ward until the very end of life. However, in the last days of life, patients can rarely express their needs and little is known about SPC outcomes as reported by multiprofessional SPC teams and family caregivers., Methods: Using the Palliative Care Outcome Scale (POS; Score 0-40), proxy assessments of SPC outcomes in the patient's last 3 days of life were performed by SPC teams and primary family caregivers of three home care and three inpatient services. Additional questions were asked about problems solved 'particularly well' or 'inadequately' (last 7 days), which were content analyzed and quantified., Results: Proxy assessments by SPC teams were available in 142 patients (of whom 51% had died at home). Family caregiver assessments exist for a subgroup of 60 of these patients. SPC teams (POS total score: mean 13.8, SD 6.3) reported SPC outcomes slightly better than family caregivers (mean 16.7, SD 6.8). The POS items consistently rated as least affected (= 0) by both, SPC teams and family caregivers, were 'not wasted time' (team 99%/family caregivers 87%), 'information' (84%/47%) and 'support' (53%/31%). Items rated as most affected (= 4) were 'patient anxiety' (31%/51%), 'life not worthwhile' (26%/35%) and 'no self-worth' (19%/30%). Both groups indicated more problems solved 'particularly well' than 'inadequately'; the latter concerned mainly clinically well-known challenges during end-of-life care and family caregiver care., Conclusions: This study shows the range and type of symptoms and other concerns reported in the patient's last days. Starting points for further improvements in family caregiver care and psychosocial and spiritual issues were identified., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Personal last wishes of people facing a life-limiting illness may change closer to death and may vary across different forms of specialist palliative care (SPC)., Aims: To explore the presence and common themes of last wishes over time and according to the SPC settings (inpatient vs. home-based SPC), and to identify factors associated to having a last wish., Methods: Patients enrolled in a longitudinal study completed questionnaires at the onset (baseline, t 0 ) and within the first 6 weeks (follow-up, t 1 ) of SPC including an open-ended question on their personal last wishes. Last wishes were content analyzed, and all  wishes were coded for presence or absence of each of the identified themes. Changes of last wishes (t 0 -t 1 ) were analyzed by a McNemar test. The chi-square-test was used to compare the two SPC settings. Predictors for the presence of a last wish were identified by logistic regression analysis., Results: Three hundred sixty-one patients (mean age, 69.5 years; 49% female) answered at t 0 , and 130 at t 1 . In cross-sectional analyses, the presence of last wishes was higher at t 0 (67%) than at t 1 (59%). Comparisons revealed a higher presence of last wishes among inpatients than those in home-based SPC at t 0 (78% vs. 62%; p = .002), but not at t 1 . Inpatient SPC (OR = 1.987, p = .011) and greater physical symptom burden over the past week (OR = 1.168, p < .001) predicted presence of a last wish at t 0 . Common themes of last wishes were Travel, Activities, Regaining health, Quality of life, Being with family and friends, Dying comfortably, Turn back time, and Taking care of final matters. The most frequent theme was Travel, at both t 0 (31%) and t 1 (39%). Themes did not differ between SPC settings, neither at t 0 nor at t 1 . Longitudinal analyses (t 0 -t 1 ) showed no significant intra-personal changes in the presence or any themes of last wishes over time., Conclusions: In this late phase of their illness, many patients voiced last wishes. Our study suggests working with such wishes as a framework for person-centered care. Comparisons of SPC settings indicate that individualized approaches to patients' last wishes, rather than setting-specific approaches, may be important., (© 2022. The Author(s).)

Background: We investigated the need for additional professional support and associated factors in patients (pts) at initiation and in the course of in- and outpatient specialist palliative care (I-SPC/O-SPC)., Methods: Pts entering an urban SPC network consecutively completed questionnaires on psychosocial/spiritual problems and support needs within 72 h (T0) as well as within the first 6 weeks (T1) of SPC. Hierarchical linear regression analysis was used to investigate the impact of sociodemographic / disease-related variables, psychological / physical burden, social support, and SPC setting on the extent of support needs., Results: Four hundred twenty-five pts (70 years, 48% female, 91% cancer, 67% O-SPC) answered at T0, and 167 at T1. At T0, main problems related to transportation, usual activities, and dependency (83-89%). At T1, most prevalent problems also related to transportation and usual activities and additionally to light housework (82-86%). At T0, support needs were highest for transportation, light housework, and usual activities (35-41%). Cross-sectional comparisons of SPC settings revealed higher problem scores in O-SPC compared to I-SPC at T0 (p = .039), but not at T1. Support need scores were higher in O-SPC at T0 (p < .001), but lower at T1 (p = .039). Longitudinal analyses showed a decrease of support need scores over time, independent from the SPC setting. At T0, higher distress (p = .047), anxiety/depression (p < .001), physical symptom burden (p < .001) and I-SPC (p < .001) were associated with higher support need scores (at T1: only higher distress, p = .037)., Conclusion: Need for additional professional psychosocial/spiritual support was identified in up to 40% of pts. with higher need at the beginning of O-SPC than of I-SPC. During SPC, this need decreased in both settings, but got lower in O-SPC than in I-SPC over time. Support need scores were not only associated with psychological, but also physical burden., (© 2021. The Author(s).)

Health care facility-onset Clostridium difficile infections (HO-CDI) are an important national problem, causing increased morbidity and mortality. HO-CDI is an important metric for the Center for Medicare and Medicaid Service's (CMS) performance measures. Hospitals that fall into the worst-performing quartile in preventing hospital-acquired infections, including HO-CDI, may lose millions of dollars in reimbursement. Under pressure to reduce CDI and without a clear optimal method for C. difficile detection, health care facilities are questioning how best to use highly sensitive nucleic acid amplification tests (NAATs) to aid in the diagnosis of CDI. Our institution has used a two-step glutamate dehydrogenase (GDH)/toxin immunochromatographic assay/NAAT algorithm since 2009. In 2016, our institution set an organizational goal to reduce our CDI rates by 10% by July 2017. We achieved a statistically significant reduction of 42.7% in our HO-CDI rate by forming a multidisciplinary group to implement and monitor eight key categories of infection prevention interventions over a period of 13 months. Notably, we achieved this reduction without modifying our laboratory algorithm. Significant reductions in CDI rates can be achieved without altering sensitive laboratory testing methods., (Copyright © 2018 American Society for Microbiology.)