Citations

Background The objective is to examine and synthesise the best available experimental evidence about the effect of ambulatory consultation duration on quality of healthcare. Methods We included experimental studies manipulating the length of outpatient clinical encounters between adult patients and clinicians (ie, therapists, pharmacists, nurses, physicians) to determine their effect on quality of care (ie, effectiveness, efficiency, timeliness, safety, equity, patient-centredness and patient satisfaction). Information sources Using controlled vocabulary and keywords, without restriction by language or year of publication, we searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews and Scopus from inception until 15 May 2023. Risk of bias Cochrane Risk of Bias instrument. Data synthesis Narrative synthesis. Results 11 publications of 10 studies explored the relationship between encounter duration and quality. Most took place in the UK’s general practice over two decades ago. Study findings based on very sparse and outdated evidence—which suggested that longer consultations improved indicators of patient-centred care, education about prevention and clinical referrals; and that consultation duration was inconsistently related to patient satisfaction and clinical outcomes—warrant low confidence due to limited protections against bias and indirect applicability to current practice. Conclusion Experimental evidence for a minimal or optimal duration of an outpatient consultation is sparse and outdated. To develop evidence-based policies and practices about encounter length, randomised trials of different consultation lengths—in person and virtually, and with electronic health records—are needed. Trial registration number OSF Registration DOI:10.17605/OSF.IO/EUDK8.

Introduction: Swan neck deformity develops as a sequela of chronic mallet finger. Surgical management can include soft tissue reconstruction or distal interphalangeal joint (DIPJ) fusion. Studies examining the incidence and management of posttraumatic swan neck deformity following mallet fracture are limited. Methods: A retrospective, single-institution review of patients undergoing surgical management of swan neck deformity following a traumatic mallet finger from 2000 to 2021 was performed. Patients with preexisting rheumatoid arthritis were excluded. Injury, preoperative clinical, and surgical characteristics were recorded along with postoperative outcomes and complications. Results: Twenty-five patients were identified who had surgical intervention for swan neck deformity. Sixty-four percent of mallet fingers were chronic. Median time to development of mallet finger was 2 months. Twelve (48%) mallet fingers were Doyle class I, 6 (24%) were class III, and 7 (28%) were class IVB. Forty percent of injuries failed nonoperative splinting trials. Sixteen (64%) underwent primary DIPJ arthrodesis, 8 (32%) underwent DIPJ pinning, and 1 underwent open reduction and internal fixation of mallet fracture. The complication rate was 50% overall, and 33% of surgeries experienced major complications. The overall reoperation rate was 33%. Proximal interphalangeal joint hyperextension improved by 11° on average. Median follow-up was 61.2 months. Conclusions: The development of symptomatic swan neck deformity following traumatic mallet finger injury is rare. All patients warrant an attempt at nonsurgical management. Attempts at surgical correction had a high rate of complications, and DIPJ fusion appeared to provide the most reliable solution.

Abstract The approach to patients with high-risk smoldering multiple myeloma (SMM) varies among clinicians; while some advocate early intervention, others reserve treatment at progression to multiple myeloma (MM). We aimed to describe the myeloma-defining events (MDEs) and clinical presentations leading to MM diagnosis among SMM patients seen at our institution. We included 406 patients diagnosed with SMM between 2013-2022, seen at Mayo Clinic, Rochester, MN. The 2018 Mayo 20/2/20 criteria were used for risk stratification. Median follow-up was 3.9 years. Among high-risk patients who did not receive treatment in the SMM phase (n=71), 51 progressed by last follow-up; the MDEs included: bone lesions(37%), anemia(35%), hypercalcemia(8%), and renal failure(6%); 24% met MM criteria based on marrow plasmacytosis (≥60%) and/or free light chain ratio (>100); 45% had clinically significant MDEs (hypercalcemia, renal insufficiency, and/or bone lesions). MM diagnosis was made based on surveillance labs/imaging(45%), testing obtained due to provider suspicion for progression(14%), bone pain(20%), and hospitalization/ED presentations due to MM complications/symptoms(4%). The presentation was undocumented in 14%. A high proportion (45%) of patients with high-risk SMM on active surveillance develop end-organ damage at progression. About a quarter of patients who progress to MM are not diagnosed based on routine interval surveillance testing.

Abstract Background Levothyroxine (LT4) monotherapy is the standard treatment for hypothyroidism; however, 10–15% of patients have persistent hypothyroid symptoms despite normalizing thyroid hormone levels with LT4. This study aims to summarize the best available evidence on interventions to improve symptomatology in patients with hypothyroidism and persistent symptoms. Methods A systematic search was conducted in March 2022 for randomized controlled trials (RCTs) and observational studies on interventions for adult patients with persistent hypothyroid symptoms despite biochemical euthyroidism on thyroid hormone replacement. Results Of 277 articles, seven fulfilled the inclusion criteria. 455 participants were included. Most intervention participants were female (78.6%) with a mean age of 47.5 years. Five clinical trials evaluating ginger (vs. starch), L-carnitine (vs. placebo), combination LT4 and liothyronine (LT3) (vs. LT4 or placebo), and surgery for patients with serum antithyroid peroxidase (TPO Ab) titers greater than 1000 IU/ml (vs. LT4) found inconsistent improvement in hypothyroidism related symptoms and general health. Of these clinical trials, the use of ginger and surgery showed the largest improvements in fatigue scores. One observational study comparing thyroidectomy vs observation found no impact difference on general health. Lastly, another observational study evaluating combination LT4/LT3 (vs. LT4 monotherapy) found improvement in fatigue and QoL. There were 31 (12%) adverse events in the intervention group and 18 (10.8%) in the comparator group. Conclusions There is no high-quality evidence supporting any intervention for persistent symptoms in hypothyroidism. Available evidence, limited by the risk of bias, inconsistency, and heterogeneity, suggests that some persistent symptoms, particularly fatigue, could improve with ginger and thyroidectomy. Trial registry number:PROSPERO (CRD42022318720)

Abstract Objectives Active RA has been associated with an increased risk of both cardiovascular and peripheral vascular disease. We aimed to compare cerebrovascular changes in patients with and without RA, both with and without a neuropathologic diagnosis of neurodegenerative disease. Methods Patients with RA (n = 32) who died and underwent autopsy between 1994 and 2021 were matched to non-RA controls (n = 32) on age, sex and level of neurodegenerative proteinopathy. Routine neuropathologic examination was performed at the time of autopsy. Cerebrovascular disease severity was evaluated using modified Kalaria and Strozyk scales. Clinical dementia diagnoses were manually collected from patients’ medical records. Results Prior to death, 15 (47%) RA patients and 14 (44%) controls were diagnosed with dementia; 9 patients in each group (60% and 64%, respectively) had Alzheimer’s disease. The prevalence of cerebral amyloid angiopathy, microinfarcts, infarcts or strokes was found to be similar between groups. Patients with RA were more likely to have more severe vascular changes in the basal ganglia by Kalaria scale (P = 0.04), but not in other brain areas. There were no significant differences in the presence of large infarcts, lacunar infarcts or leukoencephalopathy by Strozyk scale. Among patients with RA and no clinical diagnosis of dementia, the majority had mild–moderate cerebrovascular abnormalities, and a subset of patients had Alzheimer’s disease neuropathologic changes. Conclusion In this small series of autopsies, patients with and without RA had largely similar cerebrovascular pathology when controlling for neurodegenerative proteinopathies, although patients with RA exhibited more pronounced cerebrovascular disease in the basal ganglia.

Abstract Background Cathepsin D (CatD) is a lysosomal protease that degrades both the amyloid-β protein (Aβ) and the microtubule-associated protein, tau, which accumulate pathognomonically in Alzheimer disease (AD), but few studies have examined the role of CatD in the development of Aβ pathology and tauopathy in vivo. Methods CatD knockout (KO) mice were crossed to human amyloid precursor protein (hAPP) transgenic mice, and amyloid burden was quantified by ELISA and immunohistochemistry (IHC). Tauopathy in CatD-KO mice, as initially suggested by Gallyas silver staining, was further characterized by extensive IHC and biochemical analyses. Controls included human tau transgenic mice (JNPL3) and another mouse model characterized by pronounced lysosomal dysfunction (Krabbe A). Additional experiments examined the effects of CatD inhibition on tau catabolism in vitro and in cultured neuroblastoma cells with inducible expression of human tau. Results Deletion of CatD in hAPP transgenic mice triggers large increases in cerebral Aβ, manifesting as intense, exclusively intracellular aggregates; extracellular Aβ deposition, by contrast, is neither triggered by CatD deletion, nor affected in older, haploinsufficient mice. Unexpectedly, CatDKO mice were found to develop prominent tauopathy by just ~ 3 weeks of age, accumulating sarkosyl-insoluble, hyperphosphorylated tau exceeding the pathology in aged JNPL3 mice. CatDKO mice exhibit pronounced perinuclear Gallyas silver staining reminiscent of mature neurofibrillary tangles in human AD, together with widespread phospho-tau immunoreactivity. Striking increases in sarkosyl-insoluble phospho-tau (~ 1250%) are present in CatD-KO mice, but notably absent from Krabbe A mice collected at an identical antemortem interval. In vitro and in cultured cells, we show that tau catabolism is slowed by blockade of CatD proteolytic activity, including via competitive inhibition by Aβ42. Conclusions Our findings support a major role for CatD in the proteostasis of both Aβ and tau in vivo. To our knowledge, CatD-KO mice are the only model to develop detectable Aβ acumulation and profound tauopathy in the absence of overexpression of hAPP or human tau with disease-associated mutations. Given that tauopathy emerges from disruption of CatD, which can itself be potently inhibited by Aβ42, our findings suggest that impaired CatD activity may represent a key mechanism linking amyloid accumulation and tauopathy in AD.