Effectiveness of the adapted bivalent mRNA COVID-19 vaccines against hospitalisation in individuals aged ≥ 60 years during the Omicron XBB lineage-predominant period: VEBIS SARI VE network, Europe, February to August, 2023.

We conducted a multicentre hospital-based test-negative case-control study to measure the effectiveness of adapted bivalent COVID-19 mRNA vaccines against PCR-confirmed SARS-CoV-2 infection during the Omicron XBB lineage-predominant period in patients aged ≥ 60 years with severe acute respiratory infection from five countries in Europe. Bivalent vaccines provided short-term additional protection compared with those vaccinated > 6 months before the campaign: from 80% (95% CI: 50 to 94) for 14-89 days post-vaccination, 15% (95% CI: -12 to 35) at 90-179 days, and lower to no effect thereafter.

Interim 2023/24 influenza A vaccine effectiveness: VEBIS European primary care and hospital multicentre studies, September 2023 to January 2024.

Influenza A viruses circulated in Europe from September 2023 to January 2024, with influenza A(H1N1)pdm09 predominance. We provide interim 2023/24 influenza vaccine effectiveness (IVE) estimates from two European studies, covering 10 countries across primary care (EU-PC) and hospital (EU-H) settings. Interim IVE was higher against A(H1N1)pdm09 than A(H3N2): EU-PC influenza A(H1N1)pdm09 IVE was 53% (95% CI: 41 to 63) and 30% (95% CI: -3 to 54) against influenza A(H3N2). For EU-H, these were 44% (95% CI: 30 to 55) and 14% (95% CI: -32 to 43), respectively.

Radiation-Induced Macrophage Senescence Impairs Resolution Programs and Drives Cardiovascular Inflammation.

Radiation is associated with tissue damage and increased risk of atherosclerosis, but there are currently no treatments and a very limited mechanistic understanding of how radiation impacts tissue repair mechanisms. We uncovered that radiation significantly delayed temporal resolution programs that were associated with decreased efferocytosis in vivo. Resolvin D1 (RvD1), a known proresolving ligand, promoted swift resolution and restored efferocytosis in sublethally irradiated mice. Irradiated macrophages exhibited several features of senescence, including increased expression of p16INK4A and p21, heightened levels of SA-ß-gal, COX-2, several proinflammatory cytokines/chemokines, and oxidative stress (OS) in vitro, and when transferred to mice, they exacerbated inflammation in vivo. Mechanistically, heightened OS in senescent macrophages led to impairment in their ability to carry out efficient efferocytosis, and treatment with RvD1 reduced OS and improved efferocytosis. Sublethally irradiated Ldlr -/- mice exhibited increased plaque necrosis, p16INK4A cells, and decreased lesional collagen compared with nonirradiated controls, and treatment with RvD1 significantly reduced necrosis and increased lesional collagen. Removal of p16INK4A hematopoietic cells during advanced atherosclerosis with p16-3MR mice reduced plaque necrosis and increased production of key intraplaque-resolving mediators. Our results demonstrate that sublethal radiation drives macrophage senescence and efferocytosis defects and suggest that RvD1 may be a new therapeutic strategy to limit radiation-induced tissue damage.

Systematic Review of Clinical Results After Medial Meniscus Allograft Transplantation Reveals Improved Patient Reported Outcomes at Greater Than 5 Years Follow-Up.

PURPOSE: To systematically summarize the medial meniscus allograft transplantation (MAT) reported outcomes and evaluate whether the surgical technique is associated with allograft extrusion and knee function. METHODS: Systematic review was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Inclusion criteria were English-language clinical studies involving arthroscopically assisted medial MAT that reported the surgical technique and the presence of graft extrusion or functional outcomes after surgery. Studies in which outcomes for medial MAT could not be separated from lateral MAT were excluded. Surgical technique, allograft-related characteristics, and clinical outcomes were extracted. RESULTS: Twenty-four studies with 328 medial MAT were included, 58.3% studies qualified as level 4 of evidence, 29.2% as level 3, and 12.5% as level 2. Allograft fixation techniques were bone plug (235/328 [71.6%]), bone bridge/trough (55/328 [16.8%]), and soft-tissue suture fixation only (38/328 [11.6%]). Relative percentage of extrusion after surgery ranged from 24.8% to 53.7%. Major extrusion (>3 mm) ranged from zero to 78%. Overall, functional scores improved after medial MAT. None of surgical techniques were associated with poor functional outcomes or extruded meniscus; however, nonanatomical placement of the anterior and posterior horns appeared to increase meniscus extrusion. CONCLUSION: Medial MAT provides favorable outcomes, with acceptable rates of complication and failure regardless of surgical technique. Although allograft extrusion appears equivalent for both bone plug and soft-tissue fixation techniques, positioning allograft horns at the native meniscal footprint may be critical for preventing extrusion. However, the heterogeneity and low level of evidence of the studies included in this review prevent decisive conclusions regarding optimal MAT fixation techniques, clinical significance of allograft extrusion, or comparative clinical outcomes after medial MAT. LEVEL OF EVIDENCE: Level IV - systematic review of Level II to IV studies.

Interim 2022/23 influenza vaccine effectiveness: six European studies, October 2022 to January 2023.

BackgroundBetween October 2022 and January 2023, influenza A(H1N1)pdm09, A(H3N2) and B/Victoria viruses circulated in Europe with different influenza (sub)types dominating in different areas.AimTo provide interim 2022/23 influenza vaccine effectiveness (VE) estimates from six European studies, covering 16 countries in primary care, emergency care and hospital inpatient settings.MethodsAll studies used the test-negative design, but with differences in other study characteristics, such as data sources, patient selection, case definitions and included age groups. Overall and influenza (sub)type-specific VE was estimated for each study using logistic regression adjusted for potential confounders.ResultsThere were 20,477 influenza cases recruited across the six studies, of which 16,589 (81%) were influenza A. Among all ages and settings, VE against influenza A ranged from 27 to 44%. Against A(H1N1)pdm09 (all ages and settings), VE point estimates ranged from 28% to 46%, higher among children (< 18 years) at 49-77%. Against A(H3N2), overall VE ranged from 2% to 44%, also higher among children (62-70%). Against influenza B/Victoria, overall and age-specific VE were ≥ 50% (87-95% among children < 18 years).ConclusionsInterim results from six European studies during the 2022/23 influenza season indicate a ≥ 27% and ≥ 50% reduction in disease occurrence among all-age influenza vaccine recipients for influenza A and B, respectively, with higher reductions among children. Genetic virus characterisation results and end-of-season VE estimates will contribute to greater understanding of differences in influenza (sub)type-specific results across studies.

Vaccine effectiveness against COVID-19 hospitalisation in adults (≥ 20 years) during Alpha- and Delta-dominant circulation: I-MOVE-COVID-19 and VEBIS SARI VE networks, Europe, 2021.

IntroductionTwo large multicentre European hospital networks have estimated vaccine effectiveness (VE) against COVID-19 since 2021.AimWe aimed to measure VE against PCR-confirmed SARS-CoV-2 in hospitalised severe acute respiratory illness (SARI) patients ≥ 20 years, combining data from these networks during Alpha (March-June)- and Delta (June-December)-dominant periods, 2021.MethodsForty-six participating hospitals across 14 countries follow a similar generic protocol using the test-negative case-control design. We defined complete primary series vaccination (PSV) as two doses of a two-dose or one of a single-dose vaccine ≥ 14 days before onset.ResultsWe included 1,087 cases (538 controls) and 1,669 cases (1,442 controls) in the Alpha- and Delta-dominant periods, respectively. During the Alpha period, VE against hospitalisation with SARS-CoV2 for complete Comirnaty PSV was 85% (95% CI: 69-92) overall and 75% (95% CI: 42-90) in those aged ≥ 80 years. During the Delta period, among SARI patients ≥ 20 years with symptom onset ≥ 150 days from last PSV dose, VE for complete Comirnaty PSV was 54% (95% CI: 18-74). Among those receiving Comirnaty PSV and mRNA booster (any product) ≥ 150 days after last PSV dose, VE was 91% (95% CI: 57-98). In time-since-vaccination analysis, complete all-product PSV VE was > 90% in those with their last dose < 90 days before onset; ≥ 70% in those 90-179 days before onset.ConclusionsOur results from this EU multi-country hospital setting showed that VE for complete PSV alone was higher in the Alpha- than the Delta-dominant period, and addition of a first booster dose during the latter period increased VE to over 90%.

Vaccine effectiveness against COVID-19 hospitalisation in adults (≥ 20 years) during Omicron-dominant circulation: I-MOVE-COVID-19 and VEBIS SARI VE networks, Europe, 2021 to 2022.

IntroductionThe I-MOVE-COVID-19 and VEBIS hospital networks have been measuring COVID-19 vaccine effectiveness (VE) in participating European countries since early 2021.AimWe aimed to measure VE against PCR-confirmed SARS-CoV-2 in patients ≥ 20 years hospitalised with severe acute respiratory infection (SARI) from December 2021 to July 2022 (Omicron-dominant period).MethodsIn both networks, 46 hospitals (13 countries) follow a similar test-negative case-control protocol. We defined complete primary series vaccination (PSV) and first booster dose vaccination as last dose of either vaccine received ≥ 14 days before symptom onset (stratifying first booster into received < 150 and ≥ 150 days after last PSV dose). We measured VE overall, by vaccine category/product, age group and time since first mRNA booster dose, adjusting by site as a fixed effect, and by swab date, age, sex, and presence/absence of at least one commonly collected chronic condition.ResultsWe included 2,779 cases and 2,362 controls. The VE of all vaccine products combined against hospitalisation for laboratory-confirmed SARS-CoV-2 was 43% (95% CI: 29-54) for complete PSV (with last dose received ≥ 150 days before onset), while it was 59% (95% CI: 51-66) after addition of one booster dose. The VE was 85% (95% CI: 78-89), 70% (95% CI: 61-77) and 36% (95% CI: 17-51) for those with onset 14-59 days, 60-119 days and 120-179 days after booster vaccination, respectively.ConclusionsOur results suggest that, during the Omicron period, observed VE against SARI hospitalisation improved with first mRNA booster dose, particularly for those having symptom onset < 120 days after first booster dose.

Incremental peritoneal dialysis is a safe and feasible prescription in incident patients with preserved residual kidney function.

BACKGROUND: Incremental peritoneal dialysis (PD) is recommended as a component of high-quality care by the international society for PD; however, its feasibility and clinical outcomes have not been widely reported. The aim of this study is to describe our experience with incremental PD. METHODS: This was a retrospective cohort study of incident PD patients at Eastern Health between 2015 and 2019. Patients who stopped PD within 30 days were excluded. Incremental PD was defined in CAPD as using <8 L/day of exchange volume and in automated PD as dialysing without a last fill. Dialysis modality accorded with patient and physician preferences. RESULTS: The 96 patients were included in this study; 54 with incremental PD. Compared to full-dose PD, incremental PD patients were more likely to be female, had less comorbid diabetes (28% vs. 52%) and higher residual kidney function (RKF) (Kt/V 2.0 ± 0.7 vs. 1.4 ± 0.7). Age, BMI and starting eGFR did not differ between groups. Incremental PD exposed patients to lower exchange volumes (4.4 ± 2.1 vs. 8.5 ± 1.1 L/day), glucose load (46 ± 41 g/day vs. 119 ± 46) and was associated with a longer peritonitis-free survival. PD technique survival, rates of peritonitis or hospitalization were comparable between groups. Predictors for longer incremental PD use included older age and higher starting eGFR. CONCLUSIONS: Incremental PD is a feasible, goal-directed initial prescription in patients with RKF with comparable peritonitis rates and technique survival. Validation of this prescription in prospective studies is warranted.

Cutting Edge: Core Binding Factor ß Is Required for Group 2 Innate Lymphoid Cell Activation.

Group 2 innate lymphoid cells (ILC2) are tissue-resident, long-lived innate effector cells implicated in allergy and asthma. Upon activation, mature ILC2 rapidly secrete large amounts of type-2 cytokines and other effector molecules. The molecular pathways that drive ILC2 activation are not well understood. In this study, we report that the transcriptional controller core binding factor ß (CBFß) is required for ILC2 activation. Deletion or inhibition of CBFß did not impair the maintenance of ILC2 at homeostasis but abolished ILC2 activation during allergic airway inflammation. Treatment with CBFß inhibitors prevented ILC2-mediated airway hyperresponsiveness in a mouse model of acute Alternaria allergen inhalation. CBFß promoted expression of key ILC2 genes at both transcriptional and translational levels. CBF transcriptional complex directly bound to Il13 and Vegfa promoters and enhancers, and controlled gene transcription. CBFß further promoted ribosome biogenesis and enhanced gene translation in activated ILC2. Together, these data establish an essential role for CBFß in ILC2 activation.

Gsx2 controls region-specific activation of neural stem cells and injury-induced neurogenesis in the adult subventricular zone.

Neural stem cells (NSCs) reside in widespread regions along the lateral ventricle and generate diverse olfactory bulb (OB) interneuron subtypes in the adult mouse brain. Molecular mechanisms underlying their regional diversity, however, are not well understood. Here we show that the homeodomain transcription factor Gsx2 plays a crucial role in the region-specific control of adult NSCs in both persistent and injury-induced neurogenesis. In the intact brain, Gsx2 is expressed in a regionally restricted subset of NSCs and promotes the activation and lineage progression of stem cells, thereby controlling the production of selective OB neuron subtypes. Moreover, Gsx2 is ectopically induced in damaged brains outside its normal expression domains and is required for injury-induced neurogenesis in the subventricular zone (SVZ). These results demonstrate that mobilization of adult NSCs is controlled in a region-specific manner and that distinct mechanisms operate in continuous and injury-induced neurogenesis in the adult brain.

Emerging Pathogens and a Current-Use Pesticide: Potential Impacts on Eastern Hellbenders.

Populations of the eastern hellbender Cryptobranchus alleganiensis alleganiensis have been declining for decades, and emerging pathogens and pesticides are hypothesized to be contributing factors. However, few empirical studies have attempted to test the potential effects of these factors on hellbenders. We simultaneously exposed subadult hellbenders to environmentally relevant concentrations of either Batrachochytrium dendrobatidis (Bd) or a frog virus 3-like ranavirus (RV), a combination of the pathogens, or each pathogen following exposure to a glyphosate herbicide (Roundup). Additionally, we measured the ability of the skin mucosome to inactivate Bd and RV in growth assays. We found that mucosome significantly inactivated RV by an average of 40% but had no negative effects on Bd growth. All treatments that included RV exposure experienced reduced survival compared to controls, and the combination of RV and herbicide resulted in 100% mortality. Histopathology verified RV as the cause of mortality in all RV-exposed treatments. No animals were infected with Bd or died in the Bd-only treatment. Our results suggest that RV exposure may be a significant threat to the survival of subadult hellbenders and that Roundup exposure may potentially exacerbate this threat.

Mangrove blue carbon stocks and dynamics are controlled by hydrogeomorphic settings and land-use change.

Globally, carbon-rich mangrove forests are deforested and degraded due to land-use and land-cover change (LULCC). The impact of mangrove deforestation on carbon emissions has been reported on a global scale; however, uncertainty remains at subnational scales due to geographical variability and field data limitations. We present an assessment of blue carbon storage at five mangrove sites across West Papua Province, Indonesia, a region that supports 10% of the world's mangrove area. The sites are representative of contrasting hydrogeomorphic settings and also capture change over a 25-years LULCC chronosequence. Field-based assessments were conducted across 255 plots covering undisturbed and LULCC-affected mangroves (0-, 5-, 10-, 15- and 25-year-old post-harvest or regenerating forests as well as 15-year-old aquaculture ponds). Undisturbed mangroves stored total ecosystem carbon stocks of 182-2,730 (mean ± SD: 1,087 ± 584) Mg C/ha, with the large variation driven by hydrogeomorphic settings. The highest carbon stocks were found in estuarine interior (EI) mangroves, followed by open coast interior, open coast fringe and EI forests. Forest harvesting did not significantly affect soil carbon stocks, despite an elevated dead wood density relative to undisturbed forests, but it did remove nearly all live biomass. Aquaculture conversion removed 60% of soil carbon stock and 85% of live biomass carbon stock, relative to reference sites. By contrast, mangroves left to regenerate for more than 25 years reached the same level of biomass carbon compared to undisturbed forests, with annual biomass accumulation rates of 3.6 ± 1.1 Mg C ha-1  year-1 . This study shows that hydrogeomorphic setting controls natural dynamics of mangrove blue carbon stocks, while long-term land-use changes affect carbon loss and gain to a substantial degree. Therefore, current land-based climate policies must incorporate landscape and land-use characteristics, and their related carbon management consequences, for more effective emissions reduction targets and restoration outcomes.

The Antigen-Presenting Potential of Vγ9Vδ2 T Cells During Plasmodium falciparum Blood-Stage Infection.

During Plasmodium falciparum infections, erythrocyte-stage parasites inhibit dendritic cell maturation and function, compromising effective antimalarial adaptive immunity. Human Vγ9Vδ2 T cells can act in vitro as antigen-presenting cells (APCs) and induce αß T-cell activation. However, the relevance of this activity in vivo has remained elusive. Because Vγ9Vδ2 T cells are activated during the early immune response against P. falciparum infection, we investigated whether they could contribute to the instruction of adaptive immune responses toward malaria parasites. In P. falciparum-infected patients, Vγ9Vδ2 T cells presented increased surface expression of APC-associated markers HLA-DR and CD86. In response to infected red blood cells in vitro, Vγ9Vδ2 T cells upregulated surface expression of HLA-DR, HLA-ABC, CD40, CD80, CD83, and CD86, induced naive αß T-cell responses, and cross- presented soluble prototypical protein to antigen-specific CD8+ T cells. Our findings qualify Vγ9Vδ2 T cells as alternative APCs, which could be harnessed for therapeutic interventions and vaccine design.

Disclosure of industry payments to prescribers: industry payments might be a factor impacting generic drug prescribing.

PURPOSE: Pharmaceutical companies paid at least $3.91bn to prescribers in 2013, yet evidence indicating whether industry payments shift prescribing away from generics is limited. This study examined the association between amount of industry payments to prescribers and generic drug prescribing rates among Medicare Part D prescribers. METHODS: A cross-sectional analysis was conducted among 770 095 Medicare Part D prescribers after linking the 2013 national Open Payments data with 2013 Medicare Provider Utilization and Payment data. The exposure variable was the categorized amount of total industry payments to prescribers (i.e., meals, travel, research, and ownership). The outcome was prescriber's annual generic drug prescribing rate. Multivariable generalized linear regression models were used to examine the association between the amount of industry payments and prescriber's annual generic drug prescribing rates, controlling for prescriber's demographic and practice characteristics. RESULTS: In this sample, over one-third (38.0%) of Medicare Part D prescribers received industry payments in 2013. The mean annual generic drug prescribing rate was highest among prescribers receiving no payments and lowest among those receiving more than $500 of industry payments (77.5% vs. 71.3%, respectively; p < 0.001). The receipt of industry payments was independently associated with prescribers' generic drug prescribing rate; higher payments corresponded with lower generic drug prescribing rates. Other prescriber characteristics associated with higher annual generic drug prescribing rate included male sex, non-northeast region, specialty, and patient volume. CONCLUSIONS: Receipt of industry payments was associated with a decreased rate of generic drug prescribing. How this affects patient care and total medical costs warrants further study. Copyright © 2017 John Wiley & Sons, Ltd.

Mechanistic insights into the first Lygus-active ß-pore forming protein.

The cotton pests Lygus hesperus and Lygus lineolaris can be controlled by expressing Cry51Aa2.834_16 in cotton. Insecticidal activity of pore-forming proteins is generally associated with damage to the midgut epithelium due to pores, and their biological specificity results from a set of key determinants including proteolytic activation and receptor binding. We conducted mechanistic studies to gain insight into how the first Lygus-active ß-pore forming protein variant functions. Biophysical characterization revealed that the full-length Cry51Aa2.834_16 was a stable dimer in solution, and when exposed to Lygus saliva or to trypsin, the protein underwent proteolytic cleavage at the C-terminus of each of the subunits, resulting in dissociation of the dimer to two separate monomers. The monomer showed tight binding to a specific protein in Lygus brush border membranes, and also formed a membrane-associated oligomeric complex both in vitro and in vivo. Chemically cross-linking the ß-hairpin to the Cry51Aa2.834_16 body rendered the protein inactive, but still competent to compete for binding sites with the native protein in vivo. Our study suggests that disassociation of the Cry51Aa2.834_16 dimer into monomeric units with unoccupied head-region and sterically unhindered ß-hairpin is required for brush border membrane binding, oligomerization, and the subsequent steps leading to insect mortality.

Medial Patellofemoral Ligament Reconstruction With Concomitant Tibial Tubercle Transfer: A Systematic Review of Outcomes and Complications.

PURPOSE: To examine the outcomes and complications of medial patellofemoral ligament (MPFL) reconstruction and concomitant tibial tubercle (TT) transfer. METHODS: A systematic review of published literature on MPFL reconstruction and TT transfer was performed using the following databases: PubMed/Medline, CINAHL (Cumulative Index to Nursing and Allied Health Literature), SPORTDiscus, and Cochrane. To be included, studies were required to present outcomes and/or complication data for MPFL reconstruction performed in combination with TT transfer. Each study was assessed for quality and level of evidence. RESULTS: Five studies consisting of 92 knees met the inclusion criteria. Between 57% and 77% of the patients were female patients, and the mean age at surgery was 20.6 years (range, 19 to 31 years). The mean follow-up period was 38 months (range, 23 to 53 months). Postoperative outcome measures including the Lysholm score, Kujala score, International Knee Documentation Committee score, Knee Injury and Osteoarthritis Outcome Score, and visual analog scale score were similar to those previously reported for isolated MPFL reconstruction. Reported complication rates were lower than 15% and included wound infection, hardware irritation, and stiffness. Four studies were graded as Level IV evidence, and 1 study was graded as Level II evidence. Only 1 study scored greater than 50% in the quality analysis. CONCLUSIONS: Results from the analyzed studies indicate that MPFL reconstruction combined with TT transfer is a safe and effective procedure, with a low to moderate risk of complications but overall favorable results. TT transfer is most often performed in conjunction with MPFL reconstruction in the setting of malalignment such as an increased TT-to-trochlear groove distance, and although the surgical indications may differ, the outcomes and risk profiles are similar to those of isolated MPFL reconstruction. With the recognition that these patients are difficult to standardize, additional well-designed studies are needed to further investigate the ideal surgical candidates for MPFL reconstruction with concomitant TT transfer. LEVEL OF EVIDENCE: Level IV, systematic review of Level II and IV studies.

Phosphoantigen Burst upon Plasmodium falciparum Schizont Rupture Can Distantly Activate Vγ9Vδ2 T Cells.

Malaria induces potent activation and expansion of the Vγ9Vδ2 subpopulation of γδT cells, which inhibit the Plasmodium falciparum blood cycle through soluble cytotoxic mediators, abrogating merozoite invasion capacity. Intraerythrocytic stages efficiently trigger Vγ9Vδ2 T-cell activation and degranulation through poorly understood mechanisms. P. falciparum blood-stage extracts are known to contain phosphoantigens able to stimulate Vγ9Vδ2 T cells, but how these are presented by intact infected red blood cells (iRBCs) remains elusive. Here we show that, unlike activation by phosphoantigen-expressing cells, Vγ9Vδ2 T-cell activation by intact iRBCs is independent of butyrophilin expression by the iRBC, and contact with an intact iRBC is not required. Moreover, blood-stage culture supernatants proved to be as potent activators of Vγ9Vδ2 T cells as iRBCs. Bioactivity in the microenvironment is attributable to phosphoantigens, as it is dependent on the parasite DOXP pathway, on Vγ9Vδ2 TCR signaling, and on butyrophilin expression by Vγ9Vδ2 T cells. Kinetic studies showed that the phosphoantigens were released at the end of the intraerythrocytic cycle at the time of parasite egress. We document exquisite sensitivity of Vγ9Vδ2 T cells, which respond to a few thousand parasites. These data unravel a novel framework, whereby release of phosphoantigens into the extracellular milieu by sequestered parasites likely promotes activation of distant Vγ9Vδ2 T cells that in turn exert remote antiparasitic functions.

Influence of response shift on early patient-reported outcomes following autologous chondrocyte implantation.

PURPOSE: Response shift is the phenomenon by which an individual's standards for evaluation change over time. The purpose of this study was to determine whether patients undergoing autologous chondrocyte implantation (ACI) experience response shift. METHODS: Forty-eight patients undergoing ACI participated. The "then-test" method was used to evaluate response shift in commonly used patient-reported outcome measures (PROMs)-the SF-36 Physical Component Scale (SF-36 PCS), WOMAC, IKDC, and Lysholm. Each PROM was completed pre- and 6 and 12 months post-surgery. At 6 and 12 months, an additional "then" version of each form was also completed. The "then" version was identical to the original except that patients were instructed to assess how they were prior to ACI. Traditional change, response shift adjusted change, and response shift magnitude were calculated at 6 and 12 months. T tests (p < 0.05) were used to compare traditional change to response-shift-adjusted change, and response shift magnitude values to previously established minimal detectable change. RESULTS: There were no differences between traditional change and response-shift-adjusted change for any of the PROMs. The mean response shift magnitude value of the WOMAC at 6 months (15 ± 14, p = 0.047) was greater than the previously established minimal detectable change (10.9). The mean response shift magnitude value for the SF-36 PCS at 12 months (9.4 ± 6.8, p = 0.017) also exceeded the previously established minimal detectable change (6.6). CONCLUSIONS: There was no evidence of a group-level effect for response shift. These results support the validity of pre-test/post-test research designs in evaluating treatment effects. However, there is evidence that response shifts may occur on a patient-by-patient basis, and scores on the WOMAC and SF-36 in particular may be influenced by response shift. LEVEL OF EVIDENCE: II.

Patient-oriented and performance-based outcomes after knee autologous chondrocyte implantation: a timeline for the first year of recovery.

CONTEXT: It is well established that autologous chondrocyte implantation (ACI) can require extended recovery postoperatively; however, little information exists to provide clinicians and patients with a timeline for anticipated function during the first year after ACI. OBJECTIVE: To document the recovery of functional performance of activities of daily living after ACI. PATIENTS: ACI patients (n = 48, 29 male; 35.1 ± 8.0 y). INTERVENTION: All patients completed functional tests (weight-bearing squat, walk-across, sit-to-stand, step-up/over, and forward lunge) using the NeuroCom long force plate (Clackamas, OR) and completed patient-reported outcome measures (International Knee Documentation Committee Subjective Knee Evaluation Form, Lysholm, Western Ontario and McMaster Osteoarthritis Index [WOMAC], and 36-Item Short-Form Health Survey) preoperatively and 3, 6, and 12 mo postoperatively. MAIN OUTCOME MEASURES: A covariance pattern model was used to compare performance and self-reported outcome across time and provide a timeline for functional recovery after ACI. RESULTS: Participants demonstrated significant improvement in walk-across stride length from baseline (42.0% ± 8.9% height) at 6 (46.8% ± 8.1%) and 12 mo (46.6% ± 7.6%). Weight bearing on the involved limb during squatting at 30°, 60°, and 90° was significantly less at 3 mo than presurgery. Step-up/over time was significantly slower at 3 mo (1.67 ± 0.69 s) than at baseline (1.49 ± 0.33 s), 6 mo (1.51 ± 0.36 s), and 12 mo (1.40 ± 0.26 s). Step-up/over lift-up index was increased from baseline (41.0% ± 11.3% body weight [BW]) at 3 (45.0% ± 11.7% BW), 6 (47.0% ± 11.3% BW), and 12 mo (47.3% ± 11.6% BW). Forward-lunge time was decreased at 3 mo (1.51 ± 0.44 s) compared with baseline (1.39 ± 0.43 s), 6 mo (1.32 ± 0.05 s), and 12 mo (1.27 ± 0.06). Similarly, forward-lunge impact force was decreased at 3 mo (22.2% ± 1.4% BW) compared with baseline (25.4% ± 1.5% BW). The WOMAC demonstrated significant improvements at 3 mo. All patient-reported outcomes were improved from baseline at 6 and 12 mo postsurgery. CONCLUSIONS: Patients' perceptions of improvements may outpace physical changes in function. Decreased function for at least the first 3 mo after ACI should be anticipated, and improvement in performance of tasks requiring weight-bearing knee flexion, such as squatting, going down stairs, or lunging, may not occur for a year or more after surgery.

Creating Behavior Change for Interdental Biofi lm Disruption: Oral Irrigation as a Solution to Increasing Patient Compliance.

Interdental cleaning is critical to maintaining oral health, preventing dental issues, and promoting overall well-being. However, many patients either struggle with consistently following recommended interdental care routines or have poor technique when complying with recommendations. Addressing this problem requires a multifaceted approach comprised of tailored patient education and patient-clinician partnership to provide both an effective interdental cleaning tool and an accessible method for the patient to implement the modified interdental habit into their routine. The aim of this article is to discuss the different modalities for interdental cleaning, how to assess patient candidacy for different interdental cleaning modalities, and behavior-change strategies to promote patient compliance to recommended interdental care.