Care and rhythmanalysis: Using metastability to understand the routines of dementia care.

An increasing number of people living with dementia worldwide receive informal care from their family members. A key element of dementia care is maintaining a daily routine and familiarity, making caring an extremely rhythmic practice. To explore the rhythmic nature of informal care, we apply and advance Lefebvre's unfinished rhythmanalysis by developing an original typology of eurhythmia as a metastable equilibrium. Metastability, although appearing macroscopically stable, is a vulnerable state where a slight disturbance can result in deviation to another state (i.e., stable or unstable). Drawing upon interviews with informal caregivers, we discuss the rhythms and (dis)harmonies of caring practice, including the substantial rhythms of caring practice, the relational balance of rhythms between the caregiver and care recipient, and the various rhythmic disruptions that occur. We demonstrate how metastability provides an understanding of the ever-changing rhythms of every day and allows us to move beyond the immediacy of arrhythmic breaks and explore the subtle changes that occur in (poly)rhythms. Thus, eurhythmia as a metastable equilibrium allows us to explore the gradual and subtle development of, and changes to, dementia care and other routine practices in health geography.

"We're drowning and we're alone": a qualitative study of the lived experience of people experiencing persistent post-COVID-19 symptoms.

BACKGROUND: The "long tail" of the COVID-19 pandemic will be reflected in disabling symptoms that persist, fluctuate or recur for extended periods for an estimated 20%-30% of those who had a SARS-CoV-2 infection; development of effective interventions to address these symptoms must account for the realities faced by these patients. We sought to describe the lived experience of patients living with persistent post-COVID-19 symptoms. METHODS: We conducted a qualitative study, using interpretive description, of the lived experiences of adults experiencing persistent post-COVID-19 symptoms. We collected data from in-depth, semistructured virtual focus groups in February and March 2022. We used thematic analysis to analyze the data and met with several participants twice for respondent validation. RESULTS: The study included 41 participants (28 females) from across Canada with a mean age of 47.9 years and mean time since initial SARS-CoV-2 infection of 15.8 months. Four overarching themes were identified: the unique burdens of living with persistent post-COVID-19 symptoms; the complex nature of patient work in managing symptoms and seeking treatment during recovery; erosion of trust in the health care system; and the process of adaptation, which included taking charge and transformed self-identity. INTERPRETATION: Living with persistent post-COVID-19 symptoms within a health care system ill-equipped to provide needed resources profoundly challenges the ability of survivors to restore their well-being. Whereas policy and practice increasingly emphasize the importance of self-management within the context of post-COVID-19 symptoms, new investments that enhance services and support patient capacity are required to promote better outcomes for patients, the health care system and society.

The role of performativity in informal dementia carers' capability to be mobile.

Informal carers are and will remain a vital part of dementia care. Given the nature of their caring tasks, which focus on enabling the care recipient to engage in meaningful activities, informal dementia carers are affected in their everyday mobility. Expectations manifested by society, loved ones and the carers themselves play a critical role in how carers perform their caring role and how they perceive their opportunity, or capability, to be mobile. This article uses Butler's concept of performativity to understand informal dementia carers' capability to be mobile. In the spring and summer of 2021, we combined remote graphic elicitation with telephone interviews to gather the views of 17 informal dementia carers (aged 50+) living in England. Three key themes emerged from our analysis of the data. Firstly, participants perceived that becoming a carer changed their capability to be mobile. Secondly, the caring role in relation to the capability to be mobile resulted in an emotional toll and perceived loss of autonomy. Thirdly, the performativity of the caring role created feelings of guilt, selfishness and resentment due to the impact caring had on participants' capability to be mobile. Our study enriches the literature on informal dementia carers' mobility, as we suggest that performativity is a key factor in how this population experiences their everyday mobility. The findings suggest that existing ageing-in-place policies should take a more holistic approach by better including those ageing adults who provide the most support: informal dementia carers.

Efficacy and safety of dilpacimab (ABT-165) versus bevacizumab plus FOLFIRI in metastatic colorectal cancer: a phase II study.

Aim: This phase II study investigated safety and efficacy of dilpacimab or bevacizumab plus FOLFIRI in patients with previously treated metastatic colorectal cancer (mCRC). Materials & methods: Overall, 66 patients were treated (n = 34 dilpacimab + FOLFIRI; n = 32 bevacizumab + FOLFIRI). Progression-free survival, overall survival, response rates and tolerability were assessed. Results: Median progression-free survival for dilpacimab + FOLFIRI compared with bevacizumab + FOLFIRI was 3.78 months (95% CI: 2.07-7.20) versus 7.36 months (95% CI: 5.68-10.55) (hazard ratio: 3.57; 95% CI: 1.57-8.11; stratified). Median overall survival: 7.95 months for dilpacimab + FOLFIRI; not reached for bevacizumab + FOLFIRI. Objective response rates: 5.6% for dilpacimab + FOLFIRI and 14.7% for bevacizumab + FOLFIRI. Patients treated with dilpacimab + FOLFIRI experienced serious treatment-related adverse events (n = 4; 11.8%), including one case of intestinal perforation leading to death; none were reported for bevacizumab + FOLFIRI. Conclusion: Treatment with dilpacimab + FOLFIRI was not well tolerated and did not provide clinical benefit to patients with mCRC compared with bevacizumab + FOLFIRI. Clinical Trial Registration: NCT03368859 (Clinicaltrials.gov).

Long-Term Follow-up of Patients with Tourette's Syndrome.

BACKGROUND: Tourette's Syndrome (TS) is a childhood-onset movement disorder marked by the chronic presence of motor and vocal tics. Research shows that tics associated with TS tend to fade in severity for some (but not all) affected youth, though psychiatric comorbidities that commonly accompany TS may be more persistent. The long-term outcomes of individuals with TS have not been well characterized. OBJECTIVE: To characterize long-term clinical outcomes of individuals with TS. METHOD: We conducted a long-term (25-32 years) follow-up study of 45 patients with TS who presented to the Tourette's and Tic Disorders Clinic within the Department of Psychiatry at the University of California San Francisco Medical Center, which was staffed by the first author (Thomas L. Lowe, MD [T.L.L.]), between 1983 and 1990. Baseline data were obtained via chart review, and follow-up data were obtained by self-report surveys. RESULTS: Participants generally reported good psychosocial functioning, attainment of significant social milestones (academic attainment, gainful employment, marriage), and high subjective quality of life. The vast majority of participants (82%) reported improvement in their tics over time, though a significant minority continued to experience at least mild tic-related impairment (26%-40%, depending on metric). Lifetime rates of attention deficit hyperactivity disorder (ADHD) and anxiety disorders, including obsessive-compulsive disorder, were greater than in the general US population. Robust predictors of follow-up outcomes were not found. CONCLUSIONS: These findings reflect a positive overall long-term prognosis for individuals with TS. Providing information about this prognosis at the time of diagnosis may decrease distress in affected individuals and their families. Future studies using planned longitudinal designs that address potential confounds of survey nonresponse are needed to detail long-term outcomes of individuals with TS more precisely.

Efficacy and Safety of Onartuzumab in Combination With First-Line Bevacizumab- or Pemetrexed-Based Chemotherapy Regimens in Advanced Non-Squamous Non-Small-Cell Lung Cancer.

BACKGROUND: Onartuzumab is a monovalent monoclonal antibody that binds with the extracellular domain of the MET receptor. Given the role of MET in non-small-cell lung cancer (NSCLC), we investigated whether onartuzumab added to first-line chemotherapy efficacy in non-squamous NSCLC. METHODS: Patients with untreated stage IIIB/IV non-squamous NSCLC, stratified by MET diagnostic status, were randomized to receive onartuzumab (15 mg/kg intravenously every 3 weeks) or placebo in combination with either paclitaxel/platinum/bevacizumab (bevacizumab cohort), or in combination with platinum/pemetrexed (pemetrexed cohort) with maintenance bevacizumab or pemetrexed and onartuzumab/placebo as appropriate. Co-primary endpoints of this phase II study were progression-free survival (PFS) in all patients and in MET+ patients (2+/3+), defined by the Ventana immunohistochemistry assay; secondary endpoints included overall survival (OS), objective response rate (ORR), safety, and pharmacokinetics. RESULTS: Efficacy data were available for 139 and 120 patients in the bevacizumab and pemetrexed cohorts, respectively. No benefit was seen in the PFS endpoint in the intent-to treat population of either cohort, but was numerically worse in the onartuzumab arm of the MET+ subgroup of the bevacizumab cohort. The onartuzumab and placebo arms had similar ORR and OS results in both cohorts. A higher incidence of some adverse events was observed with onartuzumab versus placebo, including peripheral edema (30% vs. 3%, bevacizumab cohort; 48% vs. 14%, pemetrexed cohort) and venous thromboembolic events (bevacizumab cohort only, 15% vs. 6%). CONCLUSION: Onartuzumab does not appear to provide any additional clinical benefit when given in combination with current first-line standard-of-care chemotherapy for non-squamous NSCLC.

Visual Analytics for Development and Evaluation of Order Selection Criteria for Autoregressive Processes.

Order selection of autoregressive processes is an active research topic in time series analysis, and the development and evaluation of automatic order selection criteria remains a challenging task for domain experts. We propose a visual analytics approach, to guide the analysis and development of such criteria. A flexible synthetic model generator-combined with specialized responsive visualizations-allows comprehensive interactive evaluation. Our fast framework allows feedback-driven development and fine-tuning of new order selection criteria in real-time. We demonstrate the applicability of our approach in three use-cases for two general as well as a real-world example.

Exome sequencing positively identified relevant alterations in more than half of cases with an indication of prenatal ultrasound anomalies.

OBJECTIVE: Exome sequencing is a successful option for diagnosing individuals with previously uncharacterized genetic conditions, however little has been reported regarding its utility in a prenatal setting. The goal of this study is to describe the results from a cohort of fetuses for which exome sequencing was performed. METHODS: We performed a retrospective analysis of the first seven cases referred to our laboratory for exome sequencing following fetal demise or termination of pregnancy. All seven pregnancies had multiple congenital anomalies identified by level II ultrasound. Exome sequencing was performed on trios using cultured amniocytes or products of conception from the affected fetuses. RESULTS: Relevant alterations were identified in more than half of the cases (4/7). Three of the four were categorized as 'positive' results, and one of the four was categorized as a 'likely positive' result. The provided diagnoses included osteogenesis imperfecta II (COL1A2), glycogen storage disease IV (GBE1), oral-facial-digital syndrome 1 (OFD1), and RAPSN-associated fetal akinesia deformation sequence. CONCLUSION: This data suggests that exome sequencing is likely to be a valuable diagnostic testing option for pregnancies with multiple congenital anomalies detected by prenatal ultrasound; however, additional studies with larger cohorts of affected pregnancies are necessary to confirm these findings.

Contrasting catalytic profiles of multiheme nitrite reductases containing CxxCK heme-binding motifs.

The multiheme cytochromes from Thioalkalivibrio nitratireducens (TvNiR) and Escherichia coli (EcNrfA) reduce nitrite to ammonium. Both enzymes contain His/His-ligated hemes to deliver electrons to their active sites, where a Lys-ligated heme has a distal pocket containing a catalytic triad of His, Tyr, and Arg residues. Protein-film electrochemistry reveals significant differences in the catalytic properties of these enzymes. TvNiR, but not EcNrfA, requires reductive activation. Spectroelectrochemistry implicates reduction of His/His-ligated heme(s) as being key to this process, which restricts the rate of hydroxide binding to the ferric form of the active-site heme. The K M describing nitrite reduction by EcNrfA varies with pH in a sigmoidal manner that is consistent with its modulation by (de)protonation of a residue with pK a ≈ 7.6. This residue is proposed to be the catalytic His in the distal pocket. By contrast, the K M for nitrite reduction by TvNiR decreases approximately linearly with increase of pH such that different features of the mechanism define this parameter for TvNiR. In other regards the catalytic properties of TvNiR and EcNrfA are similar, namely, the pH dependence of V max and the nitrite dependence of the catalytic current-potential profiles resolved by cyclic voltammetry, such that the determinants of these properties appear to be conserved.

CNV analysis in Tourette syndrome implicates large genomic rearrangements in COL8A1 and NRXN1.

Tourette syndrome (TS) is a neuropsychiatric disorder with a strong genetic component. However, the genetic architecture of TS remains uncertain. Copy number variation (CNV) has been shown to contribute to the genetic make-up of several neurodevelopmental conditions, including schizophrenia and autism. Here we describe CNV calls using SNP chip genotype data from an initial sample of 210 TS cases and 285 controls ascertained in two Latin American populations. After extensive quality control, we found that cases (N = 179) have a significant excess (P = 0.006) of large CNV (>500 kb) calls compared to controls (N = 234). Amongst 24 large CNVs seen only in the cases, we observed four duplications of the COL8A1 gene region. We also found two cases with ∼400 kb deletions involving NRXN1, a gene previously implicated in neurodevelopmental disorders, including TS. Follow-up using multiplex ligation-dependent probe amplification (and including 53 more TS cases) validated the CNV calls and identified additional patients with rearrangements in COL8A1 and NRXN1, but none in controls. Examination of available parents indicates that two out of three NRXN1 deletions detected in the TS cases are de-novo mutations. Our results are consistent with the proposal that rare CNVs play a role in TS aetiology and suggest a possible role for rearrangements in the COL8A1 and NRXN1 gene regions.

The myosin chaperone UNC-45 is organized in tandem modules to support myofilament formation in C. elegans.

The UCS (UNC-45/CRO1/She4) chaperones play an evolutionarily conserved role in promoting myosin-dependent processes, including cytokinesis, endocytosis, RNA transport, and muscle development. To investigate the protein machinery orchestrating myosin folding and assembly, we performed a comprehensive analysis of Caenorhabditis elegans UNC-45. Our structural and biochemical data demonstrate that UNC-45 forms linear protein chains that offer multiple binding sites for cooperating chaperones and client proteins. Accordingly, Hsp70 and Hsp90, which bind to the TPR domain of UNC-45, could act in concert and with defined periodicity on captured myosin molecules. In vivo analyses reveal the elongated canyon of the UCS domain as a myosin-binding site and show that multimeric UNC-45 chains support organization of sarcomeric repeats. In fact, expression of transgenes blocking UNC-45 chain formation induces dominant-negative defects in the sarcomere structure and function of wild-type worms. Together, these findings uncover a filament assembly factor that directly couples myosin folding with myofilament formation.

Prevalence and clinical correlates of explosive outbursts in Tourette syndrome.

The aim of this study was to examine the prevalence and clinical correlates of explosive outbursts in two large samples of individuals with Tourette syndrome (TS), including one collected primarily from non-clinical sources. Participants included 218 TS-affected individuals who were part of a genetic study (N=104 from Costa Rica (CR) and N=114 from the US). The relationships between explosive outbursts and comorbid attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), tic severity, and prenatal and perinatal complications were examined using regression analyses. Twenty percent of participants had explosive outbursts, with no significant differences in prevalence between the CR (non-clinical) and the US (primarily clinical) samples. In the overall sample, ADHD, greater tic severity, and lower age of tic onset were strongly associated with explosive outbursts. ADHD, prenatal exposure to tobacco, and male gender were significantly associated with explosive outbursts in the US sample. Lower age of onset and greater severity of tics were significantly associated with explosive outbursts in the CR sample. This study confirms previous studies that suggest that clinically significant explosive outbursts are common in TS and associated with ADHD and tic severity. An additional potential risk factor, prenatal exposure to tobacco, was also identified.

A functional description of CymA, an electron-transfer hub supporting anaerobic respiratory flexibility in Shewanella.

CymA (tetrahaem cytochrome c) is a member of the NapC/NirT family of quinol dehydrogenases. Essential for the anaerobic respiratory flexibility of shewanellae, CymA transfers electrons from menaquinol to various dedicated systems for the reduction of terminal electron acceptors including fumarate and insoluble minerals of Fe(III). Spectroscopic characterization of CymA from Shewanella oneidensis strain MR-1 identifies three low-spin His/His co-ordinated c-haems and a single high-spin c-haem with His/H(2)O co-ordination lying adjacent to the quinol-binding site. At pH 7, binding of the menaquinol analogue, 2-heptyl-4-hydroxyquinoline-N-oxide, does not alter the mid-point potentials of the high-spin (approximately -240 mV) and low-spin (approximately -110, -190 and -265 mV) haems that appear biased to transfer electrons from the high- to low-spin centres following quinol oxidation. CymA is reduced with menadiol (E(m) = -80 mV) in the presence of NADH (E(m) = -320 mV) and an NADH-menadione (2-methyl-1,4-naphthoquinone) oxidoreductase, but not by menadiol alone. In cytoplasmic membranes reduction of CymA may then require the thermodynamic driving force from NADH, formate or H2 oxidation as the redox poise of the menaquinol pool in isolation is insufficient. Spectroscopic studies suggest that CymA requires a non-haem co-factor for quinol oxidation and that the reduced enzyme forms a 1:1 complex with its redox partner Fcc3 (flavocytochrome c3 fumarate reductase). The implications for CymA supporting the respiratory flexibility of shewanellae are discussed.

Synthetic generation of high-dimensional datasets.

Generation of synthetic datasets is a common practice in many research areas. Such data is often generated to meet specific needs or certain conditions that may not be easily found in the original, real data. The nature of the data varies according to the application area and includes text, graphs, social or weather data, among many others. The common process to create such synthetic datasets is to implement small scripts or programs, restricted to small problems or to a specific application. In this paper we propose a framework designed to generate high dimensional datasets. Users can interactively create and navigate through multi dimensional datasets using a suitable graphical user-interface. The data creation is driven by statistical distributions based on a few user-defined parameters. First, a grounding dataset is created according to given inputs, and then structures and trends are included in selected dimensions and orthogonal projection planes. Furthermore, our framework supports the creation of complex non-orthogonal trends and classified datasets. It can successfully be used to create synthetic datasets simulating important trends as multidimensional clusters, correlations and outliers.

The Scoliosis Research Society Health-Related Quality of Life (SRS-30) age-gender normative data: an analysis of 1346 adult subjects unaffected by scoliosis.

STUDY DESIGN: Prospective, cross-sectional study. OBJECTIVE: To determine Scoliosis Research Society (SRS)-30 health-related quality of life (HRQOL) reference values by age and gender in an adult population unaffected by scoliosis thereby allowing clinicians and investigators to compare individual and/or groups of spinal deformity patients to their generational peers. SUMMARY OF BACKGROUND DATA: Normative data are collected to establish means and standard deviations of health-related quality of life outcomes representative of a population. The SRS HRQOL questionnaire has become the standard for determining and comparing treatment outcomes in spinal deformity practices. With the establishment of adult SRS-30 HRQOL population values, clinicians, and investigators now have a reference for interpretation of individual scores and/or the scores of subgroups of adult patients with spinal deformities. METHODS: The SRS-30 HRQOL was issued prospectively to 1346 adult volunteers recruited from across the United States. Volunteers self-reported no history of scoliosis or prior spine surgery. Domain medians, means, confidence intervals, percentiles, and minimum/maximum values were calculated for six generational age-gender groups: male/female; 20-39, 40-59, and 60-80 years of age. RESULTS: Median and mean domain values ranged from 4.1 to 4.6 for all age-gender groups. The older the age-gender group, the lower (worse) the reported domain median and mean scores. The only exception was the mental health domain scores in the female groups which improved slightly. Males reported higher (better) scores than females but only the younger males were significantly higher in all domains than their female counterparts. In addition, all male groups reported higher Mental Health domain scores than their female counterparts (P=0.003). CONCLUSION: This study reports population medians, means, standard deviations, percentiles, and confidence intervals for the domains of the SRS-30 HRQOL instrument. Clinicians must be mindful of age-gender differences when assessing deformity populations. Generational decreases noted in the older adult volunteer scores may provide a basis for future investigators to interpret observed score decreases in patient cohorts at long-term follow-up.

Preservation of thoracic kyphosis is critical to maintain lumbar lordosis in the surgical treatment of adolescent idiopathic scoliosis.

STUDY DESIGN: Retrospective analysis of prospectively collected multicenter series. OBJECTIVE: To evaluate the sagittal profile of surgically treated adolescent idiopathic scoliosis (AIS) patients. SUMMARY OF BACKGROUND DATA: With the increasing popularity of segmental pedicle screw spinal instrumentation, thoracic kyphosis (TK) is often sacrificed to achieve coronal and axial plane correction. METHODS: Radiographs of AIS patients with a Lenke type 1 deformity and minimum 2-year follow-up after selective thoracic fusion (lowest instrumented vertebra of T11, T12, or L1) were evaluated. Changes in TK were correlated with changes in lumbar lordosis (LL). Patients were divided according to approach (open/thoracoscopic anterior vs. posterior). Analysis of variance was used to compare pre and postoperative radiographic measures. RESULTS: Two hundred fifty-one patients (age: 14 +/- 2 years) were included. Sixty seven percentages of the patients had anterior surgery (97 open anterior, 71 thoracoscopic) and 33% (83 patients) had posterior spinal fusion. A decrease in postoperative TK was significantly correlated (P < or = 0.001) with a decrease in LL at first erect (r = 0.3), 1 year (r = 0.4) and 2 years (r = 0.4), independent of surgical approach. LL decreased significantly at the first erect regardless of approach (P = 0.003); however, at 2-year postoperative TK and LL were significantly decreased after a posterior approach (P < or = 0.001) when compared with an anterior approach that added kyphosis. The decrease in LL (5.6 degrees +/- 9.7 degrees) was nearly twice the decrease in TK (2.8 degrees +/- 11.4 degrees) in the posterior group at 2-years. CONCLUSION: Given that thoracic AIS is often associated with a preexisting reduction in TK, ideal surgical correction should address this deformity. Procedures which further reduce TK also reduce LL. It is unclear if the loss of LL from thoracic scoliosis correction will compound the loss of LL that occurs with age and lead to further decline in sagittal balance. With this concern, we recommend a posterior column lengthening and/or an anterior column shortening to achieve restoration of normal TK and maximal LL.

Dissecting the effects of spinal fusion and deformity magnitude on quality of life in patients with adolescent idiopathic scoliosis.

STUDY DESIGN: A retrospective review of scores from the Scoliosis Research Society outcomes instrument (SRS-24 questionnaire). OBJECTIVE: To quantify the isolated effects of spinal fusion and deformity magnitude on quality of life in patients with adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: Significant improvements in 2-year postoperative SRS-24 questionnaire scores have been reported despite the loss of spinal motion due to instrumentation and arthrodesis. As deformity reduction may influence patient perception, it has been difficult to isolate the effect of spinal fusion on quality of life after scoliosis surgery. METHODS: SRS-24 scores were compared between 3 cohorts of AIS patients (preoperative, postoperative, and nonoperative) using an ANOVA (P < 0.05) to determine the isolated effects of spinal fusion and deformity magnitude. Preoperative SRS-24 scores were collected from a group of patients with preoperative major Cobb angles greater than 40 degrees (n = 194). Postoperative SRS-24 scores were collected from patients with preoperative major Cobb angles greater than 40 degrees and 2-year postoperative major Cobb angles between 20 degrees and 40 degrees (n = 196). Finally, SRS-24 scores were collected from a nonoperative group of patients with major Cobb angles between 20 degrees and 40 degrees (n = 112). RESULTS: Spinal fusion was found to have a negative isolated effect on the Activity domain (-0.3) and on the Total score (-0.2) (P = 0.001) of the SRS-24 questionnaire (score range: 1-5). A smaller deformity magnitude, on the other hand, was found to have a significantly positive isolated effect on all 4 preoperative domains (P < 0.001) and on the Total score (P < 0.001). The combined effect of surgery (spinal fusion and deformity correction) was found to be significantly positive for the Total score (P < 0.001) and for the domains of Pain, Self-Image, and Function (P < 0.001). CONCLUSION: Spinal fusion has an isolated negative effect on AIS patients' quality of life (Total score) mostly due to a decrease in scores of the Activity domain. The overall positive effect of surgery depends on the individual effects of spinal fusion (slight reduction in quality of life) and deformity reduction (modest improvement in quality of life).

Restoration of thoracic kyphosis after operative treatment of adolescent idiopathic scoliosis: a multicenter comparison of three surgical approaches.

STUDY DESIGN: Multicenter analysis of 3 groups of patients who underwent surgical treatment for adolescent idiopathic scoliosis (AIS). OBJECTIVE.: To evaluate 3 surgical approaches to determine the modality that has the greatest influence on improving thoracic kyphosis. SUMMARY OF BACKGROUND DATA: AIS is characterized by thoracic hypokyphosis which may be restored to normal to varying degrees with surgery. METHODS: A multicenter retrospective AIS surgical database was reviewed. Patients with only a structural main thoracic curve (Lenke 1, 2, or 3), and instrumentation of only the main thoracic curve were included. Lateral radiographs were analyzed to determine sagittal plane measurements before surgery, after surgery at 6 to 8 weeks, 1 year, and 2 years. The 3 groups were compared and statistical significance was defined as P < 0.05. RESULTS: Three groups were analyzed: (1) ASF group (n = 135), Anterior spinal fusion and instrumentation, (2) PSF-Hybrid group (n = 86), PSF with proximal hooks, +/- apical wires and distal pedicle screws, and 3) PSF-Hooks group (n = 132), PSF with only hooks. All groups had similar preoperative coronal main thoracic curve magnitudes (ASF: 50.6 degrees , PSF-Hybrid: 49.1 degrees , PSF-Hooks: 52.0 degrees ) and thoracic kyphosis (ASF: 23.7 degrees , PSF-Hybrid: 19.3 degrees , PSF-Hooks: 21.9 degrees ). After surgery, the T5-T12 kyphosis was greater in the ASF group (25.1 degrees ) compared with PSF-Hooks (19.0 degrees ) and PSF-Hybrid (18.5 degrees (P < 0.05). At 1 year, thoracic kyphosis (T5-T12) remained greater in the ASF group (28.8 degrees ) compared with PSF-Hooks (22.6 degrees ) and PSF-Hybrid (20.2 degrees ) (P < 0.05), and was also greater at 2 years (29.9 degrees vs. 23.8.8 degrees and 19.7 degrees ) (P < 0.05). Kyphosis at the thoracolumbar junction was not seen in the PSF-Hybrid group. Lumbar lordosis increased only in the ASF group in response to the increase in thoracic kyphosis. CONCLUSION: ASFI is the best method to restore thoracic kyphosis when compared with posterior approaches using only hooks or a hybrid construct in the treatment of thoracic adolescent idiopathic scoliosis.

Age-gender matched comparison of SRS instrument scores between adult deformity and normal adults: are all SRS domains disease specific?

STUDY DESIGN: Prospective, observational study. OBJECTIVE: To further validate the Scoliosis Research Society (SRS) instrument by comparing scores of adult deformity patients with no prior history of spine surgery to the scores of normal adult volunteers in age-gender matched groups. SUMMARY OF BACKGROUND DATA: Efforts have been made to validate the SRS questionnaire in adolescent and adult deformity patients. An important psychometric attribute of any quality of life tool is its ability to discriminate between subjects with and without the condition of interest. Discriminate validity of the SRS questionnaire has not been established in the primary (no prior surgical treatment) adult deformity population. METHODS: The SRS questionnaire was issued prospectively to 935 primary adult deformity patients with a diagnosis of idiopathic or de novo scoliosis and minimum Cobb angle of 30 degrees (average Cobb angle: 54 degrees; range: 30 degrees-132 degrees). Five hundred forty-three patients were treated nonsurgically while 392 patients underwent surgical intervention. Baseline SRS scores of the deformity population were compared to 1222 volunteers with no history of spine disease randomly sampled from the US population. Analysis between the 2 populations was broken down into 6 age-gender groups: male/female; 20-40, 41-60, 61-80 years of age. RESULTS: SRS domain scores of the deformity subgroups demonstrated significant statistical differences from their corresponding age-gender matched normative group. The only exceptions were the mental health domain in the older males, 61-80 years of age. The average SRS subscore for each age-gender subgroup was less than the tenth percentile in the corresponding normative population, indicating substantial limitations in these patients. CONCLUSION: Our findings confirm the SRS instrument has excellent discriminate validity in the adult population. It appears to be disease-specific in the domains of pain, appearance and activity in adult spinal deformity patients who have not had prior surgery.