Longitudinal Clinical Study Research Articles

A Retrospective Pragmatic Longitudinal Case-Series Clinical Study to Evaluate the Clinical Outcome of Triple-Frequency Ultrasound in Treatment of Cellulite.

In this single-centre, retrospective, pragmatic, longitudinal case-series clinical study triple-frequency LDM (TF-LDM) technology with frequencies of 1/3/10 MHz and 3/10/19 MHz was applied for treatment of cellulite to reveal the effect of these waves on the cellulite skin and assess the sustainability of treatment outcomes during the long-term follow-up controls. Twenty Caucasian females with mild-to-severe gynoid lipodystrophy aged 27-53 years who received cellulite monotherapy with TF-LDM were included in this study. All participants were evaluated at three time points: baseline (T1), on the day of the last treatment (T2), and during the last follow-up (T3). Cellulite severity was assessed by six independent clinicians using the five-grade Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS). Patient satisfaction was evaluated using a 10-grade GAIS scale, ranging from 0 to 10 (0 - dissatisfied; 10 - fully satisfied). To objectify the treatment outcomes, 17 subjects were investigated using B-mode ultrasonography and real-time compression elastography at baseline and during follow-up. The average values of CR-PCSS (T1), CR-PCSS (T2) and CR-PCSS (T3) over all participants were 2.22±0.82, 1.18±0.77, and 0.84±0.77, respectively, which corresponded to the skin improvement between T1 and T2 of 0.93±0.27 (p < 0.0001) as well as between T1 and T3 of 1.38±0.47 (p < 0.0001). Assessment of elasticity of the dermis and adipose tissue on the basis of the 5-grade coloration scale revealed significant reinforcement of both tissues as well as of the superficial fascia at follow-up as compared to their baseline values. The obtained treatment outcomes were long-lasting and could be clearly observed even in individuals with a long-term follow-ups. Assessment of the satisfaction of participants with the treatment results revealed a high satisfaction of 8.95 ± 1.49. The method demonstrated no side effects, was pain-free, well-tolerated, and highly accepted by patients.

Ultrasound-guided high-intensity focused ultrasound for symptomatic uterine fibroids: clinical outcome of two European centers.

The aim of this study is to assess the clinical outcome and mid-term efficacy of ultrasound-guided high-intensity focused ultrasound (USgHIFU) as a treatment for symptomatic uterine fibroids at two major European HIFU centers. This bi-center longitudinal clinical study involved the treatment of 100 patients with symptomatic uterine fibroids using USgHIFU (n = 59 in Germany, n = 41 in Bulgaria). Clinical outcomes were evaluated at 6 weeks, 6 months, and 1 year follow-up utilizing the uterine fibroid symptoms-quality of life questionnaire for fibroid-related symptoms and health-related quality of life as well as MRI imaging for determining the fibroid volume. The mean fibroid volume reduction rate was 33.2 ± 22.9%, 51.3 ± 24.2%, and 59.1 ± 28.0% at 6 weeks, 6 months, and 1 year, respectively (each p < 0.001). The mean symptom severity score decreased from 43.9 ± 18.8 at baseline to 35.4 ± 18.2 at 6 weeks, 31.1 ± 20.0 at 6 months, and 23.1 ± 14.0 at 1 year (each p < 0.001). The mean QOL score improved from 56.5 ± 23.4 at baseline to 65.4 ± 22.2 at 6 weeks, 72.5 ± 19.5 at 6 months, and 79.4 ± 15.3 at 1 year (each p < 0.001). No major complications were observed, though two patients experienced temporary sciatic nerve irritation following the procedure. Four patients had pregnancies and deliveries without any complications after USgHIFU therapy. To our knowledge, this is the first longitudinal study conducted in two major European HIFU centers that reveals the clinical efficacy of USgHIFU ablation on symptomatic uterine fibroids. Our results confirm that USgHIFU is a non-invasive approach with a low risk of complications, offering an innovative treatment option for affected women. Question To evaluate mid-term clinical efficacy and safety of US-guided high-intensity focused ultrasound (HIFU) for treating symptomatic uterine fibroids and patient outcomes across two European centers. Findings US-guided HIFU treatment resulted in significant fibroid volume reduction (up to 59.1% after 1 year) improving symptoms and quality of life with no major complications. Clinical relevance This prospective longitudinal study provides preliminary data assessing mid-term efficacy and clinical outcomes of ultrasound-guided HIFU. It is shown to be a low-risk, non-invasive treatment option for symptomatic uterine fibroids that reduces fibroid size and improves patients' quality of life.

Healthy Dietary Patterns and Lower Atherosclerosis in High-Risk Individuals.

This study investigates associations between diet patterns and the risk of intracranial atherosclerosis (ICAD) in individuals with preexisting hypertension (HTN) or myocardial infarction (MI). 676 autopsied participants (mean age at death =91.1±6.1, 71% women) of a longitudinal clinical neuropathological cohort study, with complete dietary and neuropathology data, were included. Diet scores were computed (median interval to death = 5.9 (3.0, 8.7 years). HTN and MI history was self-reported. Large vessel atherosclerosis was evaluated at the circle of Willis, and severity of intracranial atherosclerosis was assessed based on number of atherosclerotic plaques, extent of vessel involvement, and degree of vessel occlusion to create a 4-level grading system (0-3). All regression models were adjusted for age, sex, education, caloric intake, and APOE4. Of the 676 subjects, 361 (53%) had mild, 142 (21%) had moderate, and 29 (5%) had severe atherosclerosis. There was no direct relationship between diet and atherosclerosis. The relationship between ICAD and MI (OR = 1.38, 95% CI = 0.95, 2.00) showed a nonsignificant trend. HTN (OR = 1.598, 95% CI = 1.15, 2.18) was positively associated with intracranial atherosclerosis. The association of diet with intracranial atherosclerosis differed by history of MI (MIND (p=0.007), MedDiet (p=0.006)). The association between ICAD and the MIND diet also differed by whether HTN was reported (β=-0.212, SE= 0.111, p=0.055) as did the relationship between ICAD and the MedDiet (β = -0.077, SE= 0.035, p=0.029). In stratified analysis, among individuals with preexisting MI (N=130), those with a better diet had lower odds of intracranial atherosclerosis (MedDiet: OR = 0.88, 95% CI = 0.81, 0.96; MIND: OR = 0.69, 95% CI = 0.53, 0.90). A healthy dietary pattern is associated with lower odds of severe intracranial large vessel atherosclerosis in high-risk older adults. In-vivo studies of dietary habits and brain health, specifically in those at high vascular risk are needed.

Correlation between dental symptoms and functional and clinical manifestations of Crohn's disease and ulcerative colitis

Objective. To analyze the correlation between dental symptoms and clinical and functional manifestations of Crohn's disease (CD) and ulcerative colitis (UC). Materials and methods. A prospective, observational, longitudinal clinical study of 70 patients with verified inflammatory bowel diseases, i.e. Crohn's disease and ulcerative colitis, has been performed. For an in-depth assessment of the oral mucosa (OM) and red lip border (RLB) condition in patients with these systemic diseases, a complete dental examination has been carried out. The validated questionnaire "7´7" was used to objectify the symptoms of functional gastric dyspepsia. Results. In patients with the main clinical manifestations of the gastrointestinal tract impairments in CD and UC, extraintestinal dental manifestations in the form of meteorological cheilitis (16 and 9, respectively; p = 0.081), glossitis (15 and 11, respectively; p = 0.323), onset of recurrent aphthous stomatitis (17 and 11; p = 0.144), chronic mechanical trauma of oral mucosa (14 and 11; p = 0.455), and the presence of scalloped tongue (28 and 21, p = 0.068) were diagnosed. At the same time, the incidence of associated pathologies of OM and RLB was significantly higher in patients with CD (p0.05) than in patients with UC. Clinical examination of patients revealed predominance of flatulence symptoms in patients with CD and UC in 74.3 and 77.1 % of cases, respectively (р = 0.771). Patients with CD prevailed in the number of dyspeptic disorders and their variability but statistically significant differences were determined only for the symptom 'abdominal pain decreasing after bowel emptying'. The correlation between the frequency of dyspeptic disorders in patients and characteristic changes in the clinical state of RLB and OM was revealed. For the CD and UC groups Chuprov conjugacy coefficients were statistically significant (ChC=0.36, ChC=0.28 respectively). In patients with CD clinically apparent changes in the RLB and OM associated with various dyspeptic disorders were manifested more often than in patients with UC. Conclusion. The conducted study has shown that in patients with CD and UC there is a correlation between the frequency and severity of the main functional and clinical symptoms/syndromes (in the form of edema, hyperemia, pitting edema of the ОМ (in fact) and the RLB) and dyspeptic disorders, this correlation being stronger in Crohn's disease (p = 0.031 vs p = 0.046).

Utility of factor D and other alternative complement factors as biomarkers in systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH)

BackgroundActivation of the complement cascade is thought to play a role in scleroderma vasculopathy. We previously showed that complement factor D was elevated in patients with limited cutaneous SSc and pulmonary arterial hypertension (PAH). In this study, we sought to assess multiple relevant components of the complement cascade to determine if they are altered in SSc-PAH, as well as their potential utility as biomarkers of disease severity and progression. MethodsComplement components (n = 14) were measured using multiplex assays in 156 patients with SSc-PAH from a multi-site repository and were compared to 33 patients with SSc without PAH, and 40 healthy controls. Data were evaluated for correlations between complement levels, right heart catheterization measures, and clinical endpoints including 6-minute walk distance. To assess complement longitudinally, serum complement levels were assayed at 0, 4, 12, 24, 36 and 48 weeks in 52 SSc-PAH patients who participated in a prior clinical trial. ResultsWe found that factor D was significantly elevated in SSc-PAH compared to SSc without PAH (p < 0.0001) and was highly sensitive and specific for SSc-PAH (AUC=0.82, p < 0.001). In SSc-PAH patients, alterations in factor H, C4, and factor D were associated with measures of PAH disease severity including right heart catheterization measurements (cardiac output, right atrial pressure, and VO2 max), survival, and 6-minute walk distance. No significant changes in complement levels or clinical associations were seen over time or associated with treatment in the longitudinal clinical trial study. ConclusionOur work confirms prior studies demonstrating a role for complement activation in SSc vascular disease and elevations of factor D in a large SSc-PAH population. Further, factor H and other complement factors are associated with severity of PAH including mortality. Taken together, these findings suggest that the alternative complement pathway plays a role in SSc-PAH pathogenesis and may serve as a biomarker to inform diagnosis and prognosis.

Caregiver burden in informal spousal caregivers predicts psychological and physical health in patients following coronary artery bypass graft surgery: a longitudinal clinical cohort study.

Previous research has shown that informal caregiver burden can have deleterious effects on patient recovery; however, this relationship has yet to be investigated in patients undergoing coronary artery bypass graft (CABG) surgery. This study aimed to examine the impact of the change of caregiver burden from pre- to post-surgery on patients' mental and physical health after CABG surgery. Ninety patient-caregiver dyads were assessed one month before the surgery, two months and one year after the surgery. Caregivers completed the Oberst Burden Scale to measure caregiver burden. Patients completed the Beck Depression Inventory to measure depressive symptoms, a subscale of the Hospital Anxiety and Depression Scale to measure anxiety symptoms, the Short Form-12 health assessment to measure health-related quality of life, and the Coronary Revascularisation Outcomes Questionnaire to measure surgery symptoms. Hierarchical linear regression analyses were conducted to explore the association between change in caregiver burden and post-surgery patient outcomes. A greater increase in caregiver burden from pre- to two-months post-surgery significantly predicted higher patients' depressive symptoms (β = 0.179, p = 0.010), anxiety symptoms (β = 0.114, p = 0.017), reported post-surgery symptoms (β = 0.335, p = 0.008) and reduced physical health-related quality of life (β = -0.358, p = 0.003), after controlling for a wide range of covariates. These findings were not replicated at a one-year follow-up. These results provide insights into the impact of caregiver burden on patient distress following CABG surgery, supporting the idea of psychological support interventions for caregivers to increase patients' short-term recovery outcomes.

Diffusion decrease in normal-appearing white matter structures following photon or proton irradiation indicates differences in regional radiosensitivity

PurposeRadio(chemo)therapy (RCT) as part of the standard treatment of glioma patients, inevitably leads to radiation exposure of the tumor-surrounding normal-appearing (NA) tissues. The effect of radiotherapy on the brain microstructure can be assessed by magnetic resonance imaging (MRI) using diffusion tensor imaging (DTI). The aim of this study was to analyze regional DTI changes of white matter (WM) structures and to determine their dose- and time-dependency. MethodsAs part of a longitudinal prospective clinical study (NCT02824731), MRI data of 23 glioma patients treated with proton or photon beam therapy were acquired at three-monthly intervals until 36 months following irradiation. Mean, radial and axial diffusivity (MD, RD, AD) as well as fractional anisotropy (FA) were investigated in the NA tissue of 15 WM structures and their dependence on radiation dose, follow-up time and distance to the clinical target volume (CTV) was analyzed in a multivariate linear regression model. Due to the small and non-comparable patient numbers for proton and photon beam irradiation, a separate assessment of the findings per treatment modality was not performed. ResultsFour WM structures (i.e., internal capsule, corona radiata, posterior thalamic radiation, and superior longitudinal fasciculus) showed statistically significantly decreased RD and MD after RT, whereas AD decrease and FA increase occurred less frequently. The posterior thalamic radiation showed the most pronounced changes after RCT [i.e., ΔRD = −8.51 % (p = 0.012), ΔMD = −6.14 % (p = 0.012)]. The DTI changes depended significantly on mean dose and time. ConclusionSignificant changes in DTI for WM substructures were found even at low radiation doses. These findings may prompt new radiation dose constraints sparing the vulnerable structures from damage and subsequent side-effects.

Long-Term Effect of Intra-Articular Adipose-Derived Stromal Vascular Fraction and Platelet-Rich Plasma in Dogs with Elbow Joint Disease-A Pilot Study.

(1) Background: The aim of the current pilot study was to describe the long-term effects of a single intra-articular injection of autologous stromal vascular fraction (SVF) with platelet-rich plasma (PRP) in dogs with confirmed elbow OA, using orthopedic lameness scoring and kinetic and kinematic gait analysis. For comparison of normal long-term variation of gait over time, a group of healthy control dogs (CDs) was also evaluated. (2) Methods: A prospective longitudinal clinical pilot study investigating 19 client-owned dogs with elbow OA (OADs) treated with SVF and PRP and eight CDs not receiving treatment. The OAD and CD groups were evaluated before and after 6 and at least 12 months following treatment with SVF and PRP (OAD group) and twice with a six-month interval (CD group), respectively, through orthopedic examinations, goniometry, and kinetic and kinematic analyses (seven variables). (3) Results: The OAD had an increase in fore-hind peak force symmetry ≥12 months after treatment (p < 0.05), but no other objective variables changed over time. Orthopedic consensus scores had improved at ≥six months follow-up evaluation (p < 0.05). None of the investigated gait variables had changed at ≥six months follow-up evaluation in the CD group. (4) Conclusions: The current study could not confirm a significant benefit from SVF and PRP treatment in OADs, but future studies should be conducted in order to fully evaluate the potential of the treatment. The improvement seen in fore-hindlimb symmetry may represent an improvement in gait or an incidental finding.

Long-term Effects of COVID-19 on Vascular Parameters: A Prospective Longitudinal Ultrasound Clinical Study for CME Credit June 2024

Long-term Effects of COVID-19 on Vascular Parameters: A Prospective Longitudinal Ultrasound Clinical Study for CME Credit June 2024

Generation and characterization of six human induced pluripotent stem cell lines (hiPSCs) from three individuals with SSADH Deficiency and CRISPR-corrected isogenic controls

Succinic Semialdehyde Dehydrogenase Deficiency (SSADHD) is an ultra-rare autosomal recessive neurometabolic disorder caused by ALDH5A1 mutations presenting with autism and epilepsy. Here, we report the generation and characterization of human induced pluripotent stem cells (hiPSCs) derived from fibroblasts of three unrelated SSADHD patients – one female and two males with the CRISPR-corrected isogenic controls. These individuals are clinically diagnosed and are being followed in a longitudinal clinical study.

'Suspension Palatoplasty' - A method of surgical correction of VPI post Cleft Palate repair.

To design the technique of 'Suspension Palatoplasty' for Velopharyngeal Insufficiency (VPI) post Cleft Palate (CP) based on optimal spatial positioning of palate at the time of VPI correction, by using a non-obstructive, high, midline pharyngeal flap for predictable velopharyngeal closure and normal speech. To evaluate the results of CP patients with VPI operated using the technique of 'Suspension palatoplasty'. An ambi-spective longitudinal clinical study. Comprehensive cleft care clinic in a private trust hospital. Patients operated using the 'Suspension Palatoplasty' technique for VPI post CP repair between 2014 and 2018 with a minimum follow-up period of 5 years. 'Suspension Palatoplasty' - Double Opposing Z (DOZ) plasty with palatal myoplasty is used to revise soft palate and a narrow superiorly based pharyngeal flap is used to suspend it for a dynamic velopharyngeal closure. Speech outcome and surgical complications. 70 out of 119 studied were found to have normal speech (59%), and another 25 patients (21%) had acceptable speech. Thus 95 out of 119 patients (80%) had normal or near-normal speech and did not require any further speech therapy or surgeries. 12 patients had snoring without difficulty in breathing. One patient had symptoms suggestive of obstructive sleep apnea. Younger patients had a higher percentage of normal speech outcomes. Many of our adult patients also attained normal speech. 'Suspension Palatoplasty' aims to achieve normal speech with little effort. It has minimal side effects. The author has performed 403 cases to date.

Healing and long-term prognosis of root-fractured permanent teeth: a retrospective longitudinal study.

The purpose of the present study was to evaluate permanent teeth with post-traumatic transversal root fractures, for their initial healing modality, the effect of candidate predictors and their long-term prognosis. A retrospective longitudinal clinical study was conducted to evaluate records from patients bearing transversal root fractures in permanent teeth in order to radiographically assess short-term healing and non-healing events in the fracture line, their prognostic factors and their relationship with long term outcomes. The inter-fragmentary tissues were classified as healing: hard tissue (HT), connective tissue (CT) or connective tissue and bone (CT + B) and non-healing: interposition of granulation tissue (GT). A competing risk survival analysis was conducted to estimate the hazards of healing and non-healing events in the short-term and the effect of demographic, clinical, and treatment variables was assessed using the subdistribution regression model (Fine & Gray). Radiographic findings showed 61.4% of healing in the short-term being strongly influenced by the presence and type of concomitant injuries to the coronal fragment. Teeth with concomitant crown fractures (sHR 24.38, 95% CI [3.16-188.3], p = 0.0022), luxations with dislocations (sHR 10.58, 95% CI [1.37-81.9], p = 0.0240) and subluxations (HR 9.66, 95% CI [1.14-81.7], p = 0.0370) were more likely to present non-healing of root fractures in the short-term. The healing rate in the long-term was of 75.9%, most of them with interposition of bone and connective tissue. Kappa statistics demonstrated an overall agreement of 67.1% between short and long-term healing patterns, in special HT and CT + Bone modalities. Healing at the fracture site was the most frequent outcome, both in the short-term and in the long-term. Short-term healing modality was strongly influenced by the presence and type of concomitant injuries to the crown fragment, being the worst prognosis observed in root-fractured teeth with concomitant crown fractures, followed by concomitant luxations with dislocation. Post-traumatic transversal root fractures have a positive prognosis supporting therefore, a more conservative approach for these teeth before considering more radical treatments.

Long-term effects of motivational interviewing vs. traditional counseling on dog owners' adherence to veterinary dental home care: a three-year follow-up study.

Periodontal disease is one of the most common health issues in dogs. However, disease is largely preventable by eliminating dental plaque, best achieved by daily tooth brushing. Unfortunately, owner adherence is low to the recommendation of daily tooth brushing in dogs. This study aimed to evaluate the impact of various communication strategies, traditional advice (TA) versus motivational interviewing (MI), and compare them to a control group receiving no additional communication (CG), on dog owners' performance of dental home care and the oral health of their dogs. The study was conducted as a longitudinal clinical intervention study spanning 3 years, and involved 75 dog owners with young dogs who were randomly assigned to one of three groups: TA, MI, or CG. Intervention groups received annual telephone consultations based on their assigned methodology. A questionnaire was administered twice to all groups, and the dental health of the dogs was assessed at the study's conclusion. Tooth brushing frequency demonstrated a significant increase in the MI group compared to the CG group (p < 0.01), albeit with a relatively low occurrence of daily brushing among owners. Dental health assessment revealed a significantly lower plaque index in the MI group compared to the CG group (p < 0.05), and a lower calculus index in the TA group compared to the CG group (p < 0.01). No statistically significant differences were observed between the MI and TA groups in terms of dental health. Regular veterinary communication appears to have a positive influence on dog owner adherence to veterinary recommendations concerning dental care in dogs. Communication with veterinarians (MI and traditional advice) improved owner knowledge, attitude, and decreased frequency of not brushing. Although dental health parameters improved, the effect size was small, suggesting the complexity of adherence. Personalized calls to dog owners offer potential for dental health improvement, warranting further comparison of MI with traditional advice.

Abstract C030: Serum levels and tumor tissue organization of decorin in pancreatic cancer: Links to chemoresistance and disease aggressiveness

Abstract Pancreatic cancer has nearly paralleling incidence and mortality rates. Only 15-20% of the tumors are resectable at presentation, and for the majority of patients the situation is palliative. Treatment options are limited to standard chemotherapy, and tumor response is often transient. The longitudinal observational clinical study Chemotherapy, Host response And Molecular dynamics in Periampullary cancer (CHAMP) aims to contribute with new insights on this devastating disease through longitudinal blood sampling during adjuvant and palliative chemotherapy and comprehensive analysis of tissue from resected as well as postmortem sampled tumor tissue. In the present study, encompassing the first 100 patients enrolled in the CHAMP study, 92 serum proteins related to inflammation and cancer were analyzed by proximity extension assay in on-treatment blood samples from baseline to six months. The results revealed that the small leucin-rich proteoglycan decorin was among the top up-regulated proteins during chemotherapy. After three months of treatment, high levels of serum decorin were significantly associated with a shorter overall survival (log rank p = 0.005). Decorin expression was also assessed by immunohistochemistry in resected tumors from 25 patients and in postmortem sampled primary tumors and metastases from 9 patients. In the latter, particularly strong expression of decorin, both in the tumor cells and in the stroma, was denoted in cases with a short overall survival. While there was no significant correlation between decorin in the tumors and in serum at baseline, strong correlations were seen at one and three months (Spearman’s rho = 0.70 and 0.85, respectively). To further validate the potential prognostic value of decorin, immunohistochemical analysis was performed on tumors from a retrospective cohort of 104 resected tumors with long-term follow-up. Survival analysis showed that high decorin expression in both the stromal compartment and in tumor cells was associated with shorter overall survival (log rank p = 0.036 and 0.001, respectively). Multivariable cox regression analysis, adjusted for conventional prognostic factors, further confirmed that decorin was an independent factor of shorter overall survival (hazard ratio: 1.74, 95% confidence interval 1.10-2.75 for stromal decorin, and hazard ratio: 1.83, 95% confidence interval 1.04-3.21 for tumor-cell specific decorin). In conclusion, these findings suggest that decorin may be associated with chemotherapy resistance in pancreatic cancer. Future studies are encouraged to further explore the mechanistic basis for these observations, and to validate the potential utility of serum-decorin as a biomarker to monitor treatment response. Citation Format: Maja Svensson, Johan Ohlsson, Sofie Olsson Hau, Alexandra Petersson, Karin Jirström. Serum levels and tumor tissue organization of decorin in pancreatic cancer: Links to chemoresistance and disease aggressiveness [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C030.

Evaluating the Sick Quitting Hypothesis for Frailty Status and Reducing Alcohol Use Among People With HIV in a Longitudinal Clinical Cohort Study.

Evaluating the Sick Quitting Hypothesis for Frailty Status and Reducing Alcohol Use Among People With HIV in a Longitudinal Clinical Cohort Study.

Comparison of Costs, Re-Intervention Rates, and Length of Hospital Stay for Three Uterus Sparing Interventions for Uterine Fibroids: A 2-Year Retrospective Claims Analysis.

To describe two-year post-operative outcomes, and healthcare utilization of three uterus-sparing interventions used to treat women with intramural and/or subserosal uterine fibroids. This was a post-market, randomized, prospective, multi-center, longitudinal, interventional, and comparative clinical study to evaluate the costs and health outcomes of LAP-RFA vs the standard uterine conserving technologies (myomectomy and UAE) for the treatment of symptomatic uterine fibroids in women who desire uterine conservation. For this RCT study, 54 subjects were randomized on a 1:1 ratio across the three procedures and followed out to two years. Their results were compared to retrospective US insurance claims from the IBM MarketScan® Commercial Database from 2017-2020 for 96,854 women who underwent a uterus-sparing procedure for fibroids. Mean ambulatory surgical center costs and the mean out-patient hospital costs were lowest for LAP-RFA ($13,134 and $14,428) and highest for UAE ($28,214 and $19,131). The total two-year re-intervention rate of any subsequent procedure (AM, LM, LAP-RFA, or UAE) was lowest in AM group (0%) followed by LM (4.2%), LAP-RFA (11%), and UAE (33%). Mean peri-operative reintervention costs and the mean reintervention total costs were $2429 and $5939 for LAP-RFA, $2122 and $8368 for LM, $4410 and $11,942 for AM, and $8113 and $46,692 for UAE subjects. In the RCT study, the average length of hospital stay was significantly less for the LAP-RFA group subjects (8.2 hours) in contrast to both the laparoscopic myomectomy group subjects (16.0 hours) and the abdominal myomectomy group subjects (33.6 hours). Despite the small numbers, two-year reintervention rates followed a similar pattern as the IBM MarketScan data. In comparing these three non-invasive approaches, LAP-RFA was associated with the lowest peri-operative cost, and UAE was associated with the highest peri-operative cost. Further studies are needed to assess the cost, effectiveness, and subject satisfaction with each procedure.

Evaluating the Sick Quitting Hypothesis for Frailty Status and Reducing Alcohol Use Among People With HIV in a Longitudinal Clinical Cohort Study.

"Sick quitting," a phenomenon describing reductions in alcohol consumption following poor health, may explain observations that alcohol appears protective for frailty risk. We examined associations between frailty and reductions in drinking frequency among people with HIV (PWH). At six Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) sites between January 2012 and August 2021, we assessed whether frailty, measured through validated modified frailty phenotype, precedes reductions in drinking frequency. We associated time-updated frailty with quitting and reducing frequency of any drinking and heavy episodic drinking (HED), adjusted for demographic and clinical characteristics in Cox models. Among 5,654 PWH reporting drinking, 60% reported >monthly drinking and 18% reported ≥monthly HED. Over an average of 5.4 years, frail PWH had greater probabilities of quitting (HR: 1.56, 95% confidence interval [95% CI] [1.13-2.15]) and reducing (HR: 1.35, 95% CI [1.13-1.62]) drinking frequency, as well as reducing HED frequency (HR: 1.58, 95% CI [1.20-2.09]) versus robust PWH. Sick quitting likely confounds the association between alcohol use and frailty risk, requiring investigation for control.

Rates of change of pons and middle cerebellar peduncle diameters are diagnostic of multiple system atrophy of the cerebellar type.

Definitive diagnosis of multiple system atrophy of the cerebellar type (MSA-C) is challenging. We hypothesized that rates of change of pons and middle cerebellar peduncle diameters on MRI would be unique to MSA-C and serve as diagnostic biomarkers. We defined the normative data for anterior-posterior pons and transverse middle cerebellar peduncle diameters on brain MRI in healthy controls, performed diameter-volume correlations and measured intra- and inter-rater reliability. We studied an Exploratory cohort (2002-2014) of 88 MSA-C and 78 other cerebellar ataxia patients, and a Validation cohort (2015-2021) of 49 MSA-C, 13 multiple system atrophy of the parkinsonian type (MSA-P), 99 other cerebellar ataxia patients and 314 non-ataxia patients. We measured anterior-posterior pons and middle cerebellar peduncle diameters on baseline and subsequent MRIs, and correlated results with Brief Ataxia Rating Scale scores. We assessed midbrain:pons and middle cerebellar peduncle:pons ratios over time. The normative anterior-posterior pons diameter was 23.6 ± 1.6 mm, and middle cerebellar peduncle diameter 16.4 ± 1.4 mm. Pons diameter correlated with volume, r = 0.94, P < 0.0001. The anterior-posterior pons and middle cerebellar peduncle measures were smaller at first scan in MSA-C compared to all other ataxias; anterior-posterior pons diameter: Exploratory, 19.3 ± 2.6 mm versus 20.7 ± 2.6 mm, Validation, 19.9 ± 2.1 mm versus 21.1 ± 2.1 mm; middle cerebellar peduncle transverse diameter, Exploratory, 12.0 ± 2.6 mm versus 14.3 ±2.1 mm, Validation, 13.6 ± 2.1 mm versus 15.1 ± 1.8 mm, all P < 0.001. The anterior-posterior pons and middle cerebellar peduncle rates of change were faster in MSA-C than in all other ataxias; anterior-posterior pons diameter rates of change: Exploratory, -0.87 ± 0.04 mm/year versus -0.09 ± 0.02 mm/year, Validation, -0.89 ± 0.48 mm/year versus -0.10 ± 0.21 mm/year; middle cerebellar peduncle transverse diameter rates of change: Exploratory, -0.84 ± 0.05 mm/year versus -0.08 ± 0.02 mm/year, Validation, -0.94 ± 0.64 mm/year versus -0.11 ± 0.27 mm/year, all values P < 0.0001. Anterior-posterior pons and middle cerebellar peduncle diameters were indistinguishable between Possible, Probable and Definite MSA-C. The rate of anterior-posterior pons atrophy was linear, correlating with ataxia severity. Using a lower threshold anterior-posterior pons diameter decrease of -0.4 mm/year to balance sensitivity and specificity, area under the curve analysis discriminating MSA-C from other ataxias was 0.94, yielding sensitivity 0.92 and specificity 0.87. For the middle cerebellar peduncle, with threshold decline -0.5 mm/year, area under the curve was 0.90 yielding sensitivity 0.85 and specificity 0.79. The midbrain:pons ratio increased progressively in MSA-C, whereas the middle cerebellar peduncle:pons ratio was almost unchanged. Anterior-posterior pons and middle cerebellar peduncle diameters were smaller in MSA-C than in MSA-P, P < 0.001. We conclude from this 20-year longitudinal clinical and imaging study that anterior-posterior pons and middle cerebellar peduncle diameters are phenotypic imaging biomarkers of MSA-C. In the correct clinical context, an anterior-posterior pons and transverse middle cerebellar peduncle diameter decline of ∼0.8 mm/year is sufficient for and diagnostic of MSA-C.

Targeted electronic health record-based recruitment strategy to enhance COVID-19 vaccine response clinical research study enrollment

Efficient recruitment of eligible participants is a significant challenge for clinical research studies. This challenge was exacerbated during the COVID-19 pandemic when in-person recruitment was not an option. In 2020, the University of Minnesota was tasked, as part of the National Cancer Institute's Serological Sciences Network for COVID-19 (SeroNet), to recruit participants for a longitudinal serosurveillance clinical research study with a goal of characterizing the COVID-19 vaccine-elicited immune response among immunocompromised individuals, which necessitated reliance on non-traditional strategies for participant recruitment. To meet our enrollment target of 300 transplant patients, 300 cancer patients, 100 persons living with HIV, and 200 immunocompetent individuals, we utilized targeted electronic health record (EHR)-based recruitment in addition to traditional recruitment tools, which was an effective combination of recruitment strategies. A significant advantage of patient portal messaging or other digital recruitment strategies such as email communication is timing. We reached 85 % (769 out of 900) of our enrollment target within one year with a 14.3 % response rate to invitations to participate in our study. This achievement is perhaps more salient given the COVID-19 pandemic-related constraints within which we were operating. We demonstrated that the EHR can be leveraged to quickly identify potentially eligible study participants either via EHR communication or mail. We also illustrate how the online portal MyChart can be used to efficiently send targeted recruitment messages.

Comparative analysis of periodontal pain and quality of life in patients with fixed multibracket appliances and aligners (Invisalign®): longitudinal clinical study

BackgroundsThe aim of this longitudinal clinical study is to analyse and compare according to location, degree and type, the pain presented by patients during their first year of treatment, as well as the quality of oral life after the placement of two types of orthodontic appliances: conventional brackets and removable Invisalign ® aligners.MethodsThe sample consisted of 140 patients grouped into 2 study groups of 70 patients each. The first group (brackets group- BG), with fixed multibracket appliances, using the MBT technique and a 0.022” slot. The second group (invisaling group- IG), in treatment with removable aligners (IG), using the Invisalign ® system. They were providen with a questionnare where they had to record the degree (mild, moderate or intense), the type and location of the pain monthly during the first year of treatment. The second form was the Spanish version of the OHIP-14, oral quality of life questionnaire, which was provided the twelfth month after the start of treatment.ResultsIn both groups, we found that the most frequent location of pain occurred during the first phase: mandibular for the IG group and maxillary in the BG group. Throughout the whole analysis, the intensity was mild-moderate with lower values in the conventional brackets’ group. The BG group reported acute pain while the IG group reported sensitive pain during the first month; later both reported sensitive pain.ConclusionsThere are differences in terms of periodontal pain in its degree, location, and type according to the different orthodontic techniques used.Trial registrationThe study was approved by the bioethics committee of the University of Salamanca (USAL_20/516).