Functional Outcome and Inflammatory Response of Patients with Extra-Articular Distal Humeral Fractures following Implantation of Anatomically Precontoured Locking Compression Plates through a Posterior Approach.

Distal humeral fractures are challenging injuries to surgically correct and account for up to 2% of all adult fractures. Surgical management of extra-articular distal humeral fractures is challenging considering surgical approach, implant selection, and position of the implant owing to the availability of different precontoured implants and plate configurations. Anatomically precontoured locking compression plates (APLCPs) allow the placement of angular stable screws right underneath the reduced joint surface fragments. To date, there is a lack of evidence supporting its superiority to conventional locking plate osteosynthesis (LPO) in treating extra-articular distal humeral fractures. The objective of the study is to evaluate the efficacy and safety of APLCPs in the treatment of extra-articular distal humeral fractures. A total of 100 patients diagnosed with humeral fractures and receiving treatments in our hospital between May 2018 and May 2020 fulfilled inclusion and exclusion criteria and were randomly assigned to LPO and APLCP groups according to the odd-even of the order of hospital admission, 50 cases per groups. Clinical endpoints were assessed including operation time; in-bed time; length of hospital stay; volume of intraoperative blood loss; VSA scores before and 24, 48, and 72 h after surgery; MEPS scores before and 3, 6, and 12 months after surgery; range of motion, flexion, and extension of the elbow; serum levels of CK, CRP, and IL-6; and incidence of complications after surgery. It was found that the APLCP group exhibited shortened operation time and in-bed time, decreased length of hospital stay, and reduced volume of intraoperative blood loss compared to the LPO group (all P < 0.001). The two groups had declined VSA scores concomitant with increased MEPS scores after surgery in a time-dependent manner (P < 0.001). Notably, the VSA scores in the APLCP group were all lower than those in the LPO group at indicated time points (24, 48, and 72 h) after surgery (P < 0.001). Besides, the MEPS scores in the APLCP group were all higher than those in the LPO group at indicated time points (3, 6, and 12 months) after surgery (P < 0.001). It was revealed that the patients receiving extra-articular distal humeral APLCP through posterior approaches exhibited greater ranges of motion, flexion, and extension of the elbow than those receiving LPO after surgery (P < 0.001). The patients receiving extra-articular distal humeral APLCP through posterior approaches exhibited lower serum levels of IL-6, CRP, and CK than those receiving LPO after surgery (IL-6: P=0.007, CRP: P=0.001, CK: P=0.001). The APLCP had a lower total incidence rate of complication than the LPO group (48.00% vs. 18.00%, P=0.003). In conclusion, these data support the notion that the implantation of anatomically precontoured APLCP through a posterior approach allows for improved functional outcomes and attenuated inflammatory response and prevents the incidence of postoperative complications compared to conventional LPO for internal fixation of extra-articular distal humeral fractures.

Design, synthesis, biological evaluation and molecular dynamics of LAR inhibitors.

In this study, firstly, the pharmacophore model was established based on LAR inhibitors. ZINC database and drug-like database were screened by Hypo-1-LAR model, and the embryonic compound ZINC71414996 was obtained. Based on this compound, we designed 9 compounds. Secondly, the synthetic route of the compound was determined by consulting Reaxys and Scifinder databases, and 9 compounds (1a-1i) were synthesized by nucleophilic substitution, Suzuki reaction and so on. Meanwhile, their structures were confirmed by 1H NMR and 13C NMR. Thirdly, the Enzymatic assays was carried out, the biological evaluation of compounds 1a-1i led to the identification of a novel PTP-LAR inhibitor 1c, which displayed an IC50 value of 4.8 µM. At last, molecular dynamics simulation showed that compounds could interact strongly with the key amino acids LYS1350, LYS1352, ARG1354, TYR1355, LYS1433, ASP1435, TRP1488, ASP1490, VAL1493, SER1523, ARG1528, ARG1561, GLN1570, LYS1681, thereby inhibiting the protein activity. This study constructed the pharmacophore model of LAR protein, designed small-molecule inhibitors, conducted compound synthesis and enzyme activity screening, so as to provide a basis for searching for drug-capable lead compounds.

Bioinformatic analysis and experimental identification of blood biomarkers for chronic nonunion.

BACKGROUND: Incomplete fracture healing may lead to chronic nonunion; thus, determining fracture healing is the primary issue in the clinical treatment. However, there are no validated early diagnostic biomarkers for assessing chronic nonunion. In this study, bioinformatics analysis combined with an experimental verification strategy was used to identify blood biomarkers for chronic nonunion. METHODS: First, differentially expressed genes in chronic nonunion were identified by microarray data analysis. Second, Dipsaci Radix (DR), a traditional Chinese medicine for fracture treatment, was used to screen the drug target genes. Third, the drug-disease network was determined, and biomarker genes were obtained. Finally, the potential blood biomarkers were verified by ELISA and qPCR methods. RESULTS: Fifty-five patients with open long bone fractures (39 healed and 16 nonunion) were enrolled in this study, and urgent surgical debridement and the severity of soft tissue injury had a significant effect on the prognosis of fracture. After the systems pharmacology analysis, six genes, including QPCT, CA1, LDHB, MMP9, UGCG, and HCAR2, were chosen for experimental validation. We found that all six genes in peripheral blood mononuclear cells (PBMCs) and serum were differentially expressed after injury, and five genes (QPCT, CA1, MMP9, UGCG, and HCAR2) were significantly lower in nonunion patients. Further, CA1, MMP9, and QPCT were markedly increased after DR treatment. CONCLUSION: CA1, MMP9, and QPCT are biomarkers of nonunion patients and DR treatment targets. However, HCAR2 and UGCG are biomarkers of nonunion patients but not DR treatment targets. Therefore, our findings may provide valuable information for nonunion diagnosis and DR treatment. TRIAL REGISTRATION: ISRCTN, ISRCTN13271153. Registered 05 April 2020-Retrospectively registered.

Medication use in breast cancer survivors compared to midlife women.

PURPOSE: Many breast cancer survivors (BCS) take multiple medications for health problems associated with the treated cancer and other noncancer comorbidities. However, there is no published, large-scale descriptive evaluation of medication use in BCS compared to midlife women. The purpose of this study was (1) to compare the number and types of prescription medications and over-the-counter medications between BCS and midlife women without cancer and (2) to assess possible drug-drug interactions by evaluating the cytochrome P450 isoform properties of medications (inductors and inhibitors) in both groups. METHODS: A cross-sectional, descriptive, comparative design was used. Baseline data from 98 BCS and 138 midlife women without cancer was analyzed from a behavioral intervention trial for menopausal symptoms. RESULTS: BCS were taking significantly more prescription medications and a larger variety of different types of medication classifications (p < 0.05) after controlling for group differences (race, noncancer comorbid conditions, marital status, income, and smoking) in demographics. Twenty-four women were taking at least one medication considered to be a cytochrome P450 isoforms (CYP) inhibitor or inducer capable of clinical drug-drug interactions with no differences in CYP inhibitors or inducers found between groups. CONCLUSION: BCS are taking a vast array of medications during survivorship. It is unclear if prescription medications are managed by a single healthcare provider or several providers. Clinical implications are to monitor for possible interactions among the various prescription medications, over-the-counter medications, and supplements. Implications for behavioral and biomedical research are that clinical studies need to carefully assess and account for multiple medication uses. RELEVANCE OF THE STUDY: The findings of this study are relevant to research and practice for both oncology and general practitioners. The importance of assessing medication information provides information about symptom management in individuals surviving cancer. In addition, the potential interaction of drugs impacts efficacy of various treatments and impacts compliance by patients.

Paced respiration for vasomotor and other menopausal symptoms: a randomized, controlled trial.

BACKGROUND: Paced respiration has been internationally recommended for vasomotor symptom management, despite limited empirical evidence. OBJECTIVE: To evaluate efficacy of a paced respiration intervention against breathing control and usual care control for vasomotor and other menopausal symptoms. DESIGN: A 16-week, 3-group, partially blinded, controlled trial with 2:2:1 randomization and stratification by group (breast cancer, no cancer), in a Midwestern city and surrounding area. PARTICIPANTS: Two hundred and eighteen randomized women (96 breast cancer survivors, 122 menopausal women without cancer), recruited through community mailings and registries (29 % minority). INTERVENTIONS: Training, home practice support, and instructions to use the breathing at the time of each hot flash were delivered via compact disc with printed booklet (paced respiration intervention) or digital videodisc with printed booklet (fast shallow breathing control). Usual care control received a letter regarding group assignment. MAIN MEASURES: Hot flash frequency, severity, and bother (primary); hot flash interference in daily life, perceived control over hot flashes, and mood and sleep disturbances (secondary). Intervention performance, adherence, and adverse events were assessed. KEY RESULTS: There were no significant group differences for primary outcomes at 8-weeks or 16-weeks post-randomization. Most intervention participants did not achieve 50 % reduction in vasomotor symptoms, despite demonstrated ability to correctly do paced respiration and daily practice. Statistically significant differences in secondary outcomes at 8 and 16 weeks were small, not likely to be clinically relevant, and as likely to favor intervention as breathing control. CONCLUSIONS: Paced respiration is unlikely to provide clinical benefit for vasomotor or other menopausal symptoms in breast cancer survivors or menopausal women without cancer.

Strategies used and data obtained during treatment fidelity monitoring.

BACKGROUND: Treatment fidelity, also called intervention fidelity, is an important component of testing treatment efficacy. Although examples of strategies needed to address treatment fidelity have been provided in several published reports, data describing variations that might compromise efficacy testing have been omitted. OBJECTIVES: The aim of this study is to describe treatment fidelity monitoring strategies and data within the context of a nursing clinical trial. METHODS: A three-group, randomized, controlled trial compared intervention (paced respiration) to attention control (fast, shallow breathing) to usual care for management of hot flashes and other menopausal symptoms. Data from both staff and participants were collected to assess treatment fidelity. RESULTS: Staff measures for treatment delivery indicated good adherence to protocols. Participant ratings of expectancy and credibility were not statistically different between intervention and attention control; however, the attention control was significantly more acceptable (p < .05). Intervention participant data indicated good treatment receipt and enactment with mean breath rates at each time point falling within the target range. Practice log data for both intervention and attention control indicated lower adherence of once-daily rather than twice-daily practice. DISCUSSION: Despite strengths in fidelity monitoring, some challenges were identified that have implications for other similar intervention studies.

Efficacy of guided imagery with relaxation for osteoarthritis symptoms and medication intake.

Supporting safe self-management interventions for symptoms of osteoarthritis (OA) may reduce the personal and societal burden of this increasing health concern. Self-management interventions might be even more beneficial if symptom control were accompanied by decreased medication use, reducing cost and potential side effects. Guided imagery with relaxation (GIR) created especially for OA may be a useful self-management intervention, reducing both symptoms and medication use. A longitudinal randomized assignment experimental design was used to study the efficacy of GIR in reducing pain, improving mobility, and reducing medication use. Thirty older adults were randomly assigned to participate in the 4-month trial by using either GIR or a sham intervention, planned relaxation. Repeated-measures analysis of variance revealed that, compared with those who used the sham intervention, participants who used GIR had a significant reduction in pain from baseline to month 4 and significant improvement in mobility from baseline to month 2. Poisson technique indicated that, compared with those who used the sham intervention, participants who used GIR had a significant reduction in over-the-counter (OTC) medication use from baseline to month 4, prescribed analgesic use from baseline to month 4, and total medication (OTC, prescribed analgesic, and prescribed arthritis medication) use from baseline to month 2 and month 4. Results of this study support the efficacy of GIR in reducing symptoms, as well as in reducing medication use. Guided imagery with relaxation may be useful in the regimen of pain management for clinicians.

Self-management practices among primary care patients with musculoskeletal pain and depression.

The objective of this study was to assess the effect of clinical depression on pain self-management practices. We employed a cross-sectional analysis of baseline data from the Stepped Care for Affective disorders and Musculoskeletal Pain (SCAMP) study. Participants included 250 patients with pain and comorbid depression and 250 patients with pain only and were enrolled from urban university and VA primary care clinics. Musculoskeletal pain was defined as low back, hip or knee pain present >or=3 months and with at least a moderate, Brief Pain Inventory severity score >or=5. Depression was defined as a PHQ-9 score >or=10. We used multiple logistic and Poisson regression to assess the relationship between individual and combined effects of depression and pain severity on two core pain self-management skills: exercise duration and cognitive strategies. Depressed patients exercised less per week than did nondepressed patients but showed a trend towards more frequent use of cognitive strategies. On multivariable analysis, depression severity substantially decreased the use of exercise as a pain self-management strategy. In contrast, depression and pain severity interacted to increase the use of cognitive strategies. Depression and pain severity have differential effects on self-management practices. Understanding the differences between preferential strategies of pain patients with and without depression may be useful in tailoring pain self-management programs.