Functional connectivity patterns are altered by low back pain and cause different responses to sham and real dry needling therapies: a systematic review of fMRI studies.

BACKGROUND: There is a relationship between low back pain (LBP) and central nervous system dysfunction. Needling therapies (e.g. acupuncture, dry needling) are proposed to impact the nervous system, however their specific influence is unclear. PURPOSE: Determine how needling therapies alter functional connectivity and LBP as measured by functional magnetic resonance imaging (fMRI). METHODS: Databases were searched following PRISMA guidelines. Studies using fMRI on individuals with LBP receiving dry needling or acupuncture compared to control or sham treatments were included. RESULTS: Eight studies were included, all of which used acupuncture. The quality of studies ranged from good (n = 6) to excellent (n = 2). After acupuncture, individuals with LBP demonstrated significant functional connectivity changes across several networks, notably the salience, somatomotor, default mode network (DMN) and limbic networks. A meta-analysis demonstrated evidence of no effect to potential small effect of acupuncture in reducing LBP (SMD -0.28; 95% CI: -0.70, 0.13). CONCLUSION: Needling therapies, like acupuncture, may have a central effect on patients beyond the local tissue effects, reducing patients' pain and disability due to alterations in neural processing, including the DMN, and potentially other central nervous system effects. The meta-analysis should be interpreted with caution due to the narrow focus and confined sample used.

Effects of Trigger Point Dry Needling on Strength Measurements and Activation Levels of the Gluteus Medius: A Quasi-Experimental Randomized Control Study.

Background: Latent trigger points have been identified as a source of impaired muscle function giving rise to a reduction in force production and alterations in muscle activation patterns and movement efficiency. There is limited investigation into the effectiveness of a treatment in reducing these clinical manifestations. Purpose: To investigate whether the application of trigger point dry needling (TDN) to latent trigger points within the gluteus medius musculature affected strength measurements and muscle activation levels immediately following intervention. Design: Quasi experimental, single group, pretest-posttest, randomized control study. Methods: A control and an intervention side were randomly assigned for each participant (N = 39). Hand held dynamometer (HHD) force measurements and raw surface electromyography (sEMG) amplitude readings were recorded during maximal volitional isometric contractions of the gluteus medius in two separate positions before and after application of TDN. Comparison of within and between group data were conducted. Results: A statistically significant interaction between time (pre-TDN to post-TDN) and groups (intervention side and control side), p < 0.001 was found for HHD measurements in both positions. Post hoc analysis revealed a statistically significant difference (p < 0.001) for all comparisons in the side lying neutral (SL0) position, while statistically significant differences (p < 0.001) were found for pre and post-TDN measurements within intervention side as well as between the intervention and control side for post-TDN measurements in the side lying internal rotation (SLIR) position. For sEMG amplitude measurements, statistically significant differences were found only in the SL0 position for within group comparisons on the intervention side (p = 0.009) and for between group comparisons for post-TDN measurements (p = 0.002). Conclusion: Application of TDN to latent trigger points within the gluteus medius can significantly increase gluteus muscle force production immediately following intervention while reducing the level of muscle activation required during contraction. Level of Evidence: Level 2.

Using Human-Centered Design to Build a Digital Health Advisor for Patients With Complex Needs: Persona and Prototype Development.

BACKGROUND: Twenty years ago, a "Guardian Angel" or comprehensive digital health advisor was proposed to empower patients to better manage their own health. This is now technically feasible, but most digital applications have narrow functions and target the relatively healthy, with few designed for those with the greatest needs. OBJECTIVE: The goal of the research was to identify unmet needs and key features of a general digital health advisor for frail elderly and people with multiple chronic conditions and their caregivers. METHODS: In-depth interviews were used to develop personas and use cases, and iterative feedback from participants informed the creation of a low-fidelity prototype of a digital health advisor. Results were shared with developers, investors, regulators, and health system leaders for suggestions on how this could be developed and disseminated. RESULTS: Patients highlighted the following goals: "live my life," "love my life," "manage my health," and "feel understood." Patients and caregivers reported interest in four functions to address these goals: tracking and insights, advice and information, providing a holistic picture of the patient, and coordination and communication. Experts and system stakeholders felt the prototype was technically feasible, and that while health care delivery organizations could help disseminate such a tool, it should be done in partnership with consumer-focused organizations. CONCLUSIONS: This study describes the key features of a comprehensive digital health advisor, but to spur its development, we need to clarify the business case and address the policy, organizational, and cultural barriers to creating tools that put patients and their goals at the center of the health system.

Increased breast cancer risk in women with neurofibromatosis type 1: a meta-analysis and systematic review of the literature.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a cancer predisposing syndrome. Studies suggest that women < 50 years old (y.o.) with NF1 have an increased breast cancer (BC) incidence and BC associated mortality. However, this has not been widely recognized secondary to small study populations. METHODS: A systematic literature review was conducted through database searches for BC and NF1: 3456 articles identified, 166 reviewed, 58 used for descriptive analysis and 4 utilized for meta-analysis. Fisher's exact tests, Kaplan-Meier curves and random-effects meta-analysis models were used for analysis. RESULTS: Two hundred eighty-six cases of NF1 and female BC were identified with a median age of 46 years at diagnosis; 53% were <  50. Peak age of BC diagnosis was between 34 to 44 years. Women < 50 y.o. presented with more advanced disease vs. those ≥50 (56% vs. 22% stage III-IV, respectively; p = 0.005). Median survival for the entire cohort was 5 years vs. the reported median BC survival of over 20 years in the general population using the SEER database. Median age at BC death was 48.5 years; 64% of deceased patients were <  50. Meta-analysis of a total of 4178 women with NF1 revealed a BC standardized incidence ratio (SIR) of 3.07 (95%CI 2.16-4.38) for women with NF1 vs. the general population. Women < 50 y.o. demonstrated a higher SIR of 5.08 (95%CI 3.77-6.81) compared to 1.92 (95%CI 1.40-2.63) if ≥50 y.o. CONCLUSIONS: This systematic literature review and meta-analysis suggests that women with NF1 <  50 y.o. have a five-fold increased risk of BC, present with more advanced disease, and may have an increased BC related mortality. Increased awareness and implementation of recent National Comprehensive Cancer Network early BC screening guidelines for this high-risk patient population is essential. Additional evaluation on the influence of NF1 gene mutations identified in patients undergoing hereditary cancer genetic testing on breast cancer risk in individuals without clinical evidence of NF1 is needed.

One-Hour Postoperative Parathyroid Hormone Levels Do Not Reliably Predict Hypocalcemia After Thyroidectomy.

INTRODUCTION: Hypocalcemia is a well-known complication after total thyroidectomy. Studies have indicated that the presence of low postoperative parathyroid hormone (PTH) levels can predict hypocalcemia. However, definitive study designs are lacking. The aim of this study was to determine whether postoperative PTH alone can accurately predict postoperative biochemical hypocalcemia. METHODS: Under IRB approval, a prospective study of 218 consecutive patients who underwent total or completion thyroidectomy by two surgeons between June 2014 and June 2016 was performed. Biochemical hypocalcemia was defined as ionized calcium <1.13 mmol/L or serum calcium <8.4 mg/dL at any time postoperatively. Three PTH thresholds, <10, <20 pg/mL, and >50% drop in PTH 1 h postoperatively from baseline were examined. RESULTS: Postoperative PTH < 10 pg/mL had a sensitivity of 36.5% (95% CI 27.4-46.3%) and a specificity of 89.2% (95% CI 81.9-94.3%). Postoperative PTH < 20 pg/mL had a sensitivity of 66.4% (95% CI 56.6-75.2%) and a specificity of 67.6% (95% CI 58.0-76.2%). Postoperative PTH decrease >50% had a sensitivity of 63.4% (95% CI 53.2-72.7%) and a specificity of 72.5% (95% CI 62.5-81.0%). Across all PTH thresholds, the false-negative rate was 33.6-63.5% indicating that up to 64% of patients with a normal PTH level could have been discharged without appropriate calcium supplementation. The false-positive rate was 10.8-32.4% indicating that up to 32.4% of patients with low PTH could have been treated with calcium supplementation unnecessarily. CONCLUSION: Following total thyroidectomy, PTH levels are unreliable in predicting hypocalcemia. Additional prospective studies are needed to understand the true utility of PTH levels post-thyroidectomy.

Association of Parathyroid Hormone Level With Postthyroidectomy Hypocalcemia: A Systematic Review.

IMPORTANCE: There has been an increased interest in measuring parathyroid hormone (PTH) levels as an early predictive marker for the development of hypocalcemia after total thyroidectomy. However, significant variation exists in the timing, type of assay, and thresholds of PTH in the literature. OBJECTIVE: We performed a systematic review to examine the utility of PTH levels in predicting temporary postthyroidectomy hypocalcemia. EVIDENCE REVIEW: A systematic literature review of studies published prior to May 25, 2016 was performed within PubMed, EMBASE, SCOPUS, and Cochrane databases using the following terms and keywords: "thyroidectomy," "parathyroid hormone," and "hypocalcaemia," "calcium," or "calcitriol." Each candidate full-text publication was reviewed by 2 independent reviewers and selected for data extraction if the study examined the prognostic significance of PTH obtained within 24 hours after thyroidectomy to predict hypocalcaemia. Studies were excluded if calcium supplementation was used routinely or based on a PTH level. Study characteristics, PTH parameters used to predict hypocalcemia, and their respective accuracies were summarized. FINDINGS: The initial search yielded 2417 abstracts. Sixty-nine studies, comprising 9163 patients, were included. Overall, for an absolute PTH threshold, the median accuracy, sensitivity, and specificity were 86%, 85%, and 86%, respectively. For a percentage change over time the median accuracy, sensitivity, and specificity were 89%, 88%, and 90%, respectively. CONCLUSIONS AND RELEVANCE: The existing literature regarding PTH levels to predict postthyroidectomy hypocalcemia is extremely heterogeneous. A single PTH threshold is not a reliable measure of hypocalcemia. Additional prospective studies controlled for timing of laboratory draws and a priori defined PTH thresholds need to be performed to ascertain the true prognostic significance of PTH in predicting postthyroidectomy hypocalcaemia.

Coordination within medical neighborhoods: Insights from the early experiences of Colorado patient-centered medical homes.

BACKGROUND: The term "medical neighborhood" refers to relationships that patient-centered medical homes (PCMHs) seek to establish with other providers to facilitate coordinated patient care. Yet, how PCMHs can accomplish this coordination is not well understood. PURPOSE: Drawing upon organizational theory (; ; ), we explored how PCMHs use coordination mechanisms to build and optimize their medical neighborhoods. METHODOLOGY: We used mixed methods, blending data collected via interviews and surveys with practice leaders and care coordinators at 30 months after a PCMH collaborative intervention in Colorado as well as surveys from all providers from 13 PCMHs before and 30 months after the intervention. We used thematic analysis to understand the role and use of coordination mechanisms by PCMHs and changes in the ability to coordinate and deliver care continuity. FINDINGS: PCMHs drew on four coordination mechanisms to build relationships with their medical neighbors: interorganizational routines to improve reliability of information flow; information connectivity to facilitate continuity and safe care; boundary spanners to integrate care across silos; and communication, negotiation, and decision mechanisms to introduce shared accountability. When providers were fairly confident of the patient's diagnosis and management required sequential interactions (such as tests or procedures), PCMHs tended to coordinate care through interorganizational routines and information connectivity. When a diagnosis was less certain and required reciprocal interaction (i.e., consultation), PCMHs employed boundary spanners and communication, negotiation, and decision mechanisms. PRACTICE IMPLICATIONS: Use of coordination mechanisms by PCMHs can help to improve care coordination in medical neighborhoods. All four mechanisms appear to be useful. The optimal mix of coordination mechanisms requires attention to patient context. Successfully building medical neighborhoods also requires meta-leaders, collaboration competencies, and high-quality relationships between providers in primary care, specialty care, and hospitals.

Retained Intraocular Perfluoro-n-octane After Valved Cannula Pars Plana Vitrectomy for Retinal Detachment.

BACKGROUND AND OBJECTIVE: To investigate cases of retained intraocular perfluoro-n-octane (PFO) after pars plana vitrectomy (PPV) for retinal detachment (RD). PATIENTS AND METHODS: Retrospective, noncomparative case series of six eyes with retained intraocular PFO after RD repair. Clinical data were supplemented with an experimental silicone eye model. RESULTS: A cluster of six cases of retained intraocular PFO after PPV for RD repair were noted shortly after transitioning to valved cannulas. PFO was noted in the anterior chamber (AC) and/or vitreous and removed with AC paracentesis, AC wash-out, and/or PPV. A silicone eye model demonstrated that PFO levels are maintained anterior to cannula insertion with valved cannulas only. CONCLUSION: The authors hypothesize that anterior PFO fill using valved cannulas can lead to sequestration within the AC, zonules, ciliary sulcus, ciliary teeth, and/or capsular bag. They suggest vigilance in not overfilling PFO, particularly when transitioning to use of valved cannulas, to minimize the risk of intraocular retention.

Defining and measuring integrated patient care: promoting the next frontier in health care delivery.

Integration of care is emerging as a central challenge of health care delivery, particularly for patients with multiple, complex chronic conditions. The authors argue that the concept of "integrated patient care" would benefit from further clarification regarding (a) the object of integration and (b) its essential components, particularly when constructing measures.To address these issues, the authors propose a definition of integrated patient care that distinguishes it from integrated delivery organizations, acknowledging that integrated organizational structures and processes may fail to produce integrated patient care. The definition emphasizes patients' central role as active participants in managing their own health by including patient centeredness as a key element of integrated patient care. Measures based on the proposed definition will enable empirical assessment of the potential relationships between the integration of organizations, the integration of patient care, and patient outcomes, providing valuable guidance to health systems reformers.

American Society of Clinical Oncology/National Comprehensive Cancer Network Quality Measures.

PURPOSE: The National Cancer Policy Board recommended the creation of quality measures and a national reporting system in 1999. Representatives from the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) collaborated to create metrics suitable for national performance measurement. METHODS: Content and methodology experts nominated by ASCO and NCCN met to select and refine metrics for breast, colon, and rectal cancer based on National Initiative for Cancer Care Quality and NCCN measures and NCCN and ASCO guidelines. Measures were selected based on their impact on disease free and overall survival, the degree to which opportunities for improvement exist, and the feasibility of data collection. RESULTS: Three breast cancer measures and four colorectal cancer measures were chosen. Measures for breast cancer included adjuvant hormone therapy for hormone receptor-positive tumors, chemotherapy for hormone receptor-negative cancer, and radiation after lumpectomy. Colorectal measures included adjuvant radiation and chemotherapy for rectal cancer, and adjuvant chemotherapy for colon cancer. All but one were recommended as accountability measures and one for quality improvement (removal and examination of 12 or more lymph nodes in colon cancer). Specifications were developed for each measure using tumor registries as the data source. CONCLUSION: ASCO/NCCN measures can be implemented by health systems, provider groups or payors for improvement or accountability using local tumor registries to furnish data on staging and treatment.

Cellulose acetate 1,2-benzenedicarboxylate protects against challenge with pathogenic X4 and R5 simian/human immunodeficiency virus.

OBJECTIVES: To evaluate the protective efficacy of cellulose acetate 1,2-benzenedicarboxylate (CAP) formulated in a glycerol-based gel against infection with CXCR4 (X4) and CCR5 (R5) viruses in the simian/human immunodeficiency virus (SHIV)/rhesus macaque model of HIV-1 transmission. DESIGN: Mucosal infection of non-human primates is a reasonable model for use in the investigation of HIV-1 intervention strategies. METHODS: Rhesus macaques treated with Depo-Provera 5 weeks prior to challenge were inoculated intravaginally twice, over a period of 6 h with mixed inocula of pathogenic X4- and R5-SHIV in the presence or absence of CAP. Plasma viral load, peripheral and mucosal CD4 T cell counts as well as the genotype of the circulating virus were determined. RESULTS: CAP protected seven of ten macaques against transmission of both X4- and R5-SHIV, reaching statistically significant values (P = 0.0256). Delayed and/or reduced virus replication, as well as blunting of peripheral and mucosal CD4 T cell loss was noted in the three macaques that were infected in the CAP treated group compared to those in the placebo group. Further, protection conferred by CAP appeared to be more effective against X4- than R5-SHIV infection. CONCLUSIONS: CAP is protective against highly permissive challenges with X4 and R5 viruses in vivo. Research on further development of this promising compound as a candidate microbicide for the prevention of sexual HIV-1 transmission is therefore warranted.

Interference with heme binding to histidine-rich protein-2 as an antimalarial strategy.

The erythrocytic growth stage of Plasmodium falciparum involves hemoglobin proteolysis as the primary nutrient source with the concomitant release of free heme. The liberated heme is processed by the parasite into hemozoin, a polymeric porphyrin dimer. Histidine-rich protein binds heme and mediates the formation of hemozoin, which is inhibited by the antimalarial drug chloroquine. Interference with heme binding was determined using a microtiterplate assay. Combinatorial libraries were screened and tested against parasite growth, revealing a good correlation between heme binding interference and the inhibition of parasite growth. Several of these compounds retain their potency against a chloroquine-resistant strain of Plasmodium falciparum. The most potent compounds have IC(50) values less than or equal to 50 nM against chloroquine-resistant and chloroquine-sensitive parasites.