Examining Resilient Pain Behaviors for Chronic Low Back Pain: A Scoping Review.

OBJECTIVES: The objective of this scoping review was to examine resilience and resilient pain behaviors for those with CLBP in relation to resilience definitions, operationalization (e.g. trait or behavior), and application of theoretical frameworks. DESIGN: This scoping review examined resilience and resilient pain behaviors for those with CLBP in relation to resilience definitions, operationalization (e.g. trait or behavior), and application of theoretical frameworks. DATA SOURCES: To gather data, we used five databases: Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Ovid MEDLINE, PsycInfo, and Scopus. REVIEW/ANALYSIS METHODS: Authors used a systematic data charting spreadsheet (Microsoft Excel) to review and analyze the extracted data. RESULTS: A total of 26 articles, from 2011-2021, were included in the final analysis. A majority of articles were conducted in the United States (11) and cross-sectional secondary data analysis design (13). Resilience definitions varied across the studies. Three studies operationalized resilience as a trait and only one as a behavior. Most studies (20) did not include a theoretical framework. CONCLUSION: The majority cross-sectional design and heterogeneity of a resilience definition indicates resilience research is still emerging. The lack of operationalized resilience, specifically as a behavior, and the limited use of theoretical frameworks suggest advancements in resilience pain research are needed. NURSING PRACTICE IMPLICATIONS: This research has implications for nursing practice to support nurse's holistic perspective and the ability to incorporate resilience within nursing care. This research provides the initial steps to developing standard resilience definitions and frameworks to guide nursing practice.

Effectiveness of spinal manipulation and biopsychosocial self-management compared to medical care for low back pain: a randomized trial study protocol.

BACKGROUND: Chronic low back pain (cLBP) is widespread, costly, and burdensome to patients and health systems. Little is known about non-pharmacological treatments for the secondary prevention of cLBP. There is some evidence that treatments addressing psychosocial factors in higher risk patients are more effective than usual care. However, most clinical trials on acute and subacute LBP have evaluated interventions irrespective of prognosis. METHODS: We have designed a phase 3 randomized trial with a 2 × 2 factorial design. The study is also a Hybrid type 1 trial with focus on intervention effectiveness while simultaneously considering plausible implementation strategies. Adults (n = 1000) with acute/subacute LBP at moderate to high risk of chronicity based on the STarT Back screening tool will be randomized in to 1 of 4 interventions lasting up to 8 weeks: supported self-management (SSM), spinal manipulation therapy (SMT), both SSM and SMT, or medical care. The primary objective is to assess intervention effectiveness; the secondary objective is to assess barriers and facilitators impacting future implementation. Primary effectiveness outcome measures are: (1) average pain intensity over 12 months post-randomization (pain, numerical rating scale); (2) average low back disability over 12 months post-randomization (Roland-Morris Disability Questionnaire); (3) prevention of cLBP that is impactful at 10-12 months follow-up (LBP impact from the PROMIS-29 Profile v2.0). Secondary outcomes include: recovery, PROMIS-29 Profile v2.0 measures to assess pain interference, physical function, anxiety, depression, fatigue, sleep disturbance, and ability to participate in social roles and activities. Other patient-reported measures include LBP frequency, medication use, healthcare utilization, productivity loss, STarT Back screening tool status, patient satisfaction, prevention of chronicity, adverse events, and dissemination measures. Objective measures include the Quebec Task Force Classification, Timed Up & Go Test, the Sit to Stand Test, and the Sock Test assessed by clinicians blinded to the patients' intervention assignment. DISCUSSION: By targeting those subjects at higher risk this trial aims to fill an important gap in the scientific literature regarding the effectiveness of promising non-pharmacological treatments compared to medical care for the management of patients with an acute episode of LBP and the prevention of progression to a severe chronic back problem. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03581123.

Development of an automated mid-scale parallel protein purification system for antibody purification and affinity chromatography.

Protein purification is often a bottleneck during protein generation for large molecule drug discovery. Therapeutic antibody campaigns typically require the purification of hundreds of monoclonal antibodies (mAbs) during the hybridoma process and lead optimization. With the increase in high-throughput cloning, faster DNA sequencing, and the use of parallel protein expression systems, a need for high-throughput purification approaches has evolved, particularly in the midsize range between 20 ml and 100 ml. To address this we modified a four channel Gilson solid phase extraction system (referred to as MG-SPE) with switching valves and sample holding loops to be able to perform standard affinity purification using commercially available columns and micro-titer format deep well blocks. By running 4 samples in parallel, the MG-SPE has the capacity to purify up to 24 samples of greater than 50 ml each using a single-step affinity purification protocol or a two-step protocol consisting of affinity chromatography followed by desalting/buffer exchange overnight (∼12 h run time). Our evaluation of affinity purification using mAbs and Fc-fusion proteins from mammalian cell supernatants demonstrates that the MG-SPE compared favorably with industry standard systems for both protein quality and yield. Overall the system is simple to operate and fills a void in purification processes where a simple, efficient, automated system is needed for affinity purification of midsize research samples.

Small Cell Carcinoma of the Gall Bladder.

Small cell carcinoma of the gall bladder (SCCGB) is a rare condition, with only 53 prior cases reported in the world literature when our case was first diagnosed. Our patient was found to have limited stage disease and was treated with sequential laparoscopic cholecystectomy, etoposide/carboplatin chemotherapy followed by consolidating loco-regional radiation therapy. She is alive and well without evidence of disease more than 132 months since diagnosis. We describe here our experience in the diagnosis, staging workup, treatment, and surveillance of a case of SCCGB and review the published literature. Treated aggressively with currently available methods, patients with limited stage SCCGB can have an excellent prognosis. The authors' intent is to provide a reasonable plan of treatment for other physicians facing such an unusual patient.

Spinal manipulation and home exercise with advice for subacute and chronic back-related leg pain: a trial with adaptive allocation.

BACKGROUND: Back-related leg pain (BRLP) is often disabling and costly, and there is a paucity of research to guide its management. OBJECTIVE: To determine whether spinal manipulative therapy (SMT) plus home exercise and advice (HEA) compared with HEA alone reduces leg pain in the short and long term in adults with BRLP. DESIGN: Controlled pragmatic trial with allocation by minimization conducted from 2007 to 2011. (ClinicalTrials.gov: NCT00494065). SETTING: 2 research centers (Minnesota and Iowa). PATIENTS: Persons aged 21 years or older with BRLP for least 4 weeks. INTERVENTION: 12 weeks of SMT plus HEA or HEA alone. MEASUREMENTS: The primary outcome was patient-rated BRLP at 12 and 52 weeks. Secondary outcomes were self-reported low back pain, disability, global improvement, satisfaction, medication use, and general health status at 12 and 52 weeks. Blinded objective tests were done at 12 weeks. RESULTS: Of the 192 enrolled patients, 191 (99%) provided follow-up data at 12 weeks and 179 (93%) at 52 weeks. For leg pain, SMT plus HEA had a clinically important advantage over HEA (difference, 10 percentage points [95% CI, 2 to 19]; P=0.008) at 12 weeks but not at 52 weeks (difference, 7 percentage points [CI, -2 to 15]; P=0.146). Nearly all secondary outcomes improved more with SMT plus HEA at 12 weeks, but only global improvement, satisfaction, and medication use had sustained improvements at 52 weeks. No serious treatment-related adverse events or deaths occurred. LIMITATION: Patients and providers could not be blinded. CONCLUSION: For patients with BRLP, SMT plus HEA was more effective than HEA alone after 12 weeks, but the benefit was sustained only for some secondary outcomes at 52 weeks. PRIMARY FUNDING SOURCE: U.S. Department of Health and Human Services.

"I know it's changed": a mixed-methods study of the meaning of Global Perceived Effect in chronic neck pain patients.

PURPOSE: Global Perceived Effect (GPE) is a commonly used outcome measure for musculoskeletal conditions like neck pain; however, little is known regarding the factors patients take into account when determining their GPE. The overall objective of this work was to describe the thematic variables, which comprise the GPE from the patient's perspective. METHODS: This was a mixed-methods study in which qualitative data were collected within a randomized clinical trial assessing exercise and manual therapy for chronic neck pain. A consecutive sample of 106 patients who completed the trial intervention took part in semi-structured interviews querying the meaning of GPE. Quantitative measures were collected through self-report questionnaires. Interview transcripts were analyzed using content analysis to identify themes, which were then quantified to assess potential relationships. RESULTS: A model of GPE for chronic neck pain emerged comprised of five main themes: neck symptoms (cited by 85%), biomechanical performance (38%), activities of daily living (31%), self-efficacy (10%), and need for other treatment (6%). Influencing factors included those contributing to GPE: treatment process (64%), biomechanical performance (51%), self-efficacy (16%), and the nature of the condition (8%). Factors, which detracted from GPE or prevented recovery included perceived nature of condition (58%), required daily activities (10%), lack of diagnosis (5%), and history of failed treatment (5%). CONCLUSIONS: GPE appears to capture chronic neck pain patient perceptions of change in different domains important to their individual pain experiences that may not be captured by other outcome instruments. Thus, GPE is a suitable patient-oriented outcome that can complement other measures in research and clinical practice. Importantly, many chronic neck pain patients believe it impossible to reach complete recovery because of a perceived intractable aspect of their neck condition; this has important implications regarding long-term disability and health-seeking behaviors.

Effectiveness of Spinal Manipulation and Biopsychosocial Self-Management compared to Medical Care for Low Back Pain: A Randomized Trial Study Protocol.

Background Chronic low back pain (cLBP) is widespread, costly, and burdensome to patients and health systems. Little is known about non-pharmacological treatments for the secondary prevention of cLBP. There is some evidence that treatments addressing psychosocial factors in higher risk patients are more effective than usual care. However, most clinical trials on acute and subacute LBP have evaluated interventions irrespective of prognosis. Methods We have designed a phase 3 randomized trial with a 2x2 factorial design. The study is also a Hybrid type 1 trial with focus on intervention effectiveness while simultaneously considering plausible implementation strategies. Adults (n = 1000) with acute/subacute LBP at moderate to high risk of chronicity based on the STarT Back screening tool will be randomized in to 1 of 4 interventions lasting up to 8 weeks: supported self-management (SSM), spinal manipulation therapy (SMT), both SSM and SMT, or medical care. The primary objective is to assess intervention effectiveness; the secondary objective is to assess barriers and facilitators impacting future implementation. Primary effectiveness outcome measures are: (1) average pain intensity over 12 months post-randomization (pain, numerical rating scale); (2) average low back disability over 12 months post-randomization (Roland-Morris Disability Questionnaire); (3) prevention of cLBP that is impactful at 10-12 months follow-up (LBP impact from the PROMIS-29 Profile v2.0). Secondary outcomes include: recovery, PROMIS-29 Profile v2.0 measures to assess pain interference, physical function, anxiety, depression, fatigue, sleep disturbance, and ability to participate in social roles and activities. Other patient-reported measures include LBP frequency, medication use, healthcare utilization, productivity loss, STarT Back screening tool status, patient satisfaction, prevention of chronicity, adverse events, and dissemination measures. Objective measures include the Quebec Task Force Classification, Timed Up & Go Test, the Sit to Stand Test, and the Sock Test assessed by clinicians blinded to the patients' intervention assignment. Discussion By targeting those subjects at higher risk this trial aims to fill an important gap in the scientific literature regarding the effectiveness of promising non-pharmacological treatments compared to medical care for the management of patients with an acute episode of LBP and the prevention of progression to a severe chronic back problem. Trial registration: ClinicalTrials.gov Identifier: NCT03581123.

Dose-Escalated Radiation Alone or in Combination With Short-Term Total Androgen Suppression for Intermediate-Risk Prostate Cancer: Patient-Reported Outcomes From NRG/Radiation Therapy Oncology Group 0815 Randomized Trial.

PURPOSE: To report patient-reported outcomes (PROs) of a phase III trial evaluating total androgen suppression (TAS) combined with dose-escalated radiation therapy (RT) for patients with intermediate-risk prostate cancer. METHODS: Patients with intermediate-risk prostate cancer were randomly assigned to dose-escalated RT alone (arm 1) or RT plus TAS (arm 2) consisting of luteinizing hormone-releasing hormone agonist/antagonist with oral antiandrogen for 6 months. The primary PRO was the validated Expanded Prostate Cancer Index Composite (EPIC-50). Secondary PROs included Patient-Reported Outcome Measurement Information System (PROMIS)-fatigue and EuroQOL five-dimensions scale questionnaire (EQ-5D). PRO change scores, calculated for each patient as the follow-up score minus baseline score (at the end of RT and at 6, 12, and 60 months), were compared between treatment arms using a two-sample t test. An effect size of 0.50 standard deviation was considered clinically meaningful. RESULTS: For the primary PRO instrument (EPIC), the completion rates were ≥86% through the first year of follow-up and 70%-75% at 5 years. For the EPIC hormonal and sexual domains, there were clinically meaningful (P < .0001) deficits in the RT + TAS arm. However, there were no clinically meaningful differences by 1 year between arms. There were also no clinically meaningful differences at any time points between arms for PROMIS-fatigue, EQ-5D, and EPIC bowel/urinary scores. CONCLUSION: Compared with dose-escalated RT alone, adding TAS demonstrated clinically meaningful declines only in EPIC hormonal and sexual domains. However, even these PRO differences were transient, and there were no clinically meaningful differences between arms by 1 year.

Multidisciplinary integrative care versus chiropractic care for low back pain: a randomized clinical trial.

BACKGROUND: Low back pain (LBP) is influenced by interrelated biological, psychological, and social factors, however current back pain management is largely dominated by one-size fits all unimodal treatments. Team based models with multiple provider types from complementary professional disciplines is one way of integrating therapies to address patients' needs more comprehensively. METHODS: This parallel group randomized clinical trial conducted from May 2007 to August 2010 aimed to evaluate the relative clinical effectiveness of 12 weeks of monodisciplinary chiropractic care (CC), versus multidisciplinary integrative care (IC), for adults with sub-acute and chronic LBP. The primary outcome was pain intensity and secondary outcomes were disability, improvement, medication use, quality of life, satisfaction, frequency of symptoms, missed work or reduced activities days, fear avoidance beliefs, self-efficacy, pain coping strategies and kinesiophobia measured at baseline and 4, 12, 26 and 52 weeks. Linear mixed models were used to analyze outcomes. RESULTS: 201 participants were enrolled. The largest reductions in pain intensity occurred at the end of treatment and were 43% for CC and 47% for IC. The primary analysis found IC to be significantly superior to CC over the 1-year period (P = 0.02). The long-term profile for pain intensity which included data from weeks 4 through 52, showed a significant advantage of 0.5 for IC over CC (95% CI 0.1 to 0.9; P = 0.02; 0 to 10 scale). The short-term profile (weeks 4 to 12) favored IC by 0.4, but was not statistically significant (95% CI - 0.02 to 0.9; P = 0.06). There was also a significant advantage over the long term for IC in some secondary measures (disability, improvement, satisfaction and low back symptom frequency), but not for others (medication use, quality of life, leg symptom frequency, fear avoidance beliefs, self-efficacy, active pain coping, and kinesiophobia). Importantly, no serious adverse events resulted from either of the interventions. CONCLUSIONS: Participants in the IC group tended to have better outcomes than the CC group, however the magnitude of the group differences was relatively small. Given the resources required to successfully implement multidisciplinary integrative care teams, they may not be worthwhile, compared to monodisciplinary approaches like chiropractic care, for treating LBP. Trial registration NCT00567333.

A descriptive analysis of pediatric post-tonsillectomy pain and recovery outcomes over a 10-day recovery period from 2 randomized, controlled trials.

Pediatric tonsillectomy involves an often painful and lengthy recovery period, yet the extended recovery process is largely unknown. This article describes postoperative recovery outcomes for 121 children aged 4 to 15 (mean 6.6 years, SD = 2.3) years enrolled in 1 of 2 clinical trials of analgesia safety and efficacy after tonsillectomy. Postoperative analgesia included scheduled opioid analgesic plus acetaminophen/ibuprofen medication use (first 5 days) and "as-needed" use (last 5 days). Clinical recovery as measured daily by the Parents' Postoperative Pain Measure (PPPM; an observational/behavioral pain measure), children's self-reported pain scores, side-effect assessments, need for unanticipated medical care, and satisfaction with recovery over 10 days was assessed. Higher Parents' Postoperative Pain Measure scores were correlated with poorer sleep, receipt of breakthrough analgesics, distressing side effects, higher self-reported pain scores, and need for unanticipated medical care. Higher self-reported pain scores were associated with more distressing adverse events, including nausea, vomiting, insomnia, lower parent satisfaction, and unplanned medical visits and hospitalizations. Pain and symptoms improved over time, although 24% of the children were still experiencing clinically significant pain on day 10. Scheduled, multimodal analgesia and discharge education that sets realistic expectations is important. This study adds to the emerging body of literature that some children experience significant postoperative pain for an extended period after tonsillectomy.

Spinal manipulative therapy and exercise for older adults with chronic low back pain: a randomized clinical trial.

Background: Low back pain (LBP) is a common disabling condition in older adults which often limits physical function and diminishes quality of life. Two clinical trials in older adults have shown spinal manipulative therapy (SMT) results in similar or small improvements relative to medical care; however, the effectiveness of adding SMT or rehabilitative exercise to home exercise is unclear. Methods: We conducted a randomized clinical trial assessing the comparative effectiveness of adding SMT or supervised rehabilitative exercise to home exercise in adults 65 or older with sub-acute or chronic LBP. Treatments were provided over 12-weeks and self-report outcomes were collected at 4, 12, 26, and 52 weeks. The primary outcome was pain severity. Secondary outcomes included back disability, health status, medication use, satisfaction with care, and global improvement. Linear mixed models were used to analyze outcomes. The primary analysis included longitudinal outcomes in the short (week 4-12) and long-term (week 4-52). An omnibus test assessing differences across all groups over the year was used to control for multiplicity. Secondary analyses included outcomes at each time point and responder analyses. This study was funded by the US Department of Health and Human Services, Health Resources and Services Administration. Results: 241 participants were randomized and 230 (95%) provided complete primary outcome data. The primary analysis showed group differences in pain over the one-year were small and not statistically significant. Pain severity was reduced by 30 to 40% after treatment in all 3 groups with the largest difference (eight percentage points) favoring SMT and home exercise over home exercise alone. Group differences at other time points ranged from 0 to 6 percentage points with no consistent pattern favoring one treatment. One-year post-treatment pain reductions diminished in all three groups. Secondary self-report outcomes followed a similar pattern with no important group differences, except satisfaction with care, where the two combination groups were consistently superior to home exercise alone. Conclusions: Adding spinal manipulation or supervised rehabilitative exercise to home exercise alone does not appear to improve pain or disability in the short- or long-term for older adults with chronic low back pain, but did enhance satisfaction with care. Trial registration: NCT00269321.

Short- or Long-Term Treatment of Spinal Disability in Older Adults With Manipulation and Exercise.

OBJECTIVE: Back and neck pain are associated with disability and loss of independence in older adults. Whether long-term management using commonly recommended treatments is superior to shorter-term treatment is unknown. This randomized clinical trial compared short-term treatment (12 weeks) versus long-term management (36 weeks) of back- and neck-related disability in older adults using spinal manipulative therapy (SMT) combined with supervised rehabilitative exercises (SRE). METHODS: Eligible participants were ages ≥65 years with back and neck disability for ≥12 weeks. Coprimary outcomes were changes in Oswestry Disability Index (ODI) and Neck Disability Index (NDI) scores after 36 weeks. An intent-to-treat approach used linear mixed-model analysis to detect between-group differences. Secondary analyses included other self-reported outcomes, adverse events, and objective functional measures. RESULTS: A total of 182 participants were randomized. The short-term and long-term groups demonstrated significant improvements in back disability (ODI score -3.9 [95% confidence interval (95% CI) -5.8, -2.0] versus ODI score -6.3 [95% CI -8.2, -4.4]) and neck disability (NDI score -7.3 [95% CI -9.1, -5.5] versus NDI score -9.0 [95% CI -10.8, -7.2]) after 36 weeks, with no difference between groups (back ODI score 2.4 [95% CI -0.3, 5.1]; neck NDI score 1.7 [95% CI 0.8, 4.2]). The long-term management group experienced greater improvement in neck pain at week 36, in self-efficacy at weeks 36 and 52, and in functional ability, and balance. CONCLUSION: For older adults with chronic back and neck disability, extending management with SMT and SRE from 12 to 36 weeks did not result in any additional important reduction in disability.

Ultra-wide dynamic range receiver for noise loaded WDM transmission systems.

We demonstrated ultra-wide input power range receivers for noise-loaded WDM applications without using optical variable attenuators. Required OSNR at 6E-5 BER exhibited less than 1dB variation across receiver input power range from -22dBm to +4Bm.

2-Methoxy antimycin reveals a unique mechanism for Bcl-x(L) inhibition.

Overexpression of Bcl-x(L) in multiple cancers correlates with resistance to chemotherapy and radiation therapy, and provides a rationale for development of small-molecule Bcl-x(L) inhibitors. Based on knockout studies, nonneoplastic cells also require Bcl-x(L) survival functions, particularly when challenged with cytotoxic agents. We analyze the selective cytotoxicity of one Bcl-x(L) inhibitor, 2-methoxy antimycin A, toward cells with excess exogenous Bcl-x(L) in isogenic cell line pairs. This selectivity, characteristic of a gain-of-function mechanism, is not shared by other known Bcl-x(L) inhibitors, including BH3I-2, HA14-1, ABT-737, gossypol, or the stapled BH3 helical peptide SAHB-BID. We show that Bcl-x(L) overexpression induces a shift in energy metabolism from oxidative phosphorylation to glycolysis. Treatment with 2-methoxy antimycin A acutely reverses the metabolic effects of Bcl-x(L), causing mitochondrial hyperpolarization and a progressive increase in mitochondrial NAD(P)H. We identify an additional small-molecule Bcl-x(L) inhibitor, NSC 310343, establishing a class of Bcl-x(L) inhibitors with gain-of-function activity. In contrast to other Bcl-x(L) inhibitors, combining gain-of-function Bcl-x(L) inhibitors with a standard inducer of apoptosis, staurosporine, enhances selective cytotoxicity toward Bcl-x(L)-overexpressing cells. These results provide an example of the intersection of bioenergetic metabolism and Bcl-x(L) functions and suggest a metabolic basis for the gain-of-function mechanism of Bcl-x(L) inhibitors.

Spinal manipulation and exercise for low back pain in adolescents: a randomized trial.

Low back pain (LBP) is common in adolescence, but there is a paucity of high-quality research to inform care. We conducted a multicenter randomized trial comparing 12 weeks of spinal manipulative therapy (SMT) combined with exercise therapy (ET) to ET alone. Participants were 185 adolescents aged 12 to 18 years with chronic LBP. The primary outcome was LBP severity at 12, 26, and 52 weeks. Secondary outcomes included disability, quality of life, medication use, patient- and caregiver-rated improvement, and satisfaction. Outcomes were analyzed using longitudinal linear mixed effect models. An omnibus test assessing differences in individual outcomes over the entire year controlled for multiplicity. Of the 185 enrolled patients, 179 (97%) provided data at 12 weeks and 174 (94%) at 26 and 52 weeks. Adding SMT to ET resulted in a larger reduction in LBP severity over the course of 1 year (P = 0.007). The group difference in LBP severity (0-10 scale) was small at the end of treatment (mean difference = 0.5; P = 0.08) but was larger at weeks 26 (mean difference = 1.1; P = 0.001) and 52 (mean difference = 0.8; P = 0.009). At 26 weeks, SMT with ET performed better than ET alone for disability (P = 0.04) and improvement (P = 0.02). The SMT with ET group reported significantly greater satisfaction with care at all time points (P ≤ 0.02). There were no serious treatment-related adverse events. For adolescents with chronic LBP, spinal manipulation combined with exercise was more effective than exercise alone over a 1-year period, with the largest differences occurring at 6 months. These findings warrant replication and evaluation of cost effectiveness.

Dose-response and efficacy of spinal manipulation for care of cervicogenic headache: a dual-center randomized controlled trial.

BACKGROUND CONTEXT: The optimal number of visits for the care of cervicogenic headache (CGH) with spinal manipulative therapy (SMT) is unknown. PURPOSE: The present study aimed to identify the dose-response relationship between visits for SMT and chronic CGH outcomes and to evaluate the efficacy of SMT by comparison with a light-massage control. STUDY DESIGN/SETTING: This is a two-site, open-label randomized controlled trial. PATIENT SAMPLE: Participants were 256 adults with chronic CGH. OUTCOME MEASURES: The primary outcome was days with CGH in the previous 4 weeks evaluated at the 12- and 24-week primary end points. Secondary outcomes included CGH days at remaining end points, pain intensity, disability, perceived improvement, medication use, and patient satisfaction. METHODS: Participants were randomized to four dose levels of chiropractic SMT: 0, 6, 12, or 18 sessions. They were treated three times per week for 6 weeks and received a focused light-massage control at sessions when SMT was not assigned. Linear dose effects and comparisons with the no-manipulation control group were evaluated at 6, 12, 24, 39, and 52 weeks. The present study was funded by the National Center for Complementary and Integrative Health (R01AT006330) and is registered at ClinicalTrials.gov (NCT01530321). The authors declare no conflicts of interest. RESULTS: A linear dose-response was observed for all follow-ups, a reduction of approximately 1 CGH day/4 weeks per additional 6 SMT visits (p<.05); a maximal effective dose could not be determined. Cervicogenic headache days/4 weeks were reduced from about 16 to 8 for the highest and most effective dose of 18 SMT visits. Mean differences in CGH days/4 weeks between 18 SMT visits and control were -3.3 (p=.004) and -2.9 (p=.017) at the primary end points, and were similar in magnitude at the remaining end points (p<.05). Differences between other SMT doses and control were smaller in magnitude (p>.05). Cervicogenic headache intensity showed no important improvement nor differed by dose. Other secondary outcomes were generally supportive of the primary outcome. CONCLUSIONS: There was a linear dose-response relationship between SMT visits and days with CGH. For the highest and most effective dose of 18 SMT visits, CGH days were reduced by half and about 3 more days per month than for the light-massage control.

Pain Experience in a US Children's Hospital: A Point Prevalence Survey Undertaken After the Implementation of a System-Wide Protocol to Eliminate or Decrease Pain Caused by Needles.

OBJECTIVES: Pain in hospitalized children remains under-assessed and undertreated. With this study, we aim to describe results from a repeat single-day, hospital-wide survey of children's pain and its treatment after the initiation of a hospital-wide quality improvement initiative used to reduce or eliminate pain caused by needle procedures. METHODS: All patients and parents listed on the inpatient morning census, in emergency department and outpatient surgery registration lists, were invited to participate in a brief single-day point prevalence survey of their experience with pain and its management in the hospital setting. Results were compared with a survey conducted 2 years earlier, before implementation of a system-wide Children's Comfort Promise needle pain treatment and prevention protocol. RESULTS: A total of 194 children and their parents participated in the current survey. A higher percentage of children reported having no pain compared with the previous survey (33% vs 24%; P = .07; not significant) and fewer experienced severe pain (score ≥7 out of 10). Fewer children identified pain caused by needles as the cause of the worst pain (21% vs 30%), although it remained the highest reported cause of the most painful experience overall. The number of pain management strategies administered and offered to children with needle pain (distraction, positioning, numbing cream, and sucrose and/or breastfeeding for infants) increased. CONCLUSIONS: The implementation of a mandatory Comfort Promise protocol used to minimize or prevent pain caused by elective needle procedures was associated with a significant reduction in overall pain prevalence and improved use of evidence-based practices for needle pain management.

Mixing in 384-well plates: issues, measurements, and solutions.

Mixing in standard 384-well plates is different from mixing in 96-well formats. The aspect ratio of a typical well, the balance of surface tension and mass of the fluids, and the scale of diffusion all add to the increased difficulty in mixing fluids in higher-density plates. Here we examine two methods to measure mixing and some common techniques for mixing in 384-well plates. While conventional shaking can suffice, alternative methods can accelerate and improve the efficiency of mixing in 384-well plates.

Chiropractic and exercise for seniors with low back pain or neck pain: the design of two randomized clinical trials.

BACKGROUND: Low back pain (LBP) and neck pain (NP) are common conditions in old age, leading to impaired functional ability and decreased independence. Manual and exercise therapies are common and effective therapies for the general LBP and NP populations. However, these treatments have not been adequately researched in older LBP and NP sufferers. The primary aim of these studies is to assess the relative clinical effectiveness of 1) manual treatment plus home exercise, 2) supervised rehabilitative exercise plus home exercise, and 3) home exercise alone, in terms of patient-rated pain, for senior LBP and NP patients. Secondary aims are to compare the three treatment approaches in regards to patient-rated disability, general health status, satisfaction, improvement and medication use, as well as objective outcomes of spinal motion, trunk strength and endurance, and functional ability. Cost-effectiveness and cost-utility will also be assessed. Finally, using qualitative methods, older LBP and NP patient's perceptions of treatment will be explored and described. METHODS/DESIGN: This paper describes the design of two multi-methods clinical studies focusing on elderly patients with non-acute LBP and NP. Each study includes a randomized clinical trial (RCT), a cost-effectiveness study alongside the RCT, and a qualitative study. Four hundred and eighty participants (240 per study), ages 65 and older, will be recruited and randomized to one of three, 12-week treatment programs. Patient-rated outcome measures are collected via self-report questionnaires at baseline and at 4, 12, 26, and 52 weeks post-randomization. Objective outcomes are assessed by examiners masked to treatment assignment at baseline and 12 weeks. Health care cost data is collected through standardized clinician forms, monthly phone interviews, and self-report questionnaires throughout the study. Qualitative interviews using a semi-structured format are conducted at the end of the 12 week treatment period. DISCUSSION: To our knowledge, these are the first randomized clinical trials to comprehensively address clinical effectiveness, cost-effectiveness, and patients' perceptions of commonly used treatments for elderly LBP and NP sufferers.