The immediate effects of cervical spine manipulation on pain and biochemical markers in females with acute non-specific mechanical neck pain: a randomized clinical trial

Study Design: Randomized clinical trial with pre-test, post-test control group design.

Objectives: To examine the immediate effects of cervical spinal manipulation (CSM) on serum concentration of biochemical markers (oxytocin, neurotensin, orexin A, and cortisol).

Background: Several studies have found an association between spinal manipulation (SM) and pain perception. However, the mechanism by which SM modulates pain remains undefined.

Methods: Twenty-eight female subjects with non-specific mechanical neck pain were randomly assigned to one of two interventions (CSM versus sham CSM). Blood samples were drawn before and immediately after the respective interventions. Oxytocin, neurotensin, orexin A, and cortisol were measured from the blood and serum using the Milliplex Map Magnetic Bead Panel Immunoassay on the Luminex 200 Platform.

Results: In the CSM group, there were significant increases in pre- versus post-manipulation mean oxytocin (154.5 ± 60.1 vs. 185.1 ± 75.6, p = .012); neurotensin (116.0 ± 26.5 vs.136.4 ± 34.1, p < . 001); orexin A (52.2 ± 31.1 vs. 73.8 ± 38.8, p < .01) serum concentration; but no significant differences in mean cortisol (p = .052) serum concentration. In the sham group, there were no significant differences in any of the biomarkers (p > .05).

Conclusion: The results of the current study suggest that the mechanical stimuli provided through a CSM may modify neuropeptide expression by immediately increasing the serum concentration of nociception-related biomarkers (oxytocin, neurotensin, orexin A, but not cortisol) in the blood of female subjects with non-specific mechanical neck pain.     

Abnormal performance of cervical stabilizer muscles in individuals with low back pain

Objectives: To compare the performance of cervical stabilizer muscles using the craniocervical flexion test (CCFT) among individuals with subacute, chronic, and asymptomatic low back pain (LBP) conditions.

Methods: Individuals with subacute (N = 23) and chronic LBP (N = 23) with their age- and gender-matched controls (N = 30) participated in this study. All recruited participants were required to perform the CCFT. The activation score (AS) and the performance index (PI) were recorded by an assessor who was blinded to the group of participants.

Results: Approximately, 74% of subacute LBP participants and 60–65% of chronic LBP participants obtained abnormal AS and PI. AS was significantly lower in participants with subacute (P = 0.0002) and chronic LBP (P = 0.0009) than the control group. Likewise, the PI was significantly lower in participants with subacute (P = 0.0002) and chronic LBP (P = 0.0036) than the control group. Participants in the subacute LBP group showed significantly greater percentages of abnormal responses on the AS (P < 0.0001) and the PI (P = 0.0001) than the control.

Discussion: Abnormal performance of cervical stabilizer muscles using the CCFT was demonstrated in a high proportion of participants with LBP. The findings highlight the plausible association in muscle control between cervical and lumbar stabilizers.

Level of Evidence: 2b.     

First-generation versus second-generation drug-eluting stents in patients with chronic kidney disease: a systematic review and meta-analysis

Background: Chronic kidney disease (CKD) patients are associated with very high rate of adverse cardiovascular outcomes after drug-eluting stents (DES) implantation. The clinical outcomes of second-generation DES versus first-generation DES in CKD patients remain controversial.

Objective: The aim of the current study was to perform a systematic review and meta-analysis to assess the safety and efficacy of second-generation DES versus first-generation DES in CKD patients.

Methods: A systematical search of databases of PubMed, EMBASE, and Cochrane Library was conducted for eligible studies comparing the clinical outcomes of first-generation DES versus second-generation DES. Sirolimus-eluting and paclitaxel-eluting stents were classified as first-generation DES, and everolimus-eluting, zotarolimus-eluting, and biolimus-eluting stent (BES) were classified as second-generation DES. A pooled odds ratio (OR) and 95% confidence interval (CI) were used to summary the estimates. Heterogeneity, subgroup analysis, sensitivity analysis and publication bias were also performed.

Results: We identified 14 trials involving 9,542 patients with CKD undergoing percutaneous coronary intervention. First-generation DES implantation was associated with higher risk of long-term all-cause mortality (OR, 1.31; 95% CI, 1.02–1.69; P = 0.04; I² = 0%), in stent restenosis (OR, 1.69; 95% CI, 1.14–2.49; P = 0.008; I² = 49%) and stent thrombosis (OR, 1.64; 95% CI, 1.00–2.69; P = 0.05; I² = 49%) compared with second-generation DES implantation. First-generation DES and second-generation DES showed similar efficacy in decreasing risk of repeat revascularization, myocardial infarction (MI), or major adverse cardiac events (MACE) between first-generation and second-generation DES implantation.

Conclusions: In CKD patients, the use of second-generation DES was associated with lower risk of long-term all-cause mortality, in stent restenosis and stent thrombosis as compared with first-generation DES. No differences were found regarding repeat revascularization, MI, and MACE.     

Immediate improvements of supination range of motion and strength following pronator teres muscle friction massage: a clinical trial comparing people with and without supination limited motion

Objectives: To investigate the effects of friction massage techniques on the pronator teres muscle on supination range of motion (ROM) and supinator strength in individuals with and without limited supination ROM.

Methods: In total, 26 subjects (13 with limited supination ROM and 13 healthy subjects) volunteered to participate in this study. We used a customized wrist cuff. Supination ROM and supinator strength were measured with a 9-axis inertial motion sensor and load cell. The friction massage protocol was executed with the pronator teres muscle in a relaxed position. Then supination ROM and supinator strength were measured again.

Results: There was no significant interaction effect on supination ROM, which was significantly greater in the limited supination and control groups. A post hoc t-test revealed that the limited supination group achieved a significantly increased post-test supination ROM (51.7 ± 7.8°) compared to the pre-test value (43.6 ± 5.2°). In addition, the control group achieved a significant increase in post-test supination ROM (67.7 ± 10.0°) compared to the pre-test value (61.4 ± 7.7°). There was no significant interaction effect on supinator strength. Supinator strength was significantly greater in the limited supination and control groups. A post hoc t-test revealed a significant difference in supinator strength between the pre- and post-test values in the limited supination group.

Discussion: Friction massage helps restore a limited ROM of the forearm supination motion and immediately increases supinator muscle strength. This technique can be used as an intervention method to improve muscle strength in patients with limited supination ROM.     

Impact of treatment modality on clinical outcome in metastatic colorectal cancer patients stratified by metastatic sites

Objectives: To investigate the impact of location of metastases, and therapeutic modality on clinical outcomes in patients with metastatic colorectal cancer (CRC).

Methods: Data for metastatic CRC patients were sourced from the Surveillance, Epidemiology, and End Results (SEER) database (SEER ID: 15309-Nov2017). Patients were classified as follows: Group 1 patients had only liver metastasis; Group 2 patients had liver and lung metastasis; Group 3 patients had more than two metastasis sites. Patients were treated with surgery alone, radiation alone, or surgery plus radiation. The main study outcomes were (1) cancer-specific mortality and (2) survival benefit associated with treatment modality.

Results: A total number of 15,510 patients were included in this study. In Groups 1 and 2, patients treated with surgery plus radiation had a higher cumulative survival compared to other treatment groups (p-value <.001). Group 3 patients showed no significant difference in cumulative survival between the different treatment modalities (p-value = .218). Group 1 patients who received surgery plus radiation had a significantly lower risk of mortality compared to the other treatment groups (p-value <.001), and Group 2 patients who either received radiation treatment alone or surgery plus radiation had a significantly lower risk for mortality than patients who received other treatment modalities (p-value <.001). Multivariate analysis adjusting for known prognostic factors such as tumor sidedness and race did not alter the observed risk conferred by metastasis sites and treatment modalities.

Conclusion: Stratification by metastases sites, and by treatment modality can help multidisciplinary teams to reach a treatment consensus for metastatic CRC.     

Pragmatic neural tissue management improves short-term pain and disability in patients with sciatica: a single-arm clinical trial

Objectives: To evaluate the clinical effect of sciatic neural mobilization in combination with the treatment of surrounding structures for sciatica patients. Secondly, we were also interested in identifying possible baseline characteristics that may be associated with improvements in pain and disability for sciatica patients.

Methods: Twenty-eight patients with a clinical diagnosis of sciatica were treated with neural mobilization, joint mobilization and soft tissue techniques. Pain intensity and lumbar disability were assessed at baseline and after treatment using a Numerical Rating Scale (0–10) and the Oswestry Disability Index (0–100), respectively. The pre- and post-intervention data were compared. The research protocol was registered under the number NCT03663842.

Results: Participants attended an average of 16 (SD±5.6) treatment?sessions over an average of 12 weeks. Decrease in pain scores (before median = 8, after median = 2; p < 0.001) and improvement in lumbar disability scores (before median = 33.3%, after median = 15.6%; p < 0.001) were observed. A multiple linear regression analysis showed that duration of pain and age of the patient predicted the disability improvement: F (2, 24) = 4.084, p < 0.030, R² = 0.254.

Discussion: Patients with sciatica may benefit from neural mobilization in combination with manual therapy for pain and lumbar disability. Longer pain duration and younger age had a negative influence on lumbar disability improvement.     

Instrument-assisted soft tissue mobilization and proprioceptive neuromuscular facilitation techniques improve hamstring flexibility better than static stretching alone: a randomized clinical trial

Objectives: Tight hamstrings contribute to inefficiency of movement and increased risk for injury. Static stretching is the most common intervention for this problem, but the use of alternatives like instrument-assisted soft tissue mobilization (IASTM) and proprioceptive neuromuscular facilitation (PNF) is increasing among clinicians. This study examined two prospective studies with the common aim of demonstrating the effectiveness of IASTM or PNF over static stretching for improving hamstring tightness.

Methods: Nondisabled adults were recruited on a university campus. IASTM study: N = 17 (11 males and 6 females). PNF study: N = 23 (7 males and 16 females). Hip flexion range of motion was measured with a passive straight leg raise (for IASTM) or active straight leg raise (for PNF) before and after stretching. Participants performed a self-static stretch on one leg and received the alternative intervention on the contralateral leg. The two studies were analyzed separately for reliability indices and significant differences between interventions.

Results: Hip flexion measures showed good reliability in both studies (intraclass correlation coefficient = 0.97) with a minimal detectable change of <4.26. Both studies showed significant interactions between time and intervention (p < 0.05). Follow-up analyses revealed PNF and IASTM interventions resulted in greater increases in hip flexion range than static stretching.

Discussion: These findings demonstrate the effectiveness of PNF and IASTM techniques over static stretching for hamstring flexibility. These interventions provide more efficient alternatives for improving flexibility in the clinic, allowing greater progress in a shorter period of time than an equivalent static stretching program.

Level of Evidence: 1b.     

Circulating levels of prolactin are elevated in patients with rheumatoid arthritis: a meta-analysis

Background: Prolactin (PRL), an inflammatory hormone with cytokine properties, has long been proposed to play a crucial role in the pathogenesis of autoimmune disorders, including rheumatoid arthritis (RA). However, the circulating levels of PRL in RA were discordant among published studies.

Methods: PubMed, Embase, and The Cochrane Library database were systematically searched from inception up to 30 June 2018. The available studies were obtained from the initial search in accordance with the rigorous inclusion and exclusion criteria. Relevant data from the included literatures were extracted. Methodological quality was evaluated in order to refine the final search results. All statistical analyses were conducted using software STATA version 12.0.

Results: Of 698 articles were yielded for eligibility, a finally analysis involving 628 RA cases and 430 controls from 14 published studies were included. When compared to healthy controls, there was a significantly higher level of circulating PRL in patients with RA with a pooled SMD of 1.08 (95% CI = 0.41 to 1.74, P< 0.001), particularly in Asians, age ≥50, enzyme-linked immunosorbent assay (ELISA) group and subjects with erythrocyte sedimentation rate (ESR) ≥25 mm/h.

Conclusions: Our meta-analysis demonstrates a significantly higher level of circulating PRL in RA patients when compared to healthy controls, and it was associated with region, age, measurement type and ESR.     

Self-reported sinus headaches are associated with neck pain and cervical musculoskeletal dysfunction: a preliminary observational case control study

Objectives: Headaches can be associated with rhinosinusitis and may present a diagnostic challenge because of symptomatic overlap with other recurring headaches. Neck pain has received extensive attention in migraine, tension-type and cervicogenic headache but not as a comorbid feature of headache in those with rhinosinusitis. This study investigated the occurrence of neck pain and cervical musculoskeletal dysfunction in individuals with self-reported sinus headaches (SRSH).

Methods: Participants with and without SRSH attended a single data collection session. Participants completed the Headache Impact Test (HIT)-6 and the Sino-Nasal Outcome Test (SNOT)-22. Cervical range of motion (ROM), segmental examination, muscle endurance and pressure-pain threshold (PPT) were measured .

Results: Participants included 31 with SRSH (77.4% female; age 43.7 (9.9) years) and 30 without headache. Average symptom duration was 89.7 (±85.6) months. Mean SNOT-22 and HIT-6 scores were 36.2 (15.3) and 56.7 (7.1), respectively. In the SRSH group, 83.9% (n = 26) reported neck pain. There was a significant difference between groups for cervical sagittal (14.3° [5.3°, 23.3°], p = 0.002) and transverse plane ROM (21.5° [12.4°, 30.6°], p < 0.001), but no difference in frontal plane motion (p = 0.017). There were significant between groups difference in neck flexor endurance (19.5 s [10.1 s, 28.9 s], <0.001), segmental dysfunction O-C4 (p < 0.001) but not in PPT (p = 0.04).

Discussion: Neck pain and cervical musculoskeletal dysfunction are common among persons with SRSH and may be a comorbid feature or contributing factor to headaches attributed to rhinosinusitis. Further research is needed to understand these associations.     

The frequency of hospitalizations and length of stay differences between schizophrenic and schizoaffective disorder inpatients who use cannabis

Background: The literature on the effects of cannabis use by patients with schizophrenia is variable.

Aims: To determine whether there are differences among urine-screened cannabis-only users, polysubstance users using cannabis, and nonusers on the number of inpatient hospitalizations and length of stay for patients with schizophrenia or schizoaffective disorder.

Method: This study (N = 116) included patients who tested positive for only cannabis (n = 20, Group 1); tested positive for cannabis and had a history of other substance use (n = 43, Group 2); and had negative drug screens (n = 53, Group 3).

Results: Groups 1 and 2 had significantly lower numbers of hospitalizations than Group 3 without controlling for any other factors, and non-significantly lower lengths of stay than Group 3.

Conclusions: Our results do not support the hypothesis that cannabis exacerbates psychotic symptoms in patients with schizophrenia or schizoaffective disorder. Our study is unique in that it utilized objective urine drug screens.     

Early age at menarche is associated with insulin resistance: a systemic review and meta-analysis

Objectives: We aimed to conduct a systemic review and meta-analysis of the relevant studies to further investigate the association between age at menarche and insulin resistance.

Methods: PubMed, EMBASE, and Web of Science (SCI) databases were systemically searched until December 2017. Observational studies comparing the incidences of insulin resistance in patients with early, average, and late menarchal ages were identified. Weighted mean difference (WMD) for HOMA-IR scores and fasting serum insulin levels in early vs late, early vs average. and average vs late comparisons were calculated with a random- or fixed-effects model.

Results: A total of eight articles involving 5504 subjects were finally included. In the analysis of HOMA-IR, the pooled WMDs in five studies were 0.45 (95% confidence interval [CI] 0.31–0.60, p < 0.001), 0.40 (95% CI 0.28–0.52, p < 0.001), and ?0.01 (95% CI ?0.09 to 0.07, p = 0.854) for early vs late, early vs average, and average vs late comparisons, respectively. The fasting serum insulin levels in eight studies were analyzed, and it was significantly higher in subjects with earlier age at menarche (WMD 1.28, 95% CI 0.92–1.63, p < 0.001 for early vs late comparison, WMD 1.28, 95% CI 1.13–1.43, p < 0.001 for early vs average comparison) with mild and acceptable heterogeneity (I² = 42.5% and 7.4%, respectively). Publication bias was not detected via funnel plots and Egger’s tests.

Conclusions: Our study revealed that earlier age at menarche was significantly associated with insulin resistance.

Trial Registration Number: CRD42018083874     

Effect of video-assisted patient education on compliance with therapy,quality of life,psychomorbidity, and cost of illness in irritable bowel syndrome

Objective: Patient education is important in irritable bowel syndrome (IBS), but its effects on outcomes have not been studied extensively.

Methods: Patients were enrolled and prospectively divided into an interventional and usual care group. Both received standard of care, but the former additionally received video-assisted patient education. Self-administered questionnaires IBS-quality of life (QOL), Beck Anxiety-Depression Inventory II (BAI, BDI), and Hospital Anxiety and Depression Scale (HADS) were administered at baseline, 3 months, and 6 months. Compliance was defined as drug intake of >80% of the prescribed dose. COI included prospective, prevalence-based, societal perspective.

Results: Of the 107 patients included, 84 [78.5%; male = 66 (78.57%); median age = 44 (range 20–77 years)] completed the follow up. While the median (inter-quartile range; IQR) QOL scores decreased significantly in both the groups (p < 0.001 for either group), the final scores were significantly better in the interventional group [49 (44–52.5) versus 80 (76–103), respectively; p < 0.005]. There was a significant improvement in the BDI; p < 0.001]. However, the rest did not achieve statistical significance. At 6 months, total median (IQR) semi-annual cost per patient was INR 14,639 (8253–17,909) [US $240 (135–294].

Conclusion: Video-assisted patient education should be a part of the treatment of IBS since it improves the QOL and depression scores.     

Psychometric properties of field-based anaerobic capacity tests in children with Developmental Coordination Disorder

Background: Assessment of anaerobic capacity in children with Developmental Coordination Disorder (DCD) is essential for treatment planning. However, available field-based measures have no established validity and reliability in this population.

Purpose: To examine the psychometric properties of selected field-based anaerobic capacity tests in children with and without DCD.

Methods: School-aged children (6–16 years) with and without DCD participated in the study. The children completed the shuttle run sub-item of the Bruninks-Oseretsky test of motor proficiency-second edition, the 10?×?5 m sprint tests (straight and slalom) and the muscle power sprint test (MPST).

Results: The shuttle run test item of the Bruninks-Oseretsky test of motor proficiency-second edition and 10?×?5?m sprint tests possess good construct validity and test–retest reliability in children with DCD. The 10?×?5?m sprint test-slalom was found to be the most responsive test among children with DCD. However, the MPST was less reliable in children with DCD compared to their typically developing peers, leading to a very large Smallest Detectable Difference.

Conclusions: The findings suggest that the selected anaerobic capacity measures have sound psychometric properties among children with DCD with the exception of the MPST. Clinicians working on children with DCD could use these tests in their practice, especially in situations where logistical resources are limited.

• Implications for Rehabilitation

• Field-based anaerobic capacity tests are suitable measures for assessing anaerobic capacity in children with Developmental Coordination Disorder, particularly in situations where laboratory assessments are not feasible.

• The shuttle run test item of the Bruninks-Oseretsky test of motor proficiency-second edition and the 10?×?5 sprint tests (straight and slalom) have good construct validity in this population.

• The 10?×?5 sprint test (slalom) is the most sensitive anaerobic capacity test among children with Developmental Coordination Disorder.

     

Medication adherence,biological and lifestyle risk factors in patients with myocardial infarction: a ten-year follow-up on socially differentiated cardiac rehabilitation

Objective: There is strong evidence that medication adherence and lifestyle changes are essential in patients undergoing secondary cardiovascular disease prevention. Cardiac rehabilitation (CR) increases medication adherence and improves lifestyle changes. Patients with cardiac diseases and a low educational level and patients with little social support are less responsive to improve medication adherence and to adapt lifestyle changes. The aim of the present study was to investigate the long-term effects of a socially differentiated CR intervention on medication adherence as well as changes in biological and lifestyle risk factors at two- five- and ten-year follow-up.

Design: A prospective cohort study.

Setting: The cardiac ward at Aarhus University Hospital, Denmark.

Intervention: A socially differentiated CR intervention in addition to the standard CR program.

Subjects: Patients admitted with first-episode myocardial infarction between 2000 and 2004, N?=?379. Patients were defined as socially vulnerable or non-socially vulnerable according to their educational level and extent of social network.

Main outcome measures: Primary outcome was medication adherence to antithrombotics, beta-blockers, statins and angiotensin-converting enzyme inhibitors. Secondary outcomes were biological and lifestyle risk factors defined as; total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, glycated hemoglobin, blood pressure and smoking status.

Results: No significant long-term effect of the intervention was found.

Conclusions: The results indicate a non-significant effect of the intervention. However, it was found that equality in health was improved in the study population except concerning smoking. General practitioners manage to support the long-term secondary cardiovascular disease prevention in all patients regardless of social status.

• Key points

• The socially differentiated intervention did not significantly improve medication adherence or biological and lifestyle risk factors.

• Despite the non-significant effect of the intervention, equality in health was improved except concerning smoking.

• General practitioners managed to support the long-term secondary cardiovascular disease prevention in all patients regardless of social status.

     

Interpersonal and intrapersonal relapse predictors in a structured group intervention for smoking cessation

Background: Cigarette smoking is a widespread behaviour and associated with increased risk for nicotine dependence, morbidity and mortality. The structured group-based intervention ‘Rauchfrei-Programm’ is effective; however, no study has yet identified psychological factors predicting immediate (within two weeks after smoking cessation), short-term (within 3 months) and middle-term relapse (within 6 months).

Methods: This naturalistic pre-post-follow-up phase-3 field study analyses self-reported smoking status, age, gender, percentage of smoking friends and questionnaire scores for self-efficacy, severity of dependence and perceived social support of N = 160 treatment-seeking outpatients (out of N = 555 overall participants) using binary logistic regressions.

Results: Immediate relapse (18.8%) was not predicted by any predictor. Short-term relapse (55.6%) was predicted by lower self-efficacy (OR = 0.87), higher percentage of smoking friends (OR = 1.02) and more severe nicotine dependence (OR = 1.19). Middle-term relapse (64.4%) was predicted by lower self-efficacy (OR = 0.90) and higher percentage of smoking friends (OR = 1.02).

Conclusions: Results support the standard relapse prediction model, proposing self-efficacy during and after the intervention as an important factor for relapse for up to 6 months after cessation. We recommend a regular assessment of self-efficacy in the ‘Rauchfrei-Programm’ and standardized strategies to intervene with low-esteem participants. Findings might be limited to multimodal and structured group interventions.     

The rise of human stem cell-derived natural killer cells for cancer immunotherapy

Introduction: Natural killer (NK) cell therapy has been proven to be safe and clinically effective for the treatment of multiple cancers, in particular blood cancers. Most of the clinical trials use primary NK cells from peripheral blood or umbilical cord blood, or NK-92 cells. Each cell source is confined by limitations, such as donor dependence, low persistence in vivo, and its difficulty to genetically modify. Thus, there is an urgent need to explore novel NK cell sources for clinical use.

Areas covered: This article highlights the recent progress in utilizing stem cell-derived NK cells as anticancer therapies and strategies to improve their antitumor activities.

Expert commentary: Stem cell-derived NK cells are homogenous, easy to genetically modify on a clonal level, and can be expanded to clinical scale. They may therefore arise as an ideal population for developing off-the-shelf, standardized adoptive NK cell therapeutic products.