The establishment of a primary spine care practitioner and its benefits to health care reform in the United States

It is widely recognized that the dramatic increase in health care costs in the United States has not led to a corresponding improvement in the health care experience of patients or the clinical outcomes of medical care. In no area of medicine is this more true than in the area of spine related disorders (SRDs). Costs of medical care for SRDs have skyrocketed in recent years. Despite this, there is no evidence of improvement in the quality of this care. In fact, disability related to SRDs is on the rise. We argue that one of the key solutions to this is for the health care system to have a group of practitioners who are trained to function as primary care practitioners for the spine. We explain the reasons we think a primary spine care practitioner would be beneficial to patients, the health care system and society, some of the obstacles that will need to be overcome in establishing a primary spine care specialty and the ways in which these obstacles can be overcome.https://doi.org/10.1186/2045-709X-19-1

GnRH-I and GnRH-II have differential modulatory effects on human peripheral blood mononuclear cell proliferation and interleukin-2 receptor γ-chain mRNA expression in healthy males

GnRH-I and its receptor (GnRHR-I) have previously been demonstrated and shown to be biologically active in the immune system, notably within peripheral lymphocytes. Recently however, a second form of GnRH (GnRH-II) has been described in the human. The functions of both these neuropeptides in PMBCs have not been understood yet. The present study was therefore designed to investigate the effects of GnRH-I and/or GnRH-II on human PMBC proliferation in males. Secondly, the effects of GnRH-I and GnRH-II on IL-2 dependent lymphocyte proliferation were examined. Finally, we analysed the role of GnRH-I and GnRH-II in IL-2R γ-chain expression. Peripheral venous blood samples were obtained from six male healthy volunteers (Mean age 27·75 ± 1·5). Non-radioactive cell proliferation assay was used for proliferation studies and we used quantitative real-time RT-PCR to examine the role of GnRH-I and GnRH-II on IL-2R γ-chain expression in PMBCs. Treatment of PMBCs with GnRH-I (10(−9) M and 10(−5) M) and with interleukin-2 (IL-2) (50 U/ml) resulted in a significant increase in cell proliferation compared with the untreated control. PMBCs cotreated with IL-2 and GnRH-I demonstrated higher proliferative responses than IL-2 treatment alone, the enhancement of GnRH-I on IL-2 response being significant only at GnRH-I concentration of 10(−5) M. Co-incubation of IL-2+ GnRH 10(−5) M with a GnRH antagonist (Cetrorelix; 10(−6) M) significantly decreased the proliferation. GnRH-II did not affect the proliferation of PMBCs alone, and did not alter the proliferative response to IL-2. The proliferative responses to GnRH-I (alone and with IL-2) were significantly attenuated by GnRH-II coincubation (each in equal molar concentrations; 10(−9) M to 10(−5) M). It was found that GnRH-I increased the expression of IL-2Rγ mRNA in a dose dependent manner, with a significant increase of percentage 162·3 ± 14 of control at 10(−5) M. In contrast, IL-2Rγ expression was significantly decreased in all concentrations of GnRH-II (10(−9) M to10(−5) M), and the maximum decrease was detected at 10(−5) M, with percentage 37·7 ± 6·6 of control. All these findings strongly suggest that regulation of IL-2R expression may therefore be an important target for GnRH-I and GnRH-II in PMBCs in males. In summary, present study clearly demonstrates the differential effects of GnRH-I and GnRH-II on PMBC proliferation, IL-2 proliferative response, and IL-2Rγ expression in PMBCs in males. To our knowledge, our observations provide the first evidence for the interactions of these local neuropeptides at lymphocyte level. Further experimental data in human are warranted to explore the clinical implications of these data

DUOGLOBE. One-Year Outcomes in a Real-World Study of Levodopa Carbidopa Intestinal Gel for Parkinson's Disease

Background: Levodopa-carbidopa intestinal gel (LCIG) is an established treatment for improving motor and some non-motor symptoms (NMS) in patients with advanced Parkinson's disease (PD). Prospective long-term data in routine clinical practice are limited. Objective: Assess LCIG effectiveness and safety in patients with advanced PD after 12 months during real-world routine clinical practice. Methods: Duodopa/Duopa in patients with advanced Parkinson's disease—a global observational study evaluating long-term effectiveness (DUOGLOBE) (NCT02611713) is an ongoing, prospective, multinational, observational study of LCIG-naïve patients treated as part of routine clinical practice; 3 years of follow-up are planned. The primary outcome is the change in patient-reported off time. Other assessments include the Unified Dyskinesia Rating Scale (UDysRS), Non-Motor Symptoms Scale (NMSS), Parkinson's Disease Sleep scale (PDSS-2), Epworth Sleepiness Scale (ESS), health-related quality of life (HR-QoL), caregiver burden, and serious adverse events (SAEs). Outcomes from baseline to month (M) 12 are presented. Results: In this 12-month follow-up, patients (N = 195) had baseline characteristics similar to other LCIG studies. Significant improvements (mean change to M12) were observed in off time (−3.9 ± 3.6 hr/day, P < 0.001), dyskinesia assessed using the UDysRS (−9.6 ± 22.5, P < 0.001), NMSS (−23.1 ± 41.4, P < 0.001), sleep and sleepiness symptoms on the PDSS-2 (−6.5 ± 12.2, P < 0.001) and ESS (−1.0 ± 5.7, P < 0.05), HR-QoL (−9.0 ± 21.6, P < 0.001), and caregiver burden (−1.9 ± 6.7, P = 0.008). Overall, 40.5% (n = 79) of patients experienced SAEs; fall (n = 6; 3.1%) and urinary tract infection (n = 6; 3.1%) were SAEs reported in ≥3% of patients. Conclusions: These 12-month outcome data show sustained, long-term improvements and support the real-world effectiveness of LCIG in patients with advanced PD. Safety was consistent with previous studies

Outcomes Impacting Quality of Life in Advanced Parkinson’s Disease Patients Treated with Levodopa-Carbidopa Intestinal Gel

Background: It is believed that motor symptoms, including dyskinesia, and non-motor symptoms impact health-related quality of life (HRQoL) in patients with Parkinson’s disease (PD), and that improvements in these metrics are correlated. Objective: Investigate the relationship between HRQoL and measures of PD severity and treatment efficacy, including motor and non-motor symptoms. Methods: This was a planned investigation of an international, prospective, single-arm, post-marketing observational study of the long-term effectiveness of levodopa-carbidopa intestinal gel (LCIG) in patients with advanced PD. Pearson correlation coefficients (PCC) were calculated for baseline and change from baseline at 12 months between HRQoL and motor and non-motor symptoms. Results: A total of 195 patients were included. At baseline, HRQoL was moderately positively correlated with Activities of Daily Living (UPDRS II, PCC=0.44), non-motor symptoms (0.48), and measures of sleep (0.50 and 0.40); all p<0.001. After 12 months of treatment with LCIG, improvements in HRQoL were moderately positively correlated with improvement from baseline in non-motor symptoms (PCC=0.42), sleep (0.54), and daytime sleepiness (0.40; all p<0.001), and weakly correlated with improvement in dyskinesia signs and symptoms (PCC=0.23; p=0.011). Improvement in HRQoL was not correlated with improvements in OFF time or dyskinesia time. Conclusion: Both at baseline and for change from baseline at 12 months, HRQoL was correlated with baseline and change from baseline in dyskinesia, Activities of Daily Living, and non-motor symptoms, including sleep; but not with baseline or change in OFF time

Cost-effectiveness analysis of prostate cancer screening

To determine the optimal strategy for prostate cancer screening, the cost-effectiveness of screening was analyzed using a medical decision model. One hundred thousand asymptomatic males between the ages of 40 and 69 were modeled with and without screening. The subjects were divided into three 10-year age groups. We used a 5-year survival rate as an effectiveness point and assumed after 5 year survival free from prostate cancer. We considered three potential programs: 1) screening with digital rectal examination (DRE), 2) screening with prostate specific antigen (PSA), and 3) screening with a combination of DRE and PSA. The study was analyzed from the payer’s perspective, and only direct medical costs were included. For each of the three age groups, PSA screening was more cost-effective than either DRE screening or a combination of DRE and PSA screening. The cost-effectiveness ratio for the combination of DRE and PSA screening was 1.1–2.3 times more expensive dian that of PSA screening. If the compliance rate for work-up exams is 80%, the cost-effectiveness of prostate cancer screening is approximate to that of gastric cancer screening. In conclusion, PSA screening is the most cost-effective strategy for prostate cancer screening when compared with both DRE and the combination of DRE and PSA screening. But prostate cancer screening should be carefully conducted, taking the cost-effectiveness of the different strategies and target groups into consideration