IMPLEMENTING BACK PAIN TREATMENT PATHWAYS IN CLINICAL PRACTICE: QUALITATATIVE ANALYSIS OF STAKEHOLDER PERCEPTIONS

Background
Evidence-based practice advocates utilising best current research evidence, while reflecting patient preference and clinical expertise in decision making. Successfully incorporating this evidence into practice is a complex process. Based on recommendations of existing guidelines and systematic evidence reviews conducted using the GRADE approach, treatment pathways for common spinal pain disorders were developed.

Aims
The aim of this study was to identify important potential facilitators to the integration of these pathways into routine clinical practice.

Methods
A 22 person stakeholder group consisting of patient representatives, clinicians, researchers and members of relevant clinical interest groups took part in a series of moderated focus groups, followed up with individual, semi-structured interviews. Data were analysed using content analysis.

Results
Participants identified a number of issues which were categorized into broad themes. Common facilitators to implementation included continual education and synthesis of research evidence which is reflective of everyday practice; as well as the use of clear, unambiguous messages in recommendations. Meeting additional training needs in new or extended areas of practice was also recognized as an important factor. Different stakeholders identified specific areas which could be associated with successful uptake. Patients frequently defined early involvement in a shared decision making process as important. Clinicians identified case based examples and information on important prognostic indicators as useful tools to aiding decisions.

Conclusion
A number of potential implementation strategies were identified. Further work will examine the impact of these and other important factors on the integration of evidence-based treatment recommendations into clinical practice.

Clinical and microbiological evaluation of high intensity diode laser adjutant to non-surgical periodontal treatment: a 6-month clinical trial

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Visual results with the use of prismatic lenses in the treatment of congenital nystagmus: a clinical case

Purpose: It is important to establish a differential diagnosis between the different types of nystagmus, in order to give the appropriate clinical approach to every situation and to improve visual acuity. The nystagmus is normally blocked when the eyes are positioned in a particular way. This makes the child adopt a posture of ocular torticollis that reduces the nistagmiformes movements, improving the vision in this position. A way to promote the blocking of the nystagmic movements is by using prismatic lenses with opposite bases, to block or minimize the oscillatory movements. This results in a vision improvement and it reduces the anomalous head position. There is limited research on the visual results in children with nystagmus after using prisms with opposing bases. Our aim is to describe the impact on the visual acuity (VA ) of theprescription prism lenses in a nystagmus patient starting at 3 months of age. Methods: Case report on thirty month old caucasian male infant, with normal growth and development for their age, with an early onset of horizontal nystagmus at 3 months of age. Ophthalmic examination included slit lamp examination, fundus, refractive study, electrophysiological and magnetic resonance tests, measurement of VA over time with the Teller Acuity Cards (TAC ) in the distance agreed for the age. At age ten months, the mother noted a persistent turn to the right of the child’s head, which became increasingly more severe along the months. There’s no oscillopcia. At 24 months, an atropine refraction showed the following refractive error: 0D.: -1,50, OS: -0,50 and prismatic lens adapting OD 8 Δ nasal base and OE 8 Δ temporal base. Results: Thirty month old child, with adequate development for their age, with onset of idiopatic horizontal nystagmus, at 3 months of age. Normal ocular fundus and magnetic ressoance without alterations, sub-normal results in electrophysiological tests and VA with values below normal for age. At 6 months OD 20/300; OE 20/400; OU 20/300. At 9 months OD 20/250; OE 20/300; OU 20/150 (TAC a 38 cm). At 18 months OD 20/200; OE 20/100; OU 20/80 (TAC at 38 cm), when the head is turned to the right and the eyes in levoversão, the nystagmus decreases in a “neutral” area. At 24 month, with the prismatic glasses, OD 20/200 OE 20/100, OU20/80 (TAC at 54 cm, reference value is 20/30 – 20/100 para OU e 20/40 – 20/100 monocular), there was an increase in the visual acuity. The child did visual stimulation with multimedia devices and using glasses. After adaptation of prisms: at 30 months VA (with Cambridge cards) OD e OE = 6/18. The child improved the VA and reduced the anomalous head position. There is also improvement in mobility and fine motricity. Conclusion: Prisms with opposing bases., were used in the treatment of idiopathic nystagmus. Said prisms were adapted to reduce the skewed position of the head, and to improve VA and binocular function. Monitoring of visual acuity and visual stimulation was done using electronic devices. Following the use of prismatic, the patient improved significantly VA and the anomalous head position was reduced.

Clinical practice guideline on diagnosis and treatment of hyponatraemia

Hyponatraemia, defined as a serum sodium concentration <135 mmol/l, is the most common disorder of body fuid and electrolyte balance encountered in clinical practice. It can lead to a wide spectrum of clinical symptoms, from subtle to severe or even life threatening, and is associated with increased mortality, morbidity and length of hospital stay in patients presenting with a range of conditions. Despite this, the management of patients remains problematic. The prevalence of hyponatraemia in widely different conditions and the fact that hyponatraemia is managed by clinicians with a broad variety of backgrounds have fostered diverse institution-and speciality-based approaches to diagnosis and treatment. To obtain a common and holistic view, the European Society of Intensive Care Medicine (ESICM), the European Society of Endocrinology (ESE) and the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA), represented by European Renal Best Practice (ERBP), have developed the Clinical Practice Guideline on the diagnostic approach and treatment of hyponatraemia as a joint venture of three societies representing specialists with a natural interest in hyponatraemia. In addition to a rigorous approach to methodology and evaluation, we were keen to ensure that the document focused on patient-important outcomes and included utility for clinicians involved in everyday practice.

Vandetanib for the Treatment of Advanced Medullary Thyroid Cancer Outside a Clinical Trial: Results from a French Cohort

International audience

Surgical treatment of a pseudoaneurysm of the femoral artery secondary to a gunshot wound: clinical case report

We report a case of a 18-year-old male patient with a diagnosis of pseudoaneurysm of the right supericial femoral artery secondary to penetrating injury by gunshot, which was treated in our Hospital with an aneurysm resection and a saphenous vascular graft inverted with a satisfactory evolution.

Flixweed vs. Polyethylene Glycol in the Treatment of Childhood Functional Constipation: A Randomized Clinical Trial

Background: Polyethylene glycol (PEG) is often considered as the first-line treatment for functional constipation in children. Descurainia sophia (L.) Webb et Berth (D. sophia) is a safe recommended medicine in Iranian folk and Traditional Persian Medicine for the treatment of constipation. Objectives: To clinically compare D. sophia with PEG 4000 (without electrolyte) in pediatric constipation and to assess its efficacy and side effects. Patients and Methods: 120 patients aged 2 - 12 years with constipation for at least 3 months were included in an 8 weeks lasting randomized controlled trial within two parallel-groups. Children received either PEG, 0.4 g/kg/day, or D. sophia seeds, 2 grams (for children aged 2 - 4 years) and 3 grams (for those aged > 4 years) per day. Results: A total of 109 patients completed the study (56 in D. sophia and 53 in PEG group). At the end of the study, 36 (64.3%) patients in D. sophia group and 29 (54.7%) in PEG group were out of Rome III criteria (P = 0.205). Median weekly stool frequency in 0, 1, 2, 3 weeks of the treatment was found to be 2, 5, 5, 5 in D. sophia and 3, 4, 4, 5 in PEG group (P = 0.139, 0.076, 0.844, 0.294), respectively. The number of patients who suffered flatulence was less (5, 8.9%) in D. sophia group as compared to PEG group (6, 11.3%) at the end of the trial (P = 0.461). D. sophia taste was less tolerated. Conclusions: D. sophia is introduced as a cheap and available medication which can be applied as a safe alternative to conventional PEG in the management of pediatric chronic functional constipation.

Oral Zinc Sulfate as Adjuvant Treatment in Children With Nephrolithiasis: a Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Background: Nephrolithiasis in children is associated with a high rate of complications and recurrence. Objectives:Since some evidences reported that zinc has an important place amongst inhibitors of crystallization and crystal growth, we decided to assess the effectiveness of oral zinc sulfate as adjuvant treatment in children with nephrolithiasis. Patients and Methods: This was a randomized, double-blind, placebo-controlled clinical trial. 102 children in the age range 1 month to 11 years with first nephrolithiasis were recruited. Patients were randomly divided into two equal groups (intervention and control groups). Intervention group received conservative measures for stones and 1 mg/kg/day (maximum 20 mg/day) oral zinc sulfate syrup for 3 months. Control group received placebo in addition to conservative measures, also for 3 months. Patients were followed up by ultrasonography for 9 months, in 5 steps (at the end of 1st, 2nd, 3rd, 6th and 9th month after treatment) assessing size and number of stones in the kidneys. Results: Only at the end of the first month, the average number (intervention: 1.15 ± 3.78, control: 1.3 ± 2.84) (P = 0.001) and size (cm) (intervention: 0.51 ± 1.76, control: 0.62 ± 1.39) (P = 0.001) of stones was significantly lower in the intervention group, and in other points there was no significant therapeutic efficacy in oral zinc adjuvant treatment compared to conservative treatment alone. Also, during the 9-month follow-up, the number and size of stones in both groups decreased significantly (both: P < 0.0001) in a way that the decrease in the intervention group showed no difference with the control group. Conclusions: Adjuvant treatment with zinc is not more effective than consecutive treatment in children with nephrolithiasis. However, further studies are recommended due to the lack of clinical evidence in this field.

Clinical Studies on conformal radiotherapy combined with epidermal growth factor receptor-tyrosine kinase inhibitor in second-line treatment of non-small cell lung cancer

Purpose: To study the effect of conformal radiotherapy combined with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in the second-line treatment of non-small cell lung cancer (NSCLC). Methods: A total of 316 patients attending Shanghai Pulmonary Hospital affiliated to Tongji University, were divided into two groups: 106 patients were treated with conformal radiotherapy combined with EGFR-TKI (gefitinib, 250 mg/day; or erlotinib, 150 mg/day), while 210 patients were treated with EGFRTKI alone. Some factors, including adverse reactions (AR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and one-year and two-year survival rate, were evaluated. Results: No obvious difference was observed in AR between the two groups (p > 0.05). In the combination therapy group, complete response (CR) was 5 cases, partial response (PR) 43 cases, and stable disease (SD) 47 cases, progressive disease (PD) was 11 cases, response rate (RR) was 45.3 %, and DCR 89.6 %. Median PFS in the combination therapy group and targeted therapy group was 6.5 and 5.0 months, respectively. On the other hand, median OS in the combination therapy group and targeted group was 14.1 and 12.6 months, respectively. One-year survival rate of the combination therapy group and EGFR-TKI group was 60.3 and 50.0 %, respectively, while the two-year survival rate was 26.3 and 19.0 %, respectively. Conclusion: Conformal radiotherapy combined with EGFR-TKI can be used as an effective second-line treatment for NSCLC.

Clinical effects of sirolimus treatment in patients with increased serum creatinine levels after renal transplant

Purpose: To observe the clinical effects of sirolimus (SRL) immunosuppressive therapy in patients with progressively increasing levels of serum creatinine (Scr) after renal transplant. Methods: In total, 180 patients whose Scr levels had been rising after renal transplant were given an oral calcineurin inhibitor (CNI): either cyclosporine A (CsA) or tacrolimus (FK506). All patients were treated at People’s Hospital of Zhengzhou, China, between January 2011 and December 2013, and were given SRL-based conversion treatment. Scr level and glomerular filtration rate (GFR) were observed before and 1, 3, and 6 months after treatment initiation. In addition, liver function, blood glucose, blood lipid levels, rejection reaction incidence, and mortality were recorded to evaluate the effects of SRL. Results: Scr levels were 116.60 ± 30.60 μmol/L and 119.00 ± 24.60 μmol/L, and GFR was 70.00 ± 19.70 mL/min and 75.90 ± 15.60 mL/min, at 3 and 6 months after treatment, respectively. The 3- and 6- month Scr and GFR values were statistically different (p < 0.05) compared to pre-treatment levels (Scr: 144.10 ± 61.70 μmol/L vs and GFR: 59.10 ± 16.20 mL/min. Acute rejection (AR) occurred in 20 patients (13.30 %) within 6 months of treatment initiation, but rejection was reversed with conventional methylprednisolone therapy. Twenty-one patients (11.70 %) developed lung infections, but all were cured. There were no significant differences in liver function before and after treatment. Conclusion: SRL-based immunosuppressive therapy is effective in treating patients with increased Scr levels after renal transplant.

Clinical efficacy of paclitaxel in the treatment of mid-stage and advanced malignant gastric cancer, and effect of nursing interventions

Purpose: To investigate the clinical efficacy of paclitaxel combined with additional chemotherapy for mid-stage and advanced malignant tumors, and the benefits afforded by scientific nursing. Methods: Patients with mid-stage and advanced gastric cancer were randomly divided into test and control groups. Control group was given intravenous chemotherapy (400 mg/m2 fluorouracil and 2500 mg/m2 cisplatin) and nursed conventionally, while the test group was additionally treated with 80 mg/m2 paclitaxel and underwent special scientific nursing. Clinical effects and changes in the rates of apoptosis and cell proliferation were recorded. The effect of applying scientific nursing on therapeutic outcomes was also evaluated. Results: The overall rate of treatment effectiveness, clinical control rate, mean apoptosis and proliferation rates in the test group were 56.40, 92.30, (7.10 ± 3.17 and 28.70 ± 3.22 %, respectively, while, in the control group, the values were 38.50, 64.10, 25.40 ± 2.67 and 32.60 ± 2.93 %, respectively. The differences were all statistically significant (p < 0.05). In terms of nursing efficacy, the test group had a lower pain score and higher quality-of-life scores (Karnofsky performance status score) than control group. There was no significant difference in the incidence of adverse reactions between the two groups (p > 0.05). Conclusion: Paclitaxel has a significant effect when used to treat mid-stage and advanced gastric cancer. Moreover, additional nursing not only enhances the therapeutic effect but also improves prognosis and quality-of-life.

Clinical characteristics and selection of treatment modality for patients with vitreomacular traction:real-world implementation of NICE guidance (TA297)

Aim: To investigate the qualitative aspects in patient selection and the quantitative impact of disease burden in real world treatment of vitreomacular traction (VMT) and implementation of the National Institute for Health and Care Excellence (NICE) guidance (TA297). Methods: A monocentric, retrospective review of consecutive patients undergoing optical coherence tomography (OCT) imaging over a 3 month period. Patients with VMT in at least one eye were identified for further data collection on laterality, visual acuity, symptoms, presence of epiretinal membrane, macular hole and treatment selection. Results: A total of 3472 patients underwent OCT imaging with a total of 6878 eyes scanned. Out of 87 patients, 74 patients had unilateral VMT (38 right, 36 left) and 13 patients had bilateral VMT. Eighteen patients with unilateral VMT satisfied NICE criteria of severe sight problems in the affected eye. Eight were managed for a coexisting pathology, one refused treatment, one patient did not attend, two closed spontaneously, and one received ocriplasmin prior to the study start date. Only two patients with unilateral VMT received ocriplasmin and three underwent vitrectomy. Those failing to meet NICE criteria for unilateral VMT were predominantly asymptomatic (n=49) or had coexisting ERM (n=5) or both (n=2). Conclusion: Ocriplasmin provides an alternative treatment for patients with symptomatic VMT. Our data shows that the majority of patients with VMT do not meet NICE TA297 primarily due to lack of symptoms. Those meeting NICE criteria, but not treated, tended to have coexisting macular pathology. Variation in patient selection due to subjective factors not outlined in NICE guidance suggests that real world outcomes of ocriplasmin therapy should be interpreted with caution.

Oral chondroitin sulfate and prebiotics for the treatment of canine Inflammatory Bowel Disease: a randomized, controlled clinical trial

BACKGROUND Canine inflammatory bowel disease (IBD) is a chronic enteropathy of unknown etiology, although microbiome dysbiosis, genetic susceptibility, and dietary and/or environmental factors are hypothesized to be involved in its pathogenesis. Since some of the current therapies are associated with severe side effects, novel therapeutic modalities are needed. A new oral supplement for long-term management of canine IBD containing chondroitin sulfate (CS) and prebiotics (resistant starch, β-glucans and mannaoligosaccharides) was developed to target intestinal inflammation and oxidative stress, and restore normobiosis, without exhibiting any side effects. This double-blinded, randomized, placebo-controlled trial in dogs with IBD aims to evaluate the effects of 180 days administration of this supplement together with a hydrolyzed diet on clinical signs, intestinal histology, gut microbiota, and serum biomarkers of inflammation and oxidative stress. RESULTS Twenty-seven client-owned biopsy-confirmed IBD dogs were included in the study, switched to the same hydrolyzed diet and classified into one of two groups: supplement and placebo. Initially, there were no significant differences between groups (p > 0.05) for any of the studied parameters. Final data analysis (supplement: n = 9; placebo: n = 10) showed a significant decrease in canine IBD activity index (CIBDAI) score in both groups after treatment (p < 0.001). After treatment, a significant decrease (1.53-fold; p < 0.01) in histologic score was seen only in the supplement group. When groups were compared, the supplement group showed significantly higher serum cholesterol (p < 0.05) and paraoxonase-1 (PON1) levels after 60 days of treatment (p < 0.01), and the placebo group showed significantly reduced serum total antioxidant capacity (TAC) levels after 120 days (p < 0.05). No significant differences were found between groups at any time point for CIBDAI, WSAVA histologic score and fecal microbiota evaluated by PCR-restriction fragment length polymorphism (PCR-RFLP). No side effects were reported in any group. CONCLUSIONS The combined administration of the supplement with hydrolyzed diet over 180 days was safe and induced improvements in selected serum biomarkers, possibly suggesting a reduction in disease activity. This study was likely underpowered, therefore larger studies are warranted in order to demonstrate a supplemental effect to dietary treatment of this supplement on intestinal histology and CIBDAI.

Prediction Nomogram for 68Ga-PSMA-11 PET/CT in different clinical settings of PSA failure after radical treatment for Prostate Cancer

Objective The objective of this study was to develop a clinical nomogram to predict gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA-11-PET/CT) positivity in different clinical settings of PSA failure. Materials and methods Seven hundred three (n = 703) prostate cancer (PCa) patients with confirmed PSA failure after radical therapy were enrolled. Patients were stratified according to different clinical settings (first-time biochemical recurrence [BCR]: group 1; BCR after salvage therapy: group 2; biochemical persistence after radical prostatectomy [BCP]: group 3; advanced stage PCa before second-line systemic therapies: group 4). First, we assessed 68Ga-PSMA-11-PET/CT positivity rate. Second, multivariable logistic regression analyses were used to determine predictors of positive scan. Third, regression-based coefficients were used to develop a nomogram predicting positive 68Ga-PSMA-11-PET/CT result and 200 bootstrap resamples were used for internal validation. Fourth, receiver operating characteristic (ROC) analysis was used to identify the most informative nomogram’s derived cut-off. Decision curve analysis (DCA) was implemented to quantify nomogram’s clinical benefit. Results 68Ga-PSMA-11-PET/CT overall positivity rate was 51.2%, while it was 40.3% in group 1, 54% in group 2, 60.5% in group 3, and 86.9% in group 4 (p < 0.001). At multivariable analyses, ISUP grade, PSA, PSA doubling time, and clinical setting were independent predictors of a positive scan (all p ≤ 0.04). A nomogram based on covariates included in the multivariate model demonstrated a bootstrap-corrected accuracy of 82%. The nomogram-derived best cut-off value was 40%. In DCA, the nomogram revealed clinical net benefit of > 10%. Conclusions This novel nomogram proved its good accuracy in predicting a positive scan, with values ≥ 40% providing the most informative cut-off in counselling patients to 68Ga-PSMA-11-PET/CT. This tool might be important as a guide to clinicians in the best use of PSMA-based PET imaging.

Percutaneous Cement Discoplasty: Biomechanical and clinical assessment of a minimally invasive treatment of lumbar intervertebral disc disease

With population ageing, spine diseases have an increasing prevalence and induce high economic and social costs. The development of minimally invasive surgeries allows reducing the surgery-associated risks in elderly and polymorbid patients, and save costs by treating more patients in shorter time and reducing the complications. Percutaneous Cement Discoplasty (PCD) is a minimally invasive technique developed to treat highly degenerated intervertebral discs exhibiting a vacuum phenomenon. Filling the disc with bone cement creates a stand-alone spacer which partially restores the disc height and re-opens the foraminal space. PCD has recently been introduced to clinical use. However, the spine biomechanics following this treatment remained unravelled. The aim of this PhD thesis is to bridge the clinical experience with in vitro methodologies, to provide a multilateral evaluation of PCD outcome and a better understanding of its impact on the spine biomechanics, and of its possible contraindications. Firstly, a suitable in vitro porcine model to test the biomechanics of discoplasty by comparing specimens in the preoperative and postoperative conditions was developed. The methodology was then applied to investigate the biomechanics of discoplasty in cadaveric human segments. The in vitro specimens were mechanically investigated in flexion and extension, while a DIC system quantified the range of motion, disc height, and strains on the disc surface. Then, a versatile tool to measure the impact of discoplasty on the foramen space was developed and applied both to clinical and experimental work. The vertebrae reconstructed from CT scans were registered to match the loading configuration, using ex vivo DIC measurements under loading. The foramen volumetric changes caused by PCD was measured using a 3D geometrical method clinically developed by the research group. In conclusion, this project significantly extended the understanding of PCD biomechanics, highlighting its benefits in the treatment of advanced cases of intervertebral disc degeneration.