A dynamic study of VEGF-A siDOX-EVs trafficking through the in-vitro insert co-culture blood-brain barrier model by digital holographic microscopy.

Introduction: Modeling the blood-brain barrier has long been a challenge for pharmacological studies. Up to the present, numerous attempts have been devoted to recapitulating the endothelial barrier in vitro to assess drug delivery vehicles' efficiency for brain disorders. In the current work, we presented a new approach for analyzing the morphometric parameters of the cells of an insert co-culture blood-brain barrier model using rat brain astrocytes, rat brain microvascular endothelial cells, and rat brain pericytes. This analytical approach could aid in getting further information on drug trafficking through the blood-brain barrier and its impact on the brain indirectly. Methods: In the current work, we cultured rat brain astrocytes, rat brain microvascular endothelial cells, and rat brain pericytes and then used an insert well to culture the cells in contact with each other to model the blood-brain barrier. Then, the morphometric parameters of the porous membrane of the insert well, as well as each cell type were imaged by digital holographic microscopy before and after cell seeding. At last, we performed folate conjugation on the surface of the EVs we have previously tested for glioma therapy in our previous work called VEGF-A siDOX-EVs and checked how the trafficking of EVs improves after folate conjugation as a clathrin-mediated delivery setup. the trafficking and passage of EVs were assessed by flow cytometry and morphometric analysis of the digital holographic microscopy holograms. Results: Our results indicated that EVs successfully entered through the proposed endothelial barrier assessed by flow cytometry analysis and furthermore, folate conjugation significantly improved EV passage through the blood-brain barrier. Moreover, our results indicated that the VEGF-A siDOX-EVs insert cytotoxic impact on the cells of the bottom of the culture plate. Conclusion: folate-conjugation on the surface of EVs improves their trafficking through the blood-brain barrier and by using digital holographic microscopy analysis, we could directly assess the morphometric changes of the blood-brain barrier cells for pharmacological purposes as an easy, label-free, and real-time analysis.

Extracellular vesicles derived from dendritic cells loaded with VEGF-A siRNA and doxorubicin reduce glioma angiogenesis in vitro.

BACKGROUND: Numerous attempts have been devoted to designing anti-angiogenic agents as a strategy to slow tumor growth and progression. Clinical applications of conventional anti-angiogenic agents face some challenges, e.g., off-target effects for TKIs and also low solid tumor penetration for mAbs. Furthermore, although anti-angiogenic therapy provides a normalization window for better chemo-RT response, in long-term treatments, tumor hypoxia as a result of total removal of VEGF-A by mAbs from the TME or complete blockade of TK receptors induces over-activation of compensatory angiogenic pathways, causing escape. Herein, we investigate the efficacy of si-DOX-DC-EVs to reduce glioma angiogenesis and invasiveness. METHODS: Mature DCs were generated from PBMC and EVs were isolated from the DCs culture media. siRNA and Doxorubicin were loaded into EVs by EP and incubation. Afterward, the uptake of DC-EVs was assessed by flow cytometry, and the subcellular localization of EVs was tested by confocal imaging. Tube formation assay was performed to assess the efficacy of si-DOX-DC-EVs to reduce tumor angiogenesis which was analyzed by DHM. Morphometric analysis of apoptotic cells was performed by DHM and confocal imaging and further, ELISA was performed for hypoxia-related and angiogenic cytokines. The impact of our theranostic system "si-DOX-DC-MVs" on the formation of vascular mimics, colonies, and invasion of C6 cells was checked in vitro. Afterward, orthotropic rat models of glioma were generated and the optimal administration route was selected by in vivo fluorescent analysis. Then, the microvessel density, vimentin expression, and accumulation of immune cells in tumoral tissues were assessed by IHC. Finally, necropsy and autopsy analyses were performed to check the safety of our theranostic agent. RESULTS: DC-EVs loaded with si-DOX-DC-EVs were successfully uptaken by cells with different subcellular trafficking for MVs and exosomes, reduced tumor angiogenesis in DHM analysis, and induced apoptosis in tumoral cells. Moreover, using DHM, we performed a detailed label-free analysis of tip cells which suggested that the tip cells in si-DC-MV treatments lost their geometrical migration capacity to form tube-like structures. Furthermore, the ELISAs performed highlighted that there is a mild overactivation of compensatory Tie2/Ang2 pathway after VEGF-A blockade which confers with severe hypoxia and sustains normal angiogenesis which is the optimal goal of anti-angiogenesis therapy for cancer to avoid resistance.The results of our VM analyses indicated that si-DOX-DC-MVs completely inhibited VM process. Moreover, the invasion, migration, and colony formation of the C6 cells treated with si-DOX-MVs were the least among all treatments. IN was the optimal route of administration. The MVD analyses indicated that si-DOX-DC-MVs reduced the number of tumoral microvessels and normalized vessel morphology. Intense CD8+ T cells were observed near the tumoral vessels in the si-DOX-DC-MVs group and with minimal activation of MT (low Vimentin expression). Necropsy and toxicology results proved that the theranostic system proposed is safe. CONCLUSIONS: DC-EVs loaded with VEGF-A siRNA and Doxorubicin were more potent than BV alone as a multi-disciplinary strategy that combats glioma growth by cytotoxic impacts of DOX and inhibits angiogenesis by VEGF-A siRNAs with excess immunologic benefits from DC-EVs. This next-generation anti-angiogenic agent normalizes tumor vessel density rather than extensively eliminating tumor vessels causing hypoxia and mesenchymal transition.

Efficacy of cell-based immunotherapies on patients with glioma: an umbrella review of systematic reviews and meta-analysis protocol.

INTRODUCTION: Glial brain tumours are highly mortal and are noted as major neurosurgical challenges due to frequent recurrence or progression. Despite standard-of-care treatment for gliomas, the prognosis of patients with higher-grade glial tumours is still poor, and hence empowering antitumour immunity against glioma is a potential future oncological prospect. This review is designed to improve our understanding of the efficacy of cell-based immunotherapies for glioma. METHODS AND ANALYSIS: This systematic review will be performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search of main electronic databases: PubMed/MEDLINE, Scopus, ISI Web of Science EMBASE and ProQuest will be done on original articles, followed by a manual review of review articles. Only records in English and only clinical trials will be encountered for full-text review. All the appropriate studies that encountered the inclusion criteria will be screened, selected and then will undergo data extraction step by two independent authors. For meta-analyses, data heterogeneity for each parameter will be first evaluated by Cochran's Q and I2 statistics. In case of possible heterogeneity, a random-effects meta-analysis will be performed and for homogenous data, fixed-effects models will be selected for reporting the results of the proportional meta-analysis. Bias risk will be assessed through Begg's and Egger's tests and will also be visualised by Funnel plots. ETHICS AND DISSEMINATION: As this study will be a systematic review without human participants' involvement, no ethical registration is required and meta-analysis will be presented at a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022373297.

A comprehensive update to Dendritic Cell therapy for glioma: a systematic review and meta-analysis.

BACKGROUND: Gliomas are major challenges of neuro-oncology due to high mortality. Clinical applications of dendritic cells (DCs) have yielded promising results in the clinical trial pipelines over decades. RESEARCH DESIGN: In this systematic review, we critically discuss the current status, future perspective, and challenges of DC therapy for gliomas . and summarize the study population, blinding, comparators, dosage, treatment regimens, efficacy, and safety issues of the clinical trials published on DC therapy for gliomas and also report the results of our meta-analysis on safety and immunological efficacy of DC therapy for gliomas. RESULTS: The results of our meta-analysis indicated that the most frequent grade I/II adverse event (AE) reported in phase I or phase I/II trials was fatigue (∼16% and 24%). Moreover, in phase II trials, fatigue and cytopenia were the most common AEs (∼9% and 14%). Meanwhile, Grade III/IV AEs were rare . Moreover, our meta-analysis indicated ∼64% CD8+ T cells infiltration into tumor site after DC therapy and also ∼45% IFNγ increase. CONCLUSIONS: DC therapy could serve as a potential immunotherapy for gliomas; however, limitations exist to draw certain conclusions due to diversity of the criteria applied to assess clinical response and limited data on patients' survival.

A systematic update to circulating extracellular vesicles proteome; transcriptome and small RNA-ome as glioma diagnostic, prognostic and treatment-response biomarkers.

Brain gliomas are major neurosurgical challenges due to high mortality and morbidity. Hence, development of novel biomarkers is of great value to plan appropriate treatment strategy. Evaluation of the molecular content of extracellular vesicles (EVs) as novel non-invasive biomarker repertoires can provide a real-time portrait of disease status. This study aims to provide a systematic, comprehensive and critical report of the diagnostic and prognostic significance of EV biomarkers (proteins, DNAs and RNAs) for brain gliomas, discuss their biogenesis and passage through the blood brain barrier, and also highlight the high throughput methods used for EV biomarker discovery; as well as discussing potential limitations of EV isolation and characterization methods as glioma diagnostic, prognostic or treatment response biomarkers. Moreover, we critically appraise the bias risk in the previous studies, discuss the limitations EV biomarker discovery faces to enter neurosurgical practice in the future, and highlight the need for more optimized protocols for EV isolation and biomarker discovery in high throughput studies. The current systematic review was conducted upon PRISMA guidelines [10].

The Role of Optical Coherence Tomography in Early Detection of Retinal Nerve Fiber Layer Damage in Pituitary Adenoma.

Background and objectives:This study aimed to evaluate the ability of optical coherence tomography (OCT) to differentiate eyes without obvious visual disturbances following pituitary adenomas (PAs) from normal eyes, in order to identify factors that could predict early diagnosis and timely treatment and prevent structural damage of visual pathway in patients with saddle area tumors. Material and methods:The present study was carried out between 2014-2018. Participants were divided into three groups: 23 subjects (44 eyes) in the PAs with visual field involvement (VFI) group, 10 (20 eyes) in the PAs with normal visual field (NVF) group and 22 subjects (44 eyes) in the control group. All patients received diagnostic magnetic resonance imaging (MRI), automated perimetry, visual acuity, OCT and ophthalmological assessments. Also, the degree of visual field (VF) deficit and thickness of peripapillary retinal nerve fiber layer (pRNFL) were measured by OCT and then considered for statistical analysis as predictors of early diagnostic visual involvement in the PAs. Results:All patients in the NVF and control groups (a total of 64 eyes) had normal VF. In the VFI group there were 16 eyes with complete hemianopia. Bitemporal hemianopia occurred in 20 eyes and eight eyes with concentric VF narrowing. Assessment of pRNFL thickness with OCT demonstrated the average and all quadrants of pRNFL thickness in the VFI group were significantly thinner than the pRNFL thickness in the other groups (P<0.001). The pRNFL thickness in the inferior and nasal quadrants and the average value in the NVF group were significantly thinner than the control group (P<0.05). Conclusion:If a patient has band atrophy, there is an irreversible damage and the main goal is to diagnose a nerve damage using OCT before band atrophy.

Global sagittal angle and spinopelvic sagittal alignment: a step toward investigation of sagittal plane deformity in upper lumbar disc herniation.

BACKGROUND AND OBJECTIVES: Understanding the biomechanical relationship between the spine and the pelvis is important for the management of symptomatic lumbar disease. There are several different metrics that may be used to evaluate the spine in the sagittal plane. The aim of this study is to compare spinopelvic parameters and global sagittal angle (GSA) in a cohort of patients with upper lumbar disc herniations (ULDH) to identify a correlation between the pelvic incidence (PI) and GSA with ULDH. MATERIAL AND METHODS: Eighty-six patients with ULDH and 86 asymptomatic control group underwent whole body biplanar stereographs- and magnetic resonance imaging . The spinopelvic parameters and GSA were measured. RESULTS: PI, sacral slope (SS), lumbar lordosis (LL), and thoracic kyphosis (TK) were all significantly lower than in the control group (p < 0.01) but there was no difference in the pelvic tilt (PT). The two groups were divided into subgroups. PI in the T12-L1 and L1-L2 level groups were significantly smaller than in the control group (p < 0.05). Also, there was a significant difference in TK and LL between the L3-L4 level and control group (p < 0.05), but there was no statistically significant difference in PT between all levels and the control group. CONCLUSION: This study demonstrated a unique correlation between several spinopelvic parameters and GSA and the occurrence of ULDH. Lower PI, SS, and LL in T12-L1 and L1-L2 levels indicates a flat lumbar spine which may increase mechanical stress at these levels, thereby leading to disc herniation.

Percutaneous balloon kyphoplasty in the treatment of vertebral compression fractures: a single-center analysis of pain and quality of life outcomes.

BACKGROUND: Vertebral body compression fractures are one of the most common causes of disability and morbidity, especially among the elderly population. The present study was performed in order to evaluate the effect of percutaneous balloon kyphoplasty (BKP) on patients' pain and quality of life (QOL) in Iran. METHODS: The study was conducted on a consecutive series of 54 patients with symptomatic vertebral compression fractures who failed conservative management between 2014 and 2017. A quasi-experimental design was employed in which the pain severity, quality of life, and kyphotic angle were measured before and 3 and 12 months after the PBK procedure. Pain and quality of life outcomes were determined using a Visual Analogue Scale (VAS) for Pain and the 12-Item Short Form Health Survey (SF-12) for QOL. RESULTS: Excellent improvement in VAS was documented at 3 and 12 months after the BKP procedure (p = 0.001). Improvement at 3 months was maintained through the 12 months follow-up period. A statistically significant improvement in QOL was documented at 3 months after BKP that continued to improve through 12 months follow-up. The mean kyphotic angle before PBK was 19.4 ± 5.3 degrees which after 3 months improved to 12.8 ± 3.1 degrees; this reduction was significant (p < 0.001). No new fractures occurred during the follow-up period. CONCLUSION: Balloon kyphoplasty was determined to be a safe and successful method for treating symptomatic vertebral compression fractures. It leads to significant pain relief, an improvement in self-reported QOL measures, and correction in kyphotic deformity.

Aripiprazole for prevention of delirium in the neurosurgical intensive care unit: a double-blind, randomized, placebo-controlled study.

PURPOSE: Delirium is reported in over 50% of critically ill ICU patients, and is associated with increased mortality and long-term cognitive consequences. Prevention and early management of delirium are essential components of ICU care. However, pharmacological interventions have not been effective in delirium prevention. This study investigated the effect of aripiprazole in the prevention of delirium in a neurosurgical intensive care unit. METHODS: In this prospective, randomized placebo-controlled small clinical trial, 53 patients, 18 to 80 years old, were randomized to receive enteric aripiprazole (15 mg) or placebo for up to 7 days. Delirium, detected by the Confusion Assessment Method-ICU, ICU events, laboratory studies, aripiprazole safety, time to delirium onset, delirium-free days, delirium prevalence during follow-up and ICU length of stay were recorded. RESULTS: Forty patients with similar baseline characteristics, including age, sex, neurosurgery types and APACHE II scores, completed the study. Delirium incidence and the mean days to its onset were 20% vs. 55% (p = 0.022) and 2.17 ± 0.41 vs. 2.09 ± 0.30 (p = 0.076) in the aripiprazole and placebo groups, respectively. The mean number of delirium-free days were: 5.6 (95%CI, 4.6-6.5) and 4.3 (95%CI, 3.2-5.4), in aripiprazole and placebo groups, respectively (p = 0.111). The prevalence of delirium during the follow-up was significantly lower in the aripiprazole group (p = 0.018). Serious aripiprazole adverse reactions were not observed. CONCLUSIONS: Aripiprazole can reduce the incidence of delirium in the neurosurgical ICU. Studies with larger sample size in diverse ICU settings and longer follow-up are needed to confirm our findings.

An Intraventricular Type of Chondroma: A Case Report.

Intracranial chondromas are unusual benign tumors. They commonly occur at the base of the skull, whereas an intraventricular type is very rare. We present the case of a 19-year-old female patient with a giant intraventricular chondroma detected incidentally by imaging after a car accident. The spiral head CT scan and MRI findings revealed a large solid mass with a lobular border and coarse calcified components. A wide craniotomy was performed, and a very firm tumor was observed with no internal debulking capacity. The tumor was completely removed in one piece. Differentiation of an intraventricular chondroma from other intraventricular lesions, such as choroid plexus carcinoma, meningioma, and cavernoma, is of great importance in neuroimaging and surgical planning.

Craniometrical imaging and clinical findings of adult Chiari malformation type 1 before and after posterior fossa decompression surgery with duraplasty.

Background: Posterior fossa decompression both with and without duraplasty are accepted treatments for symptomatic adult patients with Chiari Malformations Type 1 (CM-1). There is still debate of the superiority of one technique over the other. The purpose of this study was to determine the clinical and craniometrical imaging outcomes of a series of patients who underwent posterior fossa decompression with duraplasty. Materials and methods: All adult patients with symptomatic CM-1 operated at a single institution with a minimum of 6 months follow-up were enrolled prospectively. Clinical outcomes and craniometrical parameters based upon MR imaging pre- and post-surgery were analyzed. Results: A series of 33 consecutive patients who met the inclusion criteria were enrolled; mean age of 33.93 ± 10 years (range 14-56 years). The most common preoperative complaint was headache. The most common clinical sign was sensory dysfunction which was relieved or improved in 63% of patients. The mean syringomyelia size had a significant reduction after the surgery (p = .01). The mean tonsillar descent also had significant reduction (p = .00). The mean McRae line length before the surgery and after that were 33.4 and 53.1 mm respectively that this change was not statistically significant (p = .42). The odontoid process parameters had no significant changes after surgery. Conclusions: Posterior fossa decompression surgery with duraplasty can improve both clinical and imaging outcomes such as syringomyelia size and tonsillar descent for patients with symptomatic CM-1. However, no significant difference was found in craniometrical parameters before and after the surgery.

Effectiveness of an In-Service Education Program to Improve Patient Safety Directed at Surgical Residents: A Randomized Controlled Trial.

BACKGROUND: Patient safety is a critical issue in healthcare services particularly in surgical units and operation rooms because of the high prevalence and risk of medical errors in such settings. This study was conducted to determine whether a 1-day educational intervention can change the attitude and behavior of surgical residents regarding patient safety. METHODS: A total of 90 surgical residents were recruited from 6 university hospitals located in Tehran and Qazvin, Iran, and were randomized to either the intervention or a control group. Those in the intervention group participated in a 1-day workshop on patient safety, whereas the control group received no intervention. Both groups were followed for 3 months after the intervention was completed. The Safety Attitude Questionnaire and Oxford Non-Technical Skills scale were administered at 3 points in time (baseline, 1 month after the intervention, and 3 month later). The data were analyzed using repeated measures analysis of variance. RESULTS: Total score on the Safety Attitude Questionnaire improved from 54.5 (SD = 14.4) at baseline to 58.3 (SD = 13.8) 3 months after the intervention in the intervention group; all dimensions, with the exception of working condition, showed significant changes. In addition, the Oxford Non-Technical Skills scale - as assessed by attending surgeons - improved significantly in all domains (p < 0.05). More than 60% of participants in the intervention group scored in the positive range for items assessing safety and teamwork climate. CONCLUSIONS: A 1-day interactive educational workshop may be effective in changing the attitude and practice of surgical residents regarding patient safety. Further assessment of this intervention in other healthcare settings involving health professionals from various specialties and use of an objective measure such as number of reported medical errors are needed to corroborate these findings.

Health-related quality of life and medication adherence in elderly patients with epilepsy.

OBJECTIVE: Considering the high prevalence of epilepsy in the elderly and the importance of maximising their quality of life (QoL), this study aimed to investigate the relationship between medication adherence and QoL, and the mediating effects of medication adherence on the association between serum antiepileptic drug (AED) level and seizure severity with QoL in elderly epileptics. METHODS: In a longitudinal study, 766 elderly patients with epilepsy who were prescribed a minimum of one antiepileptic drug were selected by convenience sampling method. A Medication Adherence Report Scale (MARS-5) questionnaire was completed at the baseline. Seizure severity and QoL were assessed after six months using the Liverpool Seizure Severity Scale (LSSS) and the QoL in Epilepsy (QOLIE-31) questionnaires respectively. Serum level of AED was also measured at six-month follow-up. RESULTS: Medication adherence was significantly correlated with both seizure severity (ß = -0.33, p < 0.0001) and serum AED level (ß = 0.29, p < 0.0001) after adjusting for demographic and clinical characteristics. Neither QoL nor its sub-classes were correlated with seizure severity. In addition, a significant correlation was not observed between serum AED level and QoL. However, medication adherence was significantly correlated with QoL (ß = 0.30, p < 0.0001). The mediating effects of medication adherence on the association between serum AED level (Z = 3.39, p < 0.001) and seizure severity (Z = -3.47, p < 0.001) with QoL were supported by the Sobel test. CONCLUSION: This study demonstrates that medication adherence has a beneficial impact on QoL in elderly epileptics. Therefore, adherence to treatment should be monitored to improve their QoL.

Validation of the 5-Item Medication Adherence Report Scale in Older Stroke Patients in Iran.

BACKGROUND: There is a lack of feasible and validated measures to self-assess medication adherence for older patients with stroke. In addition, the potential determinants of medication adherence for older patients with stroke remain unclear. OBJECTIVES: The aims of this study were to (1) examine the psychometric properties of a 5-item questionnaire on medication adherence, specifically the 5-item Medication Adherence Report Scale (MARS-5), and (2) explore the determinants of medication adherence. METHODS: Stroke patients older than 65 years (N = 523) filled out the MARS-5 and the Hospital Anxiety and Depression Scale. The medication possession rate (MPR) was calculated to measure the objective medication adherence. Several clinical characteristics (stroke types, blood pressure, comorbidity, HbA1c, quantity of prescribed drugs, fasting blood glucose, and total cholesterol) and background information were collected. We used Rasch analysis with a differential item functioning test to examine psychometric properties. RESULTS: All 5 items in the MARS-5 fit in the same construct (ie, medication adherence), no differential item functioning items were displayed in the MARS-5 across gender, and the MARS-5 total score was strongly correlated with the MPR (r = 0.7). Multiple regression models showed that the MARS-5 and the MPR shared several similar determinants. In addition, the variance of the MARS-5 (R = 0.567) was more than that of the MPR (R = 0.300). CONCLUSIONS: The MARS-5 is a feasible and valid self-assessed medication adherence for older patients with stroke. In addition, several determinants were found to be related to medication adherence for older patients with stroke. Healthcare providers may want to take heed of these determinants to improve medication adherence for this population.

Using the Theory of Planned Behavior incorporated with perceived barriers to explore sexual counseling services delivered by healthcare professionals in individuals suffering from epilepsy.

People with epilepsy (PWE) are highly likely to suffer from sexual dysfunction, and dealing with this issue is a challenge for healthcare providers. Unfortunately, there is no theory-driven study that has investigated the counseling practice of healthcare providers for sexual problems in PWE. Therefore, we decided to apply the well-established Theory of Planned Behavior (TPB) to examine factors associated with healthcare providers' sexual counseling in PWE. Apart from TPB, perceived barriers toward providing counseling could be a possible factor that needs to be investigated as well. Therefore, two models explaining sexual counseling practice were proposed. Model 1 included only TPB and Model 2 included TPB incorporated with perceived barriers. Five hundred fifty-nine Iranian healthcare professionals responsible for PWE were recruited across several neurology clinics and asked to complete TPB-specific questionnaires. The same healthcare professionals were asked to complete an additional questionnaire on their attitudes toward sexual counseling 18months later. Structural equation modeling suggested Model 2 to be more useful in explaining sexual counseling practice compared with Model 1. Moreover, attitude and perceived behavioral control showed stronger associations with behavioral intention, whereas subjective norm showed weaker associations. The associations were similar across different healthcare professionals (i.e., medical doctors vs. nurses). In conclusion, TPB incorporated with perceived barriers might be a useful theory for different types of healthcare providers to improve and enhance sexual counseling practice.

Plasma disc decompression compared to physiotherapy for symptomatic contained lumbar disc herniation: A prospective randomized controlled trial.

INTRODUCTION: To evaluate clinical outcomes with PDD as compared with patients who underwent to standard physiotherapy intervention. MATERIAL AND METHODS: One-hundred-seventy-seven randomly assigned patients with primarily radicular pain associated with a single-level lumbar contained disc herniation were enrolled. Participants received either PDD (89 patients) or conservative physiotherapy care (88 patients). RESULTS: Patients in the PDD group had significantly greater reduction in leg pain scores and significantly improved VAS (p<0.001), Oswestry Disability Index (p<0.05), and 36-Item Short Form, than those in the physiotherapy group at 12 months. On subset analysis, patients achieved even better outcomes after PPD who: were younger, had a shorter period of radiculopathy, of male gender, and lower BMI. Patients with subacute pain reported better outcomes than those with chronic pain in the PDD group. CONCLUSIONS: Patient selection for PDD over physiotherapy favored younger patients who presented with a shorter period of pain symptoms and who had a more favorable body habitus.

Association of pain and depression in those with chronic low back pain: the mediation effect of patient sexual functioning.

OBJECTIVES: One theoretical model suggests that the pathway from pain to depression is through the disruption of social and relationship function. This study sought to test this hypothesis by considering the mediating effect of sexual functioning on the association between pain intensity and depressive symptoms in sexually active patients with chronic low back pain. MATERIALS AND METHODS: This was a cross-sectional study on consecutive patients attending a chronic pain management clinic in Iran. All measures (pain intensity, depressive symptoms, sex-specific sexual function) were obtained by a self-report questionnaire, completed by patients while attending the clinic. Sobel testing, including bias-corrected bootstrapping, was used to produce 95% confidence intervals (95% CI) to test the mediating effect of sexual function. RESULTS: A total of 742 patients (351 men, 391 women) took part in this study. Both the male and female mediation models showed a significant association between pain intensity and depressive symptoms, and both the models were significantly mediated by sexual functioning (P<0.001). Effect size calculations show a medium to large effect on male patients (κ 0.23; 95% CI, 0.15-0.39) and a medium effect for female patients (κ 0.16; 95% CI, 0.06-0.28). Both the models accounted for over 50% of the variance in depressive symptoms (model R). DISCUSSION: This study has shown that sexual functioning significantly mediates the relationship between pain intensity and depressive symptoms in sexually active patients with chronic low back pain. Clinicians may wish to consider the assessment of sexual functioning within this patient group and align treatments that address sexual dysfunction and general pain management.