Allogeneic blood transfusions and infection risk in lumbar spine surgery: An American College of Surgeons National Surgery Quality Improvement Program Study.

BACKGROUND: Allogenic blood transfusions can lead to immunomodulation. Our purpose was to investigate whether perioperative transfusions were associated with postoperative infections and any other adverse events (AEs), after adjusting for potential confounding factors, following common elective lumbar spinal surgery procedures. STUDY DESIGN AND METHODS: We performed a multivariate, propensity-score matched, regression-adjusted retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program database between 2012 and 2016. All lumbar spinal surgery procedures were identified (n = 174,891). A transfusion group (perioperative transfusion within 72 h before, during, or after principal surgery; n = 1992) and a control group (no transfusion; n = 1992) were formed. Following adjustment for between-group baseline features, adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) were calculated using a multivariate logistic regression model for any surgical site infection (SSI), superficial SSI, deep SSI, wound dehiscence, pneumonia, urinary tract infection, sepsis, any infection, mortality, and any AEs. RESULTS: Transfusion was associated with an increased risk of each specific infection, mortality, and any AEs. Statistically significant between-group differences were demonstrated with respect to any SSI (aOR: 1.48; 95% CI: 1.01-2.16), deep SSI (aOR: 1.66; 95% CI: 0.98-2.85), sepsis (aOR: 2.69; 95% CI: 1.43-5.03), wound dehiscence (aOR: 2.27; 95% CI: 0.86-6.01), any infection (aOR: 1.46; 95% CI: 1.13-1.88), any AEs (aOR: 1.80; 95% CI: 1.48-2.18), and mortality (aOR: 2.17; 95% CI: 0.77-6.36). CONCLUSION: We showed an association between transfusion and infection in lumbar spine surgery after adjustment for various applicable covariates. Sepsis had the highest association with transfusion. Our results reinforce a growing trend toward minimizing perioperative transfusions, which may lead to reduced infections following lumbar spine surgery.

Capturing adverse events in elective orthopedic surgery: comparison of administrative, surgeon and reviewer reporting

Summary: Ensuring adverse event (AE) recording is standardized and accurate is paramount for patient safety. In this discussion, we outline our comparison of AE data collected by orthopedic surgeons and independent clinical reviewers using the Spine Adverse Events Severity System (SAVES) and Orthopedic Surgical Adverse Events Severity System (OrthoSAVES) against AE data recorded by hospital administrative discharge abstract coders. In 164 spine, hip, knee and shoulder patients, reviewers recorded significantly more AEs than coders, and coders recorded significantly more AEs than surgeons. The AEs were recorded similarly by reviewers using SAVES and OrthoSAVES in 48 spine patients. Despite our small sample size and use of different AE tools, we believe it is important to highlight that coders, surgeons and reviewers recorded AEs differently. While further investigations on its utility and cost-effectiveness are necessary, we assert that it is feasible to use Ortho-SAVES to prospectively record AEs across all orthopedic subspecialties.

The Use of a Self-Administered Questionnaire to Reduce Consultation Wait Times for Potential Elective Lumbar Spinal Surgical Candidates: A Prospective, Pragmatic, Blinded, Randomized Controlled Quality Improvement Study.

BACKGROUND: In a public health-care system, patients often experience lengthy wait times to see a spine surgeon for consultation, and most patients are found not to be surgical candidates, thereby prolonging the wait time for those who are. The aim of this study was to evaluate whether a self-administered 3-item questionnaire (3IQ) could reprioritize consultation appointments and reduce wait times for lumbar spinal surgical candidates. METHODS: This prospective, pragmatic, blinded, randomized controlled quality improvement study was conducted at a single Canadian academic health-care center. This study enrolled 227 consecutive eligible participants with an elective lumbar condition who were referred for consultation with a spine surgeon. All participants were mailed the 3IQ after their referral was received. Patients were randomized into the intervention group, in which leg-dominant pain reported on the 3IQ resulted in an upgrade in priority to be seen, or into the control group, in which no change to wait-list priority occurred. The main outcome measured was time to consultation for participants who were deemed surgical candidates following consultation. RESULTS: There were no significant differences between groups with regard to demographics, overall group wait times, proportion of surgical candidates, or disability. A total of 33 patients were deemed surgical candidates after consultation. The median wait from referral to consultation was shorter for the 16 surgical candidates in the intervention group (2.5 months; interquartile range [IQR]: 2.0 to 4.8 months) compared with the 17 surgical candidates in the control group (4.5 months; IQR: 3.4 to 6.9 months; p = 0.090). The odds of seeing a surgical candidate within the acceptable time frame of 3 months were 5.4 times greater (95% confidence interval: 1.2 to 24.5 times; p = 0.024) in the intervention group. CONCLUSIONS: The use of a simple, self-administered questionnaire to reprioritize referrals resulted in shorter consultation wait times for patients who required a surgical procedure and significantly increased the number of surgical candidates seen within the acceptable time frame. It may be valuable to consider adding the 3IQ to clinical care practices to better triage these patients on waiting lists.

Increased Prevalence of Chronic Disease in Back Pain Patients Living in Car-dependent Neighbourhoods in Canada: A Cross-sectional Analysis.

OBJECTIVES: Chronic diseases, including back pain, result in significant patient morbidity and societal burden. Overall improvement in physical fitness is recommended for prevention and treatment. Walking is a convenient modality for achieving initial gains. Our objective was to determine whether neighbourhood walkability, acting as a surrogate measure of physical fitness, was associated with the presence of chronic disease. METHODS: We conducted a cross-sectional study of prospectively collected data from a prior randomized cohort study of 227 patients referred for tertiary assessment of chronic back pain in Ottawa, ON, Canada. The Charlson Comorbidity Index (CCI) was calculated from patient-completed questionnaires and medical record review. Using patients' postal codes, neighbourhood walkability was determined using the Walk Score, which awards points based on the distance to the closest amenities, yielding a score from 0 to 100 (0- 50: car-dependent; 50-100: walkable). RESULTS: Based on the Walk Score, 134 patients lived in car-dependent neighborhoods and 93 lived in walkable neighborhoods. A multivariate logistic regression model, adjusted for age, gender, rural postal code, body mass index, smoking, median household income, percent employment, pain, and disability, demonstrated an adjusted odds ratio of 2.75 (95% confidence interval, 1.16 to 6.53) times higher prevalence for having a chronic disease for patients living in a car-dependent neighborhood. There was also a significant dose-related association (p=0.01; Mantel-Haenszel chi-square=6.4) between living in car-dependent neighbourhoods and more severe CCI scores. CONCLUSIONS: Our findings suggest that advocating for improved neighbourhood planning to permit greater walkability may help offset the burden of chronic disease.

Exploration of the Inter-Relationships Between Obesity, Physical Inactivity, Inflammation, and Low Back Pain.

STUDY DESIGN: Retrospective analysis wherein 103 patients were considered, and 76 patients were included: 49 were classified as chronic non-specific low back pain (CNSLBP) (Study group) and 27 had identifiable cases of specific chronic low back pain (LBP) (Control group). OBJECTIVE: Elucidate markers of systemic inflammation in patients with CNSLBP. SUMMARY OF BACKGROUND DATA: Mechanisms of LBP are poorly understood. Pro-inflammatory cytokines are increased in obesity and involved with pain modulation; we previously proposed a theoretical model of their mediating role in LBP. METHODS: Demographic information was acquired via questionnaire, chart review, and blood test data. Univariate analysis identified factors associated with CNSLBP and markers of systemic inflammation. A receiver operating curve and Youden Index were used to select optimal cut-off points for elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Multivariable logistic regression analysis calculated the adjusted strength of relationship between factors that were proposed in our theoretical model for CNSLBP. RESULTS: Unadjusted CRP was significantly correlated with ESR (R = 0.63, P < 0.0001) and body mass index (BMI) (R = 0.38, P = 0.0015). Physically inactive patients had significantly higher CRP (6.1 vs. 1.2, P = 0.0050). ESR was significantly correlated with number of comorbidities (R = 0.34, P = 0.0047), BMI (R = 0.38, P = 0.0014), and age (R = 0.36, P = 0.0026). Physically inactive patients (10.4 vs. 3.6, P = 0.0001) and females (11.2 vs. 6.4, P = 0.0422) had significantly higher ESR. Adjusted analyses indicated significant relationships between physical inactivity and markers of systemic inflammation (adjusted odds ratios for ESR and CRP: 15.9, P = 0.0380; 15.2, P = 0.0272, respectively), and between elevated CRP and CNSLBP (adjusted odds ratio: 8.0, P = 0.0126). CONCLUSION: Systemic inflammation may act as a mediator for physical inactivity and obesity in the pathogenesis of CNSLBP. LEVEL OF EVIDENCE: 2.

Activities performed and treatments conducted before consultation with a spine surgeon: are patients and clinicians following evidence-based clinical practice guidelines?

BACKGROUND CONTEXT: Clinical practice guidelines (CPGs) are designed to ensure that evidence-based treatment is easily put into action. Whether patients and clinicians follow these guidelines is equivocal. PURPOSE: The objectives of this study were to examine how many patients complaining of low back pain (LBP) underwent evidence-based medical interventional treatment in line with CPG recommendations before consultation with a spine surgeon, and to evaluate any associations between adherence to CPG recommendations and baseline factors. STUDY DESIGN/SETTING: This is a cross-sectional cohort analysis at a tertiary care center. PATIENT SAMPLE: A total of 229 patients were referred for surgical consultation for an elective lumbar spinal condition. OUTCOME MEASURES: The outcome measures include the number of CPG-recommended treatments undertaken by patients at or before the time of referral, the validated pain score, the EuroQol-5D (EQ-5D) health status, and the Oswestry Disability Index (ODI) score. METHODS: Questionnaires assessing demographic and functional characteristics as well as overall health care use were sent to patients immediately after their referral was received by the surgeon's office. RESULTS: Medications were the most common modality before consultation (74.2% of patients), of which 46.3% received opioids. The number of medications taken was significantly related to a higher ODI score (R=0.23, p=.0004), a higher pain score (R=0.15, p=.026), and a lower EQ-5D health status (R=-0.15, p=.024). In contrast, a lower pain score (7.2 vs. 7.7, p=.037) and a lower ODI score (26.6 vs. 29.9, p=.0023) were associated with performing adequate amounts of exercise. There was a significant association between lower numbers of treatments received and higher numerical pain rating scores (R=-0.14, p=.035). The majority (61.1%) of patients received two or less forms of treatment. CONCLUSIONS: Evidence-based medical interventional treatments for patients with LBP are not being taken advantage of before spine surgery consultation. If more patients were to undertake CPG-endorsed conservative modalities, it may result in fewer unnecessary referrals from primary care physicians, and patients might not deteriorate as much while lingering on long wait lists. Further studies incorporating knowledge translation or health system pathway changes are necessary.

Can Surgeons Adequately Capture Adverse Events Using the Spinal Adverse Events Severity System (SAVES) and OrthoSAVES?

BACKGROUND: Physicians have consistently shown poor adverse-event reporting practices in the literature and yet they have the clinical acumen to properly stratify and appraise these events. The Spine Adverse Events Severity System (SAVES) and Orthopaedic Surgical Adverse Events Severity System (OrthoSAVES) are standardized assessment tools designed to record adverse events in orthopaedic patients. These tools provide a list of prespecified adverse events for users to choose from-an aid that may improve adverse-event reporting by physicians. QUESTIONS/PURPOSES: The primary objective was to compare surgeons' adverse-event reporting with reporting by independent clinical reviewers using SAVES Version 2 (SAVES V2) and OrthoSAVES in elective orthopaedic procedures. METHOD: This was a 10-week prospective study where SAVES V2 and OrthoSAVES were used by six orthopaedic surgeons and two independent, non-MD clinical reviewers to record adverse events after all elective procedures to the point of patient discharge. Neither surgeons nor reviewers received specific training on adverse-event reporting. Surgeons were aware of the ongoing study, and reported adverse events based on their clinical interactions with the patients. Reviewers recorded adverse events by reviewing clinical notes by surgeons and other healthcare professionals (such as nurses and physiotherapists). Adverse events were graded using the severity-grading system included in SAVES V2 and OrthoSAVES. At discharge, adverse events recorded by surgeons and reviewers were recorded in our database. RESULTS: Adverse-event data for 164 patients were collected (48 patients who had spine surgery, 51 who had hip surgery, 34 who had knee surgery, and 31 who had shoulder surgery). Overall, 99 adverse events were captured by the reviewers, compared with 14 captured by the surgeons (p < 0.001). Surgeons adequately captured major adverse events, but failed to record minor events that were captured by the reviewers. A total of 93 of 99 (94%) adverse events reported by reviewers required only simple or minor treatment and had no long-term adverse effect. Three patients experienced adverse events that resulted in use of invasive or complex treatment that had a temporary adverse effect on outcome. CONCLUSION: Using SAVES V2 and OrthoSAVES, independent reviewers reported more minor adverse events compared with surgeons. The value of third-party reviewers requires further investigation in a detailed cost-benefit analysis. LEVEL OF EVIDENCE: Level II, therapeutic study.

An in vitro model of degenerative lumbar spondylolisthesis.

STUDY DESIGN: A biomechanical human cadaveric study. OBJECTIVE: To create a biomechanical model of low-grade degenerative lumbar spondylolisthesis (DLS), defined by anterior listhesis, for future testing of spinal instrumentation. SUMMARY OF BACKGROUND DATA: Current spinal implants are used to treat a multitude of conditions that range from herniated discs to degenerative diseases. The optimal stiffness of these instrumentation systems for each specific spinal condition is unknown. Ex vivo models representing degenerative spinal conditions are scarce in the literature. A model of DLS for implant testing will enhance our understanding of implant-spine behavior for specific populations of patients. METHODS: Four incremental surgical destabilizations were performed on 8 lumbar functional spinal units. The facet complex and intervertebral disc were targeted to represent the tissue changes associated with DLS. After each destabilization, the specimen was tested with: (1) applied shear force (-50 to 250 N) with a constant axial compression force (300 N) and (2) applied pure moments in flexion-extension, lateral bending and axial rotation (±5 Nm). Relative motion between the 2 vertebrae was tracked with a motion capture system. The effect of specimen condition on intervertebral motion was assessed for shear and flexibility testing. RESULTS: Shear translation increased, specimen stiffness decreased and range of motion increased with specimen destabilization (P < 0.0002). A mean anterior translation of 3.1 mm (SD 1.1 mm) was achieved only after destabilization of both the facet complex and disc. Of the 5 specimen conditions, 3 were required to achieve grade 1 DLS: (1) intact, (3) a 4-mm facet gap, and (5) a combined nucleus and annulus injury. CONCLUSION: Destabilization of both the facet complex and disc was required to achieve anterior listhesis of 3.1 mm consistent with a grade 1 DLS under an applied shear force of 250 N. Sufficient listhesis was measured without radical specimen resection. Important anatomical structures for supporting spinal instrumentation were preserved such that this model can be used in future to characterize behavior of novel instrumentation prior to clinical trials.

Airway management in cervical spine ankylosing spondylitis: Between a rock and a hard place.

We report the perioperative course of a patient with long standing ankylosing spondylitis with severe dysphagia due to large anterior cervical syndesmophytes at the level of the epiglottis. He was scheduled to undergo anterior cervical decompression and the surgical approach possibly precluded an elective pre-operative tracheostomy. We performed a modified awake fibreoptic nasal intubation through a split nasopharyngeal airway while adequate oxygenation was ensured through a modified nasal trumpet inserted in the other nares. We discuss the role of nasal intubations and the use of both the modified nasopharyngeal airways we used to facilitate tracheal intubation. This modified nasal fibreoptic intubation technique could find the application in other patients with cervical spine abnormalities and in other anticipated difficult airways.

Pediatric noncontiguous spinal injuries: the 15-year experience at a level 1 trauma center.

STUDY DESIGN: Retrospective review. OBJECTIVE: To determine the incidence and clinical characteristics of noncontiguous spinal injuries (NCSI) in a pediatric population. The secondary objective is to identify high-risk patients requiring further imaging to rule out NCSI. SUMMARY OF BACKGROUND DATA: NCSI can add significant complexity to the diagnosis, management, and outcome of children. There is very little in the pediatric literature examining the nature, associated risk factors, management, and outcomes of NCSI. METHODS: All children up to 18 years of age with a spinal injury, as defined by International Classification of Diseases, Ninth Revision codes, at one pediatric trauma hospital were included (n = 211). Data for patient demographics, mechanism of injury, spinal levels involved, extent of neurological injury and recovery, associated injuries, medical complications, treatment, and outcome were recorded. RESULTS: Twenty-five (11.8%) of 211 patients had NCSI, with a median age of 13.0 years (interquartile range = 8-15). The most common pattern of injury was a double thoracic noncontiguous injury. Sixteen percent of the cases of NCSI were initially missed, with no clinical deterioration due to missed diagnosis. Associated injuries occurred in 44% of patients with NCSI. Twenty-four percent of patients with multiple NCSI had a neurological injury compared with 9.7% in patients with single-level or contiguous injuries (P = 0.046). CONCLUSION: There is a high incidence of children with multiple NCSI who are more likely to experience neurological injuries compared with patients with single-level or contiguous spinal injuries. Patients with a single-level spinal injury on existing imaging with an associated neurological injury should undergo at least plain films of the entire spine to exclude noncontiguous injuries. In patients without neurological injury and a single spinal fracture, radiography showing at least 4 levels above and below the fracture should be performed. All children with spinal injury should have associated injuries carefully excluded.

An ex vivo biomechanical comparison of a novel vertebral compression fracture treatment system to kyphoplasty.

BACKGROUND: Vertebral compression fracture repair aims to relieve pain and improve function by restoring vertebral structure and biomechanics, but is still associated with risks arising from polymethylmethacrylate cement extravasation. The Kiva® Vertebral Compression Fracture Treatment System, a stacked coil implant made of polyetheretherketone and delivered over a guide-wire, is a novel device designed to provide height restoration and mechanical stabilization, while improving cement containment and minimizing disruption of cancellous bone. The objective of this study was to determine whether the Kiva system is as effective as balloon kyphoplasty at restoring mechanical properties in osteoporotic vertebral compression fractures. METHODS: Wedge fractures were created in the middle vertebra of fourteen osteoporotic three-vertebra spine segments and then repaired with either the Kiva or kyphoplasty procedure. Height, stiffness and displacement under compression of the spine segments were measured for four conditions: intact, fractured, augmented, and post-cyclic eccentric loading (50,000cycles, 200-500N, 30mm anterior lever arm). FINDINGS: No significant differences were seen between the two procedures for height restoration, stiffness at high or low loads, or displacement under compression. However, the Kiva System required an average of 66% less cement than kyphoplasty to achieve these outcomes (mean 2.6 (SD 0.4) mL v. mean 7.5 (SD 0.8) mL 0; P<0.01). Extravasations and excessive posterior cement flow were also significantly lower with Kiva (0/7 v. 4/7; P<.05). INTERPRETATION: Kiva exhibits similar biomechanical performance to balloon kyphoplasty, but may reduce the risk of extravasation through the containment mechanism of the implant design and by reducing cement volume.

Relationship of neural axis level of injury to motor recovery and health-related quality of life in patients with a thoracolumbar spinal injury.

BACKGROUND: Outcomes following traumatic conus medullaris and cauda equina injuries are typically predicted on the basis of the vertebral level of injury. This may be misleading as it is based on the assumption that the conus medullaris terminates at L1 despite its variable location. Our primary objective was to determine whether the neural axis level of injury (the spinal cord, conus medullaris, or cauda equina) as determined with magnetic resonance imaging is better than the vertebral level of injury for prediction of motor improvement in patients with a neurological deficit secondary to a thoracolumbar spinal injury. METHODS: Patients diagnosed with a motor deficit secondary to a thoracolumbar spinal injury, and who met the inclusion criteria, were contacted. Each patient had a magnetic resonance imaging scan that was reviewed by a spine surgeon and a neuroradiologist to determine the termination of the conus medullaris and the neural axis level of injury. Patient demographic data were collected prospectively at the time of admission. Admission and follow-up neurological assessments were performed by formally trained dedicated spine physiotherapists. RESULTS: Fifty-one patients were evaluated at a median of 6.2 years (range, 2.7 to 12.3 years) postinjury. The final motor scores differed significantly according to whether the patient had a spinal cord injury (mean, 62.8 points; 95% confidence interval, 55.4 to 70.2), conus medullaris injury (mean, 78.6 points; 95% confidence interval, 70.3 to 86.9), or cauda equina injury (mean, 88.8 points; 95% confidence interval, 78.9 to 98.7) (p = 0.0007). A univariate analysis showed the improvement in the motor scores after the cauda equina injuries (mean, 17.1 points; 95% confidence interval, 8.3 to 25.9) to be significantly greater than that after the spinal cord injuries (mean, 7.7 points; 95% confidence interval, 3.1 to 12.3) (p = 0.03). A multivariate analysis showed that an absence of initial sacral sensation had a negative effect on motor recovery by a factor of 13.2 points (95% confidence interval, 4.2 to 22.1). When compared with classifying our patients on the basis of the neural axis level of injury, reclassifying them on the basis of the vertebral level of injury resulted in a misclassification rate of 33%. CONCLUSIONS: The motor recovery of patients with a thoracolumbar spinal injury and a neurological deficit is affected by both the neural axis level of injury as well as the initial motor score. The results of this study can help the clinician to determine a prognosis for patients who sustain these common injuries provided that he or she evaluates the precise level of neural axis injury utilizing magnetic resonance imaging.

The effect of posterior capsular tightening on peak subacromial contact pressure during simulated active abduction in the scapular plane.

HYPOTHESIS: Our hypothesis was that tightening of the posterior capsule would lead to increased subacromial pressure and increased superior translation during active abduction in the scapular plane. BACKGROUND: Subacromial impingement syndrome is a painful condition that occurs during overhead activities as the rotator cuff is compressed in the subacromial space. Unrecognized secondary causes of subacromial impingement may lead to treatment failure. Posterior capsular tightness, believed to alter glenohumeral joint kinematics, is often cited as a secondary cause of SI; however, scientific evidence is lacking. The primary objective of this study was to evaluate the effect of posterior capsular tightening on peak subacromial pressure during abduction in the scapular plane. MATERIALS AND METHODS: Ten fresh frozen shoulder specimens from deceased donors were mounted on a custom shoulder simulator. With the scapula fixed, the deltoid and rotator cuff muscles were loaded in discrete static steps with a constant ratio to elevate the humerus in the scapular plane. The treatment order (no tightening, 1-cm, and 2-cm tightening of the posterior capsule) was randomly assigned to each specimen. Peak subacromial contact pressure and glenohumeral kinematics at the peak pressure position were compared using a repeated measures analysis of variance. RESULTS: Peak subacromial pressures (mean +/- standard deviation) were similar between treatment groups: 345 +/- 152, 410 +/- 213, and 330 +/- 164 kPa for no tightening, 1-cm, and 2-cm tightening of the posterior capsule respectively (P > .05). No significant differences were found for superior or anterior translations at the peak pressure position (P > .05). DISCUSSION: Posterior capsular tightening, as a sole variable, did not contribute to a significant increase in peak subacromial pressure during abduction in the scapular plane. A similar study simulating active forward flexion is necessary to fully characterize the contribution of posterior capsular tightness to subacromial impingement. CONCLUSION: Tightening of the posterior capsule did not increase subacromial pressure, or increase superior or anterior translation during abduction in the scapular plane.

Factors affecting neurological outcome in traumatic conus medullaris and cauda equina injuries.

The purpose of this review was to describe the relevant factors that influence neurological outcomes in patients who sustain traumatic conus medullaris injuries (CMIs) and cauda equina injuries (CEIs). Despite the propensity for spinal trauma to affect the thoracolumbar spine, few studies have adequately characterized the outcomes of CMIs and CEIs. Typically the level of neural axis injury is inferred from the spinal level of injury or the presenting neurological picture because no study from the spinal literature has specifically evaluated the location of the conus medullaris with respect to the level of greatest canal compromise. Furthermore, the conus medullaris is known to have a small but important variable location based on the spinal level. Patients with a CMI will typically present with variable lowerextremity weakness, absent lower-limb reflexes, and saddle anesthesia. The development of a mixed upper motor neuron and lower motor neuron syndrome may occur in patients with CMIs, whereas a CEI is a pure lower motor neuron injury. Many treatment options exist and should be individualized. Posterior decompression and stabilization offers at least equivalent neurological outcomes as nonoperative or anterior approaches and has the additional benefits of surgeon familiarity, shorter hospital stays, earlier rehabilitation, and ease of nursing care. Overall, CEIs and CMIs have similar outcomes, which include ambulatory motor function and a variable persistence of bowel, bladder, and potentially sexual dysfunctions.