Endoscopic Rhizotomy for Facetogenic Back Pain: A Review of the History, Financial Considerations, Patient Selection Criteria, and Clinical Outcomes.

BACKGROUND: Chronic back pain (CBP) is a condition that places a considerable burden on society, with several million people affected in the United States alone. Treatment options to address this problem and relieve CBP are constantly evolving, and one of the most promising treatment modalities for CBP that is refractory to conservative treatment options is endoscopic rhizotomy (ER). METHODS: A thorough search of the PubMed (MEDLINE) database was conducted to assess the full progression of ER from its earliest uses to present day in a historical narrative review of ER, with treatment of facetogenic pain as a model pathology. RESULTS: ER allows for direct visualization and ablation of sensory branches of the dorsal ramus to provide pain relief in up to 80% of patients faced with refractory CBP. This technique has been built upon since the early 20th century, and the novel endoscopic approach continues to gain popularity among physicians. Benefits of ER include superior postoperative median pain-free duration compared with traditional percutaneous radiofrequency ablation, as well as direct visualization of regional anatomy. Patient selection criteria for the procedure and a modest list of contraindications allow the use of ER as a viable treatment option for a significant population of patients suffering from CBP. Potential barriers to ER include high cost of the procedure, longer intraoperative time, and expensive proprietary equipment. CONCLUSIONS: ER is an effective treatment for refractory CBP with notable advantages. As the technology and popularity of this procedure progress, improvements in the cost, training, and intraoperative time may make it a favorable alternative to the current standard of care.

Encouragement for Further Study of Tranexamic Acid Administration for Sacroiliac Joint Fusion Surgery.

TO THE EDITOR: We read with great interest the article by Huynh et al.regarding the association between tranexamic acid (TXA) and blood loss in patients undergoing surgical treatment for hip fracture (Huynh PAN, Miller M, Will R. Intravenous Tranexamic Acid Decreases Blood Transfusions and Blood Loss for Patients with Surgically Treated Hip Fractures. Geriatric Orthopedic Surg Rehabil. 2021). The authors illustrated, via retrospective chart review of 505 patients who were surgically treated for hip fractures, that patients administered TXA had statistically significant decreases in perioperative blood loss and reduced relative risk of transfusion. Huynh et al. reported no statistically significant increases in thromboembolic events in patients given TXA. Mechanistically, TXA is a synthetic anti-fibrinolytic that competitively inhibits the plasminogen activation pathway. By preventing activated plasmin from de-stabilizing the fibrin matrix, TXA promotes clot formation. Given the anti-fibrinolytic effects of TXA, concerns in the literature exist regarding its use being associated with increased risk for thromboembolic events. However, it is important to note the complication profile associated with TXA is minimal, as elucidated by Brown et al., specifically finding that no patients who were administered TXA perioperatively experienced a thromboembolic event (or at least, there were no reports of thromboembolism or any other adverse events). While administration of TXA may theoretically increase the risk for thrombosis, Brown et al. showed this does not seem to occur in spinal laminectomy and fusion with posterior instrumentation. Similarly, in a systematic review of the literature describing TXA use in intracranial tumor resection, this study revealed a statistically significant reduction in the need for intraoperative blood transfusion in patients administered TXA. Upon consideration of postoperative outcomes, no significant increase in complication rate was found. This evidence in the existing literature on TXA use in orthopedic, spinal, and cranial neurosurgery exemplifies the wide potential of TXA for reducing blood loss with minimal complications in surgical procedures, especially involving the craniospinal axis.

Interpretation of Cytochrome P-450 Inhibition and Induction Effects From Clinical Data: Current Standards and Recommendations for Implementation.

Agents that modify cytochrome P-450 (CYP) enzyme activity are characterized as strong, moderate, or weak inhibitors or inducers based on the magnitude of their impact on substrate exposure in clinical studies. Criteria for these classifications are simple and semiquantitative. However, assignment of a given agent to a CYP inhibitor or inducer category is often complicated by limitations of the published data, inconsistent study findings, and other factors. CYP inhibitor and inducer categories are commonly used as a basis for differentiating drug interaction management recommendations. For example, product labeling for a CYP substrate may recommend avoidance in combination with strong inhibitors and dose reduction in combination with moderate inhibitors. When such recommendations exist, ambiguity or variability in placement of inhibitors or inducers into categories can introduce potentially harmful variations in clinical drug interaction management. Failure to adequately reflect the drug interaction potential of an agent by under-categorizing it (e.g., calling it weak when data point to moderate effects), for example, may lead clinicians to respond inadequately to real risks, or to ignore potential interactions altogether. Over-categorization may lead to actions such as over-adjustment of substrate doses or unnecessary avoidance of optimal treatments. This review describes the current criteria for assignment of CYP inhibitor and inducer categories, summarizes common circumstances leading to ambiguous or variable CYP inhibitor and inducer categorizations, and proposes an approach to data interpretation and application of current criteria under uncertainty. When applied to > 1,000 CYP reviews, the approach described has identified a clear categorization in almost all cases.

The use of high resolution computerized tomography (HRCT) of the chest in evaluating the effect of tobramycin solution for inhalation in cystic fibrosis lung disease.

OBJECTIVES: To compare the usefulness of HRCT of the chest versus spirometric measures (PFTs) in evaluating the effect of tobramycin solution for inhalation (TSI) in cystic fibrosis (CF). METHODS: Thirty-two CF patients with mostly mild lung disease age > or = 6 years, were enrolled in a double-blind, placebo-controlled pilot study. Patients were chronically colonized with Pseudomonas aeruginosa for at least 6 months prior to and at enrollment. If patients were on TSI, they were taken off for at least 3 months prior to enrollment. Duration was 6 months; 31 subjects completed the study. HRCT and PFTs were evaluated at baseline, after 28 days of treatment and at the end of the study. Study medication was administered as 5 ml nebulized treatment twice a day for 28 days followed by 28 days off (one cycle). Study consisted of three cycles. Two radiologists scored all films using a validated system. A total HRCT score consists of the sum of subscores: linear opacities, hyperinflation, nodular opacities, peribronchial thickening, mucous plugging, and bronchiectasis; each subscore could range from 0 to 80, with potential total scores varying from 0 to 480. The percent of the maximum possible HRCT score was then calculated and used for all comparisons. RESULTS: Using two tailed paired t-test, the percent maximum HRCT score decreased by 1.4 +/- 2.6% (mean +/- SD) (P = 0.049) and 0.3 +/- 2.8% (P = 0.63) for the TSI group and decreased by 0.1 +/- 1.5% (P = 0.74) and increased by 0.6 +/- 1.8% (P = 0.23) for the placebo group between visits 1 and 2, and visits 1 and 3, respectively. The data were then analyzed using a mixed model utilizing changes in scores over the durations of the study for each group. The change of HRCT score for the TSI group was -0.24/day (P = 0.02) and -0.03/day (P = 0.22), and for the control group the change was -0.01 (P = 0.93) and 0.02 (P = 0.29) between visits 1 and 2, and visits 1 and 3 respectively. FEF(25-75)% and FEV(1)% changes were not statistically significant using both analyses. CONCLUSION: HRCT seems to be more sensitive in detecting treatment effect than PFT in CF patients with mild lung disease, especially following the first treatment period (visit 2). Total HRCT score showed some improvement at the end of the study, though not statistically significant. This is probably due to obtaining the HRCT an average of 30 days after completion of the TSI treatment, and selection of study population with mostly mild lung disease. This could indicate that the most significant improvement in the total HRCT score in this patient population occurs after the first treatment period with TSI.

Identifying barriers to treatment adherence and related attitudinal patterns in adolescents with cystic fibrosis.

INTRODUCTION: The treatment of cystic fibrosis (CF) is directed toward correction of organ dysfunction and relief of symptoms resulting from the disease. Lack of adherence to daily treatment regimens may have substantial short-term and long-term effects on patients with CF. In this study, we attempted to identify barriers to treatment adherence which could be predicted by objective measures and explore ways to improve adherence in adolescents with CF. METHODS: A questionnaire was given to patients 12.0-20.9 years of age, designed with focus on specific barriers to adhering to treatment plan and related attitudinal patterns. Observational and analytical results were collected. RESULTS: We obtained questionnaires and objective health data for 60 respondents. The most commonly identified barriers to adherence were forgetting or losing medications (32/60) and being too busy (23/60). Attitudinal patterns that played a significant role for nonadherence included unintentional forgetting (40/60), feeling that following CF treatments resulted in less freedom in their lives (30/60), and believing it is acceptable to miss a treatment every few days (18/60) or to miss treatments when busy (18/60). DISCUSSION: There were a few statistically significant differences of adherence patterns between demographic subgroups in our study. Males were more likely to agree that it is acceptable to miss doses if they are made up with extra doses later (24% vs. 3%, P = 0.04). Patients who perceived themselves to be less healthy agreed more to statements of limited freedom, nonsympathetic medical providers, and difficulty adhering during times of decreased symptoms. This highlights an unexpected risk: as CF progresses and patients perceive themselves to be less healthy, they may become less likely to be adherent during the periods they are feeling the best, while at the same time becoming less likely to perceive empathy from their physicians. CONCLUSIONS: Survey results describe a variety of beliefs and attitudinal patterns which contribute to nonadherence in CF treatment, especially relating to time management. While patients largely understood the importance of treatments to their health, predictors of risky behaviors could lead to targeted interventions by CF centers to address these challenges and improve adherence.

Effect of pharmacy practice residency training on residents' knowledge of and interest in clinical research.

PURPOSE: The effect of pharmacy practice residency training on subjectively and objectively assessed research knowledge, skills, and interests of residents was studied. METHODS: A preintervention versus post-intervention design was used. Residency year 2004- 05 residents were administered a validated Web-based survey at the beginning of residency and again at the end of residency. The survey collected resident responses to questions regarding resident and residency characteristics, subjective assessments of specific professional skills and research skills and knowledge, and objective assessments of basic research knowledge. For residents who completed beginning and end of residency surveys, results were linked when possible to allow for paired and unpaired statistical analyses. RESULTS: Totals of 346 (33.2% response rate) and 222 (21.3% response rate) surveys were completed at the beginning and the end of the residency, respectively, with 129 respondents completing both. Statistically significant improvements were observed for the total and paired population in subjectively assessed research-related skills and abilities and general professional skills. Subjectively assessed understanding of specific statistical tests revealed a significant improvement. Total population analysis and paired population analysis revealed no changes in objectively assessed research-related knowledge from the beginning of the residency to the end of the residency. CONCLUSION: Although there was improvement from the beginning to the end of residency in subjectively assessed research-related skills and abilities and in self-assessed understanding of most statistical tests, the end of residency objectively assessed research-related knowledge scores were unchanged. Residents' expectations that the residency would increase research knowledge, skills, and desire for research involvement were unmet. These results suggest that training based on residency program standards may not increase residents' interest or provide them with the skills necessary to participate in clinical research.

Impact of patient financial incentives on participation and outcomes in a statin pill-splitting program.

OBJECTIVES: To examine willingness to participate in a pill-splitting program and the impact of pill splitting on patients' adherence and lipid control. STUDY DESIGN: Nested randomized trial. METHODS: A total of 200 patients who used statins and were candidates for a pill-splitting regimen were identified from a large university-based health plan. Sixty-three percent of study participants were female, 41% were nonwhite, and 94% had at least some college education. Patients were surveyed regarding their willingness to split pills, and 111 consented to participate in a 6-month trial in which half were randomized to receive a financial incentive to split pills: a 50% reduction in their per-refill copayment. Data on patients' statin refills and lipid control were obtained from billing and medical records. RESULTS: Compared with patients unwilling to participate in the program, those agreeing to split pills were more likely to be female and white. After 6 months, most patients in the trial (89%) were willing to continue pill splitting for a 50% copayment reduction. Patients reported few problems with pill splitting and had no noticeable change in their adherence. The financial-incentive group and the control group did not differ significantly with respect to their low-density lipoprotein cholesterol levels after pill splitting: -2.0 mg/dL and -1.2 mg/dL, respectively. CONCLUSIONS: Most patients indicated that at least a 50% copayment reduction would be required to enroll in a pill-splitting program after the study ended. However, in this relatively educated population, financial incentives did not influence patients' adherence, satisfaction, or health outcomes.

Evaluation of clinical research knowledge and interest among pharmacy residents: survey design and validation.

PURPOSE: The development and validation of a survey to describe the research knowledge, attitudes, and skills of pharmacy practice residents are described. SUMMARY: A survey was drafted to determine if pharmacy practice residency experience and the American Society of Health-System Pharmacists (ASHP)-required project improve the residents' objectively and subjectively assessed research knowledge, to determine if the residency experience and the ASHP-required project affect the residents' attitudes regarding research as a component of their future professional practice, and to subjectively assess the effect of the residency experience and the ASHP-required project on other essential skills, such as problem solving, critical thinking, and time management. An initial questionnaire was developed and underwent content validation testing by clinical pharmacists and faculty, residents, and research fellows. Following content validation, the questionnaire underwent construct validity testing (for discriminative validity and responsiveness) in students, residents, and clinical pharmacists and faculty. Reliability was tested in a subgroup of subjects who completed the questionnaire twice within two to four weeks. From the content validation phase, average scores for individual questions ranged from 1.00 to 2.00. Discriminative validity testing of the revised questionnaire demonstrated the instrument's ability to discriminate between groups expected to differ. Effect-size and mean-knowledge score differences indicated high levels of responsiveness, signifying the instrument's ability to detect change over time or after an intervention. CONCLUSION: A survey questionnaire developed to measure research knowledge and interest among pharmacy practice residents demonstrated its validity and reliability with significant sensitivity and responsiveness.

Adherence to treatment in children and adolescent patients with cystic fibrosis.

PURPOSE: The purpose of this study was to monitor medication adherence in cystic fibrosis (CF) patients and its correlation with disease severity and patient age. METHODS: Children less than 12 years of age (group 1) and adolescents 12 years of age and older (group 2) were recruited from the University of Michigan CF Center. The study duration was 3 months. A total of 22 patients per group were enrolled. Adherence to ADEKs, an oral multivitamin, and dornase alfa, a nebulized mucolytic medication, was monitored. Adherence to ADEKs was monitored by using the Medication Event Monitoring System (MEMS) SmartCaps (APREX, AARDx, Inc., Union City, California). Dornase alfa adherence rate was monitored by counting empty medication vials. RESULTS: Thirty-three patients completed the study, 15 patients in group 1 and 18 patients in group 2. The overall mean adherence rates for ADEKs and dornase alfa were (+/- SD) 63.6% +/- 24.0% and 66.5% +/- 31.2%, respectively. The median ADEKs and dornase alfa adherence rate for group 1 was 84.6% and 79.1%, respectively (p = .08); and for group 2 was 56.7% vs. 78.4%, respectively (p = .07). There was a trend toward significance, suggesting that the adherence rate for ADEKs was higher than for dornase alfa (p = .08) in group 1. Group 2 showed a trend toward adherence to dornase alfa than to ADEKs (p = .07). There was a trend for ADEKs adherence between groups 1 and 2 (p = .09), but not for dornase alfa (p = .93). CONCLUSION: Parental supervision and disease severity are likely to play a major role in adherence to medical management. Partnership with patients and families about the treatment plan might be important for improving adherence rate. The MEMS SmartCaps is an electronic monitoring technology that should be used to measure drug adherence objectively both in further larger clinical trials and in the outpatient setting.

Use of laryngeal mask airway in flexible bronchoscopy in infants and children.

In the past two decades, flexible bronchoscopy (FB) has gained increasing popularity among pediatric pulmonologists. The objective of this study was to review our experience with pediatric flexible bronchoscopy over the past 15 years, with special focus on route of bronchoscopy. This is a retrospective study. We reviewed our pediatric FB procedures performed at the University of Michigan, Mott Children's Hospital, from 1988-2003. The study included 1,947 procedures in 1,548 patients, with a mean of 1.3 procedures/patient. The male:female ratio was 1.66:1, and age was 4.9 +/- 5.6 years (mean +/- SD). Patients <2 years of age represented 46.6% of the study population. The laryngeal mask airway (LMA) was the most common route for flexible bronchoscopy in children 2 years of age and above. Complication rates were lower with the use of the LMA (1.9%) compared to the nasal route (3.5%). Stridor was the most common indication in the age group <2 years (20.8%), while persistent pulmonary infiltrates were more common in the older age groups (32.2-37%). Laryngomalacia was the most common finding in patients with stridor (31.5%), while inflammatory changes were more common with other indications. Procedure-related complications were reported in 2.3% of procedures. Bronchoalveolar lavage (BAL) samples were obtained and analyzed in 51.2% of FB procedures (n=1,000), of which 19.4% yielded positive microbiology cultures. In conclusion, FB is a safe procedure in pediatrics. Children less than 7 years of age represent the majority of FB subjects. The LMA offered a lower rate of procedure-related complications when compared to the nasal route or endotracheal tube. It also reduced procedure time and anesthesia time.

The potential role of HMG-CoA reductase inhibitors in pediatric nephrotic syndrome.

OBJECTIVE: To evaluate the safety and efficacy of the hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) as a potential treatment option for the dyslipidemia associated with childhood nephrotic syndrome. DATA SOURCES: Searches of MEDLINE (1966-April 2004), Cochrane Library, International Pharmaceutical Abstracts (1977-April 2004), and an extensive manual review of journals were performed using the key search terms nephrotic syndrome, familial hypercholesterolemia, dyslipidemia, and HMG-CoA reductase inhibitor. STUDY SELECTION AND DATA EXTRACTION: Two prospective uncontrolled studies evaluating the safety and efficacy of statin therapy in pediatric nephrotic syndrome were included. DATA SYNTHESIS: While an extensive amount of data is available in adult nephrotic syndrome in which statin therapy decreases total plasma cholesterol 22-39%, low-density lipoprotein cholesterol (LDL-C) 27-47%, and total plasma triglycerides 13-38%, only 2 small uncontrolled studies have been conducted evaluating the utility of these agents in pediatric nephrotic syndrome. These studies indicate that statins are capable of safely reducing total cholesterol up to 42%, LDL-C up to 46%, and triglyceride levels up to 44%. CONCLUSIONS: Lowering cholesterol levels during childhood may reduce the risk for atherosclerotic changes and may thus be of benefit in certain patients with nephrotic syndrome. Statins have demonstrated short-term safety and efficacy in the pediatric nephrotic syndrome population. Implementing pharmacologic therapy with statins in children with nephrotic syndrome must be done with care until controlled studies are conducted in this population.