Evaluation of oncology infusion pharmacy practices: A nationwide survey.

PURPOSE: Oncology care continues to evolve at a rapid pace including provision of infusion-based care. There is currently a lack of robust metrics around oncology infusion centers and pharmacy practice. The workgroup completed a nationwide survey to learn about oncology-based infusion pharmacy services offered. The objective was to highlight consistent, measureable oncology-based infusion pharmacy metrics that will provide a foundation to describe overall productivity including emphasis on high patient-safety standards. METHODS: A nationwide survey was developed via a workgroup within the Vizient Pharmacy Cancer Care Group beginning in April 2019 and conducted electronically via the Vizient Pharmacy Network from September to November 2020. The survey was designed to capture a number of key metrics related to oncology-based infusion pharmacy services. RESULTS: Forty-one sites responded to the survey. Responses highlighted hours of operation (median = 11.5), number of infusion chairs (median = 45). Staffing metrics included 7.1 pharmacist full-time equivalent (FTE) and 7.6 technician FTE per week. 80.5% of sites had cleanrooms and 95.1% reported both hazardous and nonhazardous compounding hoods. 68.3% of sites reported using intravenous (IV) technology, 50.0% measured turnaround time, and 31.4% prepared treatment medications in advance. CONCLUSION: There was variability among oncology infusion pharmacy practices in regard to survey responses among sites. The survey results highlight the need for standardization of established productivity metrics across oncology infusion pharmacies in order to improve efficiency and contain costs in the changing oncology landscape. The survey provides insight into oncology infusion pharmacy practices nationwide and provides information for pharmacy leaders to help guide their practices.

Double-Strand Break Repair Pathways Differentially Affect Processing and Transduction by Dual AAV Vectors.

Recombinant adeno-associated viral vectors (rAAV) are a powerful tool for gene delivery but have a limited DNA carrying capacity. Efforts to expand this genetic payload have focused on engineering the vector components, such as dual trans-splicing vectors which double the delivery size by exploiting the natural concatenation of rAAV genomes in host nuclei. We hypothesized that inefficient dual vector transduction could be improved by modulating host factors which affect concatenation. Since factors mediating concatenation are not well defined, we performed a genome-wide screen to identify host cell regulators. We discovered that Homologous Recombination (HR) is inhibitory to dual vector transduction. We demonstrate that depletion or inhibition of HR factors BRCA1 and Rad51 significantly increase reconstitution of a large split transgene by increasing both concatenation and expression from rAAVs. Our results define new roles for DNA damage repair in rAAV transduction and highlight the potential for pharmacological intervention to increase genetic payload of rAAV vectors.

LuNER: Multiplexed SARS-CoV-2 detection in clinical swab and wastewater samples.

Clinical and surveillance testing for the SARS-CoV-2 virus relies overwhelmingly on RT-qPCR-based diagnostics, yet several popular assays require 2-3 separate reactions or rely on detection of a single viral target, which adds significant time, cost, and risk of false-negative results. Furthermore, multiplexed RT-qPCR tests that detect at least two SARS-CoV-2 genes in a single reaction are typically not affordable for large scale clinical surveillance or adaptable to multiple PCR machines and plate layouts. We developed a RT-qPCR assay using the Luna Probe Universal One-Step RT-qPCR master mix with publicly available primers and probes to detect SARS-CoV-2 N gene, E gene, and human RNase P (LuNER) to address these shortcomings and meet the testing demands of a university campus and the local community. This cost-effective test is compatible with BioRad or Applied Biosystems qPCR machines, in 96 and 384-well formats, with or without sample pooling, and has a detection sensitivity suitable for both clinical reporting and wastewater surveillance efforts.

Tools for interpretation of wastewater SARS-CoV-2 temporal and spatial trends demonstrated with data collected in the San Francisco Bay Area.

Wastewater surveillance for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA can be integrated with COVID-19 case data to inform timely pandemic response. However, more research is needed to apply and develop systematic methods to interpret the true SARS-CoV-2 signal from noise introduced in wastewater samples (e.g., from sewer conditions, sampling and extraction methods, etc.). In this study, raw wastewater was collected weekly from five sewersheds and one residential facility. The concentrations of SARS-CoV-2 in wastewater samples were compared to geocoded COVID-19 clinical testing data. SARS-CoV-2 was reliably detected (95% positivity) in frozen wastewater samples when reported daily new COVID-19 cases were 2.4 or more per 100,000 people. To adjust for variation in sample fecal content, four normalization biomarkers were evaluated: crAssphage, pepper mild mottle virus, Bacteroides ribosomal RNA (rRNA), and human 18S rRNA. Of these, crAssphage displayed the least spatial and temporal variability. Both unnormalized SARS-CoV-2 RNA signal and signal normalized to crAssphage had positive and significant correlation with clinical testing data (Kendall's Tau-b (τ)=0.43 and 0.38, respectively), but no normalization biomarker strengthened the correlation with clinical testing data. Locational dependencies and the date associated with testing data impacted the lead time of wastewater for clinical trends, and no lead time was observed when the sample collection date (versus the result date) was used for both wastewater and clinical testing data. This study supports that trends in wastewater surveillance data reflect trends in COVID-19 disease occurrence and presents tools that could be applied to make wastewater signal more interpretable and comparable across studies.

Interpretation of temporal and spatial trends of SARS-CoV-2 RNA in San Francisco Bay Area wastewater

Wastewater surveillance for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA can be integrated with COVID-19 case data to inform timely pandemic response. However, more research is needed to apply and develop systematic methods to interpret the true SARS-CoV-2 signal from noise introduced in wastewater samples (e.g., from sewer conditions, sampling and extraction methods, etc.). In this study, raw wastewater was collected weekly from five sewersheds and one residential facility, and wastewater SARS-CoV-2 concentrations were compared to geocoded COVID-19 clinical testing data. SARS-CoV-2 was reliably detected (95% positivity) in frozen wastewater samples when reported daily new COVID-19 cases were 2.4 or more per 100,000 people. To adjust for variation in sample fecal content, crAssphage, pepper mild mottle virus, Bacteroides ribosomal RNA (rRNA), and human 18S rRNA were evaluated as normalization biomarkers, and crAssphage displayed the least spatial and temporal variability. Both unnormalized SARS-CoV-2 RNA signal and signal normalized to crAssphage had positive and significant correlation with clinical testing data (Kendalls Tau-b ({tau})=0.43 and 0.38, respectively). Locational dependencies and the date associated with testing data impacted the lead time of wastewater for clinical trends, and no lead time was observed when the sample collection date (versus the result date) was used for both wastewater and clinical testing data. This study supports that trends in wastewater surveillance data reflect trends in COVID-19 disease occurrence and presents approaches that could be applied to make wastewater signal more interpretable and comparable across studies.

Sewage, Salt, Silica, and SARS-CoV-2 (4S): An Economical Kit-Free Method for Direct Capture of SARS-CoV-2 RNA from Wastewater.

Wastewater-based epidemiology is an emerging tool to monitor COVID-19 infection levels by measuring the concentration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in wastewater. There remains a need to improve wastewater RNA extraction methods' sensitivity, speed, and reduce reliance on often expensive commercial reagents to make wastewater-based epidemiology more accessible. We present a kit-free wastewater RNA extraction method, titled "Sewage, Salt, Silica and SARS-CoV-2" (4S), that employs the abundant and affordable reagents sodium chloride (NaCl), ethanol, and silica RNA capture matrices to recover sixfold more SARS-CoV-2 RNA from wastewater than an existing ultrafiltration-based method. The 4S method concurrently recovered pepper mild mottle virus (PMMoV) and human 18S ribosomal subunit rRNA, which have been proposed as fecal concentration controls. The SARS-CoV-2 RNA concentrations measured in three sewersheds corresponded to the relative prevalence of COVID-19 infection determined via clinical testing. Lastly, controlled experiments indicate that the 4S method prevented RNA degradation during storage of wastewater samples, was compatible with heat pasteurization, and in our experience, 20 samples can be processed by one lab technician in approximately 2 h. Overall, the 4S method is promising for effective, economical, and accessible wastewater-based epidemiology for SARS-CoV-2, providing another tool to fight the global pandemic.

Repression of Wnt/ß-catenin signaling by SOX9 and Mastermind-like transcriptional coactivator 2.

Wnt/ß-catenin signaling requires inhibition of a multiprotein destruction complex that targets ß-catenin for proteasomal degradation. SOX9 is a potent antagonist of the Wnt pathway and has been proposed to act through direct binding to ß-catenin or the ß-catenin destruction complex. Here, we demonstrate that SOX9 promotes turnover of ß-catenin in mammalian cell culture, but this occurs independently of the destruction complex and the proteasome. This activity requires SOX9's ability to activate transcription. Transcriptome analysis revealed that SOX9 induces the expression of the Notch coactivator Mastermind-like transcriptional activator 2 (MAML2), which is required for SOX9-dependent Wnt/ß-catenin antagonism. MAML2 promotes ß-catenin turnover independently of Notch signaling, and MAML2 appears to associate directly with ß-catenin in an in vitro binding assay. This work defines a previously unidentified pathway that promotes ß-catenin degradation, acting in parallel to established mechanisms. SOX9 uses this pathway to restrict Wnt/ß-catenin signaling.

Putting patients at the center of kidney care transitions: PREPARE NOW, a cluster randomized controlled trial.

Care for patients transitioning from chronic kidney disease to kidney failure often falls short of meeting patients' needs. The PREPARE NOW study is a cluster randomized controlled trial studying the effectiveness of a pragmatic health system intervention, 'Patient Centered Kidney Transition Care,' a multi-component health system intervention designed to improve patients' preparation for kidney failure treatment. Patient-Centered Kidney Transition Care provides a suite of new electronic health information tools (including a disease registry and risk prediction tools) to help providers recognize patients in need of Kidney Transitions Care and focus their attention on patients' values and treatment preferences. Patient-Centered Kidney Transition Care also adds a 'Kidney Transitions Specialist' to the nephrology health care team to facilitate patients' self-management empowerment, shared-decision making, psychosocial support, care navigation, and health care team communication. The PREPARE NOW study is conducted among eight [8] outpatient nephrology clinics at Geisinger, a large integrated health system in rural Pennsylvania. Four randomly selected nephrology clinics employ the Patient Centered Kidney Transitions Care intervention while four clinics employ usual nephrology care. To assess intervention effectiveness, patient reported, biomedical, and health system outcomes are collected annually over a period of 36 months via telephone questionnaires and electronic health records. The PREPARE NOW Study may provide needed evidence on the effectiveness of patient-centered health system interventions to improve nephrology patients' experiences, capabilities, and clinical outcomes, and it will guide the implementation of similar interventions elsewhere. TRIAL REGISTRATION: NCT02722382.

The Wnt Transcriptional Switch: TLE Removal or Inactivation?

Many targets of the Wnt/ß-catenin signaling pathway are regulated by TCF transcription factors, which play important roles in animal development, stem cell biology, and oncogenesis. TCFs can regulate Wnt targets through a "transcriptional switch," repressing gene expression in unstimulated cells and promoting transcription upon Wnt signaling. However, it is not clear whether this switch mechanism is a general feature of Wnt gene regulation or limited to a subset of Wnt targets. Co-repressors of the TLE family are known to contribute to the repression of Wnt targets in the absence of signaling, but how they are inactivated or displaced by Wnt signaling is poorly understood. In this mini-review, we discuss several recent reports that address the prevalence and molecular mechanisms of the Wnt transcription switch, including the finding of Wnt-dependent ubiquitination/inactivation of TLEs. Together, these findings highlight the growing complexity of the regulation of gene expression by the Wnt pathway.

Clinical effects of STW 5 (Iberogast) are not based on acceleration of gastric emptying in patients with functional dyspepsia and gastroparesis.

STW 5, a herbal extract, is effective for the treatment of symptoms in patients with functional dyspepsia (FD). However, its mode of action is still unclear and a modulation of gastric motility is hypothesized. This multicentre, placebo-controlled double-blind study addressed the question of whether STW 5 accelerates gastric emptying in patients with FD and gastroparesis. One-hundred and three patients diagnosed with FD were randomly assigned to a treatment with either STW 5 or a liquid placebo for 28 days. The primary end point of the study was a change of a validated gastrointestinal symptom (GIS) score under treatment. Additionally, patients underwent a (13)C octanoic acid breath test for the assessment of the gastric half-emptying time (t(1/2)). Patients with prolonged t(1/2) were diagnosed with gastroparesis and requested to repeat the test at the end of treatment. A change of t(1/2) was defined a secondary study end point. t(1/2) was prolonged in 48.6% of patients in the STW 5 group and in 43.8% of the placebo group. During treatment, t(1/2) increased non-significantly in patients treated with STW 5 (+23 +/- 109 min; P = 0.51) and slightly accelerated among patients in the placebo arm (-26 +/- 51 min; P = 0.77) (P = 0.49). The improvement of the GIS (P = 0.08) and the proportion of patients with a treatment response (P = 0.03) were more pronounced in the STW 5 group. Our findings suggest that the clinical effects of STW 5 in patients with FD and gastroparesis are not directly mediated by an acceleration of gastric emptying. A clear-cut correlation with symptom improvement is still lacking.

The placebo response in functional dyspepsia--reanalysis of trial data.

Clinical trial data rarely identify factors contributing to the placebo response. We reanalysed the data from the placebo arm (n = 157) of a functional dyspepsia (FD) trial to determine predictors of placebo response including total GIS score, change in GIS score during run-in, type of FD symptoms, duration of illness, age, gender, body mass index (BMI), family occurrence of FD-like symptoms, smoking and alcohol consumption. The same response criteria were applied to the drug arm (n = 158) of the study. Based on the initial 40% response criterion of the study, 35 (22.2%) were classified as placebo responders (PR), whilst 122 (78.8%) were placebo non-responders (PnR). Response rates for the drug arm were 41.1 and 56.9% respectively. PR had significantly lower GIS scores compared to PnR at visit 1 (10.6 +/- 0.6 and 12.3 +/- 0.4, respectively, P = 0.035), but not at visit 2 with study medication dispensing (10.9 +/- 0.5 and 11.3 +/- 0.4). Hence, PR symptoms increased during run-in by 4.2% whilst PnR symptoms decreased by 6.3% (P < 0.005). Gender, age and duration and type of FD symptoms were not different between PR and PnR. Smoking was less prevalent in PR (3%) compared to PnR (21%) (P < 0.025). Increasing the criteria for the placebo response resulted in higher BMI for PR than for PnR (P = 0.035). None of the predictors for placebo response were able to distinguish responders from non-responders to the drug. Variables predicting the PR point towards behavioural and biological mechanism of the PR, operating simultaneously and independently.

[Assessment of the efficacy and safety of the phytopharmacon STW 5 versus metoclopramide in functional dyspepsia--a retrolective cohort study]. / Wirksamkeit und Unbedenklichkeit des Phytopharmakons STW 5 versus Metoclopramid bei funktioneller Dyspepsie unter Praxisbedingungen--eine retrolektive Kohortenstudie.

AIM: The objective of this study was to assess the efficacy and safety of the phytopharmacon STW 5 versus metoclopramide in functional dyspepsia. METHODS: A retrolective, epidemiological cohort study with parallel groups in 23 randomised centres where both drugs were used routinely was performed. The main outcome variable was improvement of 10 dyspepsia-specific symptoms of a valid gastrointestinal symptom score (GIS) during therapy. For inclusion, patients had to suffer from at least three of these symptoms before therapy. Secondary outcome variables were change of single symptoms, time till complete symptom relief, investigators' judgement of efficacy and tolerability, duration of inability to work and occurrence of adverse events. RESULTS: The per protocol collective comprised 490 STW 5 and 471 MCP patients. Anamnestic data were comparable. 439 of patients had taken MCP as drops. There was no relevant difference in median treatment duration. Significantly more patients were symptom-free after STW 5 treatment (71.6 vs. 62.8% p = 0,012). Additionally, the extent of symptom improvement (excluding nausea and vomiting) and median duration of inability to work (1 vs. 3 days) were significantly different in favour of STW 5. More physicians assessed STW 5 as effective (71.6 vs. 63.1% p<0.01) and very well tolerated (90 vs. 70.6% p<0.001). Adverse drug reactions were documented only under MCP. CONCLUSION: The present study illustrates a comparable to higher efficacy of STW 5 vs. MCP with better tolerability in treating functional dyspepsia under practice conditions, especially regarding complete symptom improvement, symptom duration and quality of life. The study confirms the results of prospective trials for STW 5 as being an appropriate alternative to the frequently administered antacids and prokinetics.

Phytotherapy for functional dyspepsia: a review of the clinical evidence for the herbal preparation STW 5.

Functional gastrointestinal disorders such as functional (or non-ulcer) dyspepsia are characterized by a broad spectrum of symptoms referred to the upper abdomen without a detectable cause utilizing routine diagnostic measures. It is now believed that disordered gut function (including abnormalities like disturbances of motility such as postprandial fundic relaxation, gastric emptying and disturbed visceral sensory function) play a key role for the manifestation of these disorders. The underlying pathophysiology is not yet fully understood. However, the available data suggest that a number of factors may contribute to the manifestation of symptoms. These factors include environmental factors such as acute infections as trigger event, psychological stressors that may precede acute exacerbations and a genetic predisposition. Considering the large number of mechanisms, a treatment targeting a single mechanism is unlikely to be effective in all patients. Indeed, chemically defined treatments usually gain a 10-15% superiority over placebo. In recent years placebo-controlled studies have demonstrated superiority of a commercial multicomponent herbal preparation, STW 5, with the trade name Iberogast, for the treatment of patients with functional dyspepsia and irritable bowel syndrome. This phytopharmacon is a combination of nine plant extracts each with a number of different active constituents. Pharmacological studies have shown different effects of the single plant extracts on the (molecular) mechanisms which are discussed as underlying the manifestation of symptoms. Various well-controlled clinical trials have independently confirmed clinical efficacy and safety. The clinically efficacy of this multicomponent herbal preparation questions the current trend of highly targeted drug molecules that usually target one single receptor population while it has not been shown that a single receptor group plays a pivotal role for the control of symptoms. Herbal medicines are obtained from various plants and contain complex extracts with a large number of different active substances. While there are only limited head-to-head comparisons with conventional chemically defined medications, the combination of extracts with various gastrointestinal active ingredients appears to be advantageous for a heterogeneous condition such as functional dyspepsia.

Antioxidative properties of the gastrointestinal phytopharmaceutical remedy STW 5 (Iberogast).

Since inflammation is a common mechanism of many gastrointestinal diseases, reactive oxygen metabolites may play an important role in their pathophysiology. Therefore it is interesting to know, whether phytopharmaceuticals known to modulate gastrointestinal motor function reveal also antioxidative properties. We tested STW 5 (Iberogast), its constituent nine different plant extracts, and some isolated compounds which are present in STW 5 for characterizing their antioxidative and radical quenching activities. The test assays consisted in pure chemical and complex cellular systems in which different types of reactive species were produced. Quantification of the effects was based on chemiluminescence reactions. The results show that all extracts contribute to the effect of the complete remedy STW 5, in the chemical systems in a strongly additive manner, in the cellular systems in a supraadditive manner. The largest contributions resulted from the extracts from peppermint and melissa leaves. Comparison of effects from isolated phytochemical compounds from the extracts with that of the extracts itself shows that usually the extract is more effective than the monosubstance which indicates also the synergism within the whole plant extracts. This means that the plant extracts present in STW 5 provide strong radical quenching activities that could also be involved in the therapeutic gastrointestinal actions.

Validation of the gastrointestinal symptom score for the assessment of symptoms in patients with functional dyspepsia.

AIM: To validate the gastrointestinal symptom score as an outcome measure for functional dyspepsia. METHODS: In focus groups, 10 dyspepsia-specific items including nausea, sickness, vomiting, bloating, abdominal cramps, early satiety, acidic eructation/heartburn, loss of appetite, retrosternal discomfort, epigastric pain/upper abdominal pain were identified. Ninety-five patients with functional dyspepsia and 56 healthy controls were recruited and responsiveness evaluated by analysing gastrointestinal symptom score data from 357 patients from previous placebo-controlled trials. Gastrointestinal symptom score response data were correlated with the patient's global assessments of efficacy. Convergent validity was assessed by correlating the gastrointestinal symptom score with the results obtained by the Nepean Dyspepsia Index. RESULTS: Sensitivity: In patients and healthy controls gastrointestinal symptom score yielded consistently different scores (all P < 0.0001). TEST-RETEST RELIABILITY: Gastrointestinal symptom score determined at the two time points were significantly correlated (r-values ranging from 0.842 to 0.901). CONVERGENCE VALIDITY: Gastrointestinal symptom score of both rating groups were significantly correlated with the symptom-specific component of the Nepean Dyspepsia Index (r-vales ranging from 0.666 to 0.764, P < 0.01). RESPONSIVENESS: Responses of gastrointestinal symptom score during treatment were different for patients with a global self assessment as responders compared with non-responders (all P < 0.0055). CONCLUSION: The gastrointestinal symptom score is a valid and reliable instrument to assess symptom intensities in patients with functional dyspepsia.

Treatment of functional dyspepsia with a herbal preparation. A double-blind, randomized, placebo-controlled, multicenter trial.

BACKGROUND: We aimed to assess the efficacy and safety of a herbal preparation STW 5-II containing extracts from bitter candy tuft, matricaria flower, peppermint leaves, caraway, licorice root and lemon balm for the treatment of patients with functional dyspepsia. METHODS: 120 patients with functional dyspepsia were randomly assigned to 1 of 4 treatment groups. Each patient received the treatment for three consecutive 4-week treatment blocks. The first two treatment blocks were fixed. For the third treatment period, medication was based upon the investigator's judgement of symptom improvement during the preceding treatment period. In patients without adequate control of symptoms, the treatment was switched, or if symptoms were controlled, the treatment was continued. The primary outcome measure was the improvement of a standardized gastrointestinal symptom score (GIS). FINDINGS: During the first 4 weeks, the GIS significantly decreased in subjects on active treatment compared to the placebo (p < 0.001). During the second 4-week period, symptoms further improved in subjects who continued on active treatment or who switched to the active treatment (p < 0.001), while symptoms deteriorated in subjects who switched to placebo. After 8 weeks 43.3% on active treatment and 3.3% on placebo reported complete relief of symptoms. (p < 0.001 vs. placebo). CONCLUSION: In patients with functional dyspepsia, the herbal preparation tested improved dyspeptic symptoms significantly better than placebo.

A randomised clinical trial comparing the efficacy of a herbal preparation STW 5 with the prokinetic drug cisapride in patients with dysmotility type of functional dyspepsia.

AIM: To compare the efficacy of the herbal preparation STW 5 (Iberogast ((R))) and the research preparation STW 5-II with cisapride for treatment of patients with dysmotility type of functional dyspepsia. PATIENTS AND METHODS: After a diagnostic work-up and 7 days wash-out, 186 patients with dysmotility type of functional dyspepsia were randomly assigned in a double-blind, double-dummy study to one of three treatment arms (STW 5/cisapride-placebo; STW 5-II/cisapride-placebo; cisapride/STW-placebo) for four weeks. Main outcome variable was the improvement of a dyspepsia-specific gastrointestinal symptom score. Symptoms were assessed three times during treatment and after six months follow-up. Hypothesis of non-inferiority was tested. Secondary endpoints were efficacy and tolerability assessments, recurrences and safety parameters. RESULTS: 137 patients were included in the confirmatory analysis. The lower limit of the confidence interval for both herbal preparations was above the pre-defined lower limit of the equivalence border and hypothesis of non-inferiority was proven for STW 5 and STW 5-II. There were no statistical significant differences for the secondary endpoints. CONCLUSION: In this study STW 5 and the research preparation STW 5-II showed equivalent efficacy to cisapride for the treatment of patients with functional dyspepsia of dysmotility type.

Comparison of 2-D calculations from periapical and occlusal radiographs versus 3-D calculations from CAT scans in determining bone support for cleft-adjacent teeth following early alveolar bone grafts.

OBJECTIVE: This investigation was conducted to determine the agreement between three-dimensional (3-D) calculations from CAT scans and two-dimensional (2-D) calculations from standard dental radiographs in evaluating bone support for cleft-adjacent teeth after primary bone grafting. DESIGN: This retrospective study utilized CAT scans and dental radiographs taken of the alveolar cleft in patients an average of 11 years after primary bone grafting. SETTING: The subjects were patients treated by the Cleft Palate Team at Children's Memorial Hospital and Loyola University Medical Center, Chicago, Illinois. PATIENTS: Fourteen UCLP patients (9 males, 5 females) agreed to participate in this study by undergoing CAT scan assessment of their alveolar cleft sites. They also had to have periapical or occlusal radiographs of the grafted cleft site taken within 6 months of the CAT scan. INTERVENTIONS: All patients underwent primary lip repair, placement of a passive palatal plate, primary alveolar bone grafting (mean age 6.4 months), and palatoplasty before 1 year of age. Major tooth movement through final orthodontics was completed by the time of the radiographic assessment. MAIN OUTCOME MEASURES: CAT scan sections were reformatted and reconstructed to three-dimensionally calculate the percentage of root covered by bone support for the 15 teeth adjacent to the graft cleft sites. Dental radiographs of the same teeth were also traced and digitized. Percentages of root supported by bone were also established using the dental radiographs by dividing the amount of root covered by bone, by the anatomic root length. RESULTS: A paired, two-sample t test revealed no significant differences between the two methods of assessment, while linear regression showed a statistically significant correlation between the CAT scan assessment and the percentages found on the radiographs. CONCLUSIONS: Routine dental radiographs were able to estimate the total 3-D bone support for the roots of cleft adjacent teeth as determined by CAT scan to a statistically significant degree when groups where compared. The clinical significance for evaluation of individual cases was less impressive with a wide range of variability and a level of agreement that required acceptance of differences up to 25%.

Effect of cuspid positioning in the cleft at the time of secondary alveolar bone grafting on eventual graft success.

This investigation was to determine the relationship between the success of secondary alveolar bone grafting and the position of the permanent cuspid relative to the cleft at the time of grafting. In this retrospective study utilizing periapical radiographs take on cleft patients to evaluate bone grafting results, the subjects were patients treated at the Lancaster Cleft Palate Clinic, a private institution specializing in the care of cleft patients. Sixty-seven patients (20 BCLP; 47 UCLP) were selected for this study based on availability of quality radiographs and a minimum of 6-month post-surgical follow-up. All patients underwent alveolar bone grafting (mean age, 10 years 7 months). Presurgical radiographs were taken within 3 months of the operation. Post-surgical radiographs were taken to evaluate the outcome of grafting (mean follow-up, 2 years 10 months). Radiographs were traced and digitized on a total of 86 cleft sites. Presurgically, a ratio was used to determine the amount of cuspid crown emerged through the alveolus into the cleft site relative to the anatomic cuspid-crown length. Post-surgically, ratios of bone support for the teeth mesial and distal to the cleft were established by dividing the amount of root covered by bone by the anatomic root length. Ratios expressing the height of alveolar crest relative to the cementoenamel junction (CEJ) of adjacent teeth and amount of alveolar notching relative to the mesial tooth root length were also evaluated. Linear regressions of each of the five ratios of graft outcome on the cuspid-eruption ratio were done. No significant correlations could be found between final graft success and the amount of cuspid crown exposed in the cleft at the time of grafting. Cuspid position could not be shown to be a significant factor in determining graft success.