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Biomedical subjects

B Cole

Publications and source records attributed to B Cole.

At least 37 records · Page 2Linked to original sources

Malformation in the primary and permanent dentitions following trauma prior to tooth eruption: a case report.

Dento-facial injuries that occur prior to the eruption of teeth in the primary dentition are rare, but can result in damage to the primary dentition. We report a rare case where an injury to the anterior maxilla and mandible of an infant prior to primary tooth eruption resulted in hypoplasia, displacement and impaction of the primary dentition and damage to a developing permanent tooth.

Child, Preschool↗

Immunologic cross-reaction between HIV type 1 p17 and Mycoplasma hyorhinis variable lipoprotein.

Monoclonal antibodies directed against the HIV-1 matrix protein p17 that react with a component present on the surface of HIV-1-infected cells have previously been described. In this study we show that one of these monoclonal antibodies binds to persistently HIV-1-infected cell lines that are coinfected with Mycoplasma hyorhinis, but not to cell lines that are uninfected with mycoplasma. Mycoplasma-infected cells secrete HIV-1 at a higher rate, have a slight increase in cell surface expression of gp120 and gp41, and are less sensitive to immunotoxins than uninfected cells. The anti-p17 antibody binds to a protein of M. hyorhinis grown in cell-free culture. The variable expression and size of the protein among strains is typical of the variable lipoprotein (Vlp) system of M. hyorhinis. Confirmation of the reactivity of the antibody with a Vlp was provided by demonstrating its specific binding to recombinant VlpF expressed in E. coli, and to a synthetic peptide representing the carboxy-terminal region of VlpF, but not to other recombinant Vlp products or peptides. This is a true cross-reaction because the antibody also binds to recombinant p17 expressed in E. coli and the binding is inhibited by the VlpF peptide. These analyses highlight the potential of mycoplasma contamination of tissue culture cell lines to cause anomalous results. With regard to HIV-1, mycoplasma infection of cells results in increased rates of virus secretion, and introduces a potential confounding immunologic cross-reaction as well. The existence of a cell surface form of p17 is unlikely.

Antibodies, Monoclonal↗

Very Long-Term Memory for Information Taught in School.

Students who completed a Child Development course (N = 1168) from 3 to 16 years prior to retention testing were tested for recognition and recall of facts and application of mental skills. Students who subsequently served as course tutors were also tested for retention. Fact retention was superior to application retention and retention for both question types declined rapidly from year 3 to year 7 after which it stabilized. Recognition items were superior to recall items for high achieving students only. Tutors retained more than non-tutors for eight years after which there were no differences. Copyright 1998 Academic Press.

Journal Article↗

Prognostic analysis of survival in small breast cancers.

BACKGROUND: Routine axillary dissection in patients with invasive small breast cancer remains controversial. We previously reported a model for predicting nodal involvement in patients with T1a or T1b breast cancer that may guide the practice of selective nodal dissection. The objective of this study was to determine whether the prognosticators that predict nodal metastases also predict survival. STUDY DESIGN: This study is a retrospective review of 2,153 women with small invasive breast cancer (< or = 1 cm) diagnosed between January 1984 and December 1995. Cases were identified from a statewide tumor registry, the Hospital Association of Rhode Island, and the tumor registry at Baystate Medical Center in Massachusetts. The impact on survival of patient age (< or = 40 versus > 40 years), nodal status (positive versus negative), tumor size (T1a versus T1b), and tumor grade (1 versus 2 or 3) were analyzed. Breast cancer-specific survival (BCSS) was analyzed using the Kaplan-Meier method and the proportional hazards regression method. RESULTS: There were 388 patients with tumors 0.5 cm or less (T1a) and 1,765 with tumors 0.6-1.0 cm (T1b). Nodal status was known in 68% of cases (1,461 of 2,153), and tumor grade was recorded in 42% of cases (902 of 2,153). In univariate analysis, age, grade, and nodal status were significant in their association with BCSS. Tumor size did not influence BCSS among patients with small invasive tumors. Women older than 40 years had superior survival compared with younger women (93% versus 78% at 5 years; p = 0.01). Similarly, women with low grade (1) tumors did better than those with higher grade (2 or 3) tumors (98% versus 88% at 5 years; p = 0.03). The 5-year BCSS was 96% versus 78% for node-negative versus node-positive disease, and the 10-year BCSS was 91% versus 62% (p = 0.001). In the multivariate analysis, age and nodal status remained firmly associated with survival, although grade lost its significance. CONCLUSIONS: Small tumor size does not affect survival. Although risk profiles for nodal involvement can be constructed to help guide the practice of selective axillary lymphadenectomy in patients with small invasive breast cancers, these factors cannot serve as a surrogate to nodal status in establishing patient prognosis. Nodal status remains the most powerful determinant of survival in breast cancer patients, even those with very small tumors.

Adult↗

Histologic evidence of a radiosensitizing effect of Taxol in patients with astrocytomas.

The new anticancer agent Taxol appears to potentiate the effects of radiation on brain tumor cell lines in vitro and was recently evaluated by our group as a radiosensitizer in a phase I study for primary brain tumors. In that study, we administered Taxol as a three-hour IV infusion repeated every week for six weeks and gave daily cranial irradiation concurrently for a total of 6000 rads. We reviewed the charts of the 60 patients who participated in the study, and identified twelve patients who underwent a second surgery after treatment because of progressive symptoms and an enlarging intracranial mass on MRI. Pathologically, each patient showed prominent radionecrosis, and other evidence of accelerated radiation changes (confluent areas of coagulative necrosis, bizarre nuclei, marked thickening and fibrinoid changes in multiple blood vessels). These changes were noted many weeks earlier than would be expected after radiation therapy alone and were independent of age, and tumor histology. We postulate that the accelerated radiation changes may be due to the radiation sensitizing effects of Taxol. We also noted a change of the pattern of tumor recurrence, compared to historic reports, and a dose-necrosis relationship where the resected tumor is formed completely of necrotic tissue in patients who received 150 mg/m2 or higher dose of Taxol. These observations may be of significance for future study design.

Adult↗

Total thyroidectomy does not enhance disease control or survival even in high-risk patients with differentiated thyroid cancer.

SUMMARY BACKGROUND DATA: The extent of primary thyroidectomy for differentiated thyroid cancer is controversial. There are strong proponents for total thyroidectomy based on its presumed and theoretical disease control benefits. In contrast, there are equally strong advocates of less aggressive thyroidectomy with its lower hazard of parathyroid and recurrent nerve injury. The authors have addressed whether total thyroidectomy has a survival benefit justifying its use in patients with high-risk primary cancer. The major risk factors include age and the following the pathologic determinants follicular histology, vascular invasion, and extracapsular extension. MATERIALS AND METHODS: The clinical pathologic, therapeutic, prognostic, and outcome data were reviewed in 347 patients with well-differentiated thyroid cancer. Seventy-five percent were women, 216 patients were in the younger age group (low-risk) (21-50 years), 103 were in the intermediate-risk group (51-70 years), and 28 were in the high-risk group (>70 years). Included in the high-risk pathologic category were 158 patients who had follicular histology (55), extracapsular extension (107), or vascular invasion (119). Total thyroidectomy was performed in 56 patients, near or subtotal thyroidectomy in 47 patients and lobectomy in 55 patients. The 10-year disease specific survival in the overall patient group was 82% in patients with total thyroidectomy, 78% in patients with subtotal thyroidectomy, and 89% in patients with lobectomy (p = 0.30). There was no significant survival difference according to extent of thyroidectomy in the intermediate or high-risk groups either by age or in patients who had high-risk pathologic feature. CONCLUSIONS: Total thyroidectomy in high-risk patients with differentiated thyroid cancer (containing follicular histology, vascular invasion, or extracapsular extension) showed no benefit over partial thyroidectomy. This suggests that the general use of total thyroidectomy is not indicated, except in highly selected patients.

Adult↗

Continuous quality improvement, total quality management, and reengineering: one hospital's continuous quality improvement journey.

In recent years, there has been significantly increasing interest in the application of continuous quality improvement (CQI) and total quality management (TQM) in the health care arena. This case analysis is designed to identify and assess the strategies and processes that led to the successful implementation of CQI in the Emergency Care Center at St. Mary's Hospital in Grand Rapids, MI.

Admitting Department, Hospital↗

Multiinstitutional phase II trial of paclitaxel, carboplatin, and concurrent radiation therapy for locally advanced non-small-cell lung cancer.

PURPOSE: Combined modality therapy for non-small-cell lung cancer (NSCLC) has produced promising results. A multiinstitutional phase II clinical trial was conducted to evaluate the activity and toxicity of paclitaxel, carboplatin, and concurrent radiation therapy on patients with locally advanced NSCLC. PATIENTS AND METHODS: Forty previously untreated patients with inoperable locally advanced NSCLC entered onto a phase II study from March 1995 to December 1996. On an outpatient basis for 7 weeks, patients received paclitaxel 50 mg/m2 weekly over 1 hour; carboplatin at (area under the curve) AUC 2 weekly; and radiation therapy of 66 Gy in 33 fractions. After chemoradiation therapy, patients received an additional two cycles of paclitaxel 200 mg/m2 over 3 hours and carboplatin at AUC 6 every 3 weeks. RESULTS: Thirty-nine patients were eligible for the study. The survival rates at 12 months were 56.3%, and at 24 months, 38.3%, with a median overall survival of 20.5 months. The progression-free survival rates at 12 months were 43.6%, and at 24 months, 34.7%, with a median progression-free survival of 9.0 months. Two patients did not receive more than 2 weeks of concurrent chemoradiotherapy and were not assessable for toxicity and response. The overall response rate (partial plus complete response) of 37 assessable patients was 75.7%. The major toxicity was esophagitis. Seventeen patients (46%) developed grade 3 or 4 esophagitis. However, only two patients developed late esophageal toxicity with stricture at 3 and 6 months posttreatment. CONCLUSION: Combined modality therapy with paclitaxel, carboplatin, and radiation is a promising treatment for locally advanced NSCLC that has a high response rate and acceptable toxicity and survival rates. A randomized trial will be necessary to fully evaluate the usefulness of these findings.

Adult↗

Quality-adjusted time without symptoms or toxicity analysis of interferon maintenance in multiple myeloma.

PURPOSE: In a randomized trial conducted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG), interferon alpha-2b (IFN) maintenance therapy (2 mU/m2 subcutaneously three times per week) after successful induction with melphalan and prednisone was found to prolong time to progression in patients with multiple myeloma. A favorable effect on survival was also present, but this difference was of borderline significance. However, IFN toxicity was a concern. To evaluate the trade-off between the clinical benefits of IFN and the associated toxicity, we applied the method of quality-adjusted time without symptoms or toxicity (Q-TWiST). MATERIALS AND METHODS: Three clinical health states were defined in this analysis: time with toxicity (TOX), time without disease relapse or toxicity (TWiST), and time following disease relapse (REL). Toxicity information for IFN had been collected using patient-completed diaries so the actual duration of each adverse event could be determined. The health states TOX and REL were weighted using utility scores to account for a possible decrement in quality of life, a weighted sum of the health state durations is used as a measure of quality-adjusted time. RESULTS: The health state durations were calculated at 72 months median follow-up. Patients in the IFN group gained an average of 9.8 months without disease relapse (P = .001) and 5.8 months of overall survival (P = .074) versus the control group. However, the IFN group suffered an average of 4.1 months of moderate or worse toxicity (P < .001). CONCLUSION: The clinical benefits of IFN outweigh the negative effects associated with treatment toxicity for a wide range of plausible utilities.

Antineoplastic Agents↗

Detection of Mycobacterium tuberculosis in gastric aspirates collected from children: hospitalization is not necessary.

OBJECTIVE: To compare the yields of gastric aspirates collected for culture of Mycobacterium tuberculosis from children evaluated as outpatients versus inpatients and to determine factors associated with a positive culture. METHODS: Retrospective study of 100 children <12 years of age with tuberculosis diagnosed at a pediatric referral hospital or in one of two tuberculosis control programs in California. RESULTS: Of the 100 children who had tuberculosis, 80 had at least one gastric aspirate collected. M tuberculosis was isolated from 33 (41%) of the 80 children who had a gastric aspirate; 4 children had a positive culture from an aspirate subsequent to the first. Inpatients had a higher proportion of positive gastric aspirates than that of children who had aspirates collected as outpatients (48% vs 37%); however, this difference was not statistically significant. Resistance to isoniazid was found in three isolates (9%) of children all of whose presumptive source case had a susceptible strain of M tuberculosis. Characteristics that were associated with an approximately 50% yield from gastric aspirates were identification of a source case, age <2 years, birth in the United States, symptomatic tuberculosis, and pulmonary disease. CONCLUSIONS: The culture of M tuberculosis from gastric aspirates of children in the outpatient setting has a yield comparable to aspirates collected from hospitalized children. Collection of gastric aspirates in the outpatient setting will reduce both the cost and the inconvenience of the procedure. Although the yield from gastric aspirates is relatively low, important information including drug susceptibility patterns may be obtained. tuberculosis, gastric aspirate, children.

Adolescent↗

Correlation of plasma concentrations of cystatin C and creatinine to inulin clearance in a pediatric population.

Measurement of blood concentrations of cystatin C (cysC), a cysteine protease inhibitor present in human plasma, has been suggested for use as an indicator of glomerular filtration rate (GFR) in a manner analogous to the use of plasma creatinine (SCR). In this study, cysC and SCR were measured in plasma from pediatric patients (4-19 years) with renal disease for whom a "gold standard" measurement of GFR via inulin clearance (C(IN)) was available. The data analyses were divided into two age groups: group A (4-12 years, n = 26) and group B (12-19 years, n = 34). For both age groups, the linear correlation coefficient of [cysC](-1) vs C(IN) (mL/min/1.73 m2) (r = 0.765 for group A and r = 0.869 for group B) was less than that of the linear correlation coefficient of [SCR](-1) vs C(IN) (r = 0.841 for group A and r = 0.892 for group B). As a single measurement for detection of abnormal GFR, however, the optimum receiver-operator characteristic point for cysC measurement (for group A at cysC >1.2 mg/L, sensitivity = 80%, specificity = 91%; and for group B at cysC >1.4 mg/L, sensitivity = 87%, specificity = 100%) was numerically superior to that for SCR measurement (for group A at SCR >8.0 mg/L, sensitivity = 67%, specificity = 100%; and for group B at SCR >9.0 mg/L, sensitivity = 91%, specificity = 91%), using a reference value for normal GFR of C(IN) > 90 mL/min/1.73 m2. However, these differences were not statistically significant. CysC measurement appears to be broadly equivalent to SCR measurement for estimation of GFR in pediatric patients.

Adolescent↗

The quality-of-life effects of interferon beta-1b in multiple sclerosis. An extended Q-TWiST analysis.

BACKGROUND: A recombinant form of interferon beta-1b (Betaseron) was given Food and Drug Administration approval for use in the treatment of relapsing-remitting multiple sclerosis in 1993 based on a documented reduction in exacerbation rate. However, its effect on disease progression is less clear. It costs $11,000 per year and has documented adverse effects such as fatigue, feverlike symptoms, and depression. OBJECTIVES: To evaluate a recombinant form of interferon beta-1b in the treatment of relapsing-remitting multiple sclerosis and to discuss treatment trade-offs and comprehensive quality-of-life (QOL) outcomes. METHODS: We present a randomized evaluation of treatment with a recombinant form of interferon beta-1b in 79 patients with multiple sclerosis who participated in a random allocation lottery and were followed up for 12 months, during which data on QOL and clinical outcomes were collected. The data were analyzed using the Extended Quality-Adjusted Time Without Symptoms and Toxicity (Q-TWiST) method, which evaluates treatment trade-offs by incorporating several QOL domains and patient preferences regarding these domains. RESULTS: Over the 12 months of follow-up, the case patients reported 10.6 months of quality-adjusted time, while the control patients reported 10.4 months of quality-adjusted time (P = .50). CONCLUSIONS: Thus, the first year of treatment with interferon beta-1b did not significantly improve or detract from QOL. Results are discussed in terms of acceptable trade-offs depending on the nature of therapy. Future observational and clinical studies should incorporate measures of patient preference.

Adjuvants, Immunologic↗

The impact of histopathology on nodal metastases in minimal breast cancer.

OBJECTIVE: To establish a model based on risk factor analysis to guide selective axillary lymph node dissection in patients with T1a and T1b breast cancers. DESIGN: Retrospective review to determine histopathologic features and patient demographic profiles that may influence the incidence of nodal metastases. SETTING: Primary care and referral centers in Rhode Island and Massachusetts. PATIENTS: Women with invasive breast cancers with nodal status reported to the statewide tumor registry, the Hospital Association of Rhode Island, and the tumor registry at Baystate Medical Center, Springfield, Mass, between January 1984 and December 1995. There were 12030 patients with breast cancer reported; 2185 (18%) of these had tumors 1 cm or less in diameter. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Axillary node metastases. RESULTS: The nodal status of 377 patients with T1a tumors and 1808 patients with T1b tumors was studied. Seventy-five percent had axillary dissections, and 16% were found to have nodal metastases. Thirty-one percent (29/93) of patients younger than 40 years had positive nodes compared with 15% (241/1546) of older patients (P = .001). The T1a tumors had fewer metastases than the T1b tumors did (11% vs 17%; P = .02). Nuclear grade was available in 49% of cases. Nuclear grades 2 and 3 were associated with nodal involvement twice as often as grade 1 tumors were (P = .002). Patients with no poor prognostic factors had a 7% or less chance of nodal involvement, while patients with all 3 poor prognostic indicators had a 33.5% chance of nodal involvement. CONCLUSIONS: Selective nodal dissection may be possible through risk factor analysis. Prospective registration of complete histopathologic information will allow more comprehensive analysis and may further enhance the selective treatment of patients with minimally invasive breast cancer.

Adult↗

Preoperative chemoradiation coupled with aggressive resection as needed ensures near total control in advanced head and neck cancer.

BACKGROUND: Preoperative chemotherapy or chemoradiation protocols are generally associated with high clinical response rates, but limited pathologic responses for large primary tumors. We have initiated a prospective phase II study of weekly paclitaxel 60 mg/M2, and carboplatin (AUC of 1) plus concurrent fractionated external beam radiation (45 Gy) followed by organ-preserving (or function restorative) surgery when applicable to maximize local-regional tumor control. PATIENTS AND METHODS: Operable patients staged by triple endoscopy received a percutaneous endoscopic gastrostomy and vigorous dental and nutritional support during therapy. Weekly paclitaxel 60 mg/M2, carboplatin (AUC of 1), and radiation 45 Gy were given with rebiopsy of the primary site at 5 weeks. Patients with positive biopsy had definitive surgery in 4 to 5 weeks. Patients with negative biopsy-results received 3 additional weeks of radiation, to a total dose of 72 Gy plus carboplatin and paclitaxel. RESULTS: The 35 patients were 29 men and 6 women, aged 40 to 71 years, with stage III (12) or stage IV (23) cancer. The site of the cancer was oral cavity, 10; base of tongue, 3; oropharynx, 3; hypopharynx, 4; larynx, 12 (glottic, 6; supraglottic, 6), unknown primary, 2; other, nasal cavity, 1. Of 34 evaluable patients, 16 (47%) had a complete clinical response (CR) and 18 (53%) had a partial response (PR); total clinical response rate was 100%. A pathologic CR at the primary site occurred in 23 of 34 patients (68%; 2 had an unknown primary) who went on to completion radiation at 67 to 72 Gy. After induction chemoradiation 21 patients with N1-3 nodes had neck dissection; 6 (31%) had positive nodes. Twelve patients had residual cancer at the primary site at time of rebiopsy: mandible, 4; maxilla, 1; base of tongue, 2; larynx, 4; floor of mouth, 1; and nasal cavity, 1. All were resected with function-preserving reconstruction. At median follow-up of >12 months, progression-free and overall survivals were 71% and 83%, respectively. CONCLUSION: Preoperative treatment with paclitaxel, carboplatin, and radiation is associated with high CR at the primary site and a high level of organ preservation or functional restoration if ablation is done.

Adult↗

Variable memory profiles in Parkinson's disease.

Thirty-nine patients with Parkinson's disease (PD) were categorized into one of three subgroups using discriminant function analysis and three key indices from the California Verbal Learning Test (CVLT). Patients were classified as having one of three memory profiles: (a) a normal memory profile; (b) a memory profile often observed in patients with Huntington's disease (HD); or (c) a memory profile often observed in patients with Alzheimer's disease (AD). Twenty of the patients with PD were classified as having a normal profile, 10 as having an HD profile, and 9 as having an AD profile. The three subgroups did not differ on measures of global cognitive functioning, letter fluency, confrontation naming, or visuo-construction, suggesting that the patients with PD with an AD memory profile were not experiencing AD, per se. These results demonstrate that the memory deficits associated with PD can be similar to those found in patients with either HD or AD, and argues against the notion that the behavioral manifestations of PD are homogeneous.

Age Factors↗

Nonpalpable breast cancer in women aged 40-49 years: a surgeon's view of benefits from screening mammography.

While mammography screening among women aged 50 years or older has proven to reduce breast cancer mortality, screening in younger women has been repeatedly scrutinized. To test the effect of screening among younger women, we examined 84 consecutive patients aged 40-49 at the time of breast cancer diagnosis: 27 (32.1%) were diagnosed solely by mammography, and 57 (67.9%) had a palpable mass. The mean tumor sizes were 1.3 cm and 3.6 cm for the two groups respectively. While 68.8% nonpalpable invasive tumors were classified as Stage I cancer, only 34% of patients with palpable breast cancer had Stage I disease. None of the patients with nonpalpable breast cancer had disease beyond Stage II. In contrast, 28.3% of the patients with palpable invasive breast cancer presented with advanced disease. In addition, 6.3% versus 41.5% of patients with nonpalpable and palpable breast cancer respectively had nodal metastases. The five-year survival rates for the two groups were 100% and 73% respectively, favoring breast cancer detected mammographically. Screening of women aged 40-49 also resulted in more breast-conserving surgery and less chemotherapy. We conclude that screening in this age group should be continued, although individual assessment is needed.

Adult↗

Is surgical management compromised in elderly patients with breast cancer?

OBJECTIVE: The suggestion that breast cancer management is compromised in elderly patients had prompted our review of the results of policies regarding screening and early detection of breast cancer and the adequacy of primary treatment in older women (> or = 65 years of age) compared to younger women (40 to 64 years of age). SUMMARY BACKGROUND DATA: Although breast cancer in elderly patients is considered biologically less aggressive than similar staged cancer in younger counterparts, outcome still is a matter of stage and adequate treatment of primary cancer. For many reasons, physicians appear reluctant to treat elderly patients according to the same standards used for younger patients. There is even government-mandated alterations in early detection programs. Thus, since 1993, Medicare has mandated screening mammography on a biennial basis for women older than 65 year of age compared to the current accepted standard of yearly mammograms for women older than 50 years of age. Using State Health Department and tumor registry data, the authors reviewed screening practice and management of elderly patients with primary breast cancer to determine the effects of age on screening, detection policies (as reflected in stage at diagnosis), treatment strategies, and outcome. METHODS: Data were analyzed from 5962 patients with breast cancer recorded in the state-wide Tumor Registry of the Hospital Association of Rhoda Island between 1987 and 1995. The focus of the data collection was nine institutions with established tumor registries using AJCC classified tumor data. Additional data were provided by the State Health Department on screening mammography practice in 2536 women during the years 1987, 1989, and 1995. RESULTS: The frequency of mammographic screening for all averaged 40% in 1987, 52% in 1987, and 63% in 1995. In the 65-year-old and older patients, the frequency of screening was 34% in 1987, 45% in 1989, and 48% in 1995, whereas in the 40- to 49-year-old age group, the frequency of mammography was 47% in 1987, 61% in 1989, and 74% in 1995 (p < 0.001). There was a lower detection rate of preinvasive cancer in the 65-year-old and older patients, 8.8% versus 13.7% in patients within the 40- to 64-year-old age group (p < 0.001). There was a higher percentage of treatment by limited surgery among elderly patients with highly curable Stage IA and IB cancer with 26.6% having lumpectomy alone versus 9.4% in the younger patients. Five-year survival in that group was significantly worse (63%) than in patients treated by mastectomy (80%) or lumpectomy with axillary dissection and radiation (95%, < 0.001). A similar effect was seen in patients with Stage II cancer. CONCLUSIONS: Breast cancer management appears compromised in elderly patients (older than 65 years of age). Frequency of mammography screening is significantly less in elderly women older than 65 years of age. Early detection of preinvasive (curative cancers) is significantly less than in younger patients. The recent requirement by Medicare of mammography every other year may further reduce the opportunity to detect potentially curable cancers. Approximately 20% of patients had inferior treatment of favorable stage early primary cancer with worsened survival. Detection and treatment strategy changes are needed to remedy these deficiencies.

Adult↗