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Jeffrey N Katz

Publications and source records attributed to Jeffrey N Katz.

At least 19 recordsLinked to original sources
PubMed2025

Distinct roles of the two BRCA2 DNA-binding domains in DNA damage repair and replication fork preservation.

Homologous recombination (HR) removes DNA double-strand breaks (DSBs) and preserves stressed DNA replication forks. Successful HR execution requires the tumor suppressor BRCA2, which harbors distinct DNA-binding domains (DBDs): one that possesses three oligonucleotide/oligosaccharide-binding (OB) folds (OB-DBD) and another residing in the C-terminal recombinase binding domain (CTRB-DBD). Here, we employ multi-faceted approaches to delineate the contributions of these domains toward HR and replication fork maintenance. We show that OB-DBD and CTRB-DBD confer single-strand DNA (ssDNA)- and dsDNA-binding capabilities, respectively, and that BRCA2 variants mutated in either domain are impaired in their ability to load the recombinase RAD51 onto ssDNA pre-occupied by RPA. While the CTRB-DBD mutant is modestly affected by DNA break repair, it exhibits a strong defect in the protection of stressed replication forks. In contrast, the OB-DBD is indispensable for both BRCA2 functions. Our study thus defines the unique contributions of the two BRCA2 DBDs in genome maintenance.

BRCA2 Protein↗
PubMed2023

DNA binding and RAD51 engagement by the BRCA2 C-terminus orchestrate DNA repair and replication fork preservation.

The tumor suppressor BRCA2 participates in DNA double-strand break repair by RAD51-dependent homologous recombination and protects stressed DNA replication forks from nucleolytic attack. We demonstrate that the C-terminal Recombinase Binding (CTRB) region of BRCA2, encoded by gene exon 27, harbors a DNA binding activity. CTRB alone stimulates the DNA strand exchange activity of RAD51 and permits the utilization of RPA-coated ssDNA by RAD51 for strand exchange. Moreover, CTRB functionally synergizes with the Oligonucleotide Binding fold containing DNA binding domain and BRC4 repeat of BRCA2 in RPA-RAD51 exchange on ssDNA. Importantly, we show that the DNA binding and RAD51 interaction attributes of the CTRB are crucial for homologous recombination and protection of replication forks against MRE11-mediated attrition. Our findings shed light on the role of the CTRB region in genome repair, reveal remarkable functional plasticity of BRCA2, and help explain why deletion of Brca2 exon 27 impacts upon embryonic lethality.

DNA Replication↗
PubMed2006

Methodological approaches to developing criteria for improvement in lumbar spinal stenosis surgery.

STUDY DESIGN: The study design was an outcomes measure validation for overall patient success. OBJECTIVE: The objective of this study was to validate an established lumbar spinal stenosis outcomes measure for individual patient success. SUMMARY OF BACKGROUND DATA: The Brigham Spinal Stenosis (BSS) Questionnaire has been used to evaluate lumbar spinal stenosis patients since the early 1990s. The three-domain questionnaire has been previously validated for patient improvement in each domain, but criteria for overall patient success have not been established. METHODS: The sample consisted of preoperative and 24-month postoperative BSS scores from 197 individuals who had undergone a lumbar decompressive procedure with or without an instrumented fusion. For each of the three BSS domains, we determined a threshold score that marked a successful outcome in that domain using receiver operator characteristic (ROC) curves. We combined these threshold scores in different ways to produce varying definitions of overall surgical success. RESULTS: The threshold for changes in the Symptom Severity and Physical Function domain scores were calculated as 0.46 and 0.42, respectively, while for Patient Satisfaction it was 2.42 based on the ROC analysis. The definition for individual patient success that requires the patient achieve threshold scores in each domain was less sensitive but more specific than alternative definitions of overall success that required the patient achieve at least two criteria or at least one criterion. CONCLUSIONS: The threshold values for each domain were similar to previously established values and the most balanced definition of overall success required that a patient achieve at least two criteria.

Aged↗
PubMed2006

The validity of a rheumatoid arthritis medical records-based index of severity compared with the DAS28.

The objective of this work was to assess the convergent validity of a previously developed rheumatoid arthritis medical records-based index of severity (RARBIS) by comparing it with the 28-joint Disease Activity Score (DAS28). This study was conducted in subjects within the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS). We selected 100 patients with rheumatoid arthritis (RA) from the BRASS with DAS28 scores equally distributed in four quartiles. The medical records were reviewed to calculate the RARBIS, which includes indicators from the following categories: prior surgical history, radiologic and laboratory findings, clinical and functional status, and extra-articular manifestations. The Spearman correlation between the RARBIS and the DAS28 was assessed in the total study population and in relevant subgroups. We re-weighted on subscales and recalculated the RARBIS score. This was performed based on findings of correlations between the DAS28 and subscales; and also the result from a multiple linear regression with the DAS28 (as a dependent variable) and five subscales (as independent variables). The mean RARBIS was 4.36 (range 0-11). Among the total study cohort, the RARBIS was moderately correlated with the DAS28 (r = 0.41, 95% confidence interval [CI] 0.23-0.56). In subgroup analyses, including age, gender, rheumatoid factor status, and disease duration, we found no statistically significant differences in the correlations. After re-weighting, the correlation between the RARBIS and the DAS28 was somewhat improved (r = 0.48, 95% CI 0.31-0.62). In conclusion, the RARBIS correlated moderately well with the DAS28 in this population. The RARBIS has both face and convergent validity for patients with RA and relevant subgroups and may have application for medical records studies in patients with RA.

Arthritis, Rheumatoid↗
PubMed2006

A review of the 2001 Volvo Award winner in clinical studies: lumbar fusion versus nonsurgical treatment for chronic low back pain: a multicenter randomized controlled trial from the Swedish lumbar spine study group.

The current debate over the efficacy of lumbar fusion for low back pain has not been settled. Fritzell et al published a landmark paper entitled "Lumbar fusion versus nonsurgical treatment for chronic low back pain: a multicenter randomized controlled trial from the Swedish lumbar spine study group." Their goal was to provide objective evidence supporting lumbar fusion. While it was well designed and important to our knowledge base, it has limitations. We set out to review their work in an unbiased yet critical manner. Our goals are to summarize the strengths and weaknesses of the paper, place it in the context of current knowledge, and highlight its significance for present-day practice and research. From technical and study design perspectives, Fritzell et al were able to validate the use of lumbar fusion for the treatment of low back pain. However, their use of "usual nonoperative" care and nonspecific definition of low back pain precluded a truly genuine comparison of operative and nonoperative groups. We commend the Swedish lumbar spine study group and their remarkable efforts; they elevated the sophistication of spine research and spawned many more excellent works to help settle the ongoing controversy on the ideal treatment of low back pain.

Awards and Prizes↗
PubMed2006

Development of a preliminary index that predicts adverse events after total knee replacement.

OBJECTIVE: We undertook this study to assess the relationships between hospital characteristics, volume of procedures, and perioperative outcomes after total knee replacement (TKR), and to use this information to construct a simple predictive index for perioperative outcomes that incorporates hospital- and patient-level characteristics. METHODS: We studied Medicare beneficiaries who underwent TKR in 4 US states in 2000. Orthopedic surgery administrators from hospitals caring for patients in this sample were surveyed about a range of hospital characteristics. The relationships between these hospital characteristics, patient variables, and 90-day postoperative adverse events (including death, pulmonary embolus, pneumonia, deep wound infection, and acute myocardial infarction) were assessed using generalized estimating equations adjusting for hospital volume. These relationships were assessed in low- and high-risk patient groups. Variables from the final multivariate model were used to create an index that was tested against 90-day adverse event rates. RESULTS: Three hundred twenty-seven (3.6%) of the patients undergoing TKR in our sample experienced an adverse event. In the final multivariate regression models, variables that predicted adverse perioperative events included low hospital volume (fewer than 23 TKRs in the Medicare population per year), absence of a preoperative teaching program, fewer TKRs conducted in a dedicated orthopedic surgery operating room, patient age >70 years, male sex, and at least 1 comorbid condition. The effect of volume on perioperative adverse events was evident both in patients with few risk factors and in patients with several risk factors. An index including the 6 patient and hospital variables discriminated well, with adverse events occurring in 2.0% (95% confidence interval [95% CI] 1.4-2.7%) of patients in the lowest risk category and in 7.4% (95% CI 4.5-12.3%) of patients in the highest risk category (P for trend < 0.001). The index predicted adverse event rates both in hospitals with a low volume of TKRs and in those with a high volume of TKRs. CONCLUSION: Characteristics of hospital care, procedure volume, and patient-level factors are all associated with perioperative outcomes of TKR. A preliminary index combining hospital characteristics and volume is moderately predictive of adverse perioperative outcomes. The index is predictive of outcome in low- and high-volume hospitals.

Aged↗
PubMed2006

Performance of an automated computer-based scoring method to assess joint space narrowing in rheumatoid arthritis: a longitudinal study.

OBJECTIVE: To compare the diagnostic performance of a computer-based method for measuring joint space width with the Sharp joint space narrowing (JSN) scoring method in patients with rheumatoid arthritis (RA). METHODS: A random sample of patients with early RA, for whom sequential hand radiographs and Sharp scores were available, was selected from the National Data Bank for Rheumatic Diseases. Hand joint space width was measured using an automated, computer-based method in random order and with blinding for clinical information. We constructed a receiver operating characteristic curve and compared the diagnostic performance of the computer-based and Sharp methods based on the areas under the curve. RESULTS: One hundred twenty-nine patients with early RA who underwent serial radiography were included. Changes in the computer-based and Sharp methods were highly correlated (r = 0.75, P < 0.001). The computer-based method was significantly more discriminant than the Sharp JSN subscale. The area under the curve of the computer-based method was 0.96 (95% confidence interval [95% CI] 0.94, 0.99) compared with 0.93 (95% CI 0.89, 0.96) for the Sharp subscale (P = 0.024). At the most discriminant cutoff, specificity of the computer-based method was 88.4% compared with 81.4% for the Sharp subscale (P = 0.11); sensitivity was 87.6% for the computer-based method compared with 82.2% for Sharp subscale (P = 0.19). The signal-to-noise ratio for the computer-based method was 83% compared with 70% for the Sharp subscale (P = 0.013). CONCLUSION: The computer-based method for measuring joint space width is more discriminant than the semiquantitative Sharp JSN subscale.

Adult↗
PubMed2006

Total joint replacement in osteoarthritis.

Surgical approaches have been developed for most of the sites of osteoarthritis, including the carpal metacarpal and first metatarsal phalangeal joint, the hips, knees, shoulders, ankles and elbows. This chapter will address surgical options for advanced osteoarthritis of the hips and knees and will focus primarily on total hip and knee replacement.

Arthroplasty, Replacement↗
PubMed2006

Lumbar disc disorders and low-back pain: socioeconomic factors and consequences.

Socioeconomic factors are important risk factors for lumbar pain and disability. The total costs of low-back pain in the United States exceed $100 billion per year. Two-thirds of these costs are indirect, due to lost wages and reduced productivity. Each year, the fewer than 5% of the patients who have an episode of low-back pain account for 75% of the total costs. Because indirect costs rely heavily on changes in work status, total costs are difficult to calculate for many women and students as well as elderly and disabled patients. These methodologic challenges notwithstanding, the toll of lumbar disc disorders is enormous, underscoring the critical importance of identifying strategies to prevent these disorders and their consequences.

Adolescent↗
PubMed2005

Compliance with osteoporosis medications.

BACKGROUND: Long-term compliance with pharmacologic treatments for many asymptomatic conditions may be suboptimal, but little is known about compliance with medications used for osteoporosis. This study was undertaken to assess the level and determinants of compliance with drugs prescribed for osteoporosis. METHODS: This retrospective cohort study used pharmacy claims data from US Medicare and filled prescriptions from a state pharmaceutical benefits program. We included persons 65 years or older who initiated use of a medication for osteoporosis (alendronate sodium, calcitonin, hormone therapy, raloxifene hydrochloride, or risedronate) from January 1, 1996, through December 31, 2002. The outcome of interest was suboptimal medication compliance, defined as equal to or less than 66% of days with medication during a 60-day period. RESULTS: One year after initiating treatment for osteoporosis, 45.2% of the 40,002 patients were not continuing to fill prescriptions. Five years after initiation, 52.1% of patients were not continuing to fill prescriptions for an osteoporosis medication. Several characteristics independently predicted compliance: female sex, younger age, fewer comorbid conditions, using fewer nonosteoporosis medications, bone mineral density testing before and after initiating a medication, a fracture before and after initiating a medication, and nursing home residence during the 12 months before initiating a medication. However, models adjusted for the significant patient variables explained only 6% of the variation in compliance. CONCLUSIONS: Most patients who initiate a medication for osteoporosis do not continue to take it as prescribed. Although several patient characteristics significantly correlated with compliance, adjusted models explained little of the variation.

Age Distribution↗
PubMed2005

Offering patients the opportunity to choose their hospital for total knee replacement: impact on satisfaction with the surgery.

OBJECTIVE: To describe the extent to which patients were offered a choice between 2 or more hospitals for total knee replacement (TKR); to examine the association between having a choice of hospital for TKR and satisfaction with the surgery; and to identify population groups less likely to be offered a choice. METHODS: We studied a population-based sample of 932 Medicare beneficiaries who underwent elective TKR in 2000. We surveyed patients about their participation in choosing a hospital and their satisfaction with surgery. We examined whether lack of hospital choice influenced satisfaction with surgery after adjusting for age, sex, preoperative function, and socioeconomic status. RESULTS: Among 932 TKR recipients (mean age 74 years, 67% women), more than half (53%) reported having a lack of hospital choice. After adjusting for socioeconomic status, patients reporting lack of choice were approximately twice as likely to be dissatisfied with the results of surgery as patients who reported choosing among 2 or more hospitals for TKR (odds ratio [OR] 2.09, 95% confidence interval [95% CI] 1.13-3.87). Results of logistic regression revealed that patients reporting lack of choice were more likely to be women (OR 1.52, 95% CI 1.14-2.04), >80 years of age (as compared with 65-70 years; OR 1.63, 95% CI 1.03-2.57), living in suburban areas (OR 1.68, 95% CI 1.23-2.30), nonwhite (OR 1.57, 95% CI 0.86-2.87), and were less likely to have TKR performed by a high-volume surgeon (OR 0.71, 95% CI 0.53-0.96). CONCLUSION: More than half of the patients did not have a choice in selecting the hospital where they had TKR. Patients reporting lack of choice were more likely to be dissatisfied with surgery. Interventions to address preferences for hospital may improve satisfaction with care for patients with advanced knee arthritis.

Aged↗
PubMed2005

Pressure pain thresholds and musculoskeletal morbidity in automobile manufacturing workers.

OBJECTIVES: Reduced pressure pain thresholds (PPTs) have been reported in occupational groups with symptoms of upper extremity musculoskeletal disorders (UEMSDs). The purpose of this study was to determine whether automobile manufacturing workers (n=460) with signs and symptoms of UEMSDs had reduced PPTs (greater sensitivity to pain through pressure applied to the skin) when compared with unaffected members of the cohort, which served as the reference group. The association of PPTs with symptom severity and localization of PE findings was investigated, as was the hypothesis that reduced thresholds would be found on the affected side in those with unilateral physical examination (PE) findings. METHODS: PPTs were measured during the workday at 12 upper extremity sites. A PE for signs of UEMSDs and symptom questionnaire was administered. After comparison of potential covariates using t tests, linear regression multivariable models were constructed with the average of 12 sites (avgPPT) as the outcome. RESULTS: Subjects with PE findings and/or symptoms had a statistically significant lower avgPPT than non-cases. AvgPPT was reduced in those with more widespread PE findings and in those with greater symptom severity (test for trend, P</=0.05). No difference between side-specific avgPPT was found in those with unilateral PE findings. Reduced PPTs were associated with female gender, increasing age, and grip strength below the gender-adjusted mean. After adjusting for the above confounders, avgPPT was associated with muscle/tendon PE findings and symptom severity in multivariable models. CONCLUSIONS: PPTs were associated with signs and symptoms of UEMSDs, after adjusting for gender, age and grip strength. The utility of this noninvasive testing modality should be assessed on the basis of prospective large cohort studies to determine if low PPTs are predictive of UEMSDs in asymptomatic individuals or of progression and spread of UEMSDs from localized to more diffuse disorders.

Adult↗
PubMed2005

Development and assessment of indicators of rheumatoid arthritis severity: results of a Delphi panel.

OBJECTIVE: To develop a set of indicators for assessing the severity of rheumatoid arthritis (RA) through medical records. METHODS: A list of 47 potential indicators of RA was reviewed by an expert Delphi panel of 6 rheumatologists. The Delphi method is a formal approach for gathering expert opinion. The 47 potential indicators included items from the following 5 categories: radiologic and laboratory findings, clinical and functional status measures, extraarticular manifestations, prior surgical history, and medications. The panelists rated the potential indicators' relationship to RA disease severity. Each panelist rated each indicator on a scale of 0-6, in which 0 indicated no relationship at all with severe RA and 6 indicated a perfect relationship with severe RA. After a baseline set of ratings, a literature review was distributed to the panelists along with the panel's initial mean ratings and the ranges. The panelists then met to discuss the literature and rerate all indicators. RESULTS: After repeat ratings and review of relevant literature, the panel rated 28 of 47 (60%) potential indicators as having a strong or very strong relationship to severe RA. These 28 indicators were drawn from all 5 categories of potential indicators. There was agreement among the panelists on ratings for 41 of 47 indicators. Agreement was defined as a range of scores among the panelists </=3. CONCLUSION: A Delphi panel of rheumatologists agreed that data generally available in medical records may serve as potential indicators of severe RA.

Antirheumatic Agents↗
PubMed2005

Osteoporosis action: design of the healthy bones project trial.

Although osteoporosis is common in older adults, it is often under-diagnosed and under-treated. We developed community-based patient- and physician-directed interventions for fracture prevention and compared them in a 2 x 2 factorial randomized controlled trial. The study population included older adults who were enrolled in a state-run pharmacy benefits program (The Pharmaceutical Assistance Contract for the Elderly in Pennsylvania) for Medicare beneficiaries. We randomly assigned 826 primary care physicians and their 31,715 patients to one of four trial arms--no patient and no physician intervention, patient but no physician intervention, physician but no patient intervention, both patient and physician interventions. The patient intervention consisted of targeted communication about fall and fracture prevention and osteoporosis diagnosis and treatment. It was delivered through several mailings. The physician intervention entailed one-on-one academic detailing encounters covering the same topics. The composite primary endpoint consisted of use of osteoporosis medication or a bone mineral density test. Other endpoints included patient's knowledge and attitudes towards fractures and osteoporosis, use of lower extremity strengthening to prevent falls, and the occurrence of fractures. All outcomes will be analyzed using random effects models accounting for clustering of subjects within physicians' practices.

Aged↗
PubMed2005

Determinants of work absence following surgery for carpal tunnel syndrome.

BACKGROUND: The objective was to identify factors across multiple domains associated with return to work in a community-based cohort of workers with carpal tunnel syndrome. METHODS: Workers scheduled for carpal tunnel release were recruited into this prospective study. Subjects completed questionnaires preoperatively and at 2, 6, and 12 months postoperatively. The questionnaires contained demographic, clinical, and psychosocial factors and physical and psychosocial workplace stressors. Predictors of work absence at 6 and 12 months were examined in bivariate and multivariate logistic regression analyses. RESULTS: Six months following surgery of 181 subjects, 29 (19%) were out of work. Twelve months postoperatively 33 subjects (22%) were out of work. In bivariate analyses, the factors associated with work absence at 6 months, at P < or = 0.01, included preoperative physical functional status, change in self-efficacy between preoperative assessment and 2 months, lower income, workers' compensation, representation by an attorney, work exposure to force and repetition, higher psychological job demands and lower control, lower social support by coworkers, lower job security and more supportive organizational policies and practices. The factors associated with work absence at 12 months in bivariate analyses included preoperative physical functional status, lower self-efficacy at 2 months, workers' compensation, and less supportive organizational policies and practices. Multivariate analyses documented a multidimensional model, with predictors from multiple domains. CONCLUSIONS: Clinical, demographic, economic, and workplace factors were associated with work absence. Strategies to reduce work absence following carpal tunnel release should address multiple dimensions of the worker and workplace.

Carpal Tunnel Syndrome↗
PubMed2005

Trends in epidemiology of knee arthroplasty in the United States, 1990-2000.

OBJECTIVE: There is little information on longitudinal trends in the epidemiology of total knee arthroplasty (TKA). This study was undertaken to determine whether, during the past decade, TKA rates increased in younger adults and older adults, whether utilization of TKA increased among minorities, and whether more patients underwent surgery at high-volume hospitals. METHODS: TKA cases (n = 443,008) were extracted from the 1990-2000 Nationwide Inpatient Sample database. TKA trends for 3 time periods were obtained (1990-1993 [period I], 1994-1997 [period II], and 1998-2000 [period III]). RESULTS: Between period I and period III, the proportion of TKAs performed increased by 95.2% in the 40-49-year age group and by 53.7% in the 50-59-year age group. Black patients and Hispanic patients were more likely to undergo TKA in period III than in period I (odds ratio [OR] = 1.6, 95% confidence interval [95% CI] 1.5-1.6 and OR 2.7, 95% CI 2.5-2.9, respectively). However, white patients accounted for 93.0%, 89.9%, and 87.5% of TKAs in the 3 time periods, respectively. In period III, the proportion of patients undergoing surgery in high-volume hospitals increased compared with periods I and II. Both mortality and length of hospital stay diminished significantly in period III, but the rate of discharge to an inpatient facility increased by 89.7% (period I to period III). CONCLUSION: Over the past decade, TKA was increasingly performed in younger patients, which suggests a broadening of indications for this procedure. Although utilization of TKA increased among minorities, the vast majority of TKAs were performed in white patients. Further efforts to narrow this disparity are required. The shift toward TKAs being increasingly performed at high-volume centers may improve surgical outcomes. Finally, the effect of increased discharge to inpatient facilities on TKA outcomes needs to be ascertained.

Adult↗