The creation and validation of the Jamaica Personality Disorder Inventory.

OBJECTIVE: To describe the creation and validation of the Jamaica Personality Disorder Inventory (JPDI) screening questionnaire. METHOD: Using the phenomenological triad of power management, dependency and psychosexual issues, drafts of the JPDI were piloted on patients from psychiatric and medical wards. The JPDI consisted of 38 close-ended, yes/no questions. Validation was conducted in a sample of 200 patients, using the International Personality Disorder Examination-Screening Instrument (IPDE-S), the Brief Screen for Depression and consultant psychiatrists' Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) personality disorder interview. Construct validity was assessed through principal component factor analysis; Spearman correlation was used to assess criterion-related and discriminant validity; Cronbach's alpha was used to assess reliability of the entire scale as well as the resulting factors. The Multitrait Multimethod Matrix (MTMM) was used to assess discriminant and construct validity. RESULTS: Factor analysis revealed eight clusters consisting of 30 of the 38 questions, which had close congruence with the clinical triad. Cronbach's alpha for the entire scale was α = 0.79, ranging from a high 0.70 to 0.82 to low 0.63 to 0.45. The JPDI exhibited a sensitivity of 95.06% and a specificity of 67.71%. Significant correlation of scores for the JPDI and IPDE-S (r = 0.432, p = 0.000) and the JPDI and the DSM IV-TR diagnosis (r = 0.598, p = 0.000) established concurrent validity for the JPDI. Correlations (r = 0.293, p = 0.000) suggested that the JPDI possessed predictive validity. The complete sample matrix of the MTMM provided evidence of both convergent and discriminant validity, and thereby, construct validity. CONCLUSION: The JPDI demonstrated reliability, and criterion-related and discriminant validity.

Permanent pacemaker insertion after CoreValve transcatheter aortic valve implantation: incidence and contributing factors (the UK CoreValve Collaborative).

BACKGROUND: Permanent pacemaker (PPM) requirement is a recognized complication of transcatheter aortic valve implantation. We assessed the UK incidence of permanent pacing within 30 days of CoreValve implantation and formulated an anatomic and electrophysiological model. METHODS AND RESULTS: Data from 270 patients at 10 centers in the United Kingdom were examined. Twenty-five patients (8%) had preexisting PPMs; 2 patients had incomplete data. The remaining 243 were 81.3±6.7 years of age; 50.6% were male. QRS duration increased from 105±23 to 135±29 milliseconds (P<0.01). Left bundle-branch block incidence was 13% at baseline and 61% after the procedure (P<0.001). Eighty-one patients (33.3%) required a PPM within 30 days. Rates of pacing according to preexisting ECG abnormalities were as follows: right bundle-branch block, 65.2%; left bundle-branch block, 43.75%; normal QRS, 27.6%. Among patients who required PPM implantation, the median time to insertion was 4.0 days (interquartile range, 2.0 to 7.75 days). Multivariable analysis revealed that periprocedural atrioventricular block (odds ratio, 6.29; 95% confidence interval, 3.55 to 11.15), balloon predilatation (odds ratio, 2.68; 95% confidence interval, 2.00 to 3.47), use of the larger (29 mm) CoreValve prosthesis (odds ratio, 2.50; 95% confidence interval, 1.22 to 5.11), interventricular septum diameter (odds ratio, 1.18; 95% confidence interval, 1.10 to 3.06), and prolonged QRS duration (odds ratio, 3.45; 95% confidence interval, 1.61 to 7.40) were independently associated with the need for PPM. CONCLUSION: One third of patients undergoing a CoreValve transcatheter aortic valve implantation procedure require a PPM within 30 days. Periprocedural atrioventricular block, balloon predilatation, use of the larger CoreValve prosthesis, increased interventricular septum diameter and prolonged QRS duration were associated with the need for PPM.

Use of respiratory function tests to predict survival in amyotrophic lateral sclerosis.

Respiratory function tests (RFTs) are commonly used as a measure of progression in ALS. This study assessed the ability of various RFTs to predict survival in ALS patients. Subjects with ALS had one or more measurements of seated and supine FVC, maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP). Kaplan-Meier (KM) analysis was used to determine whether patients with abnormal RFTs had shorter survival than those with normal RFTs. The sensitivity and specificity of RFTs as predictors of two-year survival were calculated from receiver operating characteristic (ROC) curves. With KM analysis, subjects with abnormal values of seated FVC, supine FVC, MIP and MEP had significantly reduced survival compared to subjects with normal values. With ROC curves, a normal supine FVC was highly predictive for two-year survival and had superior sensitivity over seated FVC. Slower rates of decline in seated or supine FVC were strong predictors of two-year survival. Our study demonstrates that respiratory function measurements are useful to predict survival in ALS patients. We show that measurements of FVC in the supine position are worth including in the assessment of respiratory function in ALS.

Obesity pharmacotherapy from a regulatory perspective: overview and key challenges.

Obesity is an epidemic with tremendous impact on both patients and health-care systems globally. This paper explores some of the questions related to the clinical development of new pharmacotherapies in the context of an evolving regulatory perspective. These include patient entry criteria, clinical database size, study designs, weight loss end points (including those for maintenance of weight loss and prevention of weight regain), clinically important patient-reported outcomes, comorbidity/risk factor end points, and challenges in establishing safety and efficacy in adolescent/pediatric patients, and approaches to the development of combination pharmacotherapies. Ultimately, patients, physicians, academia, industry, payers, and governments must continue to partner with regulators to help establish the appropriate balance between the known adverse consequences associated with inadequate treatment of the growing obesity epidemic and the concern for potential unknown risks that may be associated with the long-term use of new pharmacotherapies.

Expression of 92-kD type IV collagenase/gelatinase (gelatinase B) in osteoarthritic cartilage and its induction in normal human articular cartilage by interleukin 1.

We report here that a 92-kD gelatinolytic metalloproteinase is expressed as protein and mRNA in human osteoarthritic cartilage, but not in normal adult articular cartilage. Western immunoblotting demonstrated that the 92-kD gelatinolytic activity corresponded to 92-kD type IV collagenase/gelatinase (gelatinase B); mRNA for gelatinase B was identified by Northern blotting. Chondrocytes from normal cartilage also exhibited mRNA for 72-kD type IV collagenase/gelatinase (gelatinase A), tissue collagenase, and stromelysin-1, and these mRNAs were increased in osteoarthritic cartilage. Regional analysis of osteoarthritic cartilage samples from four individuals revealed that gelatinase B mRNA was expressed in grossly fibrillated areas; two of four nonfibrillated cartilage samples failed to exhibit the mRNA, but did have increased levels of mRNA for other neutral metalloproteinases. IL-1 alpha treatment of normal human cartilage explants or isolated chondrocytes induced increased levels of gelatinase B and increased mRNA for tissue collagenase and stromelysin-1. Under identical conditions, mRNA levels for gelatinase A were not increased indicating that regulation of this enzyme in human articular chondrocytes is distinct from that of other metalloproteinases. Our data showing expression of gelatinase B in fibrillated cartilage suggest that it is a marker of progressive articular cartilage degradation in osteoarthritis.

Aggrecan degradation in human cartilage. Evidence for both matrix metalloproteinase and aggrecanase activity in normal, osteoarthritic, and rheumatoid joints.

To examine the activity of matrix metalloproteinases (MMPs) and aggrecanase in control and diseased human articular cartilage, metabolic fragments of aggrecan were detected with monospecific antipeptide antibodies. The distribution and quantity of MMP-generated aggrecan G1 fragments terminating in VDIPEN341 were compared with the distribution of aggrecanase-generated G1 fragments terminating in NITEGE373. Both types of G1 fragments were isolated from osteoarthritic cartilage. The sizes were consistent with a single enzymatic cleavage in the interglobular domain region, with no further proteolytic processing of these fragments. Both neoepitopes were also detected by immunohistochemistry in articular cartilage from patients undergoing joint replacement for osteoarthritis (OA), rheumatoid arthritis (RA), and in cartilage from adults with no known joint disease. In control specimens, the staining intensity for both G1 fragments increased with age, with little staining in cartilage from 22-wk-old fetal samples. There was also an increase with age in the extracted amount of MMP-generated neoepitope in relation to both aggrecan and collagen content, confirming the immunohistochemical results. After the age of 20-30 yr this relationship remained at a steady state. The staining for the MMP-generated epitope was most marked in control cartilage exhibiting histological signs of damage, whereas intense staining for the aggrecanase-generated fragment was often noted in adult cartilage lacking overt histological damage. Intense staining for both neoepitopes appeared in the more severely fibrillated, superficial region of the tissue. Intense immunostaining for both VDIPEN- and NITEGE- neoepitopes was also detected in joint cartilage from patients with OA or RA. Cartilage in these specimens was significantly more degraded and high levels of staining for both epitopes was always seen in areas with extensive cartilage damage. The levels of extracted VDIPEN neoepitope relative to collagen or aggrecan in both OA and RA samples were similar to those seen in age-matched control specimens. Immunostaining for both types of aggrecan fragments was seen surrounding the cells but also further removed in the interterritorial matrix. In some regions of the tissue, both neoepitopes were found while in others only one was detected. Thus, generation and/or turnover of these specific catabolic aggrecan fragments is not necessarily coordinated. Our results are consistent with the presence in both normal and arthritic joint cartilage of proteolytic activity against aggrecan based on both classical MMPs and "aggrecanase."

Consensus recommendations for using the Multiplate(®) for platelet function monitoring before cardiac surgery.

Patients requiring urgent cardiac surgery are usually already taking antiplatelet drugs including aspirin and a P2Y12 ADP receptor antagonist (e.g., clopidogrel, prasugrel or ticagrelor). This presents clinicians with the challenge of balancing the risk of thrombotic complications, if antiplatelet drugs are stopped before surgery, with the problems of excessive bleeding when surgery is performed in the absence of adequate platelet function. Preoperative platelet function monitoring is able to identify when patients have recovered platelet function. The Multiplate(®) (multiple electrode impedance platelet aggregometer) is a point of care device that enables monitoring of platelet function. The authors offer recommendations based on real-world, collective experience in the use of platelet function monitoring. These cover the use of the Multiplate(®) analyser to predict the need for platelet transfusion in the perioperative period and the individualized waiting period after cessation of P2Y12 ADP receptor antagonists before cardiac surgery.

The potential role of fibroblasts in periprosthetic osteolysis: fibroblast response to titanium particles.

Periprosthetic osteolysis with or without aseptic loosening is a major clinical problem in total hip arthroplasty. While the macrophage response to prosthetic wear debris and its role in periprosthetic osteolysis has been extensively studied, information regarding other cell types (fibroblasts, osteoblasts) is limited. This study explored the response of fibroblasts to particulate wear debris. Fibroblasts isolated from interfacial membranes of patients with failed total hip replacements and normal synovial tissue, when challenged with small-sized ( < 3 microns) titanium (Ti) particles, responded with significantly enhanced expressions of collagenase, stromelysin and, to a much lesser extent, their tissue inhibitor of metalloproteinases (TIMP). These "regulated" expressions at both mRNA and protein levels were correlated with the size and composition of particles. De novo protein synthesis was required for the regulation of these mRNAs. A similar effect could be induced by the treatment of the cells with particle-free conditioned medium from Ti particle-stimulated fibroblasts. Furthermore, this conditioned medium significantly suppressed the mRNA levels of procollagen alpha 1 (I) and alpha 1 (III) in osteoblast-like MG-63 cells. It is concluded that fibroblasts stimulated with certain particle debris may play an important role in periprosthetic osteolysis by releasing bone-resorbing metalloproteinases and mediator(s) which resulted in suppressed collagen synthesis in osteoblasts.

Containment of pertussis in the regional pediatric hospital during the Greater Cincinnati epidemic of 1993.

OBJECTIVE: To describe methods of preventing nosocomial pertussis in patients, employees, and visitors to a hospital during a communitywide epidemic in Greater Cincinnati. DESIGN: Six-month descriptive study of the methods, effectiveness, and cost of a program to prevent nosocomial pertussis. SETTING: Three hundred sixty-one bed, tertiary-care, university, pediatric hospital. RESULTS: We educated 3,764 hospital employees about pertussis. We evaluated 206 employees with respiratory illnesses, based on clinical presentation, pertussis exposure, and work setting. Eighty-seven had pertussis: 84 coughed for > or = 2 weeks (outbreak clinical case definition), 65 had paroxysms, 27 whooped, 22 had posttussive emesis, and 13 were positive by direct fluorescent antibody or culture for Bordetella pertussis. Seventy-nine employees were sent on 5-day furloughs. Six hundred twenty-two employees received 14 days of erythromycin (579) or trimethoprim-sulfamethoxazole (43). Symptomatic patients were identified at triage in the emergency department and placed in respiratory isolation. Suspect pertussis cases were admitted in respiratory isolation. Among 49 toddlers who were given erythromycin and managed in "coughing respiratory cohorts," eight had proven pertussis. Inpatients were restricted to assigned nursing units. Respiratory masks were required for those entering the test referral center, where more than 3,500 pertussis cultures were performed. Hospitalwide visitor restriction was enforced for those aged 14 years or younger and for those with respiratory symptoms. Only parents and guardians were permitted to visit the newborn intensive care unit. A child-care service managed 488 inpatient sibling visitors. Four symptomatic children in the employees' child-care center were excluded pending physician evaluation; one had pertussis. CONCLUSIONS: Control measures appeared effective. Pertussis occurred in 87 (2%) employees. Among 102 children hospitalized with pertussis, respiratory isolation was delayed in nine cases, and one case was nosocomial. Program expenses totalled $85,400. Adult booster immunization with acellular pertussis vaccine might represent the safest and least expensive strategy for preventing epidemic pertussis, and controlled trials of acellular pertussis vaccine in hospital employees are needed.

Clinical comparison of Sentinel, a novel blood culture system, with radiometric Bactec 460 and Isolator 10 in the detection of streptococcal and anaerobic bacteraemias.

AIMS: To compare the performance of the Sentinel blood culture system with two other systems for the recovery of streptococci and anaerobes. METHODS: Blood cultures were taken from 55 patients one to two minutes after dental extraction. The samples were tested by the radiometric Bactec 460; the Isolator 10, which works by lysis centrifugation; and Sentinel, a fully automated system, which detects bacterial growth by changes in the voltage between two electrodes in the media. Positive samples were subcultured and streptococci and anaerobes were further identified. Terminal subcultures were performed on all negative samples. RESULTS: Sentinel was comparable with Bactec, with Sentinel recovering 20 streptococci and 14 anaerobes; Bactec isolated 26 streptococci and 15 anaerobes. The recovery of Streptococcus sanguis was significantly better from Bactec than Sentinel. The Isolator 10 recovered significantly fewer streptococci and anaerobes than either Bactec or Sentinel. Sentinel was noticeably quicker in detecting anaerobes than Bactec 460. However, there was no comparable difference with streptococci. Contaminants were recovered from 10% of Isolator 10, 2.7% of Bactec, and 7.2% of Sentinel bottles. CONCLUSIONS: Sentinel and Bactec 460 were broadly comparable in the detection of viridans streptococci and oral anaerobes, and both systems were significantly better than the Isolator 10. However, the prototype Sentinel, was significantly poorer than Bactec for the recovery of S sanguis.

The clinical comparison of Oxoid Signal with Bactec blood culture systems for the detection of streptococcal and anaerobic bacteraemias.

Blood cultures were taken from 47 patients 1-2 min after dental extraction. These samples were tested by the radiometric Bactec 460 and Oxoid Signal systems for the detection of streptococcal and anaerobic bacteraemias. Streptococci were isolated from 19 (40%) patients and anaerobes from 15 (32%). In this study the Oxoid Signal system was significantly better for isolating oral anaerobes than the Bactec system; five isolates were obtained with the Bactec system and 14 with the Signal system. There was no significant difference in the isolation of streptococci between these two systems (Bactec 14, Oxoid Signal 10). The contamination rate was 4.1% for Bactec and 7.5% for the Oxoid Signal system.

Effects of fluid-induced shear on articular chondrocyte morphology and metabolism in vitro.

This study tested the effects of fluid-induced shear on high density monolayer cultures of adult articular chondrocytes. Fluid-induced shear (1.6 Pa) was applied by cone viscometer to normal human and bovine articular chondrocytes for periods of 24, 48, and 72 hours. At 48 and 72 hours, fluid-induced shear caused individual chondrocytes to elongate and align tangential to the direction of cone rotation. Fluid-induced shear stimulated glycosaminoglycan synthesis by 2-fold (p < 0.05) and increased the length of newly synthesized chains in human and bovine chondrocytes. In human chondrocytes, the hydrodynamic size of newly synthesized proteoglycans also was increased. After 48 hours of fluid-induced shear, the release of prostaglandin E2 from the chondrocytes was increased 10 to 20-fold. In human chondrocytes, mRNA signal levels for tissue inhibitor of metalloproteinase increased 9-fold in response to shear compared with the controls. In contrast, mRNA signal levels for the neutral metalloproteinases, collagenase, stromelysin, and 72 kD gelatinase, did not show such major changes. This study demonstrated that articular chondrocyte metabolism responds directly to physical stimulation in vitro and suggests that mechanical loading may directly influence cartilage homeostasis in vivo.

Ultra scale-down approach to correct dispersive and retentive effects in small-scale columns when predicting larger scale elution profiles.

Ultra scale-down approaches represent valuable methods for chromatography development work in the biopharmaceutical sector, but for them to be of value, scale-down mimics must predict large-scale process performance accurately. For example, one application of a scale-down model involves using it to predict large-scale elution profiles correctly with respect to the size of a product peak and its position in a chromatogram relative to contaminants. Predicting large-scale profiles from data generated by small laboratory columns is complicated, however, by differences in dispersion and retention volumes between the two scales of operation. Correcting for these effects would improve the accuracy of the scale-down models when predicting outputs such as eluate volumes at larger scale and thus enable the efficient design and operation of subsequent steps. This paper describes a novel ultra scale-down approach which uses empirical correlations derived from conductivity changes during operation of laboratory and pilot columns to correct chromatographic profiles for the differences in dispersion and retention. The methodology was tested by using 1 mL column data to predict elution profiles of a chimeric monoclonal antibody obtained from Protein A chromatography columns at 3 mL laboratory- and 18.3 L pilot-scale. The predictions were then verified experimentally. Results showed that the empirical corrections enabled accurate estimations of the characteristics of larger-scale elution profiles. These data then provide the justification to adjust small-scale conditions to achieve an eluate volume and product concentration which is consistent with that obtained at large-scale and which can then be used for subsequent ultra scale-down operations.

The creation and validation of the Jamaica personality disorder inventory / Creación y validación del inventario de trastornos de la personalidad en Jamaica

OBJECTIVE: To describe the creation and validation of the Jamaica Personality Disorder Inventory (JPDI) screening questionnaire. METHOD: Using the phenomenological triad of power management, dependency and psychosexual issues, drafts of the JPDI were piloted on patients from psychiatric and medical wards. The JPDI consisted of 38 close-ended, yes/no questions. Validation was conducted in a sample of 200 patients, using the International Personality Disorder Examination-Screening Instrument (IPDE-S), the Brief Screen for Depression and consultant psychiatrists' Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) personality disorder interview. Construct validity was assessed through principal component factor analysis; Spearman correlation was used to assess criterionrelated and discriminant validity; Cronbach's alpha was used to assess reliability of the entire scale as well as the resulting factors. The Multitrait Multimethod Matrix (MTMM) was used to assess discriminant and construct validity. RESULTS: Factor analysis revealed eight clusters consisting of 30 of the 38 questions, which had close congruence with the clinical triad. Cronbach's alpha for the entire scale was α = 0.79, ranging from a high 0.70 to 0.82 to low 0.63 to 0.45. The JPDI exhibited a sensitivity of 95.06% and a specificity of 67.71%. Significant correlation of scores for the JPDI and IPDE-S (r = 0.432, p = 0.000) and the JPDI and the DSM IV-TR diagnosis (r = 0.598, p = 0.000) established concurrent validity for the JPDI. Correlations (r = 0.293, p = 0.000) suggested that the JPDI possessed predictive validity. The complete sample matrix of the MTMM provided evidence of both convergent and discriminant validity, and thereby, construct validity. CONCLUSION: The JPDI demonstrated reliability, and criterion-related and discriminant validity.

OBJETIVO: Describir la creación y validación del cuestionario de tamizaje del Inventario de Trastornos de la Personalidad en Jamaica (JPDI). MÉTODO: Usando la tríada fenomenológica de manejo del poder, dependencia y problemas psicosexuales, se realizaron pruebas pilotos usando versiones p rovisionales del JPDI con pacientes de salas médicas y psiquiátricas. El JPDI constaba de 38 preguntas cerradas, del tipo que requieren sí o no. La validación se realizó con una muestra de 200 pacientes, usando el Instrumento de Tamizaje del Examen Internacional de los Trastornos de Personalidad (IPDE-S), la Prueba Breve para la Depresión, y el Manual Diagnóstico y Estadístico de los Trastornos Mentales, cuarta edición (DSM-IV) de los psiquiatras consultantes, para entrevistas de trastornos de personalidad. La validez de constructo se evaluó a través de análisis factorial de componentes principales. El coeficiente de correlación de Spearman se utilizó para evaluar la validez de criterio y la validez discriminante. El coeficiente Alfa de Cronbach fue utilizado para evaluar la fiabilidad de toda la escala, así como los factores resultantes. La matriz multirasgo-multimétodo (MTMM) fue utilizada para evaluar la validez de constructo y la validez discriminante. RESULTADOS: El análisis factorial reveló ocho clústeres que constaban de 30 de las 38 preguntas, las cuales presentaban una estrecha congruencia con la tríada clínica. El Alfa de Cronbach para toda la escala fue α = 0.79, fluctuando desde valores altos de 0.70 a 0.82 hasta valores bajos de 0.63 a 0.45. El inventario JPDI mostró una sensibilidad de 95.06% y una especificidad de 67.71%. La correlación significativa de las puntuaciones para el JPDI y el IPDE-S (r = 0.432, p = 0.000) y el JPDI y el diagnóstico de DSM IV-TR (r = 0.598, p = 0.000) estableció una validez concurrente para el JPDI. Las correlaciones (r = 0.293, p = 0.000) sugirieron que el JPDI poseía validez predictiva. La matriz completa de la muestra de la MTMM proporcionó evidencia tanto de la validez discriminante como de la validez convergente, y por ende, de la validez de constructo. CONCLUSIÓN: El inventario JPDI demostró fiabilidad, así como validez de criterio y validez discriminante.