Jonathan M. Clive

Mathematical typology: a grade of membership technique for obtaining disease definition.

Abstract This paper describes a model based on fuzzy set-theoretic concepts for quantitatively identifying and characterizing subpatterns of illness within a broad disease class, based on the analysis of discrete clinical variables. Methodological and background matters are discussed, followed by derivation of maximum likelihood estimates of the model components. A numerical example from a study of patients with a type of congenital heart disease is presented.

Endodontic infection: some biologic and treatment factors associated with outcome☆

OBJECTIVE We sought to investigate the simultaneous effect of apical periodontitis, instrumentation level, and density of root canal filling on endodontic treatment outcome. METHODS For this study, 200 endodontically treated teeth with 441 roots were used. A follow-up examination was conducted 4 +/- 0.5 years postoperatively. Data were subjected to univariate and multivariate analysis. RESULTS Periapical pathosis had the strongest effect on treatment outcome (P <.0001). The instrumentation level (mean +/- SEM of the working length) for successfully treated teeth/roots with normal preoperative pulp and periapex was farther away from the radiographic apex (1.23 +/- 0.13 mm) than for teeth/roots with an unsuccessful outcome (0.20 +/- 0.09 mm; P <.005). However, successfully treated teeth/roots with pulp necrosis and apical periodontitis had working length levels closer to the radiographic apex (0.55 +/- 0.12 mm) than did teeth/roots with unsuccessful outcomes (1.73 +/- 0.30 mm; P<.001). In teeth/roots with apical periodontitis, a millimeter loss in working length increased the chance of treatment failure by 14%. The risk of failure was higher for a fair/poor density of obturation than for a good density for all diagnoses of periradicular status. CONCLUSION Diseased periapex, level of working length relative to the radiographic apex, and fair/poor density all affect the outcome of endodontic treatment.

Clinical Pure Types as a Fuzzy Partition

Abstract This paper discusses the applicability of the ideas of fuzzy sets and grades of membership to problems encountered in the quantification of clinical (i.e., diagnostic and prognostic) judgment. The methods of constrained maximum likelihood are used to derive consensus estimates of grades of membership given a set of categorical data and an a priori set of specified pure types. A numerical example is given.

Incidence and outcome of Clostridium difficile infection following autologous peripheral blood stem cell transplantation

A retrospective evaluation of 200 consecutive recipients of autologous peripheral blood stem cell transplantation (PBSCT) was conducted to ascertain the incidence and outcome of infection with Clostridium difficile. The diagnosis was confirmed in 14 patients with diarrhea (15 episodes) at a median of 33 days after stem cell infusion. Five patients were neutropenic at the time of diagnosis. Every individual had adverse known risk factors such as recent or current use of antibiotic, corticosteroid and antiviral therapy, recent administration of myelo- ablative chemotherapy and numerous, prolonged periods of hospitalization. Diarrhea, frequently hemorrhagic, was the most common presenting feature along with fever, abdominal cramps and abdominal distention. Diagnosis was established by the stool-cytotoxin test. Response to standard treatment with oral vancomycin or metronidazole was prompt despite the presence of several adverse prognostic features in these patients. There was only one instance of relapse which was also treated successfully. Several transplant-related variables such as age, sex, underlying malignancy, myelo-ablative regimen, duration of neutropenia, and prophylactic use of oral ampicillin underwent statistical analysis but failed to be predictive of C. difficile infection in such a setting. Finally, C. difficile is not uncommon after autologous PBSCT and must be included in the differential diagnosis in any such patient with diarrhea.

Common measures of asthma severity lack association for describing its clinical course

BACKGROUND AND OBJECTIVE To address the problems of increasing asthma morbidity and mortality rates, reliable severity measures must be identified. Accordingly, we compared three measures and their relationship to beclomethasone compliance. METHODS Three clinical measures (symptom scores, morning peak expiratory flow rates, and number of as needed albuterol inhalations with Nebulizer Chronologs [Forefront Technologies, Inc., Lakewood, Colo.]) were assessed daily in 13 adults with asthma for 8.9 +/- 2.1 weeks. The relationships among these three variables were analyzed in terms of Pearson correlation coefficients. These were evaluated for each of the three possible pairs of the three clinical measures for each of the 13 patients. The relationship between inhaled beclomethasone compliance and the pairwise correlations was studied with the use of nonparametric statistical procedures. RESULTS In four of the 13 patients, no pairwise correlations between any of the three severity measures were observed. The peak expiratory flow rate-symptom score relationship was observed in eight patients, whereas peak expiratory flow rate-albuterol use and albuterol use-symptom score correlations were each seen in four patients. Mean beclomethasone compliance was 64% and was greatest in those patients whose albuterol use increased concurrently with symptom scores (94% vs 50%, p = 0.02). CONCLUSIONS The commonly used measures of asthma severity, symptom scores, peak flow rate, and beta-agonist use may not be interchangeable in describing the clinical course. Patients whose beta-agonist use is driven by symptoms tend to be more compliant with use of inhaled corticosteroids.

Varicella zoster virus infection associated with high-dose chemotherapy and autologous stem-cell rescue.

A retrospective evaluation of 215 consecutive recipients of high-dose chemotherapy (HDC) and autologous stem cell rescue (ASCR) was conducted to ascertain the incidence, temporal course, and outcome of varicella zoster virus (VZV) infection. Herpes zoster was identified in 40 individuals at a median of 69 days following ASCR. Six of these cases occurred at a median of 33 days prior to ASCR but following the initiation of high doses of stem cell mobilization chemotherapy. Twenty-five percent of patients demonstrated cutaneous or systemic dissemination and 32.5% required medical intervention for post-herpetic neuralgia. All except two individuals received antiviral chemotherapy. One patient with active VZV infection died of multiorgan failure 39 days after ASCR. Multivariate analysis of risk factors disclosed the significance of prophylactic acyclovir use in Herpes simplex virus seropositive individuals in reducing the risk of VZV infection. Moreover, the use of busulfan, thiotepa and carboplatin as the conditioning chemotherapy regimen was associated with an increased risk of subsequent VZV infection. The incidence of VZV reactivation after HDC and ASCR is similar to that observed following bone marrow transplantation but has an earlier onset. This may be related to an earlier induction of immunosuppression by stem cell mobilization chemotherapy administered prior to ASCR. We demonstrated a marked reduction in the proliferative and synthetic capacities of peripheral blood mononuclear cells obtained prior to and following stem cell mobilizing chemotherapy. Moreover, greater than 80% of VZV infections occurred within 6 months following ASCR and late cases were seldom observed compared to allogeneic and autologous bone marrow transplantation. The role of antiviral chemoprophylaxis during the period of maximum immunocompromise needs to be studied further in the HDC-ASCR setting.

Cytomegalovirus viremia, viruria and disease after autologous peripheral blood stem cell transplantation: no need for surveillance.

A retrospective evaluation of 200 consecutive recipients of autologous peripheral blood stem cell transplantation (PBSCT) was conducted to ascertain the incidence, risk factors, clinical features, complications, and outcome of cytomegalovirus (CMV) infection. A total of 26 patients (13%) developed CMV viremia (n = 5), DNAemia (n = 3), viruria (n = 18) and/or disease (n = 3) at a median of 45 days following stem cell infusion. None of the patients underwent surveillance testing for CMV. A diagnosis was established by culture and polymerase chain reaction of blood, urine or other tissue samples submitted when patients exhibited clinical features suggestive of CMV infection. Cytomegalovirus seropositivity prior to transplantation was the only statistically significant risk factor predicting subsequent identification of CMV (P < 0.001). the symptoms were severe enough in 23 patients to warrant treatment with intravenous ganciclovir. three patients developed cmv disease; two developed fatal cmv pneumonia and one developed cmv gastritis which responded to antiviral treatment. clinical signs and symptoms as well as viremia and viruria resolved with (20 patients) and without (three patients) treatment in the remaining individuals. all instances of cmv viremia, dnaemia, viruria and disease occurred within 3 months of stem cell infusion. these results demonstrate that cmv is a common pathogen after autologous pbsct and may result in fatality in rare instances. surveillance programs appear to be neither useful nor cost-effective. diagnostic evaluation should be performed only in patients exhibiting suspicious clinical features and antiviral chemotherapy should be administered for persistent and severe signs and symptoms.

Streptococcus viridans bacteremia following autologous peripheral blood stem cell transplantation.

A retrospective evaluation of 200 consecutive recipients of autologous peripheral blood stem cell transplantation was conducted to ascertain the incidence and outcome of Streptococcus viridans bacteremia as well as to determine the role of prophylactic ampicillin therapy in the peri-transplant setting. Viridans streptococci were isolated from the blood of 35 individuals at a median of 6 days (range 2–8 days) following stem cell infusion. The most common isolates were S. sanguis and S. mitis. All patients received ciprofloxacin orally during the peri-transplant period. Additionally, 79 patients received oral ampicillin prophylactically against gram-positive cocci. Although none of the patients suffered a fatal outcome, three individuals developed respiratory compromise requiring mechanical ventilation. Female sex proved to be the only independent risk factor for viridans streptococcal bacteremia (P = 0.04). The shorter duration of neutropenia observed after stem cell transplantation did not impact on the incidence of S. viridans infections. Moreover, the prophylactic use of ampicillin failed to decrease the incidence of viridans sepsis and selected out organisms that were resistant to beta-lactam antibiotics.

Inguinal hernia in preterm infants (≤32-Week Gestation)

Abstract The current incidence of inguinal hernia (IH) in premature infants is not well-established. It is also unclear whether common co-morbidities in this population, i.e., chronic lung disease (CLD) or nutritional status or both contribute to the development of IH. The purpose of this study was to establish the epidemiologic profile of preterm infants of 32 weeks gestational age (GA) or less at birth with IH and determine whether the severity of CLD or poor nutritional status predisposes to the development of IH. Perioperative profiles of infants undergoing surgery were also reviewed. A retrospective study of 1,057 infants born at 23–32 weeks GA from January 1990 to December 1995 was done. Specific risk and demographic factors were identified. Factors used to determine severity of CLD were: days on intermittent mandatory ventilation (IMV); days on positive pressure (IMV + continuous positive airway pressure); and total number of days on supplemental oxygen. Overall nutritional status was determined by weight gain in g/kg per day. The incidence of IH in preterm infants of 32 weeks GA or less who were admitted for 28 days or more was 9.34% (65/696) prior to discharge. The incidence in infants weighing 1,500 g or less was 11.11% (63/567) and in infants 1,000 g or less 17.39% (48/276). All parameters that determined the severity of CLD were statistically significant in infants with IH by univariate analysis. In a multivariate regression model, male gender was the most important variable that was significantly associated with IH (odds ratio OR=9.6; 95% confidence interval CI=3.90–23.59), followed by total days on supplemental oxygen (adjusted OR=1.00; 95% CI= 1.01–1.02). Weight gain (g/kg per day) was not significantly different between the two groups. Surgical correction before discharge was well tolerated. We conclude that the incidence of IH is GA-dependent. Factors related to severity of CLD play a more important role than weight gain in predisposing to IH.

Effects of topical l-selenomethionine with topical and oral vitamin E on pigmentation and skin cancer induced by ultraviolet irradiation in Skh:2 hairless mice

BACKGROUND The antioxidants selenium and vitamin E can be effective in reducing acute and chronic ultraviolet (UV)-induced skin damage. OBJECTIVE This study investigated whether topical L-selenomethionine with topical RRR-alpha-tocopherol (Eol) or oral RRR-alpha-tocopheryl acetate (Eac) can reduce the incidence of UV-induced skin damage more than treatment with each alone. METHODS Skh:2 hairless pigmented mice were treated with lotion vehicle, L-selenomethionine lotion, Eol lotion, oral Eac, L-selenomethionine plus Eol lotion, or L-selenomethionine lotion plus oral Eac and exposed to UVB. Skin pigmentation was scored, and the number of skin tumors per animal was counted weekly. RESULTS Mice treated with selenium and vitamin E had significantly less acute and chronic UV-induced skin damage. CONCLUSION Topical L-selenomethionine alone and combined with vitamin E gave the best protection against UV-induced blistering and pigmentation. In protecting against skin cancer, topical Eol and topical L-selenomethionine plus oral Eac were best. Significant synergy of L-selenomethionine with vitamin E was not observed.