Translation, cultural adaptation and validation of the revised patients' attitudes towards deprescribing (rPATD) questionnaire in Romanian older adults.

BACKGROUND: Deprescribing is part of ensuring appropriate medication use and may reduce medication-related harm. Capturing the beliefs and attitudes of patients towards deprescribing by using a validated tool may support optimizing medication use in practice. OBJECTIVES: To translate, culturally adapt and validate the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire in Romanian and to investigate the attitudes and beliefs of older adults towards deprescribing. METHODS: The rPATD questionnaire was translated using forward-backward translation into Romanian and culturally adapted. The psychometric properties were evaluated in older adults ≥65 years of age. Structural validity was assessed by item load on factors using an exploratory factor analysis (EFA) which was compared to the original English version and the internal consistency by Cronbach's alpha. Construct validity was evaluated by calculating the Spearman's rank correlation coefficients between the factor scores obtained using the revised version of the Romanian rPATD and scores on the Beliefs about Medicines Questionnaire (BMQ) Specific Concerns Romanian version. Floor and ceiling effect were also examined. RESULTS: We translated the questionnaire and administered it to 224 participants (median age 72 years [interquartile range: 68.0; 77.0]). In the EFA individual items loaded onto 4 factors, grouped similarly to the English version (Involvement, Burden, Appropriateness, Concerns about Stopping factors). Two items from each of the Involvement and Appropriateness factors were removed to improve factor loading and avoid cross-loading. The Cronbach's alpha values for the 4 factors ranged between 0.522 and 0.773. The scores for Burden and Concerns about Stopping factors were found to be positively correlated with BMQ Specific Concerns score. We identified a ceiling effect for one of the four factors (Involvement) and no floor effects. CONCLUSIONS: The Romanian rPATD was validated in 4 factor structure similar to the original English questionnaire. The Romanian version of the questionnaire may support the health care professionals in Romania to initiate and support patient-centered deprescribing.

The OPTIMIZE patient- and family-centered, primary care-based deprescribing intervention for older adults with dementia or mild cognitive impairment and multiple chronic conditions: study protocol for a pragmatic cluster randomized controlled trial.

BACKGROUND: Most individuals with dementia or mild cognitive impairment (MCI) have multiple chronic conditions (MCC). The combination leads to multiple medications and complex medication regimens and is associated with increased risk for significant treatment burden, adverse drug events, cognitive changes, hospitalization, and mortality. Optimizing medications through deprescribing (the process of reducing or stopping the use of inappropriate medications or medications unlikely to be beneficial) may improve outcomes for MCC patients with dementia or MCI. METHODS: With input from patients, family members, and clinicians, we developed and piloted a patient-centered, pragmatic intervention (OPTIMIZE) to educate and activate patients, family members, and primary care clinicians about deprescribing as part of optimal medication management for older adults with dementia or MCI and MCC. The clinic-based intervention targets patients on 5 or more medications, their family members, and their primary care clinicians using a pragmatic, cluster-randomized design at Kaiser Permanente Colorado. The intervention has two components: a patient/ family component focused on education and activation about the potential value of deprescribing, and a clinician component focused on increasing clinician awareness about options and processes for deprescribing. Primary outcomes are total number of chronic medications and total number of potentially inappropriate medications (PIMs). We estimate that approximately 2400 patients across 9 clinics will receive the intervention. A comparable number of patients from 9 other clinics will serve as wait-list controls. We have > 80% power to detect an average decrease of - 0.70 (< 1 medication). Secondary outcomes include the number of PIM starts, dose reductions for selected PIMs (benzodiazepines, opiates, and antipsychotics), rates of adverse drug events (falls, hemorrhagic events, and hypoglycemic events), ability to perform activities of daily living, and skilled nursing facility, hospital, and emergency department admissions. DISCUSSION: The OPTIMIZE trial will examine whether a primary care-based, patient- and family-centered intervention educating patients, family members, and clinicians about deprescribing reduces numbers of chronic medications and PIMs for older adults with dementia or MCI and MCC. TRIAL REGISTRATION: NCT03984396. Registered on 13 June 2019.

Documenting the prevalence of hiatal hernia and oesophageal abnormalities in brachycephalic dogs using fluoroscopy.

OBJECTIVES: To report the prevalence of abnormal fluoroscopic findings in brachycephalic dogs that were presented to a referral hospital for obstructive airway syndrome. METHODS: Hospital records between May 2013 and November 2015 identified 36 brachycephalic dogs investigated for obstructive airway disease: 21 French bulldogs, six bulldogs, four Boston terriers, two pugs, two boxers and one shih-tzu. The presence or absence of hiatal hernia, delayed oesophageal transit, gastro-oesophageal reflux and redundant oesophagus were recorded. RESULTS: Of the 36 dogs, 16 had hiatal hernia, all of which were French bulldogs; 31 dogs had delayed oesophageal transit time, 27 had gastro-oesophageal reflux, and four had redundant oesophagus. CLINICAL SIGNIFICANCE: Clinical Significance: The prevalence of hiatal hernia is higher than expected in the French bulldog, and there was a high prevalence of oesophageal disease in this group in general. These results suggest a need to investigate similar cases for evidence of gastrointestinal disease that may also require attention.

Fluvoxamine for children and adolescents with obsessive-compulsive disorder: a randomized, controlled, multicenter trial.

OBJECTIVE: To determine the safety and efficacy of fluvoxamine for the treatment of children and adolescents with obsessive-compulsive disorder (OCD) with a double-blind, placebo-controlled, multicenter study. METHOD: Subjects, aged 8 to 17 years, meeting DSM-III-R criteria for OCD were recruited from July 1991 to August 1994. After a 7- to 14-day single-blind, placebo washout/screening period, subjects were randomly assigned to fluvoxamine 50 to 200 mg/day or placebo for 10 weeks. Subjects who had not responded after 6 weeks could discontinue the double-blind phase of the study and enter a long-term, open-label trial of fluvoxamine. Analyses used an intent-to-treat sample with a last-observation-carried-forward method. RESULTS: Mean Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) scores with fluvoxamine were significantly (p < .05) different from those with placebo at weeks 1, 2, 3, 4, 6, and 10. Significant (p < .05) differences between fluvoxamine and placebo were observed for all secondary outcome measures at all visits. Based on a 25% reduction of CY-BOCS scores, 42% of subjects taking fluvoxamine were responders compared with 26% taking placebo. Forty-six (19 fluvoxamine, 27 placebo) of 120 randomized subjects discontinued early. Adverse events with a placebo-adjusted rate greater than 10% were insomnia and asthenia. CONCLUSIONS: Fluvoxamine has a rapid onset of action and is well tolerated and efficacious for the short-term treatment of pediatric OCD.

Psychiatric diagnoses in children with alopecia areata.

OBJECTIVE: To identify psychiatric diagnoses in a sample of 12 children with alopecia areata (AA), to assess the possible relationship between life stressors and AA and to correlate any consistent physical findings to psychiatric data. METHOD: Twelve children with AA completed systematic psychiatric evaluations. The assessments included structured and semistructured interviews, rating scales, and parent checklists. Children had previously undergone immunological and endocrinological blood testing. RESULTS: Seven of the 12 subjects met criteria for anxiety disorders (including simple phobia) on structured interviews. An additional subject met criteria for dysthymia. Self-esteem measures indicated a high positive self-concept, and rating scales measuring anxiety and depression were within normal limits. No significant difference was found between mean number of positive or negative life events of children with AA compared with a normative sample. CONCLUSIONS: Although structured interviews revealed a higher than expected rate of anxiety or depressive disorders in this small clinical sample, self-report rating scales and semistructured interviews did not support the conclusion that significant psychopathology was present.

Clinical characteristics and psychiatric comorbidity in children with trichotillomania.

Ten children with trichotillomania (hair pulling) were systematically evaluated with structured psychiatric interviews and rating scales assessing anxiety, depression, life events, self-esteem, and family functioning. Six of the subjects met diagnostic criteria for overanxious disorder on the Diagnostic Interview for Children and Adolescents--Revised--Child or Adolescent Version and/or Diagnostic Interview for Children and Adolescents--Revised--Parent Version. Two met the criteria for dysthymia, including one of the subjects with overanxious disorder. No children reported associated obsessions or compulsions. Only one subject experienced tension before hair pulling and relief associated with hair pulling. The DSM-III-R criteria for trichotillomania, which currently require an increasing sense of tension before hair pulling and gratification with hair pulling, may be overly restrictive and in need of redefinition. Additional research with increased sample size is necessary to define diagnostic criteria for trichotillomania and clarify its relationship with other psychiatric diagnoses.

Growth hormone response to L-dopa and clonidine in autistic children.

Studies have shown abnormal pituitary hormone responses to neuroendocrine agonists in autistic subjects. Two probes (clonidine and L-Dopa) were used to investigate neuroendocrine responses through changes in growth hormone levels. Seven medication-free autistic subjects (ages 6.6 to 19.1) were evaluated and compared to 14 normal controls. Growth hormone was collected at 30-min intervals during the entire study. Clonidine was administered first (dose: 0.15 mgm2), and samples were collected for 180 min. L-Dopa was then administered (dose: 250 mg for subjects less than 70 lb and 500 mg for subjects greater than 70 lb), and samples were collected for 120 min. There was no difference in the amplitude of the clonidine or L-Dopa peak growth hormone responses in the control versus the autistic subjects. In the autistic subjects, the L-Dopa-stimulated growth hormone peak was delayed and the clonidine growth hormone peak was premature. A statistical difference with the control subjects was found when consideration was given to both the premature response of growth hormone to clonidine and the delayed response to L-Dopa (p = .01, Fisher's Exact Test). These findings suggest possible abnormalities of both dopaminergic and noradrenergic neurotransmission in subjects with autism.

Clonal analysis of the lac operons from Klebsiella M5al and the Lac plasmid (pRE2) from Klebsiella V9A.

The chromosomal lac region of the coliform bacterium Klebsiella M5al was cloned into the multicopy plasmid pBR322 to give pHE7 and pHE8. pHE8 contains 12.6 kb of M5al DNA, including its complete lac operon, and pHE7 contains 2.5 kb of M5al DNA and includes the complete lac Y gene and a small segment of lacZ. The M5al operon has the same gene order as the Escherichia coli lac operon. The lac genes of the Lac plasmid of Klebsiella V9A were cloned into pBR322 to give pHE1 and pHE2, of approximately 39 and 43 kb. Both plasmids were unstable in an E. coli RecA-strain, in contrast to the stability of pHE8. Polyacrylamide gel electrophoresis tests suggested that the M5al beta-galactosidase monomer is about 5% longer, i.e. has about 50 more amino acids, than that of the E. coli Z gene. Tests made on the enzymes coded by the lac operons of M5al, another Klebsiella strain (V9A) and its resident Lac plasmid, and several Lac+ Enterobacteria, led to the conclusion that only Escherichia coli among the Enterobacteria contains an active lacA gene.

The lactose carrier of Klebsiella pneumoniae M5a1; the physiology of transport and the nucleotide sequence of the lacY gene.

A comparison has been made between the physiology and amino acid sequence of the lactose carriers of Klebsiella pneumoniae M5a1 and Escherichia coli K-12. The membrane transport of lactose was much weaker in Klebsiella than in E. coli. On the other hand o-nitrophenylgalactoside uptake by Klebsiella was distinctly greater than with E. coli. In spite of the differences in sugar transport between the two organisms, the amino acid sequences of the respective lactose carriers were remarkably similar (60% of the amino acids are identical).

Abnormal antithrombin III with defective serine protease binding (antithrombin III "Denver").

A hereditary (three family members) deficiency of antithrombin III (AT-III) in which AT-III antigen (AT-III ag) is normal in spite of low heparin cofactor and antithrombin activity is described. Plasma levels were: AT-III ag, 0.92-0.96 U/ml; AT-III heparin cofactor activity, 0.54-0.62 U/ml; progressive antithrombin activity index, 0.13-0.18; anti-Xa activity, 0.50-0.56 U/ml. Plasma crossed immunoelectrophoresis (CIE) patterns performed with and without added heparin were normal, but serum CIE revealed a decreased complex peak. Purification of the patient's plasma AT-III by heparin-sepharose affinity chromatography showed a normal protein recovery and elution profile, but the purified AT-III fraction showed only 50% of the normal progressive thrombin neutralization and anti-Xa activity. When thrombin-antithrombin (TAT) complexes were formed by incubating with excess thrombin, SDS-polyacrylamide gel electrophoresis (PAGE) analysis revealed that half the patient AT-III formed TAT complexes while the remainder migrated as free AT-III. All the control AT-III formed TAT complexes. The patient's nonreacting AT-III (AT-III "Denver"), isolated by affinity chromatography, showed CIE and SDS-PAGE migration patterns characteristic of normal AT-III but failed to bind thrombin or Xa. Calculations from turnover studies in one patient and normal subjects with autologous 131I-AT-III suggested that AT-III "Denver" is removed from the plasma slightly more rapidly than normal. These studies indicate that the patients' variant AT-III molecule was characterized by normal heparin interaction but defective binding and inhibition of thrombin and Xa. These characteristics allow isolation of the nonreactive variant molecule by heparin-sepharose affinity chromatography.

Statistical identification of compartmental models with application to plasma protein kinetics.

A numerical method for fitting linear compartmental models to data is presented which is similar to the method proposed by Jennrich and Bright (R. I. Jennrich and P. B. Bright, Technometrics 18, 385 (1976] and Feldman (H. A. Feldman. Amer. J. Physiol. 233, R1 (1977] but avoids some of the numerical difficulties. The method is direct and does not use numerical integration thereby avoiding time consuming and expensive calculations. Emphasis is on statistical procedures for model selection. In addition to the usual F tests for comparing two models, Akaike's Information Criterion (AIC) is introduced for choosing from among several models. The combined use AIC with an F test, chi-square test, or confidence intervals on estimated parameters gives a practical method to obtain a balance between underfitting and overfitting. Application to models of plasma protein kinetics illustrates the method.

Further studies of the turnover of dog antithrombin III. Study of 131I-labelled antithrombin protease complexes.

Fresh plasma containing 131I-antithrombin III (*I-AT) was coagulated and incubated at 37 degrees C for 2 hr. A "complex peak," separated on heparin-agarose contained AT and *I-AT antigen but no heparin cofactor activity. Crossed immunoelectrophoresis showed only AT complexes. SDS PAGE showed 80% of the *I-AT in a major band (approximately 80,000 daltons), 15% in a minor band (approximately 100,000 daltons) and the rest in trace bands (approximately 60,000 and/or 115,000 daltons). Ammonia treatment of the complex peak released alpha-thrombin. After i.v. injection 80% of the complexed *I-AT, chiefly as the major band, left the plasma with t 1/2 approximately 15 min and was almost immediately catabolized to low molecular weight breakdown products. A major catabolic site was the liver. A simple kinetic model describes the findings approximately.

Antithrombin III deficiency: decreased synthesis of a biochemically normal molecule.

A 29-yr-old white female has suffered from recurrent venous thromboses over the last 12 yr. Plasma antithrombin III (AT-III) levels were 48% of normal by immunoelectrophoresis and 56% by chromogenic assay. Three of four siblings and the father had similar AT-III levels without associated venous thromboses. Heparin-Sepharose chromatography demonstrated normal behavior of the patient's AT-III. Her purified AT-III could not be distinguished from AT-III purified from a normal control either by SDS polyacrylamide gel electrophoresis or by crossed immunoelectrophoresis, and the heparin cofactor activity and the progressive antithrombin activity of both AT-III samples were identical. Turnover studies were made in the patient using her own purified AT-III labeled with 131I, (*I). The results did not differ significantly from studies made with autologous *I-AT-III in two normal control women. Her fractional breakdown rate of 0.54 total plasma AT-III per day compared with 0.45 and 0.52 in the controls. These studies indicate that the patient synthesizes a normal AT-III molecule at half normal rates.

Biochemical and functional study of antithrombin III in newborn infants.

Antithrombin III (AT-III) was isolated by heparin affinity chromatography from adult venous and newborn term and preterm umbilical cord blood. The purified proteins were compared by SDS-PAGE, rocket immuno-electrophoresis, protein concentration by microbiuret relative to optical density at 280 nm, heparin cofactor specific activity, progressive neutralization of thrombin and factor Xa at 37 degree C and pH related antithrombin kinetics. The structural evaluations revealed a fetal AT-III of molecular weight, charge and electrophoretic migration indistinguishable from adult AT-III. The functional studies showed that, on an equimolar basis, the rates of thrombin and Xa interactions with fetal AT-III were as rapid as those with adult AT-III. The catalytic rates of various concentrations of heparin were also equal. The newborn infant, therefore, displays a quantitative but not quantitative deficiency of AT-III.

Experimental studies of the fibrinogen response to hemorrhage.

Rabbits were bled 20 ml/kg body wt over approximately 1 h, and the changes in hematocrit, plasma total protein, and fibrinogen concentrations, red cell and plasma volumes, and masses of total protein and fibrinogen in the plasma during and for 4 days after the hemorrhage were monitored. Ten percent of plasma fibrinogen was transferred from the interstitial fluids during the hemorrhage, and total plasma fibrinogen was raised to 140% of initial levels by 1 day later. 131I-labeled fibrinogen was given intravenously 1 day before a 20 ml/kg hemorrhage, and simulation methods described in the APPENDIX were used to define changes in the posthemorrhage fractional rates: transcapillary transfer rate (j1), lymphatic return rate (j2), and catabolic rate of fibrinogen (j3): j1 was unchanged but j2 increased and j3 briefly declined. In the day after hemorrhage fibrinogen synthetic rate increased approximately threefold to restore plasma fibrinogen concentrations to initial levels, but then returned to normal or subnormal levels. The alterations in j2 and j3 save about 20% of the synthetic work that would otherwise be required to restore plasma fibrinogen levels to normal.