Efficacy of Adderall and methylphenidate in attention deficit hyperactivity disorder: a drug-placebo and drug-drug response curve analysis of a naturalistic study

Stimulant medication has, for many years, been the pharmacological treatment of choice for children and adults with attention deficit hyperactivity disorder (ADHD). Recently, several studies have documented the efficacy of a new stimulant, Adderall. Although these initial studies provide useful information for clinicians treating ADHD children, their method of data presentation has provided limited information about the clinical significance of drug effects. Thus, to address the issue of clinical significance, we completed drug-placebo response curve analyses of a blinded, placebo-controlled study of Adderall and methylphenidate (MPH). Our results show that the efficacy of Adderall and MPH to improve functioning is seen throughout the full range of improvement scores. Both drugs prevent worsening and, for a majority of patients, lead to improvements that are well into the normal range. The analyses also highlight an important subgroup of placebo responders, which suggests that future research should focus on how to predict robust placebo response in ADHD patients.     

Atypical glandular cells of undetermined significance (AGUS): Interobserver reproducibility in cervical smears and corresponding thin-layer preparations.

Five panelists independently reviewed 135 consecutive conventional cervical smears (CPs) originally classified as atypical glandular cells of undetermined significance (AGUS). A thin-layer slide (TP), prepared from the residual material, also was reviewed in each case. All patients underwent colposcopy that yielded at least 1 histologic specimen. Three or more of 5 reviewers retained the AGUS interpretation for 29% of CPs and 12% of the corresponding TPs. Interobserver variability infrequency of use of AGUS was marked, and interobserver agreement was poor. Agreement was improved for cases cytologically interpreted as a high-grade lesion, especially in TPs. Four of 5 reviewers retained the AGUS classification in CPs for all 7 biopsy-proven neoplastic glandular lesions. Of 95 CP interpretations made by 5 reviewers in the 19 histologically diagnosed high-grade lesions, 8 were "negative/reactive" and 6 were AGUS "favor reactive." AGUS is a poorly reproducible cytologic interpretation. Although most neoplastic glandular lesions may be distinguished by cytopathologists experienced in this area from mimics originally considered AGUS, attempts to increase the diagnostic specificity of AGUS may diminish sensitivity for an underlying high-grade precursor. Interobserver agreement was better for TPs than for the corresponding CPs. However, the split-sample TP slides may not have been fully comparable to the CPs.     

Daytime pulmonary hypertension in patients with obstructive sleep apnea: the effect of continuous positive airway pressure on pulmonary hemodynamics.

BACKGROUND: Limited information exists regarding the development of pulmonary hypertension in patients with obstructive sleep apnea (OSA) in the absence of lung and heart comorbidity. OBJECTIVES: The aims of this study were to investigate whether OSA patients without any other cardiac or lung disease develop pulmonary hypertension, and to assess the effect of continuous positive airway pressure (CPAP) treatment on pulmonary artery pressure (P(PA)). METHODS: Twenty-nine patients aged 51 +/- 10 years with OSA and 12 control subjects were studied with pulsed-wave Doppler echocardiography for estimation of P(PA) before and after 6-month effective treatment with CPAP. RESULTS: A significantly higher mean P(PA) was found in OSA patients as compared to control subjects (17.2 +/- 5.2 vs. 12.1 +/- 1.9 mm Hg, p < 0.001). Six out of the 29 OSA patients had mild pulmonary hypertension (P(PA) > or = 20 mm Hg). Significant differences were observed between pulmonary hypertensive and normotensive OSA patients with respect to age (62 +/- 4 vs. 48 +/- 15 years, respectively, p < 0.05), body mass index (41 +/- 7 vs. 32 +/- 4 kg/m(2), p < 0.02) and daytime P(a)O(2) (81 +/- 9 vs. 92 +/- 9 mm Hg, p < 0.05). CPAP treatment was effective in reducing mean P(PA) in both groups of pulmonary hypertensive and normotensive OSA patients (decreases in P(PA) from 25.6 +/- 4.0 to 19.5 +/- 1.5 mm Hg, p < 0.001; from 14.9 +/- 2.2 to 11.5 +/- 2.0 mm Hg, respectively, p < 0.001). CONCLUSIONS: A proportion (20.7%) of OSA patients without any other lung or heart disease and characterized by older age, greater obesity and lower daytime oxygenation develop mild pulmonary hypertension which has been partially or completely reversed after 6-month CPAP treatment. In conclusion, OSA alone constitutes an independent risk factor for the development of pulmonary hypertension.     

The Lung Reporting and Data System (LU-RADS): A Proposal for Computed Tomography Screening

Despite the positive outcome of the recent randomized trial of computed tomography (CT) screening for lung cancer, substantial implementation challenges remain, including the clear reporting of relative risk and suggested workup of screen-detected nodules. Based on current literature, we propose a 6-level Lung-Reporting and Data System (LU-RADS) that classifies screening CTs by the nodule with the highest malignancy risk. As the LU-RADS level increases, the risk of malignancy increases. The LU-RADS level is linked directly to suggested follow-up pathways. Compared with current narrative reporting, this structure should improve communication with patients and clinicians, and provide a data collection framework to facilitate screening program evaluation and radiologist training. In overview, category 1 includes CTs with no nodules and returns the subject to routine screening. Category 2 scans harbor minimal risk, including <5 mm, perifissural, or long-term stable nodules that require no further workup before the next routine screening CT. Category 3 scans contain indeterminate nodules and require CT follow up with the interval dependent on nodule size (small [5-9 mm] or large [≥10 mm] and possibly transient). Category 4 scans are suspicious and are subdivided into 4A, low risk of malignancy; 4B, likely low-grade adenocarcinoma; and 4C, likely malignant. The 4B and 4C nodules have a high likelihood of neoplasm simply based on screening CT features, even if positron emission tomography, needle biopsy, and/or bronchoscopy are negative. Category 5 nodules demonstrate frankly malignant behavior on screening CT, and category 6 scans contain tissue-proven malignancies.     

Frontal brain lobe impairment in obstructive sleep apnoea: a proton MR spectroscopy study.

Patients with obstructive sleep apnoea syndrome frequently have cognitive deficits, especially related to executive functions, which cannot be fully explained by daytime sleepiness and are partial irreversible after nasal continuous positive airway pressure treatment. The causal mechanism of these cognitive deficits is not yet known, but it has been proposed that they are associated with chemical and structural brain cell injury. The aim of this study was to investigate brain metabolism in patients with sleep apnoea syndrome. Twenty-two patients with severe sleep apnoea and 10 healthy volunteers of comparable age were studied using single voxel proton magnetic resonance spectroscopy. Magnetic resonance spectra were obtained from prefrontal cortex, parieto-occipital and frontal periventricular white matter. N-acetylaspartate-to-creatine and choline-to-creatine ratios were significantly lower in the frontal white matter of obstructive sleep apnoea patients when compared to controls. Absolute concentrations of N-acetylaspartate and choline were also significantly reduced in the frontal white matter of patients with sleep apnoea. Frontal lobe white matter lesions are known to be associated with cognitive executive dysfunction. The findings of this study may offer an explanation for the sometimes irreversible cognitive deficits associated with sleep apnoea.     

Effects of treatment on gingival crevicular collagenase, stromelysin and tissue inhibitor of metalloproteinases and their ability to predict response to treatment

Abstract Fibroblast collagenase (FIB-CL) and stromelysin (SL) are members of a family of enzymes which are capable of degrading most of the extracellular matrix macromolecules. Extracellular control of these enzymes is performed by tissue inhibitor of metalloproteinases (TIMP). During healing, inflammation and normal tissue turnover, levels of MMPs and TIMP will change. The effect of treatment on the levels of FIB-CL. SL and TIMP as well as their ability, at baseline, to predict the outcome of therapy was investigated. 21 patients each provided 8 gingival crevicular fluid (GCF) samples from sites with probing depths ≥4 mm. Clinical recordings and GCF sampling H-ere performed at 3 time points. Assays for SL, FIB-CL and TIMP were performed by a sandwich ELISA. Attachment level changes were detected by the “tolerance method”. The ability of the GCF constituents to predict the response to treatment was assessed by comparing pre-treatment levels between sites which did or did not show attachment gain after therapy. Although no GCF constituents could reliably predict the response to treatment, SL reduced significantly (p=0.029) after the hygiene phase of therapy. In addition, both SL and TIMP levels showed a highly significant reduction at follow-up visit (p=0.003 and p=0.005 respectively). Thus. SL and TIMP levels are reduced by treatment, but these GCF proteins do not appear to have an ability lo predict treatment outcome from baseline.     

Papillomavirus found in anorectal squamous carcinoma, not in colon adenocarcinoma.

We used polymerase chain reaction DNA amplification methods for the detection and typing of genital human papillomaviruses in paraffin-embedded tissue sections of five patients with anorectal squamous cell carcinoma and 22 patients with colonic adenocarcinoma. The cases were further tested by in situ hybridization with biotin-labeled probes specific for human papillomavirus types 6/11, 16/18, and 31/33/35. By polymerase chain reaction, human papillomavirus DNA was demonstrated in all of the cases of anorectal squamous cell carcinoma and in none of the cases of colonic adenocarcinoma for which analyzable DNA was available. Tumor cell nuclei stained for human papillomavirus DNA by in situ hybridization in four of the five cases of squamous cell carcinoma and in none of the cases of colonic adenocarcinoma. We conclude that human papillomavirus types usually associated with malignant transformation are uniformly present in anorectal squamous cell carcinoma but are absent from adenocarcinoma of the colon.