Cochrane Centralised Search Service showed high sensitivity identifying randomized controlled trials: A retrospective analysis.

BACKGROUND AND OBJECTIVES: The Cochrane Central Register of Controlled Trials (CENTRAL) is compiled from a number of sources, including PubMed and Embase. Since 2017, we have increased the number of sources feeding into CENTRAL and improved the efficiency of our processes through the use of application programming interfaces, machine learning, and crowdsourcing.Our objectives were twofold: (1) Assess the effectiveness of Cochrane's centralized search and screening processes to correctly identify references to published reports which are eligible for inclusion in Cochrane systematic reviews of randomized controlled trials (RCTs). (2) Identify opportunities to improve the performance of Cochrane's centralized search and screening processes to identify references to eligible trials. METHODS: We identified all references to RCTs (either published journal articles or trial registration records) with a publication or registration date between 1st January 2017 and 31st December 2018 that had been included in a Cochrane intervention review. We then viewed an audit trail for each included reference to determine if it had been identified by our centralized search process and subsequently added to CENTRAL. RESULTS: We identified 650 references to included studies with a publication year of 2017 or 2018. Of those, 634 (97.5%) had been captured by Cochrane's Centralised Search Service. Sixteen references had been missed by the Cochrane's Centralised Search Service: six had PubMed-not-MEDLINE status, four were missed by the centralized Embase search, three had been misclassified by Cochrane Crowd, one was from a journal not indexed in MEDLINE or Embase, one had only been added to Embase in 2019, and one reference had been rejected by the automated RCT machine learning classifier. Of the sixteen missed references, eight were the main or only publication to the trial in the review in which it had been included. CONCLUSION: This analysis has shown that Cochrane's centralized search and screening processes are highly sensitive. It has also helped us to understand better why some references to eligible RCTs have been missed. The CSS is playing a critical role in helping to populate CENTRAL and is moving us toward making CENTRAL a comprehensive repository of RCTs.

Topical treatments for chronic plaque psoriasis of the scalp: a systematic review.

BACKGROUND: Chronic plaque psoriasis is the most common type of psoriasis and is characterized by redness, thickness and scaling. First-line management is with topical treatments. OBJECTIVES: Our objective was to establish the effectiveness, tolerability and safety of topical treatments for people with chronic plaque psoriasis of the scalp, assessing placebo-controlled trials of all treatments and head-to-head trials that assessed vitamin D analogues. METHODS: As part of a Cochrane review of topical treatments for psoriasis, we systematically searched electronic databases for randomized controlled trials. The review included 26 randomized controlled trials of treatments for psoriasis of the scalp with 8020 participants. Trials used several measures to assess changes in psoriasis severity: these were combined using the standardized mean difference metric and interpreted by reporting as a six-point global improvement score. RESULTS: On effectiveness grounds, very potent or potent steroid treatments should be preferred to vitamin D3 analogue with approximately an average 10% additional improvement on a six-point scale. Vitamin D3 analogue combined with potent steroid appears slightly more effective than potent steroid monotherapy (3% additional improvement on a six-point scale). Rates of withdrawal from treatment and adverse events in trials were generally low and similar to those for placebo. There remains uncertainty about the atrophic potential of corticosteroid treatments for scalp psoriasis. CONCLUSIONS: Corticosteroids are more effective than vitamin D analogues and similarly tolerated. However, further research is needed to inform long-term maintenance treatment and provide appropriate safety data.

Proteomic analysis of diaminochlorotriazine adducts in wistar rat pituitary glands and LbetaT2 rat pituitary cells.

Atrazine (ATRA) is the most commonly applied herbicide in the United States and is frequently detected in drinking water at significant levels. After oral exposure, ATRA metabolism yields diaminochlorotriazine (DACT), an electrophilic molecule that has been shown to form covalent protein adducts. This research was designed to identify ATRA-induced protein adducts formed in the pituitary gland of ATRA-exposed rats and in DACT-exposed LbetaT2 rat pituitary cells. Immunohistochemistry showed diffuse cytoplasmic and nuclear staining in both pituitary sections and LbetaT2 cells indicating the formation of DACT protein adducts. Protein targets from both rat pituitaries and LbetaT2 cell culture were identified following two-dimensional electrophoresis (2DE), immunodetection, and matrix-assisted laser desorption ionization-time of flight mass spectrometry analysis. Western blots from both exposed rats and LbetaT2 cells revealed over 30 DACT-modified spots that were not present in control animals. Protein spots were matched to concurrently run 2DE gels stained with Sypro Ruby, excised, and in-gel-digested with trypsin. Mass spectrometry analysis of digest peptides resulted in the identification of 19 spots and 8 unique proteins in the rats and 21 spots and 19 unique proteins in LbetaT2 cells. The identified proteins present in both sample types included proteasome activator complex subunit 1, ubiquitin carboxyl-terminal hydrolase isozyme L1, tropomyosin, ERp57, and RNA-binding proteins. Each of these proteins contains active-site or solvent-exposed cysteine residues, making them viable targets for covalent modification by DACT.

Monaural and binaural loudness measures in cochlear implant users with contralateral residual hearing.

OBJECTIVE: The aim was to measure the loudness of monaural and binaural stimuli in a group of cochlear implant users who had residual hearing in the nonimplanted ear, and to consider the implications of these measures for a binaural fitting consisting of a hearing aid and an implant in opposite ears. Three independent hypotheses were addressed: that the shapes of the electric and acoustic loudness growth functions would be similar, although the dynamic ranges would differ; that standard implant and hearing aid fittings would result in substantial loudness mismatches between the acoustic and electric signals; and that loudness summation would occur for binaural combinations of electric and acoustic signals. DESIGN: A modified version of the "Loudness Growth in 1/2-Octave Bands" method (Allen, Hall, & Jeng, 1990) was used to measure loudness growth for each ear of nine subjects. At the time of the experiment, the subject group included all implant users in Melbourne and Denver who were available for research and who also had sufficient residual hearing to use a hearing aid in the nonimplanted ear. Five acoustic frequencies and five electrodes were measured for each subject. The same subjects also estimated the loudness of a set of stimuli including monaural and binaural signals chosen to cover the loudness range from very soft to loud. RESULTS: The shapes of the averaged loudness growth functions were similar in impaired and electrically stimulated ears, although the shapes of iso-loudness curves were quite different in the two ears, and dynamic ranges varied considerably. Calculations based on the psychophysical data demonstrated that standard fitting procedures for cochlear implants and hearing aids lead to a complex pattern of loudness differences between the ears. A substantial amount of loudness summation was observed for the binaural stimuli, with most summation occurring when the acoustic and electric components were of equal loudness. This is consistent with observations for subjects with normal hearing and subjects with bilaterally impaired hearing. CONCLUSIONS: These experiments provide data on which criteria and methods for the binaural fitting of cochlear implants and hearing aids may be based. It is unlikely that standard monaural fitting methods for cochlear implants and hearing aids will result in balanced loudness between the two ears across a reasonably broad range of frequencies and levels. It is also likely that output levels of both devices will need to be reduced relative to a monaural fitting to compensate for the binaural summation of loudness in some listeners.

Improving searching skills and evidence retrieval.

OBJECTIVE: To evaluate the effect of a three-hour training session in formulating questions and searching databases. DESIGN: A randomised controlled trial and before and after study, with blinded outcome assessment. SETTING: Oxford University Medical School, first clinical year. SUBJECTS: Altogether 108 medical students were randomly assigned to an experimental group (54) or a control group (54), and all were given the task of searching for evidence around an ulcer related problem or a cardiac problem. Students in the experimental group were randomly allocated to research one of the two problems before training and the remaining problem afterwards. Control students received no training and were randomly allocated to search for evidence around either of these problems. MAIN OUTCOME MEASURES: Searching performance; the quality of evidence retrieved; student satisfaction. RESULTS: Training improved the students' search performance and the quality of evidence retrieved. Students' satisfaction with the training was high. CONCLUSIONS: A three-hour interactive training session improved the students' ability to search databases and retrieve evidence and was well received by the students.

Pitch comparisons of acoustically and electrically evoked auditory sensations.

Cochlear implant users with some residual hearing in the non-implanted ear compared the pitch sensations produced by acoustic pure tones and pulsatile electric stimuli. Pitch comparisons were obtained for pure tones and electrical stimuli presented at different positions (electrodes) in the scala tympani, keeping the electric pulse rate fixed at 100, 250, or 800 pps. Similarly, pitch comparisons were obtained for electrical stimuli with variable pulse rates presented to two fixed electrode positions (apical and basal) in the cochlea. Both electrode position and pulse rate influenced the perceived pitch of the electrical signal and 'matched' electric and acoustic signals were found over a wide range of frequencies. There was a large variation between listeners. For some stimuli, listeners had difficulty in deciding whether the acoustic or electric stimulus was higher in pitch. Despite the variability, consistent trends were obtained from the data: higher frequencies tended to be matched by more basal electrodes for all pulse rates. Higher frequencies tended to be matched by higher pulse rates for both electrode positions. The electrode positions that 'matched' pure tones were more basal than predicted from the characteristic frequency coordinates of the basilar membrane in a normal human cochlea.

Preliminary evaluation of a formant enhancement algorithm on the perception of speech in noise for normally hearing listeners.

The effects on speech perception in noise of dynamic filtering with bandpass filters centred at the first formant (f1) and second formant (f2) frequencies were evaluated with four normally hearing listeners. Multitalker babble was added to the speech signal with signal-to-noise ratios of -5 to -15 dB, chosen to reduce intelligibility to about 50%. The combined signal was then filtered with two-pole programmable bandpass filters centred at f1 and f2 under the control of a real-time speech processor. The f1 and f2 frequencies were estimated from the speech signal before noise was added to avoid hardware processing errors. Closed set vowel and consonant tests (using 11 /h/vowel/d/ and 12 /a/consonant/a/ stimuli), the Consonant-Nucleus-Consonant Monosyllabic Word Test and the Bamford-Kowal-Bench Sentence Test were carried out for three filter bandwidths (3/4, 1/3 and 1/6 octave) and for unprocessed speech in noise. The processing produced a small significant improvement for vowels in all three processed speech conditions and for monosyllables at the broadest filter setting compared to the unprocessed speech condition. There was no significant effect on consonants. A small negative effect was observed for sentences at the narrowest filter setting.

Combined electrical and acoustical stimulation using a bimodal prosthesis.

A new device incorporating a cochlear implant speech processor and a speech-processing hearing aid for the unimplanted ear has been designed and tested with four severely hearing-impaired patients. The aim of the device is to provide a more acceptable and effective combination of electrical and acoustic signals to the two ears. When used monaurally, and binaurally in conjunction with the cochlear implant, the speech-processing hearing aid mean scores for open-set sentences, words, and consonants were as good as or better than the mean scores for the patients' own conventional hearing aids. Some patients improved much more than did others. Although not conclusive, these results are encouraging, especially as they were achieved with a laboratory prototype that did not allow the patients to become accustomed to the processor in everyday situations.

Pattern recognition and masking in cochlear implant patients.

Studies of the temporal course of masking using pulsatile electrical stimulation provide a sensitive new technique for the investigation of central pattern recognition. The masked threshold for a single-pulse probe was studied for several different maskers as a function of the time between the probe and the start of the masker. These experiments showed the gradual development of a temporal pattern in the masked thresholds as the number of pulses in the masker was increased. For a 210 msec masker with pulses at 10 msec intervals, both backward and forward masking thresholds showed a well-defined peak at times 10 msec before and after the masker. Probe pulses presented at these times were probably perceived to be part of the masker pattern and therefore were not easily identified as probe pulses. This conclusion was confirmed by using a masker with pulses at 20 msec intervals. Only backward masking was tested, and the results showed a peak approximately 20 msec before the start of the masker, fitting in with the temporal pattern of the masker.

Personal construct systems of psoriatic patients.

Repertory grid techniques were employed to assess the personal construct systems of psoriatic patients (n = 35), controls with other skin conditions (n = 28) and controls with no skin condition (n = 29). A grid was designed with six supplied constructs representing previously reported subjective experiences of psoriatics, and 12 elements representing typical social conditions. Social adjustment was defined as the relationship between constructs. The results suggest that psoriatics are less well socially adjusted in highly visible situations. There was no difference in social adjustment between males and females specific to the psoriatic group, but body awareness in female psoriatics correlated positively with the severity of the condition.

Detection and discrimination of spectral peaks and notches at 1 and 8 kHz.

The ability of subjects to detect and discriminate spectral peaks and notches in noise stimuli was determined for center frequencies fc of 1 and 8 kHz. The signals were delivered using an insert earphone designed to produce a flat frequency response at the eardrum for frequencies up to 14 kHz. In experiment I, subjects were required to distinguish a broadband reference noise with a flat spectrum from a noise with either a peak or a notch at fc. The threshold peak height or notch depth was determined as a function of bandwidth of the peak or notch (0.125, 0.25, or 0.5 times fc). Thresholds increased with decreasing bandwidth, particularly for the notches. In experiment II, subjects were required to detect an increase in the height of a spectral peak or a decrease in the depth of a notch as a function of bandwidth. Performance was worse for notches than for peaks, particularly at narrow bandwidths. For both experiments I and II, randomizing (roving) the overall level of the stimuli had little effect at 1 kHz, but tended to impair performance at 8 kHz, particularly for notches. Experiments III-VI measured thresholds for detecting changes in center frequency of sinusoids, bands of noise, and spectral peaks or notches in a broadband background. Thresholds were lowest for the sinusoids and highest for the peaks and notches. The width of the bands, peaks, or notches had only a small effect on thresholds. For the notches at 8 kHz, thresholds for detecting glides in center frequency were lower than thresholds for detecting a difference in center frequency between two steady sounds. Randomizing the overall level of the stimuli made frequency discrimination of the sinusoids worse, but had little or no effect for the noise stimuli. In all six experiments, performance was generally worse at 8 kHz than at 1 kHz. The results are discussed in terms of their implications for the detectability of spectral cues introduced by the pinnae.

Duration discrimination of steady and gliding tones: a new method for estimating sensitivity to rate of change.

Thresholds for the detection of differences in duration were measured in a two-alternative, forced-choice task for four types of signals, all centered at 2000 Hz: (1) sinusoids fixed in frequency and level; (2) sinusoids of fixed frequency whose level was swept up or down by 5 or 10 dB; (3) sinusoids of fixed level whose frequency was swept up or down by 100 Hz; and (4) sinusoids whose level was swept up or down by 10 dB and whose frequency was swept up or down by 100 Hz. For types (2)-(4), the direction of the sweeps was fixed within a run. The duration of the standard was either fixed at 750 ms or was varied randomly from trial to trial by up to +/- 7% about 750 ms. The duration of the comparison signal was initially 100 ms greater than that of the standard and was varied adaptively to determine threshold. The pattern of results was similar for all four subjects tested. Duration-discrimination thresholds for the signals that were swept in level and/or frequency were lower than those for the fixed signal, typically by 15-20 ms. This indicates that subjects were sensitive to the rate of change of frequency and/or level and could use this as a cue for duration discrimination. The Weber fraction for rate of change was estimated to be about 0.05-0.06 and was similar for changes in level and in frequency.