Prospective Assessment of Penicillin Allergy (PAPA): Evaluating the performance of penicillin allergy testing and post-delabelling outcomes among Hong Kong Chinese.

BACKGROUND: Incorrect penicillin 'allergy' labels predispose patients to adverse outcomes but are under-recognised in many Asian countries. Studies on performance and post-delabelling outcomes of penicillin allergy evaluation among Chinese remain scarce. OBJECTIVE: To evaluate the diagnostic performance of allergy testing and post-delabelling outcomes among Chinese patients in a prospective penicillin allergy cohort - Prospective Assessment of Penicillin Allergy (PAPA). METHODS: All adult patients (age ≥ 18 years) who underwent penicillin allergy evaluation between January 2020 to December 2021 were recruited and prospectively reviewed by both medical records and individual interviews at least 6 months after delabelling or allergy confirmation. RESULTS: Out of 372 patients who completed penicillin allergy evaluation, 335 (90%) patients were delabelled. The overall negative predictive value of penicillin skin testing was 95%, but lower for patients with non-immediate type reactions (88%). History of non-immediate symptom onset (OR = 4.501 [95%CI = 2.085-9.716], p < 0.001) and duration since index reaction (OR = 0.942 [95%CI = 0.899-0.987], p = 0.012) were associated with positive skin testing. After at least 6 months, 60 (18%) of de-labelled patients had received penicillins again without any adverse reactions. Fluoroquinolone-use was significantly lower among delabelled patients compared to those with penicillin allergy (38[11%] vs 11[30%], p = 0.004). CONCLUSIONS: After at least 6 months, one in six delabelled patients already received penicillins again safely, with significantly lower fluoroquinolone usage. None experienced adverse reactions. History of non-immediate onset and shorter duration since index reaction were associated with genuine allergy. In patients with severe non-immediate reactions, skin tests should be supplemented with thorough clinical history and adjunct diagnostic evaluations.

Sensitisation profile of Chinese allergic rhinitis patients and effectiveness of a joint allergy-ENT clinic.

Purpose: House dust mite (HDM) is the predominant cause of allergic rhinitis (AR) in Hong Kong but remains under-diagnosed and -treated. The association between patient-reported outcome measures (PROMs) and nasoendoscopy findings for AR have also not been investigated. This study investigated the demographics, sensitisation patterns, quality of life, use of sublingual immunotherapy and the association of PROMs and nasoendoscopy findings in AR patients through the first allergist-otorhinolaryngologists AR joint (ARJ) clinic in Hong Kong. Methods: This single-centred, retrospective observational study was conducted between January 2021 and December 2021. Clinical data from AR patients attending the ARJ clinic were analysed to identify the prevalence of HDM allergens, change in PROMs and the association of PROMs with nasoendoscopy scores. Results: The three most common sensitising HDM allergens were Dermatophagoides pterynosinus (94.4%), Dermatophagoides farinae (88.9%) and Euroglyphus maynei (88.9%). At the 13- to 32-week follow-up (median 28 weeks), patients who attended the ARJ clinic had significant improvement in Total Nasal Symptom Score (TNSS; p = 0.038). The visual analogue scale (VAS) was associated with nasoendoscopy score (p = 0.018). Patients using SLIT (sublingual immunotherapy) showed overall improvements in PROMs. Conclusion: The ARJ clinic significantly improved AR symptoms. SLIT was effective and safe for patients who failed conventional treatments. VAS positively correlated with nasoendoscopy findings. Testing for Dermatophagoides pterynosinus as a single agent during skin testing was sufficient for the diagnosis of HDM AR and should be prioritized when resources are restricted. Further studies should be done to investigate the treatment outcome of AR patients and the effectiveness of SLIT in the Chinese population. Supplementary Information: The online version of this article (10.1007/s40629-022-00218-5) contains supplementary material, which is available to authorized users.

Comparative Effectiveness, Safety, and Real-World Outcomes of a Nurse-Led, Protocol-Driven Penicillin Allergy Evaluation From the Hong Kong Drug Allergy Delabelling Initiative (HK-DADI).

BACKGROUND: There is a high prevalence of unconfirmed penicillin allergy, which is associated with a multitude of adverse clinical outcomes. With the overwhelming burden of currently incorrect labels and the lack of allergy specialist services, new delabeling strategies are urgently needed. OBJECTIVE: To assess the effectiveness, safety, and real-world outcomes of a nurse-led, protocol-driven evaluation of penicillin allergy, the Hong Kong Drug Allergy Delabelling Initiative (HK-DADI). METHODS: Adult patients with suspected penicillin allergy were recruited into HK-DADI. Allergy and postdelabeling outcomes were retrospectively compared between patients evaluated via HK-DADI or traditional allergist evaluation. RESULTS: A total of 312 completed penicillin allergy evaluation: 84 (27%) and 228 (73%) via HK-DADI and traditional pathways, respectively. Overall, 280 penicillin allergies were delabeled (90%). The delabeling rate between HK-DADI and traditional pathways was similar (90% vs 89%; P = .796). Among patients of the HK-DADI pathway, the delabeling rate was significantly higher among low-risk (LR) compared with non-LR patients (97% vs 77%; P = .010). Skin tests did not add diagnostic value among LR patients. No patients developed severe or systemic reactions during the evaluation. Upon 6- to 12-month follow-up (median, 10 months), 123 patients experienced infective episodes (44%) and 63 used penicillins again after delabeling (23%). This proportion was significantly higher in patients who were delabeled via HK-DADI compared with the traditional pathway (32% vs 19%; P = .026). CONCLUSIONS: The Hong Kong Drug Allergy Delabelling Initiative, a nurse-led, protocol-driven evaluation, was safe and effective in penicillin allergy delabeling. It led to an even higher rate of future penicillin use after delabeling and mitigated the need for unnecessary skin testing among LR patients.

Molecular basis for the production of cyclic peptides by plant asparaginyl endopeptidases.

Asparaginyl endopeptidases (AEPs) are proteases that have crucial roles in plant defense and seed storage protein maturation. Select plant AEPs, however, do not function as proteases but as transpeptidases (ligases) catalyzing the intra-molecular ligation of peptide termini, which leads to peptide cyclization. These ligase-type AEPs have potential biotechnological applications ranging from in vitro peptide engineering to plant molecular farming, but the structural features enabling these enzymes to catalyze peptide ligation/cyclization rather than proteolysis are currently unknown. Here, we compare the sequences, structures, and functions of diverse plant AEPs by combining molecular modeling, sequence space analysis, and functional testing in planta. We find that changes within the substrate-binding pocket and an adjacent loop, here named the "marker of ligase activity", together play a key role for AEP ligase efficiency. Identification of these structural determinants may facilitate the discovery of more ligase-type AEPs and the engineering of AEPs with tailored catalytic properties.

Converging evidence for the role of relative timing in speech.

In an earlier article (Tuller, Kelso, & Harris, 1982a) we suggested that the timing of consonant-related muscle activity was constrained relative to the period between onsets of muscle activity for successive vowels. Here, we reexamine those data based on reservations posed by Barry (1983). Next, we present a kinematic study of articulation that extends and strongly supports our original observations. Finally, we very briefly survey some converging lines of evidence for a functionally significant vowel-to-vowel period in speech and how this may relate to the role of temporal invariance in motor skills in general.

Dual processing of open- and closed-class words.

A series of articles in the past two decades has suggested differential processing of open- and closed-class lexical items by normal adults. Difficulties in replicating a crucial study (Bradley, 1978), however, have weakened the dual route hypothesis. We matched 16 French open-class items to 16 closed-class items for phonological structure, world length, and relative word frequency. Three agrammatic aphasics revealed strikingly more phonological errors on closed-class than open-class items. Dysfluencies were greater on closed-class items and contributed to greater overall reading time for the closed-class words, consistent with a two-route model for the production of closed- and open-class lexical items in Broca's aphasics and, thus, normals.

The most polymorphic residue on Plasmodium falciparum apical membrane antigen 1 determines binding of an invasion-inhibitory antibody.

Apical membrane antigen 1 (AMA1) is currently one of the leading malarial vaccine candidates. Anti-AMA1 antibodies can inhibit the invasion of erythrocytes by Plasmodium merozoites and prevent the multiplication of blood-stage parasites. Here we describe an anti-AMA1 monoclonal antibody (MAb 1F9) that inhibits the invasion of Plasmodium falciparum parasites in vitro. We show that both reactivity of MAb 1F9 with AMA1 and MAb 1F9-mediated invasion inhibition were strain specific. Site-directed mutagenesis of a fragment of AMA1 displayed on M13 bacteriophage identified a single polymorphic residue in domain I of AMA1 that is critical for MAb 1F9 binding. The identities of all other polymorphic residues investigated in this domain had little effect on the binding of the antibody. Examination of the P. falciparum AMA1 crystal structure localized this residue to a surface-exposed alpha-helix at the apex of the polypeptide. This description of a polymorphic inhibitory epitope on AMA1 adds supporting evidence to the hypothesis that immune pressure is responsible for the polymorphisms seen in this molecule.

Anticipatory coarticulation: some implications from a study of lip rounding.

The anticipation of articulatory features, in particular lip rounding in anticipation of a rounded vowel, has been reported to occur as many as four segments before the segment for which the feature is specified. In the data presented here, we find that the moter commands for the rounding gesture for /u/ begin a fixed time before the onset of the vowel. This timing is unaffected by the number of consonant segments in the preceding string. Thus, the initiation of lip rounding appears to be linked to other features of the vowel articulation.

Glycolate in the diet and its conversion to urinary oxalate in the rat.

Less than 3 per cent of the [1-14C]glycolate administered, orally to fasted and nonfasted male Wistar rats was excreted in the feces in 48 hr. This finding indicates that the glycolate was readily absorbed from the digestive tract. An average of 3 per cent of the administered [1-14C]glycolate was also recovered in 48 hr as urinary [14C]oxalate from fasted and nonfasted rats. Significant amounts of glycolate were found in the vegetables, fruits, and beverages analyzed, but much lower amounts were found in meats and milk. Inasmuch as glycolate is naturally present in the diet and contributes to the formation and excretion of urinary oxalate, restricting the intake of glycolate may be beneficial in treating oxalate stone-forming patients.

A temporal model of speech production.

Existing models of speech production and coarticulation have failed to account for observations of real speech because they have considered timing to be a by-product of articulatory events instead of an integral organizing parameter of the speech motor plan. The model offered here considers time and timing relationships to be intrinsic to speech motor organization and the units of speech to be inherently dynamic gestures rather than static vocal tract configurations or invariant commands to the articulators.

Temporal patterns of coarticulation: lip rounding.

According to some theories, anticipatory coarticulation occurs when phones for which a feature is unspecified precede one for which the feature is specified, with consequent migration of the feature value to the antecedent phones. Carryover coarticulation, on the other hand, is often attributed to "articulatory sluggishness." In this paper, EMG evidence is provided that this formulation is inadequate, since the beginning of EMG activity associated with vowel lip rounding is independent of measures of the acoustic duration of adjacent lingual consonants. We suggest that the vowel-rounding gesture simply co-occurs during predictable intervals with portions of preceding and following lingual consonant articulations.

Rotation and translation of the jaw during speech.

A two-dimensional rigid-body model of jaw movement was used to describe jaw opening and closing gestures for vowels and for bilabial and alveolar consonants. Jaw movements were decomposed into three components: (a) rotation about the terminal hinge axis, (b) the horizontal translation of that axis, and (c) the vertical translation of that axis. Data were collected for 3 subjects in two separate recording sessions. Multiple regression analysis was used to examine the relationships among the three jaw movement components. For 2 subjects, but not for the third, an interdependence between jaw rotation and the first principal component of jaw translation, horizontal translation, was observed. For these 2 subjects, the first degree of freedom of jaw movement corresponded to a combination of rotation and the first principal component of jaw translation. For the third subject, the first degree of freedom of jaw movement corresponded to rotation alone. The results of this study, like those of Westbury (1988), indicate that an accurate description of jaw movement during speech requires the recording of two points of jaw movement.

A comparison of intergestural patterns in deaf and hearing adult speakers: implications from an acoustic analysis of disyllables.

Coarticulation studies in speech of deaf individuals have so far focused on intrasyllabic patterning of various consonant-vowel sequences. In this study, both inter- and intrasyllabic patterning were examined in disyllables /symbol see text #CVC/ and the effects of phonetic context, speaking rate, and segment type were explored. Systematic observation of F2 and durational measurements in disyllables minimally contrasting in vocalic ([i], [u,][a]) and in consonant ([b], [d]) context, respectively, was made at selected locations in the disyllable, in order to relate inferences about articulatory adjustments with their temporal coordinates. Results indicated that intervocalic coarticulation across hearing and deaf speakers varied as a function of the phonetic composition of disyllables (b_b or d_d). The deaf speakers showed reduced intervocalic coarticulation for bilabial but not for alveolar disyllables compared to the hearing speakers. Furthermore, they showed less marked consonant influences on the schwa and stressed vowel of disyllables compared to the hearing controls. Rate effects were minimal and did not alter the coarticulatory patterns observed across hearing status. The above findings modify the conclusions drawn from previous studies and suggest that the speech of deaf and hearing speakers is guided by different gestural organization.

Palatoglossus activity during nasal/nonnasal vowels of Hindi.

Prior electromyographic (EMG) research reveals a lack of agreement as to the role of the palatoglossus muscle in speech. Some reports have concluded that it bears primary responsibility for lowering the velum and that it actively controls velar lowering on nasal sounds in speech, whereas others have concluded that it acts to assist in the tongue-body movements associated with the production of back vowels and linguavelar articulations. To clarify these conflicting claims, EMG recordings were obtained from the palatoglossus (as well as the levator palatini) muscle of a native speaker of Hindi who produced CVC nonsense and meaningful syllables containing a nasal or nonnasal vowel in a symmetric consonantal environment. The results showed the following: Palatoglossus activity for the central and back nasal and nonnasal vowels was moderately to considerably higher than for the front nasal and nonnasal vowels. The levels of palatoglossus activity for the back rounded nasal vowels and for the front nasal vowel /e/ were comparable to those for the corresponding nonnasal vowels, while in all other vowels, the nasal vowels exhibited relatively higher levels of palatoglossus activity than their nonnasal counterparts. In all nonnasal vowels, the increase in palatoglossus activity occurred simultaneously with strong levator palatini activity. On the other hand, in nasal vowels, the increase in palatoglossus activity and the decrease in levator palatini activity were virtually synchronous for the front nasal vowels, while the increase in palatoglossus activity began much earlier than the decline in levator palatini activity for the central and back nasal vowels. This difference in temporal relationship between palatoglossus activation and levator suppression for different vowel types is important since it unambiguously supports the 'gate-pull' model (that is, active velar lowering) for the production of front nasal vowels whereas in the case of central and back vowels, nasal and nonnasal, the palatoglossus appears to be primarily involved in moving the tongue-body.