Pyroglutamic acidosis caused by the combination of two common medicines prescribed in everyday practice.

We present the case of a 71-year-old female treated for infective endocarditis with flucloxacillin and paracetamol. Her clinical course became complicated by a blood-gas demonstrating a raised anion gap metabolic acidosis. The patient was diagnosed with pyroglutamic metabolic acidosis. This is a rare interaction between high dose flucloxacillin and paracetamol, and is an important complication to recognize.

Hospital outbreak of linezolid-resistant and vancomycin-resistant ST80 Enterococcus faecium harbouring an optrA-encoding conjugative plasmid investigated by whole-genome sequencing.

BACKGROUND: Linezolid is an antibiotic used to treat infections caused by multi-drug-resistant Gram-positive bacteria. Linezolid resistance in enterococci has been reported with increasing frequency, with a recent rise in resistance encoded by optrA, poxtA or cfr. AIM: To investigate a hospital outbreak of linezolid- and vancomycin-resistant Enterococcus faecium (LVREfm) using whole-genome sequencing (WGS). METHODS: Thirty-nine VREfm from patient screening (19 isolates, 17 patients) and environmental sites (20 isolates) recovered in October 2019 were investigated. Isolates were screened using polymerase chain reaction for optrA, poxtA and cfr, and underwent Illumina MiSeq WGS. Isolate relatedness was assessed using E. faecium core genome multi-locus sequence typing (cgMLST). One LVREfm underwent MinION long-read WGS (Oxford Nanopore Technologies) and hybrid assembly with MiSeq short-read sequences to resolve an optrA-encoding plasmid. FINDINGS: Twenty isolates (51.3%) were LVREfm and optrA-positive, including the LVREfm from the index patient. A closely related cluster of 28 sequence type (ST) 80 isolates was identified by cgMLST, including all 20 LVREfm and eight linezolid-susceptible VREfm, with an average allelic difference of two (range 0-10), indicating an outbreak. Nineteen (95%) LVREfm harboured a 56,684-bp conjugative plasmid (pEfmO_03). The remaining LVREfm exhibited 44.1% sequence coverage to pEfmO_03. The presence of pEfmO_03 in LVREfm and the close relatedness of the outbreak cluster isolates indicated the spread of a single strain. The outbreak was terminated by enhanced infection prevention and control (IPC) and environmental cleaning measures, ceasing ward admissions and ward-dedicated staff. CONCLUSION: WGS was central in investigating an outbreak of ST80 LVREfm. The rapid implementation of enhanced IPC measures terminated the outbreak.

Knowledge of the risk factors and symptoms associated with endometrial cancer in British South Asian and British White women.

OBJECTIVE: To explore differences in the background knowledge of Endometrial Cancer (EC), its risk factors, symptoms and prognosis of Endometrial Cancer (EC) between British White (BW) and British South Asian (BSA) women who had undergone treatment for stage I endometrial cancer within the past 3-years. STUDY DESIGN: Face-to-face, semi-structured interviews exploring knowledge; diagnosis; treatment; follow-up; and survivorship were undertaken and analysed using Thematic Analysis. RESULTS: Twenty-one women were interviewed (13 BW and 8 BSA). BW and BSA women reported similar views, experiences and concerns with regards to EC. Knowledge appeared to differ amongst the two groups with BSA women reporting being more aware that unscheduled vaginal bleeding could be associated with a malignancy but having lower levels of knowledge of the risk factors that can lead to EC, compared to BW women. There was a lack of understanding of the difference between cervical cancer and EC and as a result, many women reported taking reassurance from negative cervical cytology as excluding EC. There was also the misconception amongst some of the women that there was a link between sexual behaviour and EC. Women from both groups used the lay healthcare system to discuss their situation/symptoms, however BSA women reported to have specifically sought out women within their social network who had previously undergone treatment for EC. CONCLUSIONS: Greater effort is needed to raise awareness in both the BW/BSA communities of the symptoms associated with EC that should prompt medical review. Educational efforts are required to overcome the reported perception that EC is synonymous with cervical cancer and cannot be detected by cervical screening.

Iatrogenic Menopause After Treatment for Cervical Cancer.

The ever-improving prognosis of women diagnosed with cervical cancer has meant that survivorship and treatment-related sequelae are being brought more into the spotlight in an attempt to try to reduce morbidity and improve women's long-term health. However, there are many issues surrounding an iatrogenic menopause in cervical cancer, a variety of potential management options and barriers to treatment. Women who have become menopausal under the age of 45 years as a result of cervical cancer are significantly less likely to start hormone replacement therapy (HRT) or continue it long term as compared with those who have undergone a surgical menopause for a benign reason. High profile media reports raising concerns about the safety of HRT use have left many women reluctant to consider HRT as a therapeutic option for menopausal symptoms and many are seeking to use complementary/alternative medicine, including non-pharmacological interventions, to alleviate symptoms. The benefits of HRT in this population have been shown to reduce these effects, although adherence to treatment regimens is a challenge due to poor compliance, which is in part due to the fear of a second malignancy. The development of non-HRT-based interventions to ameliorate menopausal symptoms and reduce the long-term health consequences are needed for women who choose not to take HRT.

Responses of track and field coaches to athletes with eating problems.

This study aimed to explore how track and field coaches respond to athletes with eating problems. Eleven experienced coaches participated in semi-structured interviews exploring their responses to, and challenges faced when, working with athletes with eating problems. The analysis revealed three themes relating to the strategies employed by coaches. The first theme indicated a supportive approach, where coaches were proactive in seeking support and in reducing training at the early stages of an eating problem. The second theme outlined an avoidant approach, characterized by coach reluctance to be involved in managing eating problems, and a lack of confidence in their knowledge of eating disorders. The third theme involved a confrontational approach, where coaches employed strict rules and engaged in coercion to persuade athletes to seek treatment. All of the coaches reported facing challenges in persuading athletes to seek treatment and were frustrated by the lack of available support. The study highlights the importance of providing resources and support services where coaches can seek advice. Coach-education packages can utilize the findings to highlight the strengths and limitations of different coach strategies, and to reinforce the importance of their role in identification and intervention when eating problems in athletes are suspected.

Postprocedural discitis of the vertebral spine: challenges in diagnosis, treatment and prevention.

BACKGROUND: Although post-procedural discitis is relatively uncommon, the consequences can be very clinically significant. AIM: We reviewed aspects on the diagnosis, management and prevention of post-procedural discitis. METHODS: We reviewed the literature published in English over the last twenty years using a variety of appropriate search terms. RESULTS: Clinical features, microbiology results, imaging and inflammatory makers should be used in diagnosis. Every effort should be made to confirm infection to avoid unnecessary antibiotics and to facilitate targeted therapy. Surgical debridement or source control is a crucial aspect of treatment and can provide diagnosis specimens to guide antibiotic treatment. When culture results are positive, antibiotic treatment should be based on the results of antibiotic susceptibilities. There are no definitive guidelines on antibiotic therapy. A combination of agents, such as a quinolone or clindamycin, with fusidic acid or rifampicin, is indicated for empirical therapy. Early intravenous to oral switch and a minimum of six weeks of antibiotic treatment is recommended. Prevention involves antimicrobial prophylaxis perioperatively, good surgical technique and minimally invasive surgery where possible. CONCLUSION: Much of the information currently available is sub-optimal with the absence of good clinical trials. Further research is required on alternative approaches to routine culture and on the potential role of local antibiotics as prevention measures.

Isolation of NDM-1-producing Klebsiella pnemoniae in Ireland, July 2011.

We report the identification of New Delhi metallo-betalactamase 1 (NDM-1)-producing Klebsiella pnemoniae in Ireland. The organism was resistant to multiple antibiotic classes, including carbapenems, and PCR and sequencing confirmed the presence of the blaNDM-1 gene, carried on a 98 kb plasmid. The organism was isolated from an infant, who was born in India and moved to Ireland at the age of four months. This is the first reported isolation of an NDM-1-producing Enterobacteriaceae strain in Ireland.

Sporobolomyces roseus in the cerebrospinal fluid of an immunocompetent patient--to treat or not to treat?

We present the case of an immunocompetent male who presented with symptoms of meningitis. Yeasts were seen in two consecutive cerebrospinal fluid samples, which were identified by PCR as Sporobolomyces roseus. This yeast is rarely encountered in clinical settings, and has only previously been seen to cause infection in immunocompromised patients. This case highlights the challenges presented by the identification of an unusual pathogen in an unexpected clinical setting.

Developing occupational health services for active age management.

AIMS: To review current occupational health (OH) approaches aimed at maintaining the health and workability of older workers. METHODS: A literature review was undertaken to identify articles on OH interventions focused on maintaining the health of older workers (published since 2000). The inclusion criteria included studies that reported interventions aimed specifically at older workers. RESULTS: A limited number of interventions targeting older workers were identified. A second literature search was therefore conducted that identified types of workplace interventions that, if used with older workers, may benefit their health, well-being and workability. CONCLUSIONS: Very few OH interventions have addressed the health and workability of older workers and there is considerable scope for developing OH provision, which accounts for the needs of the older workforce.

Loudness summation for pulsatile electrical stimulation of the cochlea: effects of rate, electrode separation, level, and mode of stimulation.

The aim of these two experiments was to gain systematic data on the amount of loudness summation measured for dual-electrode stimuli with varying temporal and spatial separation of current pulses. Loudness summation is important in the implementation of speech processing strategies for implantees. However, the loudness mapping functions used in current speech processors utilize psychophysical data (thresholds and comfortable loudness levels) derived using single-electrode stimuli, and do not take into account the temporal and spatial patterns of the speech processor output. In the first experiment, the current reduction required to equalize the loudness of a dual-electrode stimulus to that of its component (and equally loud) single-electrode stimuli was measured for three electrode separations (0.75, 2.25, and 7.5 mm), three repetition rates (250, 500, and 1000 Hz), and two loudness levels (comfortably loud, and mid-dynamic range). It was found that electrode separation had little effect on loudness summation, except for interactions with level and rate effects at the smallest separation. More current adjustment (in dB) was required for higher rates and lower levels of stimulation. The second experiment investigated the effects of mode (monopolar versus bipolar) and pulse duration on loudness summation. More current adjustment was required in bipolar mode than in monopolar mode at the lower level only. The main effects in both experiments, and their interactions, are consistent with a loudness model in which the neural excitation density is first obtained by temporal integration of excitation at each cochlear place, then converted to specific loudness via a nonlinear relationship, and finally integrated over cochlear place to obtain the loudness. The two important features which affect the loudness relationships in dual-electrode stimulation in this model are the shape of the excitation density function and the amount by which the neural spike probability per pulse is reduced in areas of overlapping excitation due to refractory effects.

Preliminary results with the AVR ImpaCt frequency-transposing hearing aid.

Currently, the only behind-the-ear hearing aid that provides a frequency transposition function is the ImpaCt DSR675, recently introduced by AVR Communications Ltd. of Israel. In tests with three hearing-impaired adults, the performance of the ImpaCt aid(s) was compared with that of each subject's own (nontransposing) hearing aids. Recognition of monosyllabic words and medial consonants did not differ significantly between the two types of aids. This suggests that the transposition function of the ImpaCt was not effective at providing these subjects with increased high-frequency speech information, at least for the programmable parameters applied in the experiments. However, the subjects' understanding of sentences in a competing noise was significantly poorer with the ImpaCt than with the subjects' own aids. In that test, the ImpaCt aids were programmed to attenuate parts of the noise. The decreased sentence recognition may have resulted from this program, which effectively reduced the bandwidth of the ImpaCt aids.

Preferred listening levels: the effect of background noise for moderate-to-profoundly hearing impaired aid users.

The effects of background noise on the choice of preferred listening level for moderately-to-profoundly hearing impaired adults were investigated. During three listening conditions: 'quiet' (isolated monosyllables), 'suppress' (speech with noise attenuated in the gaps between words), and 'steady' (speech with continuous noise), subjects chose a level that maximized intelligibility without being uncomfortable while listening through a hearing aid. The group mean preferred level for 'suppress' was significantly higher than for 'steady', indicating that the level of noise between words influenced these subjects' choice of listening level. Average word recognition scores were higher in 'suppress' than in 'steady', but the difference was not statistically significant. Subjective loudness and quality ratings indicated no reduction in comfort or quality at the higher level for 'suppress'. The results suggest that a hearing aid that attenuated the level of background noise between words, or temporarily increased the gain during each word, would enable some listeners to tolerate higher levels of speech, thereby improving audibility and possibly speech perception while maintaining listening comfort.

The relationship between speech perception and electrode discrimination in cochlear implantees.

Speech Intelligibility Index (SII) procedures were used to measure the amount of speech information perceived in five frequency bands (170-570, 570-1170, 1170-1768, 1768-2680, and 2680-5744 Hz) by 15 users of the Cochlear Ltd. CI-22M implant and Spectra-22/SPEAK processor. The speech information perceived was compared to that perceived by normal-hearing listeners. The ability of these subjects to discriminate between stimulation on adjacent electrodes corresponding to each frequency band was also investigated, using a 4IFC procedure with random current level variations of between 0% and 60% of the dynamic range. Relative to normal-hearing listeners, speech information was, on average, significantly more reduced in the four frequency regions between 170 and 2680 Hz than in the region 2680-5744 Hz. There was a significant correlation between electrode discrimination ability (when the random level variation encompassed 20% or more of the dynamic range) and the amount of speech information perceived in the four frequency regions between 170 and 2680 Hz. There was no such correlation in the region 2680-5744 Hz, regardless of the extent of random level variation. These results indicate that speech information in the low to medium frequencies is more difficult for implantees to perceive, that this difficulty is correlated with the difficulty in discriminating electrode place in the presence of random loudness variations, and that fine spectral discrimination may be relatively more important in the vowel-formant regions than in higher frequency regions.

Injury-induced reorganization in adult auditory cortex and its perceptual consequences.

Restricted cochlear lesions in adult animals result in a reorganization of auditory cortex such that the cortical region deprived of its normal input by the lesion is occupied by expanded representations of adjacent cochlear loci, and thus of the frequencies represented at those loci. Analogous injury-induced reorganization is seen in somatosensory, visual and motor cortices of adult animals after restricted peripheral lesions. The occurrence of such reorganization in a wide range of species (including simian primates), and across different sensory systems and forms of peripheral lesion, suggests that it would also occur in humans with similar lesions. Direct evidence in support of this suggestion is provided by a small body of functional imaging evidence in the somatosensory and auditory systems. Although such reorganization does not seem to have a compensatory function, such a profound change in the pattern of cortical activation produced by stimuli exciting peri-lesion parts of the receptor epithelium would be expected to have perceptual consequences. However, there is only limited psychophysical evidence for perceptual effects that might be attributable to injury-induced cortical reorganization, and very little direct evidence for the correlation between the perceptual phenomena and the occurrence of reorganization.

Speech perception with steeply sloping hearing loss: effects of frequency transposition.

Six adults with a very steeply sloping high-frequency hearing loss listened to monosyllabic words in several conditions. In the first condition, their ability to identify phonemes with a signal-to-noise ratio of 6 dB was measured. Results were similar to those of normally hearing subjects listening to the same material through low-pass filters having comparable cut-off frequencies. In the remaining two conditions, four of the hearing-impaired subjects, and a control group of five normally hearing subjects, listened to speech in quiet with and without frequency transposition. The transposition lowered all speech frequencies by a factor of 0.6. Specific auditory training with transposed speech materials different from the materials used in the tests of speech perception was provided in 10 sessions, each of one hour's duration, which were scheduled at weekly intervals. Despite this training, no significant differences were found between the two conditions in these subjects' recognition of words. It is concluded that such a frequency-transposition scheme, if implemented in a wearable hearing aid, would be unlikely to benefit people with a sloping hearing impairment of this type.

Improvements in speech perception with use of the AVR TranSonic frequency-transposing hearing aid.

Five adults with sensorineural hearing impairment participated in a trial comparing the performance of the AVR TranSonic frequency-transposing hearing aid with that of their own conventional aids. They used the TranSonic for approximately 12 weeks, during which time systematic changes were made to the transposition parameters. Speech perception was assessed with each setting of those parameters and with the participants' own hearing aids. Four participants obtained significantly higher scores with the TranSonic than with their own aids on at least one of the tests. However, analysis of the consonant confusions suggested that the improvement resulted mostly from the TranSonic's low-frequency electro-acoustic characteristics. There was only limited evidence for 2 of the participants that the frequency-lowering function was effective at improving speech perception.

The perceptual effects of current pulse duration in electrical stimulation of the auditory nerve.

In cochlear implants employing pulsatile stimulation, loudness is controlled by current amplitude and/or pulse duration. Five experiments were conducted with cochlear implantees to investigate the hypothesis that perceptual effects other than loudness result from changes in pulse duration for durations from 50 to 266 microseconds. In experiment 1, five subjects' ability to discriminate equally loud pulse trains employing differing pulse durations was measured at four electrode positions. In 11 of the 20 cases, subjects could significantly discriminate these stimuli. In experiments 2 and 3, discrimination was measured of dual-electrode stimuli which differed in overall temporal pattern but had an equal temporal pattern on each of the individual electrodes (separated by 0 to 9 mm). Discrimination was compared for stimuli employing short or long pulse durations and, in experiment 3, employing different pulse durations on each electrode. When the pulse duration was longer, six out of seven subjects could either combine temporal information across electrode positions at wider electrode separations (experiment 2) or had better discrimination at the same electrode separation (experiment 3). This result was consistent with the hypothesis that longer pulse durations result in a greater spread of excitation than equally loud stimuli using shorter pulse durations. In experiment 4, pulse rate discrimination was compared for stimuli with differing pulse durations, and in four out of five subjects, there was no effect of pulse duration. Finally, the dB change in current per doubling of pulse duration for threshold and equally loud stimuli was calculated for nine subjects (52 electrodes). Values ranged from -5.9 to -2.0 dB/doubling, and were significantly correlated with the absolute intensity of the stimulus. This result was hypothesized to be due to a relationship between the neural charging characteristics and the distance of the excited neural elements from the electrode.

Control of hearing-aid saturated sound pressure level by frequency-shaped output compression limiting.

To fit a hearing aid successfully, it is important to set the Saturated Sound Pressure Level (SSPL) or Maximum Power Output (MPO) appropriately. The SSPL should be low enough to prevent sounds from being amplified to uncomfortable loudness, and yet high enough to maximize speech intelligibility and signal quality. To help attain an optimum SSPL setting, a novel output compression limiting scheme, with shapable MPO (ShaMPO), has been devised. In ShaMPO, the SSPL is shaped across frequencies in accordance with the individual user's loudness discomfort levels (LDLs). The contributions of different frequency regions to loudness are controlled by summing the amplified signal power relative to the LDLs across frequencies, and using this signal to control a wideband compressor. This scheme and a conventional output compression limiting (AGCo) scheme have been implemented in a digital hearing aid. Ten subjects, with moderately-severe to profound sensorineural hearing losses, participated in a study comparing speech intelligibility and listening comfort for the two schemes. Results showed that there were no significant differences in the speech perception scores between AGCo and ShaMPO, even when the speech was presented at 80 dBA, at which level both schemes were in compression much of the time. However, an examination of how subjects selected the SSPL for the two schemes revealed that, in many instances, AGCo would permit some sounds with compact spectra to be amplified above LDL, whereas ShaMPO would not. Thus the ShaMPO scheme can improve listening comfort for some intense sounds without a loss of speech intelligibility. In contrast, half the subjects found speech at 80 dBA to be uncomfortably loud when listening through their own aids.

Can we justify spermatid microinjection for severe male factor infertility?

During 1995 and 1996 the first spermatid pregnancies were announced with both round spermatid (ROSI) and elongated spermatid (ELSI) injections. These publications were flanked by live births from ROSI in a number of animal species, with resulting offspring appearing normal, healthy and fertile. However, the live births in humans heralded a scientific and ethical debate on the clinical use of this technology; and in a number of countries nationwide moratoria prohibiting spermatid microinjection were enjoined. Concerns surrounded the biological condition of spermatids and clinical implications of utilizing an immature spermatozoon for conception. Nevertheless, case reports and a few scientific studies on human spermatid conception have been published in recent years, and further polemic on testicular histopathology and prognosis has ensued. This paper reviews the current arguments on the clinical use of ROSI and ELSI, and evaluates the biology of the main contributory components of a spermatozoon to the subsequent embryo, namely the genetic material, the microtubular organizing complex and the putative oocyte activating factor. We also consider the relevant testicular histopathology and likely outcome in the context of the current birth rate from ROSI and ICSI. We conclude by considering the way forward for infertile men who require this technology to become genetic fathers, and whether the time is now appropriate to consider clinical trials.

Loudness perception with pulsatile electrical stimulation: the effect of interpulse intervals.

The effect of interpulse intervals on the perception of loudness of biphasic current pulse trains was investigated in eight adult cochlear implantees at three different stimulus levels encompassing the psychophysical dynamic range. Equal-loudness contours and thresholds were obtained for stimuli in which two biphasic pulses were presented in a fixed repetition period (4 and 20 ms), and also for single-pulse/period stimuli with rates varying between 20 and 750 Hz. All stimuli were of 500-ms duration, and the phase durations of each pulse were 100 microseconds or less. The results of these experiments were consistent with predictions of a three-stage model of loudness perception, consisting of a peripheral refractory effect function, a sliding central integration time window, and a central equal-loudness decision device. Application of the model to the data allowed the estimation of neural refractory characteristics of the subjects' remaining peripheral neural population. The average neural spike probability for a 50-Hz stimulus was predicted to be about 0.77, with an associated neural refractory time of 7.3 ms. These predictions did not vary systematically with level, implying that the effect of increasing current level on loudness results more from recruitment of neurons than from any increase in average spike probability.