Escaping the cohort of concern: in vitro experimental evidence supports non-mutagenicity of N-nitroso-hydrochlorothiazide.

In recent years, nitrosamine impurities in pharmaceuticals have been subject to intense regulatory scrutiny, with nitrosamine drug substance-related impurities (NDSRIs) treated as cohort of concern impurities, regardless of predicted mutagenic potential. Here, we describe a case study of the NDSRI N-nitroso-hydrochlorothiazide (NO-HCTZ), which was positive in the bacterial reverse mutation (Ames) test but is unstable under the test conditions, generating formaldehyde among other products. The mutagenic profile of NO-HCTZ was inconsistent with that expected of a mutagenic nitrosamine, exhibiting mutagenicity in the absence of metabolic activation, and instead aligned well with that of formaldehyde. To assess further, a modified Ames system including glutathione (3.3 mg/plate) to remove formaldehyde was developed. Strains used were S. typhimurium TA98, TA100, TA1535, and TA1537, and E. coli WP2 uvrA/pKM101. In this system, formaldehyde levels were considerably lower, with a concomitant increase in levels of S-(hydroxymethyl)glutathione (the adduct formed between glutathione and formaldehyde). Upon retesting NO-HCTZ in the modified system (1.6-5000 µg/plate), a clear decrease in the mutagenic response was observed in the strains in which NO-HCTZ was mutagenic in the original system (TA98, TA100, and WP2 uvrA/pKM101), indicating that formaldehyde drives the response, not NO-HCTZ. In strain TA1535, an increase in revertant colonies was observed in the modified system, likely due to a thiatriazine degradation product formed from NO-HCTZ under Ames test conditions. Overall, these data support a non-mutagenic designation for NO-HCTZ and demonstrate the value of further investigation when a positive Ames result does not align with the expected profile.

Use of the Obstetric Quality-of-Recovery score (ObsQoR-11) to measure the impact of an enhanced recovery programme for elective caesarean section.

BACKGROUND: Enhanced recovery after caesarean (ERAC) has been shown to postoperatively reduce opioid consumption, reduce pain scores, and shorten hospital stay. Arguably, none of these measures provide for a patient-centred approach. We believe that patient-reported outcome measures (PROMs) represent a more holistic approach to the reporting of outcomes. One such PROM is the Obstetric Quality-of-Recovery Score (ObsQoR-11). This has been shown to be a valid and reliable assessment of recovery after elective caesarean section. METHODS: This before-and-after quality improvement programme studied consecutive patients undergoing elective caesarean section. We implemented an ERAC pathway with the aim of improving quality of recovery and patient satisfaction. Our primary outcome was the change in the ObsQoR-11 score. RESULTS: A total of 318 medical records were reviewed (n = 93 before ERAC, n = 225 after ERAC). There was a significant improvement in ObsQoR-11 score in ERAC patients compared with pre-ERAC patients (85.0 vs 82.3, P < 0.001). Morphine consumption (MMEQ) was reduced by 10% overall in the ERAC group, with no increase in pain scores at day 1 postoperatively and a decrease in pain scores on day 2 in the ERAC group (P = 0.02). The length of hospital stay was significantly shorter in ERAC patients (63.1 h vs 79.9 h, P < 0.001). CONCLUSIONS: Our study demonstrated an improved ObsQoR-11 score after ERAC implementation. This is the first example in the literature of using ObsQoR-11 in ERAC. We believe this is a more comprehensive way to assess patient recovery and the impact of an ERAC programme.

Evaluation of a new Perinatal Mental Health Service in a University Maternity Hospital.

OBJECTIVES: Specialist Perinatal Mental Health Services (SPMHS) are a new development in Ireland. This service evaluation examined the impact of the introduction of a SPMHS multidisciplinary team (MDT) on prescribing practices and treatment pathways in an Irish maternity hospital. METHODS: Clinical charts were reviewed to collect data on all referrals, diagnoses, pharmacological and non-pharmacological interventions delivered in a SPMHS over a 3-week period in 2019. The findings were compared to the same 3-week period in 2020 following the expansion of the SPMHS MDT. RESULTS: In 2019 (n = 32) and 2020 (n = 47), most (75 and 79%, respectively) assessments were antenatal. The proportion of patients prescribed psychotropic medication within the SPMHS was not significantly different from 2019 (31%) to 2020 (23%), though more patients were already prescribed psychotropic medications at the time of referral (22% in 2019 v. 36% in 2020). There was an increase in MDT interventions in 2020 with more input from psychology, clinical nurse specialist (CNS), and social work intervention. Adherence to prescribing standards improved from 2019 to 2020. CONCLUSION: Prescribing patterns remained unchanged between 2019 and 2020. Improvement was observed in adherence to prescribing standards and there was increased provision of MDT interventions in 2020. Broader diagnostic categories were also used in 2020, possibly suggesting that the service is now providing more individualized care.

The impact of the COVID-19 pandemic on presentations of self-harm over an 18-month period to a tertiary hospital.

OBJECTIVES: To examine and compare rates and methods of self-harm presenting to a tertiary referral hospital during an 18-month period since the onset of the COVID-19 pandemic with a similar period immediately prior to the pandemic onset. METHODS: Data from an anonymized database compared rates of self-harm presentations and methods employed between 1st March 2020 and 31st August 2021 to a similar time-frame prior to the onset of the COVID-19 pandemic. RESULTS: A 9.1% increase in presentations with self-harm was noted since the onset of the COVID-19 pandemic. Periods of more stringent restrictions were associated with higher levels of self-harm (daily rate of 2.10 v 0.77). A higher lethality of attempt was demonstrated post-COVID-19 onset (χ2 = 15.38, p < 0.001). Fewer individuals presenting with self-harm were diagnosed with an adjustment disorder since the onset of the COVID-19 pandemic (n = 84, 11.1%, v. n = 112, 16.2%, χ2 = 7.898, p = 0.005), with no other differences pertaining to psychiatric diagnosis noted. More patients actively engaged with mental health services (MHS) presented with self-harm (n = 239 (31.7%) v. n = 137, (19.8%), χ2 = 40.798, p ≤ 0.001) since the onset of the COVID-19 pandemic. CONCLUSIONS: Despite an initial reduction, an increase in rates of self-harm has occurred since the onset of the COVID-19 pandemic with higher rates evident during periods of higher government mandated restrictions. An increase in active patients of MHS presenting with self-harm potentially relates to reduced availability of supports and particularly group activities. The recommencement of group therapeutic interventions for individuals attending MHS in particular is warranted.

Attempted suicide: does lethality matter?

OBJECTIVES: To investigate whether high-lethality suicide attempters align to the demographic and clinical features observed in completed suicide in the national and international literature, and whether low-lethality attempters more closely align with the clinical profile of non-attempter ideators. METHODS: A retrospective chart review of adult suicide ideators and attempters presenting to an urban tertiary care hospital was performed. Suicide ideators (n = 50) and attempters (n = 50) were coded for variables including demographics and clinical characteristics (e.g. psychiatric diagnosis and previous suicide attempt). Method and lethality of suicide attempt were coded using the medical Lethality Rating Scale. RESULTS: High-lethality attempters were more likely to be younger in age than low-lethality attempters (p = 0.026) and ideators (p = 0.041). The lethality scores of suicide attempts were significantly inversely correlated with age (p = 0.017). CONCLUSIONS: Our study adds to the small but increasing body of literature investigating the characteristics of high-lethality suicide attempters and suggests younger adult age is a risk factor for a high-lethality attempt. Further understanding of this unique group would be aided by widespread agreement on the definition of a high-lethality suicide attempt and longitudinal studies of this cohort.

There is more to this fever than meets the eye: A case of neuroleptic malignant-like syndrome (NMLS) secondary to withdrawal of procyclidine and L-dopa on a background of long-standing flupenthixol depot use.

This case report highlights the risk of development of Neuroleptic Malignant-Like Syndrome secondary to withdrawal of procyclidine with brief withdrawal of L-dopa and long-term typical antipsychotic depot. The patient responded to reintroduction of procyclidine, sedation and supportive treatment. The mechanism and management of NMS and NMLS is also reviewed. This case emphasises that any changes in antipsychotic and antiparkinsonian medications should be undertaken with extreme caution and patient should be closely monitored for development of NMLS after alteration in these medications.

Substance use and self-harm emergency department presentations during COVID19: evidence from a National Clinical Programme for Self-Harm.

INTRODUCTION: Given the evidence that drinking patterns and self-harm hospital presentations have changed during COVID-19, this study aimed to examine any change in self-harm and suicide-related ideation presentations, together with any possible contribution made by alcohol or substance misuse, to Irish Emergency Departments in 2020, compared with 2018 and 2019. METHODS: A population-based cohort with self-harm and suicide-related ideation presenting to Irish hospitals derived from the National Clinical Programme for Self-Harm was analysed. Descriptive analyses were conducted based on sociodemographic variables and types of presentation for the period January to August 2020 and compared with the same period in 2018 and 2019. Binomial regression analyses were performed to investigate the independent effect of demographic characteristics and pre/during COVID-19 periods on the use of substances as contributory factors in the self-harm and suicide-related ideation presentations. RESULTS: 12,075 presentations due to self-harm and suicide-related ideation were recorded for the periods January-August 2018-2020 across nine emergency departments. The COVID-19 year was significantly associated with substances contributing to self-harm and suicide-related ideation ED presentations (OR = 1.183; 95% CI, 1.075-1.301, p < 0.001). No changes in the demographic characteristics were found for those with self-harm or suicide-related ideation across the years. Suicide-related ideation seemed to be increased after May 2020 compared with previous years. In terms of self-harm episodes with comorbid drug and alcohol overdose and poisoning, these were significantly increased in January-August 2020, compared with previous timepoints (χ2 = 42.424, df = 6, p < 0.001). CONCLUSION: An increase in suicide-related ideation and substance-related self-harm presentations may indicate longer term effects of the pandemic and its relevant restrictions. Future studies might explore whether those presenting with ideation will develop a risk of suicide in post-pandemic periods.

Systematic development and feasibility testing of a multibehavioural digital prehabilitation intervention for patients approaching major surgery (iPREPWELL): A study protocol.

Improving outcomes for people undergoing major surgery, specifically reducing perioperative morbidity and mortality remains a global health challenge. Prehabilitation involves the active preparation of patients prior to surgery, including support to tackle risk behaviours that mediate and undermine physical and mental health and wellbeing. The majority of prehabilitation interventions are delivered in person, however many patients express a preference for remotely-delivered interventions that provide them with tailored support and the flexibility. Digital prehabilitation interventions offer scalability and have the potential to benefit perioperative healthcare systems, however there is a lack of robustly developed and evaluated digital programmes for use in routine clinical care. We aim to systematically develop and test the feasibility of an evidence and theory-informed multibehavioural digital prehabilitation intervention 'iPREPWELL' designed to prepare patients for major surgery. The intervention will be developed with reference to the Behaviour Change Wheel, COM-B model, and the Theoretical Domains Framework. Codesign methodology will be used to develop a patient intervention and accompanying training intervention for healthcare professionals. Training will be designed to enable healthcare professionals to promote, support and facilitate delivery of the intervention as part of routine clinical care. Patients preparing for major surgery and healthcare professionals involved with their clinical care from two UK National Health Service centres will be recruited to stage 1 (systematic development) and stage 2 (feasibility testing of the intervention). Participants recruited at stage 1 will be asked to complete a COM-B questionnaire and to take part in a qualitative interview study and co-design workshops. Participants recruited at stage 2 (up to twenty healthcare professionals and forty participants) will be asked to take part in a single group intervention study where the primary outcomes will include feasibility, acceptability, and fidelity of intervention delivery, receipt, and enactment. Healthcare professionals will be trained to promote and support use of the intervention by patients, and the training intervention will be evaluated qualitatively and quantitatively. The multifaceted and systematically developed intervention will be the first of its kind and will provide a foundation for further refinement prior to formal efficacy testing.

Post-acquisition mask misalignment correction for edge illumination x-ray phase contrast imaging.

Edge illumination x-ray phase contrast imaging uses a set of apertured masks to translate phase effects into variation of detected intensity. While the system is relatively robust against misalignment, mask movement during acquisition can lead to gradient artifacts. A method has been developed to correct the images by quantifying the misalignment post-acquisition and implementing correction maps to remove the gradient artifact. Images of a woven carbon fiber composite plate containing porosity were used as examples to demonstrate the image correction process. The gradient formed during image acquisition was removed without affecting the image quality, and results were subsequently used for quantification of porosity, indicating that the gradient correction did not affect the quantitative content of the images.

Lockdown logistics in consultation-liaison psychiatry.

We describe the adaptation of services to allow flexible and practical responses to the coronavirus-19 (COVID-19) public health crisis by four Consultation-Liaison Psychiatry (CLP) services; Galway University Hospital (GUH), Beaumont Hospital, University Hospital Waterford and St Vincent's University Hospital (SVUH) CLP services. This article also illustrates close collaboration with community adult mental health services and Emergency Department (ED) colleagues to implement effective community diversion pathways and develop safe, effective patient assessment pathways within the EDs. It highlights the high levels of activity within each of the CLP services, while also signposting that many of the rapidly implemented changes to our practice may herald improvements to mental health patient care delivery in the post-COVID-19 world, if our psychiatry services receive appropriate resources.

Consultant psychiatrists' experience of the impact of the COVID-19 pandemic on mental health services.

OBJECTIVES: The novel coronavirus 2019 (COVID-19) has spread worldwide threatening human health. To reduce transmission, a 'lockdown' was introduced in Ireland between March and May 2020. The aim of this study is to capture the experiences of consultant psychiatrists during lockdown and their perception of it's impact on mental health services. METHODS: A questionnaire designed by the Royal College of Psychiatrists was adapted and circulated to consultant members of the College of Psychiatrists of Ireland following the easing of restrictions. The questionnaire assessed the perceived impact on referral rates, mental health act provision, availability of information technology (IT), consultant well-being and availability of personal protective equipment (PPE). Thematic analysis was employed to analyse free-text sections. RESULTS: Response rate was 32% (n = 197/623). Consultants reported an initial decrease/significant decrease in referrals in the first month of lockdown (68%, n = 95/140) followed by an increase/significant increase in the second month for both new (83%, n = 100/137) and previously attending patients (65%, n = 88/136). Social isolation and reduced face-to-face mental health supports were among the main reasons identified. The needs of children and older adults were highlighted. Most consultants (76%, n = 98/129) felt their working day was affected and their well-being reduced (52%, n = 61/119). The majority felt IT equipment availability was inadequate (67%, n = 88/132). Main themes identified from free-text sections were service management, relationship between patients and healthcare service and effects on consultants' lives. CONCLUSIONS: The COVID-19 pandemic has placed increased pressure on service provision and consultant wellness. This further supports the longstanding need to increase mental health service investment.

Spontaneous Escherichia coli Meningitis and Pyogenic Ventriculitis in an Adult Receiving Anti-Tumour Necrosis Factor Alpha Therapy.

Presentation A 60-year-old male taking etanercept for ankylosing spondylitis was admitted to hospital with confusion and reduced level of consciousness over the preceding 24 hours. Diagnosis Magnetic Resonance Imaging (MRI) of his brain revealed pyogenic ventriculitis, and Escherichia coli was cultured from CSF. Treatment He required placement of an external ventricular drain and was treated with a prolonged course of intravenous ceftriaxone. Conclusion To our knowledge, this is the first reported case of spontaneous Gram-negative bacillary meningitis in a patient on anti-tumour necrosis factor (TNF)-alpha therapy, highlighting the risk of rare but serious infections associated with this class of medication.

COVID-19 and its effect on emergency presentations to a tertiary hospital with self-harm in Ireland.

OBJECTIVES: This study aimed to assess the impact of COVID-19 on presentations to an acute hospital with self-harm. METHODS: All presentations to University Hospital Galway with self-harm were assessed during the peak period of the coronavirus crisis in Ireland, over the 3 months from 1 March to 31 May 2020. These data were compared with presentations in the same months in the 3 years preceding (2017-2019). Data were obtained from the anonymised service database. RESULTS: This study found that in 2020, the rate of presentation with self-harm dropped by 35% from March to April and rose by 104% from April to May, peaking from mid-May. When trends over a 4-year period were examined, there was a significantly higher lethality of attempt (p < 0.001), and significant differences in diagnosis (p = 0.031) in 2020 in comparison with the three previous years. The increased lethality of presentations remained significant after age and gender were controlled for (p = 0.036). There were also significant differences in the underlying psychiatric diagnoses (p = 0.018), notably with a significant increase in substance misuse disorders presenting during the 2020 study period. CONCLUSIONS: COVID-19 showed a reduction in self-harm presentations initially, followed by a sharp increase in May 2020. If a period of economic instability follows as predicted, it is likely that this will further impact the mental health of the population, along with rates of self-harm and suicidal behaviours. There is a need for research into the longer-term effect of COVID-19 and lockdown restrictions, especially with respect to self-harm.

The Impact of Neoadjuvant Chemotherapy on Margin Re-excision in Breast-Conserving Surgery.

BACKGROUND: Neoadjuvant chemotherapy (NAC) can improve cosmesis by reducing resection volume. Breast-conserving surgery (BCS) aims to achieve clear excision margins while optimizing cosmesis. However, the influence of NAC on margin re-excision after BCS is unclear. This study examines the rate and determinants of margin re-excision in patients undergoing BCS following NAC in our institution. METHODS: From 2011-2015, all patients treated with NAC prior to BCS were identified from a prospectively maintained database. Mann-Whitney and Fisher's exact test tests were used to compare variables in patients who did and did not require re-excision. Patients undergoing primary surgical treatment in 2015 comprised an unmatched comparison group. RESULTS: Of 211 patients treated with NAC, 69 initially underwent BCS. The re-excision rate was 32% (n = 22) compared to 17% in the primary operable group (38 of 221, p = 0.02). Re-excision rates were lowest in triple-negative and HER2+ tumors (0% and 10%, respectively). Lobular carcinoma and ER+ tumors had a significantly higher rate of re-excision (100% and 42%, respectively). Of 22 patients undergoing re-excision, 9 had further BCS and 13 had a mastectomy. CONCLUSION: The re-excision rate following NAC is almost twice that of patients who underwent primary operative management. Her2+ and triple-negative tumors have lower re-excision rates and may represent a selected cohort most suitable for BCS. Patients with invasive lobular carcinoma or ER+ disease have significantly higher rates of margin positivity, and these patients should be considered for a cavity shave during primary surgery to reduce the rates of re-excision.

Eating well, living well and weight management: A co-produced semi-qualitative study of barriers and facilitators experienced by adults with intellectual disabilities.

Adults with intellectual disabilities in England experience health inequalities. They are more likely than their non-disabled peers to be obese and at risk of serious medical conditions such as heart disease, stroke and type 2 diabetes. This semi-qualitative study engaged adults with intellectual disabilities in a co-production process to explore their perceived barriers and facilitators to eating well, living well and weight management. Nineteen participants with intellectual disabilities took part in four focus groups and one wider group discussion. They were supported by eight of their carers or support workers. Several barriers were identified including personal income restrictions, carers' and support workers' unmet training needs, a lack of accessible information, inaccessible services and societal barriers such as the widespread advertising of less healthy foodstuffs. A key theme of frustration with barriers emerged from analysis of participants' responses. Practical solutions suggested by participants included provision of clear and accessible healthy lifestyle information, reasonable adjustments to services, training, 'buddying' support systems or schemes and collaborative working to improve policy and practice.

A pilot study of an integrated mental health, social and medical model for diabetes care in an inner-city setting: Three Dimensions for Diabetes (3DFD).

AIMS: We examined the effectiveness of a service innovation, Three Dimensions for Diabetes (3DFD), that consisted of a referral to an integrated mental health, social care and diabetes treatment model, compared with usual care in improving biomedical and health economic outcomes. METHODS: Using a non-randomized control design, the 3DFD model was offered in two inner-city boroughs in London, UK, where diabetes health professionals could refer adult residents with diabetes, suboptimal glycaemic control [HbA1c ≥ 75 mmol/mol (≥ 9.0%)] and mental health and/or social problems. In the usual care group, there was no referral pathway and anonymized data on individuals with HbA1c ≥ 75 mmol/mol (≥ 9.0%) were collected from primary care records. Change in HbA1c from baseline to 12 months was the primary outcome, and change in healthcare costs and biomedical variables were secondary outcomes. RESULTS: 3DFD participants had worse glycaemic control and higher healthcare costs than control participants at baseline. 3DFD participants had greater improvement in glycaemic control compared with control participants [-14 mmol/mol (-1.3%) vs. -6 mmol/mol (-0.6%) respectively, P < 0.001], adjusted for confounding. Total follow-up healthcare costs remained higher in the 3DFD group compared with the control group (mean difference £1715, 95% confidence intervals 591 to 2811), adjusted for confounding. The incremental cost-effectiveness ratio was £398 per mmol/mol unit decrease in HbA1c , indicating the 3DFD intervention was more effective and costed more than usual care. CONCLUSIONS: A biomedical, psychological and social criteria-based referral system for identifying and managing high-cost and high-risk individuals with poor glycaemic control can lead to improved health in all three dimensions.

Paraneoplastic syndromes and oncological outcomes in renal cancer.

BACKGROUND: Paraneoplastic syndromes (PNS) have been defined as a constellation of symptoms and signs seen in patients with malignancy, which cannot be ascribed to the local or distant spread of the tumor. Renal cell carcinoma (RCC) is most commonly associated with PNS among urological malignancies. We describe the incidence of PNS and the association between the syndromes and oncological outcomes in our patients with RCC. SUBJECTS AND METHODS: A retrospective cohort study done at Lagos State University Teaching Hospital, Ikeja, Lagos. This was a retrospective review of our patients who had RCC over 11-year period (2006 to 2016). The incidence of PNS syndromes were hypercalcemia, Stauffer's syndrome, hypertension, anemia, elevated erythrocyte sedimentation rate (ESR), persistent leukocytosis, and its correlation to outcome of disease were analyzed. In addition, the age, gender, clinical features, and stage of disease were analyzed. Chi square, Fischer exact test, and Kaplan-Meier survival, curve and logistic regression. RESULTS: : In total, 101 patients were operated within the period. Age of the patients ranged from 11 to 81 years (mean of 45.17 ± 16.3). There were 46 males and 55 females with M:F ratio of 1:1.2. Majority of the patients, 74 (73%), had clear cell variant of RCC. Twenty-seven patients (26.7%) had triad of flank pain, flank mass, and hematuria. The incidence of PNS were hypercalcaemia 7 (6.9%), Stauffer's syndrome 12 (11.9%), hypertension 16 (15.8%), anemia 61 (60.4%), elevated ESR 56 (55.4%), and persistent leukocytosis 3 (3.0%). At a median follow-up of 6 months, 72 patients (71.3%) were alive, whereas 29 patients (28.7%) were dead. CONCLUSION: Among the PNS, only Stauffer's syndrome was significantly associated with poor outcome.