Comparative Outcomes of Budesonide MMX versus Prednisolone for Ulcerative Colitis: Results from a British Retrospective Multi-Centre Real-World Study

During the COVID-19 pandemic many IBD units chose Budesonide MMX (Cortiment) as the first-line treatment for flares of ulcerative colitis (UC) in outpatients for its favourable side effect profile. This retrospective study of all UC patients treated with oral steroids between 1 March 2019–30 June 2019 and 1 March 2020–30 June 2020 aimed to compare Cortiment with Prednisolone in routine clinical practice. Outcomes included the need for hospitalisation for acute severe ulcerative colitis, symptoms at four weeks and end of treatment, and the need for rescue Prednisolone. The 2019 and 2020 cohorts did not differ at the baseline. Cortiment prescriptions rose from 24.5% in 2019 to 70.1% in 2020 (p < 0.001). At week four there were significant differences between 2019 and 2020 in mean bowel frequency (3.49 vs. 5.85, p = 0.001), rectal bleeding <50% (89.7% vs. 73.1% of patients, p = 0.039), and physician global assessment (PGA) (39.2% vs. 19.8% in remission, p = 0.045). There was no significant difference in hospital admissions, rectal bleeding, and PGA at week eight. Rescue Prednisolone was required in 10% of Cortiment patients in 2019 vs. 31.3% in 2020 (p = 0.058). Active IBD is associated with worse COVID-19 outcomes prompting the careful evaluation of the choice of first-line steroid for UC, as Cortiment was associated with worse outcomes at four weeks.

High dose antipsychotic polypharmacy and dopamine partial agonists - time to rethink guidelines?

Guidelines for the treatment of schizophrenia limit the use of antipsychotic agents to clinically-established maximum doses. This acknowledges both the absence of additional efficacy of dopamine D2 receptor antagonists above a receptor occupancy threshold, and the increases in side effects that can occur at higher doses. These limits restrict the dosing of combinations of antipsychotics as they do single agents; drugs sharing the major antipsychotic mechanism of D2 receptor antagonism will act additively in blocking these receptors. Several newer antipsychotic drugs, including aripiprazole and cariprazine, act as partial agonists at the D2 receptor site and avoid action at several other receptors, effects at which are responsible for some non-dopaminergic adverse effects. This pharmacology imparts different characteristics to the drugs resulting often in a more favourable side effect profile. Their partial agonism, along with high affinities for the D2 receptor, also means that these drugs given adjunctively may in part replace, rather than enhance, the D2 antagonism of other antipsychotic agents. This can result in an improvement in certain side effects without loss of antipsychotic efficacy. This article makes the case for distinguishing the D2 partial agonists from antagonists in defining maximum doses of combined treatments, which would increase the options available to the prescriber, emphasising that pharmacological mechanisms need to be understood in identifying optimal treatments for psychotic illness.

Rapid efficacy of aripiprazole in the treatment of catatonic depression/catatonia with consideration of the drug’s unique receptor profile: a case report

Catatonia is a widespread problem in psychiatric hospitals as approximately 10% of patients present with catatonic symptoms upon admission. Catatonia carries the risk of severe, even fatal complications. The first line treatment is usually electroconvulsive therapy (ECT) or benzodiazepines, but ECT may not be readily available and benzodiazepines may not always be effective. We describe the case of a patient presenting with severe symptoms of catatonic depression who completed a 3-day course of 25 mg aripiprazole that rapidly resolved his catatonic symptoms. Several cases have already been reported where administration of aripiprazole successfully resolved catatonic symptoms after other treatment options had failed. Aripiprazole’s efficacy and advantages may lie in its unique receptor profile. It acts as a dopamine D2 receptor (D2 R) antagonist and partial D2 R agonist depending on the precise cellular milieu, which may explain its efficacy and favourable side effect profile compared to other antipsychotics used to treat catatonia. Aripiprazole also partially agonises D3 receptors and serotonin 2 C receptors (5-HT2 C), which may contribute to its antidepressant properties. Aripiprazole enhances gamma-aminobutyric acid (GABA) transmission in certain brain areas, and it is widely agreed that low GABA activity may contribute to catatonic symptoms. Pharmacokinetics studies show that peak plasma levels are reached rapidly, within 2–3 hours of intramuscular administration and 4–6 hours of oral administration. Administration of high-dose aripiprazole (>25 mg/day) should be considered as a viable alternative to ECT and benzodiazepines in patients presenting with catatonic symptoms. Aripiprazole also carries a much lower risk of complications compared to other antipsychotics.

P0321OUR EXPERIENCE OF PATIROMER (VELTASSA) USE AND POTENTIAL COST-BENEFITS AT SOUTH TYNESIDE AND SUNDERLAND NHS FT, U.K

Background and Aims Patiromer is a new medication used to manage hyperkalaemia and acts as a bowel cation-exchange polymer with a simpler dosing and more favourable side effect profile than existing agents. In May 2018, South Tyneside and Sunderland NHS Foundation Trust (STSFT) implemented a protocol for the use of Patiromer in managing chronic hyperkalaemia to enhance options for managing cardio-renal patients in clinic. Conditional on our successful formulary application, was an audit against the protocol aiming to understand utility. Our second aim was to identify potential cost-benefits of patiromer. In particular, we were interested in preventing hospital admissions, bed days saved, temporary venous lines and dialysis sessions. It is important to note this analysis is subject to interpretation based on likely outcome should patiromer not have been given. Method To be eligible, patients had to have eGFR &lt;30 and either a potassium &gt;5.5 precluding the use of RAASi/MRAs or a recurrent potassium &gt;6. Using electronic patient record system, we investigated 49 patients commenced on patiromer between October 2018 and October 2019. Results Only 14% of the incident prescriptions were in clinic with over half starting at a higher than UK licensed dose (once daily). The distribution of hyperkalaemia was varied as defining hyperkalaemia onset is challenging and what we found as more emergency use. We also identified the following clinical savings: 12 fewer bed days, 15 temporary lines and a minimum of 25 dialysis sessions avoided. Interestingly, we also found that in 2 cases, physicians utilised patiromer and avoided a referral to the renal team. Furthermore, we identified 11 uses of patiromer in the conservative/palliative setting allowing patients to withdraw from dialysis and to prevent discussions on commencing renal replacement therapy for concerns around hyperkalaemia. It would also provide a quality of life benefit avoiding recurrent cannulation to facilitate the standardised medical management of hyperkalaemia. Conclusion In conclusion, whilst this may not demonstrate an objective cost benefit, it does show the versatility of patiromer use in clinical practice. We have found an emphasis on usage in the inpatient setting to avoid dialysis and its attendant costs, rather than where its evidence base originates: as a renin-aldosterone blockade enabler in the outpatient setting. We have demonstrated awareness of adhering to the protocol criteria, whilst understanding the pitfalls of the protocol and why the medication has been administered out with of it, especially with regards to dosing. We wish to share our experience with clinicians and raise awareness of their growing armamentarium.

A study of Centchroman users with special reference to its contraceptive benefit

Background: Centchroman (INN: Ormeloxifene), was developed at CDRI, Lucknow in 1967. This drug was finally approved and licensed in 1991 and launched as Saheli and Choice-7 for marketing in 1992. The Ministry of Health and Family Welfare, India has now introduced centchroman in national family planning programme under the trade name “Chhaya” from April 2016. Centchroman is a novel nonsteroidal contraceptive that inhibits the fertilised ovum from implantation and thus prevents pregnancy. The aim of this study was to assess the effectiveness, side effects, discontinuation rates and failure rate among the users of Centchroman (Chhaya).Methods: The retrospective study was conducted by reviewing the records of Centchroman (Chhaya) contraceptives acceptor over the period of one year from September 2017 to August 2018 in family welfare clinic of Department of Obstetrics and Gynecology at Tomo Riba Institute of Health and Medical Science, a tertiary level center in Naharlagun, Arunachal Pradesh, India.Results: A total of 146 women were evaluated for the study. Majority of the women were in the age group of 20-30 years (76.02%) with mean age of 26 years. Most of the centchroman acceptors were multipara (74.65%) and women in post-abortion (38.35%) and postpartum group (36.3%). Duration of use ranged from 3 months in 146 women to 12 months in 98 women. The discontinuation rate was 31.5%. The major menstrual complaint was delayed menstrual cycle in 15.06% women and irregular cycle in 10.95%. Of the 146 women in the study group, pregnancy occurred in 3 women. Pearl index calculated for centchroman was 2.05/HWY.Conclusions: Centchroman is a non-steroidal, non-hormonal oral contraceptive drug with good therapeutic efficacy and a favourable side effect profile. Centchroman has an important place in postpartum contraception due to its safety profile in breastfeeding women.

Case study of tacrolimus as an effective treatment for idiopathic membranous glomerulonephritis in pregnancy

Background Tacrolimus has been used in pregnant women following transplantation and for management of lupus nephritis. We report a case of successful control of nephrotic syndrome due to membranous glomerulonephritis during pregnancy using tacrolimus. Case report A 26-year-old female presented with severe nephrotic syndrome in her first pregnancy. Post-partum renal biopsy confirmed idiopathic membranous glomerulonephritis. She had persistent proteinuria of 6 g/day with hypoalbuminaemia despite angiotensin receptor blockade. Treatment with tacrolimus monotherapy led to remission of proteinuria, three months prior to conceiving again. She maintained remission with tacrolimus therapy in pregnancy, resulting in a successful birth outcome. Conclusions Membranous glomerulonephritis can be successfully and safely managed with tacrolimus monotherapy during pregnancy. This provides an alternative immunosuppressant with a favourable side effect profile suitable for use in women planning a pregnancy when other immunosuppressive drugs should be avoided.

Endovenous ablation of refluxing saphenous and perforating veins

Since the end of the nineties endovenous thermal ablation and more recently non-thermal, non-tumescent techniques have been developed and improved. Until now, because of their favourable side effect profile in conjunction to sustained efficacy, in many countries they already replaced high ligation and stripping in the treatment of refluxing saphenous veins as well as for treatment of perforators and selected tributaries. Now, studies and comparative trials are available with long-term follow-ups for most of the techniques, providing valid data on occlusion and reflux rates, side effect profiles, and health related quality of life.

Vomiting and large nasogastric aspirates in the critically ill

A wide range of conditions can cause nausea and vomiting, making it a common occurrence in the critically ill. A deeper understanding of the pathophysiology of vomiting has led to the emergence of effective anti-emetics, each targeting a specific neurotransmitter in the emetic pathway. Serotonin antagonists are the first line anti-emetic of choice for most cases of nausea and vomiting due to their efficacy and favourable side effect profile. Large nasogastric aspirates are commonly encountered in the critically ill, and must be managed aggressively in order to prevent delays in enteral nutrition. Management of large gastric aspirates involves gastric drainage, prokinetic agents, and if necessary, post-pyloric feeding.

Review of treatment for late-life depression

SummaryDepressive disorder in those over the age of 60 has many clinical similarities to depression in younger adults, but biological changes related to ageing may necessitate a different approach to treatment. We present an evidence-based review of treatment for late-life depression, focusing on pharmacological approaches, including monotherapy, combination and augmentation strategies. Selective serotonin reuptake inhibitors such as sertraline and citalopram are well tolerated, have the advantage of a favourable side-effect profile, and are good options for first-line treatment. Second-line treatment options include combination therapy with a second antidepressant, or treatment augmentation with an antipsychotic or lithium. We also consider evidence for nonpharmacological treatment strategies, including psychological therapy and neurostimulation. Finally, we summarise evidence for treatment of depression in patients in dementia.

Auditing Clinical Outcomes after Introducing Off-Licence Prescribing of Atypical Antipsychotic Melperone for Patients with Treatment Refractory Schizophrenia

Aims and Method. To evaluate the practical utility of off-licence prescribing and clinical outcomes of treatment with atypical antipsychotic Melperone.Method: Prospective data collection on patient’s clinical characteristics and outcomes.Results. 17 patients with a diagnosis of refractory schizophrenia were identified as suitable for off-license prescribing of Melperone and commenced treatment (13 were previously treated with Clozapine). Seven of those currently remain on Melperone (41%), and for six patents, the BPRS symptom scores reduced significantly over time (24–61%) additionally patients displayed improvements of their quality of life. Six patients were discontinued due to noncompliance and/or side effects. Melperone was ineffective in the other four patients.Clinical Implications. The example of a small group of patients responding well to a comparably safe and inexpensive atypical antipsychotic with favourable side effect profile should encourage clinicians to use this tool as third-line treatment and to conduct more systematic clinical research.