Adverse Drug Reaction Probability Scale Research Articles

A rare case of phenobarbital-induced leukocytoclastic vasculitis.

Drug hypersensitivity reactions (DHRs) manifested as vasculitis are rare. Antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), sulphonamides, diuretics, immunosupressants and anticonvulsants are the most common culprits for drug-induced leukocytoclastic vasculitis (LCV) but there is scarce information about barbiturates. We present a case of 53-year-old female with severe vasculitis after phenobarbital- and NSAIDs-containing medications use. The preliminary diagnosis of drug-induced vasculitis was made based on anamnestic and clinical data. Further examinations confirmed the diagnosis of LCV and excluded other more common causes of vasculitis. The causative significance of used medications was assessed by long-term observation of the patient after the reaction, including the drug challenge series and Naranjo's Adverse Drug Reaction Probability Scale. It was concluded that phenobarbital is the most probable culprit drug. The patient's data were included in the Armenian Registry of Patients with Severe DHRs. Since then, the patient has avoided only barbiturate-containing drugs and no reactions were noted. Thus, the case indicates that even with limited diagnostic capabilities, the final diagnosis of rare drug-induced LCV and even rarer culprit drug can be established by comparing the available data. Awareness about phenobarbital and proper recording of the case are important in the management and prevention of DHRs manifested as vasculitis.

Clinical Profile of Patients with Lichenoid Drug Eruption: A Observational Study

Background: Lichenoid drug eruption (LDE) is an uncommon cutaneous adverse drug reaction, where a variety of drugs used in day-to-day clinical practice have been implicated. Objective: To describe the clinico-demographic characteristics of patients with LDE and to identify the most likely drugs involved. Methods: In this prospective, observational study, consecutive patients with LDE presenting to the dermatology department of a tertiary teaching hospital were included. The clinico-demographic profile of patients with LDE and implicated drugs was noted. Treatment of drug reaction along with outcome was also documented. Naranjo adverse drug reaction probability scale was used for causality assessment of the drug reactions. A thorough literature review on LDE was also undertaken due to the paucity of existing literature. Results: A total of 15 patients (11 males and 4 females) with LDE were evaluated. Their age ranged from 37 to 61 years, with a mean of 51.53 ± 7.59 years. Anti-hypertensive medications (40%) were the most common culprit agent, followed by antitubercular drugs (33.4%), anti-diabetic agents (13.3%), and others (13.3%). The latent period (time from drug initiation to the appearance of a cutaneous eruption) varied from 15 days to 6 months (mean 2.2 months). Cutaneous involvement was generalized in 73.4% and photo-distributed lesions in 26.6%. Drug provocation test was done to identify the culprit drug. According to the Naranjo adverse drug reaction probability scale, one-third of LDEs were “definite,” whereas two-thirds were designated as “probable.” Conclusion: LDE is more common in the elderly population. The latent period is comparatively longer in LDE than in other common drug reactions. Prompt recognition and withdrawal of suspected drug are essential to minimize disease morbidity.

P839 Acute interstitial nephritis in patients with Inflammatory Bowel Disease treated with vedolizumab: a systematic review

Abstract Background Acute interstitial nephritis (AIN) is a complication of drugs that may cause permanent kidney injury. AIN has been reported in inflammatory bowel disease (IBD) patients treated with the anti-integrin inbibitor vedolizumab. However, systematically collected data on cases of AIN associated with vedolizumab treatment is lacking. We therefore, through systematic review of existing literature, aimed to identify and describe reported cases of AIN. Methods We searched Medline, Embase, Cochrane, and Web of Science Core Collection between January 1, 2009 and April 25, 2023. The search yielded 1473 publications after deduplication, for which titles and abstracts were screened by two independent reviewers. Of these, 75 publications were reviewed in full-text. Demographics and clinical characteristics of AIN cases were extracted. Case causality assessment was performed according to the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) system and the Naranjo Adverse Drug Reaction Probability Scale. Results were reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A prespecified protocol was registered in the PROSPERO database. Results Eight publications met the inclusion criteria and were included in descriptive analysis of AIN in patients with IBD treated with vedolizumab. A total of nine biopsy-confirmed cases of AIN were reported in six patients with ulcerative colitis and three with Crohn’s disease. The mean age at AIN onset was 36 years (range: 19-58). The majority of patients were females (n=6/9). Time from vedolizumab treatment initiation to AIN onset spanned from hours to 12 months. Common symptoms were fever, malaise, and myalgia. Creatinine levels were elevated in all patients (mean: 219 µmol/L; range; 133-410). Rechallenge after pause and treatment with corticosteroids were reported in three cases, where one attempt was successful. Five patients sustained permanent kidney injury. According to the WHO-UMC scale, six of nine cases were assessed as “possible” or “probable”, and the remaining three cases as “unlikely” or “unclassifiable”. Three patients were treated with concomitant mesalazine or proton pump inhibitors, which both are associated with an increased risk of AIN. Conclusion In systematic review of existing literature, we identified nine cases of biopsy-confirmed AIN in patients with IBD treated with vedolizumab. Our findings suggest that vedolizumab, although rarely, could potentially cause AIN in patients with IBD. Awareness of laboratory findings and symptoms consistent with AIN, along monitoring of the kidney function, could be warranted in patients with IBD treated with vedolizumab.

Hydroxychloroquine-Induced Hypoglycemia in a Patient Without Diabetes.

Hydroxychloroquine is a disease-modifying antirheumatic drug commonly used in the treatment of autoimmune diseases. Although rare, hydroxychloroquine is associated with hypoglycemia in patients with or without diabetes due to its ability to alter insulin metabolism. There have been several cases described in the literature, but none of which, to our knowledge, detail follow-up and time to resolution of hypoglycemia. We describe a 55-year-old female who presents for episodes of hypoglycemia. She reported hypoglycemic symptoms and fasting blood glucoses in the 60-70s mg/dL regularly. Based on the Naranjo adverse drug reaction probability scale, hydroxychloroquine was the probable etiology of her hypoglycemic episodes due to the improvement at her 3-month follow up appointment after discontinuing the drug. Providers should be mindful of the hypoglycemia risk when using hydroxychloroquine and be aware that the effects may take an extended amount of time to resolve given the drug's long half-life.

A CASE POSSIBLE SEROTONIN SYNDROME CASE CAUSED BY COMBINED USE OF FLUOXETINE AND LOW DOSE TRAZODONE AND ASSESSED BY THE NARANJO ADVERSE DRUG REACTION PROBABILITY SCALE

Serotonin sendromu serotonerjik ajan kullanımı sonrasında
 oluşan serotonin reseptörlerinin aşırı uyarılması
 sonucu gelişen nadir görülen fakat mortal seyredebilen
 sendromdur. Klinik belirti ve bulgular kognitif,
 nöromüsküler ve otonomik alanda görülmektedir. Serotonerjik
 etkili bir veya daha fazla ajanın birlikte kullanılması
 bu sendroma neden olur. Klinik görünümü hafif
 şiddette olup gözden kaçabilen olgular olduğu gibi
 hayatı tehdit eden, yoğun bakım ve mekanik ventilasyon
 gerektiren şiddette de olabilmektedir. Bu yazıda
 fluoksetin tedavisine trazodon eklenmesi ve doz artırılması
 sonrasında 24 saat içerisinde gelişen serotonin
 sendromu düşündüren bir vaka sunulmuştur.

Ribociclib-induced pulmonary infiltrates in a patient with breast cancer.

Breast cancer is the most common cancer in women worldwide. One of the treatment choices used in hormone receptor positive and HER2 expression negative metastatic breast cancer is cyclin dependent kinase 4/6 (CDK) inhibitors. There are differences between the effects and adverse events of all CDK4/6 inhibitors. In this report, we describe a 48-year-old female patient with breast cancer who developed pulmonary infiltrates secondary to drug in the second year of follow-up with Ribociclib therapy. The patient who used ribociclib for metastatic breast cancer was admitted to hospital for routine controls. The patient, in the eighth month of ribociclib treatment, had no active complaints. In the patient's imaging, pulmonary infiltrates were detected in the lower lobe of the right lung. The drug was continued in the patient who was asymptomatic and had no infectious signs. Pneumonitis, interstitial lung disease, tuberculosis, COVID-19 and other viral agents were excluded in the patient. A minimal increase in pulmonary infiltrates was observed in the follow-up. However, the patient who does not have any complaints is currently continuing ribociclib at 600 mg/day. The pulmonary infiltrates that developed in the patient increased with continued use of ribociclib, suggesting that this was due to ribociclib. The Naranjo Adverse Drug Reaction Probability Scale also indicates probable relationship.

Validation of Rash and Nonspecific Eruption Diagnoses Using ICD-9 and ICD-10 Codes

Despite being common cutaneous findings in the hospital setting, cutaneous drug eruptions have not been thoroughly validated for administrative claims data. The purpose of this study was to validate primary discharge diagnoses for the ICD code rash or other nonspecific eruptions by finding the positive predictive value (PPV) and to determine how often it was used to indicate an eruption that was eventually determined to be a drug eruption. Two dermatologists independently examined each of 39 hospital patient encounters to assess the validity of the ICD code used by stating whether the code used was appropriate or inappropriate, per table 1 criteria. Since in most patients, a drug eruption was suspected, the Naranjo Adverse Drug Reaction Probability Scale was utilized to externally validate our findings. Our results yielded a PPV for nonspecific rashes of 94.87% (83.11-98.58%) for appropriateness of use. The mean Naranjo score for appropriately versus inappropriately coded cases was 5.7 versus 2.5, respectively, with a mean difference of 3.17568 (0.18833-6.16302), (pooled P-value = 0.0378). Out of the cases analyzed, 29/39 or 74% were confirmed to be drug-related. Our high PPV supports the validity of non-specific eruptions found in national patient databases and the high Naranjo criteria suggest that often, these eruptions are drug related, yet not confirmed at the point of discharge.

Teclistamab-Associated Sclerouveitis with Hypopyon.

To report a case of presumed teclistamab-associated sclerouveitis with hypopyon. Case report. A 62-year-old female with relapsed refractory multiple myeloma presented with right eye pain and decreased vision one week after starting teclistamab, and was found to have sclerouveitis with hypopyon. She received intravitreal vancomycin and ceftazidime due to concern for infectious endophthalmitis, but cultures were negative. Systemic workup for infectious and inflammatory etiologies was unremarkable. Her signs and symptoms improved with topical steroids and a one-week pause in teclistamab. This case constituted a Naranjo Adverse Drug Reaction Probability Scale score of 5, representing a "probable" association. Teclistamab, a novel bispecific antibody recently approved for the treatment of relapsed or refractory multiple myeloma, may be associated with sclerouveitis with hypopyon.

Neuropsychiatric adverse reactions in patients treated with denosumab: two case reports and a review of data from the FDA Adverse Event Reporting System (FAERS).

Denosumab is a human monoclonal antibody indicated for patients with osteoporosis and a high risk of fractures. It targets RANKL, the receptor activator of NF-κB (RANK) ligand, blocking RANKL-RANK interaction and leading to rapid osteoclast-mediated bone resorption inhibition. But RANK is widely expressed in neurons, microglia, and astrocytes. RANKL/RANK/NF-κB system can play an important role in the neuroinflammatory response, depressive behavior, memory impairments, and neurotrophism. We present two well-documented case reports of recurrent neuropsychiatric manifestations in patients treated with denosumab and a descriptive review of similar cases reported to the Food and Drug Administration Adverse Event Reporting System (FAERS) database between 2012 and 2022. Only those reported by healthcare professionals, coding denosumab as the only suspected drug, were retained. An 81-year-old woman with pre-existing mild cognitive impairment suffered two acute confusional episodes and another 81-year-old woman with depression in remission suffered two depressive recurrences with anxiety and psychomotor inhibition, in both cases following sequential administrations of denosumab without underlying calcium/phosphate imbalance. Scores on Naranjo Adverse Drug Reaction Probability Scale were 6 and 7, respectively, suggesting a probable causal relationship. Of the 91,151 cases with denosumab exposure reported to FAERS, 5.7% were related to psychiatric/neurological disorders and 23.8% of these corresponded to cognitive impairment, depressive/mood disturbances, or psychomotor retardation. Denosumab may cause transient but severe neuropsychiatric symptoms by several mechanisms involving RANKL blockade and subsequent immuno-inflammatory changes, at least in subjects with pre-existing neurobiological vulnerability. We recommend caution and careful monitoring of these patients following denosumab administrations.

Successful desensitization of a patient with hypersensitivity to pertuzumab: a case report

Abstract Introduction: Pertuzumab is a humanized monoclonal antibody used in the treatment of human epidermal growth factor receptor 2–positive early breast cancer. Its use can lead to a type-I hypersensitivity, which can be the result of an IgE-related reaction. This case describes a successful desensitization to pertuzumab in a patient diagnosed with a breast cancer. Method: A patient without a personal history of hypersensitivity and diagnosed with a human epidermal growth factor receptor 2–positive breast cancer was started on chemotherapy with association of trastuzumab, pertuzumab, and paclitaxel. While receiving the fourth cycle of pertuzumab, the patient developed a grade 2 hypersensitivity reaction resolved by the intravenous injection of dexchlorpheniramine and methylprednisolone. A premedication protocol has been setting up with a short desensitization protocol. Results: No adverse event occurred during the desensitization, which permits to continue pertuzumab at normal dose with a low occurrence of adverse events (spontaneous and favorable resolution). On analyzing the suspected adverse drug reaction, the event scored 10 and can found to be considered definite using the Naranjo Adverse Drug Reaction Probability Scale. This successful protocol of desensitization has helped to inhibit a hypersensitivity reaction. The monitoring showed the well-tolerance of the patient. Conclusion: This desensitization avoided a too early changing line treatment, which could have been deleterious. Very few cases of pertuzumab hypersensitivity occurred in France, and none benefited from a desensitization. This case illustrated the fact that rapid drug desensitization is possible, important and a simple opportunity to pursuit effective treatments.

Causality, severity, and preventability of adverse drug reactions due to multi-drug therapy in leprosy: evidence from a national level institution in Sri Lanka

Objective This study describes the causality, severity, and preventability of adverse drug reactions (ADR) in patients affected by leprosy treated with multi-drug therapy (MDT) at the dermatology and central leprosy clinics of the National Hospital of Sri Lanka. Methods This cross-sectional analytical study consisted of two components (retrospective and prospective). Prospective cases were recruited and followed up for six months. Retrospective data collection was carried out at relevant clinics in the NHSL by extracting data from the clinical records of the patients. When an ADR was suspected, it was confirmed after discussion with the clinic medical officers/consultant dermatologist and scored according to the Naranjo ADR probability scale. The intensity of an individual ADR was evaluated using the modified Hartwig and Siegel Severity Assessment Scale, and preventability assessment was performed using the modified Schumock and Thornton scale. Results One hundred and ninety-seven patients were included for ADR attributable to MDT. Approximately 145 patients (73.6%) developed ADR associated with dapsone. Another 50 cases (25.3%) were associated with rifampicin, and 10 (5.1%) were associated with clofazimine. Of the dapsone related 145 ADRs, 59 (40.7%) were definite, 64 (44.1%) were probable, and 22 (15.2%) were possible. Of the rifampicin-related cases, four (8%) were definite, 35 (70%) were probable, and 11 (22%) were possible. The most common adverse drug reactions detected were haemolytic anaemia and hepatic abnormalities due to MDT. Dapsone was discontinued in 40% (59 out of 145) of these patients, while rifampicin was stopped in 8% (4 out of 50) of patients. Clofazimine was not stopped in any of the patients. Conclusions Adverse drug reactions associated with multidrug therapy in leprosy are common among patients diagnosed with leprosy in Sri Lanka. Most ADRs reported in this study were of mild severity and preventable. Careful monitoring and objective scales are needed to identify ADRs at an early stage.

8th ABM/EABM European Regional Conference May 11–13, 2023 Split, Croatia

Breastfeeding MedicineAhead of Print AbstractsFree Access8th ABM/EABM European Regional Conference May 11–13, 2023 Split, CroatiaPublished Online:14 Apr 2023https://doi.org/10.1089/bfm.2023.29239.abstractsAboutSectionsPDF/EPUB Permissions & CitationsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Oral Presentations1. Systematic Review and Meta‐analysis of the effect of relaxation interventions on breastmilk quantity and maternal mental healthIlana Levene1, Nurul Husna Mohd‐Shukri2, Frances O'Brien3, Maria Quigley1, Mary Fewtrell41National Perinatal Epidemiology Unit, University of Oxford, United Kingdom2Universiti Putra Malaysia, Malaysia3John Radcliffe Hospital, United Kingdom4Institute for Child Health, University College London, United KingdomBackground: Breastfeeding is an important public health goal. Rates of breastfeeding are low and geographically variable. Maternal stress could impair lactation, through hormonal, neuronal or behavioural pathways.Objectives: This study aims to analyse the effect of relaxation interventions on lactation outcomes.Methods: Systematic review and meta‐analysis were performed to address the question: “in lactating mothers, does relaxation therapy, compared to standard care, improve milk quantity and maternal mental health?” Randomised studies with interventions designed to achieve relaxation through reduction in mind‐stress were included. Fixed‐effects meta‐analysis was used. A standardised mean difference (SMD) was calculated if the units of measurement varied between studies.Results: The search took place in August 2022. Twelve studies are included, with data from 1533 lactating parents. Interventions included guided relaxation, music and mindfulness. Seven studies measured milk quantity with summary SMD of 0.75. This is equivalent to an increase in daily breastmilk yield of 225ml, which is clinically significant. Five studies measured maternal anxiety and four measured maternal stress. The summary SMDs were −0.52 and −0.7 respectively, which are medium effect sizes. There was significant statistical heterogeneity in all outcomes.Conclusion: There is evidence for a clinically significant increase in breastmilk quantity and a moderate reduction in maternal stress and anxiety when a relaxation intervention is provided. Given the low potential harm and high availability of relaxation interventions, they can be recommended to lactating parents, particularly to those with concerns over milk quantity and/or stress.2. Knowledge, Attitudes and Practices on Breastfeeding and the first one thousand days of life among social and healthcare professionalsGabriella Tambascia1,2, Francesca Zambri1, Francesca Marchetti1,2, Annachiara Di Nolfi1,2, Jessica Preziosi1,2, Elise M. Chapin3 Stefania Solare3, Angela Giusti11National Center for Disease Prevention and Health Promotion, National Institute of Health, Rome, Italy2Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy3Italian National Committee for UNICEF, ItalyBackground: Healthcare professionals' (HCP) support and training on breastfeeding and the first one thousand days of life is an essential factor for successful breastfeeding.Objective: To describe the Knowledge, Attitudes and Practices (KAP) of social and healthcare professionals on breastfeeding and the first thousand days of life.Methods: During 2022, an e‐learning module was developed by the Italian National Institute of Health, in collaboration with UNICEF Italy and Local Health Authority of Rome (ASL Roma 5). A KAP pre‐assessment was carried out at course entrance, using a 37‐item questionnaire.Results: Data from 19315 professionals (Jan–Nov 2022) show a mean age of 42,6 and the most represented professions were general and pediatric nurses (37,38%), midwives (19,2%) and psychologists (11,7%). The median knowledge score was 81,8%. The most frequent incorrect answer (39,1%) was about breastfeeding duration. Likewise, 30,5% disagreed that breastfeeding can be continued beyond the second year of life. As for opinions, 65,2% of participants considered collecting donations of Breast‐milk Substitutes (BMS) in emergencies important, despite its not being recommended. Moreover, 44,3% disagreed that most medications can be used during breastfeeding. As for practices, 54,1% of respondents declared they often inform parents on the important role of fathers in managing household labor and childcare. Eighty‐nine percent thought that fathers do not lose their masculinity taking care for children.Conclusion: These results show a good level of knowledge at course entrance. Some common misconceptions, e.g. duration of breastfeeding, managing BMS donations in emergencies and the father's role in childcare, are still widespread.3. Maternal physical health and breastfeeding problems in Croatia: national online survey of new mothersLisa Amir1, Daniela Drandić2, Anita Pavicic Bosnjak3, Ana Vidović Roguljić4, Gill Thomson5, Irena Zakarija‐Grković61La Trobe University and Royal Women's Hospital, Australia2RODA‐ Parents in Action, Croatia3University Hospital Centre Zagreb, Croatia4Community Health Centre, Split‐Dalmatia County, Croatia5University of Central Lancashire, United Kingdom6University of Split School of Medicine, CroatiaBackground: Maternal physical symptoms are common in the postpartum period, yet these “hidden morbidities” receive little attention from health care providers. In addition, many mothers experience breastfeeding problems, including nipple pain and mastitis. While studies in several countries have provided prevalence estimates, there have been no studies in Croatia looking at maternal postpartum physical health.Objectives: To document maternal physical health and breastfeeding problems in the first six months after giving birth in Croatia.Methods: We conducted a cross‐sectional study using an online questionnaire between February and April 2022 among resident Croatian women who had enrolled in the RODA (‘Parents in Action’) online antenatal course. Women aged 18+ years, who had given birth in a Croatian maternity facility between February 2020 and December 2021 were eligible. The questionnaire contained 75 items, covering sociodemographic characteristics, hospital practices, community support, maternal mental and physical health.Results: Postpartum health and breastfeeding items were completed by 1760 participants. Major physical health issues were fatigue (28%; n = 487), back pain (14%; n = 252), and hemorrhoids (10%; n = 171). Urinary incontinence was a minor problem for 23% (n = 397), somewhat of a problem for 8% (n = 139) and a major problem for 4% (n = 67).The most common breastfeeding problems were nipple pain/damage 50% (n = 885), difficulty attaching 43%, (n = 761), low milk supply 28% (n = 490), mastitis 22% (n = 391), engorgement 22% (n = 393), breast refusal 22% (n = 381), and too much milk 22% (n = 380).Conclusion: Postpartum women in Croatia experienced many physical health challenges. The frequency of pain associated with breastfeeding is concerning.4. Questioning the usefulness of 24‐hour recall of exclusive breastfeedingKeiko Nanishi, Joseph Green, Akira Shibanuma, Hiroko HongoGraduate School of Medicine, the University of Tokyo, JapanBackground: The WHO recommends exclusive breastfeeding for the first six months, and it promotes the Ten Steps to Successful Breastfeeding (Ten Steps). It also recommends monitoring the proportion of infants under six months old fed exclusively with breastmilk during the previous 24 hours. Whether that 24‐hour recall usefully reflects the Ten Steps is unknown.Objective: To compare two indicators of infant feeding, exclusive breastfeeding since birth and 24‐hour recall, by quantifying each indicator's association with provision of the Ten Steps.Methods: Mothers in Japan who had had a healthy singleton delivery in the previous two years were surveyed online in August 2021. Because of Japan's recommendation to start complementary feeding five months after birth, 3,753 mothers with infants older than five months reported on their breastfeeding from birth to five months, and 1,029 mothers with infants under five months reported on their breastfeeding over the previous 24 hours. The strength of each indicator's association with provision of the Ten Steps was quantified as the area under the receiver operating characteristic curve (AUC).Results: Exclusive breastfeeding since birth (prevalence = 4.4%) was moderately‐well associated with provision of the Ten Steps: AUC = 0.72. In contrast, 24‐hour recall of exclusive breastfeeding under five months (prevalence = 31.6%) was only very weakly associated with provision of the Ten Steps: AUC = 0.59.Conclusion: The WHO's recommended indicator of exclusive breastfeeding (24‐hour recall) concealed the effectiveness of providing the WHO's Ten Steps. Using 24‐hour recall to evaluate breastfeeding‐promotion interventions may be inappropriate.5. Finding a path in a maze. Identification of an adverse reaction during lactation based on a case study of ergotamineKarolina MorzePrivate Clinic, Departament of Pharmacovigilance, PolandIntroduction: The article presents a lactating patient who contacted the pharmacy office to inquire about the alarming reaction to ergotamine. She was given ergotamine due to retention of lochia and during the treatment she experienced a severe nipple pain.Main Issue: The patient was unable to feed directly from the breast and bottle fed the baby with her own expressed milk. She was worried that the nipple pain would worsen and persist for a long time and was concerned that the situation would affect further lactation.Management: The pharmacist conducted an interview, prepared and analyzed the treatment timeline based on the reported symptoms [figure 1], provided information and possible solutions to the problem. A follow‐up was performed one, two, and 20 days after the consultation. Using Adverse Drug Reaction Probability Scale, the pharmacist identified a definite adverse event related to ergotamine intake – Raynaud syndrome in the nipple. As a result of the consultation, the patient decided to continue taking the drug, and wait for the symptom to resolve to resume direct feeding from the breast. She felt more confident and less worried with the medical supportive care.Conclusion: Ergotamine treatment caused a vasospasm in the nipple of the patient and resulted in a change in the way the infant was being fed. The situation affected the maternal ability to breastfeed, caused direct and indirect costs and negatively impacted the patient's quality of life. It had no apparent adverse effect on the baby and the situation did not impact the milk supply.6. Identifying indicators of a breastfeeding‐friendly city: A Delphi surveyMay Loong Tan1,5, Siew Cheng Foong1, Wai Cheng Foong1, Grace YW Tay2, Jacqueline J Ho1, Amal Omer‐Salim3, Elizabeth J O'Sullivan4, Fionnuala M McAuliffe51Department of Paediatrics, RCSI & UCD Malaysia Campus, Penang, Malaysia2IBCLC, Gloria Group Sdn Bhd, Penang, Malaysia3World Alliance for Breastfeeding Action, Malaysia4School of Biological, Health and Sports Science, Technological University Dublin, Ireland5UCD Perinatal Research Centre, School of Medicine, University College Dublin, National Maternity Hospital, Dublin, IrelandBackground: A breastfeeding‐friendly city is one with a synchronous and enabling environment for breastfeeding. There is currently no specific set of indicators of a breastfeeding‐friendly city. A scoping review and interviews with breastfeeding mothers identified numerous potential indicators of a breastfeeding‐friendly city.Objective: To determine a set of indicators of a breastfeeding‐friendly city through consensusMethods: A Delphi‐method survey in two rounds was used. In Round 1, participants from 3 stakeholder groups (experts, policy‐makers and families) rated a list of 52 potential indicator identified from a scoping review and interviews with breastfeeding mothers. Participants could also suggest additional indicators. In Round 2, participants were shown the ratings of the other participants and were asked to rate the items again with the choice of changing their original ratings. Consensus was defined as more than 70% participants rating an item as critical (score 7–9) or not important (1–3). Any item that did not reach consensus was discussed at a consensus meeting.Results: There were 107 participants from 14 countries. After both rounds, 50 (out of 56) items reached consensus. A consensus meeting with selected participants from the 3 stakeholder groups discussed items that did not reach consensus. The final list had 52 items that was summarized into 5 sectors – administration, community, healthcare, workplace and collaboration.Conclusion: Using a systematic approach, we identified a list of indicators in 5 sectors of a breastfeeding‐friendly city. The next step is to determine how each of these indicators can be measured and applied.7. What is known about cow's milk protein allergy in preterm infants?Mona Florquin1, An Eerdekens21Department of Pediatrics, University Hospital Leuven, KU Leuven, Belgium2Department of Neonatology, University Hospital Leuven, KU Leuven, BelgiumBackground: Cow's milk protein allergy (CMPA) is well described in term infants, as opposed to preterm infants. In preterm infants, CMPA shares many gastro‐intestinal symptoms with necrotizing enterocolitis (NEC).Objectives: To evaluate the presentation of CMPA in preterm infants and to investigate the different diagnostic and therapeutic options.Methods: We searched for relevant literature using the medical databases PubMed, Web of Science, and the Cochrane Library. We performed a post hoc analysis on the 25 case‐reports included in this study.Results: Literature was scarce and heterogeneous. The majority of preterm infants with CMPA were exposed to bovine‐based milk proteins prior to the development of symptoms. The most common clinical manifestations were bloody stools, vomiting and abdominal distension. Of the 25 cases, only seven (28%) retained human milk in their diet after diagnosis. In the larger studies, no study has human milk as primary feeding choice after diagnosis.Conclusions: Preterm infants exposed to a type of cow's milk‐based formula in their first days of life, have a higher risk of developing CMPA. Most of the preterm infants are no longer fed with human milk after the diagnosis of CMPA is made, which is in contrast with current feeding guidelines. We strongly advocate that human milk with mothers on a cow's milk free diet is the first choice of feed after the diagnosis of CMPA. Prospective studies are necessary to obtain more information regarding clinical presentation, diagnostic tools and therapeutic approaches.8. Facility‐based maternal and newborn care during the COVID‐19 pandemic: IMAgiNE EURO Study findings on breastfeeding practices in 12 countriesMarzia Lazzerini,1 Benedetta Covi,1 Ilaria Mariani,1 Zalka Drglin,2 Maryse Arendt,3 Ingvild Hersoug Nedberg,4 Helen Elden,5,6 Raquel Costa,7,8,9 Daniela Drandić,10 Jelena Radetić,11 Marina Ruxandra Otelea,12,13 Céline Miani,14 Serena Brigidi,15 Virginie Rozée,16 Barbara Mihevc Ponikvar,2 Barbara Tasch,3,17 Sigrun Kongslien,18 Karolina Linden,5 Catarina Barata,19 Magdalena Kurbanović,20 Jovana Ružičić,11 Stephanie Batram‐Zantvoort,14 Lara Martín Castañeda,21 Elise de La Rochebrochard,16 Anja Bohinec,2 Eline Skirnisdottir Vik,22 Mehreen Zaigham,23 Teresa Santos,24,25 Lisa Wandschneider,14 Ana Canales Viver,26 Amira Ćerimagić,27 Emma Sacks,28 Emanuelle Pessa Valente11WHO Collaborating Centre for Maternal and Child Health, Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy2National Institute of Public Health, Ljubljana, Slovenia3Beruffsverband vun de Laktatiounsberoderinnen zu Lëtzebuerg asbl (Professional association of the Lactation Consultants in Luxembourg), Luxembourg, Luxembourg4Department of community medicine, UiT The Arctic University of Norway5Institute of Health and Care sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden6Region Västra Götaland, Sahlgrenska university hospital, Dept of Obstetrics & Gynecology, Gothenburg, Sweden7EPIUnit, Institute of Public Health, University of Porto, Porto, Portugal8Laboratory for Integrative and Translational Research in Population Health (ITR), Porto, Portugal9Human‐Environment Interaction Laboratory, Universidade Lusófona, Portugal10Roda – Parents in Action, Zagreb, Croatia11Centar za mame, Belgrade, Serbia12University of Medicine and Pharmacy Carol Davila, Bucharest, Romania13SAMAS Association, Bucharest, Romania14Department of Epidemiology and International Public Health, School of Public Health, Bielefeld University, Bielefeld, Germany15Department of Anthropology, Philosophy and Social Work. Medical Anthropology Research Center (MARC). Rovira i Virgili University (URV), Tarragona, Spain16Sexual and Reproductive Health and Rights Research Unit, Institut National d'Études Démographiques (INED), Paris, France17Neonatal intensive care unit, KannerKlinik, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg18Department of health and care sciences, UiT The Arctic University of Norway19Institute of Social Sciences of the University of Lisbon, Lisbon, Portugal20Faculty of Health Studies, University of Rijeka, Rijeka, Croatia21Institut Català de la Salut, Generalitat de Catalunya, Spain22Department of health and caring sciences, Western Norway University of Applied Sciences, Norway23Obstetrics and Gynaecology, Department of Obstetrics and Gynecology, Institution of Clinical Sciences Lund, Lund University, Lund and Skåne University Hospital, Malmö, Sweden24Centro de Investigação Interdisciplinar em Saúde (CIIS) da Universidade Católica Portuguesa, Lisbon, Portugal25Universidade Europeia, Lisboa, Portugal26Institut Català d'Antropologia (ICA), Barcelona, Spain27NGO Baby Steps, Sarajevo, Bosnia‐HerzegovinaBackground: Evidence suggests poor quality of maternal and newborn care (QMNC) during the COVID‐19 pandemic. Few studies have investigated quality of breastfeeding practices utilising the WHO Standards as a reference, and using the same set of indicators across several countries.Objectives: Investigate the WHO Quality Measures related to breastfeeding practices during the COVID‐19 pandemic, in 12 countries of the WHO European Region.Methods: Data were collected via IMAgiNE EURO, a multi‐country, cross‐sectional study using an anonymous, online questionnaire including 40 WHO Standard‐based Quality Measures. Women who gave birth in health facilities in the WHO European Region from March 2020 to March 2021 were eligible.Results: Overall, 21027 mothers were included, of whom 85.9% (18063) underwent labour. Major heterogeneity was found across countries in breastfeeding practices: lack of skin‐to‐skin ranged from 0.5% in Luxemburg to 64.4% in Romania; lack of early breastfeeding, inadequate breastfeeding support, lack of rooming‐in were consistently higher in Serbia (69.9%, 56.9%, 55.6% respectively) and lower in Luxemburg (4.7%, 16.5%, 5.5% respectively) compared to other countries. Lack of exclusive breastfeeding at discharge ranged from 17.5% in Spain to 44.1% in Romania. Women who had a prelabour caesarean section reported gaps in breastfeeding practices more frequently than women who had experienced labour (p < 0.02).Conclusion: Large inequities exist across countries in the WHO European Region in the quality of breastfeeding‐related practices. Multi‐level actions are urgently needed to promote breastfeeding and enhance support to women during and beyond the COVID‐19 pandemic.9. Breastfeeding experiences during hospitalization for childbirth among migrant versus non‐migrant women: preliminary results of the IMAgiNE study in ItalyEmanuelle Pessa Valente1, Ilaria Mariani1, Karen Loisotto2, Gina Cervi2, Marzia Lazzerini11Institute for Maternal and Child Health ‐ IRCCS “Burlo Garofolo” ‐ WHO Collaborating Centre for Maternal and Child Health, Trieste, Italy2Trieste University, Department of Medicine, Surgery and Health Sciences, Trieste, ItalyBackground: Evidence suggests gaps in the quality of maternal and newborn care during childbirth in Italy. Migrant population is particularly vulnerable. Few studies have investigated migrant women’ perspectives, in particular when related to breastfeeding experiences, using the WHO Standards as reference.Objectives: The study aimed at investigating breastfeeding experience during hospitalization for childbirth, in migrant versus non‐migrant women, in Friuli Venezia‐Giulia (FVG) region, North‐East Italy.Methods: Cross‐sectional study using validated, anonymous, telephone interview based on WHO Standards. Women given birth in one of the nine maternity hospitals of FVG region, in the period from September 2019 – April 2022 were eligible to participate. We compared indicators related to breastfeeding experience among migrant versus non‐migrant women using a Chi‐square test. Values p < 0.05 indicate statistical significance.Results: A total of 4882 women were included, of whom 883 (18.1%) migrants (Table 1). We found no statistically significant differences between migrant and non‐migrant women reports of skin to skin (86.2% migrants vs 86.6%, p = 0.757), breastfeeding support from health workers in the first hour after birth (76.3% migrants vs 75.0% non‐migrant, p = 0.404) and rooming‐in (87.1% migrants vs 86.5% non‐migrant, p = 0.654). Overall, exclusive breastfeeding rate at discharge had a large heterogeneity across maternity hospitals, with higher rates reported by migrant women (86.1% migrants vs 78.4% non‐migrant, p < 0.001).Conclusion: Actions are needed to ensure breastfeeding promotion across facilities and high‐quality care to all women and newborns.10. A neural window on a primitive relationship: the cerebral synchronization between mothers and their newborns during breastfeedingStefano Bembich, Elena Castelpietra, Jenny Bua, Enrica Causin, Chiara Pavan, Laura TravanInstitute for Maternal and Child Health IRCCS “Burlo Garofolo” – Trieste, Italy for all authorsBackground: Early co‐regulation processes between mothers and newborns involved in the primary relationship have been described and breastfeeding is part of it. A reciprocal co‐regulation involving their brain may be hypothesized too.Objectives: This research aimed to identify a possible synchronization between mother and newborn's cerebral cortex functional activation during breastfeeding.Methods: Twenty mother‐full term newborn dyads were enrolled. Cortical activation during breastfeeding was identified by multichannel near‐infrared spectroscopy, which detects changes in haemoglobins concentration from multiple regions of the cortex. Functional activity was simultaneously detected (hyperscanning) in mothers and their newborns' frontal cortex. The first five minutes of breastfeeding were monitored and oxygenated haemoglobin increase was identified as a cortical activation estimate. Wavelet Transform Coherence (WTC) analysis was used to identify a possible synchronization between functional activations in mother and newborn's frontal cortex.Results: Newborns showed a functional activation in right somatosensory/primary motor cortex and mothers in central somatosensory/primary motor cortex. WTC analysis revealed a cyclic functional synchronization between the cortical regions found activated in mothers and newborns.Conclusion: During breastfeeding, newborns show an activation of the right somatosensory/primary motor cortex and mothers of the central somatosensory/primary motor cortex. Breastfeeding seems to be associated with an intense experience for both newborns and mothers. Moreover, the frontal cortex of both partners shows to be cyclically synchronized throughout the first five minutes of breastfeeding, revealing a common sharing of experiences associated with somatosensation, reciprocal dynamic motor adjustment and attachment related feelings, which permeates the primary dyad during such a primitive experience.11. Considering the Environmental Impact of Powdered Baby Formula in Planetary and Population Health PolicyKarin Cadwell, Anna Blair, Cindy Turner‐MaffeiHealthy Children Project, United StatesBackground: Breastfeeding is situated in the nexus between the health of the earth's environment and the health of its population. Although human milk feeding has negligible cost to the environment and is the undisputed foundation of optimal population health, around two‐thirds of humans are fed processed foods, such as powdered baby formula, as a substitute for human milk in the first 2 years after birth.Objective: Describe the environmental cost of powdered standard infant, special, follow‐on and growing‐up formula data as has been calculated for more than a dozen countries including those in the Asia Pacific region, North America, South America and Europe.Method: Compare the differences in computations of the minimal estimate of greenhouse gas (GHG) “farm to gate” emissions for powdered baby formula products sold in different parts of the world.Results: Powdered infant formula is a highly processed food that contributes GHG emission for a kilogram of milk formula (including standard infant formula, follow on formula, and toddler milk), from a low of around 4 kg CO2 eq. in Asia Pacific countries to a high of more than 10 kg CO2 eq. for “growing up” powdered formula in North America.Conclusion: Along with the acknowledged health and social benefits of breastfeeding, the cost to the environment should be considered in developing and funding infant feeding policies and supportive practices.12. Breastfeeding mothers undergoing a (surgical) procedure: health care providers' advice and experienced practices by mothersJoke Muyldermans1, Santina Gorsen2, Kristien De Paepe2, Eline Tommelein11Faculty of Medicine and Pharmacy, Department of Pharmacy, Vrije Universiteit Brussel, Jette, Belgium2Faculty of Medicine and Pharmacy, Department of Pharmacy, In Vitro Toxicology and Dermato‐Cosmetology, Vrije Universiteit Brussel, Jette, BelgiumBackground: Multiple recommendations are published considering breastfeeding mothers who need to undergo a (surgical) procedure to support and protect the continuation of breastfeeding.Objectives: To map advice of health care providers (HCPs) and experiences of breastfeeding women concerning undergoing a (surgical) procedure during breastfeeding.Methods: This cross‐sectional study ran from February 2021 to April 2022 assessing advice of HCPs and experiences of mothers through online questionnaires. HCPs could participate when they came into contact with breastfeeding mothers at least once a year. A mother could participate when she was living in Belgium, older than 18 year and underwent a (minor or major) (surgical) procedure during breastfeeding in the 2 preceding years. Participants were reached through social media channels, HCP professional organization and HCPs (for mothers).Results: Questionnaires were completed by 291 HCPs and 183 mothers. HCPs believed their knowledge about breastfeeding to be good and almost all acknowledged the superiority of breastfeeding and the importance of its continuation after surgery. However, very few HCPs are familiar with published protocols. Each recommended practice is routinely advised by less than half of HCPs. The parallel research in breastfeeding mothers confirmed that each recommended practice was given to less than 40% of mothers. For a quarter of the respondents, the use of medication during surgery was never discussed and more than 70% of mothers received no or incorrect advice about breast milk storage or use.Conclusion: There is a knowledge gap leading to inappropriate care for breastfeeding mothers undergoing a (surgical) procedure.Poster Session13. How accepted is public breastfeeding in Germany? Experiences and Attitudes of the Population and Breastfeeding Mothers 2016 and 2020Stephanie Luecke1, Severine Koch2, Gaby‐Fleur Boel2, Maria Flothkoetter11Healthy Start ‐ Young Family Network, Federal Centre for Nutrition, Bonn, Germany2Department Risk Communication, German Federal Institute for Risk Assessment, Berlin, GermanyBackground: Germany is only moderately breastfeeding‐friendly. Based on a reference study, a survey on the acceptance of breastfeeding in public was conducted.Objectives: The aim of the work is to capture perceptions and attitudes towards public breastfeeding in comparison between 2016 and 2020. In addition, differences between the general population and mothers of young children as well as between mothers with different levels of education are considered.Methods: 1,007 people aged 16 and older and 307 mothers with children up to 24 months were surveyed online about public breastfeeding in 2020.Results: In 2020, a larger percentage of mothers breastfeed in public than in 2016. Mothers with lower levels of education are less likely to breastfeed, also in public, and more likely to report mixed reactions. Among the general population, acceptance of public breastfeeding has declined. The potential for conflict noted in 2016, e.g., in restaurants, has intensified. About one in six (17%) explicitly rejects breastfeeding in public. Knowledge about the health effects of breastfeeding is lower among the general public than among mothers. As in 2016, knowledge about the positive effects of breastfeeding is associated with greater acceptance of public breastfeeding.Conclusion: The results underline the importance of measures that increase the acceptance of breastfeeding, for example, to communicate knowledge to the population, to show breastfeeding more frequently in mass media and through positive role models, and to make the settings in which families live more breastfeeding‐friendly. Measures should pay special attention

Progressive erythrocytosis under lenvatinib treatment in patients with advanced hepatocellular carcinoma

PurposeThis manuscript reports on the occurrence of early and frequent erythrocytosis in advanced hepatocellular carcinoma (HCC) patients treated with lenvatinib.MethodsA cohort of 23 patients with advanced HCC, treated with this antiangiogenic drug for at least one month, was retrospectively analyzed.ResultsThese patients (82.7% men, median age 58.3, cirrhosis in 60.8%) were treated between October 2019 and September 2020 with lenvatinib, as first-line systemic therapy for 82.6% of them. For 20 patients (87%), an early and significant increase in hemoglobin (Hb) level, up to 1.41 g/dL (p < 0.001) was reported and remained elevated. Ten patients (43.5%), all men, reached erythrocytosis (Hb > 16.5 g/dL), 7 were treated with low-dose aspirin for primary thromboprophylaxis and 2 needed phlebotomy. None underwent thromboembolic complications. A significant Hb decrease was observed after treatment discontinuation (p < 0.05). Erythropoietin (EPO) serum levels also increased, which was attributed to HCC after immunostaining for EPO in liver biopsies. The Naranjo adverse drug reaction probability scale documented the relationship between erythrocytosis and lenvatinib and regression at treatment discontinuation. Erythrocytosis was hypothesized to be a class effect of anti-VEGF therapies, the magnitude of which might depend on the IC50 value of each molecule.ConclusionThis report documents the frequent occurrence of erythrocytosis during lenvatinib treatment for advanced HCC, likely secondary to EPO secretion by tumor cells through the antiangiogenic activity levatinib. An early and close monitoring of hematologic parameters is, thus, recommended, together with thromboprophylaxis by low-dose aspirin and phlebotomy in case of symptomatic erythrocytosis.

Infliximab induced severe depression and suicidal thoughts in patient with bipolar disorder

IntroductionInfliximab is a tumor necrosis factor-alpha (TNF-α) inhibitor commonly used in the treatment of autoimmune disorders such as rheumatoid arthritis and ankylosing spondylitis. An increased risk of opportunistic infections, malignancy, and neurodegenerative diseases have been widely documented as adverse effects of IFX therapy. Few reports exist serving the notice of new-onset psychiatric symptoms linked to IFX treatment, such as suicidal behaviors in adults and elderly patients, as well as psychosis in an adolescent. Psychiatric side effects while under IFX treatment are reported to be rare.ObjectivesHere, we present a case of a female with bipolar disorder who developed a long-standing depressive episode with suicidal thoughts after her fourth infusion of infliximab for her ankylosing spondylitisMethodsRetrospective life chart was created, including infliximab infusion.Montgomery Asberg Depression Scale was applied at time of hospitalisation and discharge.The Naranjo Adverse Drug Reaction Probability Scale was applied.ResultsA 55 year old female with ankylosing spondylitis and bipolar disorder was treated with IFX for 8 months. During this period, a total of 4 infusions were administered and AS symptoms were well responding to the treatment. Patient describes the onset of depressive symptoms such as anhedonia and insomnia after the infusion of third IFX infusion, gradually progressing to loss of function and suicidal thoughts and hospitalization in a psychiatry clinic.The patient had a history of bipolar disorder for 10 years with recurrent manic and depressive episodes, 4 hospitalisations and 1 cure of ECT. Patient was on sertraline, maprotiline and diazepam at the time of hospitalization. We started treatment with aripiprazole, quetiapine and valproate, followed for 4 weeks as an inpatient, consulted with rheumatology treatment options and neurology for demyelinating disorders, no pathology was discovered. Rheumatology suggested the continuation of IFX infusion under psychiatric control. Fifth dose of IFX infusion was administered and patient was discharged after euthymic mood was established and insomnia and suicidal thoughts were deteriorated. Upon follow up, depressive symptoms recurred and lamotrigine was added for augmentation.Image:ConclusionsAlthough there is very scarce evidence that IFX causes psychiatric symptoms, there are few clinical trials too, showing evidence that TNF-alpha inhibitors may improve depressive symptoms. While we need more information and evidence to support the ideas of TNF alpha inhibitors effects on human neuropsychology, it is of great importance for especially patients with psychiatric history to be closely watched while administering the product, at least to minimize unintended adverse events.Disclosure of InterestNone Declared

Recurrent Hyponatremia: Levetiracetam - An Uncommon Cause.

Dear Editor, Hyponatremia can be an adverse drug reaction with the use of some of the anti-seizure medications (ASM). Carbamazepine and oxcarbazepine are the most common ASMs which induce hyponatremia. Rarely sodium valproate, eslicarbazepine, lamotrigine, levetiracetam, and gabapentin have also been reported to cause hyponatremia.[1] We report a case of Levetiracetam induced hyponatremia and review the English literature of similar cases. A 50-year-old male had traumatic brain injury in November 2015 and neuroimaging was normal. He was started on prophylactic levetiracetam at another facility. Since then, he had three admissions for hyponatremia: First admission was for acute symptomatic seizures due to hyponatremia, serum sodium of 118 mmol/L; second admission in February 2016 for dizziness, serum sodium 131 mmol/L; and third admission during April 2016 for drowsiness, serum sodium 108 mmol/L [Table 1]. During the latter two admissions, the work-up for hyponatremia was suggestive of syndrome of inappropriate antidiuretic hormone secretion (SIADH). During the first admission, patient was on levetiracetam 500 mg q12h and the dose was escalated to 1000 mg q12h at discharge. Patient was started on tolvaptan 15 mg q24h at discharge in the first admission (25.12.2015). During his subsequent admissions, workup for other causes of hyponatremia was negative. He was continued with tolvaptan intermittently. Review of the case records and drug chart suggested possible relation between hyponatremia and levetiracetam, a diagnosis of levetiracetam induced hyponatremia was considered and levetiracetam was discontinued. Since then, he had no further episode of hyponatremia. Patient was not started on any ASM as it is not our practice to use ASMs for primary prophylaxis in traumatic brain injury.Table 1: Admission profile of the patientIn this patient, diagnostic workup suggested that SIADH was the possible mechanism for hyponatremia. He had a mild closed traumatic brain injury and normal brain imaging. This clinical scenario is very unlikely to cause SIADH. Workup for other causes of hyponatremia was negative. When levetiracetam was discontinued patient had no further episodes of hyponatremia. On Naranjo Adverse Drug Reaction Probability Scale[2] this patient had a score of 7 suggesting levetiracetam being the “probable” culprit responsible for hyponatremia. Review of English literature revealed report of four patients with levetiracetam induced hyponatremia [Table 2]. In four patients, including the present case SIADH was the mechanism of hyponatremia. There are no specific clinical characteristics which are common among these 5 cases. In all the patients, hyponatremia was corrected after withdrawing levetiracetam. In patient “3” in addition to levetiracetam, hydrochlorothiazide would have added to the misery of hyponatremia.Table 2: Characteristics of the patientsIn conclusion this case illustrates that chronic hyponatremia in a patient with epilepsy on ASMs, one should check the ASM list to exclude the possible drug that can be associated with hyponatremia. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

A naturalistic study on side effects of selective serotonin reuptake inhibitors in psychiatric out-patient department

Introduction: &gt;Antidepressants are one of the most commonly prescribed psychotropic drugs. Six SSRIs are approved for various disorders. SSRIs have fewer side effects owing to its selective blocking the serotonin transporter. Nonetheless SSRI has several troublesome side effects, including nausea, diarrhoea, headache, dizziness, sexual side effects, tachycardia, or weight gain. Methodology: This cross-sectional comprised of 200 patients who were divided into two groups. Group 1 had participants who had received SSRI for less than 6 weeks duration and group 2 had patients who had taken SSRI for more than 6 months. Side effects of medications were recorded using UKU side effect rating scale and causality was ascertained using Naranjo adverse drug reaction probability scale. Results: Among the early side effect group consisting of 100 patients, 40% of patients reported at least one side effect. Tension/inner unrest, nausea and vomiting and orgastic dysfunction was the most common side effect reported. 30% of patients in late side effect group had at least one side effect. Orgastic dysfunction, decreased sexual desire and weight gain were the main side effects reported. All the reported side effects were probably associated due to the prescribed SSRI, as inferred from Naranjo causality scoring system.  Conclusion: Escitalopram was the most commonly prescribed SSRI among all the SSRIs. Paroxetine and fluvoxamine were the least prescribed SSRIs. Sertraline was found to cause maximum side effects in the early group and fluoxetine caused the most side effects in the late group. Tension/Inner unrest was the most commonly reported side effects followed by sexual side effects.

Relationship between piperacillin concentrations, clinical factors and piperacillin/tazobactam-associated acute kidney injury.

Piperacillin/tazobactam, a commonly used antibiotic, is associated with acute kidney injury (AKI). The relationship between piperacillin concentrations and AKI remains unknown. Estimate piperacillin exposures in critically ill children and young adults administered piperacillin/tazobactam to identify concentrations and clinical factors associated with piperacillin-associated AKI. We assessed piperacillin pharmacokinetics in 107 patients admitted to the paediatric ICU who received at least one dose of piperacillin/tazobactam. Piperacillin AUC, highest peak (Cmax) and highest trough (Cmin) in the first 24 hours of therapy were estimated. Piperacillin-associated AKI was defined as Kidney Disease: Improving Global Outcomes (KDIGO) Stage 2/3 AKI present >24 hours after initial piperacillin/tazobactam dose. Likelihood of piperacillin-associated AKI was rated using the Naranjo Adverse Drug Reaction Probability Scale. Multivariable logistic regression was performed to identify patient and clinical predictors of piperacillin-associated AKI. Out of 107 patients, 16 (15%) were rated as possibly or probably having piperacillin-associated AKI. Estimated AUC and highest Cmin in the first 24 hours were higher in patients with piperacillin-associated AKI (2042 versus 1445 mg*h/L, P = 0.03; 50.1 versus 10.7 mg/L, P < 0.001). Logistic regression showed predictors of piperacillin-associated AKI included higher Cmin (OR: 5.4, 95% CI: 1.7-23) and age (OR: 1.13, 95% CI: 1.05-1.25). We show a relationship between estimated piperacillin AUC and highest Cmin in the first 24 hours of piperacillin/tazobactam therapy and piperacillin-associated AKI, suggesting total piperacillin exposure early in the course is associated with AKI development. These data could serve as the foundation for implementation of model-informed precision dosing to reduce AKI incidence in patients given piperacillin/tazobactam.

Adverse Drug Reactions Monitoring in New Patients Admitted to the Cardiac Care Unit in a Tertiary Care Hospital

Background: Adverse Drug Reactions (ADRs) are amongst the commonly occurring event in the intensive care unit where patients are mostly on the polypharmacy. They affect the quality of life of patients and increase the burden on the health care system. Aim and Objectives: The study aimed to estimate the incidence of ADRs and to assess the causality and seriousness of such ADRs by using the Naranjo probability scale. A prospective, observational, longitudinal study was conducted on patients admitted to the cardiac care unit over a period of 10 months. ADRs profile was noted by spontaneous and intensive monitoring. For analysis, descriptive statistics with 95% CI were used. Results: A total of 77 ADRs were reported from the 173 patients, out of which 31 patients suffered from ADRs, with an incidence of 17.9%. The gastrointestinal system was the most common affected system followed by the cardiovascular and respiratory systems. When analyzed on the Naranjo ADR probability scale, the majority of the ADRs (67.5%) were rated as probable followed by possible (32.4%). It was observed that the number of drugs used as well as the duration of stay in the hospital, in patients with ADRs, was significantly higher than those who did not have any adverse effect. The pattern and spectrum of ADRs need to be studied further so that their occurrence can be prevented. Conclusion: The study can be useful in identifying and minimizing preventable ADRs and can be an effort to make the use of drugs more rational and safe

Ciprofloxacin induced toxic epidermal necrolysis with cholestatic hepatitis: A case report with literature review and revisit to the Naranjo adverse drug reaction probability scale

Ciprofloxacin, among the many Fluoroquinolones, has been widely used as a broad-spectrum antibiotic due to its wide range of action and relatively safe adverse effect profile. However, among the cutaneous adverse drug reactions due to Ciprofloxacin, toxic epidermal necrolysis occurring along with cholestatic hepatitis is a rare one. Here, we present a case of a 22-year-old male patient who was diagnosed with toxic epidermal necrolysis with cholestatic hepatitis secondary to Ciprofloxacin. Naranjo adverse drug reaction probability scale was used for the causal association.

Anti-programmed death-1 inhibitor nivolumab-induced immune-related adverse events: hepatitis, renal insufficiency, myositis, vitiligo, and hypothyroidism: a case-based review.

Nivolumab (NIVO) is a monoclonal antibody used to treat renal cell cancer. It is an anti-programmed death-1 (anti-PD-1) inhibitor, enhancing the tumor-targeted immune response of T lymphocytes, resulting in immune-mediated adverse events (AEs). We present five immunologicalAEs in a single patient treated with NIVO. A 68-year-old male patient with metastatic renal cell carcinoma and right-sided nephrectomy received NIVO after pazopanib and sunitinib treatment. Two and a half months after starting NIVO, hepatocellular enzymes and creatinine were elevated. Concomitantly, the patient noticed hypopigmentation of the hand skin and a change in voice and speech. Due to hepatitis, he has been treated with dexamethasone 16mg daily for 22days, after which hypothyroidism and increased creatine kinase were found without muscle pain and functional impairment. Dexamethasone was continued, and a rapid decline in all parameters except thyroid-stimulating hormone (TSH) and vitiligo was observed. Myositis was initially considered a part of hypothyroidism and elevated renal parameters due to hypohydration. The rapid regression on glucocorticoid treatment and a longer time for creatinine normalization than expected with hydration were noticed. Nivolumab likely induced those side effects as assessed by Naranjo Adverse Drug Reaction Probability Scale. The literature review shows that theconsequences of PD-1 inhibition are not uniform. Side effects of checkpoint inhibitors should be monitored carefully in the early and later treatment schedules evaluating subclinical manifestations like myositis and worsening of kidney parameters. Early administered higher doses of glucocorticoids can stop drug toxicity and reverse-induced tissue damage.