Dopaminergic Drugs and Valproate-associated Refractory Hyponatremia Over Levosulpiride-induced Parkinsonism in an Elderly Female Patient When Deprescribing was the Only Therapy

INTRODUCTION: Prescribing cascade is a condition in which a drug administered to a patient causes an adverse reaction that is misinterpreted as a new condition, resulting in the addition of a new drug. CASE PRESENTATION: Here, we report the case of an elderly female patient who suffered from metabolic, neurologic, and urinary consequences of a prescribing cascade of antiemetic, antiepileptic, and dopaminergic drugs. While levosulpiride caused Parkinsonian symptoms, the dopaminergic drugs and valproate caused refractory hyponatremia followed by altered sensorium, and clidinium contributed to urinary retention. CONCLUSION: The case highlights the need to be vigilant for adverse consequences of the prescribing cascade, especially for antiemetic drugs, such as levosulpiride, because of its propensity to induce extrapyramidal reactions in older patients. In cases of refractory hyponatremia, a trial of de-challenge of valproate and dopaminergic drugs should be considered. The identification and removal of the culprit drugs can rescue the patient from a disabling cycle of adverse drug reactions.

Patterns and outcomes of late onset thyroid disturbances after COVID-19 vaccination: A report of 75 cases.

Isolated cases of subacute thyroiditis exist in the early period of COVID-19 vaccination, largely after mRNA vaccines. Here we report late onset thyroid disturbances and persistent health issues in patients of thyroid disorders after COVID-19 vaccination. Seventy-five patients with post COVID-19 vaccination thyroid disturbances were identified. Among these, 41 had flare of underlying thyroid illness, majority occurring at a median time lag of 28.4 weeks since 2nd dose. Thirty-one cases of new onset hypothyroidism and three of new onset hyperthyroidism were reported, with a median time lag respectively of 17.2 and 22.6 weeks since 2nd dose. Most cases occurred after ChAdOx1-nCoV-19, which was the commonest vaccine employed in mass roll out in India. Significant improvement was observed in majority, after a median follow up of 22-26 weeks. New onset health issues persisting for ≥4 weeks were reported in 37.3% and were common in individuals with history of COVID-19 before vaccine. New onset metabolic, musculoskeletal, and reproductive disorders were the common health complaints. Active monitoring is warranted for late onset adverse events after COVID-19 vaccines of all types. Larger studies with involvement of unvaccinated individuals are required to understand the incidence and causality of late onset thyroid disturbances after COVID-19 vaccines.

Did COVID-19 or COVID-19 Vaccines Influence the Patterns of Dengue in 2021? An Exploratory Analysis of Two Observational Studies from North India.

Dengue experienced a rise in disease burden in 2021 in specific regions of India. We aimed to explore the risk factors of dengue occurrence and severity in the post-COVID-19 and post-COVID-19 vaccination era and performed an exploratory analysis involving participants from two prior observational studies conducted from February 2021 to April 2022 in a tertiary hospital in North India. Health care workers constituted the majority of the study participants. Individuals were stratified into five groups based on COVID-19 infection and timing of vaccination: COVID-No Vaccine, Vaccine-No COVID (VNC), COVID After Vaccine (CAV), Vaccine After COVID (VAC), and No Vaccine-No COVID (NVNC) groups. The occurrence of laboratory-confirmed dengue and severe forms of dengue were the main outcomes of interest. A total of 1,701 participants (1,520 vaccinated, 181 unvaccinated) were included. Of these, symptomatic dengue occurred in 133 (7.8%) and was "severe" in 42 (31.6%) cases. Individuals with a history of COVID-19 in 2020 had a 2-times-higher odds of developing symptomatic dengue (P = 0.002). The VAC group had 3.6 (P = 0.019)-, 2 (P = 0.002)-, and 1.9 (P = 0.01)-times-higher odds of developing symptomatic dengue than the NVNC, VNC, and CAV groups, respectively. The severity of dengue was not affected by COVID-19 vaccination but with marginal statistical significance, a 2-times-higher risk of severe dengue was observed with any COVID-19 of the past (P = 0.08). We conclude that COVID-19 may enhance the risk of developing symptomatic dengue. Future research should explore the predisposition of COVID-19-recovered patients toward other viral illnesses. Individuals receiving COVID-19 vaccines after recovering from COVID-19 particularly seem to be at greater risk of symptomatic dengue and need long-term watchfulness. Possible mechanisms, such as antibody-dependent enhancement or T-cell dysfunction, should be investigated in COVID-19-recovered and vaccinated individuals.

Long-Term Safety Analysis of the ChAdOx1-nCoV-19 Corona Virus Vaccine: Results from a Prospective Observational Study in Priority Vaccinated Groups in North India.

INTRODUCTION: Various vaccines for protection against COVID-19 were provided emergency approval in late 2020 to early 2021. There is a scarcity of long-term safety data for many of these. OBJECTIVE: The main aim of this study is to provide the one-year safety results of the ChAdOx1-nCoV-19/AZD1222 vaccine and determine the risk factors of adverse events of special interest (AESIs) and persistent AESIs. METHODS: This was a prospective observational study conducted from February 2021 to April 2022 in a tertiary hospital in North India and its two associated centers. Health care workers, other frontline workers, and the elderly vaccinated with the ChAdOx1-nCoV-19 vaccine constituted the study population. Individuals were contacted telephonically at pre-decided intervals for one year and health issues of significant concern were recorded. Atypical adverse events developing after a booster dose of the COVID-19 vaccine were assessed. Regression analysis was conducted to determine risk factors of AESI occurrence and determinants of AESIs persisting for at least one month at the time of final telephonic contact. RESULTS: Of 1650 individuals enrolled, 1520 could be assessed at one-year post-vaccination. COVID-19 occurred in 44.1% of participants. Dengue occurred in 8% of participants. The majority of the AESIs belonged to the MedDRA® SOC of musculoskeletal disorders (3.7% of 1520). Arthropathy (knee joint involvement) was the most common individual AESI (1.7%). Endocrinal disorders such as thyroid abnormalities and metabolic disorders such as newly diagnosed diabetes developed in 0.4% and 0.3% of individuals, respectively. Regression analysis showed females, individuals with a pre-vaccination history of COVID-19, diabetes, hypothyroidism, and arthropathy had 1.78-, 1.55-, 1.82-, 2.47- and 3.9-times higher odds of AESI development. Females and individuals with hypothyroidism were at 1.66- and 2.23-times higher risk of persistent AESIs. Individuals receiving the vaccine after COVID-19 were at 2.85- and 1.94 times higher risk of persistent AESIs compared, respectively, to individuals with no history of COVID-19 and individuals developing COVID-19 after the vaccine. Among participants receiving a booster dose of the COVID-19 vaccine (n = 185), 9.7% developed atypical adverse events of which urticaria and new-onset arthropathy were common. CONCLUSION: Nearly half of the ChAdOx1-nCoV-19 vaccine recipients developed COVID-19 over one year. Vigilance is warranted for AESIs such as musculoskeletal disorders. Females, individuals with hypothyroidism, diabetes, and pre-vaccination history of COVID-19 are at higher risk of adverse events. Vaccines received after natural SARS-CoV-2 infection may increase the risk of persistence of adverse events. Sex and endocrinal differences and timing of the COVID-19 vaccine with respect to natural infection should be explored as determinants of AESIs in the future. Pathogenetic mechanisms of vaccine-related adverse events should be investigated along with comparisons with an unvaccinated arm to delineate the overall safety profile of COVID-19 vaccines.