scholarly journals Use of antipsychotic drugs and cholinesterase inhibitors and risk of falls and fractures: self-controlled case series

BMJ ◽  
2021 ◽  
pp. n1925
Author(s):  
Grace Hsin-Min Wang ◽  
Kenneth K C Man ◽  
Wei-Hung Chang ◽  
Tzu-Chi Liao ◽  
Edward Chia-Cheng Lai

Abstract Objective To evaluate the association between the use of antipsychotic drugs and cholinesterase inhibitors and the risk of falls and fractures in elderly patients with major neurocognitive disorders. Design Self-controlled case series. Setting Taiwan’s National Health Insurance Database. Participants 15 278 adults, aged ≥65, with newly prescribed antipsychotic drugs and cholinesterase inhibitors, who had an incident fall or fracture between 2006 and 2017. Prescription records of cholinesterase inhibitors confirmed the diagnosis of major neurocognitive disorders; all use of cholinesterase inhibitors was reviewed by experts. Main outcome measures Conditional Poisson regression was used to derive incidence rate ratios and 95% confidence intervals for evaluating the risk of falls and fractures for different treatment periods: use of cholinesterase inhibitors alone, antipsychotic drugs alone, and a combination of cholinesterase inhibitors and antipsychotic drugs, compared with the non-treatment period in the same individual. A 14 day pretreatment period was defined before starting the study drugs because of concerns about confounding by indication. Results The incidence of falls and fractures per 100 person years was 8.30 (95% confidence interval 8.14 to 8.46) for the non-treatment period, 52.35 (48.46 to 56.47) for the pretreatment period, and 10.55 (9.98 to 11.14), 10.34 (9.80 to 10.89), and 9.41 (8.98 to 9.86) for use of a combination of cholinesterase inhibitors and antipsychotic drugs, antipsychotic drugs alone, and cholinesterase inhibitors alone, respectively. Compared with the non-treatment period, the highest risk of falls and fractures was during the pretreatment period (adjusted incidence rate ratio 6.17, 95% confidence interval 5.69 to 6.69), followed by treatment with the combination of cholinesterase inhibitors and antipsychotic drugs (1.35, 1.26 to 1.45), antipsychotic drugs alone (1.33, 1.24 to 1.43), and cholinesterase inhibitors alone (1.17, 1.10 to 1.24). Conclusions The incidence of falls and fractures was high in the pretreatment period, suggesting that factors other than the study drugs, such as underlying diseases, should be taken into consideration when evaluating the association between the risk of falls and fractures and use of cholinesterase inhibitors and antipsychotic drugs. The treatment periods were also associated with a higher risk of falls and fractures compared with the non-treatment period, although the magnitude was much lower than during the pretreatment period. Strategies for prevention and close monitoring of the risk of falls are still necessary until patients regain a more stable physical and mental state.

2019 ◽  
Vol 33 (4) ◽  
pp. 466-471 ◽  
Author(s):  
Ruth Brauer ◽  
Maria Herrero-Zazo ◽  
David J Barlow ◽  
Fiona Gaughran ◽  
David Taylor ◽  
...  

Background Minocycline has neurological anti-inflammatory properties and has been hypothesised to have antipsychotic effects. Aim The aim of this study was to investigate, using routinely collected United Kingdom primary health care data, whether adolescent men and women are more or less likely to receive an urgent psychiatric referral during treatment for acne with minocycline compared with periods of non-treatment. Method A self-controlled case series using United Kingdom Clinical Practice Research Datalink to calculate the incidence rate ratio of urgent psychiatric referrals for individuals, comparing periods during which minocycline was prescribed with unexposed periods, adjusted for age. Results We found 167 individuals who were at the time exposed to minocycline for a mean of 99 days and who received an urgent psychiatric referral. There was no difference in psychiatric referral risk during periods of exposure compared with periods of non-exposure: incidence rate ratio first 6 weeks of exposure 1.96, 95% confidence interval 0.82–4.71, p=0.132; incidence rate ratio remaining exposure period=1.97, 95% confidence interval 0.86–4.47, p=0.107. Conclusions We found no evidence in support of a protective effect of minocycline against severe psychiatric symptoms in adolescence.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Edward Chia-Cheng Lai ◽  
Hsun-Yin Liang ◽  
Ya-Chun Huang ◽  
Wei-I. Huang ◽  
Pi-Hui Chao ◽  
...  

AbstractTo investigate associations between isoniazid for latent tuberculosis and risk of severe hepatitis, affecting patients with rheumatoid arthritis or ankylosing spondylitis whose treatment includes tumor necrosis factor inhibitors. Our self-controlled case series study analyzed Taiwan’s National Health Insurance Database from 2003 to 2015 to identify RA or AS patients, aged ≥ 20 years, receiving TNF inhibitors and a 9-month single isoniazid treatment. The outcome of interest was hospitalization due to severe hepatitis. We defined risk periods by isoniazid exposure (days): 1–28, 29–56, 57–84, 85–168, 169–252, and 253–280. To compare risk of severe hepatitis in exposed and non-exposed periods, we performed conditional Poisson regressions to generate incidence rate ratios (IRR) and 95% confidence intervals, with adjustment of patients’ baseline covariates including age, sex, HBV, HCV and related medication. Of 54,267 RA patients and 137,889 AS patients identified between 2000 and 2015, 11,221 (20.7%) RA and 4,208 (3.1%) AS patients underwent TNFi therapy, with 722 (5%) receiving isoniazid for latent tuberculosis. We identified 31 incident cases (4.3%) of hospitalization due to severe hepatitis. Of these hospitalization events, 5 occurred in the exposed periods, 25 occurred in the INH unexposed periods, and 1 occurred in the pre-exposure period. Compared with non-exposure, the risk of severe hepatitis was higher in exposed periods (incidence rate ratio [IRR]: 5.1, 95% CI: 1.57–16.55), especially 57–84 days (IRR: 17.29, 95% CI: 3.11–96.25) and 85–168 days (IRR:10.55, 95% CI: 1.90–58.51). The INH related fatal hepatotoxicity was not identified in our study. Our findings suggest an association between risk of severe hepatitis and exposure to isoniazid in patients with RA or AS under TNFi therapy, particularly within the exposed period 57–168 days. A close monitoring of liver function is mandatory to minimize the risk, especially within the first 6 months after initiation of 9 months isoniazid.


Author(s):  
Emily J Peach ◽  
Fiona A Pearce ◽  
Jack Gibson ◽  
Andrew J Cooper ◽  
Li-Chia Chen ◽  
...  

Abstract Self-controlled study designs can be used to assess the association between exposures and acute outcomes while controlling for important confounders. Using routinely collected health data, a self-controlled case series design was used to investigate the association between opioid use and bone fractures in 2008–2017 among adults registered in the United Kingdom Clinical Practice Research Datalink. The relative incidence of fracture was estimated, comparing periods when exposed and unexposed to opioids, adjusted for time-varying confounders. Of 539,369 people prescribed opioids, 67,622 sustained fractures and were included. The risk of fracture was significantly increased when exposed to opioids, with an adjusted incidence rate ratio of 3.93 (95% confidence interval: 3.82, 4.04). Fracture-risk was greatest in the first week of starting opioids (adjusted incidence rate ratio: 7.81, 95% confidence interval: 7.40, 8.25) and declined with increasing duration of use. Re-starting opioids after a gap in exposure significantly increased fracture-risk (adjusted incidence rate ratio: 5.05, 95% confidence interval: 4.83, 5.29) when compared to non-use. These findings highlight the importance of raising awareness of fractures among patients at opioid initiation and demonstrate the utility of self-controlled methods for pharmacoepidemiologic research.


2021 ◽  
pp. 1-9
Author(s):  
Biljana Kuzmanović Elabjer ◽  
Mladen Bušić ◽  
Andrej Pleše ◽  
Mirjana Bjeloš ◽  
Daliborka Miletić ◽  
...  

<b><i>Introduction:</i></b> Ultrasound biomicroscopy (UBM) is the only widely used method for the evaluation of anterior uveal melanoma (AUM). <b><i>Objective:</i></b> Documentation of regression of AUM treated with ruthenium-106 (Ru-106) plaque types CCB and CCC using UBM. <b><i>Methods:</i></b> This single institution-based retrospective case series involved 10 Caucasian patients with AUM followed after brachytherapy with UBM from January 2014 until February 2019. The largest prominence of the tumor perpendicular to the sclera or the cornea (including scleral/corneal thickness) (<i>D</i>) and the largest basal dimension (<i>B</i>) were measured in millimeters with UBM for all patients prior to the brachytherapy and at 4-month interval follow-up. Tumor regression was calculated as a percentage of decrease in the initial <i>D</i> and <i>B</i> values. <b><i>Results:</i></b> The study involved 10 patients with a mean age of 64.4 years (yr) (range 46–80 yr). <i>D</i> ranged from 1.82 to 5.5 mm (median 2.99 mm) and <i>B</i> from 2.32 to 12.38 mm (median 4.18 mm). The apical radiation dose in all patients was 100 Gy. The median follow-up was 42.02 months. Regression for <i>D</i> was 21.11 ± 13.66%, 31.09 ± 14.66%, and 34.92 ± 19.86% at 1st, 2nd, and 3rd year of the follow-up, respectively, while for <i>B</i> it was 21.58 ± 16.05%, 28.98 ± 17.71%, and 32.06 ± 18.96%, respectively. Tumor recurrence was documented in 2/10 patients. <b><i>Conclusion:</i></b> The major regression of AUM, treated with Ru-106 plaque types CCB and CCC, was documented in the first 2 years after brachytherapy in our study group. In the following years, only minimal regression was documented that warns of the need for close monitoring and active search for local recurrences.


2005 ◽  
Vol 33 (8) ◽  
pp. 1220-1223 ◽  
Author(s):  
Joseph R. Carney ◽  
Timothy S. Mologne ◽  
Michael Muldoon ◽  
Jay S. Cox

Background Few published articles exist reporting the long-term evaluation of the Roux-Elmslie-Trillat procedure. Purpose To assess the long-term effect of the Roux-Elmslie-Trillat procedure in preventing recurrent subluxation and dislocation of the patella. Study Design Case series; Level of evidence, 4. Methods Eighteen patients who underwent the Roux-Elmslie-Trillat procedure for dislocation or subluxation of the patella were identified from a group previously evaluated at a mean follow-up of 3 years. The prevalence of recurrent subluxation or dislocation at a mean follow-up of 26 years was compared with the prevalence reported at the mean follow-up of 3 years. Although not the focus of this study, Cox functional scores were obtained from the smaller group and compared with the results at the 3-year follow-up. Results Seven percent (95% confidence interval, 0.00-0.32) of the patients had recurrent subluxation at 26 years compared with 7% (95% confidence interval, 0.03-0.13) of the study population reported at 3 years (P = 1.00). Fifty-four percent (95% confidence interval, 0.27-0.79) rated their affected knee as good or excellent at 26 years compared with 73% (95% confidence interval, 0.64-0.81) of the larger study population reported at 3 years (P = .14). Conclusion The prevalence of recurrent subluxation and dislocation in patients with patellofemoral malalignment who underwent the Roux-Elmslie-Trillat procedure for dislocation or subluxation of the patella is similar at 3 and 26 years after the procedure. The long-term functional status of the affected knee in patients who underwent the Roux-Elmslie-Trillat procedure declined.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 641.1-641
Author(s):  
Y. B. Joo ◽  
Y. J. Park

Background:Infections have been associated with a higher risk of systemic lupus erythematosus (SLE) flares, but the impact of influenza infection on SLE flares has not been evaluated.Objectives:We evaluated the association between influenza infection and SLE flares resulting in hospitalization.Methods:SLE flares resulting in hospitalization and influenza cases were ascertained from the Korean national healthcare insurance database (2014-2018). We used a self-controlled case series design. We defined the risk interval as the first 7 days after the influenza index date and the control interval was defined as all other times during the observation period of each year. We estimated the incidence rates of SLE flares resulting in hospitalization during the risk interval and control interval and compared them using a Poisson regression model.Results:We identified 1,624 influenza infections among the 1,455 patients with SLE. Among those, there were 98 flares in 79 patients with SLE. The incidence ratio (IR) for flares during the risk interval as compared with the control interval was 25.75 (95% confidence interval 17.63 – 37.59). This significantly increased the IRs for flares during the risk interval in both women (IR 27.65) and men (IR 15.30), all age groups (IR 17.00 – 37.84), with and without immunosuppressive agent (IR 24.29 and 28.45, respectively), and with and without prior respiratory diseases (IR 21.86 and 26.82, respectively).Conclusion:We found significant association between influenza infection and SLE flares resulting in hospitalization. Influenza infection has to be considered as a risk factor for flares in all SLE patients regardless of age, sex, medications, and comorbidities.References:[1]Kwong, J. C. et al. Acute Myocardial Infarction after Laboratory-Confirmed Influenza Infection. N Engl J Med 2018:378;345-353.Table 1.Incidence ratios for SLE flares resulting in hospitalization after influenza infectionRisk intervalIncidence ratio95% CIDuring risk interval for 7 days / control interval25.7517.63 – 37.59Days 1-3 / control interval21.8114.71 – 32.35Days 4-7 / control interval7.563.69 – 15.47SLE, systemic lupus erythematosus; CI, confidence intervalDisclosure of Interests:None declared


2016 ◽  
Vol 9 (1) ◽  
pp. e2017004 ◽  
Author(s):  
Shahrzad Zonoozi

Sitagliptin, a modern antidiabetic agent which is weight neutral and associated with low rate of hypoglycaemias, is being increasingly used in type 2 diabetes mellitus (DM). However there is paucity of data about its efficacy and safety in beta-thalassaemia major (β-TM).This retrospective case series of five patients (mean age of 45 years) is the first study evaluating the use of sitagliptin in patients with β-TM and DM.Four patients responded well to sitagliptin, as evidenced by decrease in fructosamine by 77 and 96µmol/L (equivalent reduction in HbA1c of 1.5% and 1.9%) observed in two patients and reduction in the frequency of hypoglycaemia without worsening glycaemic control in two others. One patient did not respond to sitagliptin. No patients reported significant side effects.This study provides evidence that sitagliptin may be considered, with caution, for use in patients with β-TM and DM, under the close monitoring of a Diabetologist.


2021 ◽  
Vol 12 ◽  
Author(s):  
Maria Luisa Imaz ◽  
Dolors Soy ◽  
Mercé Torra ◽  
Llüisa García-Esteve ◽  
Cristina Soler ◽  
...  

Background: Most guidelines advise that women taking lithium should not breastfeed. The variation in transfer is just one reason behind this advice.Objectives: To present clinical and pharmacokinetic data of nine mother–infant pairs exposed to lithium monotherapy during late pregnancy and exclusive breastfeeding at the Perinatal Psychiatric Unit (2006–2018).Methods: We obtained sociodemographic data, medical risk factors, obstetric variables, and family and personal psychiatric history by semi-structured interview, and assessed maternal psychopathology with the Hamilton Depression Rating Scale and Young Mania Rating Scale. A senior neonatologist reviewed neonatal outcomes at birth using the Peripartum Events Scale. Paired maternal and cord blood and infant venous blood samples were collected. During the breastfeeding period, we monitored serum lithium and creatinine concentrations in mother–infant pairs at delivery, and at days 1–5, 7–11, 30, and 60 postpartum, and monthly until 6-months.Results: Lithium equilibrated completely across the placenta [1.13 (0.10), range (1.02–1.30)]. No women presented symptoms of postpartum lithium intoxication, two of the neonates presented transient hypotonia (22%). Lithium exposure was significantly less during breastfeeding than during late pregnancy, and serum lithium concentrations decreased up to 44% overtime from delivery to the first-month, and up to 60% to the third-month postpartum. There was no growth or developmental delay in the follow-up period. One woman had a manic episode with psychotic features at 45 days postpartum.Conclusions: In carefully selected women with bipolar disorder, lithium therapy when breastfeeding can be an appropriate option if coupled with close monitoring of the mother-infant pair.


Circulation ◽  
2018 ◽  
Vol 138 (4) ◽  
pp. 356-363 ◽  
Author(s):  
Tzu-Ting Chen ◽  
Yi-Chun Yeh ◽  
Kuo-Liong Chien ◽  
Mei-Shu Lai ◽  
Yu-Kang Tu

Background: Invasive dental treatments (IDTs) can yield temporary bacteremia and have therefore been considered a potential risk factor of infective endocarditis (IE). It is hypothesized that, through the trauma caused by IDTs, bacteria gain entry to the bloodstream and may attach to abnormal heart valves or damaged heart tissue, giving rise to IE. However, the association between IDTs and IE remains controversial. The aim of this study is to estimate the association between IDTs and IE. Methods: The data in this study were obtained from the Health Insurance Database in Taiwan. We selected 2 case-only study designs, case-crossover and self-controlled case series, to analyze the data. The advantage of these methods is that confounding factors that do not vary with time are adjusted for implicitly. In the case-crossover design, a conditional logistic regression model with exposure to IDTs was used to estimate the risks of IE following an IDT with 4, 8, 12, and 16 weeks delay, respectively. In the self-controlled case series design, a conditional Poisson regression model was used to estimate the risk of IE for the risk periods of 1 to 4, 5 to 8, 9 to 12, and 13 to 16 weeks following an IDT. Results: In total, 9120 and 8181 patients with IE were included in case-crossover design and self-controlled case series design, respectively. In the case-crossover design, 277 cases and 249 controls received IDTs during the exposure period, and the odds ratio was 1.12 (95% confidence interval, 0.94–1.34) for 4 weeks. In the self-controlled case series design, we observed that 407 IEs occurred during the first 4 weeks after IDTs, and the age-adjusted incidence rate ratio was 1.14 (95% confidence interval, 1.02–1.26) for 1 to 4 weeks after IDTs. Conclusions: In both study designs, we did not observe a clinically larger risk for IE in the short periods after IDTs. We also found no association between IDTs and IE among patients with a high risk of IE. Therefore, antibiotic prophylaxis for the prevention of IE is not required for the Taiwanese population.


Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_5) ◽  
Author(s):  
C Njeru ◽  
A Migowa

Abstract Background Kawasaki disease (kDa) is a childhood vasculitides that affects small and medium-sized arteries. It is self-limiting but when left untreated can cause coronary artery aneurysms in about 25% of children1. The diagnosis is clinical and is made with the criteria of fever for at least five days, and at least four out of five other clinical signs: bilateral non-exudative conjunctivitis, oral mucous membrane changes, peripheral extremity changes, polymorphous rash, and cervical lymphadenopathy. Incomplete kDa is diagnosed with fever for at least five days and at least 2–3 of the principal signs, with suggestive lab investigations and lack of an alternative diagnosis1. kDa is named after Dr Tomisaku Kawasaki who first described it in 1967 in Japan2. The highest incidence of kDa continues to be reported among Asian children, with an incidence rate of 264.8 per 100 000 population aged 0–4 years as per Japan’s latest nationwide survey3. In Africa, the true incidence is unknown but several case reports have been published. A 2016 paper by Gorrab et al.4 found that the annualized incidence rate of kDa in the Maghreb children living in Quebec (18.49/year/100 000 children under 5 years of age) was 4–12 times higher than reported in their countries of origin- Tunisia, Morocco, and Algeria (0.95, 4.52, and 3.15, respectively) suggesting a likelihood of under-diagnosis. This case series sought to highlight the characteristics, presentation, and management of patients diagnosed with kDa in a tertiary hospital in Kenya. Methods This was a retrospective cross-sectional study carried out by reviewing the charts of all the patients with a discharge diagnosis of kDa from January 2013 to December 2017 at the Aga Khan University Hospital, Nairobi. Their demographics, presentation, diagnostic work-up, and management are reported. Analysis was done by descriptive statistics using the Microsoft Excel 2016 Application. Results A total of 15 cases were identified and the patient characteristics and presentation are as tabulated below: In addition to elevated inflammatory markers (C reactive protein and/or Erythrocyte Sedimentation Rate), a significant number of the patients also had sterile pyuria (9/9), hypoalbuminemia (8/10), thrombocytosis (8/15), and anaemia (11/15). Nine out of eleven had negative blood cultures. Fourteen out of the fifteen patients had echocardiograms done during admission. Only one patient was found to have abnormal findings of bilaterally dilated coronaries arteries. Five patients had at least one documented repeat echocardiogram. Fourteen patients received Intravenous Immunoglobulin (IVIG), with 13 of them responding to treatment. No adverse effects were reported after treatment. One patient did not improve and needed a second dose of IVIG and intravenous methylprednisone (30 mg/kg). Fourteen patients received aspirin but dosing varied from high (80–90 mg/kg/day) to moderate (30–50 mg/kg/day) to low dose (3 mg/kg/day). One patient on high-dose aspirin was noted to have developed symptoms consistent with aspirin-induced bronchospasm and was changed to low dose. Conclusion This case series highlights the presence of kDa in the Kenyan pediatric population with patient characteristics similar to what is reported globally. Diagnosis was made after a mean of about 7 days, possibly due to low awareness of the disease among healthcare professionals. Management with IVIG in most cases was successful but more guidance is needed around the use of steroids and the dosing of aspirin.


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