Can we check serum lithium levels less often without compromising patient safety?

Background Lithium is viewed as the first-line long-term treatment for prevention of relapse in people with bipolar disorder. Aims This study examined factors associated with the likelihood of maintaining serum lithium levels within the recommended range and explored whether the monitoring interval could be extended in some cases. Method We included 46 555 lithium rest requests in 3371 individuals over 7 years from three UK centres. Using lithium results in four categories (<0.4 mmol/L; 0.40–0.79 mmol/L; 0.80–0.99 mmol/L; ≥1.0 mmol/L), we determined the proportion of instances where lithium results remained stable or switched category on subsequent testing, considering the effects of age, duration of lithium therapy and testing history. Results For tests within the recommended range (0.40–0.99 mmol/L categories), 84.5% of subsequent tests remained within this range. Overall, 3 monthly testing was associated with 90% of lithium results remaining within range, compared with 85% at 6 monthly intervals. In cases where the lithium level in the previous 12 months was on target (0.40–0.79 mmol/L; British National Formulary/National Institute for Health and Care Excellence criteria), 90% remained within the target range at 6 months. Neither age nor duration of lithium therapy had any significant effect on lithium level stability. Levels within the 0.80–0.99 mmol/L category were linked to a higher probability of moving to the ≥1.0 mmol/L category (10%) compared with those in the 0.4–0.79 mmol/L group (2%), irrespective of testing frequency. Conclusion We propose that for those who achieve 12 months of lithium tests within the 0.40–0.79 mmol/L range, the interval between tests could increase to 6 months, irrespective of age. Where lithium levels are 0.80–0.99 mmol/L, the test interval should remain at 3 months. This could reduce lithium test numbers by 15% and costs by ~$0.4 m p.a.

Probing the distinct chemosensitivity of Plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro

Improved control of Plasmodium vivax malaria can be achieved with the discovery of new antimalarials with radical cure efficacy, including prevention of relapse caused by hypnozoites residing in the liver of patients. We screened several compound libraries against P. vivax liver stages, including 1565 compounds against mature hypnozoites, resulting in one drug-like and several probe-like hits useful for investigating hypnozoite biology. Primaquine and tafenoquine, administered in combination with chloroquine, are currently the only FDA-approved antimalarials for radical cure, yet their activity against mature P. vivax hypnozoites has not yet been demonstrated in vitro. By developing an extended assay, we show both drugs are individually hypnozonticidal and made more potent when partnered with chloroquine, similar to clinically relevant combinations. Post-hoc analyses of screening data revealed excellent performance of ionophore controls and the high quality of single point assays, demonstrating a platform able to support screening of greater compound numbers. A comparison of P. vivax liver stage activity data with that of the P. cynomolgi blood, P. falciparum blood, and P. berghei liver stages reveals overlap in schizonticidal but not hypnozonticidal activity, indicating that the delivery of new radical curative agents killing P. vivax hypnozoites requires an independent and focused drug development test cascade.

Technique to Stabilize a Lingual Retainer Under Rubber Dam Isolation

Retention is an important phase of orthodontic treatment for prevention of relapse. Over the years, many direct and indirect techniques have been practiced for placing a bonded lingual retainer. The use of rubber dam has become one of the most critical steps during fixed lingual retainer bonding procedure, as it prevents aerosols from spreading in operatory to a greater extent. This article describes a simple method of utilizing rubber dam clamps to assist in the stabilization of lingual retainer wire on teeth. It is easy, simple, reliable, timesaving, and economical as it does not require special equipment or transfer trays.

Exercise as an Add-on Strategy for the Treatment of Bipolar Disorder: Systematic Review and Meta-analysis Protocol

Background: Bipolar disorder (BD) is a severe, recurrent and chronic disorder associated with cognitive impairment, reduction in quality of life and substantially reduction in psychosocial functioning. It presents high rates of comorbidity with cardiovascular and cerebrovascular diseases, diabetes and metabolic syndrome. Individuals with bipolar disorder need to focus their attention and treatment on mental and physical health. Physical exercise is often recommended in bipolar disorder, based on extrapolation from the major depressive disorder literature, theory and clinical expertise. However, studies tend to exclude individuals with BD or make no distinction between diagnostic groups, which leads to heterogeneity and difficulty in generalizing the results. The aim of this review is to evaluate the role of physical exercise as an intervention in bipolar disorder treatment. Method: The study populations must be humans, aged 18 years or older, with a clinical diagnosis of Bipolar Disorder (BD) according to a recognised widely-used diagnostic classification approach, confirmed with a structured interview. We will evaluate two main outcomes (mood symptoms improvement and functioning) and an additional outcome (prevention of relapse/recurrence). The search strategy will be based on the PICOS framework, using medical subject headings, on the following databases: MEDLINE (via Pubmed), EMBASE, CENTRAL, SPORTDiscus (via EBSCO), PsycINFO (via APA) and OpenGrey Repository. Selection and data collection process will be carried out by two authors, independently. Risk of bias and quality of evidence will be graded acording ROB-2 and GRADE. We will present a narrative and quantitative synthesis of the results from the included studies. Regarding quantitative data, we will extract means (M) and standard deviations (SD), when available, to calculate the standardised mean difference (SMD). Effects size will be calculated using SMD and 95% confidence interval and heterogeneity will be assessed. Subgroup analysis will be conducted to explore heterogeneity across studies depending on quality and quantity of the data extracted.Discussion: To date, there wasn't a systematic review with only randomized controlled trials on effects of physical activity on BD. Because of this, we will conduct this systematic review trying to estabilish the effects of exercise on mood, functionality and prevention of relapse.Registration: submitted

Prospecting the intricate role of novel and potent biomarkers in Schizophrenia

: Schizophrenia is a serious psychiatric disorder leading to cognitive impairment and has higher rates of morbidity and mortality. There is a need to understand the mechanisms underlying onset and progression of the disease as the clinical presentation may vary in patients and inadequate knowledge of neurochemical alterations can lead to decreased efficacy in treatment which makes it necessary to identify new potent biomarkers. Identification of biomarkers in schizophrenia offers significant benefits to the well-being of patients, including better prognosis, diagnosis, detection, screening, enhancement in treatment efficacy, prevention of relapse, and better clinical results. Incorporation of advanced technological techniques is necessary to provide an approach for diagnosis and treatment of psychiatric disorders and to permit specific therapeutic interventions. This review highlights the particulars about the current use and application of various biomarkers such as proteomics, miRNAs, language biomarkers, antibodies, blood biomarkers, gut microbiota analysis, neuroimaging biomarkers, and inflammatory biomarkers in effective prognosis, detection, and treatment of schizophrenia and which would comprise as an additional tool for a psychiatrist in cases where an appropriate diagnosis is lacking clarity.

Probing the distinct chemosensitivity of Plasmodium vivax liver stage parasites and demonstration of 8-aminoquinoline radical cure activity in vitro

Improved control of malaria caused by Plasmodium vivax can be achieved with the discovery of new antimalarials with radical cure efficacy, including prevention of relapse caused by hypnozoites residing in the liver of vivax patients. We screened several compound libraries against P. vivax liver stages, including 1566 compounds against mature hypnozoites, resulting in one drug-like and several probe-like hits useful for investigating hypnozoite biology. Primaquine and tafenoquine, administered in combination with chloroquine, are currently the only FDA-approved antimalarials for radical cure, yet their activity against mature P. vivax hypnozoites has not yet been demonstrated in vitro. By developing an extended assay, we show both drugs are individually hypnozonticidal and made more potent when partnered with chloroquine, similar to clinically-relevant combinations. Post-hoc analyses of screening data revealed excellent performance of ionophore controls and the high quality of single point assays, demonstrating a platform able to support the screening of greater compound numbers. A comparison of P. vivax liver stage activity data with that of the P. cynomolgi blood, P. falciparum blood, and P. berghei liver stages reveals little activity overlap, indicating that the delivery of new radical curative agents killing P. vivax hypnozoites requires an independent, focused drug development test cascade.

Control of Graves’ hyperthyroidism with very long-term methimazole treatment: a clinical trial

Background Long-term antithyroid drug therapy has become one of the options for treatment of Graves’ hyperthyroidism. The aim of this study was to compare thyroid status in those who discontinued methimazole (MMI) treatment after 12.8 years with those who continued MMI as long as 24 years. Methods Fifty nine patients with Graves’ disease on long-term MMI for 14.2 ± 2.9 years were recruited; 32 patients (54%) decided to discontinue MMI and 27 (46%) preferred additional years of MMI treatment. All patients were followed for a mean of 6 additional years. Results Of 27 patients who continued MMI up to 24 years, suppressed serum thyrotropin (TSH) was not observed in any patient after the seventh year of treatment. Serum free thyroxine, triiodothyronine, TSH and TSH receptor antibody concentrations remained normal up to the length of the study. Mean daily dose of MMI to maintain TSH in the reference range decreased gradually and reached to 2.8 ± 1.7 mg by 24 years of MMI treatment. No adverse reaction related to MMI occured during additional years of therapy. In 32 patients who discontinued MMI, hyperthyroidism relapsed in 6 patients (19%), one left follow-up and 25 (78%) remained euthyroid during the study. Conclusions Long-term low dose MMI treatment may be a lifelong effective and safe therapeutic modality in patients with Graves’ hyperthyroidism for prevention of relapse, if studies from other centers confirm findings of this research. Trial registration IRCT201009224794N1, 2010-10-25. Retrospectively registered. https://www.irct.ir/trial/5143.

Control of Graves’ hyperthyroidism with very long-term methimazole treatment: A clinical trial

Background: Long-term antithyroid drugs therapy has become one of the options for treatment of Graves’ hyperthyroidism. The aim of this study was to compare thyroid status in those who discontinued methimazole (MMI) treatment after 12.8 years with those who continued MMI as long as 24 years.Methods: Fifty nine patients with Graves’ disease on long-term MMI for 14.2±2.9 years were recruited; 32 patients (54%) decided to discontinue MMI and 27 (46%) preferred additional years of MMI treatment. All patients were followed for a mean of 6 additional years.Results: Of 27 patients who continued MMI up to 24 years, suppressed serum thyrotropin (TSH) was not observed in any patient after the seventh year of treatment. Serum free thyroxine, triiodothyronine, TSH and TSH receptor antibody concentrations remained normal up to the length of the study. Mean daily dose of MMI to maintain TSH in the reference range decreased gradually and reached to 2.8±1.7 mg by 24 years of MMI treatment. No adverse reaction related to MMI occured during additional years of therapy. In 32 patients who discontinued MMI, hyperthyroidism relapsed in 6 patients (19%), one left follow-up and 25 (78%) remained euthyroid during the study.Conclusions: Long-term low dose MMI treatment may be a lifelong effective and safe therapeutic modality in patients with Graves’ hyperthyroidism for prevention of relapse, if studies from other centers confirm findings of this research.Trial registration: IRCT201009224794N1, 2010-10-25. Retrospectively registered.www. IRCT.IR/Trial/5143.