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To compare differences in clozapine doses and plasma levels between Bangladeshi and White British patients. Following ethical approval we identified all current Bangladeshi and White British patients on clozapine maintenance in an east London clinic. We carried out univariate and multivariate regression analyses to examine associations between clozapine doses and ethnicity, age, gender, smoking status and weight. We also compared plasma clozapine levels of the two groups.
On univariate analysis White British patients had on average 85 mg higher doses than Bangladeshi patients (P = 0.004). Older age, male gender and smoking were also associated with higher dose. On multivariate analysis only age and smoking status remained significant. A greater proportion of Bangladeshi patients had high plasma clozapine levels compared with White British (30.76% v. 20.75%), although the difference was not statistically significant.
Our findings point to the need for the broadening of data collection on ethnic differences in clozapine prescribing within big data-sets such as Prescribing Observatory for Mental Health (POM-UK). Ethnopharmacological variations can inform more person-centred guidance on prescribing.
Kidneys are sensitive to damage by drugs, with up to 20% of episodes of drug-induced acute renal failure. New prescribers must be able to identify these patients and eliminate these risks when possible; avoid potentially nephrotoxic drugs; and adjust drug doses in patients, where necessary, in those with pre-existing renal impairment to avoid drug accumulation and toxicity. This chapter identifies high-risk drug classes to avoid in renal failure, top tips to avoid drug toxicity, how to treat patients in chronic renal failure and provides a quick reference guide for drug dose reduction in those with renal impairment.
Successful anticoagulation is a fine balance between clotting and bleeding, which can easily go wrong. The good news is that basic principles can help manage this scenario effectively. The author provides background information on low molecular weight heparins, their use in the treatment and prevention of deep vein thrombosis and pulmonary embolism, its monitoring and reversal, and dose adjustment for body weight and renal function.
Choice of antibiotic should be dictated by spectrum of activity, tissue penetration, potency and cost, and local patterns of infection. While advising prescribers to check with their local microbiologist or use their smartphone formulary app, the author describes the most common infectious disease presentations, and the first- and second-line antibiotic therapy based on national guidelines.
When it comes to prescribing, children are not ‘little adults’, and indeed, the dose and frequencies of medicines can change throughout childhood. While highlighting some basic principles for prescribing in children, this chapter explores why some drugs are unlicensed in paediatric patients, provides top tips for avoiding dosing errors and discusses how to improve compliance with drug therapy in younger patients. Readers are also advised on how best to report adverse drug reactions.
Comparison of the integral dose (ID) delivered to organs at risk (OAR), non-target body and target body by using different techniques of craniospinal irradiation (CSI).
Materials and methods:
Ten CSI patients (medulloblastoma) already planned and treated either with linear accelerator three-dimensional conformal radiation therapy (Linac-3DCRT) technique or with linear accelerator RapidArc (Linac-RapidArc) technique by Novalis-Tx Linac machine have been analysed. Retrospectively, these patients are again planned on Radixact-X9 Linac with Helical, Direct-3DCRT and Direct-intensity-modulated radiation therapy (Direct-IMRT) techniques. The dose prescription to planning target volume brain (PTV-Brain) and PTV-Spine is 36 Gy in 20 fractions and is kept the same for all techniques. The target body, non-target body, OARs and total body dose are compared.
ID is lowest in the RapidArc plan for every patient in comparison to Helical and Direct-IMRT. The ID for Body-PTV was found slightly higher in the RapidArc plan in comparison to 3DCRT plans. But there is better normal tissue sparing for most of the OARs in RapidArc plans if it compares with 3DCRT plans.
RapidArc is a better alternative for the treatment of CSI. It provides better target coverage and better OARs sparing from any other treatment techniques.
Nasopharyngeal carcinoma (NPC) patients may have anatomical variations during their radiotherapy treatment course. In this study, we determine the daily accumulated dose by the deformable image registration (DIR) process for comparing with the planned dose and explore the number of fractions which the daily accumulated dose significantly changed from the planned dose.
The validation of the DIR process in MIM software has been tested. One hundred and sixty-five daily megavoltage computed tomography (MVCT) images of NPC patients who were treated by helical tomotherapy were exported to MIM software to determine the daily accumulated dose and then compared with the planned dose.
The MIM software illustrated the acceptable validation for clinical application. The accumulated dose (D50%) of the planning target volume (PTV70) showed a decrease from the planned dose with an average of 0.5 ± 0.27% at the end of the treatment and was significantly different from the planned dose after the second fraction of the treatment (p-value = 0.008). In contrast, the accumulated dose of organ at risk (OAR) tended to increase from the planned dose and was significantly different after the fifth fraction (left parotid), the twelfth fraction (right parotid) and the second fraction (spinal cord).
The inter-fractional anatomic changes cause the actual dose to be different from the planned dose. The dose differences and the number of fractions were varied in each target and OAR. The dose accumulation explored the necessary information for the radiation oncologist to consider adaptive treatment strategies to increase the efficiency of treatment.
We broaden the applicability of sparse coding, a machine learning method, to low-dose electron holography by using simulated holograms for learning and validation processes. The holograms, with shot noise, are prepared to generate a model, or a dictionary, that includes basic features representing interference fringes. The dictionary is applied to sparse representations of other simulated holograms with various signal-to-noise ratios (SNRs). Results demonstrate that this approach successfully removes noise for holograms with an extremely small SNR of 0.10, and that the denoised holograms provide the accurate phase distribution. Furthermore, this study demonstrates that the dictionary learned from the simulated holograms can be applied to denoising of experimental holograms of a p–n junction specimen recorded with different exposure times. The results indicate that the simulation-trained sparse coding is suitable for use over a wide range of imaging conditions, in particular for observing electron beam-sensitive materials.
The relationship between the subtypes of psychotic experiences (PEs) and common mental health symptoms remains unclear. The current study aims to establish the 12-month prevalence of PEs in a representative sample of community-dwelling Chinese population in Hong Kong and explore the relationship of types of PEs and common mental health symptoms.
This is a population-based two-phase household survey of Chinese population in Hong Kong aged 16–75 (N = 5719) conducted between 2010 and 2013 and a 2-year follow-up study of PEs positive subjects (N = 152). PEs were measured with Psychosis Screening Questionnaire (PSQ) and subjects who endorsed any item on the PSQ without a clinical diagnosis of psychotic disorder were considered as PE-positive. Types of PEs were characterized using a number of PEs (single v. multiple) and latent class analysis. All PE-positive subjects were assessed with common mental health symptoms and suicidal ideations at baseline and 2-year follow-up. PE status was also assessed at 2-year follow-up.
The 12-month prevalence of PEs in Hong Kong was 2.7% with 21.1% had multiple PEs. Three latent classes of PEs were identified: hallucination, paranoia and mixed. Multiple PEs and hallucination latent class of PEs were associated with higher levels of common mental health symptoms. PE persistent rate at 2-year follow-up was 15.1%. Multiple PEs was associated with poorer mental health at 2-year follow-up.
Results highlighted the transient and heterogeneous nature of PEs, and that multiple PEs and hallucination subtype of PEs may be specific indices of poorer common mental health.
Current evidences on the association between hyperuricaemia and retinol intake remain inconsistent. Furthermore, no known studies have investigated the relationship between hyperuricaemia and retinol intake from animal food and plant food separately. This study aimed to assess the relationship between different sources of retinol intake and risk of hyperuricaemia among US adults.
Univariate and multivariate weighted logistic regression models and restricted cubic spline models were used to assess the associations of total, animal-derived and plant-derived retinol intakes with the risk of hyperuricaemia. Dietary retinol was measured through two 24-h dietary recall interviews. Hyperuricaemia was defined as serum uric acid level ≥7·0 and ≥6·0 mg/dl in men and women, respectively.
Data from the National Health and Nutrition Examination Survey 2009–2014 were used in this cross-sectional study.
Overall, 12 869 participants aged ≥20 years were included.
Compared with the lowest quintile, the multivariable OR of hyperuricaemia for the highest quintile intake of total, animal-derived and plant-derived retinol were 0·71 (95 % CI 0·52, 0·96), 0·76 (95 % CI 0·59, 0·96) and 0·92 (95 % CI 0·72, 1·17), respectively. The inverse association between dietary intake of total retinol and the risk of hyperuricaemia was observed in men. Dose–response analyses revealed a novel linear trend between the risk of hyperuricaemia and total, animal-derived retinol intake separately.
Our findings indicated that intakes of total and animal-derived retinol were negatively associated with hyperuricaemia in US adults.
To investigate the effect of different energies on dose distribution in volumetric-modulated arc therapy (VMAT) plans for head and neck cancer.
Materials and methods:
Data from nine patients undergoing VMAT plans using 6 MV, 10 MV and dual-energy X-ray beams with the Pinnacle 3 V 9.10 treatment planning system (Philips Medical System, Fitchburg, WI, USA) were analysed for quality using the conformity index (CI) and homogeneity index (HI) for planning target volume (PTV), and for mean and maximum dose to the organs at risk (OARs): parotid glands, brainstem, spinal cord and optic nerves.
There were no clear differences in the HIs of the PTV dose among the different plans. The CIs for 10 MV and dual-energy VMAT plans were superior to that of the 6 MV VMAT plan (0·8 ± 0·3, 0·8 ± 0·3, and 0·7 ± 0·2, respectively; p = 0·001). There were no significant differences in mean/maximum dose to the OARs among the three VMAT plans.
Compared with the 6 MV VMAT plan, the dual-energy VMAT plan slightly increased the coverage of the PTV with the prescribed dose but did not decrease dose to the OARs.
Bolus material is frequently used on patient’s skin during radiation therapy to reduce or remove build-up effect for high-energy beams. However, the air-gaps formed between the bolus and the skin’s irregular surface reduce the accuracy of treatment planning. To achieve a good treatment outcome using bolus, experimental investigations are required to choose its thickness and to quantify the air-gap effect.
Material and methods:
Measurements for a 6 MV photon beam with a fixed source surface distance were carried out using the 31021 Semiflex 3D chamber into the water phantom. Firstly, the depth of maximum dose (R100) and the dose value at surface (Ds) were evaluated as a function of bolus thickness for some square fields. Secondly, to test the effect of the air-gaps ranged from 5 to 30 mm with a step of 5 mm between the bolus and the phantom surface, a water-equivalent RW3 (Goettingen White Water) slab form of 10 mm thickness was considered as a bolus.
We observed that the linear behaviour of R100 in terms of the bolus thickness makes the choice of this parameter more convenient depending on field size. In addition, increasing the air-gaps widens the penumbra and created electrons that have a greater probability to quit the radiation field borders before reaching the surface. The dose spread of the off-field area could have a significant influence on the patient treatment.
Based on dose distribution comparisons between the measurements with and without air-gaps for the field size of 100 mm × 100 mm, it has been demonstrated that a maximum air-gap value lower than 5 mm would be desirable for an efficient use of the bolus technique.
Use of antimicrobials for food-producing animals is a major public concern due to the risk of antimicrobial resistance. Although dairy production has a relatively low usage of antimicrobials, the potential for further reduction should be explored. The objective of the study was to estimate the current differences in antimicrobial use in Danish organic and conventional dairy herds and to describe the differences between them. Based on data from three different sources, 2604 herds (306 organic and 2298 conventional) were identified for the study. These herds had been either organic or conventional for the entire period from 2015 to 2018. Antimicrobial use was calculated as the treatment incidence in Animal Daily Doses (ADDs)/100 animals/day for three age groups: adult cattle, young stock and calves. For adult cattle, the ratio of median treatment incidence between conventional and organic production ranged from 2.8 : 1 to 3.4 : 1, depending on the specific year. For cows, 25% of the organic herds had a higher treatment incidence than the 25% of conventional herds with the lowest treatment incidence. Antimicrobial use for young stock was low and at a similar level in both the organic and conventional production systems. For calves, the median treatment incidence was 1.2 times higher in conventional herds and 1.6 times higher for the 75th percentile. Analyses of treatment incidence in adult cattle showed an overall decrease from 2015 to 2018 in both organic and conventional herds. The decrease was greater for the conventional herds (0.12 ADD/100 animals/day) compared to the organic herds (0.04 ADD/100 animals/day) over the 4-year period. In addition, herd size was an important risk factor for treatment incidence in conventional herds, increasing by 0.07 ADD/100 animals/day per 100 cows, whereas herd size had a minor influence on the treatment incidence in organic herds. The results of this study demonstrate the large variation in antimicrobial use within both organic and conventional herds, suggesting that further reduction is possible. Furthermore, herd size appears to be a risk factor in conventional herds but not in organic herds – an aspect that should be studied in more detail.
Introduction: Inhaled low dose methoxyflurane (MEOF) was recently approved in Canada for the short-term relief of moderate to severe acute pain associated with trauma or interventional medical procedures in conscious adult patients. ADVANCE-ED is an ongoing phase IV, prospective open label study undertaken to generate real-world evidence to complement the global clinical development program through evaluation of the effectiveness of low dose MEOF in Canadian emergency departments (EDs). Methods: This multi-centre study is enrolling adult (≥18 yrs) patients with moderate to severe acute pain (NRS0-10 ≥ 4) associated with minor trauma. To address limitations from the pivotal study, this study allows patients who were excluded in the pivotal trials: namely, those with severe (≥7) pain, and those using OTC or stably dosed analgesics for other conditions, including chronic pain. Eligible patients receive a single treatment of up to 2 x 3 mL MEOF (2nd 3 mL to be provided only upon request), self-administered by the patient under medical supervision. Rescue medication is permitted at any time, if required. Results: Here we describe the patient demographics and treatment satisfaction (Global Medication Performance, GMP) at 50% enrolment (n = 49). Mean (SD) patient age is 48.0 (17.1) yrs and 55.1% are female. Mean pain (SD) reported at enrolment is 8.3 (1.5), with 73.4% of patients with NRS0-10 ≥ 8. Injuries are overwhelmingly limb trauma (87.8%). The most common type is sprain/strain (40.8%), followed by fracture (32.7%). At 5 minutes post-start of administration (STA) of MEOF, 80.4% of patients reported pain relief; this increased to 91.3% at 15 minutes, and 100% of patients reported pain relief by 30 minutes post-STA. GMP was assessed as “good”, “very good” or “excellent” by ≥80% of patients both 20 minutes post-start of administration (STA) of MEOF (83.3%) and at discharge (85.8%). When asked to what extent their expectation of pain relief had been met, 32.7% responded good, 26.5% responded “very good” and 22.4% responded “excellent”. Three quarters of enrolled patients (75.5%) did not require rescue medication. The most common (≥5%) treatment-related adverse events were dizziness (n = 14, 28.6%) and euphoric mood (n = 4, 8.2%). No serious adverse events have been reported. Conclusion: Based on 50% of the patients enrolled in this prospective, open label study, responses to inhaled low-dose MEOF are within expectation for both effectiveness and tolerability.
To measure and compare the skin doses received by treated left breast and contralateral breast (CB) during whole breast radiotherapy using five treatment techniques in an indigenously prepared wax breast phantom.
Materials and methods:
Computed tomography (CT) images of the breast phantom were used for treatment planning and comparison of skin dose calculated from treatment planning system (TPS) with measured dose. Planning target volume (PTV) and the CB were drawn arbitrarily on the CT images acquired for the breast phantom with 10 numbers of calibrated optically stimulated luminescent dosimeters (OSLDs) fixed on the surface of both breasts. The TPS calculated surface doses of PTV breast and CB for five treatment planning techniques, viz., conventional wedge (CW), irregular surface compensator-based (ISC), field-in-field (FiF), intensity-modulated radiotherapy (IMRT) and rapid arc (RA) techniques were obtained for comparison. The plans were executed in Clinac iX Linear Accelerator with the OSLDs fixed at the same locations on the phantom as in simulation. The TPS calculated mean dose at the surface of the treated left breast and CB was noted for the 10 OSLDs from dose-volume histogram (DVH) and compared with the measured dose. Also, the mean chamber dose at the centre of the left breast was noted from the DVH for comparing with ion chamber measured dose.
With reference to the results, it is seen that the dose to the CB is lowest in ISC technique and FiF technique and greatest in IMRT technique. The CW technique also delivered a dose comparable to IMRT to the CB of the phantom. The dose to the surface of PTV breast was highest and comparable in CW plans and FiF plans (68% and 67%) and lowest in IMRT and RA plans (50% each).
Analysis of the results shows that the FiF and ISC techniques are preferred while planning breast radiotherapy due to the reduced dose to the CB.
The study examined psychological development in 250 children at the age of 6–7 and 10–12 years who had been exposed in the prenatal period at the time of the Chernobyl accident in 1986. These children were compared to a control group of 250 children of the same age from non- and slightly contaminated areas of Belarus. The examination included psychiatric examination and intellectual assessment as well as the estimation of thyroid exposure in utero. The mean value of thyroid doses from 131I 0.39 Gy was estimated for the prenatal exposed children. The children of the exposed group had a lower mean full-scale IQ compared to the control group (89.6 ± 10.2 vs 92.1 ± 10.5 at the age of 6–7 years, P = 0.007; and 94.3 ± 10.4 vs 95.8 ± 10.9 at the age of 10–12 years, P = 0.117). Average IQ for the subgroup of highly exposed children (thyroid doses more than 1 Gy) was lower in comparison with average IQ for the whole exposed group (85.7 ± 6.4 vs 89.6 ± 10.2 at the age of 6–7 years, P = 0.014; 89.1 ± 7.1 vs 94.3 ± 10.4 at age 10–12 years, P = 0.003). No statistically significant distinctions in average IQ were found between the different subgroups of children in relation to the gestational age at the time of the Chernobyl accident. We notice a positive moderate correlation between IQ of children and the educational level of their parents (in exposed group – mothers: r = 0.50, P < 0.01 and fathers: r = 0.52, P < 0.01; in control group – mothers: r = 0.41, P < 0.05 and fathers: r = 0.42, P < 0.05). There was a moderate correlation between high personal anxiety in parents and emotional disorders in children (for mothers r = 0.38, P < 0.05; for fathers r = 0.43, P < 0.01). The relative risk of mental and behavioural disorders has been estimated for emotional disorders OR = 2.67, P < 0.001. The frequency of the formation of mental retardation, hyperkinetic disorders and other mental and behavioural disorders in children from both groups was approximately the same. We conclude that in the genesis of borderline intellectual functioning and emotional disorders in the exposed group of children a significant role was probably played by unfavourable social-psychological and sociocultural factors such as a low educational level of the parents, the break of microsocial contacts and difficulties adapting, which appeared following the evacuation and relocation from the contaminated areas.
A meta-analysis of the published literature was performed in order to quantify the efficacy of low-dose neuroleptic therapy in reducing extrapyramidal side effects in schizophrenic patients. A low-dose regimen between 50–100 mg equivalents of chlorpromazine, in comparison to a standard-dose regimen between 200–500 mg reduced extrapyramidal side effects by a 0.30 (±0.12) standard deviation, which is only a limited effect.
We examined the relation between dosage and efficacy, and the predictors of response to milnacipran. There was no difference between 50 and 100 mg dose. However, the 100 mg dose had a faster onset of action than the 50 mg dose. An age and an episode have been predictors of milnacipran.
In our opinion the best guide to prescribing antipsychotics is the clinician’s experience with his patients and in particular the patient being treated. If treatment works, stick with it. We feel it is also important for the clinician to consider the evidence from well-controlled double-blind random-assignment studies because in “evidence-based medicine,” biases both known and unknown are controlled by blinding and randomization. The purpose of this paper is to summarize and discuss the evidence on efficacy. Choice of antipsychotic, in our opinion, is probably the most important decision that the clinician makes for the psychotic patient. This involves the choice of drug, its dose, balancing efficacy, side-effects and cost.
We assessed the relative efficacy and effectiveness of low-versus standard-dose neuroleptic therapy in reducing relapse rate in schizophrenic patients. Six long-term randomized controlled trials were retrieved through a MEDLINE search. A dose regimen between 50 and 100 mg equivalent of chlorpromazine, compared to a conventional one between 200 and 500 mg, was found to increase the likelihood of relapse in chronic schizophrenic patients. Differences, however, were statistically significant at 12 but not at 24 months of treatment.