Factors influencing presentation delay among cancer patients: a cross-sectional study in Malaysia.

BACKGROUND: Cancer represents a significant global public health challenge, with escalating incidence rates straining healthcare systems. Malaysia, like many nations, has witnessed a rise in cancer cases, particularly among the younger population. This study aligns with Malaysia's National Strategic Plan for Cancer Control Programme 2021-2025, emphasizing primary prevention and early detection to address cancer's impact. Therefore, we aim to describe the timeliness of cancer care for symptom presentation, socio-demographic, patient, as well as organizational-related factors among patients in Malaysia diagnosed with breast, colorectal, nasopharyngeal, and cervical cancer. METHODS: This cross-sectional study enrolled adult cancer patients diagnosed with breast, cervical, colorectal, or nasopharyngeal cancer from 2015 to 2020 in seven public hospitals/oncology centres across Malaysia. Data were collected through patient-administered surveys and medical records. Presentation delay, defined as the duration between symptom onset and the patient's first visit to a healthcare professional exceeding 30 days, was the primary outcome. Statistical analysis included descriptive statistics and chi-square tests. RESULTS: The study included 476 cancer patients, with breast cancer (41.6%), colorectal cancer (26.9%), nasopharyngeal cancer (22.1%), and cervical cancer (9.5%). Over half (54.2%) experienced presentation delays with a median interval of 60 days. Higher proportions of presentation delay were observed among nasopharyngeal cancer patients, employed patients with lower socioeconomic statuses, and those without family history of cancer. Most patients self-discovered their first cancer symptoms (80%), while only one-third took immediate action for medical check-ups. Emotional and organizational factors, such as long waiting times during doctor's visits (47%), were potential barriers to seeking cancer care. CONCLUSION: This study highlights the significant problem of presentation delay among cancer patients in Malaysia. The delay is influenced by various factors encompassing sociodemographic characteristics, health-seeking behaviours, and healthcare system-related issues. A comprehensive approach addressing both individual barriers and institutional obstacles is imperative to mitigate this presentation delay and improve cancer outcomes.

A Novel Respiratory Rate Estimation Algorithm from Photoplethysmogram Using Deep Learning Model.

Respiratory rate (RR) is a critical vital sign that can provide valuable insights into various medical conditions, including pneumonia. Unfortunately, manual RR counting is often unreliable and discontinuous. Current RR estimation algorithms either lack the necessary accuracy or demand extensive window sizes. In response to these challenges, this study introduces a novel method for continuously estimating RR from photoplethysmogram (PPG) with a reduced window size and lower processing requirements. To evaluate and compare classical and deep learning algorithms, this study leverages the BIDMC and CapnoBase datasets, employing the Respiratory Rate Estimation (RRest) toolbox. The optimal classical techniques combination on the BIDMC datasets achieves a mean absolute error (MAE) of 1.9 breaths/min. Additionally, the developed neural network model utilises convolutional and long short-term memory layers to estimate RR effectively. The best-performing model, with a 50% train-test split and a window size of 7 s, achieves an MAE of 2 breaths/min. Furthermore, compared to other deep learning algorithms with window sizes of 16, 32, and 64 s, this study's model demonstrates superior performance with a smaller window size. The study suggests that further research into more precise signal processing techniques may enhance RR estimation from PPG signals.

Assessing the efficacy of machine learning algorithms for syncope classification: A systematic review.

Syncope is a transient loss of consciousness with rapid onset. The aims of the study were to systematically evaluate available machine learning (ML) algorithm for supporting syncope diagnosis to determine their performance compared to existing point scoring protocols. We systematically searched IEEE Xplore, Web of Science, and Elsevier for English articles (Jan 2011 - Sep 2021) on individuals aged five and above, employing ML algorithms in syncope detection with Head-up titl table test (HUTT)-monitored hemodynamic parameters and reported metrics. Extracted data encompassed subject count, age range, syncope protocols, ML type, hemodynamic parameters, and performance metrics. Of the 6301 studies initially identified, 10 studies, involving 1205 participants aged 5 to 82 years, met the inclusion criteria, and formed the basis for it. Selected studies must use ML algorithms in syncope detection with hemodynamic parameters recorded throughout HUTT. The overall ML algorithm performance achieved a sensitivity of 88.8% (95% CI: 79.4-96.1%), specificity of 81.5% (95% CI: 69.8-92.8%) and accuracy of 85.8% (95% CI: 78.6-92.8%). Machine learning improves syncope diagnosis compared to traditional scoring, requiring fewer parameters. Future enhancements with larger databases are anticipated. Integrating ML can curb needless admissions, refine diagnostics, and enhance the quality of life for syncope patients.

One-Step Fabrication of Paper-Based Inkjet-Printed Graphene for Breath Monitor Sensors.

Irregularities in breathing patterns can be detected using breath monitor sensors, and this help clinicians to predict health disorders ranging from sleep disorders to heart failures. Variations in humidity during the inhalation and exhalation of breath have been utilized as a marker to detect breath patterns, and graphene-based devices are the favored sensing media for relative humidity (RH). In general, most graphene-based RH sensors have been used to explore resistance change as a measurement parameter to calibrate against the RH value, and they are prone to noise interference. Here, we fabricated RH sensors using graphene ink as a sensing medium and printed them in the shape of interdigital electrodes on glossy paper using an office inkjet printer. Further, we investigated the capacitance change in the sensor for the RH changes in the range of 10-70%. It exhibited excellent sensitivity with 0.03 pF/% RH, good stability, and high intraday and interday repeatability, with relative standard deviations of 1.2% and 2.2%, respectively. Finally, the sensor was embedded into a face mask and interfaced with a microcontroller, and capacitance change was measured under three different breathing situations: normal breathing, deep breathing, and coughing. The result show that the dominant frequency for normal breath is 0.22 Hz, for deep breath, it is 0.11 Hz, and there was no significant dominant cough frequency due to persistent coughing and inconsistent patterns. Moreover, the sensor exhibited a short response and recovery time (<5 s) during inhalation and exhalation. Thus, the proposed paper-based RH sensor is promising wearable and disposable healthcare technology for clinical and home care health applications.

A Comparison of Haemodynamic Responses between Head-Up Tilt and Lower Body Negative Pressure.

Orthostatic intolerance (OI), a disorder of the autonomic nervous system, it is the development of symptoms when standing upright which are relieved when reclining. Head-up tilt (HUT) table test is a common test for assessing orthostatic tolerance. However, HUT is limited with low sensitivity and specificity. Another approach to stimulate the changing direction and value of the gravity field vector is the lower body negative pressure (LBNP) chamber. The aims of the study is to evaluate the physiological responses of healthy subjects on HUT and LBNP, and examine the relations of two tests. A total of 19 subjects were recruited. A validated wearable device, Sotera Visi Mobile was use to collect physiological signals simultaneously throughout the experiment procedures. Each subject went through a baseline supine rest, 70o of HUT test, another round of baseline supine rest, followed by activation of LBNP test. Three level of suction were applied, i.e. -30 mmHg, -40 mmHg, and -50 mmHg. In this pilot study, healthy subjects showed significantly increased of heart rate, and decreased of systolic blood pressure and diastolic blood pressure, in both HUT and LBNP tests. Although both tests are capable of stimulating a decreased blood volume in the central circulation, but the physiological responses behaved differently and shown only very week correlation. This suggesting that a combination of LBNP test with HUT test might work the best in orthostatic intolerance assessment.

Appointment structure in Malaysian healthcare system during the COVID-19 pandemic: The public perspective.

INTRODUCTION: Evidence shows physical distancing of one metre or more is important to reduce person-to-person SARS-CoV-2 transmission. This puts the Malaysian public healthcare system to a test when overcrowding has always been an issue. A new clinical appointment structure was proposed in the Malaysian public healthcare system amidst the pandemic to reduce the transmission risk. We aim to explore the general public's view on the proposed clinic appointment structure. METHODS: A cross-sectional anonymous web-based survey was conducted between 10th September 2020 and 30th November 2020. The survey was open to Malaysian aged 18 years and older via various social media platforms. The questionnaire consists of sociodemographic, experience of utilising healthcare facilities, and views on clinic appointment structure. RESULTS: A total of 1,144 complete responses were received. The mean age was 41.4 ± 12.4 years and more than half of the respondents had a preference for public healthcare. Among them, 77.1% reported to have a clinical appointment scheduled in the past. Less than a quarter experienced off-office hour appointments, mostly given by private healthcare. 70.2% answered they would arrive earlier if they were given a specific appointment slot at a public healthcare facility, as parking availability was the utmost concern. Majority hold positive views for after office hour clinical appointments, with 68.9% and 63.2% agreed for weekend and weekday evening appointment, respectively. The top reason of agreement was working commitment during office hours, while family commitment and personal resting time were the main reasons for disagreeing with off-office hour appointments. CONCLUSION: We found that majority of our respondents chose to come early instead of arriving on time which disrupts the staggered appointment system and causes over crowdedness. Our findings also show that the majority of our respondents accept off-office hour appointments. This positive response suggests that off-office hour appointments may have a high uptake amongst the public and thus be a possible solution to distribute the patient load. Therefore, this information may help policy makers to initiate future plans to resolve congestions within public health care facilities which in turn eases physical distancing during the pandemic.

Emerging Biosensors to Detect Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): A Review.

Coronavirus disease (COVID-19) is a global health crisis caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) is the gold standard test for diagnosing COVID-19. Although it is highly accurate, this lab test requires highly-trained personnel and the turn-around time is long. Rapid and inexpensive immuno-diagnostic tests (antigen or antibody test) are available, but these point of care (POC) tests are not as accurate as the RT-PCR test. Biosensors are promising alternatives to these rapid POC tests. Here we review three types of recently developed biosensors for SARS-CoV-2 detection: surface plasmon resonance (SPR)-based, electrochemical and field-effect transistor (FET)-based biosensors. We explain the sensing principles and discuss the advantages and limitations of these sensors. The accuracies of these sensors need to be improved before they could be translated into POC devices for commercial use. We suggest potential biorecognition elements with highly selective target-analyte binding that could be explored to increase the true negative detection rate. To increase the true positive detection rate, we suggest two-dimensional materials and nanomaterials that could be used to modify the sensor surface to increase the sensitivity of the sensor.

Withdrawal or continuation of cholinesterase inhibitors or memantine or both, in people with dementia.

BACKGROUND: Dementia is a progressive syndrome characterised by deterioration in memory, thinking and behaviour, and by impaired ability to perform daily activities. Two classes of drug - cholinesterase inhibitors (donepezil, galantamine and rivastigmine) and memantine - are widely licensed for dementia due to Alzheimer's disease, and rivastigmine is also licensed for Parkinson's disease dementia. These drugs are prescribed to alleviate symptoms and delay disease progression in these and sometimes in other forms of dementia. There are uncertainties about the benefits and adverse effects of these drugs in the long term and in severe dementia, about effects of withdrawal, and about the most appropriate time to discontinue treatment. OBJECTIVES: To evaluate the effects of withdrawal or continuation of cholinesterase inhibitors or memantine, or both, in people with dementia on: cognitive, neuropsychiatric and functional outcomes, rates of institutionalisation, adverse events, dropout from trials, mortality, quality of life and carer-related outcomes. SEARCH METHODS: We searched the Cochrane Dementia and Cognitive Improvement Group's Specialised Register up to 17 October 2020 using terms appropriate for the retrieval of studies of cholinesterase inhibitors or memantine. The Specialised Register contains records of clinical trials identified from monthly searches of a number of major healthcare databases, numerous trial registries and grey literature sources. SELECTION CRITERIA: We included all randomised, controlled clinical trials (RCTs) which compared withdrawal of cholinesterase inhibitors or memantine, or both, with continuation of the same drug or drugs. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed citations and full-text articles for inclusion, extracted data from included trials and assessed risk of bias using the Cochrane risk of bias tool. Where trials were sufficiently similar, we pooled data for outcomes in the short term (up to 2 months after randomisation), medium term (3-11 months) and long term (12 months or more). We assessed the overall certainty of the evidence for each outcome using GRADE methods. MAIN RESULTS: We included six trials investigating cholinesterase inhibitor withdrawal, and one trial investigating withdrawal of either donepezil or memantine. No trials assessed withdrawal of memantine only. Drugs were withdrawn abruptly in five trials and stepwise in two trials. All participants had dementia due to Alzheimer's disease, with severities ranging from mild to very severe, and were taking cholinesterase inhibitors without known adverse effects at baseline. The included trials randomised 759 participants to treatment groups relevant to this review. Study duration ranged from 6 weeks to 12 months. There were too few included studies to allow planned subgroup analyses. We considered some studies to be at unclear or high risk of selection, performance, detection, attrition or reporting bias. Compared to continuing cholinesterase inhibitors, discontinuing treatment may be associated with worse cognitive function in the short term (standardised mean difference (SMD) -0.42, 95% confidence interval (CI) -0.64 to -0.21; 4 studies; low certainty), but the effect in the medium term is very uncertain (SMD -0.40, 95% CI -0.87 to 0.07; 3 studies; very low certainty). In a sensitivity analysis omitting data from a study which only included participants who had shown a relatively poor prior response to donepezil, inconsistency was reduced and we found that cognitive function may be worse in the discontinuation group in the medium term (SMD -0.62; 95% CI -0.94 to -0.31). Data from one longer-term study suggest that discontinuing a cholinesterase inhibitor is probably associated with worse cognitive function at 12 months (mean difference (MD) -2.09 Standardised Mini-Mental State Examination (SMMSE) points, 95% CI -3.43 to -0.75; moderate certainty). Discontinuation may make little or no difference to functional status in the short term (SMD -0.25, 95% CI -0.54 to 0.04; 2 studies; low certainty), and its effect in the medium term is uncertain (SMD -0.38, 95% CI -0.74 to -0.01; 2 studies; very low certainty). After 12 months, discontinuing a cholinesterase inhibitor probably results in greater functional impairment than continuing treatment (MD -3.38 Bristol Activities of Daily Living Scale (BADLS) points, 95% CI -6.67 to -0.10; one study; moderate certainty). Discontinuation may be associated with a worsening of neuropsychiatric symptoms over the short term and medium term, although we cannot exclude a minimal effect (SMD - 0.48, 95% CI -0.82 to -0.13; 2 studies; low certainty; and SMD -0.27, 95% CI -0.47 to -0.08; 3 studies; low certainty, respectively). Data from one study suggest that discontinuing a cholinesterase inhibitor may result in little to no change in neuropsychiatric status at 12 months (MD -0.87 Neuropsychiatric Inventory (NPI) points; 95% CI -8.42 to 6.68; moderate certainty). We found no clear evidence of an effect of discontinuation on dropout due to lack of medication efficacy or deterioration in overall medical condition (odds ratio (OR) 1.53, 95% CI 0.84 to 2.76; 4 studies; low certainty), on number of adverse events (OR 0.85, 95% CI 0.57 to 1.27; 4 studies; low certainty) or serious adverse events (OR 0.80, 95% CI 0.46 to 1.39; 4 studies; low certainty), and on mortality (OR 0.75, 95% CI 0.36 to 1.55; 5 studies; low certainty). Institutionalisation was reported in one trial, but it was not possible to extract data for the groups relevant to this review. AUTHORS' CONCLUSIONS: This review suggests that discontinuing cholinesterase inhibitors may result in worse cognitive, neuropsychiatric and functional status than continuing treatment, although this is supported by limited evidence, almost all of low or very low certainty. As all participants had dementia due to Alzheimer's disease, our findings are not transferable to other dementia types. We were unable to determine whether the effects of discontinuing cholinesterase inhibitors differed with baseline dementia severity. There is currently no evidence to guide decisions about discontinuing memantine. There is a need for further well-designed RCTs, across a range of dementia severities and settings. We are aware of two ongoing registered trials. In making decisions about discontinuing these drugs, clinicians should exercise caution, considering the evidence from existing trials along with other factors important to patients and their carers.

Using SERS-based microfluidic paper-based device (µPAD) for calibration-free quantitative measurement of AMI cardiac biomarkers.

Recently, surface enhanced Raman scattering (SERS) has attracted much attention in medical diagnosis applications owing to better detection sensitivity and lower limit of detection (LOD) than colorimetric detection. In this paper, a novel calibration-free SERS-based µPAD with multi-reaction zones for simultaneous quantitative detection of multiple cardiac biomarkers - GPBB, CK-MB and cTnT for early diagnosis and prognosis of acute myocardial infarction (AMI) are presented. Three distinct Raman probes were synthesised, subsequently conjugated with respective detecting antibodies and used as SERS nanotags for cardiac biomarker detection. Using a conventional calibration curve, quantitative simultaneous measurement of multiple cardiac biomarkers on SERS-based µPAD was performed based on the characteristic Raman spectral features of each reporter used in different nanotags. However, a calibration free point-of-care testing device is required for fast screening to rule-in and rule-out AMI patients. Partial least squares predictive models were developed and incorporated into the immunosensing system, to accurately quantify the three unknown cardiac biomarkers levels in serum based on the previously obtained Raman spectral data. This method allows absolute quantitative measurement when conventional calibration curve fails to provide accurate estimation of cardiac biomarkers, especially at low and high concentration ranges. Under an optimised condition, the LOD of our SERS-based µPAD was identified at 8, 10, and 1 pg mL-1, for GPBB, CK-MB and cTnT, respectively, which is well below the clinical cutoff values. Therefore, this proof-of-concept technique shows significant potential for highly sensitive quantitative detection of multiplex cardiac biomarkers in human serum to expedite medical decisions for enhanced patient care.

Effectiveness of a pharmacist-led quality improvement program to reduce medication errors during hospital discharge.

BACKGROUND: Patients requiring medications during discharge are at risk of discharge medication errors that potentially cause readmission due to medication-related events. OBJECTIVE: The objective of this study was to develop interventions to reduce percentage of patients with one or more medication errors during discharge. METHODS: A pharmacist-led quality improvement (QI) program over 6 months was conducted in medical wards at a tertiary public hospital. Percentage of patients discharge with one or more medication errors was reviewed in the pre-intervention and four main improvements were developed: increase the ratio of pharmacist to patient, prioritize discharge prescription order within office hours, complete discharge medication reconciliation by ward pharmacist, set up a Centralized Discharge Medication Pre-packing Unit. Percentage of patients with one or more medication errors in both pre- and post-intervention phase were monitored using process control chart. RESULTS: With the implementation of the QI program, the percentage of patients with one or more medication errors during discharge that were corrected by pharmacists significantly increased from 77.6% to 95.9% (p<0.001). Percentage of patients with one or more clinically significant error was similar in both pre and post-QI with an average of 24.8%. CONCLUSIONS: Increasing ratio of pharmacist to patient to complete discharge medication reconciliation during discharge significantly recorded a reduction in the percentage of patients with one or more medication errors.

Survival of patients with advanced and recurrent ovarian cancer treated using integrative medicine in Malaysia: A case series.

BACKGROUND: This case series describes the survival outcomes of patients who underwent integrative medicine (IM) protocol for ovarian cancer, a treatment protocol, that integrated a carefully selected set of complementary and alternative medicine (CAM) into the conventional treatment for ovarian cancers. MATERIALS AND METHODS: Retrospective review of patients' medical records was conducted at a private medical centre that delivered the IM protocol for patients with advanced and recurrent ovarian cancers. We explored and analysed the overall survival and disease progressions of those who received the IM treatment for at least 2 months. RESULTS: Forty patients with advanced ovarian cancers fulfilled the inclusion criteria for this case series. An overall of 75% of the cases achieved remission with initial IM treatment, 17.5% had a partial response and 7.5% showed progressive disease. The overall 5-year survival for all 40 cases is 53.1%. When explored further, the 5-year survival for cases who received CAM only is 75%, and cases who received combined limited chemotherapy with CAM had a 5-year survival of 55%. At study endpoint, 11 cases died due to ovarian cancer. CONCLUSION: These findings suggest that CAM may be a valuable addition to conventional therapy to treat and improve the survival of patients with ovarian cancers. A formal randomized control trial is required to evaluate the efficacy and long-term outcomes of using IM to treat advanced and recurrent ovarian cancers.

Feasibility of case-control and test-negative designs to evaluate dengue vaccine effectiveness in Malaysia.

BACKGROUND: The world's first dengue vaccine [Dengvaxia; Sanofi Pasteur] was licensed in 2015 and others are in development. Real-world evaluations of dengue vaccines will therefore soon be needed. We assessed feasibility of case control (CC) and test-negative (TN) design studies for dengue vaccine effectiveness by measuring associations between socio-demographic risk factors, and hospitalized dengue outcomes, in Malaysia. METHODS: Following ethical approval, we conducted hospital-based dengue surveillance for one year in three referral hospitals. Suspected cases aged 9-25 years underwent dengue virological confirmation by RT-PCR and/or NS1 Ag ELISA at a central laboratory. Two age- and geography-matched hospitalized non-dengue case-controls were recruited for a traditional CC study. Suspected cases testing negative were test-negative controls. Socio-demographic, risk factor and routine laboratory data were collected. Logistic regression models were used to estimate associations between confirmed dengue and risk factors. RESULTS: We recruited 327 subjects; 155 were suspected of dengue. The planned sample size was not met. 124 (80%) of suspected cases were dengue-confirmed; seven were assessed as severe. Three had missing RT-PCR results; the study recruited 28 test-negative controls. Only 172 matched controls could be recruited; 90 cases were matched with ≥1 controls. Characteristics of cases and controls were mostly similar. By CC design, two variables were significant risk factors for hospitalized dengue: recent household dengue contact (OR: 54, 95% CI: 7.3-397) and recent neighbourhood insecticidal fogging (OR: 2.1; 95% CI: 1.3-3.6). In the TN design, no risk factors were identified. In comparison with gold-standard diagnostics, routine tests performed poorly. CONCLUSIONS: The CC design may be more appropriate than the TN design for hospitalized dengue vaccine effectiveness studies. Selection bias in case control selection could be minimized by protocol changes more easily than increasing TN design control numbers, because early-stage dengue diagnosis in endemic countries is highly specific. MREC study approval: (39)KKM/NIHSEC/P16-1334.

Paper microfluidic device for early diagnosis and prognosis of acute myocardial infarction via quantitative multiplex cardiac biomarker detection.

The early detection of acute myocardial infarction (AMI) upon the onset of chest pain symptoms is crucial for patient survival. However, this detection is challenging, particularly without a persistent elevation of ST-segment reflected in an electrocardiogram or in blood tests. A majority of the available point-of-care testing devices allow accurate and rapid diagnosis of AMI. However, AMI diagnosis is reliable only at intermediate and later stages, with myocardial injury (> 6 h) and MI, based on the expression of specific cardiac biomarkers including troponin I or T (cTnI or cTnT), creatine kinase-MB (CK-MB), and myoglobin. Diagnosis at the early myocardial ischemia stage is not possible. To overcome this limitation, a sensitive and rapid microfluidic paper-based device (µPAD) was developed for the simultaneous detection of multiple cardiac biomarkers for the early and late diagnosis of AMI. The glycogen phosphorylase isoenzyme BB (GPBB) was detected during early (within first 4 h) ischemic myocardial injury. On the same µPAD platform, detection of prolonged elevation of levels of cTnT and CK-MB, which are only produced 6 h after the onset of chest pain in human serum, was possible. Sandwich immunoassay performed on the µPAD achieved reproducibility (RSD approximately 10% and intra-and inter-day precision (CV 10-20%, 99th percentile), as well as consistently stable test results for 28 days, with strong correlation (r2= 0.962), using the standard Siemens Centaur XPT Immunoassay system. The present findings indicate the potential of the µPAD platform as a point-of-care device for the early diagnosis and prognosis of AMI.

The impact of a prescription review and prescriber feedback system on prescribing practices in primary care clinics: a cluster randomised trial.

BACKGROUND: To evaluate the effectiveness of a structured prescription review and prescriber feedback program in reducing prescribing errors in government primary care clinics within an administrative region in Malaysia. METHODS: This was a three group, pragmatic, cluster randomised trial. In phase 1, we randomised 51 clinics to a full intervention group (prescription review and league tables plus authorised feedback letter), a partial intervention group (prescription review and league tables), and a control group (prescription review only). Prescribers in these clinics were the target of our intervention. Prescription reviews were performed by pharmacists; 20 handwritten prescriptions per prescriber were consecutively screened on a random day each month, and errors identified were recorded in a standardised data collection form. Prescribing performance feedback was conducted at the completion of each prescription review cycle. League tables benchmark prescribing errors across clinics and individual prescribers, while the authorised feedback letter detailed prescribing performance based on a rating scale. In phase 2, all clinics received the full intervention. Pharmacists were trained on data collection, and all data were audited by researchers as an implementation fidelity strategy. The primary outcome, percentage of prescriptions with at least one error, was displayed in p-charts to enable group comparison. RESULTS: A total of 32,200 prescriptions were reviewed. In the full intervention group, error reduction occurred gradually and was sustained throughout the 8-month study period. The process mean error rate of 40.7% (95% CI 27.4, 29.5%) in phase 1 reduced to 28.4% (95% CI 27.4, 29.5%) in phase 2. In the partial intervention group, error reduction was not well sustained and showed a seasonal pattern with larger process variability. The phase 1 error rate averaging 57.9% (95% CI 56.5, 59.3%) reduced to 44.8% (95% CI 43.3, 46.4%) in phase 2. There was no evidence of improvement in the control group, with phase 1 and phase 2 error rates averaging 41.1% (95% CI 39.6, 42.6%) and 39.3% (95% CI 37.8, 40.9%) respectively. CONCLUSIONS: The rate of prescribing errors in primary care settings is high, and routine prescriber feedback comprising league tables and a feedback letter can effectively reduce prescribing errors. TRIAL REGISTRATION: National Medical Research Register: NMRR-12-108-11,289 (5th March 2012).

Use of shared care and routine tests in follow-up after treatment for localised cutaneous melanoma.

BACKGROUND: Patients may decide to undertake shared care with a general practitioner (GP) during follow-up after treatment for localised melanoma. Routine imaging tests for surveillance may be commonly used despite no evidence of clinical utility. This study describes the frequency of shared care and routine tests during follow-up after treatment for localised melanoma. METHODS: We randomly sampled 351 people with localised melanoma [American Joint Cancer Committee (AJCC) substages 0 - II] who had not had recurrent or new primary melanoma diagnosed from a total of 902 people diagnosed and treated for localised melanoma at a specialist centre in 2014. We interviewed participants by telephone about their experience of follow-up in the past year, and documented the proportion of patients who were undertaking shared care follow-up with a GP. We also recorded the frequency and type of investigations during follow-up. We calculated weighted estimates that are representative of the full inception cohort. RESULTS: Of the 351 people who were invited to participate, 230 (66%) people consented to the telephone interview. The majority undertook shared care follow-up with a GP (61%). People who choose to have shared care follow-up with a GP are more likely to be male (p = 0.006), have lower AJCC stage (p for trend = 0.02), reside in more remote areas (p for trend< 0.001), and are less likely to have completed secondary school (p < 0.001). Few people saw a non-doctor health practitioner as part of their follow-up (9%). Many people report undergoing tests for melanoma, much of which may be routine tests for surveillance (37%). CONCLUSIONS: The majority of people treated for a first primary localised melanoma at a specialist centre, without recurrent or new melanoma, choose to undertake shared care follow-up with a GP. Many appear to have routine diagnostic imaging as part of their melanoma surveillance.

Patient Preferences for Follow-up After Recent Excision of a Localized Melanoma.

Importance: The standard model of follow-up posttreatment of localized melanoma relies on clinician detection of recurrent or new melanoma, through routinely scheduled clinics (clinician-led surveillance). An alternative model is to increase reliance on patient detection of melanoma, with fewer scheduled visits and increased support for patients' skin self-examination (SSE) (eg, using smartphone apps to instruct, prompt and record SSE, and facilitate teledermatology; patient-led surveillance). Objective: To determine the proportion of adults treated for localized melanoma who prefer the standard scheduled visit frequency (as per Australian guideline recommendations) or fewer scheduled visits (adapted from the Melanoma Follow-up [MELFO] study of reduced follow-up). Design, Setting, and Participants: This survey study used a telephone interview for surveillance following excision of localized melanoma at an Australian specialist center. We invited a random sample of 400 patients who had completed treatment for localized melanoma in 2014 to participate. They were asked about their preferences for scheduled follow-up, and experience of follow-up in the past 12 months. Those with a recurrent or new primary melanoma diagnosed by the time of interview (0.8-1.7 years since first diagnosis) were asked about how it was first detected and treated. SSE practices were also assessed. Main Outcomes and Measures: Proportion preferring standard vs fewer scheduled clinic visits, median delay between detection and treatment of recurrent or new primary melanoma, and SSE practices. Results: Of the 262 people who agreed to be interviewed, the mean (SD) age was 64.3 (14.3) years, and 93 (36%) were women. Among the 230 people who did not have a recurrent or new primary melanoma, 149 vs 81 preferred the standard vs fewer scheduled clinic visits option (70% vs 30% after adjusting for sampling frame). Factors independently associated with preferring fewer visits were a higher disease stage, melanoma on a limb, living with others, not having private health insurance, and seeing a specialist for another chronic condition. The median delay between first detection and treatment of recurrent or new primary melanoma was 7 and 3 weeks, respectively. Only 8% missed a scheduled visit, while 40% did not perform SSE or did so at greater than 3-month intervals. Conclusions and Relevance: Some patients with melanoma may prefer fewer scheduled visits, if they are supported to do SSE and there is rapid clinical review of anything causing concern (patient-led surveillance).

Microfluidic paper-based analytical devices for potential use in quantitative and direct detection of disease biomarkers in clinical analysis.

Clinicians, working in the health-care diagnostic systems of developing countries, currently face the challenges of rising costs, increased number of patient visits, and limited resources. A significant trend is using low-cost substrates to develop microfluidic devices for diagnostic purposes. Various fabrication techniques, materials, and detection methods have been explored to develop these devices. Microfluidic paper-based analytical devices (µPADs) have gained attention for sensing multiplex analytes, confirming diagnostic test results, rapid sample analysis, and reducing the volume of samples and analytical reagents. µPADs, which can provide accurate and reliable direct measurement without sample pretreatment, can reduce patient medical burden and yield rapid test results, aiding physicians in choosing appropriate treatment. The objectives of this review are to provide an overview of the strategies used for developing paper-based sensors with enhanced analytical performances and to discuss the current challenges, limitations, advantages, disadvantages, and future prospects of paper-based microfluidic platforms in clinical diagnostics. µPADs, with validated and justified analytical performances, can potentially improve the quality of life by providing inexpensive, rapid, portable, biodegradable, and reliable diagnostics.

Metronidazole leads to enhanced uptake of imatinib in brain, liver and kidney without affecting its plasma pharmacokinetics in mice.

OBJECTIVES: The pharmacokinetic interaction between metronidazole, an antibiotic-antiparasitic drug used to treat anaerobic bacterial and protozoal infections, and imatinib, a CYP3A4, P-glycoprotein substrate kinase inhibitor anticancer drug, was evaluated. METHODS: Male imprinting control region mice were given 50 mg/kg imatinib PO (control group) or 50 mg/kg imatinib PO, 15 min after 40 mg/kg PO metronidazole (study group). Imatinib plasma, brain, kidney and liver concentrations were measured by HPLC and non-compartmental pharmacokinetic parameters estimated. KEY FINDINGS: Metronidazole coadministration resulted in a double-peak imatinib disposition profile. The maximum concentration (C(max)) decreased by 38%, the area under the curve (AUC(0-∞)) decreased by 14% and the time to C(max) (T(max)) was earlier (50%) in plasma. Apparent volume of distribution (V(SS)/F) and oral clearance (Cl/F) increased by 21% and 17%, respectively. Imatinib tissue penetration was higher after metronidazole coadministration, with 1.7 and 2.1-fold AUC(0-∞) increases in liver and kidney, respectively. Metronidazole increased imatinib's tissue-to-plasma AUC(0-∞) ratio in liver from 2.29 to 4.53 and in kidney from 3.04 to 7.57, suggesting higher uptake efficiency. Brain C(max) was 3.9-fold higher than control and AUC(0-t last) was 2.3-fold greater than plasma (3.5% in control group). No tissue-plasma concentration correlation was found. CONCLUSIONS: Metronidazole slightly decreased imatinib systemic exposure but enhanced liver, kidney and brain penetration, probably due to metronidazole-mediated inhibition of P-glycoprotein and other efflux transporters. The high brain exposure opens possibilities for treatment of glioma and glioblastoma. Renal and hepatic functions may need to be monitored due to potential renal and hepatic toxicity.