The implementation of a zero-suicide framework in a child and youth mental health service in Australia: processes and learnings.

Suicide in children is a significant and growing problem. The "zero suicide" framework (ZSF) is one approach to suicide prevention used in health services for adults and children. This paper reports on the introduction of the first suicide prevention pathway (SPP) based on ZSF at a Child and Youth Mental Health Service (CYMHS) in Australia. It begins by describing the adaptations made to elements of the SPP originally designed for adults to meet the needs of children. Lessons learned in applying the SPP in the service are then discussed. The aim is to inform and improve practice in the use of zero suicide approaches in child and youth mental health settings in Australia and worldwide.

Optical Flow Analysis of Paralaryngeal Muscle Movement.

OBJECTIVES: The paralaryngeal muscles are thought to be hyperfunctional with phonation in patients with primary muscle tension dysphonia (pMTD). However, objective, quantitative tools to assess paralaryngeal movement patterns lack. The objectives of this study were to (1) validate the use of optical flow to characterize paralaryngeal movement patterns with phonation, (2) characterize phonatory optical flow velocities and variability of the paralaryngeal muscles before and after a vocal load challenge, and (3) compare phonatory optical flow measures to standard laryngoscopic, acoustic, and self-perceptual assessments. METHODS: Phonatory movement velocities and variability of the paralaryngeal muscles at vocal onsets and offsets were quantified from ultrasound videos and optical flow methods across 42 subjects with and without a diagnosis of pMTD, before and after a vocal load challenge. Severity of laryngoscopic mediolateral supraglottic compression, acoustic perturbation, and ratings of vocal effort and discomfort were also obtained at both time points. RESULTS: There were no significant differences in optical flow measures of the paralaryngeal muscles with phonation between patients with pMTD and controls. Patients with pMTD had significantly more supraglottic compression, higher acoustic perturbations, and higher vocal effort and vocal tract discomfort ratings. Vocal load had a significant effect on vocal effort and discomfort but not on supraglottic compression, acoustics, or optical flow measures of the paralaryngeal muscles. CONCLUSION: Optical flow methods can be used to study paralaryngeal muscle movement velocity and variability patterns during vocal productions, although the role of the paralaryngeal in pMTD diagnostics (e.g., vocal hyperfunction) remains suspect. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:1792-1801, 2024.

Relationships Among Stimulability Testing, Patient Factors, and Voice Therapy Compliance.

OBJECTIVE: Voice stimulability testing to determine voice therapy efficacy and prognosis is commonly used during the voice evaluation, but little is known about how patient factors (eg, voice diagnosis, dysphonia severity) can influence stimulability outcomes. The predictability of voice therapy success with different stimulability facilitating techniques (eg, hums, pitch glides) is also unknown. The goals of this study were to identify relationships between patient factors, voice therapy compliance, and stimulability testing. METHODS: A retrospective chart review was conducted on 50 patients who were seen for their initial voice therapy evaluation at the UT Southwestern Clinical Center for Voice Care. Chart review included documentation of the stimulability tasks that yielded/did not yield voice changes, level of stimulability, voice diagnosis, clinician-rated auditory-perceptual analysis of vocal quality, therapy attendance, and compliance with voice therapy recommendations. Statistical analysis was conducted to determine whether the types of facilitating techniques, voice diagnosis, and dysphonia severity could predict how stimulable patients were and whether any stimulability techniques could predict voice therapy attendance and compliance. RESULTS: Patients diagnosed with functional voice disorders (eg, muscle tension dysphonia) were 11 times more likely to be stimulable for voice improvements than patients with neurological voice disorders (eg, vocal fold paralysis). Patients with lower dysphonia severity were more likely to be stimulable than patients with high dysphonia severity. Specific facilitating voice tasks did not predict the level of stimulability. Stimulability level was not predictive of therapy attendance or compliance with therapy recommendations. CONCLUSIONS: Voice diagnosis and severity of dysphonia influenced stimulability levels. However, voice stimulability was not predictive of voice therapy attendance or compliance, and no specific facilitative task predicted the level of stimulability. Future investigations should focus on other means of measuring a patient's motivation for change and on the predictive power of stimulability testing on voice therapy outcomes.

Relationships Between Laryngoscopic Analysis Metrics of Supraglottic Compression and Vocal Effort in Primary Muscle Tension Dysphonia.

PURPOSE: Supraglottic compression is thought to underlie vocal effort in patients with primary muscle tension dysphonia (pMTD). However, the relationship between supraglottic compression and vocal effort in this clinical population remains unclear. Gold standard laryngoscopic assessment metrics for supraglottic compression are also lacking. The goals of this study were to identify metrics proposed in the literature that could distinguish patients diagnosed with pMTD from typical voice users and determine their relationships to the vocal effort. METHODS: Flexible laryngeal endoscopy was performed on 50 participants (25 pMTD, 25 controls). The presence of supraglottic compression was characterized using a categorical (nominal) scale and severity was quantified on ordinal and continuous scales. The three laryngoscopic metrics were correlated with self-perceived ratings of vocal effort on a 100 mm visual analog scale. RESULTS: Inter-rater reliability was strongest for the continuous scale (P's < 0.0001) compared to categorical (P's < 0.001) and ordinal (P's < 0.001) scales. The presence of different supraglottic compression patterns varied in both groups, and there were no significant group differences on categorical (P's > 0.05) scales. Mediolateral (M-L) supraglottic compression was significantly greater in the pMTD group (P < 0.0001), and anteroposterior (A-P) compression was significantly greater in the control group (P = 0.001) using continuous scales. There were no significant relationships between any of the three laryngoscopic metric types and vocal effort ratings (P's > 0.05), except for a significantly positive relationship between anterior-posterior compression on the ordinal scale and vocal effort in the control group (P = 0.047). CONCLUSIONS: Continuous scales are reliable and valid for distinguishing individuals with pMTD from those without voice disorders, especially occupational voice users. M-L supraglottic compression may be a better indicator of pMTD than A-P compression. However, the poor correlation between supraglottic compression and vocal effort suggests that one may not influence the other. Future studies should focus on other mechanisms underlying vocal effort in patients with pMTD.

Extrinsic Laryngeal Muscle Tension in Primary Muscle Tension Dysphonia with Shear Wave Elastography.

OBJECTIVES: It has been assumed that patients with primary muscle tension dysphonia (pMTD) have more extrinsic laryngeal muscle (ELM) tension, but tools to study this phenomenon lack. Shear wave elastography (SWE) is a potential method to address these shortcomings. The objectives of this study were to apply SWE to the ELMs, compare SWE measures to standard clinical metrics, and determine group differences in pMTD and typical voice users before and after vocal load. METHODS: SWE measurements of the ELMs from ultrasound examinations of the anterior neck, supraglottic compression severities from laryngoscopic images, cepstral peak prominences (CPP) from voice recordings, and self-perceptual ratings of vocal effort and discomfort were obtained in voice users with (N = 30) and without (N = 35) pMTD, before and after a vocal load challenge. RESULTS: ELM tension significantly increased from rest-to-voiced conditions in both groups. However, the groups were similar in their ELM stiffness levels at SWE at baseline, during vocalization, and post-vocal load. Levels of vocal effort and discomfort and supraglottic compression were significantly higher and CPP was significantly lower in the pMTD group. Vocal load had a significant effect on vocal effort and discomfort but not on laryngeal or acoustic patterns. CONCLUSION: SWE can be used to quantify ELM tension with voicing. Although the pMTD group reported significantly higher levels of vocal effort and vocal tract discomfort and, on average, exhibited significantly more severe supraglottic compression and lower CPP values, there were no group differences in levels of ELM tension using SWE. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:3482-3491, 2023.

Use of Motion Capture Technology to Study Extrinsic Laryngeal Muscle Tension and Hyperfunction.

OBJECTIVES: Patients with primary muscle tension dysphonia (pMTD) commonly report paralaryngeal pain and discomfort, and extrinsic laryngeal muscle (ELM) tension and hyperfunction are commonly implicated. However, quantitative physiological metrics to study ELM movement patterns for the characterization of pMTD diagnosis and monitoring of treatment progress are lacking. The objectives of this study were to validate motion capture (MoCap) technology to study ELM kinematics, determine whether MoCap could distinguish ELM tension and hyperfunction between individuals with and without pMTD, and investigate relationships between common clinical voice metrics and ELM kinematics. METHODS: Thirty subjects (15 with pMTD and 15 controls) were recruited for the study. Sixteen markers were placed on different anatomical landmarks on the chin and anterior neck. Movements across these regions were tracked during four voice and speech tasks using two three-dimensional cameras. Movement displacement and variability were determined based on 16 key-points and 53 edges. RESULTS: Intraclass correlation coefficients demonstrated high intra- and inter-rater reliability (p's < 0.001). Other than greater movement displacements around the thyrohyoid space during longer phrasing (reading passage, 30-s diadochokinetics) and more movement variability in patients with pMTD, kinematic patterns between groups were similar across the 53 edges for the four voice and speech tasks. There were also no significant correlations between ELM kinematics and standard voice metrics. CONCLUSION: Results demonstrate the feasibility and reliability of MoCap for the study of ELM kinematics. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3472-3481, 2023.

Key role for Kv11.1 (ether-a-go-go related gene) channels in rat bladder contractility.

In addition, to their established role in cardiac myocytes and neurons, ion channels encoded by ether-a-go-go-related genes (ERG1-3 or kcnh2,3 and 6) (kcnh2) are functionally relevant in phasic smooth muscle. The aim of the study was to determine the expression and functional impact of ERG expression products in rat urinary bladder smooth muscle using quantitative polymerase chain reaction, immunocytochemistry, whole-cell patch-clamp and isometric tension recording. kcnh2 was expressed in rat bladder, whereas kcnh6 and kcnh3 expression were negligible. Immunofluorescence for the kcnh2 expression product Kv11.1 was detected in the membrane of isolated smooth muscle cells. Potassium currents with voltage-dependent characteristics consistent with Kv11.1 channels and sensitive to the specific blocker E4031 (1 µM) were recorded from isolated detrusor smooth muscles. Disabling Kv11.1 activity with specific blockers (E4031 and dofetilide, 0.2-20 µM) augmented spontaneous contractions to a greater extent than BKCa channel blockers, enhanced carbachol-driven activity, increased nerve stimulation-mediated contractions, and impaired ß-adrenoceptor-mediated inhibitory responses. These data establish for the first time that Kv11.1 channels are key determinants of contractility in rat detrusor smooth muscle.

Clinical Characteristics and Effects of Vocal Demands in Occupational Voice Users With and Without Primary Muscle Tension Dysphonia.

OBJECTIVES: The objectives of this study were to (1) compare laryngeal configuration patterns in occupational voice users with and without primary muscle tension dysphonia (pMTD), (2) characterize laryngeal configurations in relation to other clinical metrics (acoustic, perceptual), and (3) determine the effects of vocal demands (load) on these clinical parameters. METHODS: Thirty subjects (15 pMTD, 15 control) were recruited for the study. Laryngoscopic examinations and voice samples for sustained /i/ were obtained before and after a half hour vocal load task. Subjects rated their vocal effort and discomfort before and after the vocal load. Laryngeal configurations were analyzed subjectively with dichotomous and categorical rating scales and hyper function severity quantified (endolaryngeal area outlets). Overall dysphonia severity and vocal instability of each voice sample was rated on 100mm visual analog scales and cepstral peak prominence (CPP) extracted from each voice sample. RESULTS: Laryngeal configurations between groups or vocal load condition were not distinguishable with any of the dichotomous, categorical, or quantitative laryngeal metrics. Vocal effort and discomfort ratings were significantly higher in the pMTD group compared to the control group. Vocal load also had significant effects across groups on vocal effort and vocal tract discomfort ratings. Although CPP values fell within the normal range in both groups, CPP was significantly lower in the pMTD group at both pre-load and post-load time points. Auditory-perceptual ratings were also significantly worse in the pMTD group. Vocal load did not have a significant effect on acoustic or auditory-perceptual measures. CONCLUSION: Similar laryngeal configurations between groups at both pre- and post-vocal load suggests classic patterns of laryngeal "hyperadduction" may occur variably in occupational voice users and may not be indicative of pMTD pathophysiology. Greater vocal effort, discomfort, instability, and perturbation within the vocal system may better define pMTD than laryngeal configuration in occupational voice users with pMTD.

A lived experience co-designed study protocol for a randomised control trial: the Attempted Suicide Short Intervention Program (ASSIP) or Brief Cognitive Behavioural Therapy as additional interventions after a suicide attempt compared to a standard Suicide Prevention Pathway (SPP).

BACKGROUND: Despite being preventable, suicide is a leading cause of death and a major global public health problem. For every death by suicide, many more suicide attempts are undertaken, and this presents as a critical risk factor for suicide. Currently, there are limited treatment options with limited underpinning research for those who present to emergency departments with suicidal behaviour. The aim of this study is to assess if adding one of two structured suicide-specific psychological interventions (Attempted Suicide Short Intervention Program [ASSIP] or Brief Cognitive Behavioural Therapy [CBT] for Suicide Prevention) to a standardised clinical care approach (Suicide Prevention Pathway [SPP]) improves the outcomes for consumers presenting to a Mental Health Service with a suicide attempt. METHODS: This is a randomised controlled trial with blinding of those assessing the outcomes. People who attempt suicide or experience suicidality after a suicide attempt, present to the Gold Coast Mental Health and Specialist Services, are placed on the Suicide Prevention Pathway (SPP), and meet the eligibility criteria, are offered the opportunity to participate. A total of 411 participants will be recruited for the study, with 137 allocated to each cohort (participants are randomised to SPP, ASSIP + SPP, or CBT + SPP). The primary outcomes of this study are re-presentation to hospitals with suicide attempts. Presentations with suicidal ideation will also be examined (in a descriptive analysis) to ascertain whether a rise in suicidal ideation is commensurate with a fall in suicide attempts (which might indicate an increase in help-seeking behaviours). Death by suicide rates will also be examined to ensure that representations with a suicide attempt are not due to participants dying, but due to a potential improvement in mental health. For participants without a subsequent suicide attempt, the total number of days from enrolment to the last assessment (24 months) will be calculated. Self-reported levels of suicidality, depression, anxiety, stress, resilience, problem-solving skills, and self- and therapist-reported level of therapeutic engagement are also being examined. Psychometric data are collected at baseline, end of interventions, and 6,12, and 24 months. DISCUSSION: This project will move both ASSIP and Brief CBT from efficacy to effectiveness research, with clear aims of assessing the addition of two structured psychological interventions to treatment as usual, providing a cost-benefit analysis of the interventions, thus delivering outcomes providing a clear pathway for rapid translation of successful interventions. TRIALS REGISTRATION: ClinicalTrials.gov NCT04072666 . Registered on 28 August 2019.

A systematic review and meta-analysis of thiazide-induced hyponatraemia: time to reconsider electrolyte monitoring regimens after thiazide initiation?

AIMS: Hyponatraemia is one of the major adverse effects of thiazide and thiazide-like diuretics and the leading cause of drug-induced hyponatraemia requiring hospital admission. We sought to review and analyze all published cases of this important condition. METHODS: Ovid Medline, Embase, Web of Science and PubMed electronic databases were searched to identify all relevant articles published before October 2013. A proportions meta-analysis was undertaken. RESULTS: One hundred and two articles were identified of which 49 were single patient case reports. Meta-analysis showed that mean age was 75 (95% CI 73, 77) years, 79% were women (95% CI 74, 82) and mean body mass index was 25 (95% CI 20, 30) kg m(-2) . Presentation with thiazide-induced hyponatraemia occurred a mean of 19 (95% CI 8, 30) days after starting treatment, with mean trough serum sodium concentration of 116 (95% CI 113, 120) mm and serum potassium of 3.3 (95% CI 3.0, 3.5) mm. Mean urinary sodium concentration was 64 mm (95% CI 47, 81). The most frequently reported drugs were hydrochlorothiazide, indapamide and bendroflumethiazide. CONCLUSIONS: Patients with thiazide-induced hyponatraemia were characterized by advanced age, female gender, inappropriate saliuresis and mild hypokalaemia. Low BMI was not found to be a significant risk factor, despite previous suggestions. The time from thiazide initiation to presentation with hyponatraemia suggests that the recommended practice of performing a single investigation of serum biochemistry 7-14 days after thiazide initiation may be insufficient or suboptimal. Further larger and more systematic studies of thiazide-induced hyponatraemia are required.

On the alert: future priorities for alerts in clinical decision support for computerized physician order entry identified from a European workshop.

BACKGROUND: Clinical decision support (CDS) for electronic prescribing systems (computerized physician order entry) should help prescribers in the safe and rational use of medicines. However, the best ways to alert users to unsafe or irrational prescribing are uncertain. Specifically, CDS systems may generate too many alerts, producing unwelcome distractions for prescribers, or too few alerts running the risk of overlooking possible harms. Obtaining the right balance of alerting to adequately improve patient safety should be a priority. METHODS: A workshop funded through the European Regional Development Fund was convened by the University Hospitals Birmingham NHS Foundation Trust to assess current knowledge on alerts in CDS and to reach a consensus on a future research agenda on this topic. Leading European researchers in CDS and alerts in electronic prescribing systems were invited to the workshop. RESULTS: We identified important knowledge gaps and suggest research priorities including (1) the need to determine the optimal sensitivity and specificity of alerts; (2) whether adaptation to the environment or characteristics of the user may improve alerts; and (3) whether modifying the timing and number of alerts will lead to improvements. We have also discussed the challenges and benefits of using naturalistic or experimental studies in the evaluation of alerts and suggested appropriate outcome measures. CONCLUSIONS: We have identified critical problems in CDS, which should help to guide priorities in research to evaluate alerts. It is hoped that this will spark the next generation of novel research from which practical steps can be taken to implement changes to CDS systems that will ultimately reduce alert fatigue and improve the design of future systems.

A practical guide to monitoring for adverse drug reactions during antihypertensive drug therapy.

Monitoring of patients taking antihypertensive treatment can identify potential adverse drug reactions (ADRs). However, published guidelines give divergent or incomplete recommendations on monitoring for ADRs. Using a predetermined strategy, we undertook a systematic review to identify hypertension guidelines published from January 2001 to October 2011 with recommendations for monitoring for ADRs. We screened 88 abstracts and 187 web-based guidelines, and identified 19 published guidelines on monitoring the biochemical effects of antihypertensive drug therapy. We then produced a set of practical clinical guidelines, synthesized from those recommendations. Our recommendations are designed to provide efficient monitoring. They reduce the number of tests to a minimum consistent with safe practice and align monitoring schedules, so that creatinine, potassium and sodium concentrations are measured at the same times in all cases. The instructions for biochemical monitoring in current guidelines differ greatly, both in the extent of advice and in the detail provided. The current lack of consistent and workable instructions poses serious difficulties for practitioners. The recommendations distilled from this systematic review should help practitioners when they monitor therapy with antihypertensive drugs.

Developing consensus on hospital prescribing indicators of potential harms amenable to decision support.

AIMS: To develop a list of prescribing indicators specific for the hospital setting that would facilitate the prospective collection of high-severity and/or high-frequency prescribing errors, which are also amenable to electronic clinical decision support. METHODS: A two-stage consensus technique (electronic Delphi) was carried out with 20 experts across England. Participants were asked to score prescribing errors using a five-point Likert scale for their likelihood of occurrence and the severity of the most likely outcome. These were combined to produce risk scores, from which median scores were calculated for each indicator across the participants in the study. The degree of consensus between the participants was defined as the proportion that gave a risk score in the same category as the median. Indicators were included if a consensus of 80% or more was achieved. RESULTS: A total of 80 prescribing errors were identified by consensus as being high or extreme risk. The most common drug classes named within the indicators were antibiotics (n = 13), antidepressants (n = 8), nonsteroidal anti-inflammatory drugs (n = 6) and opioid analgesics (n = 6). The most frequent error type identified as high or extreme risk were those classified as clinical contraindications (n = 29 of 80). CONCLUSIONS: Eighty high-risk prescribing errors in the hospital setting have been identified by an expert panel. These indicators can serve as a standardized, validated tool for the collection of prescribing data in both paper-based and electronic prescribing processes. This can assess the impact of safety improvement initiatives, such as the implementation of electronic clinical decision support.

Improvement in the detection of adverse drug events by the use of electronic health and prescription records: an evaluation of two trigger tools.

PURPOSE: To test if two of the adverse event triggers proposed by the Institute of Healthcare Improvement can detect adverse drug events (ADEs) in a UK secondary care setting, using an electronic prescribing and health record system. METHODS: In order to identify triggers for over-anticoagulation and potential opioid overdose and we undertook a retrospective review of electronic medical and prescription records from 54,244 hospital admissions over a 1-year period, alongside a review of medical incident reports. Once prescription data were linked to triggers and duplicates were removed, case note review eliminated the false positive ADEs. Additionally, we tested the use of an electronic algorithm for the International Normalized Ratio (INR) ≥6 trigger. RESULTS: The INR ≥6 electronic trigger identified 46 potential ADEs and the naloxone electronic trigger identified 82 ADEs. Based on the available case note review, the INR ≥6 trigger had a positive predictive value (PPV) of 38 % (14/37) and the naloxone trigger had a PPV of 91 % (61/67). The electronic algorithm for the INR ≥6 trigger identified 12 ADEs, thus reducing the need of case note review. This was in comparison with one and two critical incidents reported in the trust medical incident reports system, which respectively related to over-coagulation with warfarin and over-sedation with opioid medication. CONCLUSIONS: We have integrated automated and manual methods of detecting ADEs using previously defined triggers. Incorporating electronic triggers in already established electronic health records with prescription and laboratory test data can improve the detection of ADEs, and potentially lead to methods to avert them.

Dose omissions in hospitalized patients in a UK hospital: an analysis of the relative contribution of adverse drug reactions.

BACKGROUND: The omission of charted (prescribed) doses for hospitalized patients is an important problem in the UK. Inappropriate drug omission can clearly lead to harm from lack of therapeutic effect. However, healthcare professionals administering medicines may decide that omission of a dose is appropriate in certain circumstances, e.g. when patients show signs of a possible adverse drug reaction (ADR). OBJECTIVE: The aim of this study was to characterize dose omissions to understand the factors that influence non-administration of therapy and to determine the proportion of doses that are appropriately omitted due to ADRs. METHODS: We used data from a bespoke hospital-wide electronic prescribing and administration system at University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. We extracted data on 6.01 million drug administrations during 2010 and then randomly selected four 7-day periods, concentrating on doses that were charted but not given. Omitted medicines were counted if either there was a charted 'non-administration' (i.e. an active acknowledgement of the omitted dose) or there was no charting of that dose (i.e. no record of either administration or omission). Paused medicines were not counted. When a dose was omitted, staff indicated the reasons for non-administration using codes ('hard coded') or free text in the electronic system. We used both to compare the contribution of different factors, including ADRs, to the total rates of dose omissions. RESULTS: In the four 7-day periods analysed, 60 763 (12.4%) of the 491 894 charted doses were omitted. The most common code was 'patient refused drug' (45.4%). Only 1.6% of doses were omitted for reasons of patient safety, of which 4 in 1000 omissions were coded as directly due to an ADR. CONCLUSIONS: Measures to improve the quality of care should seek to reduce dose omissions, but in some cases omission may be rational. Electronic medication administration records allow for detailed analysis of decisions made by healthcare professionals at the point of administration. While dose omissions related to ADRs are uncommon, they are important both for patient safety and for therapeutic decision making.

The potential of the internet.

The internet and the World Wide Web have changed the ways that we function. As technologies grow and adapt, there is a huge potential for the internet to affect drug research and development, as well as many other aspects of clinical pharmacology. We review some of the areas of interest to date and discuss some of the potential areas in which internet-based technology can be exploited. Information retrieval from the web by health-care professionals is common, and bringing evidence-based medicine to the bedside affects the care of patients. As a primary research tool the web can provide a vast array of information in generating new ideas or exploring previous research findings. This has facilitated systematic reviewing, for example. The content of the web has become a subject of research in its own right. The web is also widely used as a research facilitator, including enhancement of communication between collaborators, provision of online research tools (such as questionnaires, management of large scale multicentre trials, registration of clinical trials) and distribution of information. Problems include information overload, ignorance of early data that are not indexed in databases, difficulties in keeping web sites up to date and assessing the validity of information retrieved. Some web-based activities are viewed with suspicion, including analysis by pharmaceutical companies of drug information to facilitate direct-to-consumer advertising of novel pharmaceuticals. Use of these technologies will continue to expand in often unexpected ways. Clinical pharmacologists must embrace internet technology and include it as a key priority in their research agenda.

Biochemical monitoring of patients treated with antihypertensive therapy for adverse drug reactions: a systematic review.

Biochemical monitoring of patients treated with antihypertensive therapy is recommended in order to identify potential adverse reactions to treatment. We aimed to review the literature investigating the nature of biochemical monitoring in adults treated in primary care with antihypertensive drugs. Specifically, we wished to establish (i) the proportion of patients with biochemical baseline testing prior to the initiation of antihypertensive therapy; (ii) the proportion of patients with biochemical monitoring after initiation of antihypertensive therapy; (iii) the patient characteristics associated with biochemical monitoring; (iv) the frequency of biochemical monitoring after the initiation of antihypertensive therapy; and (v) the relationship, if any, between biochemical monitoring and adverse patient outcomes. We searched MEDLINE, EMBASE and Google Scholar from 1948 to 31 December 2010 using a combination of text words and search terms. Retrospective and prospective cohort studies, cross-sectional studies, randomized controlled trials or quasi-randomized controlled trials, and audits of current clinical practice were included. Clinical trials, case reports and case series were excluded. Studies were included if they provided data on the proportion of patients treated with antihypertensive therapy in primary care who had any biochemical monitoring before or after the initiation of therapy. In total, 15 studies were included in our review, which used a wide variety of definitions of monitoring prior to and after the initiation of antihypertensive therapy. From 17% to 81% of patients treated with antihypertensive drugs had a baseline biochemical test and from 20% to 79% had any follow-up monitoring. In only 7 of the 12 studies that examined follow-up monitoring did more than half of the patients have any monitoring. Overall, this systematic review provides evidence that monitoring as recommended by published guidelines is not commonly undertaken. Only two studies were identified that examined patients with both baseline testing and follow-up monitoring. Omission of one or the other limits the ability to analyse the effect of treatment on electrolyte concentrations or renal function. There is limited research on the patient factors associated with monitoring and further work is required to determine the impact of monitoring on adverse patient outcomes. Important barriers to effective monitoring exist and this review emphasizes that these have not yet been overcome.

Metal ions: supporting actors in the playbook of small ribozymes.

Since the 1980s, several small RNA motifs capable of chemical catalysis have been discovered. These small ribozymes, composed of between approximately 40 and 200 nucleotides, have been found to play vital roles in the replication of subviral and viral pathogens, as well as in gene regulation in prokaryotes, and have recently been discovered in noncoding eukaryotic RNAs. All of the known natural small ribozymes - the hairpin, hammerhead, hepatitis delta virus, Varkud satellite, and glmS ribozymes--catalyze the same self-cleavage reaction as RNase A, resulting in two products, one bearing a 2'-3' cyclic phosphate and the other a 5'-hydroxyl group. Although originally thought to be obligate metalloenzymes like the group I and II self-splicing introns, the small ribozymes are now known to support catalysis in a wide variety of cations that appear to be only indirectly involved in catalysis. Nevertheless, under physiologic conditions, metal ions are essential for the proper folding and function of the small ribozymes, the most effective of these being magnesium. Metal ions contribute to catalysis in the small ribozymes primarily by stabilizing the catalytically active conformation, but in some cases also by activating RNA functional groups for catalysis, directly participating in catalytic acid-base chemistry, and perhaps by neutralizing the developing negative charge of the transition state. Although interactions between the small ribozymes and cations are relatively nonspecific, ribozyme activity is quite sensitive to the types and concentrations of metal ions present in solution, suggesting a close evolutionary relationship between cellular metal ion homeostasis and cation requirements of catalytic RNAs, and perhaps RNA in general.

Republished paper: Where errors occur in the preparation and administration of intravenous medicines: a systematic review and Bayesian analysis.

OBJECTIVE: To investigate the overall probability of error in preparing and administering intravenous medicines; to identify at which stage of the process an error is most likely to occur; and to determine the impact of error correction on the error probability. Design Systematic review and random-effects Bayesian conditional independence modelling. METHODS: Medline and EMBASE were searched for studies on intravenous medicines. The error rates of each stage were extracted. These, expert estimates, and error rates from generic tasks, were used in a Bayesian conditional independence model to find error 'hot-spots.' The main outcome measure was the probability of at least one error occurring during intravenous therapy. RESULTS: Nine published studies were identified for inclusion in the systematic review and meta-analysis. The overall probability of making at least one error in intravenous therapy was 0.73 (95% credible interval (CrI) 0.54 to 0.90). If error-checking was introduced at each stage of the process, the overall rate fell to 0.22 (95% CrI 0.14 to 0.31). Errors were most likely in the reconstitution step. Removing the reconstitution step by providing preprepared injections would reduce the overall error rate to 0.17 (95% CrI 0.09 to 0.27). CONCLUSIONS: Intravenous therapy is complex and error-prone. Error-checking at each stage could reduce the error probability. The use of preprepared injections may help by eliminating errors in the reconstitution of drug and diluent. However, it will be important to ensure that benefits are not outweighed by practical disadvantages such as an increase in selection errors.