Pharmacotherapy for hypertension in adults 60 years or older.

BACKGROUND: This is the second substantive update of this review. It was originally published in 1998 and was previously updated in 2009. Elevated blood pressure (known as 'hypertension') increases with age - most rapidly over age 60. Systolic hypertension is more strongly associated with cardiovascular disease than is diastolic hypertension, and it occurs more commonly in older people. It is important to know the benefits and harms of antihypertensive treatment for hypertension in this age group, as well as separately for people 60 to 79 years old and people 80 years or older. OBJECTIVES: Primary objective• To quantify the effects of antihypertensive drug treatment as compared with placebo or no treatment on all-cause mortality in people 60 years and older with mild to moderate systolic or diastolic hypertensionSecondary objectives• To quantify the effects of antihypertensive drug treatment as compared with placebo or no treatment on cardiovascular-specific morbidity and mortality in people 60 years and older with mild to moderate systolic or diastolic hypertension• To quantify the rate of withdrawal due to adverse effects of antihypertensive drug treatment as compared with placebo or no treatment in people 60 years and older with mild to moderate systolic or diastolic hypertension SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to 24 November 2017: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We contacted authors of relevant papers regarding further published and unpublished work. SELECTION CRITERIA: Randomised controlled trials of at least one year's duration comparing antihypertensive drug therapy versus placebo or no treatment and providing morbidity and mortality data for adult patients (≥ 60 years old) with hypertension defined as blood pressure greater than 140/90 mmHg. DATA COLLECTION AND ANALYSIS: Outcomes assessed were all-cause mortality; cardiovascular morbidity and mortality; cerebrovascular morbidity and mortality; coronary heart disease morbidity and mortality; and withdrawal due to adverse effects. We modified the definition of cardiovascular mortality and morbidity to exclude transient ischaemic attacks when possible. MAIN RESULTS: This update includes one additional trial (MRC-TMH 1985). Sixteen trials (N = 26,795) in healthy ambulatory adults 60 years or older (mean age 73.4 years) from western industrialised countries with moderate to severe systolic and/or diastolic hypertension (average 182/95 mmHg) met the inclusion criteria. Most of these trials evaluated first-line thiazide diuretic therapy for a mean treatment duration of 3.8 years.Antihypertensive drug treatment reduced all-cause mortality (high-certainty evidence; 11% with control vs 10.0% with treatment; risk ratio (RR) 0.91, 95% confidence interval (CI) 0.85 to 0.97; cardiovascular morbidity and mortality (moderate-certainty evidence; 13.6% with control vs 9.8% with treatment; RR 0.72, 95% CI 0.68 to 0.77; cerebrovascular mortality and morbidity (moderate-certainty evidence; 5.2% with control vs 3.4% with treatment; RR 0.66, 95% CI 0.59 to 0.74; and coronary heart disease mortality and morbidity (moderate-certainty evidence; 4.8% with control vs 3.7% with treatment; RR 0.78, 95% CI 0.69 to 0.88. Withdrawals due to adverse effects were increased with treatment (low-certainty evidence; 5.4% with control vs 15.7% with treatment; RR 2.91, 95% CI 2.56 to 3.30. In the three trials restricted to persons with isolated systolic hypertension, reported benefits were similar.This comprehensive systematic review provides additional evidence that the reduction in mortality observed was due mostly to reduction in the 60- to 79-year-old patient subgroup (high-certainty evidence; RR 0.86, 95% CI 0.79 to 0.95). Although cardiovascular mortality and morbidity was significantly reduced in both subgroups 60 to 79 years old (moderate-certainty evidence; RR 0.71, 95% CI 0.65 to 0.77) and 80 years or older (moderate-certainty evidence; RR 0.75, 95% CI 0.65 to 0.87), the magnitude of absolute risk reduction was probably higher among 60- to 79-year-old patients (3.8% vs 2.9%). The reduction in cardiovascular mortality and morbidity was primarily due to a reduction in cerebrovascular mortality and morbidity. AUTHORS' CONCLUSIONS: Treating healthy adults 60 years or older with moderate to severe systolic and/or diastolic hypertension with antihypertensive drug therapy reduced all-cause mortality, cardiovascular mortality and morbidity, cerebrovascular mortality and morbidity, and coronary heart disease mortality and morbidity. Most evidence of benefit pertains to a primary prevention population using a thiazide as first-line treatment.

Eplerenone for hypertension.

BACKGROUND: Eplerenone is an aldosterone receptor blocker that is chemically derived from spironolactone. In Canada, it is indicated for use as adjunctive therapy to reduce mortality for heart failure patients with New York Heart Association (NYHA) class II systolic chronic heart failure and left ventricular systolic dysfunction. It is also used as adjunctive therapy for patients with heart failure following myocardial infarction. Additionally, it is indicated for the treatment of mild and moderate essential hypertension for patients who cannot be treated adequately with other agents. It is important to determine the clinical impact of all antihypertensive medications, including aldosterone antagonists, to support their continued use in essential hypertension. No previous systematic reviews have evaluated the effect of eplerenone on cardiovascular morbidity, mortality, and magnitude of blood pressure lowering in patients with hypertension. OBJECTIVES: To assess the effects of eplerenone monotherapy versus placebo for primary hypertension in adults. Outcomes of interest were all-cause mortality, cardiovascular events (fatal or non-fatal myocardial infarction), cerebrovascular events (fatal or non fatal strokes), adverse events or withdrawals due to adverse events, and systolic and diastolic blood pressure. SEARCH METHODS: We searched the Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE, Embase, and two trials registers up to 3 March 2016. We handsearched references from retrieved studies to identify any studies missed in the initial search. We also searched for unpublished data by contacting the corresponding authors of the included studies and pharmaceutical companies involved in conducting studies on eplerenone monotherapy in primary hypertension. The search had no language restrictions. SELECTION CRITERIA: We selected randomized placebo-controlled trials studying adult patients with primary hypertension. We excluded studies in people with secondary or gestational hypertension and studies where participants were receiving multiple antihypertensives. DATA COLLECTION AND ANALYSIS: Three review authors independently reviewed the search results for studies meeting our criteria. Three review authors independently extracted data and assessed trial quality using a standardized data extraction form. A fourth independent review author resolved discrepancies or disagreements. We performed data extraction and synthesis using a standardized format on Covidence. We conducted data analysis using Review Manager 5. MAIN RESULTS: A total of 1437 adult patients participated in the five randomized parallel group studies, with treatment durations ranging from 8 to 16 weeks. The daily doses of eplerenone ranged from 25 mg to 400 mg daily. Meta-analysis of these studies showed a reduction in systolic blood pressure of 9.21 mmHg (95% CI -11.08 to -7.34; I2 = 58%) and a reduction of diastolic pressure of 4.18 mmHg (95% CI -5.03 to -3.33; I2 = 0%) (moderate quality evidence).There may be a dose response effect for eplerenone in the reduction in systolic blood pressure at doses of 400 mg/day. However, this finding is uncertain, as it is based on a single included study with low quality evidence. Overall there does not appear to be a clinically important dose response in lowering systolic or diastolic blood pressure at eplerenone doses of 50 mg to 400 mg daily. There did not appear to be any differences in the number of patients who withdrew due to adverse events or the number of patients with at least one adverse event in the eplerenone group compared to placebo. However, only three of the five included studies reported adverse events. Most of the included studies were of moderate quality, as we judged multiple domains as being at unclear risk in the 'Risk of bias' assessment. AUTHORS' CONCLUSIONS: Eplerenone 50 to 200 mg/day lowers blood pressure in people with primary hypertension by 9.21 mmHg systolic and 4.18 mmHg diastolic compared to placebo, with no difference of effect between doses of 50 mg/day to 200 mg/day. A dose of 25 mg/day did not produce a statistically significant reduction in systolic or diastolic blood pressure and there is insufficient evidence for doses above 200 mg/day. There is currently no available evidence to determine the effect of eplerenone on clinically meaningful outcomes such as mortality or morbidity in hypertensive patients. The evidence available on side effects is insufficient and of low quality, which makes it impossible to draw conclusions about potential harm associated with eplerenone treatment in hypertensive patients.

Loop diuretics for patients receiving blood transfusions.

BACKGROUND: Blood transfusions are associated with significant morbidity and mortality. Prophylactic administration of loop diuretics (furosemide, bumetanide, ethacrynic acid, or torsemide) is common practice, especially among people who are at risk for circulatory overload, pulmonary oedema or both. OBJECTIVES: This review aimed to determine if the prophylactic administration of loop diuretics (furosemide, bumetanide, ethacrynic acid, or torsemide) provides a therapeutic advantage (that is, a favourable risk benefit ratio) in adults and children who are recipients of any blood product transfusion versus placebo, no treatment, or general fluid restriction measures. SEARCH METHODS: We searched the Cochrane Renal Group's Specialised Register to 13 January 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs assessing a loop diuretic in patients receiving any blood transfusion were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. Study authors were contacted for additional information. Results were to be expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Mean effect sizes were to be calculated using the random-effects models. MAIN RESULTS: We included four studies that involved 100 participants. Furosemide was the only diuretic investigated in all four studies.None of the included studies assessed the clinically important outcomes noted in our protocol. The studies focused on various markers of respiratory function. An improvement in fraction of inspired oxygen (in favour of furosemide) was noted in one study. An improvement in pulmonary capillary wedge pressure (in favour of furosemide) was noted in two studies. AUTHORS' CONCLUSIONS: There was insufficient evidence to determine whether premedicating people undergoing blood transfusion with loop diuretics prevents clinically important transfusion-related morbidity. Due to the continued use of prophylactic loop diuretics during transfusions, and because this review highlights the absence of evidence to justify this practice, well-conducted RCTs are needed. Given the high mortality, severe morbidity and increasing incidence of transfusion-associated circulatory overload, determining the therapeutic utility of pre-transfusion loop diuresis is an urgent need.

Probiotics for preventing urinary tract infections in adults and children.

BACKGROUND: Urinary tract infection (UTI) is a common bacterial infection that can lead to significant morbidity including stricture, abscess formation, fistula, bacteraemia, sepsis, pyelonephritis and kidney dysfunction. Mortality rates are reported to be as high as 1% in men and 3% in women due to development of pyelonephritis. Because probiotic therapy is readily available without a prescription, a review of their efficacy in the prevention of UTI may aid consumers in making informed decisions about potential prophylactic therapy. Institutions and caregivers also need evidence-based synopses of current evidence to make informed patient care decisions. OBJECTIVES: Compared to placebo or no therapy, did probiotics (any formulation) provide a therapeutic advantage in terms of morbidity and mortality, when used to prevent UTI in susceptible patient populations?Compared to other prophylactic interventions, including drug and non-drug measures (e.g. continuous antibiotic prophylaxis, topical oestrogen, cranberry juice), did probiotics (any formulation) provide a therapeutic advantage in terms of morbidity and mortality when used to prevent UTIs in susceptible patient populations? SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register to 21 September 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA: Randomised controlled trials (RCTs) of susceptible patients (e.g. past history of UTI) or healthy people in which any strain, formulation, dose or frequency of probiotic was compared to placebo or active comparators were included. DATA COLLECTION AND ANALYSIS: All RCTs and quasi-RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) looking at comparing probiotics to no therapy, placebo, or other prophylactic interventions were included. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes. MAIN RESULTS: We included nine studies that involved 735 people in this review. Four studies compared probiotic with placebo, two compared probiotic with no treatment, two compared probiotics with antibiotics in patients with UTI, and one study compared probiotic with placebo in healthy women. All studies aimed to measure differences in rates of recurrent UTI.Our risk of bias assessment found that most studies had small sample sizes and reported insufficient methodological detail to enable robust assessment. Overall, there was a high risk of bias in the included studies which lead to inability to draw firm conclusions and suggesting that any reported treatment effects may be misleading or represent overestimates.We found no significant reduction in the risk of recurrent symptomatic bacterial UTI between patients treated with probiotics and placebo (6 studies, 352 participants: RR 0.82, 95% CI 0.60 to 1.12; I(2) = 23%) with wide confidence intervals, and statistical heterogeneity was low. No significant reduction in the risk of recurrent symptomatic bacterial UTI was found between probiotic and antibiotic treated patients (1 study, 223 participants: RR 1.12, 95% CI 0.95 to 1.33).The most commonly reported adverse effects were diarrhoea, nausea, vomiting, constipation and vaginal symptoms. None of the included studies reported numbers of participants with at least one asymptomatic bacterial UTI, all-cause mortality or those with at least one confirmed case of bacteraemia or fungaemia. Two studies reported study withdrawal due to adverse events and the number of participants who experienced at least one adverse event. One study reported withdrawal occurred in six probiotic participants (5.2%), 15 antibiotic participants (12.2%), while the second study noted one placebo group participant discontinued treatment due to an adverse event. AUTHORS' CONCLUSIONS: No significant benefit was demonstrated for probiotics compared with placebo or no treatment, but a benefit cannot be ruled out as the data were few, and derived from small studies with poor methodological reporting.There was limited information on harm and mortality with probiotics and no evidence on the impact of probiotics on serious adverse events. Current evidence cannot rule out a reduction or increase in recurrent UTI in women with recurrent UTI who use prophylactic probiotics. There was insufficient evidence from one RCT to comment on the effect of probiotics versus antibiotics.

Switching Topical Diclofenac from Higher to Lower Strength: Financial and Clinical Evaluation.

Background: In February 2020, the Fraser Health Authority in British Columbia introduced an automatic therapeutic interchange policy, whereby orders for any strength of topical diclofenac would be automatically interchanged to the commercially available diclofenac 2.32% gel for twice-daily administration. The new policy was intended mainly as a cost-saving measure but had the potential for clinical impacts that needed to be considered. Objectives: To evaluate the financial and clinical impact of the automatic therapeutic interchange policy for topical diclofenac. Methods: A financial evaluation and a clinical evaluation were conducted. Expenditures for topical diclofenac before and after implementation of the automatic therapeutic interchange policy were compared. To obtain information about the clinical impact of the interchange, a retrospective chart review was conducted at long-term care sites. The primary outcome was a composite of 7 components that could indicate worsening of pain in 3 prespecified scenarios. Results: The financial evaluation showed that the interchange could potentially save the health authority more than $200 000 over 12 months. The clinical evaluation showed that 25%-48% of patients met the primary outcome of worsening pain (analyzed according to 3 different scenarios) after the switch to lower-strength diclofenac, with increases in use of as-needed topical diclofenac and other analgesics being the main indicators of worsening pain. Conclusions: An automatic therapeutic interchange policy that switched orders for higher strengths of diclofenac to the 2.32% concentration resulted in large financial savings and, in most cases (52%-75% of patients), did not appear to affect pain control. Prospective studies comparing the clinical impact of higher- and lower-strength topical diclofenac products are warranted.

Contexte: En février 2020, la Fraser Health Authority en Colombie-Britannique a introduit une politique d'échange thérapeutique automatique, selon laquelle les commandes de diclofénac topique (n'importe quelle concentration) seraient automatiquement échangées contre du diclofénac à 2,32 % (formule en gel) disponible dans le commerce pour une administration deux fois par jour. La nouvelle politique visait principalement à réduire les coûts, mais pouvait avoir une incidence clinique, qui devait être prise en compte. Objectifs: Évaluer l'impact financier et clinique de la politique d'échange thérapeutique automatique pour le diclofénac topique. Méthodes: Une évaluation financière et une évaluation clinique ont été réalisées. Les dépenses liées au diclofénac topique avant et après la mise en œuvre de la politique d'échange thérapeutique automatique ont été comparées. Pour obtenir des informations sur l'incidence clinique de l'échange, un examen rétrospectif des dossiers a été réalisé dans les sites de soins de longue durée. Le résultat principal était un composite de 7 éléments pouvant indiquer une aggravation de la douleur dans 3 scénarios prédéfinis. Résultats: L'évaluation financière a montré que l'échange pourrait potentiellement permettre à l'autorité sanitaire d'économiser plus de 200 000 $ sur 12 mois. L'évaluation clinique a quant à elle démontré que 25 à 48 % des patients ont atteint le principal résultat d'aggravation de la douleur (analysé selon 3 scénarios différents) après le passage au diclofénac à plus faible concentration. L'augmentation de l'utilisation au besoin de diclofénac topique et d'autres analgésiques constituait le principal indicateur d'aggravation de la douleur. Conclusions: Une politique d'échange thérapeutique automatique qui remplaçait les ordonnances de concentrations plus élevées de diclofénac par une concentration de 2,32 % a permis de réaliser d'importantes économies financières et, dans la plupart des cas (52 à 75 % des patients), cet échange ne semble pas avoir eu d'effet sur le contrôle de la douleur. Des études prospectives comparant l'incidence clinique des produits topiques à base de diclofénac à concentration plus élevée et plus faible sont justifiées.

Understanding medication recycling practices in Canadian hospitals.

BACKGROUND: Medication recycling within hospitals has proven financial and possible environmental benefits according to local evaluations done in British Columbia. Despite this, the extent of medication recycling in Canadian hospitals remains unclear in the literature. OBJECTIVE(S): To determine if Canadian hospitals recycle medications, provide an estimate of how much medication is recycled by dosage form, and identify medication recycling barriers through the distribution of a cross-sectional survey. METHODS: A nine-question survey was distributed to 171 hospital pharmacy departments across Canada that consented to complete the survey. The survey identified whether sites recycled unused medications, an estimate of how much is recycled based on dosage form, and barriers to recycling. KEY FINDINGS: Of 62 respondents, the majority indicated they do have medication recycling procedures; however, the frequency of recycling is suboptimal (30-50% of medications are not recycled), and not all medication types are always recycled. Individually packaged oral tablets were most often recycled, and oral liquid medications were least often recycled. Many multi-dose medications were not tamper-proofed. Most respondents selected "sanitization/infection control" and "resource constraint" as reasons for not recycling all medications. CONCLUSIONS: Among respondents, the proportion and type of unused medicines that are recycled varied. For sites that did not respond, this might suggest that medication recycling is not a priority. This could represent a missed opportunity to standardize practices and increase medication recycling in hospitals, both of which could represent a meaningful step towards responsible use of medications and reduction of negative impacts on human health and the environment.

How Patient-Centred Are Inhaler Device Choices? A Survey of Canadian Prescribers.

Background: The choice of inhaler device type can play a crucial role in managing asthma and chronic obstructive pulmonary disease (COPD). With various devices available, differences in choice and application may lead to confusion for both prescribers and patients. Furthermore, improper use of a device may lead to suboptimal or inadequate treatment. Objectives: The primary objective was to identify factors that prescribers consider when selecting an inhaler device for a patient. The secondary objective was to evaluate the rankings of these factors, including identification of which factors had greater importance and frequency for prescribers' choice of inhaler device for patients. Methods: A 10-question online survey was developed and distributed in late 2021 to prescribers (physicians, nurse practitioners, and pharmacists) in western Canada in an outpatient setting. Prescribers were asked to use their own words to describe the factors they considered important and were then asked to rank the stated factors in order of importance for 2 scenarios: an 83-year-old woman with COPD and a 21-year-old man with asthma. The results were examined qualitatively and quantitatively. Recurring themes were identified, and each response was categorized on the basis of its corresponding theme. Results: In all, 82 respondents completed the survey (yielding a total of 164 responses across the 2 scenarios). Overall, prescriber experience (84/164, 51%), cost (84/164, 51%), patient ease of use (59/164, 36%), and other patient considerations (49/164, 30%) were the factors most frequently mentioned. The prescriber's experience was most often mentioned as a factor for scenario 1 (COPD), whereas cost was most often mentioned for scenario 2 (asthma). In both scenarios, prescriber experience was the highest-ranked factor. Conclusions: When determining the appropriate type of inhaler device, respondents frequently prioritized their own experience, as well as cost and ease of use. However, many respondents ranked prescriber experience higher than all other factors.

Contexte: Le choix du type d'inhalateur peut jouer un rôle crucial dans la gestion de l'asthme et de la maladie pulmonaire obstructive chronique (MPOC). Étant donné la diversité des dispositifs disponibles, les différences de choix et d'application peuvent prêter à confusion tant pour les prescripteurs que pour les patients. De plus, la mauvaise utilisation d'un appareil peut conduire à un traitement sous-optimal ou inadéquat. Objectifs: L'objectif principal consistait à identifier les facteurs pris en compte par les prescripteurs lors de la sélection de l'inhalateur pour un patient. L'objectif secondaire consistait à évaluer le classement de ces facteurs, notamment l'identification des facteurs les plus importants et des inhalateurs les plus fréquemment choisis par les prescripteurs. Méthodes: Un sondage en ligne de 10 questions a été préparé et distribué fin 2021 aux prescripteurs (médecins, infirmières praticiennes et pharmaciens) de l'ouest du Canada en milieu ambulatoire. Les prescripteurs devaient, dans leurs propres mots, décrire les facteurs qui leur semblaient importants avant de les classer par ordre d'importance dans le cadre de deux scénarios : une femme de 83 ans atteinte de MPOC et un homme de 21 ans avec de l'asthme. Les résultats ont fait l'objet d'un examen qualitatif et quantitatif. Des thèmes récurrents ont été identifiés et chaque réponse a été catégorisée en fonction du thème correspondant. Résultats: Au total, 82 répondants ont répondu au sondage (total de 164 réponses dans les 2 scénarios). Dans l'ensemble, l'expérience du prescripteur (84/164, 51 %), le coût (84/164, 51 %), la facilité d'utilisation pour le patient (59/164, 36 %) et d'autres considérations en rapport avec le patient (49/164, 30 %) étaient les facteurs déterminants les plus fréquemment mentionnés. Pour le scénario 1 (MPOC), l'expérience du prescripteur était le facteur le plus souvent mentionné, alors que le coût l'était pour le scénario 2 (asthme). Dans les deux scénarios, l'expérience du prescripteur était le facteur le plus important. Conclusions: Lors de la détermination du type d'inhalateur approprié, les répondants ont souvent donné la priorité à leur expérience personnelle, ainsi qu'au coût et à la facilité d'utilisation. Cependant, de nombreux répondants ont accordé une note plus élevée à l'expérience du prescripteur qu'à d'autres facteurs.

Prescribing Portraits to Optimize Prescribing of Proton Pump Inhibitors in Long-Term Care: PPI-T STOP Study.

Background: Proton pump inhibitors (PPIs) are among the most commonly prescribed medications in Canada, particularly for older adults (at least 65 years of age). Overprescribing of long-term PPIs leads to health care system waste and is associated with adverse effects, including infections and fractures. The high prevalence of PPI prescribing in long-term care (LTC) facilities prompted an evaluation of systematic approaches to PPI deprescribing. Objective: To assess the impact of individualized prescribing portraits, a type of audit-and-feedback quality improvement intervention, on PPI deprescribing in the LTC setting. Methods: This prospective, nonblinded, uncontrolled, pre-post quality improvement study was conducted from December 2021 to April 2022 at a 126-bed LTC facility in Vancouver, British Columbia. A PPI prescribing portrait was developed for each prescriber (n = 5) at the LTC facility, containing the prescriber's personal PPI prescribing metrics as compared with those of their peers across all LTC facilities within the same health authority; an evidence summary for PPI deprescribing; and a personalized list of the prescriber's PPI-treated residents, along with their respective PPI indications and strategies for PPI deprescribing. Three months after the prescribers received their PPI prescribing portraits, the number and types of PPI deprescribing orders were recorded. Results: The implementation of prescribing portraits resulted in 17 (61%) of 28 PPI-treated residents receiving a deprescribing order by the end of the study period. Of the 28 PPI-treated residents, 20 were determined to be eligible for PPI deprescribing according to the evidence summary presented in the prescribing portrait; of these 20 residents, 16 (80%) appropriately received PPI deprescribing. Conclusions: Individualized prescribing portraits had the potential to increase evidence-based PPI deprescribing among LTC residents, beyond the extent of deprescribing previously achieved through standard of care.

Contexte: Les inhibiteurs de la pompe à protons (IPP) comptent parmi les médicaments les plus couramment prescrits au Canada, particulièrement chez les personnes âgées (au moins 65 ans). La prescription excessive d'IPP à long terme entraîne un gaspillage pour le système de santé et est associée à des effets indésirables, notamment des infections et des fractures. La prévalence élevée de la prescription d'IPP dans les établissements de soins de longue durée (SLD) a entraîné une évaluation des approches systématiques de déprescription des IPP. Objectif: Évaluer l'incidence des schémas de prescription individualisés, un type d'intervention d'amélioration de la qualité basée sur l'audit et la rétroaction, sur la déprescription des IPP dans les établissements de SLD. Méthodes: Cette étude prospective, sans insu et non contrôlée sur l'amélioration de la qualité pré-post a été menée entre décembre 2021 et avril 2022 dans un établissement de SLD de 126 lits à Vancouver, en Colombie-Britannique. Un schéma de prescription d'IPP a été élaboré pour chaque prescripteur (n = 5) de l'établissement de SLD, contenant les paramètres personnels de prescription d'IPP du prescripteur par rapport à ceux de ses pairs dans tous les établissements de SLD au sein de la même autorité sanitaire; un résumé des données probantes pour la déprescription des IPP; et une liste personnalisée des résidents du prescripteur traités par IPP, ainsi que, respectivement, leurs indications d'IPP pour la déprescription des IPP. Trois mois après la réception des schémas de prescription d'IPP des prescripteurs, le nombre et les types d'ordonnances de déprescription d'IPP ont été enregistrés. Résultats: La mise en œuvre de schémas de prescription a permis à 17 (61 %) des 28 résidents traités par IPP de recevoir une ordonnance de déprescription pendant la période d'étude. Sur les 28 résidents traités par IPP, 20 ont été jugés admissibles à la déprescription des IPP sur la base du résumé des données probantes présentées dans le schéma de prescription; sur ces 20 résidents, 16 (80 %) ont reçu de manière appropriée une déprescription d'IPP. Conclusions: Les schémas de prescription individualisés avaient le potentiel d'augmenter la déprescription d'IPP fondée sur des données probantes chez les résidents des établissements de SLD, au-delà de l'étendue de la déprescription précédemment atteinte grâce aux normes de soins.

Continuous versus intermittent infusions of antibiotics for the treatment of severe acute infections.

BACKGROUND: Intravenous broad-spectrum antibiotics are indicated for the treatment of severe infections. However, the emergence of infections caused by multi-drug resistant organisms in conjunction with a lack of novel antibiotics has prompted the investigation of alternative dosing strategies to improve clinical efficacy and tolerability. To optimise pharmacokinetic and pharmacodynamic antibiotic parameters, continuous antibiotic infusions have been compared to traditional intermittent antibiotic infusions. OBJECTIVES: To compare the clinical efficacy and safety of continuous intravenous administration of concentration-dependent and time-dependent antibiotics to traditional intermittent intravenous administration in adults with severe acute bacterial infections. SEARCH METHODS: The following electronic databases were searched in September 2012: The Cochrane Injuries Group Specialised Register, Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE (OvidSP), EMBASE (OvidSP), CINAHL, ISI Web of Science: Science Citation Index Expanded (SCI-EXPANDED), ISI Web of Science: Conference Proceedings Citation Index-Science (CPCI-S). The reference lists of all relevant material, the Internet and the trials registry www.clinicaltrials.gov for completed and ongoing trials were also searched. SELECTION CRITERIA: Randomized controlled trials in adults with a bacterial infection requiring intravenous antibiotic therapy comparing continuous versus intermittent infusions of antibiotics were included. Both time-dependent and concentration-dependent antibiotics were considered. DATA COLLECTION AND ANALYSIS: Three independent authors performed data extraction for the included studies. All data was cross-checked and disagreements resolved by consensus. An intention to treat analysis was conducted using a random-effects model. MAIN RESULTS: Twenty-nine studies met inclusion criteria with a combined total of over 1,600 patients. The majority of included studies were judged to be at unclear or high risk of bias with regard to randomisation sequence generation, allocation concealment, blinding, management of incomplete outcome data, selective outcome reporting, and other potential threats to validity. No studies were judged to be at low risk of bias for all methodological quality items assessed. There were no differences in all-cause mortality (n=1241, RR 0.89, 95% CI 0.67 - 1.20, p=0.45), infection recurrence (n=398, RR 1.22, 95% CI 0.35 - 4.19, p=0.76), clinical cure (n=975, RR 1.00, 95% CI 0.93 - 1.08, p=0.98), and superinfection post-therapy (n=813, RR 1.08, 95% CI 0.60 - 1.94, p=0.79). There were no differences in safety outcomes including adverse events (n=575, RR 1.02, 95% CI 0.94 - 1.12, p=0.63), serious adverse events (n=871, RR 1.36, 95% CI 0.80 - 2.30, p=0.26), and withdrawal due to adverse events (n=871, RR 2.03, 95% CI 0.52 - 7.95, p=0.31). A difference was observed in the subgroup analyses of clinical cure in septic versus non-septic patients, where intermittent antibiotic infusions were favoured for clinical cure in septic patients. However, this effect was not consistent between random-effects and fixed-effects analyses. No differences were found in sensitivity analyses conducted. AUTHORS' CONCLUSIONS: There were no differences in mortality, infection recurrence, clinical cure, superinfection post-therapy, and safety outcomes when comparing continuous infusions of intravenous antibiotics to traditional intermittent infusions of antibiotics. However, the wide confidence intervals suggest that beneficial or harmful effects cannot be ruled out for all outcomes. Therefore, the current evidence is insufficient to recommend the widespread adoption of continuous infusion antibiotics in the place of intermittent infusions of antibiotics. Further large prospective randomised trials, with consistent and complete reporting of clinical outcome measures, conducted with concurrent pharmacokinetic and pharmacodynamic studies in special populations are required to determine whether adoption of continuous antibiotic infusions is warranted in specific circumstances.

Intravenous immunoglobulin as adjuvant therapy for Wegener's granulomatosis.

BACKGROUND: Wegener's granulomatosis (WG) is a necrotizing small-vessel vasculitis that can affect any organ in the body but mainly affects the upper and lower respiratory tract, the kidneys, joints, skin and eyes. The current mainstay of remission induction therapy is systemic corticosteroids in combination with oral daily cyclophosphamide (CYC) which induces remission in 75% to 100% of cases. Although standard therapy is effective in inducing partial or complete remission, 50% of complete remissions are followed by at least one relapse. This is an update of a review first published in 2009. OBJECTIVES: To determine if intravenous immunoglobulin (IVIg) adjuvant therapy provides a therapeutic advantage over and above treatment with systemic corticosteroids in combination with immunosuppressants for the treatment of WG. SEARCH METHODS: For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched November 2012) and CENTRAL (2012, Issue 11). Trial databases were searched by the TSC for details of ongoing and unpublished studies. No date or language restrictions were applied. SELECTION CRITERIA: Randomized controlled trials (RCTs), or quasi RCTs, or randomized cross-over trials. Participants had to be adults with a confirmed diagnosis of WG. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed trial quality. Relative risk was used to analyze dichotomous variables, and mean difference (MD) was used to analyze continuous variables. MAIN RESULTS: We included one RCT with 34 participants who were randomly assigned to receive IVIg or placebo once daily in addition to azathioprine and prednisolone for remission maintenance. There were no significant differences between adjuvant IVIg and adjuvant placebo in mortality, serious adverse events, time to relapse, open-label rescue therapy, and infection rates. The fall in disease activity score, derived from patient-reported symptoms, was slightly greater in the IVIg group than in the placebo group at one month (MD 2.30; 95% Confidence interval (CI) 1.12 to 3.48, P < 0.01) and three months (MD 1.80; 95% CI 0.35 to 3.25, P = 0.01). There was a significant increase in total adverse events in the IVIg group (relative risk (RR) 3.50; 95% CI 1.44 to 8.48, P < 0.01). AUTHORS' CONCLUSIONS: There is insufficient evidence from one RCT that IVIg adjuvant therapy provides a therapeutic advantage compared with the combination of steroids and immunosuppressants for patients with WG. Given the high cost of IVIg (one dose at 2 g/kg for a 70 kg patient = $8,400), it should be limited to treat WG in the context of a well conducted RCT powered to detect patient-relevant outcomes.

Magnesium for alcohol withdrawal.

BACKGROUND: Patients have been given magnesium to treat or prevent alcohol withdrawal syndrome (AWS). Evidence to support this practice is limited, and is often based on the controversial link between hypomagnesaemia and AWS. OBJECTIVES: To assess the effects of magnesium for the prevention or treatment of AWS in hospitalised adults. SEARCH METHODS: We searched the Cochrane Drugs and Alcohol Group Register of Controlled Trials (August 2012), PubMed (from 1966 to August 2012 ), EMBASE (from 1988 to August 2012), CINAHL (from 1982 to March 2010), Web of Science (1965 to August 2012). We also carried out Internet searches. SELECTION CRITERIA: Randomised or quasi-randomised trials of magnesium for hospitalised adults with, or at risk for, acute alcohol withdrawal. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data with a standardised data extraction form, contacting the correspondence investigator if the necessary information was not available in the reports. Dichotomous outcomes were analysed by calculating the risk ratio (RR) for each trial, with the uncertainty in each result expressed with a 95% confidence interval (CI). Continuous outcomes were to be analysed by calculating the standardised mean difference (SMD) with 95% CI. For outcomes assessed by scales we compared and pooled the mean score differences from the end of treatment to baseline (post minus pre) in the experimental and control groups. MAIN RESULTS: Four trials involving 317 people met the inclusion criteria. Three trials studied oral magnesium, with doses ranging from 12.5 mmol/day to 20 mmol/day. One trial studied parenteral magnesium (16.24 mEq q6h for 24 hours). Each trial demonstrated a high risk of bias in at least one domain. There was significant clinical and methodological variation between trials.We found no study that measured all of the identified primary outcomes and met the objectives of this review. Only one trial measured clinical symptoms of seizure, delirium tremens or components of the Clinical Institute Withdrawal Assessment for Alcohol (CIWA) score. A single outcome (handgrip strength) in three trials (113 people), was amenable to meta-analysis. There was no significant increase in handgrip strength in the magnesium group (SMD 0.04; 95% CI -0.22 to 0.30). No clinically important changes in adverse events were reported. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine whether magnesium is beneficial or harmful for the treatment or prevention of alcohol withdrawal syndrome.

Recycling unused medications in hospitals is financially viable and good for the environment.

OBJECTIVES: Considerable pharmaceutical waste is generated in hospital settings which can be reduced by recycling of unused medications. We sought to determine the recycling practices as well as quantify the volume and the value of oral solid medications returned from nursing units to the pharmacy departments at three urban hospitals. METHODS: Unused oral solid medications were recycled at three sites and the net financial impact of this practice was calculated (cost recovered - labour costs). The results were extrapolated to all 21 hospitals within the health system. KEY FINDINGS: Recycling medications in 21 hospitals could divert ~461 000 units of medication from the incinerator, with an estimated net value of ~$415 000 per year. CONCLUSIONS: Recycling unused medications could save substantial amounts of money and reduce negative environmental impacts from disposal/incineration.

Hiding in Plain Sight: Quantifying Salbutamol and Ipratropium Inhaler Wastage in Hospitals.

Background: Previous studies have found significant inhaler wastage in the inpatient setting, which contributes to unnecessary health care expenditures. Wastage may involve inhalers available in automated dispensing cabinets (ADCs). Objectives: To evaluate whether salbutamol and ipratropium inhalers were unnecessarily withdrawn from ADCs for hospital inpatients. Methods: This cross-sectional study included patients from 16 health care facilities in British Columbia. ADC reports were run for the period August 2021 to January 2022 to identify salbutamol and ipratropium inhalers removed from ADCs. Results: Over the study period, 8.3% (2180/26 324) of salbutamol and ipratropium inhalers were withdrawn from ADCs unnecessarily for the same patient encounter within a 2-day timeframe, and another 1118 (4.2%) represented instances when multiple inhalers were withdrawn for the same patient at the same time. Overall, 12.5% (3298/26 324) of all salbutamol and ipratropium inhalers were withdrawn unnecessarily. The total cost of these inhalers was about $31 600 over the 6-month period. Conclusions: This evaluation revealed considerable wastage of inhalers, leading to wasted expenditures. Other health authorities should conduct similar analyses to determine whether similar problems exist in their settings.

Contexte: De précédentes études ont mis au jour un gaspillage important d'inhalateurs en milieu hospitalier, ce qui contribue à des dépenses de soins de santé inutiles. Ce gaspillage peut comprendre des inhalateurs disponibles dans des cabinet de distribution automatisé (CDA). Objectif: Évaluer si les inhalateurs de salbutamol et d'ipratropium ont été inutilement retirés des CDA pour les patients hospitalisés. Méthodes: Cette étude transversale comprenait des patients provenant de 16 établissements de soins de santé en Colombie-Britannique. Des rapports portant sur les CDA ont été générés pour la période d'août 2021 à janvier 2022 afin de recenser les inhalateurs de salbutamol et d'ipratropium qui ont été retirés des CDA. Résultats: Pendant la période de l'étude, 8,3 % (2180/26 324) des inhalateurs de salbutamol et d'ipratropium ont été inutilement retirés des CDA pour la même rencontre avec le patient dans une fenêtre de 2 jours, et dans le cas de 1118 (4,2 %) inhalateurs, plusieurs inhalateurs ont été retirées en même temps pour un même patient. Dans l'ensemble, 12,5 % (3298/26 324) de tous les inhalateurs de salbutamol et d'ipratropium ont été inutilement retirés. Le coût total de ces inhalateurs s'élevait à environ 31 600 $ sur une période de 6 mois. Conclusions: Cette évaluation a révélé un gaspillage considérable d'inhalateurs, ce qui entraîne des dépenses inutiles. D'autres autorités sanitaires devraient mener des analyses similaires pour savoir si des problèmes similaires se produisent dans leurs établissements.

Garlic for the prevention of cardiovascular morbidity and mortality in hypertensive patients.

BACKGROUND: Garlic is widely used by patients for its blood pressure lowering effects. A meta-analysis published in 2008 concluded that garlic consumption lowers blood pressure in hypertensive and normotensive patients. Therefore, it is important to review the currently available evidence to determine whether garlic may also have a beneficial role in the reduction of cardiovascular events and mortality rates in patients with hypertension. OBJECTIVES: To determine whether the use of garlic as monotherapy, in hypertensive patients, lowers the risk of cardiovascular morbidity and mortality compared to placebo. SEARCH METHODS: A systematic search for trials was conducted in the Cochrane Hypertension Group Specialised Register, CENTRAL, MEDLINE, EMBASE, AGRICOLA, AMED, and CINAHL up to November 2011. A hand search of reference lists of identified reviews was conducted. Experts in the area were also contacted to identify trials not found in the electronic search. Clinicaltrials.gov was searched for ongoing trials. SELECTION CRITERIA: Randomized, placebo-controlled trials of any garlic preparation versus placebo for the treatment of hypertension were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality using the risk of bias tool. Data synthesis and analysis was performed using RevMan 5. MAIN RESULTS: The search identified two randomized controlled trials for inclusion. One trial included 47 hypertensive patients and showed that garlic significantly reduces mean supine systolic blood pressure by 12 mmHg (95% CI 0.56 to 23.44 mmHg, p=0.04) and mean supine diastolic blood pressure by 9 mmHg (95% CI 2.49 to 15.51 mmHg, p=0.007) versus placebo. The authors state that garlic was "free from side effects" and that no serious side effects were reported. There were 3 cases "where a slight smell of garlic was noted."The second trial could not be meta-analysed as they did not report the number of people randomized to each treatment group. They did report that 200 mg of garlic powder given three times daily, in addition to hydrochlorothiazide-triamterene baseline therapy, produced a mean reduction of systolic blood pressure by 10-11 mmHg and of diastolic blood pressure by 6-8 mmHg versus placebo.Neither trial reported clinical outcomes and insufficient data was provided on adverse events. AUTHORS' CONCLUSIONS: There is insufficient evidence to determine if garlic provides a therapeutic advantage versus placebo in terms of reducing the risk of mortality and cardiovascular morbidity in patients diagnosed with hypertension. There is also insufficient evidence to determine the difference in withdrawals due to adverse events between patients treated with garlic or placebo.Based on 2 trials in 87 hypertensive patients, it appears that garlic reduces mean supine systolic and diastolic blood pressure by approximately 10-12 mmHg and 6-9 mmHg, respectively, over and above the effect of placebo but the confidence intervals for these effect estimates are not precise and this difference in blood pressure reduction falls within the known variability in blood pressure measurements. This makes it difficult to determine the true impact of garlic on lowering blood pressure.

Carnitine for fatigue in multiple sclerosis.

BACKGROUND: Fatigue is reported to occur in up to 92% of patients with multiple sclerosis (MS) and has been described as the most debilitating of all MS symptoms by 28% to 40% of MS patients. OBJECTIVES: To assess whether carnitine (enteral or intravenous) supplementation can improve the quality of life and reduce the symptoms of fatigue in patients with MS-related fatigue and to identify any adverse effects of carnitine when used for this purpose. SEARCH METHODS: A literature search was performed using Cochrane MS Group Trials Register (09 September 2011), Cochrane Central Register of Controlled Trials (CENTRAL) "The Cochrane Library 2011, issue 3", MEDLINE (PubMed) (1966-09 September 2011), EMBASE (1974-09 September 2011), and www.clinicaltrials.gov for ongoing trials retrieval. Reference lists of review articles and primary studies were also screened. A hand search of the abstract book of recent relevant conference symposia was also conducted. Personal contact with MS experts and a manufacturer (Source Naturals, United States) of carnitine formulation was contacted to determine if they knew of other clinical trials. No language restrictions were applied. SELECTION CRITERIA: Full reports of published and unpublished randomized controlled trials and quasi-randomized trials of any carnitine intervention in adults affected by multiple sclerosis with a clinical diagnosis of fatigue associated with multiple sclerosis were included. DATA COLLECTION AND ANALYSIS: Data from the eligible trials was extracted and coded using a standardized data extraction form and entered into RevMan 5. Discrepancies were to be resolved by discussion with a third reviewer, however this was not necessary.The quality items to be assessed were method of randomization, allocation concealment, blinding (participants, investigators, outcome assessors and data analysis), intention-to-treat analysis and completeness of follow up. MAIN RESULTS: The search identified one ongoing randomized, placebo-controlled, cross-over trial (expected completion 2013) and one completed randomized, active-comparator, cross-over trial. In the completed study, adult patients with relapsing-remitting and secondary progressive MS were exposed to both acetyl L-carnitine 2 grams daily and amantadine 200 mg daily The effects of carnitine on fatigue are unclear. There was no difference between carnitine and amantadine for the number of patients withdrawing from the study due to an adverse event (relative risk ratio 0.20; 95% confidence interval 0.03 to 1.55) and no patients experienced a serious adverse event in either treatment group. Mortality and quality of life were not reported. AUTHORS' CONCLUSIONS: There is insufficient evidence that carnitine for the treatment of MS-related fatigue offers a therapeutic advantage over placebo or active comparators. Results of the ongoing trial are eagerly anticipated in order to provide clarity.

Assessment of Intravenous versus Oral Antimicrobials in a Large Regional Health Authority.

Background: Many antimicrobials given by the intravenous (IV) route have oral (PO) formulations with high oral bioavailability. The advantages of using the PO rather than the IV formulation include lower risk of adverse reactions, shorter length of hospital stay, and lower health care costs. Objectives: The primary objective was to determine the proportions of patients who received the IV and PO formulations of antimicrobials with high oral bioavailability. The secondary objectives were to determine the proportion of patients who were eligible to receive PO antimicrobials from the start of treatment, the proportion who qualified for IV-to-PO step-down, and areas of improvement to increase use of PO antimicrobials. Methods: A retrospective chart review was conducted in hospitals in the Fraser Health Authority, British Columbia, between October 18, 2019, and March 5, 2020. Two hundred charts were randomly selected for patients who had received either azithromycin, ciprofloxacin, clindamycin, fluconazole, levofloxacin, linezolid, moxifloxacin, metronidazole, sulfamethoxazole-trimethoprim, or voriconazole. Results: Of the 200 patients, 124 (62.0%) received the PO formulations, while 76 (38.0%) received the IV formulations. Of the 76 patients receiving IV antimicrobials, 39 (51.3%; 95% confidence interval 44.7%-57.9%) were eligible to receive PO antimicrobials from the start of treatment or could have been stepped down from IV to PO administration. Conclusions: More than half of patients who received IV therapy were eligible to receive the PO formulation of antimicrobials known to have high oral bioavailability; relative to earlier studies, this proportion has not improved over time. This finding highlights the need for continued vigilance in encouraging the use of PO rather than IV formulations for hospitalized patients.

Contexte: De nombreux antimicrobiens administrés par voie intraveineuse (IV) ont des formulations orales (PO) avec une biodisponibilité orale élevée. Les avantages de l'utilisation de cette formulation plutôt que de la formulation IV comprennent un risque moins élevé d'effets indésirables, une durée d'hospitalisation plus courte et des coûts de soins de santé inférieurs. Objectifs: L'objectif principal visait à déterminer les proportions de patients ayant reçu les formulations IV et PO d'antimicrobiens à haute biodisponibilité orale. Les objectifs secondaires consistaient, quant à eux, à déterminer la proportion de patients pouvant recevoir des antimicrobiens par voie orale dès le début du traitement, la proportion de patients qualifiés pour passer de l'administration IV à l'administration par voie orale et les domaines d'amélioration pour augmenter l'utilisation des antimicrobiens par voie orale. Méthodes: Un examen rétrospectif des dossiers a été effectué dans les hôpitaux de la Fraser Health Authority, en Colombie-Britannique, entre le 18 octobre 2019 et le 5 mars 2020. Deux cents dossiers ont été sélectionnés au hasard pour les patients qui avaient reçu soit de l'azithromycine, de la ciprofloxacine, de la clindamycine, du fluconazole, de la lévofloxacine, du linézolide, de la moxifloxacine, du métronidazole, de la sulfaméthoxazole-triméthoprime ou du voriconazole. Résultats: Sur les 200 patients, 124 (62,0 %) ont reçu les formulations PO, tandis que 76 (38,0 %) ont reçu les formulations IV. Sur les 76 patients recevant des antimicrobiens par voie intraveineuse, 39 (51,3 %; intervalle de confiance à 95 % 44,7 % à 57,9 %) étaient admissibles pour recevoir des antimicrobiens par voie orale dès le début du traitement ou auraient pu passer de l'administration IV à l'administration par voie orale. Conclusions: Plus de la moitié des patients ayant reçu une thérapie IV étaient admissibles pour recevoir la formulation PO d'antimicrobiens connus pour avoir une biodisponibilité orale élevée; par rapport aux études antérieures, cette proportion ne s'est pas améliorée avec le temps. Cette découverte souligne la nécessité d'une vigilance continue pour encourager l'utilisation de formulations PO plutôt que IV pour les patients hospitalisés.