To STOPP or to START? Potentially inappropriate prescribing in older patients with falls and syncope.

OBJECTIVES: To investigate the prevalence of potentially inappropriate prescribing (PIP) according to the revised STOPP/START criteria in older patients with falls and syncope. STUDY DESIGN: We included consecutive patients with falls and syncope aged ≥65 years at the day clinic of the Northwest Clinics, the Netherlands, from 2011 to 2016. All medication use before and after the visit was retrospectively investigated using the revised STOPP/START criteria. MAIN OUTCOME MEASURES: The prevalence/occurrence of PIP before the visit, persistent PIP after the visit, and unaddressed persistent PIP not explained in the patient's chart. RESULTS: PIP was present in 98 % of 374 patients (mean age 80 (SD ±â€¯7) years; 69 % females). 1564 PIP occurrences were identified. 1015 occurrences persisted (in 91 % of patients). 690 occurrences (in 80 % of patients) were not explained in the patient's chart. The most frequent unaddressed persistent forms of PIP were prescriptions of vasodilator drugs for patients with orthostatic hypotension (16 %), and benzodiazepines for >4 weeks (10 %) or in fall patients (8 %), and omission of vitamin D (28 %), antihypertensive drugs (24 %), and antidepressants (17 %). 54 % of all medication changes were initiated for reasons beyond the scope of the STOPP/START criteria. CONCLUSIONS: Almost every patient in our study population suffered from PIP. In 80 %, PIP continued after the clinical visit, without an explanation in the patient's chart. The most frequent PIP concerned medication that increased the risk of falls or syncope, specifically vasodilator drugs and benzodiazepines. Physicians should be aware of PIP in older patients with falls and syncope. Further studies should investigate whether a structured medication review may improve clinical outcomes.

The Effect of Glycopyrrolate on Nocturnal Sialorrhea in Patients Using Clozapine: A Randomized, Crossover, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Nocturnal sialorrhea is one of the most frequent adverse events in clozapine treatment. Symptomatic management of sialorrhea usually consists of off-label treatment with anticholinergic agents. The aim of the current study is to evaluate the efficacy and safety of glycopyrrolate in patients using clozapine that experience sialorrhea. METHODS: In a double-blind randomized crossover trial, patients with nocturnal sialorrhea (n = 32) were randomized to treatment with glycopyrrolate 1 mg or placebo. This double-blinded phase was followed by an optional open label extension phase with glycopyrrolate 2 mg. Exposure periods consisted of 6 consecutive days and were separated with 1 washout week. The primary outcome was clinical improvement of nocturnal sialorrhea assessed by the Patient Global Impression of Improvement (PGI-I). RESULTS: The proportion of patients with a clinical improvement according to PGI-I did not significantly differ between 1 mg and placebo (18.8% vs 6.3%, P = 0.289); however, in patients using glycopyrrolate 2 mg once daily versus placebo, it did (43.5% vs 6.3%, P = 0.039). Glycopyrrolate was not associated with severe adverse events or worsening of cognitive adverse events. CONCLUSIONS: Glycopyrrolate 1 mg was not superior to placebo, whereas 2 mg showed a significant clinical improvement of nocturnal sialorrhea compared with placebo. Glycopyrrolate seemed to be a tolerable anticholinergic agent in the treatment of clozapine-associated sialorrhea.

Risk of New-Onset Diabetes After Long-Term Treatment With Clozapine in Comparison to Other Antipsychotics in Patients With Schizophrenia.

It has been suggested that clozapine has one of the largest diabetic effects of all atypical antipsychotics. To confirm these findings, we examined retrospectively the risk of new-onset diabetes in long-term clozapine treatment compared to treatment with other antipsychotics in a matched control population with schizophrenia or schizoaffective disorder. Ninety-four adult patients with schizophrenia or schizoaffective disorder who had been treated with clozapine for 5 years or longer were matched on age, diagnosis, and sex to 94 patients without any use of clozapine. The groups were followed up for as long as 20 years. The cumulative incidence of new detection of diabetes in the clozapine group was 22.3% (mean follow-up, 12.3 years; absolute risk difference, 6.3%; 95% confidence interval, -4.9% to 17.5%). An additional rigorous analysis of the 83 matched pairs with normal glucose measurement before end point showed a significant risk difference between the 2 groups (21.7% compared with 8.4%) but may have been biased against clozapine. We conclude that definitive evidence showing a clinically significant larger risk for new-onset diabetes after long-term treatment with clozapine in comparison to other antipsychotics is lacking.

QT interval prolongation in users of selective serotonin reuptake inhibitors in an elderly surgical population: a cross-sectional study.

OBJECTIVE: To investigate the association between the use of a selective serotonin reuptake inhibitor (SSRI) and the occurrence of QT interval prolongation in an elderly surgical population. METHOD: A cross-sectional study was conducted among patients (> 60 years) scheduled for outpatient preanesthesia evaluation in the period 2007 until 2012. The index group included elderly users of an SSRI. The reference group of nonusers of antidepressants was matched to the index group on sex and year of scheduled surgery (ratio, 1:1). The primary outcome was the occurrence of QT interval prolongation shown on electrocardiogram. The QT interval was corrected for heart rate (QTc interval). The secondary outcome was the duration of the QTc interval. The outcomes were adjusted for confounding by using regression techniques. RESULTS: The index and reference groups included 397 users of an SSRI and 397 nonusers, respectively. QTc interval prolongation occurred in 25 (6%) and 19 (5%) index and reference patients, respectively. After adjustment for confounding, users of an SSRI did not have a higher risk for QTc interval prolongation compared to nonusers: OR = 1.1 (95% CI, 0.5 to 2.0). The adjusted mean QTc interval length in users of an SSRI and nonusers was comparable (difference of 1.5 milliseconds [95% CI, -1.8 to 4.8]). Use of the most frequently used SSRIs citalopram and paroxetine was not associated with a higher risk of QTc interval prolongation nor with lengthening of the QTc interval duration. CONCLUSIONS: The use of an SSRI by elderly surgical patients was not associated with the occurrence of QT interval prolongation.

['Postoperative pain treatment' practice guideline revised]. / Herziene richtlijn 'Postoperatieve pijn'.

On the initiative of the Dutch Association of Anaesthesiologists, a multidisciplinary workgroup has revised the 2003 practice guideline on 'Postoperative pain treatment' for adults and children. The main reason for revision was the availability of new drugs and new methods of administration. The most important deviations from the previous edition are the following. The organisation of care has been amended according to the current themes of the Safety Management System in the Netherlands, and a prediction model for postoperative pain was added. The drugs oxycodone, S-ketamine, pregabalin, gabapentin and metamizole were added, as well as new methods of administration and techniques for preventing postoperative pain. This revised guideline is more conservative than the previous one in the choice of epidural analgesia. In patients with relative contraindications for epidural analgesia, peripheral and locoregional blocks or multimodal pain treatment are advised. In the case of postoperative nausea and vomiting, administration of dexamethasone, droperidol and 5-HT3-antagonists is recommended, preferably in combination. Non-medicinal treatment options are not recommended.

The effect of a preoperative erythropoietin protocol as part of a multifaceted blood management program in daily clinical practice (CME).

BACKGROUND: The effectiveness of a preoperative erythropoietin (EPO) protocol to reduce allogeneic blood transfusions (ABTs) in daily clinical practice has been insufficiently studied. This study evaluated the effect of such a protocol, as part of a multifaceted blood management program, in patients undergoing total hip arthroplasty (THA). STUDY DESIGN AND METHODS: This retrospective observational study was designed as an interrupted time series (1999-2010). The intervention was the introduction of an EPO protocol in THA patients in 2003. Patients were classified according to preoperative hemoglobin (Hb) level: 10 to 13 g/dL (eligible patients for EPO) and more than 13 g/dL. The primary outcome was the percentage of patients receiving an ABT. Segmented regression analysis was used to estimate changes in outcome after the intervention. RESULTS: A total of 4568 THA patients were included. The absolute reductions in ABTs after the intervention were 17% (95% confidence interval [CI], 6%-29%) for the total study population and 25% (95% CI, 11%-39%) and 8% (95% CI, -5% to 21%) for the Hb groups 10 to 13 and more than 13 g/dL, respectively. In the postintervention period, 46% of the eligible patients (Hb level, 10-13 g/dL) actually received EPO. The transfusion rate in the EPO group was lower compared to the non-EPO group: 14 and 50%, respectively (p < 0.01). CONCLUSION: Introduction of a preoperative EPO protocol reduced the transfusion rate in THA patients in daily clinical practice. The reduction must be seen as part of a multifaceted blood management program, in which increased awareness of blood transfusion contributes simultaneously and substantially to the reduction in transfusion rate.

Antidepressive treatment with monoamine oxidase inhibitors and the occurrence of intraoperative hemodynamic events: a retrospective observational cohort study.

OBJECTIVE: To investigate the occurrence of intraoperative hemodynamic events when antidepressive treatment with monoamine oxidase inhibitors (MAOIs) was continued during anesthesia. METHOD: A retrospective observational cohort study was conducted among patients who were admitted for elective surgery requiring anesthesia in 8 Dutch hospitals (2004-2010). The index group included current users of irreversible (tranylcypromine) and reversible (moclobemide) MAOIs. The reference group included a sample of nonusers matched to the index group on hospital, type and period of surgery, and type of anesthesia (ratio 1:3). The outcome of interest was the occurrence of the following intraoperative hemodynamic events: hypotension or hypertension and tachycardia or bradycardia. RESULTS: Approximately 280,000 surgical procedures were performed in the participating hospitals in the total observational period of 33 years. The index group included 26 and 25 users of tranylcypromine and moclobemide, respectively. The reference groups included 149 nonusers. Intraoperative hypotension occurred less frequently in users of tranylcypromine (46%) than in nonusers (73%) (P = .01). The occurrence of hypertension, bradycardia, and tachycardia during anesthesia was not different between users of tranylcypromine (27%, 50%, and 12%, respectively) and those in the reference group (35%, 61%, and 26%, respectively). The occurrence of hypotension, hypertension, bradycardia, and tachycardia was not different between users of moclobemide and the reference group. CONCLUSIONS: Severe adverse hemodynamic events, such as hypertension and tachycardia, did not occur more frequently in users of both the irreversible MAOI tranylcypromine and the reversible MAO-A inhibitor moclobemide compared to nonusers. These findings suggest that there is no longer much justification to discontinue these MAOIs before surgery, with the considerable risk of compromising patients' psychiatric status.

Selective serotonin reuptake inhibitors and intraoperative blood pressure.

BACKGROUND: The influence of selective serotonin reuptake inhibitors (SSRIs) on blood pressure is poorly understood. We hypothesized that if SSRIs have an influence on blood pressure, this might become manifest in changes in intraoperative blood pressure. We aimed to study the association between perioperative use of SSRIs and changes in intraoperative blood pressure by measuring the occurrence of intraoperative hyper- and hypotension. METHODS: We conducted a retrospective observational follow-up study among patients who underwent elective primary total hip arthroplasty. The index group included users of SSRIs. The reference group included a random sample (ratio 1:3) of nonusers of an antidepressant agent. The outcome was the occurrence of intraoperative hypo- and hypertensive episodes (number, mean and total duration, and area under the curve (AUC)). The outcome was adjusted for confounding factors using regression techniques. RESULTS: The index group included 20 users of an SSRI. The reference group included 60 nonusers. Users of SSRIs showed fewer intraoperative hypotensive episodes, a shorter mean and total duration, and a smaller AUC when compared to the reference group. After adjustment for confounders, SSRI use was associated with a significantly shorter total duration of hypotension: mean difference of -29.4 min (95% confidence interval (CI) -50.4 to -8.3). Two users of an SSRI and two patients in the reference group had a hypertensive episode. CONCLUSIONS: Continuation of treatment with SSRIs before surgery was associated with a briefer duration of intraoperative hypotension.

Use of serotonergic antidepressants and bleeding risk in orthopedic patients.

BACKGROUND: Selective serotonin reuptake inhibitors have been associated with an increased bleeding tendency. Information on the impact of a possible impaired hemostasis associated with the perioperative use of selective serotonin reuptake inhibitors is limited. This study aimed to determine the association between the perioperative use of selective serotonin reuptake inhibitors and the amount of blood loss during surgery and perioperative transfusion requirements. METHODS: The authors conducted a retrospective cohort study among patients who underwent elective primary total hip arthroplasty in two hospitals from the period of July 1, 2004 until July 1, 2008. The index group included all users of both serotonergic and nonserotonergic antidepressants. The reference group included a random sample (ratio 1:3) of nonusers. The primary outcome was the amount of intraoperative blood loss. The requirement for blood transfusion was a secondary outcome. The outcomes were adjusted for confounding factors (comorbidity and comedication) using regression techniques. RESULTS: The index group included 66 users of serotonergic and 29 users of nonserotonergic antidepressants, and the reference group included 285 patients. After adjustment for confounding factors, mean blood loss during surgery was significantly higher in the users of selective serotonin reuptake inhibitors when compared with the reference group: 95 ml (95% CI 9-181). Mean blood loss in the users of nonserotonergic antidepressants did not differ from the reference group. Users of antidepressants did not have a higher risk for transfusion. CONCLUSIONS: Patients undergoing total hip arthroplasty who continue the use of serotonergic antidepressants show a significantly higher, but clinically unimportant, intraoperative blood loss, without an increase in perioperative transfusion requirements.

[Pain treatment following knee and hip replacement surgery]. / Pijnbehandeling na heup- of knievervangende operatie.

OBJECTIVE: To gain insight into the outcomes of postoperative pain treatment using patient-controlled intravenous analgesia (PCIA) with morphine and oral analgesics after total hip or knee arthroplasty (THA or TKA). DESIGN: Prospective observational study. METHOD: In 2006-2007, 154 THA and 110 TKA patients who underwent arthroplasty at the Medical Centre Alkmaar were included in this study. Postoperative pain treatment consisted of a PCIA pump with morphine and oral analgesics. Primary endpoints were effectiveness of pain treatment and the incidence of side effects. RESULTS: After THA, 65% of the patients had an acceptable pain score at rest on the day of surgery (day 0), increasing to >95% from 2 days after the operation onwards. On day 1, 43% had an acceptable pain score during movement, increasing to >90% from day 2 onwards. On day 0, nausea occurred in 24% and vomiting in 25% of patients; on day 1, these figures were 21% and 29% respectively. After TKA, 45% of the patients had acceptable pain at rest on day 0, increasing to >or=95% from day 3 onwards. On day 1, pain during movement was acceptable in 24% of the patients, increasing to 80% on day 4. On day 0 following TKA nausea occurred in 37% and vomiting in 39% of patients; on day 1, these figures were 26% and 23%, respectively. CONCLUSION: In view of the somewhat disappointing effectiveness and the side effects of a PCIA pump with morphine and oral analgesics, adjustments in the treatment of pain following THA and TKA are required. The greatest improvement can be realised on the day of surgery and the first postoperative day.