THE ECONOMIC PLIGHT OF THE FIFTH TOKUGAWA SHOGUN

This article discusses the economic conditions at the accession of the fifth Tokugawa Shogun Tsunayoshi in 1680. It is argued that Tsunayoshi was the first Tokugawa ruler who inherited a government without substantial financial reserves, but at the same time had to take responsibility for a wide range of obligations his predecessors had contracted

Severe toxic damage to the rabbit spinal cord after intrathecal administration of preservative-free S(+)-ketamine

BACKGROUND: Ketamine and S(+)-ketamine have been advocated for neuraxial use in the management of postoperative pain and severe intractable pain syndromes unresponsive to opioid escalation. Although clinical experience has accumulated with S(+)-ketamine, safety data on toxicity in the central nervous system after neuraxial administration of S(+)-ketamine are conflicting. In this study, neurologic and toxicologic effects on the spinal cord from repeated daily intrathecal administration of commercially available, preservative-free S(+)-ketamine were evaluated against placebo in a randomized, blinded design. METHODS: Eighteen white New Zealand rabbits were assigned to two groups receiving either 0.5 ml intrathecal S(+)-ketamine, 0.5% solution (12 rabbits), or 0.5 ml saline (6 rabbits) once a day for 7 consecutive days. During general anesthesia, an intrathecal catheter was placed between the fifth and sixth spinous processes (lumbar). Neurologic (according to Tarlov criteria) and histopathologic assessments were performed after 7 days of treatment. RESULTS: Postmortem investigation of the spinal cord and nerve roots revealed histopathologic lesions suggestive of toxic damage in 11 rabbits, from the group of 12 animals receiving S(+)-ketamine. These results were significantly different compared with 5 control animals (no histologic changes observed). There was no significant difference in neurologic status between the two groups after 7 days of intrathecal treatment. CONCLUSIONS: The authors conclude that repeated intrathecal administration of preservative-free S(+)-ketamine in a clinically relevant concentration and dosage has, considering the extent and severity of the lesions, a toxic effect on the central nervous system of rabbit

The impact of mental state altering medications on preventable falls after total hip or total knee arthroplasty: a systematic review and meta-analysis

Abstract Background Joint replacement surgery of the lower extremities are common procedures in elderly persons who are at increased risk of postoperative falls. The use of mental state altering medications, such as opioids, antidepressants or benzodiazepines, can further contribute to impaired balance and risk of falls. The objective of the current systematic review was to evaluate the risk of the use of mental state altering medications on postoperative falls in patients undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA). Methods A comprehensive search of Medline, Embase and Cochrane Controlled Trials Register was conducted from 1 October 1975 to 1 September 2021. The search was repeated in may 2023 and conducted from 1 October 1975 to 1 June 2023. Clinical trials that evaluated the risk of medication on postoperative THA and TKA falls were eligible for inclusion. Articles were evaluated independently by two researchers for risk of bias using the Newcastle-Ottawa Scale. A meta-analysis was performed to determine the potential effect of postoperative use of mental state altering medications on the risk of falls. Lastly, a qualitative synthesis was conducted for preoperative mental state altering medications use. Results Seven cohort studies were included, of which five studies focussed on the postoperative use of mental state altering medications and two investigated the preoperative use. Meta-analysis was performed for the postoperative mental state altering medications use. The postoperative use of mental state altering medications was associated with fall incidents (OR: 1.81; 95% CI: 1.04; 3.17) (p  6 months was associated with a higher risk of fall incidents, whereas a preoperative opioid prescription up to 3 months before a major arthroplasty had a similar risk as opioid-naïve patients. Conclusions The postoperative use of mental state altering medications increases the risk of postoperative falls after THA and TKA. Prior to surgery, orthopaedic surgeons and anaesthesiologists should be aware of the associated risks in order to prevent postoperative falls and associated injuries

Treatment of acute sciatica with transforaminal epidural corticosteroids and local anesthetic: Design of a randomized controlled trial

Background: Transforaminal epidural injections with steroids (TESI) are used increasingly for patients with sciatica. However there is much debate about their safety and effectiveness. It is important to identify patients that benefit most from TESI and only few trials have yet evaluated the effects in patients with acute sciatica. Methods: We describe a prospective, randomized controlled trial (RCT), with the aim to evaluate the hypothesis that TESI plus Levobupivacaine (TESI-plus) added to oral pain medication is more effective compared to pain medication alone or compared to transforaminal injection with a local anesthetic of short duration among patients with acute sciatica. We will recruit a total of 264 patients with sciatica (<8 weeks) caused by a herniated disc, from two clinical sites. Participants are randomly assigned one of three study groups: 1) oral pain medication (control group), 2) oral pain medication and TESI-plus (intervention group one), 3) oral pain medication and transforaminal epidural injection (TEI) with Levobupivaine and saline solution (intervention group two). Primary outcomes are functional status (Roland-Morris Disability Questionnaire), pain intensity for both leg and back, (100 mm visual analogous scale (VAS)), and global perceived recovery (GPR, reported on a 7-point Likert scale, dichotomized into 'recovered' and 'not recovered'). The secondary outcomes are health-related quality of life (EQ5D-5 L) and patient satisfaction (7-point Likert scale). We will also collect information on healthcare utilization and costs, to perform an economic evaluation. All outcomes are measured at three and six weeks, three and six months after randomization. We defined a minimal clinically relevant difference between groups as a difference between both intervention groups and the control group of 20 points for pain (100-point VAS), four points for functional status (24-point RDQ) and a 20% difference on dichotomized GPR (recovered versus not recovered). Discussion: A clinically relevant outcome in favor of TESI-plus implies that future patients with acute sciatica should be recommended TESI-plus within the first few weeks rather than being treated with pain medication alone in order to relieve pain and improve their functioning. In case of a negative result (no relevant differences in outcome between the three study arms), pain medication will remain the mainstay of treatment in the acute stages of sciatica. Trial registration: Dutch National trial register: NTR4457 (March, 6th, 2014