The effect of intrathecal bupivacaine/morphine on quality of recovery in robot-assisted radical prostatectomy: a randomised controlled trial.

Robot-assisted radical prostatectomy causes discomfort in the immediate postoperative period. This randomised controlled trial investigated if intrathecal bupivacaine/morphine, in addition to general anaesthesia, could be beneficial for the postoperative quality of recovery. One hundred and fifty-five patients were randomly allocated to an intervention group that received intrathecal 12.5 mg bupivacaine/300 µg morphine (20% dose reduction in patients > 75 years) or a control group receiving a subcutaneous sham injection and an intravenous loading dose of 0.1 mg.kg-1 morphine. Both groups received standardised general anaesthesia and the same postoperative analgesic regimen. The primary outcome was a decrease in the Quality of Recovery-15 (QoR-15) questionnaire score on postoperative day 1. The intervention group (n = 76) had less reduction in QoR-15 on postoperative day 1; median (IQR [range]) 10% (1-8 [-60% to 50%]) vs. 13% (5-24 [-6% to 50%]), p = 0.019, and used less morphine during the admission; 2 mg (1-7 [0-41 mg]) vs. 15 mg (12-20 [8-61 mg]), p < 0.001. Furthermore, they perceived lower pain scores during exertion; numeric rating scale (NRS) 3 (1-6 [0-9]) vs. 5 (3-7 [0-9]), p = 0.001; less bladder spasms (NRS 1 (0-2 [0-10]) vs. 2 (0-5 [0-10]), p = 0.001 and less sedation; NRS 2 (0-3 [0-10]) vs. 3 (2-6 [0-10]), p = 0.005. Moreover, the intervention group used less rescue medication. Pruritus was more severe in the intervention group; NRS 4 (1-7 [0-10]) vs. 0 (0-1 [0-10]), p = 0.000. We conclude that despite a modest increase in the incidence of pruritus, multimodal pain management with intrathecal bupivacaine/morphine remains a viable option for robot-assisted radical prostatectomy.

Beware of thermal epiglottis! A case report describing 'teapot syndrome'.

BACKGROUND: The type of scalding injury known as 'teapot syndrome', where hot liquid is grabbed by the child with the aim of ingestion and falls over a child causing burns on the face, upper thorax and arms, is known to cause peri-oral and facial oedema. Thermal epiglottitis following scalds to face, neck and thorax is rare and can occur even in absence of ingestion of a damaging agent or intraoral burns, Awareness of the possibility of thermal epiglottitis, also in scald burns, is imperative to ensure prompt airway protection. CASE PRESENTATION: We report the case of a child with thermal epiglottitis after a scalding burn from boiling milk resulting in mixed deep burns of the face, neck and chest, but no history of ingestion. Upon presentation there was a progressive stridor and signs of respiratory distress requiring intubation. Laryngoscopy revealed epiglottis oedema, confirming the diagnosis of thermal epiglottitis. Final extubation took place 5 days after initial burn. CONCLUSIONS: Thermal epiglottitis following scalds to face, neck and thorax is rare and can occur even in absence of ingestion and intra-oral damage. Burns to the peri-oral area should raise suspicion of additional damage to oral cavity and supraglottic structures, even in absence of intra-oral injury or initial respiratory distress. Awareness of the occurrence of thermal epiglottitis in absence of intra-oral injury is important to diagnose impending upper airway obstruction requiring intubation.

Effect of holding a racket on propulsion technique of wheelchair tennis players.

The purpose of this study was to determine possible differences in propulsion technique between propelling the wheelchair with and without a racket in the hand. Eight experienced wheelchair tennis players performed three submaximal exercise tests and six sprint tests on a wheelchair ergometer. Torque and velocity were measured during the tests and power output and timing variables were calculated. Differences between the conditions with and without racket were analyzed. When propelling with the racket, the racket side showed a significantly lower push time (P = 0.03), lower percentage push time (P = 0.001), shorter contact angle (P < 0.001), more power loss before (P = 0.006) and after (P = 0.001) the push, a higher peak (P = 0.009) and mean (P = 0.005) power output during the push, and a lower mean overall velocity (P = 0.03). When the same hand is compared when propelling with and without racket or when the sprint data were analyzed, similar significant differences were found. Propelling the wheelchair while holding a racket has negative effects on the propulsion technique and may lead to injuries of the upper extremity. The longer time needed to couple the hand with the racket to the rim leads to higher power losses and subsequently higher power output generation during the shorter push phase.

Dynamic Variation in Sexual Contact Rates in a Cohort of HIV-Negative Gay Men.

Human immunodeficiency virus (HIV) transmission models that include variability in sexual behavior over time have shown increased incidence, prevalence, and acute-state transmission rates for a given population risk profile. This raises the question of whether dynamic variation in individual sexual behavior is a real phenomenon that can be observed and measured. To study this dynamic variation, we developed a model incorporating heterogeneity in both between-person and within-person sexual contact patterns. Using novel methodology that we call iterated filtering for longitudinal data, we fitted this model by maximum likelihood to longitudinal survey data from the Centers for Disease Control and Prevention's Collaborative HIV Seroincidence Study (1992-1995). We found evidence for individual heterogeneity in sexual behavior over time. We simulated an epidemic process and found that inclusion of empirically measured levels of dynamic variation in individual-level sexual behavior brought the theoretical predictions of HIV incidence into closer alignment with reality given the measured per-act probabilities of transmission. The methods developed here provide a framework for quantifying variation in sexual behaviors that helps in understanding the HIV epidemic among gay men.

The effect of propidium monoazide treatment on the measured bacterial composition of clinical samples after the use of a mouthwash.

OBJECTIVES: The use of an anti-microbial mouthwash results not only in a reduction of the number of viable cells in dental plaque but potentially also in a shift in the oral microbiome. DNA-based techniques may be appropriate to monitor these shifts, but these techniques amplify DNA from both dead and living cells. Propidium monoazide (PMA) has been used to overcome this problem, by preventing the amplification of DNA from membrane-damaged cells. The aim of this study was to evaluate the use of PMA when measuring compositional shifts in clinical samples after mouthwash use. MATERIALS AND METHODS: On two consecutive days, baseline samples from buccal surfaces, tongue, and saliva were obtained from six volunteers, after which they used a mouthwash (Meridol, GABA, Switzerland) twice daily for 14 days. Subsequently similar samples were obtained on two consecutive days. The microbial composition of the samples, with or without ex vivo PMA treatment, was assessed with 16S rRNA gene amplicon sequencing. RESULTS: Data showed a clear effect of mouthwash usage on the tongue and saliva samples. PMA treatment enhanced the observed differences only for the saliva samples. Mouthwash treatments did not affect the composition of the plaque samples irrespective of the use of PMA. CONCLUSION: The necessity to use a PMA treatment to block the DNA from dead cells in clinical studies aimed at measuring compositional shifts after the use of a mouthwash is limited to salivary samples. CLINICAL RELEVANCE: Measuring shifts in the oral microbiome could be hampered by the presence of DNA from dead cells.

The effects of propidium monoazide treatment on the measured composition of polymicrobial biofilms after treatment with chlorhexidine.

BACKGROUND: The treatment of polymicrobial biofilms with antimicrobial compounds results in not only an overall loss of viability, but also compositional shifts. While DNA-based technologies may be more appropriate for the assessment of bacterial composition than culturing, these techniques amplify DNA from both live and dead cells. Propidium monoazide (PMA) has been used to discriminate between live and dead cells by blocking the DNA from membrane-damaged cells from being amplified. AIM: This study evaluated the use of PMA in a saliva-derived polymicrobial biofilm model subjected to a single chlorhexidine (CHX) treatment. MATERIALS AND METHODS: The effects of PMA on viable cells were tested using both untreated and PMA-treated saliva as an inoculum. Viability was determined by plate counts, metabolic activity was determined by lactic acid production, and biofilm composition was assessed by 16S rRNA gene amplicon sequencing. RESULTS: Exposure to a 0.2% CHX rinse (meridol® perio) reduced the viability and metabolic activity of 48-hour biofilms. The shift in biofilm composition observed after the CHX exposure was enhanced after a post-rinse PMA treatment. PMA treatment had a small effect on the measured composition of water-rinsed biofilms. Treating saliva with PMA reduced bacterial viability and shifted the bacterial composition of saliva and saliva-derived biofilms. CONCLUSION: The removal of DNA from non-viable cells with PMA treatment was shown to elicit an improvement in the detection of shifts in in vitro polymicrobial biofilms after antimicrobial treatment. However, PMA also influenced the ability of cells to grow, indicating that PMA should be used with caution.

Efficacy of tranexamic acid versus placebo in reducing blood loss during burn excisional surgery: a multi-center, double-blind, parallel, randomized placebo-controlled clinical trial (TRANEX).

BACKGROUND: Despite an increase in knowledge, blood loss during burn excisional surgery remains a major challenge and is an independent predictor of mortality. During burn surgery, limited measures are available to control the bleeding. Increased fibrinolysis could be one of the contributing factors of blood loss during burn excisional surgery. Tranexamic acid inhibits the fibrinolytic response, and a small body of evidence shows positive effects of tranexamic acid on the volume of blood loss. METHODS: The main objectives of this study are twofold, (1) to investigate whether tranexamic acid reduces blood loss and (2) to investigate the changes in coagulation after burn trauma and during burn excisional surgery. This study is a multicenter double-blind randomized clinical trial in patients scheduled for burn excisional surgery within the Dutch burn centers. All adult patients scheduled for burn surgery with an expected blood loss of ≥ 250 are eligible for inclusion in this study. The study is powered on a blood loss reduction of 25% in the intervention group. In total, 95 subjects will be included. The intervention group will receive 1500 mg tranexamic acid versus placebo in the other group. Primary endpoint is reduction of blood loss. Secondary endpoints include occurrence of fibrinolysis during surgery, graft take of the split skin graft, and differences in coagulation and blood clot formation. DISCUSSION: This protocol of a randomized controlled trial aims to investigate the efficacy of tranexamic acid in reducing blood loss during burn excisional surgery. Furthermore, this study aims to clarify the coagulation status after burn trauma and during the surgical process. TRIAL REGISTRATION: EudraCT: 2020-005405-10; ClinicalTrial.gov: NCT05507983 (retrospectively registered in August 2022, inclusion started in December 2021).

[Bell's palsy: a broad differential diagnosisHouse-Brackmann-schaal]. / Bellse parese: een brede differentiaaldiagnose.

Peripheral facial palsy is a common clinical symptom and is most often caused by Bell's palsy. The pathogenesis is largely unknown, but inflammation of the facial nerve, possibly after a viral infection, may play a role. Bell's palsy has a monophasic course with usually - but not always - a good recovery. Even though Bell's palsy exhibits clear clinical features, in clinical practice diagnosis and choice of treatment remain difficult and other causes of an isolated facial palsy may easily be overlooked. Score INormale functie van aangezicht op alle gebieden Score II Globaal: lichte zwakte bij nauwkeurig onderzoek; mogelijk zeer lichte synkinesieën. In rust: normale symmetrie en tonus. Motoriek: - Voorhoofd: matig tot goede functie. - Oog: volledige sluiting met minimale inspanning. - Mond: lichte asymmetrie. Score IIIGlobaal: duidelijke, maar niet-ontsierend verschil tussen twee zijdes; opvallende, maar geen ernstige synkinesieën, contracturen of hemifacialisspasmen. In rust: normale symmetrie en tonus. Motoriek: - Voorhoofd: lichte tot matige beweging. - Oog: volledige sluiting met inspanning. - Mond: lichte zwakte met maximale inspanning. Score IV Globaal: duidelijke zwakte of ontsierende asymmetrie. In rust: normale symmetrie en tonus. Motoriek: - Voorhoofd: geen. - Oog: onvolledige sluiting. - Mond: asymmetrie met maximale inspanning. Score V Globaal: nauwelijks waarneembare beweging. In rust: asymmetrie. Motoriek: - Voorhoofd: geen. - Oog: onvolledige sluiting. - Mond: lichte beweging. Score VI Geen beweging.

[Bell's palsy: a broad differential diagnosis]. / Bellse parese: een brede differentiaaldiagnose.

Peripheral facial palsy is a common clinical symptom and is most often caused by Bell's palsy. The pathogenesis is largely unknown, but inflammation of the facial nerve, possibly after a viral infection, may play a role. Bell's palsy has a monophasic course with usually - but not always - a good recovery. Even though Bell's palsy exhibits clear clinical features, in clinical practice diagnosis and choice of treatment remain difficult and other causes of an isolated facial palsy may easily be overlooked.

Quality of recovery after day care surgery with app-controlled remote monitoring: study protocol for a randomized controlled trial.

BACKGROUND: The majority of surgical interventions are performed in day care and patients are discharged after the first critical postoperative period. At home, patients have limited options to contact healthcare providers in the hospital in case of severe pain and nausea. A smartphone application for patients to self-record pain and nausea when at home after day care surgery might improve patient's recovery. Currently patient experiences with smartphone applications are promising; however, we do not know whether remote monitoring with such an application also improves the patient's recovery. This study aims to evaluate the experienced quality of recovery after day care surgery between patients provided with the smartphone application for remote monitoring and patients receiving standard care without remote monitoring. METHODS: This non-blinded randomized controlled trial with mixed methods design will include 310 adult patients scheduled for day care surgery. The intervention group receives the smartphone application with text message function for remote monitoring that enables patients to record pain and nausea. An anaesthesia professional trained in empathetic communication, who will contact the patient in case of severe pain or nausea, performs daily monitoring. The control group receives standard care, with post-discharge verbal and paper instructions. The main study endpoint is the difference in perceived quality of recovery, measured with the QoR-15 questionnaire on the 7th day after day care surgery. Secondary endpoints are the overall score on the Quality of Recovery-15 at day 1, 4 and 7-post discharge, the perceived quality of hospital aftercare and experienced psychological effects of remote monitoring during postoperative recovery from day care surgery. DISCUSSION: This study will investigate if facilitating patients and healthcare professionals with a tool for accessible and empathetic communication might lead to an improved quality of the postoperative recovery period. TRIAL REGISTRATION: The 'Quality of recovery after day care surgery with app-controlled remote monitoring: a randomized controlled trial' is approved and registered on 23 February 2022 by Research Ethics Committees United with registration number R21.076/NL78144.100.21. The protocol NL78144.100.21, 'Quality of recovery after day care surgery with app-controlled remote monitoring: a randomized controlled trial', is registered at the ClinicalTrials.gov public website (registration date 16 February 2022; NCT05244772).

Pulmonary inflammation promoted by type-2 dendritic cells is a feature of human and murine schistosomiasis.

Schistosomiasis is a parasitic disease affecting over 200 million people in multiple organs, including the lungs. Despite this, there is little understanding of pulmonary immune responses during schistosomiasis. Here, we show type-2 dominated lung immune responses in both patent (egg producing) and pre-patent (larval lung migration) murine Schistosoma mansoni (S. mansoni) infection. Human pre-patent S. mansoni infection pulmonary (sputum) samples revealed a mixed type-1/type-2 inflammatory cytokine profile, whilst a case-control study showed no significant pulmonary cytokine changes in endemic patent infection. However, schistosomiasis induced expansion of pulmonary type-2 conventional dendritic cells (cDC2s) in human and murine hosts, at both infection stages. Further, cDC2s were required for type-2 pulmonary inflammation in murine pre-patent or patent infection. These data elevate our fundamental understanding of pulmonary immune responses during schistosomiasis, which may be important for future vaccine design, as well as for understanding links between schistosomiasis and other lung diseases.

[Hyperkalemia due to low-molecular-weight heparin]. / Hyperkaliëmie bij laag-molecuulgewicht heparine.

BACKGROUND: The cause of hyperkalemia is frequently iatrogenic. Patient's prescriptions should therefore be checked in the analysis of the hyperkalemia. Low-molecular-weight heparin is not often suspected to cause this. CASE DESCRIPTION: A 64-year-old man, hospitalized because of a complicated clinical course of pancreatitis, developed an acute severe hyperkalemia. Further analysis was susceptive for hypoaldosteronism, which was confirmed with biochemical testing. The only drug that could cause hyperkalemia in this case was nadroparin, which was prescribed because of vena lienalis and a superior mesenteric vein thrombosis. A rechallenge with nadroparin showed a rapid rise in serum potassium, confirming our suspicion. CONCLUSION: In the diagnostic work-up of hyperkalemia, hypoaldosteronism should be considered in patients using LMWH. In particular when other risk factors for hyperkalemia are present, monitoring of potassium could be advised in patients receiving these agents.

'Why, why did you have me treated?': the psychotic experience in a literary narrative.

In this paper, the authors suggest an approach that may be helpful in teaching medical humanities to medical students. In the context of an honours class on medicine and literature, students (1) read a novel on an illness, (2) interviewed a patient with the medical condition described in the novel and (3) wrote an essay on the biomedical, narrative and literary aspects of these sources of information. The authors compared the story of Chekhov's literary protagonist Kovrin in The Black Monk with the personal story of patient H., who was diagnosed with schizophrenia. The narratives of the two patients were compared, based on Chekhov's literary narrative and the narrative of the patient. Both patients appeared to somehow regret losing their symptoms, following various psychiatric treatments. Both narratives show the ambivalence between the gain and loss that adequate psychiatric treatment may bring. Studying novels and other literary sources may help in understanding the story of the patient better, with associated improvements in various aspects of medical outcome. Reading literary fiction may help to increase an understanding of patients' emotions, experiences, cognitions and perspectives. It may also reduce the emotional distance between the self and the patient. The educational approach that was explored in the authors' honours class may be helpful to others when developing methods for teaching medical humanities to (medical) students.

Continuous erector spinae plane block versus thoracic epidural analgesia in video-assisted thoracic surgery: a study protocol for a prospective randomized open label non-inferiority trial.

BACKGROUND: Thoracic epidural analgesia is considered the gold standard for pain relief in video-assisted thoracoscopic surgery. This neuraxial technique blocks pain sensation by injecting a local anesthetic agent in the epidural space near the spinal cord to block spinal nerve roots. Recently, the erector spinae plane block has been introduced as a practical alternative to the thoracic epidural. This interfascial regional anesthesia technique interrupts pain sensation by injecting a local anesthetic agent in between the muscular layers of the thoracic wall. Several case series and three RCTs described it as an effective pain management technique in video-assisted thoracoscopic surgery (Scimia et al., Reg Anesth Pain Med 42:537, 2017; Adhikary et al., Indian J Anaesth 62:75-8, 2018; Kim, A randomized controlled trial comparing continuous erector spinae plane block with thoracic epidural analgesia for postoperative pain management in video-assisted thoracic surgery, n.d.; Yao et al., J Clin Anesth 63:109783, 2020; Ciftci et al., J Cardiothorac Vasc Anesth 34:444-9, 2020). The objective of this study is to test the hypothesis that a continuous erector spinae plane block incorporated into an opioid-based systemic multimodal analgesia regimen is non-inferior in terms of the quality of postoperative recovery compared to continuous thoracic epidural local anesthetic-opioid analgesia in patients undergoing elective unilateral video-assisted thoracoscopic surgery. METHODS: This is a prospective randomized open label non-inferiority trial. A total of 90 adult patients undergoing video-assisted thoracoscopic surgery will be randomized 1:1 to receive pain treatment with either (1) continuous erector spinae plane block plus intravenous patient-controlled analgesia with piritramide (study group) or (2) continuous thoracic epidural analgesia with a local anesthetic-opioid infusate (control group). All patients will receive additional systemic multimodal analgesia with paracetamol and non-steroidal anti-inflammatory drugs. The primary endpoint is the quality of recovery as measured by the Quality of Recovery-15 score. Secondary endpoints are postoperative pain as Numerical Rating Score scores, length of hospital stay, failure of analgesic technique, postoperative morphine-equivalent consumption, itching, nausea and vomiting, total operative time, complications related to surgery, perioperative hypotension, complications related to pain treatment, duration of bladder catheterization, and time of first assisted mobilization > 20 m and of mobilization to sitting in a chair. DISCUSSION: This randomized controlled trial aims to confirm whether continuous erector spinae plane block plus patient-controlled opioid analgesia can equal the analgesic effect of a thoracic epidural local anesthetic-opioid infusion in patients undergoing video-assisted thoracoscopic surgery. TRIAL REGISTRATION: Netherlands Trial Register NL6433 . Registered on 1 March 2018. This trial was prospectively registered.

Dynamics of the bacterial gut microbiota during controlled human infection with Necator americanus larvae.

Hookworms are soil-transmitted helminths that use immune-evasive strategies to persist in the human duodenum where they are responsible for anemia and protein loss. Given their location and immune regulatory effects, hookworms likely impact the bacterial microbiota. However, microbiota studies struggle to deconvolute the effect of hookworms from confounders such as coinfections and malnutrition. We thus used an experimental human hookworm infection model to explore temporal changes in the gut microbiota before and during hookworm infection. Volunteers were dermally exposed to cumulative dosages of 50, 100 or 150 L3 Necator americanus larvae. Fecal samples were collected for microbiota profiling through 16S rRNA gene amplicon sequencing at weeks zero, four, eight, fourteen and twenty. During the acute infection phase (trial week zero to eight) no changes in bacterial diversity were detected. During the established infection phase (trial week eight to twenty), bacterial richness (Chao1, p = .0174) increased significantly over all volunteers. No relation was found between larval dosage and diversity, stability or relative abundance of individual bacterial taxa. GI symptoms were associated with an unstable microbiota during the first eight weeks and rapid recovery at week twenty. Barnesiella, amongst other taxa, was more abundant in volunteers with more GI symptoms throughout the study. In conclusion, this study showed that clinical GI symptoms following N. americanus infection are associated with temporary microbiota instability and relative abundance of specific bacterial taxa. These results suggest a possible role of hookworm-induced enteritis on microbiota stability.

Value of Endolymphatic Hydrops and Perilymph Signal Intensity in Suspected Ménière Disease.

BACKGROUND AND PURPOSE: Ménière disease is characterized by endolymphatic hydrops, whereas perilymphatic enhancement on MR imaging has been suggested to be of additional value in diagnosing Ménière disease. This study evaluates the presence of endolymphatic hydrops and perilymphatic enhancement in patients with Ménière disease and with other vertigo-associated inner ear pathology. MATERIALS AND METHODS: A 3D-FLAIR sequence 4 hours after intravenous gadolinium injection was performed to visualize the endolymph and perilymph in 220 patients suspected of having Ménière disease. Patients' ears were retrospectively categorized as having Ménière disease (probable or definite) or other vertigo-associated inner ear pathology not attributable to Ménière disease. Endolymphatic hydrops was evaluated using a visual classification system, and perilymphatic enhancement was scored both visually and quantitatively. RESULTS: Endolymphatic hydrops was present in 137 (91.9%) of the definite Ménière disease ears and in 9 (7.0%) of the ears with other vertigo-associated inner ear pathology (P < .001). The combination of endolymphatic hydrops and visually increased perilymphatic enhancement was present in 122 (81.9%) definite Ménière disease ears compared with 4 (3.1%) ears with other vertigo-associated inner ear pathology (P < .001). This combination increases the positive predictive value from 0.94 for endolymphatic hydrops and 0.91 for perilymphatic enhancement to 0.97. The addition of measured perilymphatic enhancement leads to a moderate decrease in sensitivity from 0.92 for endolymphatic hydrops to 0.86. CONCLUSIONS: The combination of perilymphatic enhancement and endolymphatic hydrops in patients suspected of having Ménière disease increases the positive predictive value in the diagnosis of definite Ménière disease.

Diagnosis and treatment of C3 glomerulopathy in a center of expertise.

C3 glomerulopathy is a rare renal disease that has been distinguished as a renal disease for about 10 years. It is caused by an excessive activation of the alternative complement pathway in the circulation, which leads to deposition of complement factor C3 in glomeruli. It is diagnosed based on clinical presentation, histological patterns in a kidney biopsy and tests of the complement pathways. It can closely resemble immune complexmediated glomerulonephritis and postinfectious glomerulonephritis. Renal failure develops in up to half of all patients within 10 years after presentation. A curative treatment is not available. Treatment relies on renoprotective measures, occasional immunosuppressive medication and experimental novel complement inhibitors. Because the disease is rare, its care and cure are concentrated in centers of expertise. Here we provide an overview of the state-ofthe-art diagnosis and treatment of C3 glomerulopathy in a center of expertise in the Netherlands.

Sublingual sufentanil for postoperative pain relief: first clinical experiences.

BACKGROUND: The sublingual sufentanil tablet system (SSTS) is a novel hand-held patient-controlled analgesia device developed for treatment of moderate-to-severe postoperative pain. Here we present the first results of its clinical use. METHODS: Adult patients undergoing major surgery in five hospitals in the Netherlands received the SSTS for postoperative pain relief as part of multimodal pain management that further included paracetamol and a nonsteroidal anti-inflammatory drug (NSAID). The following variables were collected: postoperative pain scores using the 11-point numerical rating score (NRS) at rest, number of tablets used, occurrence of nausea, and patient satisfaction scores. RESULTS: We included 280 patients in the study; the majority underwent laparoscopic abdominal (49%) or orthopedic (knee replacement) surgery (34%). The median NRS was 3.5 (interquartile range 2.3-4.0) on the day of surgery, 3.3 (2.3-4.0) on the first postoperative day, and 2.8 (2.0-4.0) on the second postoperative day; pain scores did not differ between surgery types. Mean number of tablets used was 19 (range 0-86). Nausea occurred in 34% of patients, more often in women (45% vs 19%). Overall satisfaction was high in 73% of patients. Satisfaction was correlated with pain relief (p<0.001) and inversely correlated with occurrence of nausea (p=0.01). DISCUSSION: In this data set obtained under real-life conditions we show that the SSTS effectively managed postoperative pain in abdominal and orthopedic surgeries. Future studies should determine patient populations that benefit most from the SSTS, assess the added values versus intravenous patient-controlled analgesia, and determine the pharmacoeconomics of the system.

Molecular basis of fibrinogen Naples associated with defective thrombin binding and thrombophilia. Homozygous substitution of B beta 68 Ala----Thr.

In an abnormal fibrinogen (fibrinogen Naples) associated with congenital thrombophilia we have identified a single base substitution (G----A) in the B beta chain gene that results in an amino acid substitution of alanine by threonine at position 68 in the B beta chain of fibrinogen. The propositus and two siblings were found to be homozygous for the mutation, whereas the parents and another sibling were found to be heterozygous. Individuals homozygous for the defect had a severe history of both arterial and venous thrombosis; heterozygous individuals had no clinical symptoms. The three homozygotes had a prolonged thrombin clotting time in plasma, whereas the heterozygotes had a normal thrombin clotting time. Fibrinopeptide A and B (FpA and FpB) release from purified fibrinogen by human alpha-thrombin was delayed in both the homozygous propositus and a heterozygous family member. Release of FpA from the normal and abnormal amino-terminal disulfide knot (NDSK) corresponded to that found with the intact fibrinogens, indicating a decreased interaction of thrombin with the NDSK part of fibrinogen Naples. Binding studies showed that fibrin from homozygous abnormal fibrinogen bound less than 10% of active site inhibited alpha-thrombin as compared with normal fibrin, while fibrin formed from heterozygous abnormal fibrinogen bound approximately 50% of alpha-thrombin. These results suggest that the mutation of B beta Ala 68----Thr affects the binding of alpha-thrombin to fibrin, and that defective binding results in a decreased release of FpA and FpB in both homozygous and heterozygous abnormal fibrinogens.