Explore the vast range of titles available.

Acute intermittent porphyria results in excess activity of ALA synthase and overproduction of neurotoxic metabolites that cause attacks of severe abdominal pain. Givosiran, an interfering RNA, blocks synthesis of the enzyme, reduces the attack rate, and has only mild-to-moderate side effects.

Patients with type 2 diabetes at high risk for cardiovascular disease who were already taking a renin–angiotensin system blocker were randomly assigned to the direct renin inhibitor aliskiren or placebo. The study was discontinued early for no benefit, or even possible harm. Mortality associated with type 2 diabetes remains nearly twice that when diabetes is absent. 1 Complications of diabetes, particularly renal and cardiovascular disease, substantially increase the risk of subsequent severe illness and death. When a patient has both renal and cardiovascular disease, the risk is magnified further. 2 , 3 Blood-pressure lowering is beneficial in slowing renal-disease progression, reducing cardiovascular disease events, and preventing premature death. 4 Renin–angiotensin–aldosterone system (RAAS) blockers are highly effective, with apparent benefits extending beyond simple blood-pressure lowering 5 – 8 ; such agents have become the preferred first-line interventions in high-risk persons with diabetes. Theoretically, dual RAAS blockade should be more . . .

In this trial, 7016 patients with heart failure were assigned to aliskiren, enalapril, or both. At 36 months, the rate of cardiovascular death or heart-failure hospitalization was not lower with combination therapy than with enalapril. Aliskiren was not noninferior to enalapril. Angiotensin-converting–enzyme (ACE) inhibitors are effective in lowering the risks of death and hospitalization among patients with chronic heart failure and reduced ejection fraction. 1 , 2 As a consequence, there has been interest in other approaches to interruption of the renin–angiotensin system in patients with heart failure. Angiotensin-receptor blockers (ARBs) were the first alternative tested, and in one placebo-controlled trial, candesartan was associated with lower risks of death from cardiovascular causes and hospitalization for heart failure among patients who could not take ACE inhibitors. 3 However, in a head-to-head comparison, losartan was not as effective as captopril. 4 The combination of an ARB and . . .

In this study, patients with type 2 diabetes and nephropathy received either aliskiren, an oral direct renin inhibitor, or placebo, in addition to the maximal recommended dose of losartan and optimal antihypertensive therapy. Aliskiren was associated with a reduction in the mean urinary albumin-to-creatinine ratio. This direct renin inhibitor may be renoprotective independently of its blood-pressure–lowering effects in this patient population. In patients with type 2 diabetes and nephropathy, aliskiren was associated with a reduction in the mean urinary albumin-to-creatinine ratio. This direct renin inhibitor may be renoprotective independently of its blood-pressure–lowering effects in this patient population. The pathogenesis of diabetic nephropathy is multifactorial, and the renin−angiotensin−aldosterone system plays an important role. 1 , 2 Persistent proteinuria is the hallmark of diabetic nephropathy, a condition that is characterized by a progressive rise in blood pressure, a declining glomerular filtration rate, and a high risk of fatal or nonfatal cardiovascular events. The degree of proteinuria is closely associated with the rates of renal and cardiovascular events. 3 , 4 Furthermore, a reduction in proteinuria is associated with a slowing of both the decline in the glomerular filtration rate 5 and the progression to end-stage renal disease. 6 In addition, decreasing proteinuria is associated with . . .

Favipiravir is considered a potential treatment for COVID-19 due its efficacy against different viral infections. We aimed to explore the safety and efficacy of favipiravir in treatment of COVID-19 mild and moderate cases. It was randomized-controlled open-label interventional phase 3 clinical trial [NCT04349241]. 100 patients were recruited from 18th April till 18th May. 50 patients received favipiravir 3200 mg at day 1 followed by 600 mg twice (day 2-day 10). 50 patients received hydroxychloroquine 800 mg at day 1 followed by 200 mg twice (day 2-10) and oral oseltamivir 75 mg/12 h/day for 10 days. Patients were enrolled from Ain Shams University Hospital and Assiut University Hospital. Both arms were comparable as regards demographic characteristics and comorbidities. The average onset of SARS-CoV-2 PCR negativity was 8.1 and 8.3 days in HCQ-arm and favipiravir-arm respectively. 55.1% of those on HCQ-arm turned PCR negative at/or before 7th day from diagnosis compared to 48% in favipiravir-arm (p = 0.7). 4 patients in FVP arm developed transient transaminitis on the other hand heartburn and nausea were reported in about 20 patients in HCQ-arm. Only one patient in HCQ-arm died after developing acute myocarditis resulted in acute heart failure. Favipiravir is a safe effective alternative for hydroxychloroquine in mild or moderate COVID-19 infected patients.

•The pharmacokinetics and pharmacodynamics of ropivacaine at different concentrations (Group L:0.25%, Group M:0.5%, Group H:0.75%) in SAPB were evaluated simultaneously.•The analgesic effects of Group M and Group H were better than Group L.•The Cmax and AUC increased with rising ropivacaine concentration, and both Group H and Group M had significantly higher half-life than Group L•The use of 0.5% ropivacaine is recommended for SAPB to provide satisfactory perioperative analgesia. Investigate the analgesia effects and pharmacokinetics of ropivacaine at different concentrations in Serratus Anterior Plane Block (SAPB) and assess the efficacy and safety. Thirty-six patients undergoing video-assisted thoracoscopic surgery (VATS) pulmonary resections were enrolled. Ultrasound-guided SAPB was induced with 3 mg/kg ropivacaine at different concentrations (0.25%, 0.5%, and 0.75%, referred to as Group L, Group M, and Group H, respectively). The concentration of ropivacaine in the plasma at 1, 15, 30, 45, 60 min, 2, 4, 8, 12, and 24 h after SAPB was determined by LC-MS/MS. Other evaluated measures included the Numerical Rating Scale (NRS) scores at rest and on movement, the frequency of dermatomes blocked, onset time and effective plane, Quality of Requirements(QoR)-15 scale, chronic postsurgical pain, and the level of IL-6 and IL-8. The NRS scores were significantly higher in Group L than those in other groups (P < 0.05), indicating that the analgesic effect of Group L was the worst among the three groups. Group H had a lower effective plane of anesthesia and significantly higher incidence of chronic postsurgical pain. The IL-8 level was significantly lower in Group H than in other groups at 1 min, 1 h, and 24 h after SAPB. The ropivacaine concentrations were the highest in Group H, followed by Group M and Group L. The high blood concentration of ropivacaine in Group H may increase the risk of systemic toxicity from local anesthetics. Compared to Group L and Group H, Group M had superior analgesic effects and better safety. Among the three groups, Cmax, t1/2, and AUC0-∞ differed significantly. For patients undergoing VATS, using 0.5% ropivacaine for SAPB is recommended. [Display omitted]

The aim of this study was to assess dual renin system intervention with the maximum recommended doses of aliskiren and valsartan, compared with each drug alone in patients with hypertension. In this double-blind study, 1797 patients with hypertension (mean sitting diastolic blood pressure 95–109 mm Hg and 8-h daytime ambulatory diastolic blood pressure ≥90 mm Hg) were randomly assigned to receive once-daily aliskiren 150 mg (n=437), valsartan 160 mg (455), a combination of aliskiren 150 mg and valsartan 160 mg (446), or placebo (459) for 4 weeks, followed by forced titration to double the dose to the maximum recommended dose for another 4 weeks. The primary endpoint was change in mean sitting diastolic blood pressure from baseline to week 8 endpoint. Analyses were done by intention to treat. This trial is registered at ClinicalTrials.gov with the number NCT00219180. 196 (11%) patients discontinued study treatment before the end of the trial (63 in the placebo group, 53 in the aliskiren group, 43 in the valsartan group, and 37 in the aliskiren/valsartan group), mainly due to lack of therapeutic effect. At week 8 endpoint, the combination of aliskiren 300 mg and valsartan 320 mg lowered mean sitting diastolic blood pressure from baseline by 12·2 mm Hg, significantly more than either monotherapy (aliskiren 300 mg 9·0 mm Hg decrease, p<0·0001; valsartan 320 mg, 9·7 mm Hg decrease, p<0·0001), or with placebo (4·1 mm Hg decrease, p<0·0001). Rates of adverse events and laboratory abnormalities were similar in all groups. The combination of aliskiren and valsartan at maximum recommended doses provides significantly greater reductions in blood pressure than does monotherapy with either agent in patients with hypertension, with a tolerability profile similar to that with aliskiren and valsartan alone.

Background and ObjectivesThe transversus abdominis plane (TAP) block is a widely used nerve block. However, basic block characteristics are poorly described. The purpose of this study was to assess the cutaneous sensory block area, muscle-relaxing effect, and block duration.MethodsSixteen healthy volunteers were randomized to receive an ultrasound-guided unilateral TAP block with 20 mL 7.5 mg/mL ropivacaine and placebo on the contralateral side. Measurements were performed at baseline and 90 minutes after performing the block. Cutaneous sensory block area was mapped and separated into a medial and lateral part by a vertical line through the anterior superior iliac spine. We measured muscle thickness of the 3 lateral abdominal muscle layers with ultrasound in the relaxed state and during maximal voluntary muscle contraction. The volunteers reported the duration of the sensory block and the abdominal muscle–relaxing effect.ResultsThe lateral part of the cutaneous sensory block area was a median of 266 cm2 (interquartile range, 191–310 cm2) and the medial part 76 cm2 (interquartile range, 54–127 cm2). In all the volunteers, lateral wall muscle thickness decreased significantly by 9.2 mm (6.9–15.7 mm) during a maximal contraction. Sensory block and muscle-relaxing effect duration were 570 minutes (512–716 minutes) and 609 minutes (490–724 minutes), respectively.ConclusionsCutaneous sensory block area of the TAP block is predominantly located lateral to a vertical line through the anterior superior iliac spine. The distribution is nondermatomal and does not cross the midline. The muscle-relaxing effect is significant and consistent. The block duration is approximately 10 hours with large variation.

Background Although laparoscopic surgery significantly reduces surgical trauma compared to open surgery, postoperative ileus is a frequent and significant complication after abdominal surgery. Unlike laparoscopic colorectal surgery, the effects of epidural analgesia on postoperative recovery after laparoscopic gastrectomy are not well established. We compared the effects of epidural analgesia to those of conventional intravenous (IV) analgesia on the recovery of bowel function after laparoscopic gastrectomy. Method Eighty-six patients undergoing laparoscopic gastrectomy randomly received either patient-controlled epidural analgesia with ropivacaine and fentanyl (Epi PCA group) or patient-controlled IV analgesia with fentanyl (IV PCA group), beginning immediately before incision and continuing for 48 h thereafter. The primary endpoint was recovery of bowel function, evaluated by the time to first flatus. The balance of the autonomic nervous system, pain scores, duration of postoperative hospital stay, and complications were assessed. Results The time to first flatus was shorter in the epidural PCA group compared with the IV PCA group (61.3 ± 11.1 vs. 70.0 ± 12.3 h, P  = 0.001). Low-frequency/high-frequency power ratios during surgery were significantly higher in the IV PCA group, compared with baseline and those in the epidural PCA group. The epidural PCA group had lower pain scores during the first 1 h postoperatively and required less analgesics during the first 6 h postoperatively. Conclusions Compared with IV PCA, epidural PCA facilitated postoperative recovery of bowel function after laparoscopic gastrectomy without increasing the length of hospital stay or PCA-related complications. This beneficial effect of epidural analgesia might be attributed to attenuation of sympathetic hyperactivation, improved analgesia, and reduced opioid use.

Background and ObjectivesEffective postoperative analgesia may enhance early rehabilitation after orthopedic surgery. This randomized double-blind trial investigates the relative contributions of adductor canal block and low-dose intrathecal morphine (ITM) to postoperative analgesia and functional recovery after total knee arthroplasty.MethodsTwo-hundred one patients undergoing elective unilateral total knee arthroplasty under spinal anesthesia were randomized to 3 groups. All patients received standardized intraoperative local infiltration analgesia and postoperative oral analgesics. Patients in group 1 received a “sham” adductor canal block with 30 mL of normal saline. Patients in group 2 received an adductor canal block with 30 mL of ropivacaine 0.5% with 1:400,000 epinephrine, whereas patients in group 3 received the adductor canal block with the active drug and 100 μg of ITM. The primary outcome measure was the Timed Up and Go (TUG) test on the second postoperative day. Secondary outcomes included postoperative pain scores and opioid requirements, distance walked, time to hospital discharge, and self-reported functional outcomes at 3 months.ResultsAll 3 groups had similar values of TUG test on postoperative day (POD) 2 (46 [36–62], 45 [33–61], and 52 [41–69]; P = 0.166) as well as other short-term and 3-month functional outcomes. Patients in group 3 showed a favorable analgesic profile as evidenced by 3 positive secondary outcomes. These positive outcomes were lower pain scores 12 hours postoperatively both at rest (4 [2–6.3], 4 [2.3–6], and 3 [1–4]; P = 0.007) and on movement (6 [4–8], 6 [3–8], and 4 [2–6]; P = 0.002), a lower incidence of “rescue” intravenous patient-controlled analgesia (42%, 34%, and 20%; P = 0.031), and the lowest cumulative opioid requirements for the first 48 hours postoperatively (86 ± 71, 68 ± 46, and 59 ± 39; P < 0.005, group 3 compared with group 1).ConclusionsOur data suggest that there is no difference in either the primary outcome of TUG test on POD 2, other immediate functional secondary outcomes, or in global functional outcome at 3 months postoperatively across all 3 groups. Our data also suggest an improved analgesic profile in the first 48 hours postoperatively when both adductor canal block and low-dose ITM (100 μg) are added to local infiltration analgesia as evidenced by several positive secondary outcomes of lower pain scores and opioid requirements.Clinical Trial RegistrationThis study was registered at ClinicalTrials.gov, identifier NCT02411149.