To the Editor,
I am writing in response to Dr Sharon Galper Grossman’s recent fascinating article, “Vape Gods and Judaism—E-cigarettes and Jewish Law.”1 The author extrapolates from rabbinic literature regard-ing combustible cigarettes and suggests that the preliminary data establishing the dangers of e-cigarettes, and the government warnings against usage, would render these products prohibited under Jewish law, especially for youth and pregnant women.
United States (US) and European Union (EU) laws attempt to counterbalance the presumed discrimination of children in drug treatment and drug development. The US Food and Drug Administration (FDA)-rewarded pediatric studies with antidepressants triggered in 2004 an FDA black-box warning of suicidality in young patients. Fewer antidepressants were prescribed, and the number of completed suicides of young persons increased. The dilemma between this warning and the need to adequately treat young depressed patients remains unsolved. We analyzed the history of drug development, the evolving view of diseases in young patients, US/EU pediatric laws, and pediatric studies triggered by FDA/European Medicines Agency (EMA) in depression and other diseases on the background of developmental pharmacology; financial, institutional, and other interests; and the literature. The FDA/EMA define children administratively, not physio¬logically, as <17 (FDA)/<18 years old (EMA). But young persons mature physiologically well before their 17th/18th birthday. Depression occurs in young persons, has special characteristics, but is not fundamentally different from adult depression. Young persons are not another species. Regulatory requirements for “pediatric” studies focus on “pediatric” labels. Many “pediatric” studies, including those in depression, lacked and lack medical sense and harm patients by placebo treatment although effective drugs exist. The FDA has partially abandoned separate “pediatric” efficacy studies, but not in psychiatry. Clinicians, parents, institutional review boards, and ethics committees should become aware of questionable “pediatric” studies, should re-evaluate ongoing ones, consider to suspend them, and to reject new ones. The concept of separate “pediatric” drug approval needs to be abandoned.
Objective. To compare the reported accuracy and sensitivity of the various modalities used to diagnose autism spectrum disorders (ASD) in efforts to help focus further biomarker research on the most promising methods for early diagnosis.
Methods. The Medline scientific literature database was searched to identify publications assessing potential clinical ASD biomarkers. Reports were categorized by the modality used to assess the putative markers, including protein, genetic, metabolic, or objective imaging methods. The reported sensitivity, specificity, area under the curve, and overall agreement were summarized and analyzed to determine weighted averages for each diagnostic modality. Heterogeneity was measured using the I2 test.
Results. Of the 71 papers included in this analysis, each belonging to one of five modalities, protein-based followed by metabolite-based markers provided the highest diagnostic accuracy, each with a pooled overall agreement of 83.3% and respective weighted area under the curve (AUC) of 89.5% and 88.3%. Sensitivity provided by protein markers was highest (85.5%), while metabolic (85.9%) and protein markers (84.7%) had the highest specificity. Other modalities showed degrees of sensitivity, specificity, and overall agree¬ments in the range of 73%–80%.
Conclusions. Each modality provided for diagnostic accuracy and specificity similar or slightly higher than those reported for the gold-standard Autism Diagnostic Observation Schedule (ADOS) instrument. Further studies are required to identify the most predictive markers within each modality and to evaluate biological pathways or clustering with possible etiological relevance. Analyses will also be necessary to determine the potential of these novel biomarkers in diagnosing pediatric patients, thereby enabling early intervention.
Objectives: To analyze, perioperatively and in follow-up, transilluminated powered phlebectomy (TIPP), a surgical technique for the treatment of varicose veins.
Method: Retrospective study in one medical institution of patients undergoing TIPP between July 2015 and December 2017. Data analyzed included demographic data, surgery, and results. Postoperatively, pain was evaluated by a 10-point visual analogue scale. The Venous Clinical Severity Score (VCSS) was assessed 5–8 weeks following surgery.
Results: Sixty-six patients with extensive varicosities who underwent TIPP were included. Postoperative pain scores were higher in patients undergoing bilateral compared to unilateral TIPP (visual analogue score 7 versus 5; P=0.031). Following surgery, the VCSS improved in 81.8% (54/66) of the patients. However, 39.7% (25/63; data missing in 3 patients) reported that they would not be willing to undergo a similar procedure in the future. Pain was the most common reason for dissatisfaction.
Conclusions: Transilluminated powered phlebectomy was associated with considerable pain and discom¬fort in many patients included in this study. For this reason, it should be reserved for a select group of patients in whom other treatment options are limited; TIPP could be considered in the following cases: patients with a large number of varicosities, reoperations, after extensive thrombophlebitis, obesity, or following bariatric surgery.
Beyond the increase in medical knowledge and biotechnology during the last decades, doctors have adopted professional norms that would have been considered heretical only two generations ago. The changes transpired between the 1970s and 1990s, and generated controversies between those who upheld the traditional values of patient care, and those who welcomed the new professional norms. Professor Dr Johannes Juda Groen (1903–1990) predicted and promoted some of these changes. As early as the 1940s through the 1960s, he recognized the need to teach interviewing skills and advocated an orientation to patients, rather than to diseases; he supported decision-making based on evidence, rather than on personal experience and pathophysiologic rationale; and he demonstrated that psychosocial determinants predict, rather than only correlate with, disease. These views led to confrontations with the medical establishments in the Netherlands and in Israel. Still, many of his colleagues recognized the value of his contributions. The author, for one, admires Groen’s commitment in challenging the prevailing clinical wisdom after the end of World War 2, and his courage in opposing the views of his colleagues.
Objectives: We hypothesized that preoperative (pre-op) ultrasound (US)-guided posterior transversus abdominis plane block (TAP) and US-guided ilioinguinal and iliohypogastric nerve block (ILI+IHG) will produce a comparable analgesia after Lichtenstein patch tension-free method of open inguinal hernia repair in adult men. The genital branch of the genitofemoral nerve will be blocked separately.
Methods: This is a prospective, randomized, controlled, and observer-blinded clinical study. A total of 166 adult men were randomly assigned to one of three groups: a pre-op TAP group, a pre-op ILI+IHG group, and a control group. An intraoperative block of the genital branch of the genitofemoral nerve was performed in all patients in all three groups, followed by postoperative patient-controlled intravenous analgesia with morphine. The pain intensity and morphine consumption immediately after surgery and during the 24 hours after surgery were compared between the groups.
Results: A total of 149 patients completed the study protocol. The intensity of pain immediately after surgery and morphine consumption were similar in the two “block” groups; however, they were significantly decreased compared with the control group. During the 24 hours after surgery, morphine consumption in the ILI+IHG group decreased compared with the TAP group, as well as in each “block” group versus the control group. Twenty-four hours after surgery, all evaluated parameters were similar.
Conclusion: Ultrasound-guided ILI+IHG provided better pain control than US-guided posterior TAP following the Lichtenstein patch tension-free method of open inguinal hernia repair in men during 24 hours after surgery. (ClinicalTrials.gov number: NCT01429480.)
Background: The PROSPECT (Procedure-Specific Postoperative Pain Management) Group recommended a single injection femoral nerve block in 2008 as a guideline for analgesia after total knee arthroplasty. Other authors have recommended the addition of sciatic and obturator nerve blocks. The lateral femoral cutaneous nerve is also involved in pain syndrome following total knee arthroplasty. We hypothesized that preoperative blocking of all four nerves would offer superior analgesia to femoral nerve block alone.
Methods: This is a prospective, randomized, controlled, and observer-blinded clinical study. A total of 107 patients were randomly assigned to one of three groups: a femoral nerve block group, a multiple nerve block group, and a control group. All patients were treated postoperatively using patient-controlled intravenous analgesia with morphine. Pain intensity at rest, during flexion and extension, and morphine consumption were compared between groups over three days.
Results: A total of 90 patients completed the study protocol. Patients who received multiple nerve blocks experienced superior analgesia and had reduced morphine consumption during the postoperative period compared to the other two groups. Pain intensity during flexion was significantly lower in the “blocks” groups versus the control group. Morphine consumption was significantly higher in the control group.
Conclusions: Pain relief after total knee arthroplasty immediately after surgery and on the first postoperative day was significantly superior in patients who received multiple blocks preoperatively, with morphine consumption significantly lower during this period. A preoperative femoral nerve block alone produced partial and insufficient analgesia immediately after surgery and on the first postoperative day. (Clinical trial registration number (NIH): NCT01303120)
Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are both more common among people of North European decent than among Mediterranean people. Women are 2–3 times more commonly affected. Giant cell arteritis and PMR are extremely rare before age 50 years. Polymyalgia rheumatica may be “isolated” or associated with GCA. There is increased expression of inflammatory cytokines in temporal arteries of PMR patients, without overt histological evidence of arteritis. One-third of “isolated” PMR patients have vascular uptake in positron emission tomography (PET) scans, suggesting clinically unrecognized, “hidden” GCA. Typical manifestations of GCA are headache, tenderness over temporal arteries, jaw claudication, PMR, acute vision loss, and low-grade fever. Bilateral aching of the shoulders with morning stiffness is typical for PMR. In both conditions sedimentation rate and C-reactive protein are elevated, and anemia and thrombocytosis may occur. Color duplex ultrasonography of the temporal arteries may aid in GCA diagnosis. Temporal artery biopsy showing vasculitis, often with giant cells, confirms GCA diagnosis. In cases with negative biopsy one must rely on the clinical presentation and laboratory abnormalities. The diagnosis of PMR is made primarily on clinical grounds. Other conditions that may mimic GCA or PMR must be excluded. Glucocorticoids are the treatment of choice for both conditions. Prompt treatment is crucial in GCA, to prevent irreversible complications of acute vision loss and stroke. Addition of low-dose aspirin may further prevent these complications. The average duration of treatment is 2–3 years, but some patients require a prolonged course of treatment, and some may develop disease-related or treatment-related complications. No steroid-sparing agent has been proven to be widely effective thus far, but some promising therapeutic agents are currently being studied.
Ehlers–Danlos syndrome (EDS)—hypermobility type (HT) is considered to be the most common subtype of EDS and the least severe one; EDS-HT is considered to be identical to the joint hypermobility syndrome and manifests with musculoskeletal complaints, joint instability, and soft tissue overuse injury. Musculoskeletal complaints manifest with joint pain of non-inflammatory origin and/or spinal pain. Joint instability leads to dislocation or subluxation and involves peripheral joints as well as central joints, including the temporomandibular joints, sacroiliac joints, and hip joints. Soft tissue overuse injury may lead to tendonitis and bursitis without joint inflammation in most cases. Ehlers–Danlos syndrome-HT carries a high potential for disability due to recurrent dislocations and subluxations and chronic pain. Throughout the years, extra-articular manifestations have been described, including cardiovascular, autonomic nervous system, gastrointestinal, hematologic, ocular, gynecologic, neurologic, and psychiatric manifestations, emphasizing the multisystemic nature of EDS-HT. Unfortunately, EDS-HT is under-recognized and inadequately managed, leading to neglect of these patients, which may lead to severe disability that almost certainly could have been avoided. In this review article we will describe the known manifestations of the extra-articular systems.
To the Editor,
We read with great interest the original research published by Anatoli Stav et al.1 in which they com-pared supraclavicular (SCL), infraclavicular (ICL), and axillary (AX) approaches to the brachial plexus with ultrasonography for upper limb surgeries.1 They concluded that all approaches can be used to provide adequate anesthesia for upper limb sur-geries below the shoulder. Nevertheless, they also experienced some sparing and failed blocks: 3 patients from the SCL group, 3 from the ICL group, and 4 from the AX group had a positive pin-prick test; 2 patients from the AX group received sedation supplementation; and 1 patient in the AX group experienced ulnar sparing which required a general anesthetic. ...
