Acute renal failure with sodium-glucose-cotransporter-2 inhibitors: Analysis of the FDA adverse event report system database.

BACKGROUND AND AIMS: Sodium-glucose-cotransporter-2 (SGLT2) inhibitors have recently been approved for the treatment of type II diabetes mellitus (T2DM). It has been proposed that these agents could induce acute renal failure (ARF) under certain conditions. This study aimed to evaluate the association between SGLT2-inhibitors and ARF in the FDA adverse event report system (FAERS) database. METHODS AND RESULTS: We analyzed adverse event cases submitted to FAERS between January 2013 and September 2016. ARF cases were identified using a structured medical query. Medications were identified using both brand and generic names. During the period evaluated, 18,915 reports (out of a total of 3,832,015 registered in FAERS) involved the use of SGLT2-inhibitors. SGLT2-inhibitors were reportedly associated with ARF in 1224 of these cases (6.4%), and were defined as the "primary" or "secondary" cause of the adverse event in 96.8% of these cases. The proportion of reports with ARF among reports with SGLT2 inhibitor was almost three-fold higher compared to reports without these drugs (ROR 2.88, 95% CI 2.71-3.05, p < 0.001). The proportion of ARF reports among cases with SGLT2-inhibitors was significantly greater than the proportion of ARF among cases with T2DM without SGLT2-inhibitors (ROR 1.68, 95% CI 1.57-1.8, p < 0.001). Among the SGLT2-inhibitors, canagliflozin was associated with a higher proportion of reports of renal failure (7.3%), compared to empagliflozin and dapagliflozin (4.7% and 4.8% respectively, p < 0.001). CONCLUSION: SGLT2-inhibitors are associated with an increase in the proportion of reports of ARF compared to other medications. SGLT2-inhibitor agents may differ from one another in their respective risk for ARF.

Self-Reported bruxism and associated factors in Israeli adolescents.

Little is known about the epidemiological characteristics of sleep and awake bruxism (SB and AB) in adolescents. The aims of the study were: to assess the prevalence rates of self-reported SB and AB in Israeli adolescents; to determine the associations between SB/AB and several demographical, exogenous and psychosocial factors in Israeli adolescents; and to investigate the possible concordance between SB and AB. The study made use of a questionnaire. The study population included 1000 students from different high schools in the centre of Israel. Prevalence of self-reported SB and AB in the Israeli adolescents studied was 9·2% and 19·2%, respectively. No gender difference was found regarding the prevalence of SB and AB. Multiple variable regression analysis revealed that the following predicting variables were related to SB: temporomandibular joint sounds (P = 0·002) and feeling stressed (P = 0·001). The following predicting variables were related to AB: age (P = 0·018), temporomandibular joint sounds (P = 0·002), oro-facial pain (P = 0·006), and feeling stressed (P = 0·002) or sad (P = 0·006). A significant association was found between SB and AB; that is, an individual reporting SB had a higher probability of reporting AB compared with an individual who did not report SB (odds ratio = 5·099). Chewing gum was the most common parafunction reported by adolescents. The results of this study demonstrate that self-reports of AB and SB are common in the Israeli adolescents population studied and are not related to gender. The significant correlation found between SB and AB may be a confounding bias that affects proper diagnosis of bruxism through self-reported questionnaires only.

Concomitance of IgA nephropathy and diabetic nephropathy in a kidney allograft: case report and review of the literature.

Whereas diabetic nephropathy is the most common cause of end-stage renal disease (ESRD), IgA nephropathy is the most common glomerulonephritis in the world. We report a case of a kidney transplant recipient whose native renal disease was presumptive diabetic nephropathy. Five years after transplantation, the patient developed proteinuria, hematuria, and allograft dysfunction. Transplant biopsy revealed IgA nephropathy superimposed on diabetic nephropathy.

Masticatory muscle disorders diagnostic criteria: the American Academy of Orofacial Pain versus the research diagnostic criteria/temporomandibular disorders (RDC/TMD).

In this study, relevant cases were retrospectively reviewed to identify patients who were diagnosed as suffering from myofascial pain only according to the research diagnostic criteria/temporomandibular disorders (RDC/TMD) criteria, in order to examine whether or not they could fulfil the American Academy of Orofacial Pain (AAOP) diagnostic criteria for TMD-related masticatory muscle disorders. One hundred and twenty-seven patients, diagnosed according to the RDC/TMD criteria as having myofascial pain with or without limited jaw opening only, were allocated to two groups according to their answers to the RDC/TMD 'jaw disability checklist'. The two groups were compared for Axis I and II data taken from the RDC/TMD questionnaire. Thirty-eight of the patients (29·9%) did not associate their symptoms with jaw functions (e.g. chewing and yawning). This group was characterised by increased range of motion (ROM) and older average age. The AAOP diagnostic criteria for TMD require pain on function in all subtypes of TMD-related muscle disorders. An association between pain and jaw function is common and research is needed to determine whether this should be categorised differently to muscle pain unrelated to jaw function. There may well be different pathophysiological mechanisms and consequently different management strategies for these two pain conditions.

Bruxism, oral parafunctions, anamnestic and clinical findings of temporomandibular disorders in children.

The reported prevalence of temporomandibular disorders (TMD) present during childhood and adolescence ranges between 7% and 68%. The range of the reported prevalence of sleep bruxism in children is also wide. The purpose of the current study was threefold: (i) determine the prevalence of oral parafunctions, sleep bruxism and of anamnestic and clinical findings of TMD among Israeli children with primary or mixed dentition; (ii) to establish whether the parafunctional activities are associated with anamnestic and clinical findings of TMD in this population and (iii) to examine the possible impact of stressful life events on the prevalence of bruxism, oral parafunctions, and anamnestic and clinical findings of TMD in children. A total of 244 children (183 girls and 61 boys) aged 5-12 years were included in the study. Each participant underwent a full TMD examination. Parents, in collaboration with their children, completed a questionnaire on TMD symptoms, oral parafunctions and stressful life events in their children's life. Most participants (78·8%) reported at least one oral habit. Of these, only 'jaw play' was associated with TMD anamnestic and clinical findings. Stressful life events were associated only with the performance of multiple oral habits. These findings indicate that the performance of oral parafunctions is commonplace during childhood, with younger children exhibiting fewer oral parafunctions than adolescents. Stressful life events are related with an increase in the performance of multiple oral parafunctions in children but the later are not necessarily associated with anamnestic and clinical findings of TMD in the paediatric population.

[Do temporomandibular disorders really exist?].

Temporomandibular Disorders (TMD) is a collective term embracing a number of clinical problems that involve the muscles of mastication, the temporomandibular joint (TMJ) and associated structures or both. This group of disorders has been identified as the chief cause of pain, which is not of dental origin, in the orofacial area, and is defined as a subgroup in the category of musculoskeletal disorders. These disorders impair the quality of life of those suffering from them due to the extent of the pain and the chronic nature of its symptoms. It is known that chronic pain causes the development of psychological disturbances (anxiety, depression, etc.). The most common symptoms of TMD are the pain that usually appears as the result of mandibular activity (speaking or chewing), and is usually located in the masticulatory muscles, in the preauricular area and the temporomandibular joint (TMJ). Additional common symptoms are: a. restriction in jaw movement; b. asymmetry in jaw movement; c. noises from the joint. Patients suffering from TMD are likely to exhibit additional symptoms: hypertrophy of the muscles of mastication (an adaptive and asymptomatic phenomenon), abnormal occlusar erosion due to nighttime or daytime bruxism, or teeth grinding. Most functional temporomandibular disorders have similar signs and symptoms. As a result, diagnosis of the various disorders presents a serious problem. Functional temporomandibular disorders are often accompanied by mental symptoms such as depression, anxiety and/or somatization on various levels. One of today's accepted methods of classification also refers to the mental aspect and thus enables, for the first time, a suitable scientific comparison of the epidemiological, diagnostic and treatment data in the various studies. This method, initiated by Dworkin and LeResche (1992) is known as Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). The purpose of this method is to classify every subgroup of TMD according to agreed upon, clear and measurable diagnostic criteria, both from the physical (AXIS I) and the mental (AXIS II) aspect. The method includes a scale which grades the extent of severity, damage and limitations caused by the illness, in a manner which now can make scientific comparisons between the various studies and between the population of patients and the general population. Temporomandibular disorders are very common and affect between 30%-50% of the population, and appear to be more prevalent among women than among men. Studies conducted on youth revealed significant relationships between oral parafunctions (especially chewing gum and "jaw playing"), and functional temporomandibular disorders. The significance of this finding is in the need to warn young people of the possible risks of engaging in intensive oral practices. The high prevalence of signs and symptoms among the Israeli population obligates us, in our opinion, to change the physical examination for identification of these disorders, to a routine procedure in all dental clinics in Israel.

Adenine toxicity and transport in the moderately halophilic eubacterium Halomonas elongata.

The presence of adenine in the L-alanine defined medium substantially inhibited the growth of the moderately halophilic eubacterium Halomonas elongata. Extensive attempts to reverse the adenine toxicity for growth were made using a variety of purine and pyrimidine compounds, vitamins, and amino acids. Of the compounds tested, only cytosine was found to reverse the adenine growth inhibition. This indicates a mechanism similar to that found for some strains of Escherichia coli in which the presence of exogenous purines (e.g. adenine) was found to stop purine de novo synthesis and repress the synthesis of the pyrimidine salvage enzyme cytosine deaminase. H. elongata was found to possess an active adenine uptake system that was sodium dependent with only lithium having a considerable capacity to replace the sodium. A competition study indicated that the adenine transport system was quite specific. This paper represents the initial study of purine and pyrimidine salvage pathways and adenine uptake for the moderately halophilic eubacteria.

Old age is associated with a pattern of relatively intact and relatively impaired task-set switching abilities.

In three experiments, we examined the effects of old age on the reaction time (RT) decrement associated with task alternation. Old age was associated with increased mixing-cost, which is the RT difference between two conditions: mixed-task, where trials involving two tasks were intermixed, and single-task, where all the trials involved the same task. Old age was also associated with an increased switching-cost, which is the RT difference between trials in which the task was just changed and trials in which it was repeated. There was also indication of a slowed passive dissipation of task set adopted in the preceding trial. In contrast to these impairments, old age was also associated with an almost intact ability to prepare for an upcoming task switch. This ability was indicated by a normal reduction in switching-cost due to an increase in the time allowed to prepare for the switch. We discuss the implications of the results in relation to theories of task-switching and to the underlying brain mechanisms, especially with respect to the effect of old age on the prefrontal cortex.

Delaware's first serial killer.

The violent murder of Shirley Ellis on November 29, 1987, marked the beginning of the strange and terrible tale of Steven Bryan Pennell's reign as the state of Delaware's first convicted serial killer. Three more bodies followed the first victim, and all had been brutally beaten and sadistically tortured. The body of a fifth woman has never been found. State and county police collaborated with the FBI to identify and hunt down their suspect, forming a task force of over 100 officers and spending about one million dollars. Through their knowledge and experience with other serial killers, the FBI was able to make an amazingly accurate psychological profile of Delaware's serial killer. After months of around-the-clock surveillance, Steven Pennell was arrested on November 29, 1988, one year to the day after the first victim was found. Pennell was found guilty in the deaths of the first two victims on November 29, 1989, and plead no contest to the murder of two others on October 30, 1991. Still maintaining his innocence, he asked for the death penalty so that he could spare his family further agony. Steven Pennell was executed by lethal injection on March 15, 1992.

Respiratory and acoustic signals associated with bolus passage during swallowing.

In order to advance our understanding of the relation between respiration and deglutition, simultaneous videofluoroscopy and respirodeglutometry was performed. Fifteen normal, healthy, young adults (20-29 years of age) were connected to a respirodeglutometer and positioned for simultaneous videofluoroscopic assessment in the lateral plane. Subjects performed three swallows each of a 5-ml and a 10-ml bolus of liquid barium and a 5-ml bolus of paste barium, for a total of nine swallows per subject. Location of the bolus head as identified with videofluoroscopy was associated with eight respirodeglutometric variables. In addition, temporal relations for seven respirodeglutometric variables were calculated as a function of bolus volume and viscosity. Significant temporal differences were found for five of the variables by volume. No significant temporal differences were noted by viscosity. Expiration occurred before 79% and after 96% of the swallows. The number of inspirations preceding a swallow suggested a possible effect resulting from the need to hold a bolus in the mouth before receiving instructions to swallow during videofluoroscopic assessment. This effect may be important during patient evaluation. For a significant number of swallows, respiratory flow ceased before the velum was fully elevated.

Talking with patients about alternative and complementary medicine.

The growing use of alternative and complementary therapies in the United States as well as other parts of the world is a trend that the responsible rheumatologist cannot ignore. With chronic musculoskeletal conditions being the leading indication for the use of alternative and complementary therapies, rheumatologists must become experts on talking to patients and advising them about the use or avoidance of such therapies. Currently, there is a growing body of literature on the safety and efficacy of the multiple alternative and complementary therapies available. Much of this information is reliable and of high methologic quality; however, much of it is not. With an increase in the budget of the Office of Alternative Medicine from $20 to $50 million in 1999 and the status of the office changing to an independent center, an important step has been taken to try to assure improved research in the near future to validate or disprove many of the current alternative and complementary therapies. In the meantime, our patients are using these therapies and are likely to continue to do so, with or without our guidance. We must get beyond the "don't ask, don't tell" approach that characterizes many physicians' attitudes toward the subject of alternative and complementary therapies. Although all discussions need not end in agreement, they are still opportunities for shared decision making and "relationship-centered care." Ultimately, we should not be concerned with practicing what is perceived to be traditional versus alternative and complementary medicine or biomedicine versus naturalistic medicine but only with what is truly "good" medicine.

Electromyographic activity from human laryngeal, pharyngeal, and submental muscles during swallowing.

The durations and temporal relationships of electromyographic activity from the submental complex, superior pharyngeal constrictor, cricopharyngeus, thyroarytenoid, and interarytenoid muscles were examined during swallowing of saliva and of 5- and 10-ml water boluses. Bipolar, hooked-wire electrodes were inserted into all muscles except for the submental complex, which was studied with bipolar surface electrodes. Eight healthy, normal, subjects produced five swallows of each of three bolus volumes for a total of 120 swallows. The total duration of electromyographic activity during the pharyngeal stage of the swallow did not alter with bolus condition; however, specific muscles did show a volume-dependent change in electromyograph duration and time of firing. Submental muscle activity was longest for saliva swallows. The interarytenoid muscle showed a significant difference in duration between the saliva and 10-ml water bolus. Finally, the interval between the onset of laryngeal muscle activity (thyroarytenoid, interarytenoid) and of pharyngeal muscle firing patterns (superior pharyngeal constrictor onset, cricopharyngeus offset) decreased as bolus volume increased. The pattern of muscle activity associated with the swallow showed a high level of intrasubject agreement; the presence of somewhat different patterns among subjects indicated a degree of population variance.

Temporal and durational patterns associating respiration and swallowing.

This study obtained initial normative data on the temporal coordination of respiration and swallowing events in 12 young adults using a first-generation Respirodeglutometer. In addition, direction of airflow before and after deglutive apnea was obtained. Three swallows of two viscosities of bolus material were performed by each subject, yielding a total of 72 swallows. Qualitative and quanitative analyses were performed. Time of onset of submental surface electromyography and time of laryngeal movement were found to differ between males and females. Males began submental muscle contraction before females and laryngeal movement after females. Duration of deglutition apnea for all swallows was 0.75 +/- 0.14 sec. Expiration occurred before the deglutition apnea 93% of the time and after the deglutition apnea 100% of the time. A modal pattern of events obtained with the Respirodeglutometer was present in 42% of the swallows, and an additional 47% had only one event differ from that order.

Spontaneous splenic rupture and infectious mononucleosis in a forensic setting.

In this report we present two fatal cases of spontaneous splenic rupture. The prodromal symptoms, clinical presentations, autopsy findings and histologic findings are discussed, pertinent literature reviewed and the implication for the forensic pathologist stressed.

Three unusual cases of multiple suicidal gunshot wounds to the head.

We describe three unusual cases of suicide involving multiple gunshot wounds, in which all of the victims suffered gunshot wounds to the head, yet none was rendered immediately incapacitated. Injuries were confined to the same area in two of the cases and were located in different areas in the other case. Two of the cases initially appeared to be homicides rather than suicides.

Propane-associated autoerotic fatalities.

We describe 3 unusual autoerotic fatalities in which propane gas was used to induce hypoxia. To our knowledge, these are the first cases of their kind to be reported and described in depth, although brief references to similar cases have appeared. The case histories of 3 white males, aged 22, 42, and 62 years, are described with emphasis on the scene and circumstances and the identification of propane from autopsy materials. In one case, unusual paraphilia and multiple foreign bodies in the rectum were noted. These 3 cases illustrate an unusual form of autoerotic practice in which hypoxia is induced by propane inhalation, unlike the usual neck compression that has been previously described in depth. The importance of scene reconstruction and an awareness of this phenomenon is stressed.