How and when to treat the most common adverse effects of antipsychotics: Expert review from research to clinical practice.

OBJECTIVE: As most treatment guidelines for antipsychotics focus on clinical efficacy, we will instead focus on adverse effects and how to manage them. In this review, we aim to provide an up-to-date clinical resource for providers who prescribe antipsychotics and have included here "what's new" and "what to do" for numerous antipsychotic-induced adverse effects. METHODS: A review was performed of relevant literature, studies, randomized clinical trials, and systematic reviews. This information was combined with the clinical experience of the authors to formulate a practical guide for treating adverse effects of antipsychotics with an emphasis on metabolic and movement disorder adverse effects and brief mention of some others (sedation and sexual dysfunction). CONCLUSIONS: Antipsychotics are an integral part of psychiatric care and are often prescribed lifelong. When choosing an antipsychotic, special consideration must be given to adverse effects which have an undeniable impact on quality of life and can often be the deciding factor in patients' medication compliance. While patients may respond well to one specific medication, they may still experience adverse effects that lead them to discontinue it or switch to a more tolerable but less effective option. However, strategies do exist for managing and treating adverse effects, especially metabolic and movement adverse effects, allowing better personalization of antipsychotic choice.

Can Na18F PET/CT bone scans help when deciding if early intervention is needed in patients being treated with a TSF attached to the tibia: insights from 41 patients.

PURPOSE: To demonstrate the usefulness of positron emission tomography (PET)/computed tomography (CT) bone scans for gaining insight into healing bone status earlier than CT or X-ray alone. METHODS: Forty-one prospective patients being treated with a Taylor Spatial Frame were recruited. We registered data obtained from successive static CT scans for each patient, to align the broken bone. Radionuclide uptake was calculated over a spherical volume of interest (VOI). For all voxels in the VOI, histograms and cumulative distribution functions of the CT and PET data were used to assess the type and progress of new bone growth and radionuclide uptake. The radionuclide uptake difference per day between the PET/CT scans was displayed in a scatter plot. Superimposing CT and PET slice data and observing the spatiotemporal uptake of 18F- in the region of healing bone by a time-sequenced movie allowed qualitative evaluation. RESULTS: Numerical evaluation, particularly the shape and distribution of Hounsfield Units and radionuclide uptake in the graphs, combined with visual evaluation and the movies enabled the identification of six patients needing intervention as well as those not requiring intervention. Every revised patient proceeded to a successful treatment conclusion. CONCLUSION: Numerical and visual evaluation based on all the voxels in the VOI may aid the orthopedic surgeon to assess a patient's progression to recovery. By identifying slow or insufficient progress at an early stage and observing the uptake of 18F- in specific regions of bone, it might be possible to shorten the recovery time and avoid unnecessary late complications.

Scientists, society, and stuttering.

More than 70 million people worldwide are affected by developmental stuttering. It is important to reach out to the public, scientific and medical communities, and those who stutter with a goal to raise awareness about stuttering. In this short perspective, we argue that to educate, advocate, and spread awareness about stuttering, we need role models, support, and opportunities.

Accuracy and precision of a CT method for assessing migration in shoulder arthroplasty: an experimental study.

BACKGROUND: Radiostereometric analysis (RSA) is the gold standard to measure early implant migration which is a predictive factor for implant survival. PURPOSE: To validate an alternative computed tomography (CT) technique to measure implant migration in shoulder arthroplasty. MATERIAL AND METHODS: A cadaver proximal humerus and a scapula, which had tantalum beads incorporated within them, were prepared to accept a short-stemmed humeral component and a two-pegged glenoid component of a commercial total shoulder arthroplasty (TSA) system. A five degree of freedom micrometer and goniometer equipped rig was used to translate and rotate the implant components relative to the respective bone to predetermined positions. Double CT examinations were performed for each position and CT motion analysis software (CTMA) was used to assess these movements. The accuracy and precision of the software was estimated using the rig's micrometers and goniometers as the gold standard. The technique's effective dose was also assessed. RESULTS: The accuracy was in the range of 0.07-0.23 mm in translation and 0.22-0.71° in rotation. The precision was in the range of 0.08-0.15 mm in translation and 0.23-0.54° in rotation. The mean effective dose for the CT scans was calculated to be 0.27 mSv. CONCLUSION: In this experimental setting, accuracy, precision, and effective dose of the CTMA technique were found to be comparable to that of RSA. Therefore, we believe clinical studies are warranted to determine if CTMA is a suitable alternative to traditional RSA for migration measurements in TSA.

Ecopipam as a pharmacologic treatment of stuttering.

BACKGROUND: Stuttering, also known as childhood-onset fluency disorder, is a chronic neurodevelopmental disorder that affects 1% of the population and can greatly impact an individual's social, occupational, and academic functioning. Prior research has shown dopamine D2 antagonists are effective in reducing the severity of stuttering symptoms, but these compounds can be associated with metabolic and movement disorder adverse effects. Ecopipam is an investigational medication that acts as a selective dopamine D1 receptor antagonist. This mechanism should reduce the likelihood of metabolic and movement disorder adverse effects of D2 antagonists. METHOD: This open-label pilot study investigated ecopipam in the treatment of adults who stutter. RESULTS: The results showed that a majority of participants demonstrated improvement in their stuttering. The medication was well tolerated. CONCLUSIONS: These positive, preliminary findings suggest that a doubleblind, randomized controlled clinical trial to examine the efficacy of ecopipam in the treatment of stuttering is warranted.

Prosthetic liner wear in total hip replacement: a longitudinal 13-year study with computed tomography.

This case report follows a woman who had a total hip replacement in 1992 when she was 45 years old. Six serial computed tomography (CT) examinations over a period of 13 years provided information that allowed her revision surgery to be limited to liner replacement as opposed to replacement of the entire prosthesis. Additionally, they provided data that ruled out the presence of osteolysis and indeed none was found at surgery. In 2004, when the first CT was performed, the 3D distance the femoral head had penetrated into the cup was determined to be 2.6 mm. By 2017, femoral head penetration had progressed to 5.0 mm. The extracted liner showed wear at the thinnest part to be 5.5 mm, as measured with a micrometer. The use of modern CT techniques can identify problems, while still correctable without major surgery. Furthermore, the ability of CT to assess the direction of wear revealed that the liner wear changed from the cranial to dorsal direction.

A case series on the effectiveness of lurasidone in patients with stuttering.

BACKGROUND: The prevalence of stuttering is approximately 1% of the population, affecting an estimated 3 million individuals in the United States. The dopamine hypothesis of stuttering explains that abnormally increased cerebral dopamine affects the balanced levels that maintain the basal ganglia circuits, which helps with timing cues in initiating speech. This is especially significant when considering treatment strategies. We report a reduction in stuttering with lurasidone, a potent D2 receptor antagonist with a relatively favorable adverse effects profile. METHODS: We conducted a non-randomized, open-label study of lurasidone in patients with stuttering (N = 7). Patients self-reported stuttering severity, locus of control, and avoidance using the Subjective Screening of Stuttering (SSS) scale and were assessed with the Clinical Global Impression (CGI) Scale. RESULTS: We observed a notable, statistically significant improvement in all areas of stuttering, as rated by the SSS scale. According to the CGI-Improvement Scale, 2 patients were scored as "very much improved" and 5 were scored as "much improved." CONCLUSIONS: This open-label study of lurasidone in patients with stuttering showed improvement in subjective symptoms, in CGI scores, and on the SSS scale.

Can Spatiotemporal Fluoride (18F-) Uptake be Used to Assess Bone Formation in the Tibia? A Longitudinal Study Using PET/CT.

BACKGROUND: When a bone is broken for any reason, it is important for the orthopaedic surgeon to know how bone healing is progressing. There has been resurgence in the use of the fluoride (18F-) ion to evaluate various bone conditions. This has been made possible by availability of positron emission tomography (PET)/CT hybrid scanners together with cyclotrons. Absorbed on the bone surface from blood flow, 18F- attaches to the osteoblasts in cancellous bone and acts as a pharmacokinetic agent, which reflects the local physiologic activity of bone. This is important because it shows bone formation indicating that the bone is healing or no bone formation indicating no healing. As 18F- is extracted from blood in proportion to blood flow and bone formation, it thus enables determination of bone healing progress. QUESTIONS/PURPOSES: The primary objective of this study was to determine whether videos showing the spatiotemporal uptake of 18F- via PET bone scans could show problematic bone healing in patients with complex tibia conditions. A secondary objective was to determine if semiquantification of radionuclide uptake was consistent with bone healing. METHODS: This study investigated measurements of tibia bone formation in patients with complex fractures, osteomyelitis, and osteotomies treated with a Taylor Spatial FrameTM (TSF) by comparing clinical healing progress with spatiotemporal fluoride (18F-) uptake and the semiquantitative standardized uptake value (SUV). This procedure included static and dynamic image acquisition. For intrapatient volumes acquired at different times, the CT and PET data were spatially registered to bring the ends of the bones that were supposed to heal into alignment. To qualitatively observe how and where bone formation was occurring, time-sequenced volumes were reconstructed and viewed as a video. To semiquantify the uptake, the mean and maximum SUVs (SUVmean, SUVmax) were calculated for the ends of the bones that were supposed to heal and for normal bone, using a spherical volume of interest drawn on the registered volumes. To make the semiquantitative data comparable for all patients with multiple examinations, the SUVmean and SUVmax difference per day (SUVmeanDPD and SUVmaxDPD) between the first PET/CT scan and each subsequent one was calculated. Indicators of poor healing progress were (1) uneven distribution of the radionuclide uptake between ends of the bones that were supposed to heal as seen in the video or, (2) low absolute magnitude of the SUV difference data. Twenty-four patients treated between October 2013 and April 2015 with a TSF gave informed consent to be examined with 18F- PET/CT bone scans. Twenty-two patients successfully completed treatment, one of whom had only one PET/CT scan. RESULTS: Observation of 18F- uptake was able to identify three patients whose healing progress was poor, indicated by uneven distribution of radionuclide uptake across the ends of the bones that were supposed to heal. An absolute magnitude of the SUVmaxDPD of 0.18 or greater indicated good bone formation progress. This was verified in 10 patients by the days between the operation to attach and to remove the TSF being less than 250 days, whereas other SUVmaxDPD values were ambiguous, with 11 patients achieving successful completion. CONCLUSIONS: Observation of the spatiotemporal uptake of 18F- appears to be a promising method to enable the clinician to assess the progress of bone formation in different parts of the bone. Bone uptake which is uneven across the ends of bone that were supposed to heal or very low bone uptake might indicate impaired bone healing where early intervention may then be needed. However, semiquantification of 18F- uptake (SUVmaxDPD), SUVmeanDPD) was ambiguous in showing consistency with the bone-healing progress. LEVEL OF EVIDENCE: Level III, diagnostic study.

Remote, Synchronous, Hands-On Ultrasound Education.

BACKGROUND: Ultrasound has become a major diagnostic tool in many parts of the world, with broad clinical applications. Ultrasound provides a noninvasive, painless mode of diagnostics that produces instant results. Disseminating ultrasound skills to remote and rural communities has become a challenge for many medical schools, particularly those where distances are great and the density of population is low. MATERIALS AND METHODS: The University of California, Irvine School of Medicine and the University of New England School of Rural Medicine in Australia piloted the use of dual video feeds in two scenarios: (1) to display the instructor's ultrasound feed and the instructor's transducer placement to provide guidance for remote students; and (2) to display side-by-side views of the instructor's and the remote student's ultrasound feeds to allow the instructor to guide the remote student in his or her transducer placement. RESULTS AND CONCLUSIONS: Using high-speed broadband connections, the two schools demonstrated the feasibility of remote, synchronous, practical, and hands-on ultrasound training and instruction over international distances. This opens up a broad range of possibilities for future remote ultrasound education.

A new automated way to measure polyethylene wear in THA using a high resolution CT scanner: method and analysis.

As the most advantageous total hip arthroplasty (THA) operation is the first, timely replacement of only the liner is socially and economically important because the utilization of THA is increasing as younger and more active patients are receiving implants and they are living longer. Automatic algorithms were developed to infer liner wear by estimating the separation between the acetabular cup and femoral component head given a computed tomography (CT) volume. Two series of CT volumes of a hip phantom were acquired with the femoral component head placed at 14 different positions relative to the acetabular cup. The mean and standard deviation (SD) of the diameter of the acetabular cup and femoral component head, in addition to the range of error in the expected wear values and the repeatability of all the measurements, were calculated. The algorithms resulted in a mean (± SD) for the diameter of the acetabular cup of 54.21 (± 0.011) mm and for the femoral component head of 22.09 (± 0.02) mm. The wear error was ± 0.1 mm and the repeatability was 0.077 mm. This approach is applicable clinically as it utilizes readily available computed tomography imaging systems and requires only five minutes of human interaction.

Can Na18F PET/CT be used to study bone remodeling in the tibia when patients are being treated with a Taylor Spatial Frame?

Monitoring and quantifying bone remodeling are of interest, for example, in correction osteotomies, delayed fracture healing pseudarthrosis, bone lengthening, and other instances. Seven patients who had operations to attach an Ilizarov-derived Taylor Spatial Frame to the tibia gave informed consent. Each patient was examined by Na(18)F PET/CT twice, at approximately six weeks and three months after the operation. A validated software tool was used for the following processing steps. The first and second CT volumes were aligned in 3D and the respective PET volumes were aligned accordingly. In the first PET volume spherical volumes of interest (VOIs) were delineated for the crural fracture and normal bone and transferred to the second PET volume for SUVmax evaluation. This method potentially provides clinical insight into questions such as, when has the bone remodeling progressed well enough to safely remove the TSF? and when is intervention required, in a timelier manner than current methods? For example, in two patients who completed treatment, the SUVmax between the first and second PET/CT examination decreased by 42% and 13%, respectively. Further studies in a larger patient population are needed to verify these preliminary results by correlating regional Na(18)F PET measurements to clinical and radiological findings.

In vivo and ex vivo measurement of polyethylene wear in total hip arthroplasty: comparison of measurements using a CT algorithm, a coordinate-measuring machine, and a micrometer.

BACKGROUND: Determination of the amount of wear in a polyethylene liner following total hip arthroplasty (THA) is important for both the clinical care of individual patients and the development of new types of liners. PATIENTS AND METHODS: We measured in vivo wear of the polyethylene liner using computed tomography (CT) (obtained in the course of regular clinical care) and compared it to coordinate-measuring machine (CMM) readings. Also, changes in liner thickness of the same retrieved polyethylene liner were measured using a micrometer, and were compared to CT and CMM measurements. The distance between the centers of the acetabular cup and femoral head component was measured in 3D CT, using a semi-automatic analysis method. CMM readings were performed on each acetabular liner and data were analyzed using 3D computer-aided design software. Micrometer readings compared the thickest and thinnest regions of the liner. We analyzed 10 THA CTs and retrievals that met minimal requirements for CT slice thickness and explanted cup condition. RESULTS - For the 10 cups, the mean difference between the CT readings and the CMM readings was -0.09 (-0.38 to 0.20) mm. This difference was not statistically significant (p = 0.6). Between CT and micrometer, the mean difference was 0.11 (-0.33 to 0.55) mm. This difference was not statistically significant (p = 0.6). INTERPRETATION - Our results show that CT imaging is ready to be used as a tool in clinical wear measurement of polyethylene liners used in THA.

Psychedelics in developmental stuttering to modulate brain functioning: a new therapeutic perspective?

Developmental stuttering (DS) is a neurodevelopmental speech-motor disorder characterized by symptoms such as blocks, repetitions, and prolongations. Persistent DS often has a significant negative impact on quality of life, and interventions for it have limited efficacy. Herein, we briefly review existing research on the neurophysiological underpinnings of DS -specifically, brain metabolic and default mode/social-cognitive networks (DMN/SCN) anomalies- arguing that psychedelic compounds might be considered and investigated (e.g., in randomized clinical trials) for treatment of DS. The neural background of DS is likely to be heterogeneous, and some contribution from genetically determinants of metabolic deficiencies in the basal ganglia and speech-motor cortical regions are thought to play a role in appearance of DS symptoms, which possibly results in a cascade of events contributing to impairments in speech-motor execution. In persistent DS, the difficulties of speech are often linked to a series of associated aspects such as social anxiety and social avoidance. In this context, the SCN and DMN (also influencing a series of fronto-parietal, somato-motor, and attentional networks) may have a role in worsening dysfluencies. Interestingly, brain metabolism and SCN/DMN connectivity can be modified by psychedelics, which have been shown to improve clinical evidence of some psychiatric conditions (e.g., depression, post-traumatic stress disorder, etc.) associated with psychological constructs such as rumination and social anxiety, which also tend to be present in persistent DS. To date, while there have been no controlled trials on the effects of psychedelics in DS, anecdotal evidence suggests that these agents may have beneficial effects on stuttering and its associated characteristics. We suggest that psychedelics warrant investigation in DS.

Stuttering as a spectrum disorder: A hypothesis.

Childhood-onset fluency disorder, commonly referred to as stuttering, affects over 70 million adults worldwide. While stuttering predominantly initiates during childhood and is more prevalent in males, it presents consistent symptoms during conversational speech. Despite these common clinical manifestations, evidence suggests that stuttering, may arise from different etiologies, emphasizing the need for personalized therapy approaches. Current research models often regard the stuttering population as a singular, homogenous group, potentially overlooking the inherent heterogeneity. This perspective consolidates both historical and recent observations to emphasize that stuttering is a heterogeneous condition with diverse causes. As such, it is crucial that both therapeutic research and clinical practices consider the potential for varied etiologies leading to stuttering. Recognizing stuttering as a spectrum disorder embraces its inherent variability, allowing for a more nuanced categorization of individuals based on the underlying causes. This perspective aligns with the principles of precision medicine, advocating for tailored treatments for distinct subgroups of people who stutter, ultimately leading to personalized therapeutic approaches.

Polypharmacy- Purpose, Benefits and Limitations.

With what has become increasingly common among nearly all medical specialties, the number of patients who have various comorbid diseases both psychiatrically and mentally challenges the field of psychiatry. As a result, it is not uncommon for physicians to be imposed with treatment decisions regarding polypharmacy, the use of multiple medications to treat different diseases, or even the same illness several times. In recent years, the concept of polypharmacy has been known to have a negative undertone, implying that its use is inappropriate or causes more harm than the potential benefit. Although the use of any medication should involve risk versus benefit discussion, when used with good clinical judgment and pharmacologically sound knowledge, this practice can be potentially life-altering for patients.