Evaluation of measured and calculated small dense low-density lipoprotein in capillary blood and association with the metabolic syndrome.

BACKGROUND AND AIMS: Small-dense-low-density-lipoprotein cholesterol (sdLDL-C) is proatherogenic and not commonly measured. The aims were to evaluate capillary blood and its stability for sdLDL-C measurement and measure sdLDL-C in patients with metabolic syndrome (MS). METHODS: 182 patients were studied (49 with MS). sdLDL-C was measured by electrophoresis (LipoPrint®), direct measurement (Roche Diagnostics) and Sampson equation. Intima-media thickness (IMT) and presence of atheroma was evaluated. sdLDL-C was compared in paired venous and capillary blood according to CLSI-EP09c (n = 40). sdLDL-C stability was studied after 24 h at room temperature (RT). RESULTS: sdLDL-C in capillary blood and venous blood showed agreement with the direct measurement (bias: 4.17 mg/dL, LOA 95 %:-5.66; 13.99) and estimation (bias:8.12 mg/dL, LOA 95 %:-8.59; 24.82). sdLDL-C is stable in capillary blood for 24 h at RT. The electrophoretic method yielded lower (p < 0.05) sdLDL-C than the equation or direct measurement. Patients with MS had (p < 0.05) higher sdLDL-C (%) than patients without MS. Patients with atheroma plaques had higher sdLDL-C (p < 0.05). Estimated sdLDL-C correlated with IMT (r = 0.259, p < 0.001). CONCLUSIONS: Capillary blood is an alternative to venous blood for sdLDL-C measurement and is stable for 24 h after collection. Estimated and directly measured sdLDL-C associate with the MS being accessible tools for cardiovascular risk assessment.

Proyecto Piloto de Unidad Funcional para Mujeres con Esquizofrenia: Modelo Asistencial de Observatorio-Monitorización-Intervención / Pilot project of a functional unit for women with Schizophrenia: observatory-monitoring-intervention Care model

En los Centros de Salud Mental de Adultos (CSMAs) del Hospital Universitari Mutua Terrassa, en enero de 2023, iniciamos un proyecto piloto de innovación asistencial denominado Unidad Funcional para Mujeres con Esquizofrenia. El objetivo principal de esta comunicación es describir el proceso de designación de las mujeres diana en la unidad, y describir las funciones de los Observatorios de salud física, salud mental y de factores de riesgo psicosocial e inclusión de estas pacientes en los observatorios de salud. De forma complementaria, se describirá el diseño de las Estaciones de Monitorización /Equipos de Vigilancia y las actuaciones o intervenciones específicas centradas en la atención de las necesidades individuales. En la primera fase del proyecto (Enero-Marzo 2023) se revisan las historias clínicas de las mujeres con esquizofrenia para revisar vinculación a profesionales y programas comunitarios. Se describen necesidades de salud física y se revisan antecedentes de consumo de sustancias, uso de benzodiazepinas y opioides, así como aspectos de seguridad farmacológica. En la segunda fase del proyecto (Abril-Junio 2023) se han desarrollado 5 grupos de trabajo (Observatorios de Salud y de Riesgo Psicosocial): 1)Morbi-mortalidad somática, 2)hiperprolactinemia, 3)consumo de sustancias, 4)exclusión social y discriminación, y 5)prescripción y seguridad farmacológica. En la tercera fase del proyecto (Jumio-Septiembre 2023) se desarrollan los Equipos de Vigilancia/Monitorización en Morbi-Mortalidad Somática, hiperprolactinemia, consumo de sustancias, exclusión social/discriminación y seguridad farmacológica, así como intervenciones específicas: colaboración con otras especialidades médicas, consultoría con atención primaria, grupos de ejercicio físico y equipos de intervención en crisis.(AU)

In the context of the Adult Community Mental Health Units (CMHUs) of the Mutua Terrassa University Hospital, we initiated a pilot project of clinical innovation called the Functional Unit for Women with Schizophrenia in January 2023. The main objective of this report is to describe the process of designing a unit targeting women, to characterize the functions of the observatories of Physical Health, Mental Health, and Psychosocial Risk Factors, and to illustrate how these observatories provide surveillance of women’s health needs. The report also describes Monitoring Stations, Vigilance teams, and specific interventions.In the first phase of the project (January - March 2023), medical records from all women with schizophrenia were reviewed to ascertain compliance with clinical appointments and community programs. During this phase, we reviewed physical health records, history of substance use disorders including the use of benzodiazepines and opioid drugs, as well as related aspects of drug safety. In the second phase of the project (April - June 2023), five Observatories of health and social risk factors were developed: 1) somatic morbi-mortality, 2) hyperprolactinemia, 3) use of substances, 4) social exclusion and discrimination, and 5) prescription and drug safety. In the third phase of the project (June-September 2023), we are developing Monitoring Stations or Vigilance teams in these five areas as well as introducing specific interventions: collaboration with primary care and other medical specialties, consultation with primary care teams, physical exercise groups, and crisis intervention units.(AU)

Monitoring the Effectiveness of Treatment in Women with Schizophrenia: New Specialized Cooperative Approaches.

Women with schizophrenia have specific health needs that differ from those of men and that change through successive life stages. We aimed to review the biopsychosocial literature on schizophrenia that addresses clinically important questions related to the treatment of women, including somatic morbi-mortality, hyperprolactinemia, comorbid substance use disorders, social risk factors, and medication effectiveness/safety. Data search terms were as follows: (Morbidity AND mortality) OR hyperprolactinemia OR ("substance use disorders" OR addictions) OR ("social risk factors") OR ("drug safety" OR prescription) AND women AND schizophrenia. A secondary aim was to describe a method of monitoring and interdisciplinary staff strategies. Schizophrenia patients show an increased risk of premature death from cardiovascular/respiratory disease and cancer compared to the general population. The literature suggests that close liaisons with primary care and the introduction of physical exercise groups reduce comorbidity. Various strategies for lowering prolactin levels diminish the negative long-term effects of hyperprolactinemia. Abstinence programs reduce the risk of victimization and trauma in women. Stigma associated with women who have serious psychiatric illness is often linked to reproductive functions. The safety and effectiveness of antipsychotic drug choice and dose differ between men and women and change over a woman's life cycle. Monitoring needs to be multidisciplinary, knowledgeable, and regular.

Schizophrenia: A Review of Social Risk Factors That Affect Women.

Social risk factors are long-term or repeated environmental exposures in childhood and youth that change the brain and may, via epigenetic effects, change gene expression. They thus have the power to initiate or aggravate mental disorders. Because these effects can be mediated via hormonal or immune/inflammatory pathways that differ between men and women, their influence is often sex-specific. The goal of this narrative review is to explore the literature on social risk factors as they affect women with schizophrenia. We searched the PubMed and Scopus databases from 2000 to May 2023 using terms referring to the various social determinants of health in conjunction with "women" and with "schizophrenia". A total of 57 studies fulfilled the inclusion criteria. In the domains of childhood and adult abuse or trauma, victimization, stigma, housing, and socioeconomics, women with schizophrenia showed greater probability than their male peers of suffering negative consequences. Interventions targeting appropriate housing, income support, social and parenting support, protection from abuse, violence, and mothering-directed stigma have, to different degrees, yielded success in reducing stress levels and alleviating the many burdens of schizophrenia in women.

Silencing of SbPPCK1-3 Negatively Affects Development, Stress Responses and Productivity in Sorghum.

Phosphoenolpyruvate carboxylase (PEPC) plays central roles in photosynthesis, respiration, amino acid synthesis, and seed development. PEPC is regulated by different post-translational modifications. Between them, the phosphorylation by PEPC-kinase (PEPCk) is widely documented. In this work, we simultaneously silenced the three sorghum genes encoding PEPCk (SbPPCK1-3) by RNAi interference, obtaining 12 independent transgenic lines (Ppck1-12 lines), showing different degrees of SbPPCK1-3 silencing. Among them, two T2 homozygous lines (Ppck-2 and Ppck-4) were selected for further evaluation. Expression of SbPPCK1 was reduced by 65% and 83% in Ppck-2 and Ppck-4 illuminated leaves, respectively. Expression of SbPPCK2 was higher in roots and decreased by 50% in Ppck-2 and Ppck-4 in this tissue. Expression of SbPPCK3 was low and highly variable. Despite the incomplete gene silencing, it decreased the degree of phosphorylation of PEPC in illuminated leaves, P-deficient plants, and NaCl-treated plants. Both leaves and seeds of Ppck lines had altered metabolic profiles and a general decrease in amino acid content. In addition, Ppck lines showed delayed flowering, and 20% of Ppck-4 plants did not produce flowers at all. The total amount of seeds was lowered by 50% and 36% in Ppck-2 and Ppck-4 lines, respectively. The quality of seeds was lower in Ppck lines: lower amino acid content, including Lys, and higher phytate content. These data confirm the relevance of the phosphorylation of PEPC in sorghum development, stress responses, yield, and quality of seeds.

Sleep Disturbances in At-Risk Mental States and First Episode of Psychosis: A Narrative Review on Interventions.

Sleep disturbances are a common yet often overlooked symptom of psychosis that can drastically affect the quality of life and well-being of those living with the condition. Sleep disorders are common in people diagnosed with schizophrenia and have significant negative effects on the clinical course of the illness and the functional outcomes and quality of life of patients. There is a limited number of studies addressing this question in first-episode psychosis (FEP). In this narrative review, we aimed to provide an overview of sleep disorders in populations with FEP and at-risk mental states (ARMS). The review was focused on the various treatments currently used for sleep disorders, including both non-pharmacological and pharmacological treatments. A total of 48 studies were included. We found that sleep disturbances are associated with attenuated psychotic symptoms and other psychopathological symptoms in ARMSs. The association of sleep disturbances with the transition to psychosis has been poorly investigated. Sleep disturbances have an impact on the quality of life and the psychopathological symptoms of people suffering from FEP. The non-pharmacological treatments include cognitive behavioral therapy for insomnia, bright light therapy, cognitive restructuring techniques, sleep restriction therapy, basic sleep hygiene education, and the provision of portable sleep trackers. Other treatments include antipsychotics in acute phases and melatonin. The early intervention in sleep disturbances may improve overall prognosis in emerging psychosis populations.

Critical Issues in the Management of Agitation, Aggression, and End-of-Life in Delusional Disorder: A Mini-Review.

Background: Compared to other psychotic disorders, there is little information about staging care in delusional disorder (DD). Unlike schizophrenia, this is a disorder that begins in middle age, a time at which chronic medical comorbidities have already begun to impact global functioning. With age, the combination of psychological and somatic conditions leads to new behaviours, e.g., agitation, aggression, and behaviours that require specific preventive and interventive measures. With further age, knowledgeable end-of-life care becomes necessary for this population. Aim: The aim of this article was to review existing evidence on the management of these successive phases. Methods: We conducted a narrative review using PubMed and ClinicalTrials.gov and searched for the following terms: (agitation OR aggressivity OR aggression OR palliative OR "end-of-life") AND ("delusional disorder"). Results: We found that the literature was sparse. Existing evidence suggests that medical causes are frequently at the root of agitation and aggression. With respect to management, de-escalation strategies are generally preferred over pharmacotherapy. Specific delusional syndromes, e.g., de Clérambault, Othello, Capgras, Fregoli, as well as folie à deux, are associated with aggression. The somatic subtype of DD is the one most often requiring palliative care at the end of life. Conclusions: We conclude that insufficient attention has been given to the care needs of the accelerated aging process in DD.

Switching from risperidone to paliperidone palmitate in schizophrenia: Changes in social functioning and cognitive performance.

BACKGROUND: Previous studies suggest that paliperidone might show a better profile for social functioning and cognitive abilities than risperidone. We aimed to study whether switching from risperidone to paliperidone palmitate (PP) is associated with improved cognitive abilities at 3 or 6 months after the switch. METHODS: Thirty-eight patients with a DSM-IV diagnosis of schizophrenia were studied. All patients were treated with oral risperidone or risperidone long-acting injection (RLAI) and had an indication to be switched to PP by their psychiatrists. Statistical analyses were conducted in a final sample of 27 patients who completed the follow-up visits. Three assessments were completed: 1) baseline (preswitch), 2) 3 months postswitch, and 3) 6 months postswitch. Social functioning at each visit was assessed with the Personal and Social Performance Scale. Cognitive assessment was conducted at each visit with the MATRICS Consensus Cognitive Battery. Statistical analyses were performed with R. Linear mixed models were used to explore longitudinal changes in social functioning and cognitive outcomes. RESULTS: PSP scores significantly improved over time after the switch from risperidone to PP. A sensitivity analysis found a significant negative interaction between time and PP maintenance doses (greater improvement in those patients receiving lower doses when compared to higher doses). Regarding longitudinal changes in cognitive functioning, patients improved in 6 out of 10 cognitive tasks involving processing speed, working memory, visual memory, reasoning and problem solving, and attention and vigilance. CONCLUSIONS: Our study suggests that switching from risperidone to PP in patients with schizophrenia is associated with an improvement in social functioning and cognitive performance.

Seventy Years of Treating Delusional Disorder with Antipsychotics: A Historical Perspective.

For many decades, delusional disorder (DD) has been considered a treatment-resistant disorder, with antipsychotics acknowledged as the best, though imperfect, treatment. It is possible that the discovery of the right drug could turn treatment resistance into treatment response. The goal of this narrative review is to provide a historical perspective of the treatment of DD since the introduction of antipsychotics 70 years ago. The following search terms were used to scan the literature: antipsychotics AND "delusional disorder". Findings were that therapy for DD symptoms has changed over time. Initial reports suggested that the drug of choice was the antipsychotic pimozide, and that this drug was especially effective for the somatic subtype of DD. Subsequent studies demonstrated that other antipsychotics, for instance, risperidone and olanzapine, were also highly effective. Treatment response may vary according to the presence or absence of specific symptoms, such as cognitive defect and depression. Clozapine, partial D2 agonists, and long-acting injectable drugs may be more effective than other drugs, but the evidence is not yet in. Because of the absence of robust evidence, treatment guidelines for the optimal management of DD are not yet available.

Neck Circumference for NAFLD Assessment during a 2-Year Nutritional Intervention: The FLiO Study.

Neck circumference (NC) and its relationship to height (NHtR) and weight (NWtR) appear to be good candidates for the non-invasive management of non-alcoholic fatty liver disease (NAFLD). This study aimed to evaluate the ability of routine variables to assess and manage NAFLD in 98 obese subjects with NAFLD included in a 2-year nutritional intervention program. Different measurements were performed at baseline, 6, 12 and 24 months. The nutritional intervention significantly improved the anthropometric, metabolic and imaging variables. NC was significantly associated with the steatosis degree at baseline (r = 0.29), 6 m (r = 0.22), 12 m (r = 0.25), and 24 m (r = 0.39) (all p < 0.05). NC was also significantly associated with visceral adipose tissue at all the study time-points (basal r = 0.78; 6 m r = 0.65; 12 m r = 0.71; 24 m r = 0.77; all p < 0.05). NC and neck ratios combined with ALT levels and HOMA-IR showed a good prediction ability for hepatic fat content and hepatic steatosis (at all time-points) in a ROC analysis. The model improved when weight loss was included in the panel (NC-ROC: 0.982 for steatosis degree). NC and ratios combined with ALT and HOMA-IR showed a good prediction ability for hepatic fat during the intervention. Thus, their application in clinical practice could improve the prevention and management of NAFLD.

A systematic review and meta-analysis of suicidality in psychotic disorders: Stratified analyses by psychotic subtypes, clinical setting and geographical region.

We studied the prevalence of suicide attempts and cumulative incidence of completed suicide in schizophrenia (SZ), schizoaffective disorder (SZAF), delusional disorder (DD) and first-episode psychosis (FEP). A systematic review was performed using Scopus and PubMed databases (1990- July 2020). A random effects meta-analysis was conducted. Stratified analyses were conducted by diagnosis, clinical setting and geographical region. The prevalence of attempted suicide was 20.3% for SZ, 46.8% for SZAF, 11.1% for DD and 12.5% for FEP. Suicide attempts rates were higher for outpatient samples than for inpatient samples in SZ, SZAF and DD (but not FEP) studies. Analyses by geographical region in SZ showed greater prevalence of suicide attempts in North America and Northern Europe. The cumulative incidence of completed suicide was 2.0% for SZ, 2.4% for SZAF; 2.2% for DD and 1.9% for FEP. In schizophrenia and FEP studies, Northern European studies reported higher rates of completed suicide when compared to Western European countries. In conclusion, suicidal behaviour rates in psychoses differ by diagnoses, clinical setting and geographical region.

The Effect of Menopause on Antipsychotic Response.

Background: It has been hypothesized that, whenever estrogen levels decline, psychosis symptoms in women increase. At menopause, this can happen in two main ways: (a) the loss of estrogen (mainly estradiol) can directly affect central neurotransmission, leading to increase in schizophrenia-related symptoms, and (b) the loss of estrogen can decrease the synthesis of enzymes that metabolize antipsychotic drugs, thus weakening their efficacy. Aims and Methods: The aim of this narrative review was to investigate the second possibility by searching PubMed and ClinicalTrials.gov for studies over the last two decades that investigated the metabolism of antipsychotics and their efficacy before and after menopause in women or that studied systemic and local estrogen level effects on the pharmacokinetics and pharmacodynamics of individual antipsychotic drugs. Results: The evidence suggests that symptom level in women with schizophrenia rises after menopause for many reasons beyond hormones but, importantly, there is an estrogen-dependent loss of efficacy related to antipsychotic treatment. Conclusion: Effective clinical intervention is challenging; nevertheless, several promising routes forward are suggested.

Ciclación Rápida en el Trastorno Bipolar: una Metarevisión / Rapid cycling in bipolar disorder: a meta-review

El descriptor evolutivo "Ciclación Rápida" (CR) en el Trastorno Bipolar constituye uno de los retos más importantes a la hora de realizar un plan terapéutico. Sin embargo, a pesar de su uso habitual en la clínica y los libros generalistas, existe poca bibliografía original y escasas publicaciones de investigación sobre el tema. La presente metarevisión analiza los datos más recientes al respecto, enfatizando especialmente los aspectos etiopatogénicos, evolutivos y de tratamiento. Para ello, hemos utilizado las revisiones y artículos recogidos en las bases de datos PubMed y Psychinfo en los últimos 10 años (entre abril del 2011 y abril del 2021), publicadas en inglés o castellano. Después de descartar duplicados, por consenso pudimos seleccionar 76 publicaciones que cumplían los criterios de inclusión. Como principales resultados, destacan los estudios que relacionan la futura aparición de CR con un inicio más precoz del trastorno bipolar, la comorbilidad con el trastorno límite de la personalidad y con el consumo de sustancias. Entre los factores biológicos favorecedores, estarían las alteraciones tiroideas, la obesidad, las alteraciones de los ritmos circadianos, la migraña y otros factores inflamatorios y (quizás) los tratamientos antidepresivos continuados. Entre los aspectos terapéuticos, destacan los bajos niveles de recomendación y de evidencia entre las pautas propuestas en las diferentes revisiones y guías terapéuticas, lo cual se corresponde también con las dificultades de tratamiento en la práctica clínica. Por otra parte, se evidencia la falta de ensayos clínicos y estudios randomizados adecuados y específicos para poder extraer mejores conclusiones al respecto.(AU)

The clinical descriptor “Rapid Cycling” (RC) in Bipolar Disorder is one of the most important challenges in designing a therapeutic plan. However, despite its usual use in medical practice and in general books, there is little original literature and few publications related to it. This umbrella review analyses most recent publications referred to Rapid Cycling, emphasizing specially in their etiology, outcomes and treatment aspects. Reviews from the databases PubMed and Psychinfo have been collected, including the ones from the last 10 years (between April 2011 and April 2021), published in English or Spanish. After discharging duplicates, we applied a consensus to finally recruit 76 publications that fulfilled the inclusion criteria.As main results it must be mentioned the studies that relate RC to early age of onset, the ones that relate it with Borderline Personality Disorder comorbidity and finally the ones with Substance Abuse. Biological factors considered for the etiology of RC would be thyroidal disorders, obesity, circadian rhythms disorders and other inflammatory factors, migraine and (maybe) the maintained antidepressant treatments. Among the therapeutic aspects, the low level of recommendation and evidence in the different therapeutic guidelines stands out. This corresponds with the treatment difficulties observed in the clinical practice. Finally, it is important to mention the lack of clinical trials and randomized studies that are necessary to obtain better conclusions in the area.(AU)

Transient Rectangular Alopecia after Endovascular Embolization: A Case Series of four Patients Describing Dermoscopic and Histopathologic Findings.

Transient rectangular alopecia after endovascular embolization (TRAEE) is considered a specific form of radiodermatitis that is probably underreported in the literature. We present a case series of four patients from our hospital describing dermoscopic and histopathologic findings. Dermoscopic findings overlap with those of alopecia areata; therefore, TRAAE may be misdiagnosed without a precise history. Histopathology analysis of one of our cases showed different characteristics from the only report in the literature (high proportion of follicles in telogen phase). Initial reports considered that total radiation doses between 3 and 5 Gy produced TRAEE, whereas doses higher than 7Gy could trigger permanent alopecia. However, one of our patients exposed to a total dose of 7.6 Gy had complete hair regrowth.

Collaboration between Psychiatrists and Other Allied Medical Specialists for the Treatment of Delusional Disorders.

BACKGROUND: There is increasing evidence that individuals with psychosis are at increased risk for cardiovascular disease, diabetes, metabolic syndrome, and several other medical comorbidities. In delusional disorder (DD), this is particularly so because of the relatively late onset age. AIMS: The aim of this narrative review is to synthesize the literature on the necessity for medical collaboration between psychiatrists and other specialists. METHODS: A non-systematic narrative review was carried out of papers addressing referrals and cooperation among specialists in the care of DD patients. RESULTS: Psychiatrists, the primary care providers for DD patients, depend on neurology to assess cognitive defects and rule out organic sources of delusions. Neurologists rely on psychiatry to help with patient adherence to treatment and the management of psychotropic drug side effects. Psychiatrists require ophthalmology/otolaryngology to treat sensory deficits that often precede delusions; reciprocally, psychiatric consults can help in instances of functional sensory impairment. Close collaboration with dermatologists is essential for treating delusional parasitosis and dysmorphophobia to ensure timely referrals to psychiatry. CONCLUSIONS: This review offers many other examples from the literature of the extent of overlap among medical specialties in the evaluation and effective treatment of DD. Optimal patient care requires close collaboration among specialties.

Biological and Clinical Aspects on the Treatment of Schizophrenia and Related Disorders: New Challenges.

For several decades, it has been postulated that dopaminergic pathways explain the neurobiology of schizophrenia, the biological underpinnings of treatment responses and the main mechanisms of action of antipsychotics [...].

Do Sex/Gender and Menopause Influence the Psychopathology and Comorbidity Observed in Delusional Disorders?

Background: While sex differences and gonadal hormone levels are taken seriously in the understanding and treatment of schizophrenia, their influence in the psychopathology of delusional disorders (DD) remains unknown. Methods: Our strategy was to conduct a narrative review of the effects of (a) sex/gender difference and (b) menopause on delusional content, affective and anxiety-related comorbidity, substance use disorders, cognition, aggressivity, and suicide risk in DD. Results: Because the literature is scarce, our results are tentative. We found that erotomania was more prevalent in women than in men, and especially in women with premenopausal onset. In contrast, jealous and somatic delusions were more commonly seen in DD women with postmenopausal onset. With respect to depressive comorbidity, women with premenopausal onset appear more vulnerable to depression than those with later onset. Age at menopause is reported to correlate positively with intensity of suicidal ideation. Anxiety symptoms may be related to estrogen levels. Men present with higher rates of substance use disorders, particularly alcohol use. Conclusions: Many male/female differences in DD may be attributable to sociocultural factors but menopause, and, therefore, levels of female hormones, influence symptom expression in women and mediate the expression of psychiatric comorbidities. Further research in this area promises to lead to improved individualized treatment.

Delusional Disorder in Old Age: A Hypothesis-Driven Review of Recent Work Focusing on Epidemiology, Clinical Aspects, and Outcomes.

The theme, strength, and duration of a delusion are considered important in distinguishing one psychosis of old age from another. Research results, however, are mostly based on studies conducted on one form of psychosis, namely schizophrenia. The aim of this hypothesis-driven narrative review is to gather clinically important information about the psychosis identified as delusional disorder (DD), as it affects persons of senior age. We hypothesized that DD becomes relatively prevalent in old age, especially in women; and that it is associated with demonstrable brain changes, which, in turn, are associated with cognitive defects and poor pharmacological response, thus increasing the risk of aggression and suicide. Computerized searches in PubMed and ClinicalTrials.gov were conducted using the following search terms: (delusional disorder) AND (elderly OR old OR aged OR psychogeriatrics). A total of 16 recent studies (including case reports) were reviewed. Our hypotheses could not be definitively confirmed because research evidence is lacking. In order to improve eventual outcomes, our literature search demonstrates the need for more targeted, well-designed studies.