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On August 13, 2021, the FDA approved belzutifan (WELIREG, Merck), a first-in-class hypoxia-inducible factor (HIF) inhibitor for adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery. The FDA granted approval based on the clinically meaningful effects on overall response rate (ORR) observed in patients enrolled in Study MK-6482-004. All 61 patients had VHL-associated RCC; some also had CNS hemangioblastomas and/or pNET. For VHL disease–associated RCC, ORR was 49% [95% confidence interval (CI), 36–62], median duration of response (DoR) was not reached, 56% of responders had DoR ≥12 months, and median time to response was 8 months. Twenty-four patients had measurable CNS hemangioblastomas with an ORR of 63% (95% CI, 41–81), and 12 patients had measurable pNET with an ORR of 83% (95% CI, 52–98). For these tumors, median DoR was not reached, with 73% and 50% of patients having response durations ≥12 months for CNS hemangioblastomas and pNET, respectively. The most common adverse reactions, including laboratory abnormalities, reported in ≥20% were anemia, fatigue, increased creatinine, headache, dizziness, increased glucose, and nausea. Belzutifan can render some hormonal contraceptives ineffective and can cause embryo-fetal harm during pregnancy. This article summarizes the data and the FDA thought process supporting traditional approval of belzutifan for this indication.

It has been suggested that law enforcement officer (LEO) weight on the backs of prone subjects may cause asphyxia.Law enforcement officers used their agency-trained "local" single- and double-knee techniques, the "Wisconsin" 3-Point Ground Stabilization, and the Human Factor Research Group Inc single-knee tactical handcuffing techniques, and the weight force was measured.Forty-one LEOs (36 men, 5 women) participated, aged 38.4 ± 8.3 years, and weighing 96.2 ± 19.4 kg. The double-knee technique transmitted more weight than single knee (P0.0001). Wisconsin technique force was lower than other single-knee techniques (P0.0001). Double-knee weight was 23.3 kg plus 24% of LEO's body weight. Mean values for local and Human Factor Research Group Inc single-knee were 30.9 and 32.9 kg, respectively. The Wisconsin single knee weight force was given by 15.4 kg plus 9.5 kg for a male.A double-knee technique applies more weight force than single-knee techniques. The Wisconsin single-knee technique provides the least weight force of single-knee techniques. Law enforcement officer body weight is irrelevant to prone-force weight with single-knee techniques. With double-knee restraint, it has a modest influence. Our data do not support the hypothesis of restraint asphyxia.

Purpose While generally reducing morbidity and mortality, TASER® electrical weapons have risks associated with their usage, including burn injuries and head and cervical trauma associated with uncontrolled falls. The primary non-fatal complications appear to be significant eye injury but no analysis of the mechanisms or suggested treatments has been published. Methods We used a biomechanical model to predict the risk of eye injury as a function of distance from the weapon muzzle to the eye. We compared our model results to recently published epidemiological findings. We also describe the typical presentation and suggest treatment options. Results The globe rupture model predicted that a globe rupture can be expected (50% risk) when the eye is within 6 m of the muzzle and decreases rapidly beyond that. This critical distance is 9 m for lens and retinal damage which is approximately the range of the most common probe cartridges. Beyond 9 m, hyphema is expected along with a perforation by the dart portion of the probe. Our prediction of globe rupture out to 6 m (out of a typical range of 9 m) is consistent with the published risk of enucleation or unilateral blindness being 69 ± 18%, with an eye penetration. Conclusions Significant eye injury is expected from a penetration by an electrical weapon probe at close range. The risk decreases rapidly at extended distances from the muzzle. Not all penetrating globe injuries from electrical weapon probes will result in blindness.

Background Acquired thrombophilia is a potential sequela of malignancy, chronic inflammation, and conditions characterized by severe protein deficiency (for example, nephrotic syndrome, protein-losing enteropathy). As such, venous thrombosis is often a feature, and occasionally a presenting sign, of systemic disease. Ménétrier’s disease is a rare hyperplastic gastropathy that may lead to gastrointestinal protein loss and hypoalbuminemia. To date, reports of venous thrombosis associated with Ménétrier’s disease are exceedingly scarce. Case presentation We report the case of a 40-year-old white man who presented with unprovoked deep venous thrombosis, pulmonary embolism, and renal vein thrombosis. Upon receiving therapeutic anticoagulation, he developed severe gastrointestinal bleeding, and endoscopic evaluation led to a diagnosis of Ménétrier’s disease. A laboratory workup revealed deficiency of protein C, protein S, and antithrombin III, as well as markedly elevated levels of factor VIII. He was determined to have an acquired thrombophilia as a direct result of Ménétrier’s disease. Conclusions This case describes an acquired thrombophilic state in a patient with Ménétrier’s disease and profound hypoalbuminemia. Although this association is rarely described, we discuss the probable mechanisms leading to our patient’s thrombosis. Specifically, we posit that his gastrointestinal protein loss led to a deficiency of several anticoagulant proteins and a compensatory elevation in factor VIII, as occurs in nephrotic syndrome and inflammatory bowel disease. Of note, this patient’s recurrent venous thrombosis was the initial clinical sign of his gastrointestinal pathology.

Risks of handheld electrical weapons include head impact trauma associated with uncontrolled falls, ocular probe penetration injuries, thermal injuries from the ignition of volatile fumes, and weapon confusion police-involved shooting. There is also an uncommon but critical risk of a shooting after a subject gained control of an officer's electrical weapons.The authors searched for police shooting incidents involving loss of control of TASER® weapons via open-source media reports, crowd-sourced internet sites, litigation filings, and a survey of Axon law-enforcement master instructors.The authors report 131 incidents of subjects attempting to or gaining control of an officer's electrical weapon from 2004 to 2020, 53 of which resulting in a shooting. These incidents demonstrated a risk of 11.8 shootings per million electrical weapon discharges (95% confidence limits of 9.0 to 15.1 per million by Wilson score interval).The use of electrical weapons presents a rare but real risk of injury and death from a shooting following a subject's attempts to gain control of the weapon.

Introduction: Our study aimed to determine 1) the association between time spent in the emergency department (ED) hallway and the development of delirium and 2) the hospital location of delirium development. Methods: This single-center, retrospective chart review included patients 18+ years old admitted to the hospital after presenting, without baseline cognitive impairment, to the ED in 2018. We identified the Delirium group by the following: key words describing delirium; orders for psychotropics, special observation, and restraints; or documented positive Confusion Assessment Method (CAM) screen. The Control group included patients not meeting delirium criteria. We used a multivariable logistic regression model, while adjusting for confounders, to assess the odds of delirium development associated with percentage of ED LOS spent in the hallway. Results: A total of 25,156 patients met inclusion criteria with 1920 (7.6%) meeting delirium criteria. Delirium group vs. Control group patients spent a greater percentage of time in the ED hallway (median 50.5% vs 10.8%, P

Background: Vaccination coverages need to be constantly maintained and improved with the implementation of vaccination strategies. This paper describes the development of an evidence-based tool to guide their planning and evaluation.Methods: A scoping review was performed in MEDLINE and institutional websites to search for similar available tools. A first version of the tool was developed considering review results and a four-step method used for the control and continuous improvement of processes and products, namely the Deming cycle. A panel of eight experts was then involved in a Delphi study for the finalization of the tool that was eventually discussed in a face-to-face meeting.Results: The scoping review found only one document and the first version of the tool was composed of 30 items. After the Delphi first round, 11 additional items were suggested and 5 original items amended. After the Delphi second round 41 items were eventually included. During the face-to-face meeting, 7 items were recognized as requisites for setting vaccination strategies, whereas 17 as relevant ones.Conclusions: Current public health challenges impose the need for evidence-based tools to organize effective vaccination strategies. Our tool is a first proposal which aims to reflect this focus.

Summary Background Between March and December, 2020, more than 20 000 laboratory-confirmed cases of SARS-CoV-2 infection were reported in Zambia. However, the number of SARS-CoV-2 infections is likely to be higher than the confirmed case counts because many infected people have mild or no symptoms, and limitations exist with regard to testing capacity and surveillance systems in Zambia. We aimed to estimate SARS-CoV-2 prevalence in six districts of Zambia in July, 2020, using a population-based household survey. Methods Between July 4 and July 27, 2020, we did a cross-sectional cluster-sample survey of households in six districts of Zambia. Within each district, 16 standardised enumeration areas were randomly selected as primary sampling units using probability proportional to size. 20 households from each standardised enumeration area were selected using simple random sampling. All members of selected households were eligible to participate. Consenting participants completed a questionnaire and were tested for SARS-CoV-2 infection using real-time PCR (rtPCR) and anti-SARS-CoV-2 antibodies using ELISA. Prevalence estimates, adjusted for the survey design, were calculated for each diagnostic test separately, and combined. We applied the prevalence estimates to census population projections for each district to derive the estimated number of SARS-CoV-2 infections. Findings Overall, 4258 people from 1866 households participated in the study. The median age of participants was 18·2 years (IQR 7·7–31·4) and 50·6% of participants were female. SARS-CoV-2 prevalence for the combined measure was 10·6% (95% CI 7·3–13·9). The rtPCR-positive prevalence was 7·6% (4·7–10·6) and ELISA-positive prevalence was 2·1% (1·1–3·1). An estimated 454 708 SARS-CoV-2 infections (95% CI 312 705–596 713) occurred in the six districts between March and July, 2020, compared with 4917 laboratory-confirmed cases reported in official statistics from the Zambia National Public Health Institute. Interpretation The estimated number of SARS-CoV-2 infections was much higher than the number of reported cases in six districts in Zambia. The high rtPCR-positive SARS-CoV-2 prevalence was consistent with observed community transmission during the study period. The low ELISA-positive SARS-CoV-2 prevalence might be associated with mitigation measures instituted after initial cases were reported in March, 2020. Zambia should monitor patterns of SARS-CoV-2 prevalence and promote measures that can reduce transmission. Funding US Centers for Disease Control and Prevention.

Objective A 12-lead electrocardiogram (ECG) is the standard of care for chest pain patients. However, 12-lead ECGs have difficulty detecting ischemia of the right ventricle or posterior wall of the heart. New technology exists to mathematically synthesize these leads from a 12-lead ECG; however, this technology has not been evaluated in the emergency department (ED). We assessed the level of agreement between synthesized 18-lead ECGs and actual 18-lead ECGs in identifying ST elevations, ST depressions, and T wave inversions in ED patients. Methods Actual 12- and 18-lead ECGs were acquired and synthesized 18-lead ECGs were produced based on waveforms from 12-lead ECGs. A blinded cardiologist interpreted the actual and synthesized 18-lead ECGs to identify the presence of abnormalities. Using actual 18-lead ECGs as the reference, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and kappa of synthesized 18-lead ECGs in identifying abnormalities were determined. Results Data from 295 patients were analyzed. There was 100% agreement between synthesized 18-lead ECGs and actual 18-lead ECGs in identifying ST elevations and ST depressions (sensitivity, specificity, PPV, and NPV of 100%, and kappa of 1.00). Synthesized 18-lead ECGs had 95% sensitivity, 80% specificity, 97% PPV, and 70% NPV in identifying T wave inversions, when compared with actual 18-lead ECGs (kappa: 0.70). Conclusion Synthesized 18-lead ECGs demonstrated 100% agreement with actual 18-lead ECGs in the identification of ST elevations and ST depressions and good agreement in the identification of T wave inversions in a sample of patients ED patients with complaints suspicious of cardiac origin.

PURPOSE To assess the relationship among tumor response rate, overall survival, and the development of related adverse events of special interest (AESIs) or related immune-mediated adverse events (imAEs) in patients with urothelial cancer treated with anti–programmed death protein 1 or ligand 1 (anti–PD-1/L1) antibodies. PATIENTS AND METHODS We examined seven trials in 1,747 patients with metastatic or locally advanced urothelial cancer that led to approval of an anti–PD-1/L1 antibody. Five trials enrolled patients who had received prior platinum-based therapy, and two enrolled patients who were cisplatin ineligible. The data sets were searched for AESIs, related AESIs, imAEs, and related imAEs. The relationship to study drug was determined by the investigator. ImAEs were defined as AESIs treated with topical or systemic corticosteroids. RESULTS In these exploratory analyses, a related AESI was reported in 64% of responding patients and in 34% of patients who did not respond to the anti–PD-1/L1 antibody, whereas a related imAE occurred in 28% and 12% of patients who did and did not respond to study drug, respectively. In a responder analysis, an increase in overall survival was seen in patients with related AESIs compared with those with no related AESIs (hazard ratio, 0.45; 95% CI, 0.39 to 0.52). Fifty-seven percent of responding patients with a related AESI reported the AESI before documentation of response. CONCLUSION Patients who responded to treatment with an anti–PD-1/L1 antibody were more likely to report a related AESI or related imAE. This relationship did not seem to be due to the increased duration of exposure in responding patients. Systemic corticosteroid use did not appear to affect the duration of response.

Although there is literature concentrating on cross-cultural approaches to academic and community partnerships with Native communities, few address the process and experiences of American Indian women leading federally funded and culturally grounded behavioral health intervention research in Native communities. This paper summarizes relevant literature on community-engaged research with Native communities, examines traditional roles and modern challenges for American Indian women, describes the culturally grounded collaborative process for the authors' behavioral health intervention development with Native communities, and considers emergent themes from our own research experiences navigating competing demands from mainstream and Native communities. It concludes with recommendations for supporting and enhancing resilience.

The U.S. Food and Drug Administration approved enzalutamide for the treatment of patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). At the prespecified interim analysis, a statistically significant improvement in overall survival was demonstrated for patients in the enzalutamide arm compared with patients in the placebo arm. The overall benefit-risk profile supports the expanded indication for enzalutamide. On September 10, 2014, the U.S. Food and Drug Administration approved enzalutamide for the treatment of patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). Enzalutamide was initially approved in 2012 for use in patients with mCRPC who had previously received docetaxel. The current approval was based on the results of a randomized, placebo-controlled, double-blind trial conducted in 1,717 asymptomatic or minimally symptomatic patients with chemotherapy-naïve mCRPC. Patients were assigned to receive either enzalutamide 160 mg or placebo orally once daily. The coprimary endpoints were overall survival (OS) and radiographic progression-free survival (rPFS), which was assessed by independent central radiology review. At the prespecified interim analysis, a statistically significant improvement in OS was demonstrated for patients in the enzalutamide arm compared with patients in the placebo arm (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.60–0.84). The median OS was 32.4 and 30.2 months in the enzalutamide and placebo arms, respectively. A statistically significant prolongation of rPFS was observed in patients in the enzalutamide arm (HR, 0.17; 95% CI, 0.14–0.21). In addition, the time to initiation of cytotoxic chemotherapy was prolonged in the enzalutamide arm (HR, 0.35; 95% CI, 0.30–0.40), with median times of 28.0 and 10.8 months in the enzalutamide and placebo arms, respectively. The safety profile was similar to that previously reported for enzalutamide. Adverse reactions of interest included seizure, hypertension, and falls. Enzalutamide should be discontinued if a seizure occurs during treatment. The overall benefit-risk profile supports the expanded indication for enzalutamide. Implications for Practice: This new approval expands the enzalutamide indication, allowing health care providers and patients to use enzalutamide for the treatment of metastatic castration-resistant prostate cancer either before or after cytotoxic chemotherapy.

Purpose While generally reducing morbidity and mortality, electrical weapons have risks associated with their usage, including burn injuries and trauma associated with uncontrolled fall impacts. However, the prevalence of significant eye injury has not been investigated. Methods We searched for incidents of penetrating eye injury from TASER® conducted electrical weapon (CEW) probes via open source media, litigation filings, and a survey of CEW law-enforcement master instructors. Results We report 20 previously-unpublished cases of penetrating eye injury from electrical weapon probes in law-enforcement field uses. Together with the 8 previously published cases, there are a total of 28 cases out of 3.44 million field uses, giving a demonstrated CEW field-use risk of penetrating eye injury of approximately 1:123 000. Confidence limits [85 000, 178 000] by Wilson score interval. There have been 18 cases of total unilateral blindness or enucleation. We also present legal decisions on this topic. Conclusions The use of electrical weapons presents a rare but real risk of total or partial unilateral blindness from electrical weapon probes. Catastrophic eye injuries appear to be the dominant non-fatal complication of electronic control.

While the physiologic effects of modern conducted electrical weapons (CEW) have been the subject of numerous studies, their effects on neurocognitive functioning, both short-term and long-term, are less well understood. It is also unclear how these effects compare to other use-of-force options or other arrest-related stressors. We compared the neurocognitive effects of an exposure to a TASER(®) (TASER International, Inc, Scottsdale, AZ) X26™ CEW to four other use-of-force scenarios during a training exercise using a well-established neurocognitive metric administered repeatedly over 1 h. Overall, we found that there was a decline in neurocognitive performance immediately post-scenario in all groups, but this effect was transient, of questionable clinical significance, and returned to baseline by 1 h post-scenario.

On April 25, 2016, the FDA approved cabozantinib (Cabometyx; Exelixis, Inc.) for the treatment of advanced renal cell carcinoma (RCC) in patients who have received prior antiangiogenic therapy. The approval was based on data from one randomized, open-label, multicenter study in which patients with RCC who had received prior antiangiogenic therapy were treated with either cabozantinib 60 mg orally once daily (n = 330) or everolimus 10 mg orally once daily (n = 328). The major efficacy outcome measure was progression-free survival (PFS) as assessed by a blinded independent radiology review committee in the first 375 randomized patients. A statistically significant improvement in PFS was seen, with a median PFS of 7.4 and 3.8 months in the cabozantinib and everolimus arms, respectively [hazard ratio (HR), 0.58; 95% confidence interval (CI), 0.45–0.74; P < 0.0001]. At a second interim analysis, a statistically significant improvement in overall survival (OS) in the intent-to-treat population was also demonstrated, with a median OS of 21.4 and 16.5 months in the cabozantinib and everolimus arms, respectively (HR, 0.66; 95% CI, 0.53–0.83; P = 0.0003). The most common (greater than or equal to 25%) adverse reactions included diarrhea, fatigue, nausea, decreased appetite, palmar–plantar erythrodysesthesia syndrome, hypertension, vomiting, weight loss, and constipation. Clin Cancer Res; 23(2); 330–5. ©2016 AACR.

Importance Chronic cerebrospinal venous insufficiency (CCSVI) is characterized by restricted venous outflow from the brain and spinal cord. Whether this condition is associated with multiple sclerosis (MS) and whether venous percutaneous transluminal angioplasty (PTA) is beneficial in persons with MS and CCSVI is controversial. Objective To determine the efficacy and safety of venous PTA in patients with MS and CCSVI. Design, Setting, and Participants We analyzed 177 patients with relapsing-remitting MS; 62 were ineligible, including 47 (26.6%) who did not have CCSVI on color Doppler ultrasonography screening. A total of 115 patients were recruited in the study timeframe. All patients underwent a randomized, double-blind, sham-controlled, parallel-group trial in 6 MS centers in Italy. The trial began in August 2012 and concluded in March 2016; data were analyzed from April 2016 to September 2016. The analysis was intention to treat. Interventions Patients were randomly allocated (2:1) to either venous PTA or catheter venography without venous angioplasty (sham). Main Outcomes and Measures Two primary end points were assessed at 12 months: (1) a composite functional measure (ie, walking control, balance, manual dexterity, postvoid residual urine volume, and visual acuity) and (2) a measure of new combined brain lesions on magnetic resonance imaging, including the proportion of lesion-free patients. Combined lesions included T1 gadolinium-enhancing lesions plus new or enlarged T2 lesions. Results Of the included 115 patients with relapsing-remitting MS, 76 were allocated to the PTA group (45 female [59%]; mean [SD] age, 40.0 [10.3] years) and 39 to the sham group (29 female [74%]; mean [SD] age, 37.5 [10.6] years); 112 (97.4%) completed follow-up. No serious adverse events occurred. Flow restoration was achieved in 38 of 71 patients (54%) in the PTA group. The functional composite measure did not differ between the PTA and sham groups (41.7% vs 48.7%; odds ratio, 0.75; 95% CI, 0.34-1.68;P = .49). The mean (SD) number of combined lesions on magnetic resonance imaging at 6 to 12 months were 0.47 (1.19) in the PTA group vs 1.27 (2.65) in the sham group (mean ratio, 0.37; 95% CI, 0.15-0.91;P = .03: adjustedP = .09) and were 1.40 (4.21) in the PTA group vs 1.95 (3.73) in the sham group at 0 to 12 months (mean ratio, 0.72; 95% CI, 0.32-1.63;P = .45; adjustedP = .45). At follow-up after 6 to 12 months, 58 of 70 patients (83%) in the PTA group and 22 of 33 (67%) in the sham group were free of new lesions on magnetic resonance imaging (odds ratio, 2.64; 95% CI, 1.11-6.28;P = .03; adjustedP = .09). At 0 to 12 months, 46 of 73 patients (63.0%) in the PTA group and 18 of 37 (49%) in the sham group were free of new lesions on magnetic resonance imaging (odds ratio, 1.80; 95% CI, 0.81-4.01;P = .15; adjustedP = .30). Conclusion and Relevance Venous PTA has proven to be a safe but largely ineffective technique; the treatment cannot be recommended in patients with MS. Trial Registration clinicaltrials.gov Identifier:NCT01371760

Background: Spanish-speaking individuals comprise a growing percentage of the United States population. They have greater difficulty than most in accessing and remaining in psychiatric treatments, including psychotherapy, their stated preference. The literature on cultural competence in treating Hispanic patients provides few details of psychotherapeutic adaptations. Objective: This article, based on interpersonal psychotherapy (IPT) supervision for a low-socioeconomic sample of monolingual Spanish-speaking New York City patients, describes culturally specific psychotherapy. Method: In conducting IPT for Spanish-speaking patients with DSM-IV major depressive disorder, we reviewed cases in weekly supervision over 3 years (January 2005 to January 2008) to explore treatment themes and evaluate the congruence of IPT in addressing them. Important themes are illustrated by case example. Results: Key themes include (1) the centrality of family, (2) conflicts due to migration and acculturation, (3) gender roles, (4) need to avoid humiliating or irrevocable social confrontation, and (5) equanimity in facing an unpredictable environment. Conclusions: IPT appears a compatible intervention, focusing on and adaptable to these important issues for Hispanic patients.

To examine the prevalence of common psychiatric disorders and associated treatment-seeking, stratified by gender, among American Indians/Alaska Natives and non-Hispanic whites in the United States. Lifetime and 12-month rates are estimated, both unadjusted and adjusted for sociodemographic correlates. Analyses were conducted with the American Indians/Alaska Native (n = 701) and Non-Hispanic white (n = 24,507) samples in the 2001–2002 National Epidemiologic Survey on Alcohol and Related Conditions [(NESARC) n = 43,093]. Overall, 70 % of the American Indian/Alaska Native men and 63 % of the women met criteria for at least one Diagnostic and Statistical Manual-IV lifetime disorder, compared to 62 and 53 % of Non-Hispanic white men and women, respectively. Adjusting for sociodemographic correlates attenuated the differences found. Nearly half of American Indians/Alaska Natives had a psychiatric disorder in the previous year; again, sociodemographic adjustments explained some of the differences found. Overall, the comparisons to non-Hispanic whites showed differences were more common among American Indian/Alaska Native women than men. Among those with a disorder, American Indian/Alaska Native women had greater odds of treatment-seeking for 12-month anxiety disorders. As the first study to provide national estimates, by gender, of the prevalence and treatment of a broad range of psychiatric disorders among American Indians/Alaska Natives, a pattern of higher prevalence of psychiatric disorder was found relative to Non-Hispanic whites. Such differences were more common among women than men. Prevalence may be overestimated due to cultural limitations in measurement. Unmeasured risk factors, some specific to American Indians/Alaska Natives, may also partially explain these results.

We examined health disparities among American Indian men and boys within the framework of historical trauma, which incorporates the historical context of collective massive group trauma across generations. We reviewed the impact of collective traumatic experiences among Lakota men, who have faced cross-generational challenges to enacting traditional tribal roles. We describe historical trauma–informed interventions used with two tribal groups: Lakota men and Southwestern American Indian boys. These two interventions represent novel approaches to addressing historical trauma and the health disparities that American Indians face. We offer public health implications and recommendations for strategies to use in the planning and implementation of policy, research, and program development with American Indian boys and men.

Purpose: On December 15, 2008, the US Food and Drug Administration approved plerixafor (Mozobil®; Genzyme Corp.), a new small-molecule inhibitor of the CXCR4 chemokine receptor, for use in combination with granulocyte colony-stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSC) to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM). This summary reviews the database supporting this approval. Experimental Design: The safety and efficacy of plerixafor were demonstrated by 2 multicenter, randomized, placebo-controlled studies in patients with NHL and MM who were eligible for autologous HSC transplantation. The primary efficacy end points were the collection of ≧5 × 106 CD34+ cells/kg from the peripheral blood in 4 or fewer apheresis sessions in patients with NHL or ≧6 × 106 CD34+ cells/kg from the peripheral blood in 2 or fewer apheresis sessions in patients with MM. Results: The 2 randomized studies combined enrolled 600 patients (298 with NHL and 302 with MM). Fifty-nine percent of patients with NHL who were mobilized with G-CSF and plerixafor had peripheral blood HSC collections of ≧5 × 106 CD34+ cells/kg in 4 or fewer apheresis sessions, compared with 20% of patients with NHL who were mobilized with G-CSF and placebo (p < 0.001). Seventy-two percent of patients with MM who were mobilized with Mozobil and G-CSF had peripheral blood HSC collections of ≧6 × 106 CD34+ cells/kg in 2 or fewer apheresis sessions, compared with 34% of patients with MM who were mobilized with placebo and G-CSF (p < 0.001). Common adverse reactions included diarrhea, nausea, vomiting, flatulence, injection site reactions, fatigue, arthralgia, headache, dizziness, and insomnia. Conclusions: This report describes the Food and Drug Administration review supporting the approval of plerixafor.

Historical trauma (HT) is cumulative emotional and psychological wounding over the lifespan and across generations, emanating from massive group trauma experiences; the historical trauma response (HTR) is the constellation of features in reaction to this trauma. The HTR often includes depression, self-destructive behavior, suicidal thoughts and gestures, anxiety, low self-esteem, anger, and difficulty recognizing and expressing emotions. It may include substance abuse, often an attempt to avoid painful feelings through self-medication. Historical unresolved grief is the associated affect that accompanies HTR; this grief may be considered fixated, impaired, delayed, and/or disenfranchised. This article will explain HT theory and the HTR, delineate the features of the HTR and its grounding in the literature, offer specific Native examples of HT and HTR, and will suggest ways to incorporate HT theory in treatment, research and evaluation. The article will conclude with implications for all massively traumatized populations.

A rare case of intrabony angiomyoma affecting the mandible is presented. The patient was 25 years old male who complained of swelling and pain in the posterior segment of his lower jaw. Histopathologically diagnosed angiomyoma is discussed with emphasis on the pathogenesis in the present case. Literature concerning the lesion is reviewed. In the present paper we report a case of angiomyoma affecting the mandible. Angiomyomas are also known as vascular leiomyomas which commonly occur in the wrist and ankle region. They are painful tumours as was also evident in our case. These tumours are characterized histopathologically by convuluted thick walled vessels associated with bundles of well differentiated smooth muscle elements. They rarely affect the oral cavity. Therefore our case is one of the few cases affecting the oral cavity as reported earlier. Tumours of the smooth muscle cells which form involuntary muscle are known as leiomyomas. These commonly affect the alimentary tract. They are rarely found to affect the oral cavity.