Ketamine for Refractory Headache: A Retrospective Analysis.

BACKGROUND AND OBJECTIVES: The burden of chronic headache disorders in the United States is substantial. Some patients are treatment refractory. Ketamine, an N-methyl-D-aspartate antagonist, provides potent analgesia in subanesthetic doses in chronic pain, and limited data suggest it may alleviate headache in some patients. METHODS: We performed a retrospective study of 61 patients admitted over 3 years for 5 days of intravenous therapy that included continuous ketamine to determine responder rate and patient and ketamine infusion characteristics. Pain ratings at 2 follow-up visits were recorded. An immediate responder was a patient with decrease of 2 points or greater in the numerical rating scale (0-10) from start to final pain in the hospital. Sustained response at office visits 1 and 2 was determined based on maintaining the 2-point improvement at those visits. Patients were assessed daily for pain and adverse events (AEs). RESULTS: Forty-eight (77%) of the 61 patients were immediate responders. There were no differences regarding demographics, opioid use, or fibromyalgia between immediate responders and nonresponders. Maximum improvement occurred 4.56 days (mean) into treatment. Sustained response occurred in 40% of patients at visit 1 (mean, 38.1 days) and 39% of patients at visit 2 (mean, 101.3 days). The mean maximum ketamine rate was 65.2 ± 2.8 mg/h (0.76 mg/kg per hour). Ketamine rates did not differ between groups. Adverse events occurred equally in responders and nonresponders and were mild. CONCLUSIONS: Ketamine was associated with short-term analgesia in many refractory headache patients with tolerable adverse events. A prospective study is warranted to confirm this and elucidate responder characteristics

What’s Sex (Composition) Got to Do with It? The Importance of Sex Composition of Gangs for Female and Male Members’ Offending and Victimization

Sex composition of groups has been theorized in organizational sociology and found in prior work to structure female and male members’ behaviors and experiences. Peer group and gang literature similarly finds that the sex gap in offending varies across groups of differing sex ratios. Drawing on this and other research linking gang membership, offending, and victimization, we examine whether sex composition of gangs is linked to sex differences in offending in this sample, further assess whether sex composition similarly structures females’ and males’ victimization experiences, and if so, why. Self-report data from gang members in a multi-site, longitudinal study of 3,820 youths are employed. Results support previous findings about variations in member delinquency by both sex and sex composition of the gang and also indicate parallel variations in members’ victimization. These results are further considered within the context of facilitating effects such as gender dynamics, gang characteristics, and normative orientation

Ketamine for Refractory Chronic Migraine: An Observational Pilot Study and Metabolite Analysis.

Patients with refractory chronic migraine have substantial disability and have failed many acute and preventive medications. When aggressive intravenous therapy is indicated, both lidocaine and (R,S)-ketamine infusions have been used successfully to provide relief. Retrospective studies have shown that both agents may be associated with short-term analgesia. In this prospective, observational pilot study of 6 patients, we compared the effects of lidocaine and (R,S)-ketamine infusions and performed metabolite analyses of (R,S)-ketamine to determine its metabolic profile in this population. One of (R,S)-ketamine\u27s metabolites, (2R,6R)-hydroxynorketamine, has been shown in animal studies to reduce pain, but human studies in patients undergoing continuous (R,S)-ketamine infusions for migraine are lacking. All 6 patients tolerated both infusions well with mild adverse effects. The baseline mean pain rating (0-10 numeric rating scale) decreased from 7.5 ± 2.2 to 4.7 ± 2.8 by end of lidocaine treatment ( P≤.05 role= presentation \u3eP≤.05 ) but increased to 7.0 ± 1.4 by the postdischarge visit at 4 weeks (P \u3e .05 vs baseline). The baseline mean pain rating prior to ketamine treatment was 7.4 ± 1.4, which decreased to 3.7 ± 2.3 by the end of the hospitalization ( P≤.05 role= presentation \u3eP≤.05 ) but increased to 7.2 ± 1.7 by the postdischarge visit at 6 weeks (P \u3e .05 vs baseline). For the primary outcome the change in pain from baseline to end of treatment was greater for ketamine than lidocaine (-3.7 vs -2.8; P≤.05 role= presentation \u3eP≤.05 ), but this has minimal clinical significance. Ketamine metabolite analysis revealed that (2R,6R)-hydroxynorketamine was the predominant metabolite during most of the infusion, consistent with previous studies

Outcomes of relapsed clinical stage I versus de novo metastatic testicular cancer patients: an analysis of the IGCCCG Update database.

BACKGROUND Active surveillance after orchiectomy is the preferred management in clinical stage I (CSI) germ-cell tumours (GCT) associated with a 15 to 30% relapse rate. PATIENTS AND METHODS In the IGCCCG Update database, we compared the outcomes of gonadal disseminated GCT relapsing from initial CSI to outcomes of patients with de novo metastatic GCT. RESULTS A total of 1014 seminoma (Sem) [298 (29.4%) relapsed from CSI, 716 (70.6%) de novo] and 3103 non-seminoma (NSem) [626 (20.2%) relapsed from CSI, 2477 (79.8%) de novo] were identified. Among Sem, no statistically significant differences in PFS and OS were found between patients relapsing from CSI and de novo metastatic disease [5-year progression-free survival (5y-PFS) 87.6% versus 88.5%; 5-year overall survival (5y-OS) 93.2% versus 96.1%). Among NSem, PFS and OS were higher overall in relapsing CSI patients (5y-PFS 84.6% versus 80.0%; 5y-OS 93.3% versus 88.7%), but there were no differences within the same IGCCCG prognostic groups (HR = 0.89; 95% CI: 0.70-1.12). Relapses in the intermediate or poor prognostic groups occurred in 11/298 (4%) Sem and 112/626 (18%) NSem. CONCLUSION Relapsing CSI GCT patients expect similar survival compared to de novo metastatic patients of the same ICCCCG prognostic group. Intermediate and poor prognosis relapses from initial CSI expose patients to unnecessary toxicity from more intensive treatments

A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder

Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data

Beyond the Raskin Protocol: Ketamine, Lidocaine, and Other Therapies for Refractory Chronic Migraine.

PURPOSE OF REVIEW: The purpose of this review is to discuss the available evidence and therapeutic considerations for intravenous drug therapy for refractory chronic migraine. RECENT FINDINGS: In carefully monitored settings, the inpatient administration of intravenous lidocaine and ketamine can be successful in treating refractory chronic migraine. Many patients with refractory chronic migraine have experienced treatment failure with the Raskin protocol. The use of aggressive inpatient infusion therapy consisting of intravenous lidocaine or ketamine, along with other adjunctive medications, has become increasingly common for these patients when all other treatments have failed. There is a clear need for prospective studies in this population comprised of patients who have largely been excluded from other studies

Paternal age and psychiatric disorders: findings from a Dutch population registry.

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