Clinical and laboratory characteristics of patients with symptomatic secondary immunodeficiency following the treatment of haematological malignancies.

Secondary immunodeficiency (SID), manifesting as increased susceptibility to infection, is an emergent clinical problem in haematoncology. Management of SID includes vaccination, prophylactic antibiotics (pAbx) and immunoglobulin replacement therapy (IgRT). We report clinical and laboratory parameters of 75 individuals, treated for haematological malignancy, who were referred for immunological assessment due to recurrent infections. Forty-five were managed with pAbx while thirty required IgRT after failing to improve on pAbx. Individuals requiring IgRT had significantly more bacterial, viral and fungal infections resulting in hospitalization at least 5 years after their original haemato-oncological diagnosis. Following immunological assessment and intervention, a 4.39-fold reduction in the frequency of hospital admissions to treat infection was observed in the IgRT cohort and a 2.30-fold reduction in the pAbx cohort. Significant reductions in outpatient antibiotic use were also observed in both cohorts following immunology input. Patients requiring IgRT were more hypogammaglobulinaemic and had lower titres of pathogen-specific antibodies and smaller memory B cell populations than those requiring pAbx. Test vaccination with pneumococcal conjugate vaccine discriminated poorly between the two groups. Patients requiring IgRT could be distinguished by combining wider pathogen-specific serology with a frequency of hospital admissions for infection. If validated in larger cohorts, this approach may circumvent the need for test vaccination and enhance patient selection for IgRT.

An operating room audit to examine for patterns of staff entry/exit: pattern sequencing as a method of traffic reduction.

BACKGROUND: Surgical site infections (SSIs) are estimated at over 16,000 annually and cost hospitals an estimated $1.6 billion per year. Therefore, most operating rooms (ORs) seek methods to reduce the risk of SSI, especially during the intraoperative period. Prior work has established a link between excess traffic through the OR and increased microbial counts, which create a higher risk for SSIs. AIM/OBJECTIVES: To identify patterns of staff entry into the OR to further reduce the risk of SSIs after total joint arthroplasties. METHODS: Researchers directly observed 31 total joint arthroplasties, recording every instance the door to the OR suite opened and the personnel, reason for opening and timing during surgical incision. Researchers then utilised the sequential data analysis to search for patterns. RESULTS: Despite expected patterns in staff movement during the patterned surgery, researchers found no significant patterns to staff movement during total joint arthroplasty. DISCUSSION: This study's results suggest purposeful education targeted to circulating registered nurses could induce purposeful creation of traffic flow patterns to further decrease traffic and risk of SSI. CONCLUSION: There is no singular pattern to entering and exiting the OR during surgery. Thus, a single-solution approach is not recommended.

Prevention and Treatment of Bleeding with Direct Oral Anticoagulants.

Anticoagulant-related bleeding carries considerable morbidity and mortality. Major or life-threatening bleeding is among the most severe of these complications. As the number of patients treated with direct oral anticoagulants (DOACs) continues to increase, so does the number of DOAC-related bleeding events. The incidence of CRNM bleeding related to DOAC therapy ranges from 15 to 18% per 100-year patients, while the incidence of major bleeding ranges from 2.71 to 3.6%. Many of these bleeding events can be prevented with tailored dosing regimens or proper peri-procedural management. When unable to be prevented, DOAC-related bleeding can lead to significant long-term disability or death. Management with newer reversal agents such as andexanet alfa and idarucizumab, as well as prothrombin complex concentrates, may improve outcomes for patients with DOAC-related bleeding. The purpose of this review is to explore strategies for preventing and treating bleeding in patients receiving DOACs for anticoagulant therapy.

Glaucoma Diagnosis: from the Artisanal to the Defined.

In 400BC, Hippocrates wrote the first record of glaucoma. Since then, increasingly objective diagnostic techniques have enabled earlier detection of glaucoma and its progression, providing greater certainty in decision-making and early medical and surgical intervention.

TIA1 is a gender-specific disease modifier of a mild mouse model of spinal muscular atrophy.

Spinal muscular atrophy (SMA) is caused by deletions or mutations of Survival Motor Neuron 1 (SMN1) gene. The nearly identical SMN2 cannot compensate for SMN1 loss due to exon 7 skipping. The allele C (C +/+) mouse recapitulates a mild SMA-like phenotype and offers an ideal system to monitor the role of disease-modifying factors over a long time. T-cell-restricted intracellular antigen 1 (TIA1) regulates SMN exon 7 splicing. TIA1 is reported to be downregulated in obese patients, although it is not known if the effect is gender-specific. We show that female Tia1-knockout (Tia1 -/-) mice gain significant body weight (BW) during early postnatal development. We next examined the effect of Tia1 deletion in novel C +/+/Tia1 -/- mice. Underscoring the opposing effects of Tia1 deletion and low SMN level on BW gain, both C +/+ and C +/+/Tia1 -/- females showed similar BW gain trajectory at all time points during our study. We observed early tail necrosis in C +/+/Tia1 -/- females but not in males. We show enhanced impairment of male reproductive organ development and exacerbation of the C +/+/Tia1 -/- testis transcriptome. Our findings implicate a protein factor as a gender-specific modifier of a mild mouse model of SMA.

Gender-Specific Amelioration of SMA Phenotype upon Disruption of a Deep Intronic Structure by an Oligonucleotide.

Spinal muscular atrophy (SMA), the leading genetic disease of children, is caused by low levels of survival motor neuron (SMN) protein. Here, we employ A15/283, an antisense oligonucleotide targeting a deep intronic sequence/structure, to examine the impact of restoration of SMN in a mild SMA mouse model. We show gender-specific amelioration of tail necrosis upon subcutaneous administrations of A15/283 into SMA mice at postnatal days 1 and 3. We also demonstrate that a modest increase in SMN due to early administrations of A15/283 dramatically improves testicular development and spermatogenesis. Our results reveal near total correction of expression of several genes in adult testis upon temporary increase in SMN during early postnatal development. This is the first demonstration of in vivo efficacy of an antisense oligonucleotide targeting a deep intronic sequence/structure. This is also the first report of gender-specific amelioration of SMA pathology upon a modest peripheral increase of SMN.

HIV risks and seroprevalence among Mexican American injection drug users in California.

Latinos in the United States are an ethnically diverse group disproportionately affected by HIV/AIDS. We describe HIV seroprevalence, HIV risk behaviors and utilization of health services among Mexican American injection drug users (IDUs) in California (n = 286) and compare them to White (n = 830) and African American (n = 314) IDUs. Study participants were recruited from syringe exchange programs (n = 24) in California. HIV seroprevalence among Mexican Americans (0.5%) was dramatically lower than Whites (5%) and African Americans (8%). Mexican Americans reported fewer sex-related risks than Whites and African Americans though injection-related risks remained high. Compared to Whites, Mexican Americans were more likely to participate in drug treatment during a 6 month period (AOR 1.5, 95% CI 1.1, 2.0) but less likely to receive any health care (AOR 0.6, 95% CI 0.5, 0.8). Exploring cultural and structural factors among Mexican American IDUs may offer new insights into how to maintain low rates of HIV seroprevalence and reduce barriers to health care utilization.

Pseudomonas aeruginosa colonization of the allograft after lung transplantation and the risk of bronchiolitis obliterans syndrome.

Long-term survival after lung transplantation remains limited by the development of bronchiolitis obliterans syndrome (BOS). Allograft colonization with Pseudomonas aeruginosa is common particularly in recipients with BOS, but a possible etiological relationship remains unexplored. In 155 consecutive lung transplants, the development of allograft colonization with Pseudomonas was strongly associated with the development of BOS within 2 years of transplant (23.4% vs. 7.7% in those colonized and not colonized, respectively, P=0.006). Freedom from BOS was significantly shorter in those patients without any pretransplant bacterial reservoir developing de novo allograft pseudomonal colonization as compared with those remaining free of colonization (Kaplan-Meier log-rank P=0.014). The isolation of Pseudomonas preceded the diagnosis of BOS in 14 of 18 (78%) and by a median of 204 days (95% confidence interval 115-492) in patients developing both these complications. We conclude that de novo colonization of the lung allograft by Pseudomonas is strongly associated with the subsequent development of BOS.

Pulmonary fibrosis: rate of disease progression as a trigger for referral for lung transplantation.

BACKGROUND: Lung transplantation is the only treatment modality that provides a survival advantage in pulmonary fibrosis, but many patients deemed suitable will die awaiting lung transplantation. While donor organ shortage undoubtedly contributes to this, late referral to the transplant centre may also play a role. This study investigates factors influencing the chance of patients with pulmonary fibrosis reaching lung transplantation. METHODS: A single-centre retrospective review of patient demographic data, assessment investigations and subsequent clinical outcomes was performed for patients with pulmonary fibrosis assessed for lung transplantation over a 5-year period. RESULTS: Between March 1999 and March 2004, 129 patients with pulmonary fibrosis underwent formal transplant assessment. Sixty-nine were accepted and listed for lung transplantation. Of these, 17 were transplanted, 37 died while waiting, 4 were removed from the list and 11 were still waiting at the conclusion of the study. The median waiting time on the list for those transplanted was 103 days (range 6-904) compared with 125 days (range 2-547) for those who died while on the list (p = 0.65). There was no significant difference in age, spirometry, total lung capacity, gas transfer measures or 6 min walk distance between those who died waiting and those transplanted. However, time from onset of symptoms to transplant assessment was significantly shorter in those who died on the waiting list (median 29 months (range 2-120)) than in those transplanted (median 46 months (range 6-204), p = 0.037). CONCLUSION: Patients with pulmonary fibrosis who died awaiting transplantation had similar disease severity at assessment as those who achieved transplantation. However, the interval between symptom onset and transplant referral was significantly shorter in those who died while on the waiting list, suggesting they had more rapidly progressive disease. The rate of disease progression appears to be a more sensitive indicator for transplantation referral than any single physiological measure of disease severity and should act as an important trigger for early transplant referral.

Human immunodeficiency virus and hepatitis C virus testing services at syringe exchange programs: availability and outcomes.

We described the availability and outcomes of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) testing services at syringe exchange programs throughout California, using interviews with 24 syringe exchange program directors and 560 syringe exchange clients. Both HIV and HCV testing services were available in 62% of programs, 21% had HIV testing only, and 17% had neither. Programs administered by health care/social service providers were more likely than independent syringe exchange programs to have HIV and HCV testing services available. Among clients of programs with testing available, clients of illegal programs were significantly less likely than clients of legal programs to have used syringe exchange HIV and HCV testing services. The availability of HIV and HCV testing services at syringe exchange programs varies, and the use of existing testing services by clients is not universal. Efforts to increase both the availability of HIV and HCV testing services at syringe exchange programs and the use of existing testing services are needed.

Secondary syringe exchange among users of 23 California syringe exchange programs.

This article describes the secondary syringe exchange (SSE) practices of injection drug users (IDUs) attending 23 syringe exchange programs (SEPs) in the state of California during 2002 (n=539). The sample was primarily heroin injecting, about two thirds male, half White and half other racial/ethnic groups. Participants were interviewed with a structured questionnaire that included items on sociodemographic factors, drug use practices, sexual practices, use of SEP and other social services, and satisfaction with SEP services. Interviews lasted about 30 minutes. SSE was highly prevalent: 75% of IDUs reported participating in SSE in the 6 months before interview. Program characteristics, such as legal status, SSE policy, and exchange policy, did not affect the prevalence of SSE among SEP clients. Infectious disease risk behaviors were significantly more common among SSE participants than nonparticipants. SSE participants were more likely to share syringes (p<.001) and cookers (p<.001) in the previous 6 months. SSE was significantly associated with being stuck with another person's syringe (needle-stick), a little-discussed "occupational hazard" of this practice. In multivariate analysis, the adjusted odds ratio of needle-stick among SSE participants was 2.8 (95% confidence interval, 1.3, 6.0). The high prevalence of SSE and the infectious disease risk associated with it warrant additional research to determine the causality of these associations. In the interim, SEPs should consider reinforcing HIV prevention education messages and training IDUs who engage in SSE in safe handling of biohazardous materials.

Unmet need for community-based mental health and substance use treatment among rural adolescents.

This research assessed the extent of unmet service need for rural youth with mental health (MH) and/or substance use (SU) problems. All adolescents (12-18 years old) living in a three-county region of Iowa and discharged from outpatient MH or SU treatment were included (n = 177). Chart review was used to retrospectively assess service utilization and clinical characteristics at time of admission and discharge. Two-thirds (64%) of adolescents with co-occurring disorders did not receive treatment consistent with widely supported guidelines recommending that individuals with co-occurring disorders receive treatment for both their MH and SU problems. Higher severity of depression, more supports, prior MH service utilization and lower prevalence of prior abuse predicted the receipt of dual services. Finally, adolescents with co-occurring problems who received only MH treatment showed improvement on MH needs at discharge but no improvement on SU needs. Similarly, adolescents with co-occurring problems who received only SU treatment showed improvement on SU needs but not on MH needs. There is considerable unmet treatment need among rural adolescents with co-occurring disorders. Efforts to improve care must focus on adolescent, familial, program, funding and policy factors that act as barriers to unifying philosophies and practices needed to advance appropriate care.

Validity and reliability of the Minimum Data Set Depression Rating Scale (MDSDRS) for older adults in nursing homes.

OBJECTIVE: this research examined the psychometric properties of the Minimum Data Set Depression Rating Scale for use among older adults living in nursing homes. METHODS: interviews with 145 older adults in three nursing homes were conducted to complete the Hamilton Depression Rating Scale and the Geriatric Depression Scale. Information relevant to completing the Minimum Data Set Depression Rating Scale was gathered from the Minimum Data Set. RESULTS: the Minimum Data Set Depression Rating Scale did not perform well when validated against the Hamilton Depression Rating Scale and the Geriatric Depression Scale. Minimum Data Set Depression Rating Scale cut-off levels of > or =2 and > or =3 were associated with relatively low total score correlations and sensitivity rates, but acceptable specificity. CONCLUSIONS: findings suggest that the Minimum Data Set Depression Rating Scale may be of limited clinical value to identify depression among older adults living in nursing homes.