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BACKGROUND: Antimicrobial overprescription is common for lower respiratory tract infections (LRTI), as viral and bacterial infections generally present with similar clinical features. Overprescription is associated with downstream antimicrobial resistance. This study aims to identify the prevalence and predictors of antibiotic prescription among patients hospitalized with viral LRTI. METHODS: A prospective cohort study was conducted among patients aged ≥1 year hospitalized with viral LRTI in a tertiary care hospital in Southern Province, Sri Lanka from 2018-2021. Demographic, clinical, and laboratory data were recorded. Nasopharyngeal and blood samples were collected for multiplex polymerase chain reaction testing for 21 respiratory pathogens and procalcitonin (PCT) detection, respectively. Demographic and clinical features associated with antibiotic prescription were identified using Chi Square and t-tests; significant variables (p<0.05) were further included in multivariable logistic regression models. The potential impact of biomarker testing on antibiotic prescription was simulated using standard c-reactive protein (CRP) and PCT cut-offs. RESULTS: Of 1217 patients enrolled, 438 (36.0%) had ≥1 respiratory virus detected, with 48.4% of these patients being male and 30.8% children. Influenza A (39.3%) and human rhinovirus/ enterovirus (28.3%) were most commonly detected. A total of 114 (84.4%) children and 266 (87.8%) adults with respiratory viruses were treated with antibiotics. Among children, neutrophil percentage (median 63.6% vs 47.6%, p = 0.04) was positively associated with antibiotic prescription. Among adults, headache (60.6% vs 35.1%, p = 0.003), crepitations/crackles (55.3% vs 21.6%, p<0.001), rhonchi/wheezing (42.9% vs 18.9%, p = 0.005), and chest x-ray opacities (27.4% vs 8.1%, p = 0.01) were associated with antibiotic prescription. Access to CRP and procalcitonin test results could have potentially decreased inappropriate antibiotic prescription in this study by 89.5% and 83.3%, respectively. CONCLUSIONS: High proportions of viral detection and antibiotic prescription were observed among a large inpatient cohort with LRTI. Increased access to point-of-care biomarker testing may improve antimicrobial prescription.
Subject(s)
Anti-Bacterial Agents , Respiratory Tract Infections , Humans , Male , Female , Sri Lanka/epidemiology , Anti-Bacterial Agents/therapeutic use , Child , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/virology , Respiratory Tract Infections/epidemiology , Adult , Adolescent , Child, Preschool , Middle Aged , Prospective Studies , Prevalence , Infant , Hospitalization , Young Adult , Procalcitonin/blood , Aged , C-Reactive Protein/analysis , C-Reactive Protein/metabolismABSTRACT
Background: Index-cluster studies may help characterize the spread of communicable infections in the presymptomatic state. We describe a prospective index-cluster sampling strategy (ICSS) to detect presymptomatic respiratory viral illness and its implementation in a college population. Methods: We enrolled an annual cohort of first-year undergraduates who completed daily electronic symptom diaries to identify index cases (ICs) with respiratory illness. Investigators then selected 5-10 potentially exposed, asymptomatic close contacts (CCs) who were geographically co-located to follow for infections. Symptoms and nasopharyngeal samples were collected for 5 days. Logistic regression model-based predictions for proportions of self-reported illness were compared graphically for the whole cohort sampling group and the CC group. Results: We enrolled 1379 participants between 2009 and 2015, including 288 ICs and 882 CCs. The median number of CCs per IC was 6 (interquartile range, 3-8). Among the 882 CCs, 111 (13%) developed acute respiratory illnesses. Viral etiology testing in 246 ICs (85%) and 719 CCs (82%) identified a pathogen in 57% of ICs and 15% of CCs. Among those with detectable virus, rhinovirus was the most common (IC: 18%; CC: 6%) followed by coxsackievirus/echovirus (IC: 11%; CC: 4%). Among 106 CCs with a detected virus, only 18% had the same virus as their associated IC. Graphically, CCs did not have a higher frequency of self-reported illness relative to the whole cohort sampling group. Conclusions: Establishing clusters by geographic proximity did not enrich for cases of viral transmission, suggesting that ICSS may be a less effective strategy to detect spread of respiratory infection.
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BACKGROUND: Mobile health (mHealth) has become an increasingly popular strategy to improve healthcare delivery and health outcomes. Communicating results and health education via text may facilitate program planning and promote better engagement in care for women undergoing human papillomavirus (HPV) screening. We sought to develop and evaluate an mHealth strategy with enhanced text messaging to improve follow-up throughout the cervical cancer screening cascade. METHODS: Women aged 25-65 participated in HPV testing in six community health campaigns (CHCs) in western Kenya as part of a single arm of a cluster-randomized trial. Women received their HPV results via text message, phone call, or home visit. Those who opted for text in the first four communities received "standard" texts. After completing the fourth CHC, we conducted two semi-structured focus group discussions with women to develop an "enhanced" text strategy, including modifying the content, number, and timing of texts, for the subsequent two communities. We compared the overall receipt of results and follow-up for treatment evaluation among women in standard and enhanced text groups. RESULTS: Among 2368 women who were screened in the first four communities, 566 (23.9%) received results via text, 1170 (49.4%) via phone call, and 632 (26.7%) via home visit. In the communities where enhanced text notification was offered, 264 of the 935 screened women (28.2%) opted for text, 474 (51.2%) opted for phone call, and 192 (20.5%) for home visit. Among 555 women (16.8%) who tested HPV-positive, 257 (46.3%) accessed treatment, with no difference in treatment uptake between the standard text group (48/90, 53.3%) and the enhanced text group (22/41, 53.7%). More women in the enhanced text group had prior cervical cancer screening (25.8% vs. 18.4%; p < 0.05) and reported living with HIV (32.6% vs. 20.2%; p < 0.001) than those in the standard text group. CONCLUSIONS: Modifying the content and number of texts as an enhanced text messaging strategy was not sufficient to increase follow-up in an HPV-based cervical cancer screening program in western Kenya. A one-size approach to mHealth delivery does not meet the needs of all women in this region. More comprehensive programs are needed to improve linkage to care to further reduce structural and logistical barriers to cervical cancer treatment.
Subject(s)
Papillomavirus Infections , Text Messaging , Uterine Cervical Neoplasms , Female , Humans , Cryotherapy , Early Detection of Cancer/methods , Kenya , Papillomavirus Infections/diagnosis , Prospective Studies , Uterine Cervical Neoplasms/prevention & control , Adult , Middle Aged , AgedABSTRACT
BACKGROUND: CKD of unknown etiology (CKDu) disproportionately affects young people in Central America who lack traditional CKD risk factors (diabetes and hypertension) and has instead been variably linked to heat stress, occupational and environmental exposures, nephrotoxic medications, and/or genetic susceptibility. This study aimed to estimate the prevalence of CKD and identify risk factors for traditional CKD and CKDu in Nicaragua. METHODS: Surveys and assessment for CKD markers in urine and serum were performed in 15-59 year olds in households of the León municipality of Nicaragua. The survey included questions on demographics, health behaviors, occupation, and medical history. Participants with CKD were subdivided into traditional CKD and suspected CKDu based on history of diabetes, hypertension, or other specified conditions. A multinomial logistic regression model was used to identify factors associated with traditional CKD and suspected CKDu, compared to the non-CKD reference group. RESULTS: In 1795 study participants, CKD prevalence was 8.6%. Prevalence in males was twofold higher than females (12% vs 6%). Of those with CKD, 35% had suspected CKDu. Both traditional CKD and CKDu were associated with male sex and increasing age. Traditional CKD was associated with a family history of CKD, history of urinary tract infections, and lower socioeconomic status, while CKDu was associated with drinking well water and a lower body mass index. CONCLUSIONS: Both traditional CKD and CKDu are significant burdens in this region. Our study supports previous hypotheses of CKDu etiology and emphasizes the importance of CKD screening.
Subject(s)
Diabetes Mellitus , Hypertension , Renal Insufficiency, Chronic , Adolescent , Adult , Female , Humans , Male , Middle Aged , Hypertension/epidemiology , Hypertension/complications , Nicaragua/epidemiology , Prevalence , Renal Insufficiency, Chronic/epidemiology , Risk Factors , Chronic Kidney Diseases of Uncertain Etiology/epidemiologyABSTRACT
BACKGROUND: Hematogenous vertebral osteomyelitis (HVOM) is an incompletely understood complication of Staphylococcus aureus bacteremia (SAB). METHODS: Eligible SAB patients with and without HVOM were prospectively enrolled from 1995 through 2019 at Duke University Health System. HVOM was diagnosed either radiographically or microbiologically. Multivariable logistic regression analysis was performed to identify clinical and microbial factors associated with HVOM risk. All bloodstream S. aureus isolates were genotyped using spa typing. RESULTS: Of 3165 cases of SAB, 127 (4.0%) developed HVOM. Patients who experienced HVOM were more likely to have community-acquired SAB (30.7% vs 16.7%, P < .001), have a longer time to diagnosis of SAB (median, 5 days; interquartile range [IQR], 2-10.5 vs median, 2 days; IQR, 0-4; P < .001), and to exhibit persistent bacteremia (48.8% vs 20.6%, P < .001). A significant number of HVOM patients developed infective endocarditis (26% vs 15.2%, P = .002). Overall, 26.2% (n = 33) of SAB patients with HVOM underwent surgical intervention. Methicillin resistance (46.6% vs 41.7%, P = .318) and bacterial genotype were not associated with the development of HVOM. At the 12-month follow-up, 22% of patients with HVOM had died. Of the surviving patients, 20.4% remained on antibiotic therapy, and 29.6% had recurrence of either HVOM or SAB. CONCLUSIONS: Among patients with SAB, HVOM risk was associated with clinical factors and not bacterial genotype. Despite being a rare complication of SAB, patients with HVOM had high all-cause mortality rates and healthcare resource requirements up to 1 year after their HVOM diagnosis. Close clinical monitoring is indicated in this vulnerable population.
Subject(s)
Bacteremia , Osteomyelitis , Staphylococcal Infections , Humans , Staphylococcus aureus , Staphylococcal Infections/complications , Staphylococcal Infections/drug therapy , Staphylococcal Infections/epidemiology , Bacteremia/complications , Bacteremia/epidemiology , Risk Factors , Osteomyelitis/complications , Osteomyelitis/epidemiology , Anti-Bacterial Agents/therapeutic useABSTRACT
BACKGROUND: Approximately one third of individuals with major depressive disorder have treatment-resistant depression (TRD). Glutamatergic modulators such as the N -methyl- d -aspartate receptor antagonist ketamine have rapid and robust antidepressant effects, but their use has been limited by accessibility and route of administration. This open-label pilot study assessed the adjunctive antidepressant efficacy of dextromethorphan/quinidine (DM/Q) in TRD. METHODS: Inpatients with TRD (n = 17, 40.8 ± 12.3 years; 9 females/8 males) received adjunctive open-label DM/Q (20 mg/10 mg) up to 3 times daily. The study had no set endpoint; participants were followed until they discontinued DM/Q or were discharged. Montgomery-Asberg Depression Rating Scale (MADRS) scores were obtained at baseline (before DM/Q administration) and regularly during hospitalization. Full response was defined as a ≥50% reduction in baseline MADRS score, partial response as a 25% to 50% decrease in baseline MADRS score, and nonresponse as a <25% reduction or an increase in baseline MADRS score. RESULTS: The 17 inpatients received open-label DM/Q for 5.1 ± 2.7 weeks. Forty-seven percent of participants responded to DM/Q-12% achieved a full response and 35% achieved a partial response. The largest MADRS difference observed at any time point was -6.4 ± 8.4 (-21.0% ± 29.9%), and the MADRS difference observed at time of DM/Q discontinuation or hospital discharge was -4.8 ± 8.4 (-15.9% ± 29.7%). Twenty-four percent of participants experienced a nonserious adverse event; none experienced a serious adverse event. CONCLUSIONS: In this open-label pilot study, 47% of participants responded to adjunctive DM/Q, which was well tolerated. Larger placebo-controlled trials are needed to determine the real-world efficacy of DM/Q.
Subject(s)
Depressive Disorder, Major , Depressive Disorder, Treatment-Resistant , Male , Female , Humans , Quinidine/adverse effects , Dextromethorphan/pharmacology , Depressive Disorder, Major/drug therapy , Treatment Outcome , Depression , Pilot Projects , Antidepressive Agents/adverse effects , Depressive Disorder, Treatment-Resistant/drug therapy , Double-Blind MethodABSTRACT
Background: Mobile health (mHealth) has become an increasingly popular strategy to improve healthcare delivery and health outcomes. Communicating results and health education via text may facilitate program planning and promote better engagement in care for women undergoing human papillomavirus (HPV) screening. We sought to develop and evaluate an mHealth strategy with enhanced text messaging to improve follow-up throughout the cervical cancer screening cascade. Methods: Women aged 25-65 participated in HPV testing in six community health campaigns (CHCs) in western Kenya. Women received their HPV results via text message, phone call, or home visit. Those who opted for text in the first four communities received "standard" texts. After completing the fourth CHC, we conducted two focus group discussions with women to develop an "enhanced" text strategy, including modifying the content, number, and timing of texts, for the subsequent two communities. We compared the overall receipt of results and follow-up for treatment evaluation among women in standard and enhanced text groups. Results: Among 2,368 women who were screened in the first four communities, 566 (23.9%) received results via text, 1,170 (49.4%) via phone call, and 632 (26.7%) via home visit. In the communities where enhanced text notification was offered, 264 of the 935 screened women (28.2%) opted for text, 474 (51.2%) opted for phone call, and 192 (20.5%) for home visit. Among 555 women (16.8%) who tested HPV-positive, 257 (46.3%) accessed treatment, with no difference in treatment uptake between the standard text group (48/90, 53.3%) and the enhanced text group (22/41, 53.7%). More women in the enhanced text group had prior cervical cancer screening (25.8% vs. 18.4%; p < 0.05) and reported living with HIV (32.6% vs. 20.2%; p < 0.001) than those in the standard text group. Conclusions: Modifying the content and number of texts as an enhanced text messaging strategy was not sufficient to increase follow-up in an HPV-based cervical cancer screening program in western Kenya. A one-size approach to mHealth delivery does not meet the needs of all women in this region. More comprehensive programs are needed to improve linkage to care to further reduce structural and logistical barriers to cervical cancer treatment.
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OBJECTIVES: The association of biological female sex with outcome in patients with Staphylococcus aureus bacteraemia remains unresolved. The aim of this study was to determine the independent association of female sex with management and mortality in patients with S. aureus bacteraemia. METHODS: This is a post hoc analysis of prospectively collected data from the S. aureus Bacteraemia Group Prospective Cohort Study. Adult patients with monomicrobial S. aureus bacteraemia at Duke University Medical Center were enrolled from 1994 to 2020. Univariable and multivariable Cox regression analyses were performed to assess differences in management and mortality between females and males. RESULTS: Among 3384 patients with S. aureus bacteraemia, 1431 (42%) were women. Women were, as compared with men, more often Black (581/1431 [41%] vs. 620/1953 [32%], p < 0.001), haemodialysis dependent (309/1424 [22%] vs. 334/1940 [17%], p 0.001) and more likely to be infected with methicillin-resistant S. aureus (MRSA) (697/1410 [49%] MRSA in women vs. 840/1925 [44%] MRSA in men, p 0.001). Women received shorter durations of antimicrobial treatment (median 24 [interquartile range 14-42] vs. 28 [interquartile range 14-45] days, p 0.005), and were less likely to undergo transesophageal echocardiography as compared with men (495/1430 [35%] vs. 802/1952 [41%], p < 0.001). Despite these differences, female sex was not associated with 90-day mortality in either univariable (388/1431 [27%] in women vs. 491/1953 [25%] in men, p 0.204) or multivariable analysis (adjusted hazard ratio for women 0.98 [95% CI, 0.85-1.13]). DISCUSSION: Despite significant differences in patient characteristics, disease characteristics, and management, women and men with S. aureus bacteraemia have a similar mortality risk.
Subject(s)
Bacteremia , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Adult , Male , Humans , Female , Staphylococcal Infections/microbiology , Staphylococcus aureus , Bacteremia/microbiology , Anti-Bacterial Agents/therapeutic use , Prospective StudiesABSTRACT
BACKGROUND: Large geographic health disparities are well-documented within the U.S. Although approximately 60 million Americans-or roughly 20% of the total U.S. population-live in rural areas, rural residents may be less likely to participate in health research, including mental health research, due to multiple barriers. This retrospective analysis evaluated the urbanity and rurality of inpatient research participants and potential research participants over a five-year period at the Experimental Therapeutics and Pathophysiology Branch (ETPB), NIMH-NIH (Bethesda, Maryland), which conducts experimental medicine and neurobiological research in mood disorders. METHODS: Participant and potential participant zip codes were converted to Rural Urban Commuting Area (RUCA) codes (1-3 urban, 4-10 rural). These results were compared with each other and with U.S. population data. RESULTS: The analysis included 182 research participants and 1864 potential research participants; the former were admitted to an in-person research unit and the latter were screened by phone or online. ETPB research participants had an urban residence rate of 93.4% and a rural residence rate of 6.6%. Potential ETPB research participants had an urban residence rate of 90.9% and a rural residence rate of 9.1%. In comparison, the U.S. urban residence rate is 80% and the rural rate is 20%. CONCLUSION: At the ETPB, both research participants with mood disorders admitted to an in-person research unit and potential research participants screened online or by phone from rural areas were under-represented relative to participants from more urban areas. Further study of research recruitment barriers in rural areas of the U.S is needed.
Subject(s)
Mental Health , Mood Disorders , Humans , United States , Urban Population , Retrospective Studies , Mood Disorders/epidemiology , Rural PopulationABSTRACT
Peripheral nerve injuries not repaired in an effective and timely manner may lead to permanent functional loss and/or pain. For gaps greater than 5 mm, autograft has been the gold standard. Allograft has recently emerged as an attractive alternative, delivering comparable functional recovery without risk of second surgical site morbidities. Cost is an important factor when considering surgical options, and with a paucity of nerve repair cost data, this study aimed to compare allograft and autograft procedure costs. Methods: A retrospective cross-sectional observational study using the US all-payer PINC AI Healthcare Database examined facility procedure costs and cost drivers in patients undergoing allograft or autograft repair of an isolated single peripheral nerve injury between January 2018 and August 2020. Inpatient repairs were limited to nerve-specific DRGs. Multivariable regression evaluated risk-adjusted procedure cost differences. Results: Peripheral nerve graft repairs (n = 1363) were more frequent in the outpatient setting, and more than half involved the use of allograft nerve. Procedure costs for allograft and autograft repair were not significantly different in the outpatient (P = 0.43) or inpatient (P = 0.71) setting even after controlling for other risk factors. Operating room cost was significantly higher for autograft in outpatient (P < 0.0001) but not inpatient (P = 0.46), whereas allograft implant cost was significantly higher in both settings (P < 0.0001). Conclusions: No significant differences in procedure costs for autograft and allograft repair in inpatient and outpatient settings were found using real-world data. Future research should explore longer-term costs.
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BACKGROUND: Preclinical evidence indicates that the κ-opioid receptor (KOR)/dynorphin pathway is implicated in depressive-like behaviors. Ketamine is believed to partly exert its antidepressant effects by modulating the opioid system. This post hoc study examined the following research questions: (1) at baseline, were there differences in KOR or dynorphin plasma levels between individuals with major depressive disorder (MDD) and healthy volunteers (HVs) or between men and women? (2) in individuals with MDD, did KOR or dynorphin baseline plasma levels moderate ketamine's therapeutic effects or adverse effects? and (3) in individuals with MDD, were KOR or dynorphin plasma levels affected after treatment with ketamine compared with placebo? METHODS: Thirty-nine unmedicated individuals with MDD (23 women) and 25 HVs (16 women) received intravenous ketamine (0.5 mg/kg) and placebo in a randomized, crossover, double-blind trial. Blood was obtained from all participants at baseline and at 3 postinfusion time points (230 minutes, day 1, day 3). Linear mixed model regressions were used. RESULTS: At baseline, participants with MDD had lower KOR plasma levels than HVs ( F1,60 = 13.16, P < 0.001), and women (MDD and HVs) had higher KOR plasma levels than men ( F1,60 = 4.98, P = 0.03). Diagnosis and sex had no significant effects on baseline dynorphin levels. Baseline KOR and dynorphin levels did not moderate ketamine's therapeutic or adverse effects. Compared with placebo, ketamine was not associated with postinfusion changes in KOR or dynorphin levels. CONCLUSIONS: In humans, diagnosis of MDD and biological sex are involved with changes in components of the KOR/dynorphin pathway. Neither KOR nor dynorphin levels consistently moderated ketamine's therapeutic effects or adverse effects, nor were levels altered after ketamine infusion. TRIAL REGISTRATION: NCT00088699 ( ClinicalTrials.gov ).
Subject(s)
Depressive Disorder, Major , Ketamine , Male , Humans , Female , Depressive Disorder, Major/drug therapy , Ketamine/therapeutic use , Receptors, Opioid, kappa/therapeutic use , Dynorphins/therapeutic use , Antidepressive Agents/therapeutic useABSTRACT
Well-established animal models of depression have described a proximal relationship between stress and central nervous system (CNS) inflammation - a relationship mirrored in the peripheral inflammatory biomarkers of individuals with depression. Evidence also suggests that stress-induced proinflammatory states can contribute to the neurobiology of treatment-resistant depression. Interestingly, ketamine, a rapid-acting antidepressant, can partially exert its therapeutic effects via anti-inflammatory actions on the hypothalamic-pituitary adrenal (HPA) axis, the kynurenine pathway or by cytokine suppression. Further investigations into the relationship between ketamine, inflammation and stress could provide insight into ketamine's unique therapeutic mechanisms and stimulate efforts to develop rapid-acting, anti-inflammatory-based antidepressants.
Subject(s)
Depression , Ketamine , Animals , Depression/drug therapy , Ketamine/pharmacology , Ketamine/therapeutic use , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Inflammation/drug therapy , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic useABSTRACT
BACKGROUND: Staphylococcus aureus bacteremia (SAB) disproportionately affects Black patients. The reasons for this disparity are unclear. METHODS: We evaluated a prospectively ascertained cohort of patients with SAB from 1995 to 2020. Clinical characteristics, bacterial genotypes, and outcome were compared among Black and White patients with SAB. Multivariable logistic regression models were used to determine factors independently associated with the outcomes. RESULTS: Among 3068 patients with SAB, 1107 (36%) were Black. Black patients were younger (median, 56 years vs 63 years; P < .001) and had higher rates of diabetes (47.5% vs 34.5%, P < .001), hemodialysis dependence (40.0% vs 7.3%, P < .001), and human immunodeficiency virus (6.4% vs 0.6%, P < .001). Black patients had higher rates of methicillin-resistant S. aureus (49.3% vs 44.9%, P = .020), including the USA300 hypervirulent clone (11.5% vs 8.4%, P = .007). White patients had higher rates of corticosteroid use (22.4% vs 15.8%, P < .0001) and surgery in the preceding 30 days (28.1% vs 18.7%, P < .001). Although the median Acute Physiology Score (APS) at the time of initial SAB diagnosis was significantly higher in Black patients (median APS, 9; interquartile range [IQR], 5-14 vs median APS, 7; IQR, 4-12; P < .001), race was not associated with 90-day mortality (risk ratio, 1.02; 95% confidence interval, .93-1.12), and rates of metastatic infection were lower among Black patients (37.2% vs 41.3% White, P = .029). CONCLUSIONS: Despite differences in Black patients' higher APS on presentation and more risk factors, including a 5 times higher risk of hemodialysis dependence, 90-day mortality among Black and White patients with SAB was similar.
Subject(s)
Bacteremia , Staphylococcal Infections , Humans , Bacteremia/ethnology , Bacteremia/microbiology , Methicillin-Resistant Staphylococcus aureus , Risk Factors , Staphylococcal Infections/ethnology , Staphylococcal Infections/microbiology , Staphylococcus aureus , White People , Black PeopleABSTRACT
BACKGROUND: The causes and clinical characteristics of recurrent gram-negative bacterial bloodstream infections (GNB-BSI) are poorly understood. METHODS: We used a cohort of patients with GNB-BSI to identify clinical characteristics, microbiology, and risk factors associated with recurrent GNB-BSI. Bacterial genotyping (pulsed-field gel electrophoresis [PFGE] and whole-genome sequencing [WGS]) was used to determine whether episodes were due to relapse or reinfection. Multivariable logistic regression was used to identify risk factors for recurrence. RESULTS: Of the 1423 patients with GNB-BSI in this study, 60 (4%) had recurrent GNB-BSI. Non-White race (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.38-4.01; P = .002), admission to a surgical service (OR, 2.18; 95% CI, 1.26-3.75; P = .005), and indwelling cardiac device (OR, 2.73; 95% CI, 1.21-5.58; P = .009) were associated with increased risk for recurrent GNB-BSI. Among the 48 patients with recurrent GNB-BSI whose paired bloodstream isolates underwent genotyping, 63% were due to relapse (30 of 48) and 38% were due to reinfection (18 of 48) based on WGS. Compared with WGS, PFGE correctly differentiated relapse and reinfection in 98% (47 of 48) of cases. Median time to relapse and reinfection was similar (113 days; interquartile range [IQR], 35-222 vs 174 days; IQR, 69-599; P = .13). Presence of a cardiac device was associated with relapse (relapse: 7 of 27, 26%; nonrelapse: 65 of 988, 7%; P = .002). CONCLUSIONS: In this study, recurrent GNB-BSI was most commonly due to relapse. PFGE accurately differentiated relapse from reinfection when compared with WGS. Cardiac device was a risk factor for relapse.
Subject(s)
Bacteremia , Gram-Negative Bacterial Infections , Sepsis , Humans , Reinfection , Bacteremia/microbiology , Gram-Negative Bacterial Infections/diagnosis , Gram-Negative Bacterial Infections/microbiology , Sepsis/complications , Recurrence , Risk Factors , Retrospective StudiesABSTRACT
Ketamine is a treatment for both refractory depression and chronic pain syndromes. In order to explore ketamine's potential mechanism of action and whether ketamine or its metabolites cross the blood brain barrier, we examined the pharmacokinetics of ketamine and its metabolites-norketamine (NK), dehydronorketamine (DHNK), and hydroxynorketamines (HNKs)-in cerebrospinal fluid (CSF) and plasma, as well as in an exploratory proteomic analysis in the CSF of nine healthy volunteers who received ketamine intravenously (0.5 mg/kg IV). We found that ketamine, NK, and (2R,6R;2S,6S)-HNK readily crossed the blood brain barrier. Additionally, 354 proteins were altered in the CSF in at least two consecutive timepoints (p < 0.01). Proteins in the classes of tyrosine kinases, cellular adhesion molecules, and growth factors, including insulin, were most affected, suggesting an interplay of altered neurotransmission, neuroplasticity, neurogenesis, synaptogenesis, and neural network functions following ketamine administration.
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Background: Over 5 million people annually die from injuries and millions more sustain non-fatal injuries requiring medical care. Ninety percent of injury deaths occur in low- and middle-income countries (LMICs). This study describes the characteristics, predictors and outcomes of adult acute injury patients presenting to a tertiary referral hospital in a low-income country in sub-Saharan Africa. Methods: This secondary analysis uses an adult acute injury registry from Kilimanjaro Christian Medical Centre (KCMC) in Moshi, Tanzania. We describe this patient sample in terms of socio-demographics, clinical indicators, injury patterns, treatments, and outcomes at hospital discharge. Outcomes include mortality, length of hospital stay, and functional independence. Associations between patient characteristics and patient outcomes are quantified using Cox proportional hazards models, negative binomial regression, and multivariable logistic regression. Results: Of all injury patients (n=1365), 39.0% were aged 30 to 49 years and 81.5% were men. Most patients had at least a primary school education (89.6%) and were employed (89.3%). A majority of injuries were road traffic (63.2%), fall (16.8%), or assault (14.0%) related. Self-reported comorbidities included hypertension (5.8%), HIV (3.1%), and diabetes (2.3%). Performed surgeries were classified as orthopedic (32.3%), general (4.1%), neurological (3.7%), or other (59.8%). Most patients reached the hospital at least four hours after injury occurred (53.9%). Mortality was 5.3%, median length of hospital stay was 6.1 days (IQR: 3.1, 15.0), self-care dependence was 54.2%, and locomotion dependence was 41.5%. Conclusions: Our study sample included primarily young men suffering road traffic crashes with delayed hospital presentations and prolonged hospital stays. Being older, male, and requiring non-orthopedic surgeries or having HIV portends a worse prognosis. Prevention and treatment focused interventions to reduce the burden of injury mortality and morbidity at KCMC are needed to lower injury rates and improve injury outcomes.
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BACKGROUND: Mobile phone ownership among women of reproductive age in western Kenya is not well described, and our understanding of its link with care-seeking behaviors is nascent. Understanding access to and use of mobile phones among this population as well as willingness to participate in mobile health interventions are important in improving and more effectively implementing mobile health strategies. OBJECTIVE: This study aims to describe patterns of mobile phone ownership and use among women attending cervical cancer screening and to identify key considerations for the use of SMS text message-guided linkage to treatment strategies and other programmatic implications for cervical cancer screening in Kenya. METHODS: This analysis was nested within a cluster randomized trial evaluating various strategies for human papillomavirus (HPV)-based cervical cancer screening and prevention in a rural area in western Kenya between February and November 2018. A total of 3299 women were surveyed at the time of screening and treatment. Questionnaires included items detailing demographics, health history, prior care-seeking behaviors, and patterns of mobile phone ownership and use. We used bivariate and multivariable log-binomial regression to analyze associations between independent variables and treatment uptake among women testing positive for high-risk HPV. RESULTS: Rates of mobile phone ownership (2351/3299, 71.26%) and reported daily use (2441/3299, 73.99%) were high among women. Most women (1953/3277, 59.59%) were comfortable receiving their screening results via SMS text messages, although the most commonly preferred method of notification was via phone calls. Higher levels of education (risk ratio 1.23, 95% CI 1.02-1.50), missing work to attend screening (risk ratio 1.29, 95% CI 1.10-1.52), and previous cervical cancer screening (risk ratio 1.27, 95% CI 1.05-1.55) were significantly associated with a higher risk of attending treatment after testing high-risk HPV-positive, although the rates of overall treatment uptake remained low (278/551, 50.5%) among this population. Those who shared a mobile phone with their partner or spouse were less likely to attend treatment than those who owned a phone (adjusted risk ratio 0.69, 95% CI 0.46-1.05). Treatment uptake did not vary significantly according to the type of notification method, which were SMS text message, phone call, or home visit. CONCLUSIONS: Although the rates of mobile phone ownership and use among women in western Kenya are high, we found that individual preferences for communication of messages about HPV results and treatment varied and that treatment rates were low across the entire cohort, with no difference by modality (SMS text message, phone call, or home visit). Therefore, although text-based results performed as well as phone calls and home visits, our findings highlight the need for more work to tailor communication about HPV results and support women as they navigate the follow-up process.
Subject(s)
Cell Phone , Papillomavirus Infections , Uterine Cervical Neoplasms , Early Detection of Cancer/methods , Female , Humans , Kenya/epidemiology , Ownership , Papillomavirus Infections/diagnosis , Papillomavirus Infections/prevention & control , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/prevention & controlABSTRACT
Subanesthetic-dose racemic (R,S)-ketamine (ketamine) produces rapid, robust, and sustained antidepressant effects in major depressive disorder (MDD) and bipolar disorder (BD) and has also been shown to effectively treat neuropathic pain, complex regional pain syndrome, and post-traumatic stress disorder (PTSD). However, to date, its mechanism of action remains unclear. Preclinical studies found that (2 R,6 R;2 S,6 S)-hydroxynorketamine (HNK), a major circulating metabolite of ketamine, elicits antidepressant effects similar to those of ketamine. To help determine how (2 R,6 R)-HNK contributes to ketamine's mechanism of action, an exploratory, targeted, metabolomic analysis was carried out on plasma and CSF of nine healthy volunteers receiving a 40-minute ketamine infusion (0.5 mg/kg). A parallel targeted metabolomic analysis in plasma, hippocampus, and hypothalamus was carried out in mice receiving either 10 mg/kg of ketamine, 10 mg/kg of (2 R,6 R)-HNK, or saline. Ketamine and (2 R,6 R)-HNK both affected multiple pathways associated with inflammatory conditions. In addition, several changes were unique to either the healthy human volunteers and/or the mouse arm of the study, indicating that different pathways may be differentially involved in ketamine's effects in mice and humans. Mechanisms of action found to consistently underlie the effects of ketamine and/or (2 R,6 R)-HNK across both the human metabolome in plasma and CSF and the mouse arm of the study included LAT1, IDO1, NAD+, the nitric oxide (NO) signaling pathway, and sphingolipid rheostat.
Subject(s)
Depressive Disorder, Major , Ketamine , Animals , Antidepressive Agents/therapeutic use , Brain/metabolism , Depressive Disorder, Major/drug therapy , Depressive Disorder, Major/metabolism , Humans , Ketamine/therapeutic use , Metabolomics , MiceABSTRACT
This manuscript reviews the clinical evidence regarding single-dose intravenous (IV) administration of the novel glutamatergic modulator racemic (R,S)-ketamine (hereafter referred to as ketamine) as well as its S-enantiomer, intranasal esketamine, for the treatment of major depressive disorder (MDD). Initial studies found that a single subanesthetic-dose IV ketamine infusion rapidly (within one day) improved depressive symptoms in individuals with MDD and bipolar depression, with antidepressant effects lasting three to seven days. In 2019, esketamine received FDA approval as an adjunctive treatment for treatment-resistant depression (TRD) in adults. Esketamine was approved under a risk evaluation and mitigation strategy (REMS) that requires administration under medical supervision. Both ketamine and esketamine are currently viable treatment options for TRD that offer the possibility of rapid symptom improvement. The manuscript also reviews ketamine's use in other psychiatric diagnoses-including suicidality, obsessive-compulsive disorder, post-traumatic stress disorder, substance abuse, and social anxiety disorder-and its potential adverse effects. Despite limited data, side effects for antidepressant-dose ketamine-including dissociative symptoms, hypertension, and confusion/agitation-appear to be tolerable and limited to around the time of treatment. Relatively little is known about ketamine's longer-term effects, including increased risks of abuse and/or dependence. Attempts to prolong ketamine's effects with combined therapy or a repeat-dose strategy are also reviewed, as are current guidelines for its clinical use. In addition to presenting a novel and valuable treatment option, studying ketamine also has the potential to transform our understanding of the mechanisms underlying mood disorders and the development of novel therapeutics.
ABSTRACT
INTRODUCTION: Despite the increased risk of cervical cancer among HIV-positive women, many HIV-care programs do not offer integrated cervical cancer screening. Incorporating self-collected Human Papillomavirus (HPV) testing into HIV programs is a potential strategy to identify women at higher risk for cervical cancer while leveraging the staffing, infrastructure and referral systems for existing services. Community-based HIV and HPV testing has been effective and efficient when offered in single-disease settings. METHODS: This cross-sectional study was conducted within a community outreach and multi-disease screening campaigns organized by the Family AIDS Care and Education Services in Kisumu County, Kenya. In addition to HIV testing, the campaigns provided screening for TB, malaria, hypertension, diabetes, and referrals for voluntary medical male circumcision. After these services, women aged 25-65 were offered self-collected HPV testing. Rates and predictors of cervical cancer screening uptake and of HPV positivity were analyzed using tabular analysis and Fisher's Exact Test. Logistic regression was performed to explore multivariate associations with screening uptake. RESULTS: Among the 2016 women of screening age who attended the outreach campaigns, 749 women (35.6%) were screened, and 134 women (18.7%) were HPV-positive. In bivariate analysis, women who had no children (p < 0.01), who were not pregnant (p < 0.01), who were using contraceptives (p < 0.01), who had sex without using condoms (p < 0.05), and who were encouraged by a family member other than their spouse (p < 0.01), were more likely to undergo screening. On multivariable analysis, characteristics associated with higher screening uptake included: women aged 45-54 (OR 1.62, 95% CI 1.05-2.52) compared to women aged 25-34; no children (OR 1.65, 95% CI 1.06-2.56); and family support other than their spouse (OR 1.53, 95% CI 1.09-2.16). Women who were pregnant were 0.44 times (95% CI 0.25-0.76) less likely to get screened. Bivariate analyses with participant characteristics and HPV positivity found that women who screened HPV-positive were more likely to be HIV-positive (p < 0.001) and single (p < 0.001). CONCLUSIONS: The low screening uptake may be attributed to implementation challenges including long waiting times for service at the campaign and delays in procuring HPV test kits. However, given the potential benefits of integrating HPV testing into HIV outreach campaigns, these challenges should be examined to develop more effective multi-disease outreach interventions.