Dose-Dense Docetaxel-Cyclophosphamide and Epirubicin-Cisplatin(ddDCEP): Analysis of an Alternative Platinum-Containing Regimen in 116 Patients with Early Triple Negative Breast Cancer.

We assessed the efficacy, tolerability, and cost-effectiveness of a novel neoadjuvant regimen comprising docetaxel-cyclophosphamide alternating with epirubicin-cisplatin (ddDCEP) administered biweekly for 16 weeks in 116 patients with early triple-negative breast cancer. This regimen achieved a high pathological complete response (ypT0/TisN0) rate of 55.2% and favorable survival outcomes (30-month event-free survival, 91.2%; overall survival, 97%). Febrile neutropenia was observed in 4.3% of patients, and 98% completed at least six of eight cycles. ddDCEP was more cost-effective than contemporary carboplatin-based regimens. This novel approach offers an economically viable and effective alternative to current chemoimmunotherapy regimens, and merits further investigation.

Association Between Ischemic Stroke Subtype and Stroke Severity: The Atherosclerosis Risk in Communities Study.

BACKGROUND AND OBJECTIVES: Disability after stroke occurs across ischemic stroke subtypes, with a suggestion that embolic strokes are more devastating. Whether this difference is as a result of differences in comorbidities or differences in severity at the time of the stroke event is not known. The primary hypothesis was that participants with embolic stroke would have more severe stroke at the time of admission and a higher risk of mortality, compared with thrombotic stroke participants even with consideration of confounders over time, with a secondary hypothesis that this association would differ by race and sex. METHODS: Atherosclerosis Risk in Communities (ARIC) study participants with incident adjudicated ischemic stroke, stroke severity and mortality data, and complete covariates were included. Multinomial logistic regression models determined the association between stroke subtype (embolic vs thrombotic) and admission NIH Stroke Scale (NIHSS) category (minor [≤5], mild [6-10], moderate [11-15], severe [16-20], and very severe [>20]) adjusted for covariates from visits most proximal to the stroke. Separate ordinal logistic models evaluated for interaction by race and sex. Adjusted Cox proportional hazard models estimated the association between stroke subtype and all-cause mortality (through December 31, 2019). RESULTS: Participants (N = 940) were mean age 71 years (SD = 9) at incident stroke, 51% female, and 38% Black. Using adjusted multinomial logistic regression, the risk of having a more severe stroke (reference NIHSS ≤5) was higher among embolic stroke vs thrombotic stroke patients, with a step-wise increase for embolic stroke patients when moving from mild (odds ratio [OR] 1.95, 95% CI 1.14-3.35) to very severe strokes (OR 4.95, 95% CI 2.34-10.48). After adjusting for atrial fibrillation, there was still a higher risk of having a worse NIHSS among embolic vs thrombotic strokes but with attenuation of effect (very severe stroke OR 3.91, 95% CI 1.76-8.67). Sex modified the association between stroke subtype and severity (embolic vs thrombotic stroke, p interaction = 0.03, per severity category, females OR 2.38, 95% CI 1.55-3.66; males OR 1.75, 95% CI 1.09-2.82). The risk of death (median follow-up 5 years, interquartile range 1-12) was also increased for embolic vs thrombotic stroke patients (hazard ratio 1.66, 95% CI 1.41-1.97). DISCUSSION: Embolic stroke was associated with greater stroke severity at the time of the event and a higher risk of death vs thrombotic stroke, even after careful adjustment for patient-level differences.

Methods for stroke severity assessment by chart review in the Atherosclerosis Risk in Communities study.

Stroke severity is the most important predictor of post-stroke outcome. Most longitudinal cohort studies do not include direct and validated measures of stroke severity, yet these indicators may provide valuable information about post-stroke outcomes, as well as risk factor associations. In the Atherosclerosis Risk in Communities (ARIC) study, stroke severity data were retrospectively collected, and this paper outlines the procedures used and shares them as a model for assessment of stroke severity in other large epidemiologic studies. Trained physician abstractors, who were blinded to other clinical events, reviewed hospital charts of all definite/probable stroke events occurring in ARIC. In this analysis we included 1,198 ischemic stroke events occurring from ARIC baseline (1987-1989) through December 31, 2009. Stroke severity was categorized according to the National Institutes of Health Stroke Scale (NIHSS) score and classified into 5 levels: NIHSS ≤ 5 (minor), NIHSS 6-10 (mild), NIHSS 11-15 (moderate), NIHSS 16-20 (severe), and NIHSS > 20 (very severe). We assessed interrater reliability in a subgroup of 180 stroke events, reviewed independently by the lead abstraction physician and one of the four secondary physician abstractors. Interrater correlation coefficients for continuous NIHSS score as well as percentage of absolute agreement and Cohen Kappa Statistic for NIHSS categories were presented. Determination of stroke severity by the NIHSS, based on data abstracted from hospital charts, was possible for 97% of all ischemic stroke events. Median (25%-75%) NIHSS score was 5 (2-8). The distribution of NIHSS category was NIHSS ≤ 5 = 58.3%, NIHSS 6-10 = 24.5%, NIHSS 11-15 = 8.9%, NIHSS 16-20 = 4.7%, NIHSS > 20 = 3.6%. Overall agreement in the classification of severity by NIHSS category was present in 145/180 events (80.56%). Cohen's simple Kappa statistic (95% CI) was 0.64 (0.55-0.74) and weighted Kappa was 0.79 (0.72-0.86). Mean (SD) NIHSS score was 5.84 (5.88), with a median score of 4 and range 0-31 for the lead reviewer (rater 1) and mean (SD) 6.16 (6.10), median 4.5 and range 0-36 in the second independent assessment (rater 2). There was a very high correlation between the scores reported in both assessments (Pearson r = 0.90). Based on our findings, we conclude that hospital chart-based retrospective assessment of stroke severity using the NIHSS is feasible and reliable.

Association of Ischemic Stroke Incidence, Severity, and Recurrence With Dementia in the Atherosclerosis Risk in Communities Cohort Study.

IMPORTANCE: Ischemic stroke is associated with increased risk of dementia, but the association of stroke severity and recurrence with risk of impaired cognition is not well known. OBJECTIVE: To examine the risk of dementia after incident ischemic stroke and assess how it differed by stroke severity and recurrence. DESIGN, SETTING, AND PARTICIPANTS: The Atherosclerosis Risk in Communities (ARIC) study is an ongoing prospective cohort of 15 792 community-dwelling individuals from 4 US states (Mississippi, Maryland, Minnesota, and North Carolina). Among them, 15 379 participants free of stroke and dementia at baseline (1987 to 1989) were monitored through 2019. Data were analyzed from April to October 2021. Associations between dementia and time-varying ischemic stroke incidence, frequency, and severity were studied across an average of 4.4 visits over a median follow-up of 25.5 years with Cox proportional hazards models adjusted for sociodemographic characteristics, apolipoprotein E, and vascular risk factors. EXPOSURES: Incident and recurrent ischemic strokes were classified by expert review of hospital records, with severity defined by the National Institutes of Health Stroke Scale (NIHSS; minor, ≤5; mild, 6-10; moderate, 11-15; and severe, ≥16). MAIN OUTCOMES AND MEASURES: Dementia cases adjudicated through expert review of in-person evaluations, informant interviews, telephone assessments, hospitalization codes, and death certificates. In participants with stroke, dementia events in the first year after stroke were not counted. RESULTS: At baseline, the mean (SD) age of participants was 54.1 (5.8) years, and 8485 of 15 379 participants (55.2%) were women. A total of 4110 participants (26.7%) were Black and 11 269 (73.3%) were White. A total of 1378 ischemic strokes (1155 incident) and 2860 dementia cases were diagnosed 1 year or more after incident stroke in participants with stroke, or at any point after baseline in participants without stroke, were identified through December 31, 2019. NIHSS scores were available for 1184 of 1378 ischemic strokes (85.9%). Risk of dementia increased with both the number and severity of strokes. Compared with no stroke, risk of dementia by adjusted hazard ratio was 1.76 (95% CI, 1.49-2.00) for 1 minor to mild stroke, 3.47 (95% CI, 2.23-5.40) for 1 moderate to severe stroke, 3.48 (95% CI, 2.54-4.76) for 2 or more minor to mild strokes, and 6.68 (95% CI, 3.77-11.83) for 2 or more moderate to severe strokes. CONCLUSIONS AND RELEVANCE: In this study, risk of dementia significantly increased after ischemic stroke, independent of vascular risk factors. Results suggest a dose-response association of stroke severity and recurrence with risk of dementia.

The impact of demonetisation on the utilisation of hospital services, patient outcomes and finances: a multicentre observational study from India.

BACKGROUND: This study assessed trends in healthcare utilisation in relation to the implementation of an economic policy in India wherein 500 and 1000 rupee notes were demonetised. METHODS: In this ambidirectional observational study of private not-for-profit hospitals, data on hospital outpatient and inpatient numbers, surgeries, emergency department (ED) visits, obstetric admissions and mortality were obtained for pre-demonetisation (September/October 2016), early (November/December 2016) and late demonetisation (January/February 2017), and post-demonetisation periods (March/April 2017) and compared with the control period (2015-2016) from 11 centres (three tertiary hospitals; eight secondary). A Bayesian regression analysis was performed to adjust for seasonal (winter) effect. Monthly financial data, including the proportion of cash versus non-cash transactions, were collected. FINDINGS: Overall, at the pooled all-hospital level, Bayesian analysis showed non-significant increase in outpatients (535.4, 95% CI -7097 to 8116) and decrease in deaths (-6.3 per 1000 inpatients, 95% CI -15.45 to 2.75) and a significant decrease in inpatients (-145.6, 95% CI -286.4 to -10.63) during demonetisation. Analysis at the level of secondary and tertiary hospitals showed a variable effect. For individual hospitals, after adjusting for the seasonal effect, some hospitals observed a significant reduction in outpatient (n=2) and inpatient (n=3) numbers, ED visits (n=4) and mortality (n=2) during demonetisation, while others reported significantly increased outpatient numbers (n=3) and ED visits (n=2). Deliveries remained unchanged during demonetisation in the hospitals that provided the service. There was no significant reduction in hospital incomes during demonetisation. In tertiary hospitals, there was a significant increase in non-cash component of transactions from 35% to 60% (p=0.02) that persisted beyond the demonetisation period. CONCLUSIONS: The effect of demonetisation on healthcare utilisation was variable. Some hospitals witnessed a significant reduction in utilisation in some areas, while others reported increased utilisation. There was an increase in non-cash transactions that persisted beyond the period of demonetisation.

The Johns Hopkins Primary Care for Cancer Survivor Clinic: lessons learned in our first 4 years.

PURPOSE: We established the Primary Care for Cancer Survivor (PCCS) Clinic in 2015 to address transition and care delivery challenges unique to cancer survivors. We describe the clinical program, detail patients from the first 4 years of implementation, and discuss lessons learned during the process. METHODS: We abstracted relevant patient information from the electronic medical record, administered a needs assessment survey at initial visits, and collected relative value unit (RVU) data. RESULTS: Between August 2015 and May 2019, we saw 230 PCCS patients with an increasing number of referrals yearly; nearly half were breast cancer survivors. At the initial visit, patients reported a median of 9 needs, with emotional needs most prevalent; over a third received at least one referral. PCCS patients generated higher billing codes and average RVUs compared with general patients. CONCLUSIONS: In its first 4 years, the PCCS program has thrived as a unique model of cancer survivorship centered in primary care. PCCS patients reported numerous needs, emphasizing the critical need for a multi-disciplinary approach in this population. With increasing referrals, we have considered different risk stratification and staffing models for capacity and expansion. By generating more RVUs per visit compared with the general clinic, PCCS has demonstrated financial sustainability. Buy-in from our oncology colleagues, divisional support from general medicine, along with our collaboration of like-minded internists have allowed us to be a robust program. IMPLICATIONS FOR CANCER SURVIVORS: Models of survivorship care embedded in primary care can provide meaningful, patient-centered care for cancer survivors.

Clinical Outcomes in Musculoskeletal Involvement of Burkholderia Pseudomallei Infection.

BACKGROUND: Musculoskeletal involvement in melioidosis is often seen in conjunction with a disseminated illness. Recent reports suggest that operative management of musculoskeletal melioidosis has favourable results. The purpose of this study was to review the patient profile and clinical outcomes of Burkholderia pseudomallei infection in the musculoskeletal system. METHODS: Hospital records of 163 patients who were diagnosed to have B. pseudomallei infection between January 2009 and December 2014 were reviewed. Patients underwent surgical and nonsurgical management depending upon the tissue of involvement. Epidata software was used to record the data. The SPSS ver. 17.0 was used for analysis. RESULTS: Eighteen out of 24 patients who had musculoskeletal melioidosis were available for follow-up. Septic arthritis, osteomyelitis, and intramuscular abscess were the common diagnosis, with 6 patients in each group. Twelve patients required surgical intervention. All patients received a full course of parenteral ceftazidime followed by oral doxycycline and co-trimoxazole. Two out of 6 patients (33.3%) died among those who had nonsurgical management as compared to none in the group who had surgical management. This was significant at 10% level of significance (p = 0.098). The rest were followed up for a minimum of 1 year with no evidence of disease recurrence. CONCLUSIONS: This series describing musculoskeletal involvement in melioidosis is the largest such study from a recently recognized 'endemic' region. Of importance are the patterns of musculoskeletal involvement, pitfalls in diagnosis and adequate clinical response with timely diagnosis and appropriate surgical management.

Elusive treatment for human rhinosporidiosis.

OBJECTIVES: The aim of this study was to clarify the contentious taxonomic classification of Rhinosporidium seeberi, the cause of human rhinosporidiosis, which may have treatment implications. METHODS: PCR was used to amplify the internal transcribed spacer (ITS)-2 region from the genomic DNA of the aetiological agent obtained from a sample of human rhinosporidiosis lesions. The amplicon was sequenced and the organism identified using the Basic Local Alignment Search Tools (BLAST). RESULTS: Phylogenetic analysis revealed that the aetiological agent clustered along with the R. seeberi isolated from humans and also with Amphibiocystidium ranae from frogs. This organism is a member of the order Dermocystida in the class Mesomycetozoea. A patient with disseminated rhinosporidiosis did not respond to conventional therapy with dapsone and surgical excision, and treatment with amphotericin B also proved futile. CONCLUSION: An effective treatment for R. seeberi-a eukaryote belonging to the class Mesomycetozoea-is still elusive.

Scrub typhus meningitis: An under-recognized cause of aseptic meningitis in India.

BACKGROUND: Central nervous system (CNS) involvement in scrub typhus is seen in up to a quarter of patients. However, the literature on cerebrospinal fluid (CSF) analysis and outcome in meningitis/meningo-encephalitis due to scrub typhus is scant. MATERIALS AND METHODS: This retrospective study included patients who were admitted to a medical college hospital with scrub typhus meningitis/meningo-encephalitis between 2005 and 2011. The clinical and laboratory profile, details of CSF analysis and outcome were documented. RESULTS: The study included 189 patients with meningitis/meningo-encephalitis due to scrub typhus. The mean age of the patients was 41 ± 4 years. The mean duration of fever before presentation was 9.4 ± 3 days. The common presenting complaints were headache (64.2%), nausea/vomiting (60%), altered sensorium (53.7%) and seizures (22.1%). The presence of an eschar was documented in 27.5% of the patients. The mean CSF white blood count was 80 cells/cu mm (range: 5-740). There was a clear lymphocyte predominance (mean 87.6%). The mean CSF protein level was 105 mg% (range: 13-640). The mean CSF sugar level was 63.9 mg% (range 25-350), and was less than 40 mg% in 11.1% of the cases. The case fatality rate was 5.8% (11/189). Univariate analysis showed the presence of an eschar (15.4% vs 2.2%; Odds Ratio [OR]: 8.1) and altered sensorium (9.8% vs 1.1%; OR: 9.2) to be significant predictors of mortality. CONCLUSIONS: In endemic regions, scrub typhus should be considered in the differential diagnosis of aseptic meningitis. Modest elevation of cells in the CSF with lymphocytic pleocytosis and multi-organ involvement may indicate scrub typhus meningitis/meningo-encephalitis.

Bilateral Renal Vein Thrombosis due to Elevated Factor VIII Levels.

Recent evidence has shown that high level of factor VIII is associated with increased risk of thromboembolism. High factor VIII levels are associated with a seven-fold increase in the risk of venous thrombosis. Renal vein thrombosis is usually associated with nephrotic syndrome, procoagulant state or oral contraceptive pills. We report a case of a lady who presented with bilateral renal vein thrombosis due to high factor VIII levels and oral contraceptive pills (OCP) use.

Multiple relapses of visceral leishmaniasis in a patient with HIV in India: a treatment challenge.

Visceral Leishmaniasis (VL) is an opportunistic infection amongst HIV-infected people in several endemic countries, and the clinical management of this co-infection poses several challenges. Here we describe a co-infected patient in India who failed to respond to miltefosine monotherapy and subsequently relapsed following two further (different) regimens of liposomal amphotericin B. He was then successfully treated with a combination of 30 mg/kg liposomal amphotericin B and 14 days of 100mg/day oral miltefosine.

Electrolytes assessed by point-of-care testing - Are the values comparable with results obtained from the central laboratory?

BACKGROUND AND AIMS: When dealing with very sick patients, the speed and accuracy of tests to detect metabolic derangements is very important. We evaluated if there was agreement between whole blood electrolytes measured by a point-of-care device and serum electrolytes measured using indirect ion-selective electrodes. MATERIALS AND METHODS: In this prospective study, electrolytes were analyzed in 44 paired samples drawn from critically ill patients. Whole blood electrolytes were analyzed using a point-of-care blood gas analyzer and serum electrolytes were analyzed in the central laboratory on samples transported through a rapid transit pneumatic system. Agreement was summarized by the mean difference with 95% limits of agreement (LOA) and Lin's concordance correlation (p(c)). RESULTS: There was a significant difference in the mean (±standard deviation) sodium value between whole blood and serum samples (135.8 ± 5.7 mmol/L vs. 139.9 ± 5.4 mmol/L, P < 0.001), with the agreement being modest (p(c) = 0.71; mean difference -4.0; 95% LOA -8.78 to 0.65). Although the agreement between whole blood and serum potassium was good (p(c) = 0.96), and the average difference small (-0.3; 95% LOA -0.72 to 0.13), individual differences were clinically significant, particularly at lower potassium values. For potassium values <3.0 mmol/L, the concordance was low (p(c) = 0.53) and the LOA was wide (1.0 to -0.13). The concordance for potassium was good (p(c) = 0.96) for values ≥3.0 (mean difference -0.2; 95% LOA -0.48 to 0.06). CONCLUSIONS: Clinicians should be aware of the difference between whole blood and serum electrolytes, particularly when urgent samples are tested at point of care and routine follow-up electrolytes are sent to the central laboratory. A correction factor needs to be determined at each center.

Agreement between paired blood gas values in samples transported either by a pneumatic system or by human courier.

BACKGROUND: Rapid accurate assessment of metabolic derangements is crucial in the critically ill. We evaluated if arterial blood gas (ABG) samples transported through a pneumatic tube system (PTS) agreed with values transported by a human courier. METHODS: In this prospective study of 50-paired ABG samples, the couriered reference ABG was compared with those transported by PTS. Agreement was summarised by the mean difference with 95% limits of agreement (LOA) and Lin's concordance correlation (pc). RESULTS: The mean (±SD) time from sampling to analysis was 35.7±23.2 (courier) and 38.6±22.1 (PTS) minutes. Agreement was good between courier and PTS for pH, PaCO(2), bicarbonate, oxygen saturation and PaO(2) values (pc>0.97). Although the mean difference in PaO(2) values between PTS and courier was small (-0.9 mm Hg) and the agreement was good, individual differences were clinically significant (95% LOA -40.8 to 39.0). For PaO(2) <160 mm Hg, analysis of PTS samples yielded erroneously high PaO(2) values and vice versa for PaO(2)>160 mm Hg compared to manual courier. This suggested exaggerated oxygen movement between the blood sample and air in the PTS. CONCLUSIONS: In this study, analysis of samples transported through the PTS resulted in clinically unacceptable PaO(2) values. Delay in transport and analysis of ABG samples should be avoided and samples transported manually if they cannot be assessed on-site.