Efficacy and safety of ruxolitinib after and versus interferon use in the RESPONSE studies.

Ruxolitinib was well tolerated and superior to best available therapy (including interferon [IFN]) in controlling hematocrit without phlebotomy eligibility, normalizing blood counts, and improving polycythemia vera-related symptoms in the Study of Efficacy and Safety in Polycythemia Vera Subjects Who Are Resistant to or Intolerant of Hydroxyurea: JAK Inhibitor INC424 (INCB018424) Tablets Versus Best Available Care (RESPONSE) studies. This ad hoc analysis focuses on ruxolitinib in relation to IFN in the RESPONSE studies, with attention on the following: (1) safety and efficacy of ruxolitinib and best available therapy in patients who received IFN before study randomization, (2) safety and efficacy of IFN during randomized treatment in best available therapy arm, and (3) use of ruxolitinib after crossover from best available therapy in IFN-treated patients. IFN exposure before randomization had little effect on the efficacy or safety of ruxolitinib. In the randomized treatment arms, ruxolitinib was superior to IFN in efficacy [hematocrit control (RESPONSE = 60% of ruxolitinib vs 23% of IFN patients; RESPONSE-2 = 62% of ruxolitinib vs 15% of IFN patients)] and was tolerated better in hydroxyurea-resistant or hydroxyurea-intolerant patients. After crossing over to receive ruxolitinib, patients who had initially received IFN and did not respond had improved hematologic and spleen responses (62% of patients at any time after crossover) and an overall reduction in phlebotomy procedures. Rates and incidences of the most common adverse events decreased after crossover to ruxolitinib, except for infections (primarily grade 1 or 2). These data suggest that ruxolitinib is efficacious and well tolerated in patients who were previously treated with IFN. The RESPONSE (NCT01243944) and RESPONSE-2 (NCT02038036) studies were registered at clinicaltrials.gov .

Bloodletting puncture in the treatment of acute ischemic stroke: protocol for a mixed-method study of a multi-center randomized controlled trial and focus group.

This study is to investigate the effectiveness and safety of bloodletting puncture (BP) for acute ischemic stroke (AIS) when used in combination with standard treatment, as well as the patients' feelings and attitudes toward the treatment. This is a mixed method research which includes a multi-center, superiority, randomized controlled clinical trial, and focus group interview. A total of 360 AIS participants will be enrolled. They will be randomized into one of the following two groups for 7 d: (a) BP with standard treatment group (n = 180); (b) standard treatment group (n = 180). The primary outcome will be National Institute of Health stroke scale (NIHSS) score at day 7 after treatment. Secondary outcomes will be changes of Glasgow Coma Scale score, NIHSS score, mRS and Traditional Chinese Medicine syndrome score from baseline to 7, 14, and 30 d after treatment, recurrence rate and all-cause mortality rate within 30 d, and the safety assessments. The focus group will be conducted with a purposive sample of 1-2 acupuncturists and 1-2 patients respectively at each center at 7 and 30 d after treatment. We designed a mixed method study to evaluate the effect of BP, an acupuncture therapy for patients with AIS. If the findings of this study confirm the effectiveness of BP to reduce the NIHSS score and other related outcomes and patients are willing to accept the therapy, we believe this study will help the implementation of this therapy in clinical practice, and provide new evidence for the treatment of AIS.

Effect of Bloodletting at Shaoshang and Shangyang Acupuncture Points on Outcome and Prognosis of Severe Community-Acquired Pneumonia in the Elderly.

OBJECTIVES: The aim of this study was to explore, whether treatment with bloodletting at Shaoshang and Shangyang acupuncture points would affect therapy outcome and prognosis for severe community-acquired pneumonia (SCAP) in the elderly. METHODS: A total of 62 patients, who met the diagnostic criteria for SCAP, were enrolled in the study and randomly divided into two groups, i.e., treatment group (n = 31) and control group (n = 31). All patients received a therapy according to the Chinese Clinical Practice and Expert Consensus of Emergency Severe Pneumonia from 2016. In addition to that, a bloodletting at Shaoshang (LU11) and Shangyang (LI1) acupuncture points was applied for the treatment group. This intervention was repeated for three times (ones daily), bloodletting a volume of 2-3 ml at each time point. Differences in a main index of clinical efficacy, body temperature (T), respiratory rate (RR), heart rate (Hr), white blood cell count (WBC), neutrophil percentage (N%), and C-reactive protein level (CRP) as well as different scores (CURB-65 score, SOFA score, and Apache II score) were compared between groups. Moreover, the 28-day mortality was compared between treatment and control group. The statistical methods involved in carrying out the current study include t-test, Wilcoxon test, and chi-square test. RESULTS: The clinical effective rate of the treatment group was 82.9%, which was significantly higher than the 17.1% in the control group (P < 0.05). After finishing the intervention, the treatment group showed significantly lower T (37.28 ± 0.54 vs. 37.82 ± 0.81), RR (20.06 ± 2.67 vs. 23.71 ± 6.85), Hr (81.71 ± 10.38 vs. 93.84 ± 15.39), CUBR-65 score (2.16 ± 0.74 vs. 3.03 ± 0.98), and SOFA score (5.84 ± 3.83 vs. 8.16 ± 4.2) compared to the control group (P < 0.05). The 28-day mortality rate of the treatment group was significantly lower than in the control group (12.9% vs. 45.2%, P = 0.05). CONCLUSIONS: Bloodletting at Shaoshang and Shangyang acupuncture points can support improving the clinical treatment efficacy for SCAP and reduce the 28-day mortality rate in the elderly.

Efficacy and safety of bloodletting for herpes zoster: A protocol for systematic review and meta-analysis.

BACKGROUND: The study aims to evaluate the effectiveness and safety of bloodletting therapy for herpes zoster. METHODS: The following electronic databases will be searched from PubMed (1966 to March 2020), the Cochrane Central Register of Controlled Trials (update to March 2020), EMBASE (1980 to March 2020), China National Knowledge Infrastructure (1979 to March 2020), Wan Fang Data (1980 to March 2020), Chinese Scientific Journal Database (1989 to March 2020), Chinese Biomedical Database (1978 to March 2020) and traditional Chinese medicine Literature Analysis and Retrieval Database (1949 to March 2020). All randomized controlled trials without any limitation of blinding or publication language about this topic will be included, exclude cohort studies and case reports. Two independent researchers will operate article retrieval, duplication removing, screening, quality evaluation, and data analyses by Review Manager (V.5.3.5). Meta-analyses, subgroup analysis, and/or descriptive analysis will be performed based on the included data conditions. RESULTS: High-quality synthesis and/or descriptive analysis of current evidence will be provided from cure rate, converting to clinical diagnosis rate, and side effects of bloodletting. CONCLUSION: This study will provide the evidence of whether bloodletting is an effective and safe intervention for herpes zoster. PROSPERO REGISTRATION NUMBER: CRD42020171976.

Pain assessment of a new bloodletting device: A study protocol for a randomized, controlled, double-blind, matched-paired clinical trial.

BACKGROUND: The bloodletting device has been used by many institutions for about 100 years. Many patients feel fear from the pain caused by applying the bloodletting device for treatment. We used bloodletting device using the principle of "prestimulation neurodisturbance," which can mask the subject undetectable for pain. In this study, we will investigate pain of bloodletting device during blood collection and will identify the safety of the device. METHODS: This study will be a randomized, controlled, double-blind, and matched-paired-designed clinical trial. Four groups, RTLC, LTRC, RCLT, and LCRT (T = test device, C = control device, L = left, R = right), will be randomly allocated. Total duration of the clinical trial will be 3 months. The subjects will be performed from 1 to 3 times only on the day of the procedure. The primary outcomes will be measured using pain visual analog scale score and the secondary outcomes will include verbal rating scale and the time at which the pain disappears after blood collection (second), the total number of "nonbleeding" cases and subjects, the number of "blood collection failure" and subjects, the presence of "delayed hemostasis," and the number of subjects. Repeated-measure analysis will be used to measure primary efficacy based on full analysis set. DISCUSSION: This study has limited inclusion and exclusion criteria and a well-controlled intervention, and it will be the first randomized controlled trial to investigate pain of bloodletting device using the principle of "prestimulation neurodisturbance." This study provides insights into the underlying mechanisms of the pain-reducing effect of the developed bloodletting device and will lay the groundwork for further studies.

Bloodletting Therapy for Patients with Chronic Urticaria: A Systematic Review and Meta-Analysis.

BACKGROUND: Many trials have reported that bloodletting therapy is effective when treating chronic urticaria. There are currently no systematic reviews of bloodletting therapy for chronic urticaria. OBJECTIVE: The aim of this review is to assess the effectiveness and safety of bloodletting therapy for chronic urticaria. METHODS: A systematic review and meta-analysis of randomized controlled trials were performed. Disease activity control was assessed as the primary outcome. Response rate, recurrence rate, and adverse events were assessed as secondary outcomes. RESULTS: Seven studies with 512 participants were included. One trial showed a significant difference between bloodletting therapy plus medicine and medicine alone in disease activity control (MD 0.67; 95% CI 0.03 to 1.31; p=0.04). Six trials (372 participants) showed a significant difference between bloodletting therapy and pharmacological medication in response rate (RR 1.10; 95% CI 0.97-1.26; P =0.15). Two studies (170 participants) showed a significant difference between bloodletting therapy plus pharmacological medication and pharmacological medication in response rate (RR 1.34; 95% CI 1.10-1.63; p=0.003). Two studies (126 participants) reported a statistically significant difference between bloodletting therapy and pharmacological medication in recurrence rate. No serious adverse events related to bloodletting therapy were reported. CONCLUSIONS: Bloodletting therapy might be an effective and safe treatment for chronic urticaria, but the evidence is scarce. More high quality trials are needed in the future.

Bloodletting therapy for treating patients with chronic urticaria: A systematic review and meta-analysis protocol.

BACKGROUND: Chronic urticaria is a common disease affecting patients' quality of life, and leading to substantial burden to both patients and society. Many trials have shown that bloodletting therapy is effective in treating chronic urticaria. There are currently no systematic reviews of bloodletting therapy for chronic urticaria. This protocol aims to present the methods used to assess the effectiveness and safety of bloodletting therapy for patients with chronic urticaria. METHODS: The following databases will be searched from their inception: the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP database), and Wan-Fang Database. Clinical randomised controlled trials related to bloodletting therapy for treating chronic urticaria will be included, regardless of publication status and languages. Study selection, data collection, and quality assessment will be independently conducted by 2 researchers. For data synthesis, we will select either the fixed-effects or random-effects model according to heterogeneity assessment. Disease activity control will be assessed as the primary outcomes. Response rate, recurrence rate and adverse events will be evaluated as secondary outcomes. If it is appropriate for meta-analysis, RevMan V.5.3 statistical software will be used. Otherwise, a systematic narrative synthesis will be conducted. The results will be presented as risk ratio (RR) with 95% confidence intervals (CIs) for dichotomous data and weight mean difference (WMD) or standard mean difference (SMD) 95% CIs for continuous data. DISSEMINATION AND ETHICS: The protocol of this systematic review will be disseminated in a peer-reviewed journal and presented at relevant conferences. It is not necessary for a formal ethical approval because the data are not individualised. TRIAL REGISTRATION NUMBER: PROSPERO CRD42018111143.

The effect of traditional wet cupping on shoulder pain and neck pain: A pilot study.

OBJECTIVES: Wet cupping therapy (WCT) is a traditional complementary method recommended to decrease the symptoms of a lot of diseases and used in the treatment of pain syndromes. In this pilot study, the possible effects of wet cupping therapy on nonspecific neck and upper shoulder pain were investigated. METHODS: Sixty one eligible volunteer participants with nonspecific neck and upper shoulder pain for at least 3 months were allocated. The Numeric Rating Scale (NRS) was used to assess pain scores. Pain scores were recorded before and after wet cupping therapy. RESULTS: The mean scores of neck pain in study group were 7.02 (SD = 1.8) before and 3.70 (SD = 2.2) after cupping therapy. The decrease of pain scores between pre- and post-test was statistically significant (p < 0.05). DISCUSSION: It can be stated that WCT has potential therapeutic effect in nonspecific neck and upper shoulder pain. Future full-scale randomized controlled trials will be needed to provide firm evidence of the effectiveness of this intervention.

Cardiovascular responses to phlebotomy and sitting in middle-aged and elderly subjects.

BACKGROUND: Responding appropriately to hypotensive challenges is an important determinant of health and functional independence in elderly individuals. Cardiovascular responses to phlebotomy and postural change were evaluated using a large database developed in a study designed to establish the safety of blood donation by older individuals. METHODS: The groups studied included 464 subjects aged 65 years and younger (range, 52 to 65 years) and 532 subjects more than 65 years old (range, 66 to 78 years old). Blood pressure and pulse rate measurements were followed by the withdrawal of 500 mL of blood. These measurements were repeated, first in the supine and then in the sitting position. RESULTS: Nearly all individuals studied remained hemodynamically stable after these two challenges. Age was not an independent predictor of blood pressure change after either phlebotomy or postural change. Large decreases in diastolic blood pressure were equally rare in both age groups. However, more older subjects (15.2%) exhibited a decline of 20 mm Hg or more in systolic blood pressure following phlebotomy, compared with the middle-aged group (6.9%). These age-related differences did not persist after controlling for the higher initial systolic blood pressures observed in the older subjects. Postphlebotomy postural change to the sitting position had little additional effect. CONCLUSIONS: These results indicate that the ability to respond to hypovolemia and postural change remains relatively intact in healthy elderly individuals. The higher prevalence of a significant drop in systolic blood pressure after phlebotomy, orthostasis, and possibly other homeostatic challenges in older subjects is probably due to the presence of higher basal blood pressure readings, including hypertension. In spite of these differences, blood donation is appropriate and should be encouraged in healthy elderly individuals in this age group.

Increased mouse minor hemoglobin during erythroid stress: a model for hemoglobin regulation.

In mice with "diffuse" hemoglobin (Hb), the decrease in the proportion of minor Hb during ontogeny qualitatively resembles the decline observed in human Hb F. Since Hb F reappears during some forms of erythroid stress, we investigated the effect of hematopoietic stress on minor Hb in DBA/2 mice. The stresses were acetlyphenylhydrazine-induced hemolysis, phlebotomy, or infection with Friend erythroleukemia virus. Recovery from anemia was associated with a transient increase in the synthesis of minor Hb similar to the reappearance of Hb F in man. Minor Hb synthesis also increased during the evolution of erythroleukemia induced by both the anemic and the polycythemic strains of virus. Thus, the mouse model can be used to study Hb regulation, since changes in the modulation of minor Hb synthesis occur under conditions which are associated with alterations in Hb F synthesis in humans.

Dr Robert Robertson (1742-1829): Fever Specialist and Philosopher-Experimenter in the Treatment of Fevers with Peruvian Bark in the Latter Eighteenth-century Royal Navy.

The life and works of Dr Robert Robertson are reviewed set against the background of the extant British management of fevers during the latter 18th-century. Commencing in 1769, using the febrifuge Peruvian bark (cortex Peruvianus; Jesuit's Powder), he experimented and tested Peruvian bark mono-therapy protocols in the tropics in the cure and prevention of intermittent fever (predominantly malaria). His later work also showed the benefit of the bark in the acute care of developed continuous fevers (largely Ship Fever due to Epidemic Louse-borne Typhus Fever) in both the Temperate and Torrid Zones. In the realm of comparative statistics Robertson first demonstrated the safety and effectiveness of bark therapy against the dangerous depleting processes of the antiphlogistic regimen. He was the first to alert the Admiralty to the efficacy of bark in both the cure of acute fevers as well as a prophylactic in the tropics, and signalled the dangers of bloodletting in treating fevers of the tropics. He authored 13 books devoted to fevers outlining his theory of Febrile Infection and its treatment. The essay concludes with his role as the Physician-in-Charge of the Royal Hospital, Greenwich over a 28-year period, as an acknowledged expert in the small British group of 18th-century fever specialists.

Review of neonatal red cell transfusion practices.

In the United States in 1991, 290,000 or 7.1% of the 4,110,907 live births were premature infants; 53,299 or 1.3% were infants with birth weights of less than 1500 grams. Many if not all of these very low birth weight infants will require red blood cell transfusions for one of several reasons. These include exchange transfusions for hyperbilirubinemia, but most often transfusions are simple small volume transfusion also called 'topper' transfusions. Most of these small volume transfusions are given for iatrogenic blood loss or 'bleeding into the laboratory.' Studies have demonstrated that the sicker the infant, the more blood sampling is needed and the greater the exposure to red blood cell (RBC), platelet and plasma products. Simple RBC transfusions may also be given for specific clinical indications or to maintain a predetermined hemoglobin concentration. This manuscript will review the criteria for RBC transfusion in neonates and selection of product as regards anticoagulant and specialized processing. In addition, the results of recombinant erythropoietin (r-EPO) clinical trials in neonates will be discussed.

Peripheral nerve injury and causalgia secondary to routine venipuncture.

I examined 11 patients with upper-extremity causalgia secondary to peripheral nerve injury occurring during routine venipuncture. The nerves affected were the medial (n = 5) and lateral (n = 2) antebrachial cutaneous in the antecubital fossa, the superficial radial at the wrist (n = 2), and the dorsal sensory branches in the hand (n = 2). Anatomically, nerves lie on a plane just beneath and in close proximity to veins, making them vulnerable to injury during the procedure.

The effects of quality and timing of venepuncture on markers of blood coagulation in healthy middle-aged men.

Effects of the quality and the time of venepuncture on factor VII coagulant activity (VIIc) and the concentrations of fibrinogen, prothrombin fragment 1 + 2 (F1 + 2) and fibrinopeptide A (FPA) were sought in 2665 men, of whom 2334 were re-examined after about one year. Venepunctures were categorised as satisfactory, not fully satisfactory or unsatisfactory according to pre-defined criteria. Neither the quality nor timing of the venepuncture influenced VIIc or fibrinogen concentration. However, at baseline and re-examination F1 + 2 and FPA were increased on average by about 9% and 45% respectively when venepunctures were not fully satisfactory, and by about 11% and 100% when unsatisfactory. Plasma collected after 1500 h had slightly but significantly lower levels of F1 + 2 and FPA than samples taken earlier, possibly due to circadian rhythm. The results emphasise the need for careful surveillance of the venepuncture procedure and the value of FPA when using F1 + 2 as a marker of risk of thrombosis.

Phlebotomy--a minimalist approach.

For each patient, laboratories usually collect more blood than is needed for specific determinations. We reviewed the amount of blood collected for laboratory measurements for an entire hospital stay of 113 patients admitted during a 1-week period to a medical ward or to a medical intensive-care unit in our tertiary-care facility. The amount of blood obtained was also compared with the minimal amount needed for analysis for 18 of the most frequently ordered laboratory tests in our facility. For routine collections, a mean of 45 times the required volume of specimen (range, 2 to 102 times) was obtained. For optimal utilization of laboratory services, both the positive and the negative consequences of testing must be thoughtfully considered. Two potential adverse effects of withdrawal of blood for laboratory determinations are iatrogenic anemia and infection. Moreover, the cost of care is increased with additional analyses. Practical strategies for decreasing the amount of blood collected include an increased awareness of ordering practices, a thorough knowledge of the volume of blood needed for each laboratory test, experienced phlebotomy personnel, storage of blood specimens for potential subsequent use, and communication of accurate minimal volumes needed for specific measurements.

Pacemaker system failure secondary to air entrapment within the pulse generator pocket. A complication of subclavian venipuncture for lead placement.

Air entrapment within the pulse generator pocket may produce pacemaker system malfunction if the anodal contract plate becomes insulated by the accumulation of air. Unipolar pulse generators are predisposed to this complication. We describe a pacemaker-dependent patient who, early after implantation, experienced pacemaker system failure as a complication of subclavian venipuncture. This patient had an unsuspected pneumothorax that progressed to subcutaneous air entrapment within the pulse generator pocket. Management of this previously unreported complication of subclavian venipuncture is rapid, noninvasive and effective. With the growing use of subclavian venipuncture technique for lead placement one should avoid the predisposing factors that can lead to subcutaneous air entrapment.

Reducing adult phlebotomy blood loss with the use of pediatric-sized blood collection tubes.

The feasibility of collecting smaller blood volumes during phlebotomy for diagnostic laboratory testing was evaluated by substituting pediatric-size for adult-size blood collection tubes. The volume of blood drawn with the use of pediatric-size tubes from 41 patients in an intensive care unit (120.2 mL total; 32.2 mL/day) was 46.8% lower than in that of a control population for which adult-size tubes were used (226.1 mL total; 55.6 mL/day). Sufficient blood was available for performance of all laboratory tests ordered at the time of the phlebotomy. Although substituting pediatric-size tubes does not address the problem of excessive use of laboratory tests, smaller tubes may reduce the severity of phlebotomy-induced anemia in adults without compromising laboratory test procedures.

Blood exchanged in ritual ceremonies as a possible route for infection with hepatitis C virus.

Of 52 blood donors (25 men and 27 women) counselled because their donation tested positive for hepatitis C virus antibody, seven (13.5%) gave a history of practising the ritual of blood exchange in their childhood or early adult life. This practice can cause transmission of blood borne infections or alloimmunisation, or both.

Autologous blood donation during pregnancy: analysis of safety and blood use.

Forty-eight women in the third trimester of pregnancy who requested autologous blood donations were enrolled in an experimental protocol to evaluate the safety of this procedure. Risk factors suggesting the possible need for postpartum transfusion were present in 17 women, including previous history of transfusion, scheduled cesarean section, placenta previa, and previous pregnancy-induced hypertension. Nine women were unable to meet donation criteria. Thirty-nine participants donated one to three units each. There was one vasovagal reaction among 61 donations. Fetal monitoring performed during each donation to assess cardiovascular and neurologic effects of maternal hypovolemia revealed no abnormalities. Three women with symptomatic postpartum anemias were transfused with autologous blood; two of these patients were identified antepartum as being at risk for possible transfusion. Autologous donation during pregnancy was safe for both mother and fetus. However, the likelihood of postpartum transfusion, while possibly predictable based on antepartum history, was low in this study.