Slow versus fast subcutaneous heparin injections for prevention of bruising and site pain intensity.

BACKGROUND: Heparin is an anticoagulant medication that is usually injected subcutaneously. Subcutaneous administration of heparin may result in complications such as bruising, haematoma, and pain at the injection site. One of the factors that may affect pain, haematoma, and bruising is injection speed. Several studies have been carried out to determine if speed of injection affects the amount of pain and bruising where the injection is given; however, the results of these studies have differed, and study authors have not reached a clear final conclusion. This is the second update of a review first published in 2014. OBJECTIVES: To assess the effects of duration (speed) of subcutaneous heparin injection on pain and bruising at the injection site in people admitted to hospitals or clinics who require treatment with unfractionated heparin (UFH) or low molecular weight heparin (LMWH). We also looked at haematoma at the injection site. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 22 June 2020. We undertook reference checking of included studies to identify additional studies. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) comparing the effects of different durations of subcutaneous injection of heparin on pain, bruising, and haematoma at the injection site. DATA COLLECTION AND ANALYSIS: For this update, two review authors independently selected studies and extracted data via Covidence software and assessed methodological quality using Cochrane's risk of bias tool. The primary outcomes of interest were pain intensity at injection site and size and incidence of bruising. The secondary outcomes of interest were size and incidence of haematoma at injection site. We calculated the odds ratio (OR), mean difference (MD), or standardised mean difference (SMD) with corresponding 95% confidence intervals (CIs). We assessed the certainty of the evidence using GRADE criteria. MAIN RESULTS: We identified one new study for this update, resulting in a total of five included studies with 503 participants who received subcutaneous injections of LMWH into the abdomen. Given the nature of the intervention, it was not possible to blind participants and caregivers (personnel) in any of the included studies. Two studies described blinding of outcome assessors. Overall, the methodological quality of included studies was moderate. The duration of the fast injection was 10 seconds, and the duration of the slow injection was 30 seconds in all included studies. Four studies reported site pain intensity after each injection at different time points. Two studies assessed site pain intensity immediately after each injection; meta-analysis showed no evidence of a difference in site pain intensity immediately after slow injection when compared to fast injection (MD -1.52, 95% CI -3.56 to 0.53; 140 participants; low-certainty evidence). Meta-analysis of three studies indicated that site pain intensity may be slightly reduced 48 hours after the slow heparin injection compared to fast injection (MD -1.60, 95% CI -2.69 to -0.51; 103 participants; low-certainty evidence). Five studies assessed bruise size at 48 hours, and two studies assessed bruise size at 60 hours. Meta-analysis showed there may be a reduction in bruise size 48 hours (SMD -0.54, 95% CI -1.05 to -0.02; 503 participants; 5 studies; very low-certainty evidence) and 60 hours (SMD -0.49, 95% CI -0.93 to -0.06; 84 participants; 2 studies; low-certainty evidence) after slow injection compared to fast injection. There was no evidence of a difference in bruise size 72 hours after slow injection compared to fast injection (SMD -0.27, 95% CI -0.61 to 0.06; 140 participants; 2 studies; low-certainty evidence). Three studies evaluated incidence of bruising and showed there may be a reduction in bruise incidence 48 hours (OR 0.39, 95% CI 0.26 to 0.60; 444 participants; low-certainty evidence) and 60 hours (OR 0.25, 95% CI 0.10 to 0.65; 84 participants; 2 studies; low-certainty evidence) after slow injection compared to fast injection. We downgraded the certainty of the evidence due to risk of bias concerns, imprecision, and inconsistency. None of the included studies measured size or incidence of haematoma. AUTHORS' CONCLUSIONS: Administering medication safely and enhancing patient comfort are the main aims of clinical nurses. In this review, we identified five RCTs that evaluated the effect of subcutaneous heparin injection duration on pain intensity, bruise size and incidence. We found that pain may be slightly reduced 48 hours after slow injection. Similarly, there may be a reduction in bruise size and incidence after slow injection compared to fast injection 48 and 60 hours postinjection. We downgraded the certainty of the evidence for all outcomes to low or very low due to risk of bias concerns, imprecision, and inconsistency. Accordingly, new trials with a more robust design, more participants, and a focus on different injection speeds will be useful in strengthening the certainty of the available evidence.

Phase 3, Randomized, Double-Blind, Active-Comparator (Darbepoetin Alfa) Study of Oral Roxadustat in CKD Patients with Anemia on Hemodialysis in Japan.

BACKGROUND: Roxadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor approved in China for dialysis-dependent CKD anemia. METHODS: This phase 3, 24-week, double-blind, double-dummy study evaluated roxadustat's noninferiority to darbepoetin alfa for hemodialysis-dependent CKD anemia. We randomly assigned Japanese patients to oral roxadustat three times weekly or to darbepoetin alfa injections once weekly, titrating doses to maintain hemoglobin between 10-12 g/dl. The primary end point was change of average hemoglobin from baseline to weeks 18-24 (∆Hb18-24). Secondary end points were average hemoglobin and proportion of patients with hemoglobin between 10-12 g/dl (maintenance rate) at weeks 18-24, and iron parameters. Safety assessments included treatment-emergent adverse events and adjudicated ophthalmologic findings. RESULTS: We randomly assigned 303 patients to roxadustat (n=151) or darbepoetin alfa (n=152). The difference between roxadustat and darbepoetin alfa in ∆Hb18-24 was -0.02 g/dl (95% confidence interval, -0.18 to 0.15), confirming roxadustat's noninferiority to darbepoetin alfa. Average hemoglobin at weeks 18-24 with roxadustat was 10.99 g/dl (95% confidence interval: 10.88 to 11.10), confirming its efficacy. Among patients with one or more hemoglobin value during weeks 18-24, the maintenance rate was 95.2% with roxadustat and 91.3% with darbepoetin alfa. Serum iron, ferritin, and transferrin saturation remained clinically stable with roxadustat; transferrin and total iron binding capacity increased through week 4 before stabilizing. Common treatment-emergent adverse events were nasopharyngitis, shunt stenosis, diarrhea, contusion, and vomiting. The proportion of patients with new or worsening retinal hemorrhage was 32.4% with roxadustat and 36.6% with darbepoetin alfa. We observed no clinically meaningful changes in retinal thickness groups. CONCLUSIONS: Roxadustat maintained hemoglobin within 10-12 g/dl in patients on hemodialysis and was noninferior to darbepoetin alfa. Treatment-emergent adverse events were consistent with previous reports. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: A Study of Intermittent Oral Dosing of ASP1517 in Hemodialysis Chronic Kidney Disease Patients with Anemia, NCT02952092 (ClinicalTrials.gov).

Facial aesthetic injections in clinical practice: Pretreatment and posttreatment consensus recommendations to minimise adverse outcomes.

Facial aesthetic treatment with injectable neuromodulators and hyaluronic acid fillers is well established, with favourable safety profiles and consistent outcomes. As with any medical treatment, adverse events and complications may occur. Adverse events associated with these products are typically transient and mild to moderate in severity. Serious adverse events, such as infection and intravascular occlusion, are rare. Proper patient selection, consent and counselling, preparation and impeccable injection technique are important risk reduction strategies. Both clinicians and patients must be alert to the signs and symptoms of complications so that appropriate treatment can be started promptly. In this article, the authors review the current literature and provide their consensus recommendations for minimising adverse outcomes when treating patients with botulinum toxin or hyaluronic acid fillers.

Quantifying cutaneous adverse effects of systemic glucocorticoids in patients with rheumatoid arthritis: a cross-sectional cohort study.

OBJECTIVES: EULAR guidelines state that adverse effects (AEs) of glucocorticoid (GC) therapy should be considered and discussed with the patient before treatment is initiated. However, reliable quantitative data, especially on cutaneous AEs of low-to-medium dose GCs are lacking. We performed a study assessing the occurrence of cutaneous AEs of GCs and its association with current and cumulative GC doses in patients with rheumatoid arthritis (RA). METHODS: In a cross-sectional study performed in 2 outpatient rheumatology centres, 381 RA patients were enrolled. They were classed into 4 groups, according their mean daily dose during the past 12 months: 0 mg (n=87), <5mg (n=108), 5-7.5 mg (n=130), and >7.5 mg (n=56) of prednisone equivalent. AEs of GC on the skin were assessed by physical examination using a predefined scoring system, and by patients' self-assessments. Data were analysed according GC dose categories and cumulative doses. RESULTS: Cushingoid habitus, easy bruising, skin atrophy, and impaired wound healing as reported by patients occurred significantly more frequently in those using a GC the past 12 months, compared to those not using a GC. At physicians' assessments, only Cushingoid habitus and ecchymosis were more prevalent in GC users. The prevalence of these AEs was statistically significantly positively associated with current and cumulative GC dose. There was low occurrence of abnormal stretch marks, acne, perioral dermatitis, alopecia and hirsutism, which were not correlated with GC use. CONCLUSIONS: Certain GC-associated cutaneous AEs are common in RA, but other AEs of GC occur infrequently at the low-to-medium GC doses used in RA.

Slow versus fast subcutaneous heparin injections for prevention of bruising and site pain intensity.

BACKGROUND: Heparin is an anticoagulant medication that is usually injected subcutaneously. Subcutaneous administration of heparin may result in complications such as bruising, haematoma, and pain at the injection site. One of the factors that may affect pain, haematoma, and bruising is injection speed. For patients and healthcare providers, strategies that can reduce pain and bruising are considered important. Reducing patients' discomfort and concerns whenever and wherever possible is an important aim of nursing. Several studies have been carried out to see if speed of injection affects the amount of pain and bruising where the injection is given, but results of these studies have differed and study authors have not reached a clear final conclusion. This is the first update of the review first published in 2014. OBJECTIVES: To assess the effects of duration (speed) of subcutaneous heparin injection on pain, haematoma, and bruising at the injection site in people admitted to hospitals or clinics who require treatment with unfractionated heparin (UFH) or low molecular weight heparin (LMWH). SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (last searched March 2017) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2). The CIS also searched trials registries for details of ongoing or unpublished studies. Review authors searched two Persian databases - Iranmedex and Scientific Information Database (SID) - as well as Google Scholar. SELECTION CRITERIA: We sought randomised controlled trials (RCTs) comparing the effects of different durations of subcutaneous injection of heparin on pain, bruising, and haematoma at the injection site. DATA COLLECTION AND ANALYSIS: Two review authors (MM, LJ), working independently, extracted data onto a structured form and assessed study quality. We used the criteria recommended by Cochrane to assess the risk of bias of included studies. For the outcomes, we calculated the mean difference (MD) or the standardised MD (SMD) with corresponding 95% confidence intervals (CIs). We pooled data using fixed-effect and random-effects models. We used GRADE to assess the overall quality of evidence supporting outcomes assessed in this review. MAIN RESULTS: For this update, we identified three new studies and therefore included in the Review four studies with a total of 459 participants who received subcutaneous injections of LMWH into the abdomen. Only one trial reported the injected drug volume (0.4 mL). Owing to the nature of the intervention, it was not possible to blind participants and care givers (personnel) in any included study. Two studies described blinding of outcome assessors; therefore overall, the methodological quality of included studies was moderate. The duration of the fast injection was 10 seconds and the duration of the slow injection was 30 seconds in all included studies.Three studies reported site pain intensity after each injection at different time points. Two studies assessed site pain intensity immediately after each injection, and meta-analysis on 140 participants showed no clear difference in site pain intensity immediately post slow injection when compared to fast injection (low-quality evidence; P = 0.15). In contrast, meta-analysis of two studies with 59 participants showed that 48 hours after the heparin injection, slow injection was associated with less pain intensity compared to fast injection (low-quality evidence; P = 0.007). One study (40 participants) reported pain intensity at 60 and 72 hours after injection. This study described no clear difference in site pain intensity at 60 and 72 hours post slow injection compared to fast injection.All four included studies assessed bruise size at 48 hours after each injection. Meta-analysis on 459 participants showed no difference in bruise size after slow injection compared to fast injection (low-quality evidence; P = 0.07). None of the included studies measured the incidence of haematoma as an outcome. AUTHORS' CONCLUSIONS: We found four RCTs that evaluated the effect of subcutaneous heparin injection duration on pain intensity and bruise size. Owing to the small numbers of participants, we found insufficient evidence to determine any effect on pain intensity immediately after injection or at 60 and 72 hours post injection. However, slow injection may reduce site pain intensity 48 hours after injection (low-quality evidence). We observed no clear difference in bruise size after slow injection compared to fast injection (low-quality evidence). We judged this evidence to be of low quality owing to imprecision and inconsistency.

Slow versus fast subcutaneous heparin injections for prevention of bruising and site pain intensity.

BACKGROUND: Heparin is an anticoagulant medication that is usually injected subcutaneously. Subcutaneous administration of heparin may result in complications such as bruising, haematoma, and pain at the injection site. One of the factors that may affect pain, haematoma, and bruising is injection speed. For patients and healthcare providers, strategies that can reduce pain and bruising are considered important. Reducing patients' discomfort and concerns whenever and wherever possible is an important aim of nursing. Several studies have been carried out to see if speed of injection affects the amount of pain and bruising where the injection is given, but results of these studies have differed and study authors have not reached a clear final conclusion. This is the first update of the review first published in 2014. OBJECTIVES: To assess the effects of duration (speed) of subcutaneous heparin injection on pain, haematoma, and bruising at the injection site in people admitted to hospitals or clinics who require treatment with unfractionated heparin (UFH) or low molecular weight heparin (LMWH). SEARCH METHODS: For this update, the Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (last searched March 2017) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2). The CIS also searched trials registries for details of ongoing or unpublished studies. Review authors searched two Persian databases - Iranmedex and Scientific Information Database (SID) - as well as Google Scholar. SELECTION CRITERIA: We sought randomised controlled trials (RCTs) comparing the effects of different durations of subcutaneous injection of heparin on pain, bruising, and haematoma at the injection site. DATA COLLECTION AND ANALYSIS: Two review authors (MM, LJ), working independently, extracted data onto a structured form and assessed study quality. We used the criteria recommended by Cochrane to assess the risk of bias of included studies. For the outcomes, we calculated the mean difference (MD) or the standardised MD (SMD) with corresponding 95% confidence intervals (CIs). We pooled data using fixed-effect and random-effects models. We used GRADE to assess the overall quality of evidence supporting outcomes assessed in this review. MAIN RESULTS: For this update, we identified three new studies and therefore included in the Review four studies with a total of 459 participants who received subcutaneous injections of LMWH into the abdomen. Only one trial reported the injected drug volume (0.4 mL). Owing to the nature of the intervention, it was not possible to blind participants and care givers (personnel) in any included study. Two studies described blinding of outcome assessors; therefore overall, the methodological quality of included studies was moderate. The duration of the fast injection was 10 seconds and the duration of the slow injection was 30 seconds in all included studies.Three studies reported site pain intensity after each injection at different time points. Two studies assessed site pain intensity immediately after each injection, and meta-analysis on 140 participants showed no clear difference in site pain intensity immediately post slow injection when compared to fast injection (low-quality evidence; P = 0.15). In contrast, meta-analysis of two studies with 59 participants showed that 48 hours after the heparin injection, slow injection was associated with less pain intensity compared to fast injection (low-quality evidence; P = 0.007). One study (40 participants) reported pain intensity at 60 and 72 hours after injection. This study described no clear difference in site pain intensity at 60 and 72 hours post slow injection compared to fast injection.All four included studies assessed bruise size at 48 hours after each injection. Meta-analysis on 459 participants showed no difference in bruise size after slow injection compared to fast injection (low-quality evidence; P = 0.07). None of the included studies measured the incidence of haematoma as an outcome. AUTHORS' CONCLUSIONS: We found four RCTs that evaluated the effect of subcutaneous heparin injection duration on pain intensity and bruise size. Owing to the small numbers of participants, we found insufficient evidence to determine any effect on pain intensity immediately after injection or at 60 and 72 hours post injection. However, slow injection may reduce site pain intensity 48 hours after injection (low-quality evidence). We observed no clear difference in bruise size after slow injection compared to fast injection (low-quality evidence). We judged this evidence to be of low quality owing to imprecision and inconsistency.

Efficacy and safety of collagenase clostridium histolyticum for Dupuytren disease nodules: a randomized controlled trial.

BACKGROUND: To determine the safety and efficacy of collagenase clostridium histolyticum (CCH) injection for the treatment of palmar Dupuytren disease nodules. METHODS: In this 8-week, double-blind trial, palpable palmar nodules on one hand of adults with Dupuytren disease were selected for treatment. Patients were randomly assigned using an interactive web response system to receive a dose of 0.25 mg, 0.40 mg, or 0.60 mg (1:1:1 ratio) and then allocated to active treatment (CCH) or placebo (4:1 ratio). All patients and investigators were blinded to treatment. One injection was made in the selected nodule on Day 1. Caliper measurements of nodule length and width were performed at screening and at Weeks 4 and 8. Investigator-reported nodular consistency and hardness were evaluated at baseline and Weeks 1, 4, and 8. Investigator-rated patient improvement (1 [very much improved] to 7 [very much worse]) and patient satisfaction were assessed at study end. RESULTS: In the efficacy population (n = 74), percentage changes in area were significantly greater with CCH 0.40 mg (-80.1%, P = 0.0002) and CCH 0.60 mg (-78.2%, P = 0.0003), but not CCH 0.25 mg (-58.3%, P = 0.079), versus placebo (-42.2%) at post-treatment Week 8. Mean change in nodular consistency and hardness were significantly improved with CCH versus placebo at Weeks 4 and 8 (P ≤ 0.0139 for all). At Week 8, investigator global assessment of improvement was significantly greater with CCH 0.40 mg and 0.60 mg (P ≤ 0.0014) but not statistically significant with CCH 0.25 mg versus placebo (P = 0.13). Most patients were "very satisfied" or "quite satisfied" with CCH 0.40 mg and 0.60 mg. Contusion/bruising (50.0% to 59.1%) was the most common adverse event with CCH treatment. CONCLUSION: In patients with Dupuytren disease, a single CCH injection significantly improved palmar nodule size and hardness. The safety of CCH was similar to that observed previously in patients with Dupuytren contracture. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02193828 . Date of trial registration: July 2, 2014 to December 5, 2014.

A randomized, evaluator-blinded, controlled study of effectiveness and safety of small particle hyaluronic acid plus lidocaine for lip augmentation and perioral rhytides.

OBJECTIVE: To compare the safety and effectiveness of small particle hyaluronic acid plus lidocaine (SPHAL) versus no treatment for lip augmentation and perioral rhytides. METHODS AND MATERIALS: Adults scoring 1 (very thin) to 2 (thin) on the Medicis Lip Fullness Scale (MLFS) for upper and lower lips were randomized (3:1) to SPHAL or no treatment. Treatment success was an MLFS increase ≥1 point at Week 8. Secondary end points (MLFS score, independent photographic review, Global Aesthetic Improvement Scale, Wrinkle Assessment Scale for Upper Lip Lines) and safety were assessed throughout. RESULTS: Statistically significantly more patients were treatment successes with SPHAL (upper lip [80.2% vs 11.9%], lower lip [84.2% vs 18.4%], and upper and lower lips combined [76.1% vs 11.6%]), compared with no treatment (p <.001, all outcomes). Patients treated for both lip augmentation and perioral rhytides were rated as having an aesthetically meaningful improvement in perioral rhytides (p <.001). Most common treatment-emergent adverse events (AEs) included lip bruising, swelling, and pain and were mostly mild and transient in nature, without anticipated device AEs. CONCLUSION: Small particle hyaluronic acid plus lidocaine was effective and well tolerated and significantly more effective when both lips and perioral rhytides were treated, with improvement evident up to 6 months after treatment.

Slow versus fast subcutaneous heparin injections for prevention of bruising and site-pain intensity.

BACKGROUND: Heparin is an anticoagulant medication that is normally injected subcutaneously. Subcutaneous administration of heparin may result in complications such as bruising, haematoma and pain at the injection site. One of the factors that may affect pain, haematoma and bruising is injection speed. OBJECTIVES: To assess the effects of the duration (speed) of subcutaneous heparin injection on pain, haematoma and bruising at the injection site in people admitted to hospitals or clinics who require treatment with unfractionated heparin or low molecular weight heparin. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched August 2013) and CENTRAL (2013, Issue 7). We searched MEDLINE, EMBASE, CINAHL and two Persian databases Iranmedex and SID (August 2013). SELECTION CRITERIA: We sought randomised controlled trials (RCTs) comparing the effects of different durations of subcutaneous injections of heparin on pain, bruising and haematoma at the injection site. DATA COLLECTION AND ANALYSIS: Two review authors, working independently, extracted data onto a structured form and assessed study quality. We used the criteria recommended by the Cochrane Handbook to assess the quality of included studies. The study outcomes were summarised using quantitative and qualitative methods. MAIN RESULTS: One RCT was identified which met the inclusion criteria, involving 50 participants with a mean age of 55.25 (± 12.37) years. In this trial it was not possible to blind the participants and care givers. The method of sequence generation and allocation concealment was not described. The overall quality of the evidence was moderate due to the single small included study. Each participant had two injections, one in the left side and one in right side of the abdomen. One of these was injected slowly (intervention) and the other was injected fast (control). The second injection was 12 hours after the first injection. The duration of fast injection was 10 seconds and the duration of slow injection was 30 seconds. The study reported a significantly lower pain intensity for slow versus fast injection. The mean pain intensity was 13.9 ± 17.1 mm with the slow injection and 20.6 ± 22.3 mm with the fast injection (P < 0.001). In addition the bruising sizes were smaller with slow injections compared to fast injections at 48 hours follow-up (mean bruising size 18.76 ± 9.32 mm(2) with the slow injection and 109.2 ± 468.66 mm(2) with the fast injection, P = 0.033) and 72 hours follow-up (mean bruising size 21.72 ± 76.16 mm(2) with the slow injection and 110.12 ± 472.86 mm(2) with the fast injection, P = 0.025). The incidence of haematoma was not measured as an outcome. AUTHORS' CONCLUSIONS: There is only limited evidence of any difference in pain intensity and bruising sizes following slow versus fast injections due to the inclusion of only one small unblinded trial. The single included study suggests that slow injection might have slightly lower pain intensity and bruising size at the heparin injection site, but the results should be considered with caution. Until more reliable evidence emerges, slow injection might be the preferred approach.

Diagnosis and management of filler adverse effects: an algorithm.

Fillers are frequently used in beautifying procedures. Despite major advancements of the chemical and biological features of injected materials, filler-related adverse events may occur, and can substantially impact the clinical outcome. Filler granulomas become manifest as visible grains, nodules, or papules around the site of the primary injection. Early recognition and proper treatment of filler-related complications is important because effective treatment options are available. In this report, we provide a comprehensive overview of the differential diagnosis and diagnostics and develop an algorithm of successful therapy regimens.

A questionable bruise.

It is occasionally difficult to distinguish between a self-inflicted bruise and true bruise. The important point of diagnosis is a good, thorough history taking and detailed examination of the affected area.

Does needle size matter? Effects of micro-hypodermic needle injections of botulinum toxin type A in patients with hemifacial spasm.

INTRODUCTION: Botulinum toxin type A (BoNT/A) injections are the first-line treatment for primary hemifacial spasms (HFS), but require frequent painful injections. Although micro-hypodermic needles are commonly used for aesthetic BoNT/A injections to lessen pain and bruising, their benefits in HFS remain unclear. OBJECTIVE: To compare side effects of BoNT/A injection, specifically pain and bruising, between primary HFS patients who received injections using micro-hypodermic needles (34-G) and those using standard needles (30-G). METHODS: This cross-over, double-blind, randomised controlled trial involved HFS patients who received BoNT/A injections using either a 34-G or 30-G needle at two visits 12 weeks apart. Primary outcomes, pain and bruising were assessed immediately after injection using the Visual Analogue Scale (VAS) and Short-form McGill Pain Questionnaire (Thai version, SF-MPQ). Bruise assessment was also conducted one week after each injection. Secondary outcomes involved comparing efficacy of BoNT/A between the two types of needles and assessing other complications beyond pain and bruising. RESULTS: 65 HFS patients (47 women and 18 men; mean age 59.46 ± 11.48 years; mean disease duration 5.86 ± 4.16 years) were included in the study. Patients who received 34-G needle injections reported significantly reduced pain, as indicated by VAS, total SF-MPQ scores, and bruise scores, compared to those who received 30-G needle injections (p < 0.001, each). There were no differences in efficacy or occurrence of other complications associated with BoNT/A between the two needle types. CONCLUSION: In HFS patients, BoNT/A injections using micro-hypodermic needles resulted in reduced pain and bruising, compared to standard needles, while maintaining similar BoNT/A benefits.

Aspirin plus heparin or aspirin alone in women with recurrent miscarriage.

BACKGROUND: Aspirin and low-molecular-weight heparin are prescribed for women with unexplained recurrent miscarriage, with the goal of improving the rate of live births, but limited data from randomized, controlled trials are available to support the use of these drugs. METHODS: In this randomized trial, we enrolled 364 women between the ages of 18 and 42 years who had a history of unexplained recurrent miscarriage and were attempting to conceive or were less than 6 weeks pregnant. We then randomly assigned them to receive daily 80 mg of aspirin plus open-label subcutaneous nadroparin (at a dose of 2850 IU, starting as soon as a viable pregnancy was demonstrated), 80 mg of aspirin alone, or placebo. The primary outcome measure was the live-birth rate. Secondary outcomes included rates of miscarriage, obstetrical complications, and maternal and fetal adverse events. RESULTS: Live-birth rates did not differ significantly among the three study groups. The proportions of women who gave birth to a live infant were 54.5% in the group receiving aspirin plus nadroparin (combination-therapy group), 50.8% in the aspirin-only group, and 57.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, -2.6 percentage points; 95% confidence interval [CI], -15.0 to 9.9; aspirin only vs. placebo, -6.2 percentage points; 95% CI, -18.8 to 6.4). Among 299 women who became pregnant, the live-birth rates were 69.1% in the combination-therapy group, 61.6% in the aspirin-only group, and 67.0% in the placebo group (absolute difference in live-birth rate: combination therapy vs. placebo, 2.1 percentage points; 95% CI, -10.8 to 15.0; aspirin alone vs. placebo -5.4 percentage points; 95% CI, -18.6 to 7.8). An increased tendency to bruise and swelling or itching at the injection site occurred significantly more frequently in the combination-therapy group than in the other two study groups. CONCLUSIONS: Neither aspirin combined with nadroparin nor aspirin alone improved the live-birth rate, as compared with placebo, among women with unexplained recurrent miscarriage. (Current Controlled Trials number, ISRCTN58496168.)

Occurrence and extent of bruising according to duration of administration of subcutaneous low-molecular-weight heparin: a quasi-experimental case-crossover study.

BACKGROUND: Several authors have documented the role of low-molecular-weight heparin injection techniques in bruising. However, few researchers have measured the influence of injection duration on the occurrence and extent of bruising. PURPOSE: The aim of this study was to evaluate the influence of different durations of subcutaneous heparin injection on the occurrence and extent of bruising. METHODS: A quasi-experimental case-crossover study design was adopted in 2010. A consecutive series of patients admitted to 2 orthopedic units in a large (600 beds) teaching hospital located in northern Italy were eligible for enrolment. Injections were administered following a standard procedure. The manipulated variable was the duration of the injection, 10 seconds (treatment A) and 30 seconds (treatment B). The evaluation of bruise occurrence and extension performed after 48 hours and data analysis were conducted in a blinded fashion. RESULTS: A total of 150 patients receiving their first and second subcutaneous heparin injections (300 injections) were enrolled. Eighty-seven bruises were observed out of 300 injections (29%): 57 of 150 (38%) after injections lasting 10 seconds and 30 of 150 (20%) after injections lasting 30 seconds (relative risk, 1.50; 95% confidence interval, 1.21-1.86; P = .00). Of the 87 bruises that occurred, 69 (79.3%) were small (2-5 mm) and 18 (20.6%) were large (>5 mm), with no difference in size between 10- and 30-second injections (relative risk, 0.91; 95% confidence interval, 0.39-2.12; P = .83). CONCLUSIONS: Low-molecular-weight heparin injection should be administered over 30 seconds to decrease bruising. CLINICAL IMPLICATIONS: There is a need to reflect on the feasibility of such a practice because injecting low-molecular-weight heparin at 30 seconds requires accuracy, a steady hand, the absence of tremor, a calm environment, and the ability to administer an infinitesimally small amount of liquid (eg, 0.4 mL) per second.

High versus low concentration botulinum toxin A for benign essential blepharospasm: does dilution make a difference?

PURPOSE: To evaluate the efficacy and side effects of concentrated versus dilute botulinum toxin A in treating benign essential blepharospasm. METHODS: The authors performed a prospective randomized clinical trial of 16 patients with an established diagnosis of benign essential blepharospasm. Patients were randomized to receive low concentration (control, 10 U/ml) injections on one side and high concentration (experimental, 100 U/ml) injections on the other. They were surveyed on a scale of 1 to 10 regarding pain, bruising, and redness immediately after the injection. During their return visit, at an established interval of 1 to 3 months, patients were questioned regarding complications (ptosis, diplopia, tearing, and dry eye), duration of relief, and side preferred. Patients were followed over 8 months for 1 to 6 repeat injections, with the side given the higher concentration alternated at each visit. RESULTS: With 16 patients, there were a total of 42 visits and 84 observations (eyes) documented. Using the Wilcoxon rank sum test, there was a statistically significant reduction in pain scores (1.94 vs. 4.59, p < 0.001) on the experimental side versus the control side. Patient assessment revealed no significant difference in bruising, redness, complications of injection, side preference, or length of relief of symptoms. CONCLUSIONS: Compared with the control, the high concentration botulinum toxin A demonstrated a 58% reduction in perceived pain. Patients did not report a significant difference in efficacy or complications with either dilution.