Results of the First American Prospective Study of IV Iron in Oral Iron Intolerant Iron Deficient Gravidas

Abstract INTRODUCTION: Herein we present safety and efficacy results of the first American prospective study of intravenous (IV) iron (Fe) for oral (PO) Fe intolerant patients with iron deficient anemia (IDA) in the 2nd or 3rdtrimester (IND 114696, ClinTrials.gov NCT 02038023). Anemia affects up to 42% of gravidas. Neonatal Fe deficiency (ID) is associated with low birth weight, delayed growth, development and statistically significant increment in cognitive and behavioral abnormalities up to 10 years after Fe repletion. Although PO Fe is simple to use, inexpensive, up to 70% of gravidas to whom it is prescribed report significant gastrointestinal (GI) side effects. The availability of formulations convenient to administer in a brief single setting with favorable side-effect profiles may help decrease rates of anemia in pregnancy and improve hemoglobin (Hb) responses, maternal and fetal outcomes in women intolerant of, or unresponsive to, PO Fe. METHODS: We treated 74 women with a Hb concentration <10.5 g/dl during the 2nd or <11.0 g/dl in the 3rd, with laboratory evidence of IDA (serum ferritin <20 ng/ml and/or % transferrin saturation (TSAT) <16%). A questionnaire with historical questions of metallic taste, gastric cramping, worsening or onset of constipation was administered to document PO Fe intolerance before enrollment. Women diagnosed during the 1st trimester were eligible for inclusion, however due to a lack of published 1st trimester safety, IV Fe infusion was delayed until beginning of 2nd. All received 1,000 mg LMWID (INFeD, Allergan, CA) diluted in 250 ml of normal saline. 15 minutes after a 25 mg test dose administered over 2 minutes, the remainder was infused over the balance of 1 hour. Subjects were observed for 1 hour for signs of acute hypersensitivity and called at 24, 48 hours and 7 days later to assess delayed reactions. Prior to treatment a visual linear analog scale analysis (LASA) for energy and activity was completed. 4 weeks post- infusion or post-partum depending on confinement, a follow-up visit for Hb levels, Fe parameters (TSAT and serum ferritin) and repeat LASA were performed. Paired T-test was used to assess changes in Hb and Fe parameters, and the Wilcoxin Signed-Rank Test for LASA changes. Following accrual of the final subject 58/73 were contacted and questioned for abnormalities in growth or development of their babies. RESULTS: 73 of 74 enrolled subjects were treated. 1 experienced a minor infusion reaction (facial flushing) and requested treatment on another day. 72 hours later, labor commenced. 2 months post-partum IV Fe was given off study. Follow-up data were available in 58/73 subjects. The mean pre and post treatment Hb concentrations were 9.8 (SD 0.74) and 10.8 (SD 1.30) g/dl respectively (P<0.00001). The mean pre and post TSATs were 11.6 (SD 8.72) and 23.2 and the mean pre and post serum ferritins were 14.2 (SD 22.96) and 129.4 (SD 89.48) ng/mL. respectively (P<0.000001 for both). Data for 58 infants was available; one was low on its growth charts for 11 months after which the curve normalized. The remaining 57, ages 6 weeks to 3 years, were all normal with no evidence of any developmental or growth lag. None were diagnosed with IDA. 6 (8%) experienced minor self-limited infusion reactions consisting of facial flushing or myalgias of the chest or back. All resolved without therapy. 5 of 6 received the planned therapy. 2 developed mild myalgias and headache 24 hours after the infusion, with complete resolution at 48 hours. 85% reported improvements on repeat LASA (P<0.01). DISCUSSION: The high prevalence of IDA in gravidas and its association with adverse maternal and infant outcomes, with a reported 2-fold increment of preterm labor and 3-fold increase in low birth weight, is concerning. PO Fe, the current standard, is fraught with GI toxicity and poor adherence in up to 70% to whom it is prescribed. Our prospective data corroborate a litany of studies, that IV Fe is a safe, effective and convenient method of Fe repletion. No significant adverse events have been reported. 96% had significant improvements in Hb, and 85% energy and activity. No adverse fetal outcomes were observed. The improved side effect profile of IV formulations allowing Fe repletion in a single, brief visit supports moving IV iron closer to frontline. Compared to PO Fe, IV Fe has fewer side effects and nearly always effective. Our data and those of others call for large prospective studies of IV vs. PO Fe for therapy of maternal IDA. Disclosures Auerbach: AMAG Pharma: Consultancy, Research Funding; Pharmacosmos: Consultancy, Research Funding; American Regent/Luitpold: Consultancy.

Download Full-text

Safety and Efficacy of Rapid (one hour) Single Intravenous Dose Low Molecular Weight Iron Dextran for Treatment of Oral Iron Intolerant Maternal Iron Deficient Anemia

Blood ◽

10.1182/blood.v126.23.3356.3356 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3356-3356

Author(s):

Michael Auerbach ◽

Lilee Wong ◽

Jessica McClintock ◽

Steven Lenowitz ◽

Nicola London ◽

...

Keyword(s):

Molecular Weight ◽

Post Partum ◽

Oral Iron ◽

Low Molecular Weight ◽

Iron Dextran ◽

Iron Deficient ◽

The Mean ◽

Low Molecular Weight Iron ◽

Change In Mean

Abstract OBJECTIVE: Determine safety and efficacy of rapid (one hour) intravenous infusion of 1,000 mg low molecular weight iron dextran to pregnant women with moderate to severe iron deficient anemia. INTRODUCTION: Up to 70% of pregnant women to whom oral iron is prescribed report significant gastrointestinal side effects. Intravenous iron is an efficient, but often overlooked, therapeutic alternative. METHODS: We conducted an observational treatment study of 1000 mg low molecular weight iron dextran for moderate to severe iron deficient anemia of pregnancy in 189 consecutive, unselected second and third trimester gravidas intolerant of, or unresponsive to, oral iron. All received an intravenous test dose of approximately 25 mg low molecular weight iron dextran. They were then monitored closely for adverse reactions during the balance of a 60 minute infusion. No premedication was administered unless two or more drug allergies or asthma was present in which case prophylactic intravenous methylprednisolone was administered. All subjects were followed through pregnancy and delivery. Monitored parameters included hemoglobin (Hgb), mean corpuscular volume (MCV), serum ferritin, and percent transferrin saturation. RESULTS: One hundred eighty-nine subjects received a single intravenous dose of 1000 mg low molecular weight iron dextran. No first trimester gravidas were treated. No serious adverse events occurred. Minor, self-limited infusion reactions (myalgias or flushing), occurred in 2% of subjects. The mean number of days from treatment to delivery was 58.6 (range 5-190) days. The change in Hgb was positively correlated with the time from treatment to delivery (r2 =0.17, p=0.0039). The initial Hgb was 10.1 g/dl (SD 1.03, SE 0.07) and at delivery 11.5 g/dl (SD=1.04, SE 0.10), with the mean change from diagnosis to delivery of 1.39 g/dl (p<0.0001). An improvement in Hgb was observed in 174 (92% (Figure 1)). In 110 (58%) the observed increment was 1.00-1.99 g/dl (hemoglobin response) and in 45 (24%) ≥ 2.00 g/dl (hematopoietic response). Second trimester treatment was not associated with a greater improvement in Hgb than third trimester treatment. MCV increased by 3.27 femtoliters (fl) for those treated in the second (p<0.0001), and 1.34 in the third(p<0.0001). The mean increment in MCV for those treated in the second trimester was 1.93 fl higher than those treated in the third (p=0.02). Post-partum data were available on 64 (34%). For this subgroup the mean change in Hgb from diagnosis to delivery was 1.48 g/dl, not significantly different than the observed increment for the entire group of 189. From delivery to post-partum follow-up, an additional Hgb increment of 0.66 g/dl was observed (p<0.0001) consistent with sustained iron repletion and post-partum contraction of plasma volume. The increment in Hgb from diagnosis to delivery and diagnosis to post-partum was similar irrespective of trimester of treatment. Anemia resolved in 95%. CONCLUSION: Administration of a rapid (one hour) single large dose (1000 mg) of intravenous low molecular weight iron dextran is a convenient, effective, well tolerated and safe treatment for maternal iron deficient anemia in women who are intolerant of, or unresponsive to, oral iron. These data are relevant in light of recent publications reporting iron deficient neonates have both delayed growth and development and a statistically significant increment in both cognitive and behavioral abnormalities persisting up to ten years after iron repletion. Figure 1. Change in mean hemoglobin concentration (g/dL) +/- SE from diagnosis to delivery to postpartum follow up. Figure 1. Change in mean hemoglobin concentration (g/dL) +/- SE from diagnosis to delivery to postpartum follow up. Disclosures Off Label Use: Total dose infusion of low molecular weight iron dextran is off label.

Download Full-text

Long-Term Effect of Endoscopic Sympathetic Nerve Reconstruction for Side Effects after Endoscopic Sympathectomy

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0036-1582431 ◽

2016 ◽

Vol 65 (06) ◽

pp. 484-490 ◽

Cited By ~ 3

Author(s):

Timo Telaranta ◽

Tuomo Rantanen

Keyword(s):

Side Effects ◽

Sympathetic Nerve ◽

Nerve Reconstruction ◽

Endoscopic Thoracic Sympathectomy ◽

Thoracic Sympathectomy ◽

Long Term Effect ◽

Primary Hyperhidrosis ◽

The Mean

Background Endoscopic thoracic sympathectomy (ETS) is an effective treatment for primary hyperhidrosis. However, compensatory sweating (CS) may occur in many patients. Sympathetic nerve reconstruction (SNR) can be used to counteract severe CS, but the studies on the effects of SNR are few. Patients and Methods Nineteen out of 150 SNR patients were contacted by employing a long-term questionnaire. In this questionnaire, different kinds of sweating were evaluated using a four-graded symptom analysis and the visual analog scale before ETS, after ETS, and after SNR. Results The mean age of the 16 male and 3 female patients at the SNR was 32 years. The mean follow-up was 87 months. According to the long-term questionnaire, the benefit was either excellent (4 patients, 21%), good (3 patients, 15.8%), or reasonable (7 patients, 36.8%) in 14 patients (73.8%), while the benefit was questionable in 1 patient (5.3%). For three patients (15.8%), no benefit was found, and in one patient (5.3%), the situation had deteriorated. Conclusions Improvement in the side effects of ETS after SNR was found in nearly 75% of the patients. This indicates that SNR can be considered as an alternative treatment for patients with severe CS after ETS that is unresponsive to conservative treatment.

Download Full-text

Long-Term Sustained Responses Following Ibrutinib Discontinuation after Frontline Therapy with Obinutuzumab Plus Ibrutinib in Patients with Chronic Lymphocytic Leukemia

Blood ◽

10.1182/blood-2020-143473 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 33-34

Author(s):

Paula A. Lengerke Diaz ◽

Michael Y. Choi ◽

Eider F. Moreno Cortes ◽

Jose V. Forero ◽

Juliana Velez-Lujan ◽

...

Keyword(s):

Bone Marrow ◽

Side Effects ◽

Chronic Lymphocytic Leukemia ◽

Disease Progression ◽

Research Funding ◽

Lymphocytic Leukemia ◽

Combination Regimen ◽

Grade 3

Single oral targeted therapies have emerged as a standard of care in chronic lymphocytic leukemia (CLL). However, accessibility, side effects, and financial burden associated with long term administration limit their clinical use. Mainly, it is unclear in what clinical situation discontinuation of oral therapy can be recommended. The combination of type II anti-CD20 antibody obinutuzumab-Gazyva® with ibrutinib (GI) has shown a significant progression-free survival benefit in patients (pts) with CLL, including those with high-risk genomic aberrations. We conducted a phase 1b/2, single-arm, open-label trial to evaluate the safety and efficacy of GI as first-line treatment in 32 CLL pts. We report the outcome in pts that discontinued ibrutinib (either after 3 years of sustained complete response (CR) as stipulated in the clinical protocol, or due to other reasons). CLL pts enrolled in this protocol were ≥65 years old, or unfit/unwilling to receive chemotherapy. Pts received GI for six cycles, followed by daily single-agent ibrutinib. The protocol was designed to ensure that pts with a sustained CR after 36 months were allowed to discontinue ibrutinib. The median age was 66 years (IQR 59-73), and 6% of the evaluated pts had 17p deletion. All pts were able to complete the six planned cycles of obinutuzumab. The combination regimen was well-tolerated, and the most common adverse events (>5% CTCAE grade 3-4) were neutropenia, thrombocytopenia, and hyperglycemia. The rate and severity of infusion-related reactions (IRR) were much lower than expected (Grade≥ 3, 3%), and pts without IRR had lower serum levels of cytokines/chemokines CCL3 (P=0.0460), IFN-γ (P=0.0457), and TNF-α (P=0.0032) after infusion. The overall response rate was 100%, with nine pts (28%) achieving a CR, and four pts (12.5%) with undetectable minimal residual disease (uMRD) in the bone marrow, defined as <10-4 CLL cells on multicolor flow cytometry. At a median follow-up of 35.5 months (IQR 24.5-42.7) after starting treatment, 91% of the enrolled pts remain in remission with a 100% overall survival. Sixteen pts have completed a long-term follow-up of 36 months. Six pts showed CR, with three of them achieving uMRD in the bone marrow. Ten of these pts were in PR, and only one had disease progression and started treatment for symptomatic stage I disease with obinutuzumab plus venetoclax. In total, thirteen pts (41%) have stopped ibrutinib, with a median time on treatment prior to discontinuation of 35 months. Five (16%) of these pts had CRs and discontinued after 36 months. Eight additional pts (25%) had PRs and discontinued ibrutinib without being eligible: three pts discontinued prior to 36 months due to toxicities, and five pts discontinued after 36 months (3 due to side effects, and 2 due to financially driven decision). One patient eligible to discontinue ibrutinib, decided to remain on treatment despite sustained CR. After a median follow up time following ibrutinib discontinuation of 8 months (IQR 3.5-17), only two out of 13 pts have progressed (10 and 17 months after Ibrutinib discontinuation). None of the pts that stopped ibrutinib after achieving a CR have shown signs of disease progression. Of note, the pharmaceutical sponsor provided ibrutinib for the first 36 months, after which pts or their insurer became financially responsible. This particular scenario could bias the discontinuation pattern compared to a real world experience. It also provided us with a perspective about diverse factors affecting the treatment choices of pts. In summary, the obinutuzumab plus ibrutinib combination therapy was well-tolerated, with a much lower IRR rate. Efficacy compares favorably with historical controls with all pts responding to therapy, no deaths associated with treatment or disease progression, and a longer than expected time-to-progression after discontinuation of ibrutinib. The rate of ibrutinib discontinuation was higher than reported in the literature, most likely influenced by the protocol design and financial decisions driven by the switch from sponsor-provided ibrutinib to insurance or self-paid medication. Our observations regarding safety, efficacy and lack of disease progression after ibrutinib discontinuation are encouraging, and warrant confirmation in long-term prospective studies. Clinicaltrials.gov Identifier NCT02315768. Funding: Pharmacyclics LLC. Disclosures Choi: AbbVie: Consultancy, Speakers Bureau. Amaya-Chanaga:AbbVie: Ended employment in the past 24 months, Other: Research performed while employed as an investigator of this study at UCSD.. Kipps:Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Castro:Kite Pharma: Research Funding; Pharmacyclics: Research Funding; Fate Therapeutics: Research Funding.

Download Full-text

Incidences Of Nasal Septal Deviation And Its Effect On Surgical Success In Patients With Congenital Nasolacrimal Dacryostenosis

10.21203/rs.3.rs-358906/v1 ◽

2021 ◽

Author(s):

fatma esin özdemir ◽

selin Üstün Bezgin ◽

Zeliha Karademir

Keyword(s):

Birth Weight ◽

Endoscopic Examination ◽

Septal Deviation ◽

Nasal Septal Deviation ◽

Surgical Success ◽

Time Of Surgery ◽

Vaginal Deliveries ◽

The Mean ◽

Type Of Delivery

Abstract OBJECTIVE: An investigation of incidences of nasal septal deviation (NSD) and its effect on surgical success in patients with congenital nasolacrimal dacryostenosis (CNLDO).METHODS: A retrospective review was made of the medical records of patients who presented to the ophthalmology clinic due to epiphora, were diagnosed with CNLDO and underwent probing. The diagnosis was established by history, clinical examination, and fluorescein disappearance test (FDT)1. Patients with FDT grade 2 and 3 underwent surgery. Success was defined as postoperative FDT grade 0–1. The patients were assessed in terms of gestational week, birth weight, type of delivery, nasal endoscopic examination findings (presence of NSD), time of surgery, treatments received, recurrence and complications.RESULTS: The study comprised 72 eyes of 58 patients who were diagnosed with CNLDO and underwent surgical treatment. Of the patients, 44 (75.86%) had unilateral, and 14 (24.14%) had bilateral CNLDO; 41 (56.94%) were female and 31 (43.06%) were male. The mean gestational age at birth was 38.01 weeks (32–41 weeks), the mean birth weight was 3321.25 (2020–4500 g), the number of cases delivered by cesarean section was 40 (55.56%), and 32 (44.44%) were vaginal deliveries. There were 13 (18.06%) patients with detected NSD after endonasal examination and 59 (81.94%) patients with normal endonasal examination in the Otorhinolaryngology (ORL) department. The time of surgery was 10 –34 months (mean: 19.06 months, SD: 5.73), the length of follow-up was 6–16 months (mean: 9.90 months, SD: 2.58). The rate of probing success was 80.6% (58 eyes), and there was recurrence in 19.4% (14 eyes).The success rate of the probing did not statistically significantly differ by gender (p=0.323), the mean birth week (p=0.123), the mean birth weight (p=0.186), the involved eye (p=0.891), the type of delivery (p=0.891), the mean length of follow-up (months) (p=0.701), the mean month of surgery (p=0.607), and the side of NSD (p=0.853). The incidence of NSD was statistically significantly higher in the group in which the probing failed, than in the group in which the probing was successful (p=0.004).CONCLUSION: NSD was identified in 18% of the patients who were diagnosed with CNLDO and underwent surgery. The incidence of NSD was significantly higher in the group where the probing procedure failed. Pre-treatment nasal endoscopy is important for the treatment planning and prognosis of CNLDO patients.

Download Full-text

Neurodevelopmental Outcome at 36 Months' Corrected Age of Preterm Infants in the Multicenter Indomethacin Intraventricular Hemorrhage Prevention Trial

PEDIATRICS ◽

10.1542/peds.98.4.714 ◽

1996 ◽

Vol 98 (4) ◽

pp. 714-718 ◽

Cited By ~ 5

Author(s):

Laura R. Ment ◽

Betty Vohr ◽

William Oh ◽

David T. Scott ◽

Walter C. Allan ◽

...

Keyword(s):

Birth Weight ◽

Low Birth Weight ◽

Intraventricular Hemorrhage ◽

Maternal Education ◽

Low Dose ◽

Very Low Birth Weight ◽

Cranial Ultrasound ◽

The Mean ◽

English Monolingual

Objectives. Low-dose indomethacin has been shown to prevent intraventricular hemorrhage (IVH) in very low birth weight neonates, and long-term neurodevelomental follow-up data are needed to validate this intervention. We hypothesized that the early administration of low-dose indomethacin would not be associated with adverse cognitive outcome at 36 months' corrected age (CA). Methods. We enrolled 431 neonates of 600 to 1250 g birth weight with no IVH at 6 to 12 hours in a randomized, prospective trial to determine whether low-dose indomethacin would prevent IVH. A priori, neurodevelopmental follow-up examinations, including the Stanford-Binet Intelligence Scale and Peabody Picture Vocabulary Test-Revised, and standard neurologic examinations were planned at 36 months' CA. Results. Three hundred eighty-four of the 431 infants survived (192 [92%] of 209 infants receiving indomethacin versus 192 [86%] of 222 infants receiving saline), and 343 (89%) children were examined at 36 months' CA. Thirteen (8%) of the 166 infants who received indomethacin and 14 (8%) of 167 infants receiving the placebo were found to have cerebral palsy. There were no differences in the incidence of deafness or blindness between the two groups. For the 248 English-monolingual children for whom IQ data follow, the mean gestational age was significantly younger for the infants who received indomethacin than for those who received the placebo. None of the 115 infants who received indomethacin was found to have ventriculomegaly on cranial ultrasound at term, compared with 5 of 110 infants who received the placebo. The mean ± SD Stanford-Binet IQ score for the 126 English-monolingual children who had received indomethacin was 89.6 ± 18.92, compared with 85.0 ± 20.79 for the 122 English-monolingual children who had received the placebo. Although maternal education was strongly correlated with Stanford-Binet IQ at 36 months' CA, there was no difference in educational levels between mothers of the infants receiving indomethacin and the placebo. Conclusions. Indomethacin administered at 6 to 12 hours as prophylaxis against IVH in very low birth weight infants does not result in adverse cognitive or motor outcomes at 36 months' CA.

Download Full-text

Association of early postnatal growth trajectory with body composition in term low birth weight infants

Journal of Developmental Origins of Health and Disease ◽

10.1017/s2040174414000178 ◽

2014 ◽

Vol 5 (3) ◽

pp. 189-196 ◽

Cited By ~ 12

Author(s):

P. Khandelwal ◽

V. Jain ◽

A. K. Gupta ◽

M. Kalaivani ◽

V. K. Paul

Keyword(s):

Body Composition ◽

Birth Weight ◽

Low Birth Weight ◽

Postnatal Growth ◽

Early Infancy ◽

Low Birth Weight Infants ◽

Z Scores ◽

The Mean ◽

And Gender

Growth acceleration or catch-up growth (CUG) in early infancy is a plausible risk factor for later obesity and cardiovascular disease. We postulate that this risk may be mediated by an adverse programming of body composition by CUG in early infancy. The study was aimed at evaluating the association between the pattern of gain in weight and length of term low birth weight (LBW) infants from birth to 6 months, with fat mass percent (FM%) at 6 months. Term healthy singleton LBW infants were enrolled. Baby’s weight and length z-scores were measured at birth and three follow-up visits. Body composition was measured by dual-energy absorptiometry at last visit. A total of 54 babies (28 boys) were enrolled. The mean birth weight and gestation were 2175±180 g and 37.6±0.6 weeks. Follow-up visits were at 1.4±0.0, 3.0±0.3 and 7.2±0.8 months. The proportion of babies who showed CUG [increase in weight for age z-score (∆WAZ)>0.67] from birth to 1.4, 3.0 and 7.2 months was 29.6, 26.4 and 48.5%, respectively. The mean FM% at 7.2 months was 16.6±7.8%. Infants with greater ∆WAZ from birth to 3 and 7.2 months had significantly greater FM% at 7.2 months after adjusting for current age, size and gender. Infants with early CUG (<1.4 months) had higher FM% than infants with no CUG. We conclude that earlier and greater increment in WAZ is positively associated with FM%.

Download Full-text

TREATMENT OF TRIGGER FINGERS BY INJECTION OF METHYLPREDNISOLONE ACETATE AND LIDOCAINE (DEPO-MEDROL®)

Hand Surgery ◽

10.1142/s021881049600018x ◽

1996 ◽

Vol 01 (02) ◽

pp. 103-105

Author(s):

J. Joris Hage ◽

Jaap D.K. Munting

Keyword(s):

Side Effects ◽

Prospective Study ◽

Success Rate ◽

Adult Patients ◽

Methylprednisolone Acetate ◽

Short Term ◽

Local Injections ◽

One Year ◽

A Prospective Study

Thirty-six adult patients with 44 trigger fingers of less than four months' duration entered a prospective study on the efficiency of treatment with local injections of a combination of corticosteroids and lidocaine. From this study it may be concluded that the short-term success rate (93%) of one to three injections of methylprednisolone and lidocaine 2% (Depo-Medrol®) is comparable to that achieved by surgical or percutaneous tenolysis. At one year of follow-up, this success rate still amounted to 86%. In our hands, this therapy is without complications or side effects.

Download Full-text

Immediate post placental insertion of intrauterine contraceptive device at caesarean delivery: a prospective study

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20202068 ◽

2020 ◽

Vol 9 (6) ◽

pp. 2244

Author(s):

Sravani Mukka ◽

Madhavi Y.

Keyword(s):

Family Planning ◽

Prospective Study ◽

Post Partum ◽

Unmet Need ◽

Intrauterine Contraceptive Device ◽

Efficacy Rate ◽

Contraceptive Device ◽

Intrauterine Contraceptive ◽

A Prospective Study

Background: In India almost 65% of the women have an unmet need for family planning in the first postpartum year. Increasing rates of institutional deliveries creates an opportunity for providing quality post-partum family planning services. Post-partum Intrauterine contraceptive device (PPIUCD), a form of long acting reversible contraception (LARC) is one of the most affective and safest method available. The present study aims at evaluating the safety, efficacy, rate of acceptance and rate of discontinuation of Intra caesarean inserted contraceptive device Copper T-380A.Methods: This was a prospective study conducted at ESIC Medical College, Sanathnagar in women delivered by caesarean section during the period between March 2018 to February 2019. Recruitment was done based on the WHO medical eligibility criteria (MEC) for PPIUCD and also their willingness to participate in the study. Follow-up visits were scheduled at 6 weeks, 3 months and 6 months.Results: Of the 265 women fulfilling the WHO MEC, 180 (67.92%) were willing to participate in the study. Total acceptance rate was 67.7%. Majority of them belonged to the age group 21-30 years (80%) and para 2 (53.88). 93.3% of the women were literates. 12 (6.66%) cases lost to follow up and the complications were studied in the rest 168 women. During follow up -38.69% had missing strings, 12.5% menstrual disturbances, 4.76% abdominal pain and spontaneous expulsion in 4.1%. No cases of perforation and pregnancy were reported. Total continuation rate was 84%.Conclusions: PPIUCD is a safe and convenient option of contraception with low expulsion rates and high continuation rates.

Download Full-text

Maintenance Treatment with 5-Azacitidine for Patients with High Risk Myelodysplastic Syndr–ome (MDS) or Acute Myeloid Leukemia Following MDS (MDS-AML) in Complete Remission (CR) after Induction Chemotherapy

Blood ◽

10.1182/blood.v112.11.223.223 ◽

2008 ◽

Vol 112 (11) ◽

pp. 223-223 ◽

Cited By ~ 6

Author(s):

Michael Grövdal ◽

Rasheed Khan ◽

Anni Aggerholm ◽

Petar Antunovic ◽

Jan Astermark ◽

...

Keyword(s):

Overall Survival ◽

Side Effects ◽

High Risk ◽

Induction Chemotherapy ◽

Maintenance Treatment ◽

Methylation Status ◽

Induction Treatment ◽

The Mean ◽

Pre Treatment

Abstract Around 50% of patients with high-risk MDS or MDS-AML may enter CR after induction chemotherapy, but CR duration, as well as overall survival is usually short. To address this clinical problem the Nordic MDS Group designed a prospective multicenter phase II study, which assessed the clinical feasibility and utility of long-term maintenance treatment with azaciditine. Sixty patients with high-risk MDS (IPSS intermediate-2 or high) (n=23) or AML following a previous known MDS (n=37) were enrolled between 2004 and 2006. The mean age was 68 (54–83) and patients should not be eligible for stem cell transplantation. Induction treatment consisted of standard doses of daunorubicin and ara-C. Patients in CR received low dose azacitidine subcutaneously 5/28 days until relapse, unless unacceptable toxicity developed. Methylation status of the P15ink4b (P15), E-cadherine (CDH) and Hypermethylated in Cancer 1 (HIC) gene was analysed at study start, in CR and in some patients during follow up. Last follow up was on August 1 2008, 24 months after the last CR was reported. Twenty-four patients (40%) reached CR and 23 of these started maintenance treatment with azacitidine. The initial dose of azacitidine was 75 mg/m2 but as four of the first five enrolled patients developed grade 4 cytopenia, the starting dose was lowered to 60 mg/m2, and was allowed to be reduced to 45 or 30 mg/m2 to avoid severe cytopenias. The mean dose of azacitidine was 54.3 mg/m2. Azacitidine was well tolerated. In 52% of the cases no side effects at all were reported. The most commonly reported side effect was mild rashes at the injection site (35%). Twenty-two percent developed fever or some kind of infection, mostly mild. Myelosuppression (grade 1–3) was seen in 22% of the cases. As previously reported, the probability of reaching CR was negatively correlated to promoter hypermethylation of CDH (p=0.008) and none of the 6 patients hypermethylated on all 3 genes reached CR (p=0.03) and hence only four patients hypermethylated on other genes than P15 received demethylating therapy. The median CR duration for the azacididine treated group was 13.5 months (2–49+) and median survival time from time of inclusion in the study for the same group was 20 months (4–52+). Four of 23 patients (17%) had a CR exceeding 24 months (32–52+). The two patients hypermethylated on CDH pre-induction had CR durations of only 2 and 5 months respectively. By last follow up 3 patients were still in CR. Of 10 patients without any methylation pre-treatment, all but one maintained this pattern in CR. Of the nine patients with pre treatment methylation of at least one gene, only one remained hypermethylated in CR. This patient had a CR duration of only 5 months. One patient showed development of P15 hypermethylation in the bone marrow sampled at 12 months and relapsed at 15 months. These findings support previous reports on P15 hypermethylation as a marker for minimal residual disease (MRD) and threatening relapse. In the whole group, survival was significantly shorter in patients with CDH methylation (3 vs 9 months, p=0.005), while pre-treatment p15 methylation status did not affect CR duration or overall survival. In conclusion, we show for the first time that maintenance treatment with azacytidine is feasible and associated with a median CR duration of 13.5 months, and very mild side effects. However azacytidine does not seem to prevent relapse in the majority of patients, including those with hypermethylation pre-treatment and/or in CR. Hypermethylation of multiple genes is a strong negative factor for survival, probability of CR, and CR duration. We observe a subset of patients, 17%, with a CR duration of >24 months; but no persistent pattern regarding cytogenetics, methylation or morphology could be identified in this group. The strong negative impact of E-Cadherin methylation, a gene involved in adhesion, warrants further investigation.

Download Full-text

Chronic Idiopathic Neutropenia In Adults: Clinical Features In a 4-Year Prospective Study

Blood ◽

10.1182/blood.v122.21.1026.1026 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1026-1026

Author(s):

Bruno Fattizzo ◽

Tommaso Radice ◽

Francesca Guidotti ◽

Anna Zaninoni ◽

Alberto Ciani ◽

...

Keyword(s):

Bone Marrow ◽

Prospective Study ◽

Nk Cells ◽

Oral Antibiotic ◽

Upper Respiratory Tract ◽

Chronic Idiopathic Neutropenia ◽

Immune Phenotyping ◽

The Mean ◽

Tract Infections

Abstract Chronic idiopathic neutropenia (CIN) is a rare acquired hematological condition, defined by an absolute neutrophil count (ANCs) lower than 1.8 x103/µL in white and 1.5 x103/µL in black people for more than 3 months, either in the absence or in the presence of anti-neutrophils antibodies (autoimmune forms). CIN is usually diagnosed after the exclusion of congenital and secondary forms. The former are usually marked by frequent and severe infections, that occur early in life, and by and increased risk of evolution to acute myeloid leukemia or myelodisplastic syndromes. In this prospective study we followed up 56 patients with CIN (21 males and 35 females, median age 55 years, range 25-86 years) for a median time of 48 months from January 2009 (10 patients had a previous follow-up of 8 years and 2 of 10 years), focusing on 1) severity of neutropenia, 2) ANCs variations (by general estimating equations GEE models), 3) positivity for anti-neutrophil antibodies (by direct and indirect granulocyte immunofluorescence test), 4) bone marrow features, 5) incidence of infectious episodes, and 6) evolution to definite clonal hematologic diseases (hairy cell leukemia HCL, chronic expansion of NK cells and myelodisplastic syndrome MDS). The mean ANCs were stably under the normal range (1.5-6.5 x103/µL) at all the time points considered; by GEE analysis, a great inter-subject variability was observed during the follow-up (p=0.012), whereas no significant intra-subject variations were found. Considering the severity of neutropenia, 21 patients (47%) showed neutrophils lower than 1x103/µL at enrollment (median 0.49 x103/µL, range 0.1-0.969 x103/µL), and 8 cases <0.5 x103/µL. The mean ANCs observed during the follow up were significantly lower in males than in females (p=0.023) and in cases with mild splenomegaly, although not significantly (11 cases, 20%, mean maximal diameter 11,4 cm by ultrasonography), independently from gender (multivariate analysis). Anti-neutrophil antibodies were detected in 19/56 patients (34%), and mean ANCs values over the follow up were significantly lower in positive versus negative cases (p=0.027). Lymphocyte values greater than the upper normal value of our series (3.4 x103/µL) were observed in 5/56 patients (9%). By peripheral blood immunophenotyping (N=23), 13 (56.5%) patients displayed absolute NK+ cells greater than 0.2 x103/mL (normal NK cut-off value), but all under below 2 x103/µL. Bone marrow evaluation was performed in 27 patients: median cellularity was 35% (range 13-75), and 10/27 (37%) displayed a value lower than 25% (threshold for hypocellularity in aplastic anemia); 19/27 (70%) showed some dysplastic cells, even if less than 10% dysplastic cells and without coexistent MDS-related karyotype; cytogenetic was normal in 24 cases (89%), while 3 males, all older than 60 years, displayed a 45, X0 karyotype (7, 6 and 3 metaphases respectively. Finally, 10 patients (18%) showed monocytosis, and 6 (10%) a MGUS. An infection needing oral antibiotic or antiviral therapy occurred in 13 patients (25%) (2 pneumonias, 7 upper respiratory tract, 3 Herpes Zoster Virus and 1 urinary tract infections), without relationship with the patient’s mean ANCs value, the nadir of ANC value, nor with the presence of anti-neutrophil antibodies. During the follow-up, because of suspected progression/evolution, 14 patients were re-evaluated by bone marrow biopsy or peripheral immune-phenotyping: 4 cases were diagnosed with chronic NK expansion, 4 with HCL, and 2 with MDS, one refractory cytopenia with unilineage dysplasia (RCUD) and one with multilineage dysplasia (RCMD). No association was found between evolution and ANCs, both as values at enrolment and mean counts over the follow up, nor with gender, presence of anti-neutrophils antibodies, monocytosis, splenomegaly, electrophoresis abnormalities and infections. All 4 patients, who developed an NK-expansion, showed peripheral lymphocytes >3.4 x103/µL at enrolment (>5x103/µL in only 1 case), and 3 cases displayed increased NK cells at peripheral immune-phenotyping (p= 0.018). In conclusion, CIN in adults is a benign disease, with an infectious rate not superior to that of the general population and a great variability in ANCs values. During this prospective observation, 10 CIN patients evolved, reaching the criteria for clonal hematological diseases, suggesting that this condition deserves clinical follow up. Disclosures: No relevant conflicts of interest to declare.

Download Full-text