Moms' Chemotherapy Has No Apparent Effect on Fetal Development

An ongoing study finds no apparent neurological, cardiac, or other developmental ill effects on fetuses exposed to their mothers' chemotherapy.

The interim analysis, reported in the Lancet Oncology, surveys some 70 pregnancies followed for a median of two years after delivery, with assessments at birth and at 18 months and beyond. Chemotherapy, mostly with anthracycline drugs, had begun in all pregnancies after the first trimester. 

Children generally showed normal growth and development. Those born prematurely (most often for nonobstetric reasons) had lower measures of cognitive development, but this was similar to the effect seen in other studies of premature infants without exposure to chemotherapy.

The authors conclude that their findings "do not support a strategy of delay in chemotherapy administration." 

MY COMMENT is that induced preterm deliveries should be restricted to those cases where the mother's survival would otherwise be in jeopardy.

Summary of the study

Background

Chemotherapy for the treatment of maternal cancers during pregnancy has become more acceptable in the past decade; however, the effect of prenatal exposure to chemotherapy on cardiac and neurodevelopmental outcomes of the offspring is still uncertain. We aimed to record the general health, cardiac function, and neurodevelopmental outcomes of children who were prenatally exposed to chemotherapy.

Methods

Interim analysis of a multicentre observational cohort study assessing children who were prenatally exposed to maternal cancer staging and treatment, including chemotherapy. The assessed children at birth, at age 18 months, and at age 5—6, 8—9, 11—12, 14—15, or 18 years. We did clinical neurological examinations, tests of the general level of cognitive functioning (Bayley or intelligence quotient [IQ] test), electrocardiography and echocardiography, and administered a questionnaire on general health and development. From age 5 years, we also did audiometry, the Auditory Verbal Learning Test, and subtasks of the Children's Memory Scale, and the Test of Everyday Attention for Children, and we also completed the Child Behavior Checklist.

Findings

236 cycles of chemotherapy were administered in 68 pregnancies. We assessed 70 children, born at a median gestational age of 35·7 weeks (range 28·3—41·0; IQR 3·3; 47 women at <37 weeks), with a median follow-up period of 22·3 months (range 16·8—211·6; IQR 54·9). Although neurocognitive outcomes were within normal ranges, cognitive development scores were lower for children who were born preterm than for those born at full term. When controlling for age, sex, and country, the score for IQ increased by an average 11·6 points (95% CI 6·0—17·1) for each additional month of gestation (p<0·0001). Our measurements of the children's behaviour, general health, hearing, and growth corresponded with those of the general population. Cardiac dimensions and functions were within normal ranges. We identified a severe neurodevelopmental delay in both members of one twin pregnancy.

Interpretation

Fetal exposure to chemotherapy was not associated with increased CNS, cardiac or auditory morbidity, or with impairments to general health and growth compared with the general population. However, subtle changes in cardiac and neurocognitive measurements emphasise the need for longer follow-up. Prematurity was common and was associated with impaired cognitive development. Therefore, iatrogenic preterm delivery should be avoided when possible.

ORIGINAL ARTICLE: Long-term cognitive and cardiac outcomes after prenatal exposure to chemotherapy in children aged 18 months or older: an observational study. 

http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70363-1

by

Akshaya Srikanth

Pharm.D Internee

Hyderabad, India

PEDIATRIC LYMPHOMAS

Lymphomas are diseases in which cancerous cells form in the system that makes lymph (fluid that contains white blood cells that protect the body against infection).The outlook for patients with lymphoma depends on the type of tumor and whether the tumor has spread outside the lymph nodes (small glands that circulate lymph around the body).

Types of lymphomas:

• Hodgkin lymphomas develop when abnormal B cells (an immune system cell) accumulate in the immune system.
• Non-Hodgkin lymphomas, which are more common than Hodgkin lymphomas, occur when the body produces too many white blood cells called lymphocytes.

Symptoms of Pediatric Lymphomas

Symptoms vary depending on the type of cancer. Many of the symptoms of childhood cancers can also be symptoms of other diseases. Be sure to consult your doctor if your child has symptoms that seem unusual for him or her.

1. Breathing problems

2. Fever

3. Night sweats

4. Shortness of breath

5. Swollen lymph nodes

6. Weight loss

7. Wheezing

Stages

Hodgkin lymphoma

Stage I: Cancer is confined to lymph nodes in one group, or it is found outside the lymph nodes but in only one organ.

Stage II: The cancer is in two or more different lymph node groups, or it is in one organ as well as nearby lymph nodes. But it is still limited to either the area above or the area below the diaphragm.

Stage III: The cancer is found in lymph nodes both above and below the diaphragm. The cancer may also be in one organ or tissue near the lymph nodes, or in the spleen.

Stage IV: Cancer is found in several parts of one or more organs or tissues such as the bones, the liver, or the lungs.

Non-Hodgkin lymphoma

In addition to being divided into four stages, non-Hodgkin lymphoma is referred to as low stage (it has not spread outside the area where it began) or high stage (it has spread beyond its original location). The specific stages are:

Stage I: Cancer is found in one group of lymph nodes (such as in the neck or under the arm), or it is not found in lymph nodes but in one organ or area, such as the liver or the lung.

Stage II: Cancer is found in two different groups of lymph nodes or in one group of lymph nodes and one organ outside the lymph nodes.

Stage III: Cancer is found in lymph nodes both below and above the diaphragm (the muscle separating the chest from the abdomen). The cancer may also be in organs nearby.

Stage IV: Cancer is found in the brain, bone marrow, or cerebrospinal fluid, or it is found in several different organs or areas of the body.

Concerns in enlarged LN:Size >1-2 cm Increasing size over 2-4 weeks Matted or fixed Supraclavicular LN Fevers >38.5 for 2-4 weeks Constitutional symptoms HSM

When to biopsy: Supraclavicular node Increasing size over 2-4 weeks Constitutional symptoms Asymptomatic enlarged node-not decreasing in size over 6 weeks or not normal after 8-12 weeks

Staging Evaluation: 

Staging Evaluation Laboratory: 

CBC with smear -Chem profile LHD, uric acid Disease specific -ESR, IL2R for HD -LP if head/neck NHL -BMA/Bx for all NHL, only IIB or higher HD Radiology -CXR (PA & Lat) -CT scans neck, chest, abdomen -Gallium, bone scan -PET scan

Lymphoma Staging:

Murphy Ann Arbor I: tumor at one site (nodal or extranodal -- “E”) II: two or more sites; same side of body (or resectable GI primary) III: both sides of body but not IV (& unresec. GI & mediastinal for NHL) IV: CNS or marrow involvement (Murphy); lung, liver, marrow, or bone for Ann Arbor (< 25% marrow) “B” sxs are defined for HD, as is “bulky disease” Head and neck (possibility of CNS involvement) is a further consideration for NHL PET or gallium Non-Hodgkin’s Lymphoma:Malignant solid tumor of immune system Undifferentiated lymphoid cells Spread: aggressive, diffuse, unpredictable Lymphoid tissue; BM and CNS infiltration High growth fraction and doubling time Dx and Rx ASAP Rapid CTX response; tumor lysis concern Incidence/Etiology - NHL:6% childhood cancer 60% of childhood lymphomas Peak age of 5-15; M:F ratio of 2.5:1 Increased with SCIDS, HIV, EBV post t-cell depleted BMT post solid organ transplant Geographic, viral, genetic & immunologic factors Types of NHL:Lymphoblastic (30-35%) 90 % immature T cells (very similar to T-ALL) remainder pre-B phenotype (as in ALL) 50-70% anterior mediastinum neck, supraclavicular, axillary adenopathy Classic: older child with intussusception Clinical Presentations:Abdomen: (35%): pain, distention, jaundice, GI problems, mass Head/neck (13%): lymphadenopathy, jaw swelling, single enlarged tonsil, nasal obstruction, rhinorrhea, cranial nerve palsies Mediastinum (26%): SVC syndrome CNS (rare): HA, V, irritability, papilledema +Fever, malaise, night sweats, wt. loss, Staging of NHL:I Single tumor /node NOT in mediastinum or abdomen II 1-2 nodes same side of diaphragm or resectable GI primary III 2+ nodes both sides of diaphragm; intrathoracic or extensive intra-abd IV Any of above with CNS and/or BM Prognosis affected by…:Incomplete remission in first 2 mos. Rx Large tumor burden (LDH >1000) Stages III and IV: CNS or BM involvement Delay in treatment Relapse **More favorable: Stage I or II, head/neck, peripheral nodes, GI tract

NHL Treatment:

Surgery for diagnostic bx or second look Radiation Therapy: emergency airway obstruction or CNS complication – may be used for local control of residual mass Chemotherapy: Combination chemo is usual, with overall cure rates 60-80+%; high risk of tumor lysis and hyperuricemia Relapse: Re-induction, followed by BMT

NHL chemotherapy overview:

Low-stage NHL’s are treated with CHOP (+/- rituximab – anti-CD20) Higher-stage lymphoblastic lymphomas are treated on leukemia protocols Higher-stage non-lymphoblastic NHLs require extremely aggressive chemotherapy with significant infectious risks, but still have generally good remission rates High-dose chemotherapy with stem cell rescue is considered an option for relapse, though without the success rates of HD; T cell disease probably requires an allogeneic response...

Source: Duke Cancer Health

by

Akshaya Srikanth

Pharm.D Intern

Hyderabad, India

"Pharm.D" The No.1 Employer in Medical Research

"Celebrating 100th post with SPECIAL"

The pharmacy community contributes to biomedicine at multiple levels including education, scholarly activity, and service through patient care. Pharm.D have a broad base of knowledge in pharmacology, including pharmacokinetics, pharmacodynamics, pharmacogenetics, pharmacotherapy, pharmacoepidemiological and pharmacoeconomics, as well as a strong understanding of human metabolism, transport, and elimination. Because of significant interest in clinical research questions related to drug development and therapeutics, the field of pharmacy is in a unique position to conduct research toward achieving the goal of individualized prescription drug therapy. With the ability to envision translational endpoints, Pharm.D is a valuable component of the current biomedical research enterprise.  

Pharmaceutical scientists can offer unique perspectives to clinical and translational research, such as introducing and integrating pharmacogenomic approaches and methods to clinical trials in various disease areas. In addition, Pharm.D researchers can play an important bridging role between clinical investigators who may not otherwise find each other. Broad training in physiology and drug metabolism enables Pharm.D scientists to pursue research interests in a range of therapeutic areas, including but not limited to oncology, cardiology, HIV/AIDS, liver disease, and health services research. Pharmaceutical scientists that are currently conducting studies in these areas provided brief accounts of their research, described their own career paths, and offered suggestions on strengthening the Indian Pharm.D researcher pipeline.

Despite a wide range of individual career trajectories, these successful pharmaceutical researchers all viewed certain characteristics of their training as pivotal to their becoming productive, independent scientists. These include i) high-quality mentoring, ii) grant-writing education and experience, iii) exposure to rigorous research, and iv) clinical acumen acquired through practice experience. 

Leading pharmaceutical scientists have followed diverse paths to yield successful research careers

Historically, most of the trailblazers in pharmacy research discovered their interest and compatibility with scientific investigation relatively late in the game. Most reported that they turned to research after realizing that manufacturing & dispensing alone was not sufficient to hold their interest. Many also were dissatisfied with the lack of a literature basis for pharmacy practice. Once these investigators chose to pursue a research career, a common thread to their eventual success was the significant value of mentoring (occasionally from outside the profession). Whether on-site or from a distance, mentoring is an essential component of the professional development of junior investigators. Through continual nurturing from experienced investigators, junior scientists acquire the necessary professional skills for succeeding in research, such as grant-writing and manuscript preparation. Mentoring Pharm.D students from current level should also include a focus on raising awareness about clinical research opportunities and play their role in interpreting the research. 

Pharm.D aspirants have a wide range of research exposure and career interests in academia and industry

Some students plan to pursue Ph.D. after earning their Pharm.D degree, whereas others obtain research experience through some type of post graduate diploma in research after receiving a Pharm.D degree. There is some debate about the value of each type of training approach in our country, but general consensus exists that when it comes to training, one size does not fit all. Speakers agreed that a solid basic science education and meaningful clinical experience were both important ingredients of a successful pharmacy researcher. 

For those students who focus on research, individual preference as well as research interest and skills will influence whether that graduate suits his employment in academia, industry, or other venues such as the government. One reality is money: Every graduate who had the thought to accumulate into the industry after his Pharm.D degree will find a high-paying position in industry in future. It is also important to recognize that emerging Pharm.D graduates will surely draw their importance and contribution to industry irrespective of other concerns. Pharm.D's had the opportunity to play key leadership roles in contract research organizations (CROs), pharmacovigilance, health policy makers, pharmaceutical firms, and biotechnology companies in their careers.

 by

Akshaya Srikanth,

Pharm.D Intern,

P.R.R.M.College of Pharmacy & RIMS Hospital

Kadapa, A.P

India.

Eat sweets at breakfast to lose weight...!!!!!

Those with a weakness for sweets can now include cookies and cake in a 600 calorie breakfast menu with some proteins and carbs to shed weight in a pleasurable way and also stay slim.

Those with a weakness for sweets can now include cookies and cake in a 600 calorie breakfast menu with some proteins and carbs to shed weight in a pleasurable way and also stay slim.

Attempting to avoid sweets entirely can create a psychological addiction to these same foods in the long-term, explains Daniela Jakubowicz, professor at Tel Aviv University`s Sackler Faculty of Medicine, who led the study.

Over the course of a 32-week-long study, participants who added dessert to their breakfast - cookies, cake, or chocolate - lost an average of 40 pounds more than a group that avoided such foods, the journal Steroids reports.

What`s more, they kept off the pounds longer. A meal in the morning provides energy for the day`s tasks, aids in brain functioning, and kick-starts the body`s metabolism, making it crucial for weight loss and maintenance, according to a Tel Aviv statement.

And breakfast is the meal that most successfully regulates ghrelin, the hormone that increases hunger, explains Jakubowicz. While the level of ghrelin rises before every meal, it is suppressed most effectively at breakfast time.

These findings were based on 193 clinically obese, non-diabetic adults, who were randomly assigned to one of two diet groups with identical caloric intake - the men consumed 1,600 calories daily and the women 1,400.

However, the first group was given a low carbohydrate diet including a small 300 calorie breakfast, and the second was given a 600 calorie breakfast high in protein and carbohydrates, always including a dessert item (i.e. chocolate).

Halfway through the study, participants in both groups had lost an average of 33 pounds per person. But in the second half of the study, results differed drastically.

The participants in the low-carb group regained an average of 22 pounds each, but participants in the group with a larger breakfast lost another 15 pounds each.

At the end of the 32 weeks, those who had consumed a 600 calorie breakfast had lost an average of 40 pounds more per person than their peers.

So enjoy eating the sweets with breakfast.

by

AKSHAYA SRIKANTH

Pharm.D Intern

Hyderabad, India

Are Proton-Pump Inhibitors Safe During Early Pregnancy?

"In a large cohort study, use of PPIs during the first trimester did not increase risk for major birth defects"

Symptomatic gastroesophageal reflux disease (GERD) is a common condition associated with pregnancy. Although its prevalence increases with duration of pregnancy, symptoms often occur even in the first trimester. Proton-pump inhibitors (PPIs) are the most effective medical therapy for patients with moderate-to-severe GERD and are widely prescribed to pregnant women. However, safety data about the use of these agents during pregnancy or immediately prior to conception are limited (JW Gastroenterol Mar 29 2005). 

To evaluate the association between exposure to PPIs and the risk for birth defects, researchers conducted a retrospective cohort study of live births in Denmark using multiple national registries. The primary analysis assessed PPI exposure to women during the 4 weeks prior to conception through the first trimester of pregnancy (12 weeks). The primary outcome measure was all major birth defects.

Of 840,968 live births, 5082 involved exposure to PPIs during the study period. Exposure was associated with increased risk for birth defects (adjusted prevalence odds ratio, 1.23; 95% confidence interval, 1.05–1.44). However, when exposure was limited to the first trimester only, no significant risk for birth defects remained. In a secondary analysis, exposures to specific PPIs during the first trimester did not increase the risk for birth defects. Of note, omeprazole — the only category C drug (i.e., animal studies have shown risk to a fetus) — was associated with the lowest risk for birth defects, although this result was not statistically significant.

My Comment: Given the widespread use of both prescription and over-the-counter PPIs, these data showing an apparent lack of teratogenicity are reassuring. It is interesting that an editorialist suggests that omeprazole should perhaps be the PPI of choice in pregnancy, even though it is a category C drug. Nonetheless, my advice in treating pregnant patients is to make recommendations to the prescribing obstetrician rather than to be the primary prescriber of any agent.

Published in Journal Watch Gastroenterology January 21, 2011.

Original article:  Pasternak B and Hviid A. Use of proton-pump inhibitors in early pregnancy and the risk of birth defects. N Engl J Med 2010 Nov 25; 363:2114.

Mitchell AA. Proton-pump inhibitors and birth defects — Some reassurance, but more needed. N Engl J Med 2010 Nov 25; 363:2161.

by

Akshaya Srikanth

Pharm.D Internee

Hyderabad, India

ANTIBIOTIC FORMULATIONS

"ANTIBIOTIC FORMULATIONS" - AKSHAYA SRIKANTH
GENERIC NAME	BRAND NAME	TABS	CAPS	LIQ	INH	INJ
Aminoglycosides
Gentamicin	Gentamicin					•
Cephalosporins
Cefaclor	Cefaclor	•/E	•	•
Cefadroxil	—	•	•	•
Cefdinir	Omnicef		•	•
Cefditoren	Spectracef	•
Cefepime	Maxipime					•
Cefixime	Suprax	•		•
Cefpodoxime	Vantin	•		•
Cefprozil	Cefzil	•		•
Ceftaroline	Teflaro					•
Ceftibuten	Cedax		•	•
Ceftriaxone	Rocephin					•
Cefuroxime	Ceftin	•		•
	Zinacef					•
Cephalexin	Keflex		•
Macrolides
Azithromycin	Zithromax	•		•		•
	Zmax			•
Clarithromycin	Biaxin	•		•
	Biaxin XL	•
Erythromycin	E.E.S.	•		•
	Eryc		•
	Eryped	C		•/D
	Ery-Tab	•
	PCE	•
Nitroimidazoles
Metronidazole	Flagyl	•	•			•
Penicillins
Broad Spectrum
Amoxicillin	Amoxil	•/C	•	•/D
	Moxatag	•/E
	Amoxicillin		•	•
Ampicillin	Ampicillin		•	•		•
Penicillinase-Sensitive
Penicillin VK	Penicillin VK	•		•
Antipseudomonals
Combination Agent
Amoxicillin + clavulanate	Augmentin	•/C		•
	Augmentin ES			•
	Augmentin XR	•
Ampicillin + sulbactam	Unasyn					•
Piperacillin + tazobactam	Zosyn					•
Quinolones
Ciprofloxacin	Cipro	•		•		•
	Cipro XR	•
	ProQuin XR	•
Gemifloxacin	Factive	•
Levofloxacin	Levaquin	•		•		•
Moxifloxacin	Avelox	•				•
Norfloxacin	Noroxin	•
Ofloxacin	Floxin	•
Sulfonamides
Sulfisoxazole	Gantrisin			•
Combination Agent
Sulfamethoxazole + trimethoprim	Bactrim	•/DS
	Septra	•/DS		•		•
Tetracyclines
Doxycycline	Doryx	•
	Monodox		•
	Vibramycin		•	•
	Vibra-Tabs	•
Minocycline	Minocin		•
Tetracycline	Tetracycline		•
Other Classes
Aztreonam (monobactam)	Cayston				P
Clindamycin (lincosamide)	Cleocin		•	•		•
Daptomycin (cyclic lipopeptide)	Cubicin					•
Doripenem (carbapenem)	Doribax					•
Fosfomycin	Monurol			•
Linezolid (oxazolidinone)	Zyvox	•		•		•
Meropenem (carbapenem)	Merrem					•
Nitrofurantoin	Furadantin			•
	Macrobid		•
	Macrodantin		•
Quinupristin/dalfopristin (streptogramin)	Synercid					•
Rifampin (rifamycin)	Rifadin		•			•
Rifaximin (rifamycin)	Xifaxan	•
Telavancin	Vibativ					•
Telithromycin (ketolide)	Ketek	•
Tigecycline (glycylcycline)	Tygacil					•
Vancomycin (tricyclic glycopeptide)	Vancocin		•			•
Combination Agent
Imipenem + cilastatin (carbapenem)	Primaxin					•
NOTES
C = Chewable tablets   D = Drops   DS = Double strength tablets also available   E = Extended-release   P = Powder for nebulization after reconstitution    Not an inclusive list. copyrights@akshaypharmd.blogspot.com

by
Akshaya Srikanth, Mohammad Wasim*
Pharm.D Intern, *Phase-IV Expert (Ranbaxy Labs Ltd)
Hyderabad, India