Major Cause Of Discontinuation Research Articles

Prevalence of drug-induced liver injury in patients on antitubercular therapy

Background: As per the World Health Organization Global Tuberculosis (TB) Report 2019, there were an estimated 10.0 million new TB cases worldwide in 2018, with India (27%) having the maximum burden of the disease. Drug-induced liver injury (DILI) due to antitubercular treatment (ATT) is a serious adverse effect and a major cause of discontinuation of ATT, leading to increased drug resistance, morbidity, and mortality. Methodology: This was an observational study that was conducted at a tertiary care center in South Maharashtra having a dedicated TB nodal center. All newly detected cases of pulmonary and extrapulmonary TB and cases of TB after relapse/failure/treatment after default, who reported to this nodal center from January 2019 to June 2019 and in whom Category 1 and Category 2 ATT was started as per the Revised National Tuberculosis Programme protocol, were enrolled in this study. Results: Out of 100 enrolled patients, 10 (10%) were diagnosed to have ATT-induced DILI, which is concordant with other studies. No deaths were recorded. However, there was no statistically significant difference between male and female patients who developed DILI (12% males vs. 8% females). No correlation was found with body mass index or alcohol consumption. Conclusion: A fine balance should be struck between unnecessary discontinuation of ATT and continued safe treatment. Patient and staff education, careful selection of regimen, and close monitoring of risk factors will minimize cases of DILI.

Risk factors correlated with immunosuppressant discontinuation in antineutrophil cytoplasmic antibody-associated vasculitis patients.

The use of an immunosuppressant is recommended as a treatment for remission induction in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, the immunosuppressant is sometimes discontinued due to an adverse event. We sought to identify the cause and risk factors for immunosuppressant discontinuation in patients with AAV receiving remission induction treatment. We retrospectively analyzed the cases of AAV patients treated in 2005-2016 with immunosuppressants to induce remission. We defined "discontinuation" as stopping, switching, or delaying immunosuppressant administration due to adverse events. We performed a multivariate analysis to identify risk factors for immunosuppressant discontinuation. We identified 50 patients treated with an immunosuppressant for remission induction: cyclophosphamide was used in 45 patients (90%), methotrexate in 4 (8%), and cyclosporine A in 1 patient (2%). Among them, 26 patients (52%) underwent discontinuation of the immunosuppressant. Infection and myelosuppression were the major causes of discontinuation. Multivariate Cox proportional hazards regression analysis revealed that a cumulative dose of prednisolone≥2000mg (hazard ratio [HR] =2.18, 95% confidence interval [CI] =1.37-3.70, P<.001), performance status of 3-4 (HR=1.80, 95% CI=1.07-3.03, P=.027), and oral cyclophosphamide (HR=1.81, 95% CI=1.11-2.97, P=.018) were independent risk factors correlated with immunosuppressant discontinuation. Physicians should be aware of risk factors predicting immunosuppressant discontinuation when treating AAV patients with an immunosuppressant.

Recent advances in evaluation studies for drug-induced liver injury

With the recent progress in drug metabolism and pharmacokinetics studies, the attrition due to pharmacokinetics in clinical trials and post-marketing was reduced to less than 1%. On the other hand, attrition of clinical trials due to adverse effects and toxicity has remained high. In particular, drug-induced liver injury (DILI) is a major cause of discontinuation of clinical trials and withdrawal of drug candidates after marketing. DILI is roughly divided into intrinsic and idiosyncratic. The former is relatively easy to predict its onset in preclinical drug development, but the latter's onset mechanism is still unknown and its onset prediction is difficult. We are investigating to develop an experimental animal model of idiosyncratic DILI (iDILI), clarify the pathogenic mechanism, and apply the obtained biomarker information to the establishment of an in vitro cell-based prediction test system. In this paper, we will introduce various animal models of iDILI, present status of pathogenic mechanism study, and classification of iDILI drugs, and introduce the recent progress of in vitro cell-based prediction test system and new causative factors of iDILI.

Dimethyl Fumarate in Multiple Sclerosis

At the end of 2016, dimethyl fumarate (DMF) was approved as the sixth disease-modifying drug for multiple sclerosis by the Pharmaceuticals and Medical Devices Agency of Japan. Two randomized, placebo-controlled, phase III studies (DEFINE and CONFIRM) showed beneficial effects in patients in Western countries, with relapsing-remitting multiple sclerosis (RRMS). Some of the benefits included a decreased annual relapse rate, inhibition of disease activity (shown using brain magnetic resonance imaging), and a decreased proportion of patients with confirmed disease progression. The APEX study, which included Japanese patients with RRMS, also showed similar results, but reported some adverse effects. Flushing and gastrointestinal events (e.g., nausea, vomiting, abdominal pain, and diarrhea) occurring within 1 month of the initiation of DMF treatment are major causes of discontinuation of the drug. The most serious adverse event is progressive multifocal leukoencephalopathy (PML), which was reported in four patients with MS treated with DMF, worldwide. Grade 3 lymphopenia (less than 500/mm³) due to apoptosis occurs in some DMF-treated patients with MS and is more prevalent among older patients. A reduction in CD8⁺ T cells is more pronounced than that in CD4⁺ T cells. Patients with grade 3 lymphopenia, aged more than 50 years, are at a risk for PML development. Further studies are needed to determine the appropriate final dose and an acceptable dose-escalation method for DMF treatment, to prevent or decrease adverse effects in Japanese patients with MS.

The efficacy of clobetasol, dexpanthenol, and fucidic acid in the treatment of cetuximab-induced skin toxicity

Cetuximab (CTX) is a monoclonal antibody against the epidermal growth factor receptor (EGFR). It is used as a monotherapy or in combination with cytotoxic chemotherapy in metastatic colorectal cancer (mCRC). Severe cutaneous reactions are frequent and major causes of discontinuation of CTX treatment. This open-label study evaluated the efficacy of a mixture drug topically applied to skin lesions in patients with mCRC who developed skin toxicity caused by CTX. Twenty patients with mCRC were included in this prospective, single-center, open-labeled trial. The patients had received CTX in addition to chemotherapy and developed grade 2 or 3 skin toxicity and were treated twice daily with an ointment mixture of clobetasol, dexpanthenol, and fucidic acid. The objective response rate was 100%, and no delay, dose reduction or discontinuation of CTX treatment due to skin toxicity were necessary. Skin toxicity relapsed in the following chemotherapy cycles in all patients after discontinuation of the ointment. Repeated administration of the ointment resulted in improvement of skin toxicity and allowed continuation of CTX treatment. This ointment mixture seems to be effective in the treatment of CTX-induced skin toxicity in patients with mCRC.

Prognostic impact of Bacillus Calmette-Guérin interruption at the time of induction and consolidation.

Context:Intravesical Bacillus Calmette-Guérin (BCG) is a cause of bladder and systemic toxicity that is difficult to prevent and is responsible for treatment drop out in bladder cancer patients. More recently, BCG shortage has become the main cause of incomplete treatment.Aims:The aim of this study was to examine the impact on long-term prognosis of bladder cancer patients following discontinuation of BCG instillations.Settings and Design:In this retrospective study, data were examined from 333 consecutive nonmuscle invasive bladder cancer patients treated from 2005 to 2015 by transurethral resection (TUR) and had undergone adjuvant BCG therapy after TUR.Subjects and Methods:Rate of complete cure, the reason for the interruption, toxicity, and the associations between discontinuance of BCG therapy, tumor characteristics, association with carcinoma in situ and tumor recurrence or progression were analyzed.Statistical Analysis Used:Recurrence and progression-free survival rate curves were estimated using the Kaplan-Meier method and were compared using the log-rank test. Univariate and multivariate analyses were performed using the Cox proportional hazards model. Differences among groups were considered as statistically significant when P < 0.05.Results:Overall, 303 patients were eligible for analysis. Median follow up was 36 (confidence interval: 7–120) months. A total of 55 (18.1%) had <6 installations (Group I); 87 (28.7%) completed induction and 1-year maintenance (Group III); and 161 (53.1%) completed the induction course, but not the 1-year maintenance (Group II). Grade III–IV toxicity rates were significantly higher in Group I than Group II and III. Interruption for BCG shortage was the main cause of interrupting BCG in Group II. Multivariate analysis showed that discontinuation of BCG induction therapy was an independent predictor for tumor recurrence (P < 0.001) and 1-year BCG maintenance therapy for tumor progression (P = 0.005).Conclusions:Discontinuation of BCG therapy has a significantly deleterious effect on tumor recurrence and progression rates. Although BCG toxicity is a major cause of drop out, BCG shortage became a major cause of discontinuation. All effort must be done today to restore normal production of BCG worldwide.

Drug retention and safety of TNF inhibitors in elderly patients with rheumatoid arthritis.

BackgroundThe concerns about the development of adverse events (AEs) in elderly RA patients as a result of age-related changes in drug metabolism and the presence of comorbid illnesses are emphasizing due to increasing prevalence of rheumatoid arthritis (RA) in old age. However, they tend to be inadequately represented in RA clinical trials because of the exclusion criteria that are commonly applied. The tolerability and safety of TNF inhibitors in elderly patients have not been also evaluated in clinical practice. This study aimed to evaluate the retention rate and safety of TNF inhibitors (TNFI) in elderly RA patients.MethodsTotal 429 RA patients (838 person-years [PYs]) treated with TNFI from a retrospective biologic DMARDs registry. Patients were divided into an elderly (age ≥60 years) and a younger group (<60 years). The drug retention rates of both groups were compared using Kaplan-Meier curves. Potential predictors of TNFI discontinuation in the elderly were examined using Cox regression analysis. The incidence rate (IR) of serious adverse events (SAEs) in the elderly group was compared to that of the young group.ResultsOf the patients, 24.9 % (n = 107, 212 PYs) were in the elderly group. Regarding the retention rates of TNFI in 3 years, there was no significant difference between the elderly and younger group (p = 0.33). The major cause of discontinuation in elderly patients was AE (34.3 %), whereas that was drug ineffectiveness (41.7 %) in younger patients. Age (HR 1.09, CI 1.02-1.16) was a predictor of discontinuation, while the presence of comorbidity (HR 0.37, CI 0.15-0.91) had a protective effect against drug discontinuation in the elderly. The IR of SAEs in the elderly (6.13/100 PYs) was higher than in the younger group (5.11/100 PYs).ConclusionsThe retention rate of TNFI in the elderly was comparable with that in younger patients. The major cause of discontinuation in the elderly patients was AEs, while it was drug ineffectiveness in younger patients. The IR of SAEs in the elderly was higher than in the younger patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12891-016-1185-6) contains supplementary material, which is available to authorized users.

Rat Models of Acute and/or Chronic Peritoneal Injuries Including Peritoneal Fibrosis and Peritoneal Dialysis Complications.

Peritoneal injury is a major cause of discontinuation from long-term peritoneal dialysis. However, the precise mechanisms underlying such injury remain unclear. Suitable animal models of peritoneal injury may be useful to analyze pathogenic mechanisms and facilitate the development of therapeutic approaches. We describe herein two rat models of peritoneal injury that we have recently proposed.

Final Report of Bendamustine and Alemtuzumab (BEN CAM) Combination in Relapsed and Refractory Chronic Lymphocytic Leukemia.

AbstractAbstract 2898 Background:Notwithstanding the improved results with first-line therapy, CLL remains incurable, and patients are destined to relapse after primary treatment. The management of relapsed CLL pts is then dependent on several factors, including age, performance status, previous therapy, response and duration of response to therapy, and time from last therapy. Currently, the optimal treatment for pts with relapsed disease is not known. Bendamustine (BEN) demonstrated clinical activity in pre-treated hematological malignancies due to its unique mechanism of action distinct from standard alkylating agents. Alemtuzumab (CAM) is active in previously treated pts with CLL refractory to alkylating agents and purine nucleoside analogs. We designed a multicentric, single arm, dose escalation study to determine maximum tolerated dose (MTD) and to evaluate the efficacy and safety of Ben Cam combination in refractory/relapsed CLL pts. Methods:Previously treated CLL pts requiring therapy were enrolled. In the first part of the study, the tolerability of a stepwise dose-escalation schedule of BEN along with an increasing dose of CAM has been determined. BEN was given at a starting dose of 50 mg/sqm for 2 consecutive days along with CAM 20 mg sc on days 1 to 3; if MTD was not reached within the 1st cohort, the 2nd cohort received an increased dose of CAM 30 mg with a subsequent further increase of BEN 70 mg/sqm if MTD was not reached. Treatment was repeated every 28 d up to 4 course. If one of 3 pts at each dose level experienced DLT three additional pts were added (max 6). If 5 of the 6 subjects were able to complete the first 2 courses without experiencing DLT, this level was considered tolerable and dose-escalation continued initiating the following cohort. Results:Between July 2008 and March 2012, 50 pts with previously treated CLL requiring therapy according to IWCLL criteria were enrolled in 9 Italian centres. The median age of our population was 67 years (range 46–82), 64% were male and all pts presented with Binet stage B or C. Pts’ population was characterized by high risk biological and clinical disease profile: 44% were in Binet stage C, bulky lymph nodes were present in 24% of pts, refractory pts represented 26% of our population. According to hierarchical model, del17p was present in 28% and del11q in 24%; 66% were IGVH unmutated, 40% ZAP70+ and 36% CD38+. Median number of prior regimens was 2 (range, 1–4): 84% had previously received fludarabine-based treatment and 70% monoclonal antibodies in monotherapy or in combination. Twelve pts have been enrolled in the Phase I of this trial: 3 pts in each of the first 2 cohorts, 6 in the third cohort. BEN 70 mg/sqm and CAM 30 mg sc resulted as the MTD. Median number of courses administered was 4 (range, 1–4), 72% of pts completed treatment program being progression the major cause of discontinuation. At the time of writing 43 pts (86%) are evaluable for response, evaluation is pending in 7 pts who completed in all cases treatment program. Overall response rate resulted of 70% including 26% of CRs and 44% of PRs; 18% of pts maintained a stable disease; 12% showed a progression. Significant difference in response rate (P=0.009) was observed among pts with relapsed versus refractory disease. Previous treatment and unfavourable biological features did not affect response achievement. None of the variables considered showed to be significant in reaching a CR. In the whole series of treated pts grade III-IV hematological toxicity was: neutropenia in the 33% of courses, thrombocytopenia and anemia in 7 and 4% respectively. Febrile neutropenia developed in the 15% of courses. CMV reactivation occurred in 10% of courses without any organ involvement. We recorded 8 major infections: 3 sepsis, 4 pneumonias and 1 enteritis. Extra-hematological toxicity was mild. Median time to progression in responders was reached after a median follow-up of 15,5 months. Conclusions:Analysis of results data collected on 43/50 pts treated with 4-weekly dosing BENCAM regimen suggests that this combination is effective in relapsed and refractory CLL pts, most of them carrying adverse prognostic factors. Hematologic toxicity was the only serious adverse event observed with a manageable myelosuppression. Major infections recorded were not superior in quantity and quality to those observed using other immuno-chemotherapeutic regimens in the same setting. No toxic deaths were recorded while on treatment. Disclosures:No relevant conflicts of interest to declare.

Antipsychotics, Antidepressants, Anticonvulsants, and Placebo on the Symptom Dimensions of Borderline Personality Disorder

The aim of this study was to quantitatively review randomized controlled trials (RCTs) and open-label trials analyzing the efficacy of antidepressants, mood stabilizers, and antipsychotics for the treatment of the core symptoms of borderline personality disorder (BPD). Using a similar meta-analytic approach, the efficacy of placebo on the same core symptoms of BPD was evaluated. The risk of discontinuation of each of the medication classes reported in the studies was also analyzed to establish the major causes of discontinuation. MEDLINE (1966 to June 2010) and EMBASE (1980 to June 2010) databases were systematically searched to identify relevant RCTs and open studies. The primary outcome was improvement in the specific core symptoms of the disorder: affective dysregulation, impulsive-behavioral dyscontrol, and cognitive-perceptual symptoms. Evidence from RCTs and open studies suggests that drug treatment, especially with mood stabilizers and antipsychotics, may be effective for treating affective dysregulation and impulsive-behavioral dyscontrol. Antipsychotics were also effective in reducing cognitive-perceptual symptoms. Antidepressants failed to show efficacy in treating BPD symptom dimensions other than affective dysregulation. Our analyses of the placebo arm of RCTs showed a significant improvement of symptomatology in these patients also. There were no significant differences in overall dropout rates between patients on medications and those on placebo. In conclusion, the efficacy of pharmacological treatment on the symptom dimensions of BPD has been shown by various independent meta-analyses, with a positive effect of drug treatment on the core symptoms of BPD and some documentable differences in terms of efficacy between different drug classes in each of the symptom domains.

Contraceptive Discontinuation and Switching Patterns in Bangladesh

Contraceptive discontinuation and switching behaviour of a couple has significant influence on fertility in Bangladesh in spite of a successful national family planning programme. This study examines the determinants of contraceptive use, discontinuation and switching behaviour by using calendar data extracted from 2004 Bangladesh Demographic and Health Survey. Life table and multiple-decrement life table techniques are used to find out the contraceptive discontinuation rates and method specific discontinuation rates. The study shows that contraceptive prevalence increases with education, socioeconomic status, intention status, residence, age, parity and whether a family planning worker visited the home. Almost half of women who initiate the use of a method discontinue use within a year and nearly two-thirds discontinue within two years. The IUD has the lowest discontinuation rates, whereas the condom, followed by the injectable and oral contraceptive pill, have the highest rates. The findings indicate that side effects are the major cause of discontinuation for the pill, IUD and injectables. Determinants of switching behaviour are analyzed to identify users in need of contraception as well as those who abandoned use and would like to continue using contraception. Findings encompass the whole process of contraceptive use as well as women’s experience and difficulties in continuation of contraceptive use. Kaushalendra KUMAR SINGH, Professor, Department of Statistic, Banaras Hindu University, Varanasi – 221 005, India, E-mail: kksingh@bhu.ac.in . Tapan KUMAR ROY, Research Scholar, Department of Statistic, Banaras Hindu University, Varanasi – 221 005, India. E-mail: roy.tapan@gmail.com . Brijesh PRATAP SING, Assistant Professor, Faculty of Commerce, Banaras Hindu University, Varanasi – 221 005, India. E-mail: brijesh@bhu.ac.in . DOI: 10.4402/genus-157

ITPA Polymorphism Affects Ribavirin-Induced Anemia and Outcomes of Therapy—A Genome-Wide Study of Japanese HCV Virus Patients

Ribavirin-induced anemia is one of the major causes of discontinuation and dose reduction during anti-hepatitis C virus therapy. Factors influencing this anemia, especially host genetic factors, are poorly understood. In this study we investigated predictive factors in hepatitis C virus patients treated with combination therapy. We performed a 2-step genome-wide screening followed by replication analysis and fine-mapping using a total of 923 Japanese hepatitis C virus 1b-infected patients treated with pegylated-interferon plus ribavirin. We also applied logistic regression analysis to search for possible independent associations of clinical parameters and genetic variants with treatment-induced hemoglobin (Hb) decline as well as treatment outcomes. We identified a variant, located upstream of the inosine triphosphate pyrophosphatase gene on chromosome 20p13 that is significantly associated with treatment-induced anemia (combined P = 6.0 × 10(-14)). Resequencing and fine-mapping revealed several single nucleotide polymorphisms (SNPs) strongly associated with Hb decline, including the nonsynonymous SNP rs1127354 (P = 3.5 × 10(-44)), which was recently reported for other ethnic groups. Another reported SNP, the splicing variant-related SNP rs7270101, was not polymorphic in the Japanese population. Stratified analysis based on rs1127354 genotype revealed that inosine triphosphate pyrophosphatase expression is not correlated with Hb decline, suggesting that rs1127354 is a direct causal variant in the Japanese population. Multivariate analysis demonstrated that age, baseline Hb, baseline platelet count, and rs1127354 were independently associated with severe anemia (Hb <10 g/dL). A missense substitution in inosine triphosphate pyrophosphatase gene affects ribavirin-induced anemia in hepatitis C virus-infected Japanese patients.

Bortezomib and Thalidomide, a Steroid Free Regimen in Newly Diagnosed Patients with Multiple Myeloma.

Abstract 2867Poster Board II-843Corticosteroids have historically been the backbone of most myeloma targeted therapies. However, they are often the major cause of toxicities, especially in elderly patients. In recent years, novel agents such as bortezomib and thalidomide have demonstrated significant anti-myeloma activity with increased overall response rates. We thus designed a study combining these two agents in a steroid-free regimen. Bortezomib (B) and thalidomide (T) were examined as first line treatment in 27 patients with symptomatic multiple myeloma between September 2004 and September 2006. Patients received B 1.3 mg/m2 on days 1, 4, 8 and 11 every 21 days and T 150 mg daily for a maximum of 8 cycles. The overall response rate was 81.5%, with a near CR or greater of 25.8% and a CR (immunofixation negative) of 11%. A major response identified by greater than 90% reduction in the paraprotein was seen in 33% of the patients. Responses were rapid: median time to first response was 36.5 days (range, 14-101 days) and median time to best response was 61 days (range, 16-171 days). The most common grade 3 toxicities were peripheral neuropathy (22%), pneumonia (15%) and fatigue (7%). The only grade 3 hematologic toxicity was anemia (7%). No grade 4 toxicities were seen. 3 patients had mild peripheral neuropathy (PN) at baseline. PN was the most common reason for dose reduction with an average B dose of 1.1mg/m2 and T of 110mg daily. The major cause of discontinuation of treatment was PN. The PN completely resolved in 80% of the patients upon completion of therapy. No venous thromboembolic events (VTE) were observed even in the absence of prophylactic anticoagulation. It should be noted that upon completion of the study all patients received either B or T maintenance and no patients proceeded onto stem cell transplant immediately. The median progression free survival (PFS) was 16.8 months (95% CI 8.7-21.6 months). Median overall survival has not yet been reached at a median follow up of 39 months. The 3 year overall survival is 74%. This study demonstrates: 1) the excellent efficacy of a steroid-free regimen; 2) good PFS in the absence of stem cell transplantation; and 3) that most treatment-related PN resolves. Disclosures:Huff:Celgene: Consultancy. Borrello:Celgene: Speakers Bureau; Mellenium: Consultancy.

Hepatitis C Genotype 1 Treatment Picture in the Real World

Purpose: Clinicians treating patients with genotype 1 Chronic Hepatitis C (CHC) using pegylated interferon and ribavirin are faced with several challenges. Despite advances in therapy and use of growth factors, a majority of these patients do not achieve a sustained virologic response (SVR). We postulated that side effects play an important role in the discontinuation of therapy especially during the early weeks of treatment in clinical practice. Our aim was to explore the nature and frequency of adverse events that led to premature termination of combination therapy at our tertiary referral center. Methods: Medical records were reviewed on consecutive CHC genotype 1 patients who initiated 48 weeks of standard pegylated interferon (alpha 2a or alpha 2b) in combination with weight based ribavirin therapy. Data on the reasons for therapy discontinuation (constitutional, organic, psychiatric side effects) and response (early virologic, end of treatment, or sustained) was recorded and treatment was discontinued if early virologic response (EVR) was not obtained. Results: Overall on 100 patients with genotype 1 EVR was 60%, end of treatment response was 40%, and SVR was 28%. In the first 12 weeks 33 patients did not achieve an EVR and 7 patients discontinued therapy due to side effects. Of the 60 patients with EVR, in the next 36 weeks 8 patients did not achieve an end of treatment response and 12 patients discontinued therapy due to side effects. Overall, of the 19 patients who discontinued therapy 6 patients had psychiatric side effects (major depression, suicidal ideations, or psychosis), 4 patients had organic side effects (recalcitrant cytopenias or retinopathy) and 9 patients had various constitutional symptoms as the prominent reason for discontinuing therapy. Conclusions: In our clinical practice 19% of genotype 1 patients discontinued treatment during a planned 48-week course of standard combination therapy. Among those who discontinued therapy 7/19 (37%) patients did so prior to achieving an EVR versus an unexpected 12/19 (63%) patients post-EVR. Constitutional and psychiatric side effects prompted discontinuation in 5/7 (71%) patients pre-EVR versus 10/12 (83%) patients post-EVR. Our study shows that constitutional and psychiatric side effects are the major cause of discontinuation of therapy even after EVR. Continued post-EVR vigilance and proactive management of side effects may significantly reduce patient drop-out and improve SVR.

A clinical trial of norethisterone oenanthate (Norigest) injected every two months

A clinical trial was carried out in which Norigest (200 mg norethisterone oenanthate) was administered by intramuscular injection every 56 days into 383 women studied for 5,521 woman-months of use. No pregnancies occurred. Continuation rates at the end of one, two and three years were 76.6%, 63.7% and 33.8%. Only minor side-effects were recorded. After one year of use, 20.1% women had gained more than 2 kg in weight and 14.8% had lost more than 2 kg. There was marked disruption of the menstrual pattern and irregular bleeding was the major cause of discontinuation. In 38% of the injection intervals analysed, women were amenorrhoeic. Norigest proved an effective and acceptable method of fertility control.

A clinical trial of Neo Sampoon vaginal contraceptive tablets

Results are reported of a clinical trial of Neo Sampoon vaginal contraceptive tablets, conducted by the International Fertility Research Program (IFRP) in collaboration with the Dacca Medical College Hospital, Bangladesh. Of the 150 women enrolled, 115 remained in the study at the end of 12 months. The 12-month cumulative gross life-table rates per 100 women were 6.5 for pregnancy and 24.8 for discontinuation due to other reasons. Discomfort associated with the heat generated by the tablets' effervescence was the primary side effect of Neo Sampoon use, and was one of the major causes of discontinuation. Regularity of use and acceptability of this foaming tablet appeared to be high compared to other barrier methods. Further research is needed on Neo Sampoon and other vaginal contraceptives to develop and promote methods that can help meet the worldwide demand for fertility control.

A study of feeding and weaning pattern of sindhi children below 5 years in an urban area

Supplementary feeding was commonly started at the age of 6 months. The most popular supplementary foods were tea and milk. In a majority of the children, breast feeding was continued up to 18 months. The major causes of discontinuation or supplementation of breast feeding were inadequate breast-milk secretion, “dry” breast and another pregnancy.